Issue 20, June 16, 2021

CDC Science Clips: Volume 13, Issue 20, June 16, 2021

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions.

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
    • Communicable Diseases
      • Asymptomatic transmission and high community burden of seasonal influenza in an urban and a rural community in South Africa, 2017-18 (PHIRST): a population cohort studyexternal icon
        Cohen C, Kleynhans J, Moyes J, McMorrow ML, Treurnicht FK, Hellferscee O, Mathunjwa A, von Gottberg A, Wolter N, Martinson NA, Kahn K, Lebina L, Mothlaoleng K, Wafawanaka F, Gómez-Olivé FX, Mkhencele T, Mathee A, Piketh S, Language B, Tempia S.
        Lancet Glob Health. 2021 Jun;9(6):e863-e874.
        BACKGROUND: Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly from low-income and middle-income countries. We aimed to evaluate the community burden and transmission of influenza in a rural and an urban setting in South Africa. METHODS: In this prospective cohort study approximately 50 households were selected sequentially from both a rural setting (Agincourt, Mpumalanga Province, South Africa; with a health and sociodemographic surveillance system) and an urban setting (Klerksdorp, Northwest Province, South Africa; using global positioning system data), enrolled, and followed up for 10 months in 2017 and 2018. Different households were enrolled in each year. Households of more than two individuals in which 80% or more of the occupants agreed to participate were included in the study. Nasopharyngeal swabs were collected twice per week from participating household members irrespective of symptoms and tested for influenza using real-time RT-PCR. The primary outcome was the incidence of influenza infection, defined as the number of real-time RT-PCR-positive episodes divided by the person-time under observation. Household cumulative infection risk (HCIR) was defined as the number of subsequent infections within a household following influenza introduction. FINDINGS: 81 430 nasopharyngeal samples were collected from 1116 participants in 225 households (follow-up rate 88%). 917 (1%) tested positive for influenza; 178 (79%) of 225 households had one or more influenza-positive individual. The incidence of influenza infection was 43·6 (95% CI 39·8-47·7) per 100 person-seasons. 69 (17%) of 408 individuals who had one influenza infection had a repeat influenza infection during the same season. The incidence (67·4 per 100 person-seasons) and proportion with repeat infections (22 [23%] of 97 children) were highest in children younger than 5 years and decreased with increasing age (p<0·0001). Overall, 268 (56%) of 478 infections were symptomatic and 66 (14%) of 478 infections were medically attended. The overall HCIR was 10% (109 of 1088 exposed household members infected [95% CI 9-13%). Transmission (HCIR) from index cases was highest in participants aged 1-4 years (16%; 40 of 252 exposed household members) and individuals with two or more symptoms (17%; 68 of 396 exposed household members). Individuals with asymptomatic influenza transmitted infection to 29 (6%) of 509 household contacts. HIV infection, affecting 167 (16%) of 1075 individuals, was not associated with increased incidence or HCIR. INTERPRETATION: Approximately half of influenza infections were symptomatic, with asymptomatic individuals transmitting influenza to 6% of household contacts. This suggests that strategies, such as quarantine and isolation, might be ineffective to control influenza. Vaccination of children, with the aim of reducing influenza transmission might be effective in African settings given the young population and high influenza burden. FUNDING: US Centers for Disease Control and Prevention.

      • Reflections on 40 Years of AIDSexternal icon
        De Cock KM, Jaffe HW, Curran JW.
        Emerg Infect Dis. 2021 Jun;27(6):1553-1560.
        June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions, clarifying optimal use of HIV testing and antiretroviral therapy for prevention and treatment, continuing research, and ensuring sustainability of the response. Despite scientific and programmatic progress, the end of AIDS is not in sight. Other major epidemics over the past decade have included Ebola, arbovirus infections, and coronavirus disease (COVID-19). A benchmark against which to compare other global interventions is the HIV/AIDS response in terms of funding, coordination, and solidarity. Lessons from Ebola and HIV/AIDS are pertinent to the COVID-19 response. The fifth decade of AIDS will have to position HIV/AIDS in the context of enhanced preparedness and capacity to respond to other potential pandemics and transnational health threats.

    • Environmental Health
      • BACKGROUND/OBJECTIVES: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. SUBJECTS/METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS: After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. CONCLUSIONS: Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.

    • Health Disparities
      • PURPOSE: Differences in hysterectomy prevalence by rural or urban residence could distort comparisons of rural-urban cervical and uterine cancer incidence. Using data from a large population-based survey, we sought to understand whether hysterectomy prevalence varies by rural or urban residence and whether the relationship between hysterectomy prevalence and rurality varies by race or ethnicity. METHODS: Our analysis included 197,759 female respondents to the 2018 Behavioral Risk Factor Surveillance System, aged 20-79 years. We calculated population weighted proportions and 95% confidence intervals for hysterectomy prevalence, stratified by rural-urban residence and 5-year age groups. We also report estimates of hysterectomy prevalence by rural-urban residence for specific race and ethnic groups. FINDINGS: Hysterectomy prevalence increased with age and was more common among rural women than urban women. The largest absolute difference occurred among women aged 45-49 years; 28.6% of rural women (95% CI: 25.1-32.2) and 16.6% of urban women (95% CI: 15.3-17.8) reported a hysterectomy. For hysterectomy prevalence by race and ethnicity, rural estimates were higher than urban estimates for the following groups of women: non-Hispanic Asian, non-Hispanic other race, non-Hispanic Black, and non-Hispanic White. Among Hispanic women and non-Hispanic American Indian/Alaska Native women, rural-urban differences in hysterectomy prevalence were not statistically different at the 95% confidence level. CONCLUSIONS: Our results suggest that variation in hysterectomy prevalence, if not adjusted in the analysis, could produce distorted comparisons in measures of the relationship between rurality and uterine and cervical cancer rates. The magnitude of this confounding bias may vary by race and ethnicity.

    • Immunity and Immunization
      • Barriers and activities to implementing or expanding influenza vaccination programs in low- and middle-income countries: A global surveyexternal icon
        Kraigsley AM, Moore KA, Bolster A, Peters M, Richardson D, Arpey M, Sonnenberger M, McCarron M, Lambach P, Maltezou HC, Bresee JS.
        Vaccine. 2021 May 12.
        INTRODUCTION: Despite considerable global burden of influenza, few low- and middle-income countries (LMICs) have national influenza vaccination programs. This report provides a systematic assessment of barriers to and activities that support initiating or expanding influenza vaccination programs from the perspective of in-country public health officials. METHODS: Public health officials in LMICs were sent a web-based survey to provide information on barriers and activities to initiating, expanding, or maintaining national influenza vaccination programs. The survey primarily included Likert-scale questions asking respondents to rank barriers and activities in five categories. RESULTS: Of 109 eligible countries, 62% participated. Barriers to influenza vaccination programs included lack of data on cost-effectiveness of influenza vaccination programs (87%) and on influenza disease burden (84%), competing health priorities (80%), lack of public perceived risk from influenza (79%), need for better risk communication tools (77%), lack of financial support for influenza vaccine programs (75%), a requirement to use only WHO-prequalified vaccines (62%), and young children require two vaccine doses (60%). Activities for advancing influenza vaccination programs included educating healthcare workers (97%) and decision-makers (91%) on the benefits of influenza vaccination, better estimates of influenza disease burden (91%) and cost of influenza vaccination programs (89%), simplifying vaccine introduction by focusing on selected high-risk groups (82%), developing tools to prioritize target populations (80%), improving availability of influenza diagnostic testing (79%), and developing collaborations with neighboring countries for vaccine procurement (74%) and regulatory approval (73%). Responses varied by country region and income status. CONCLUSIONS: Local governments and key international stakeholders can use the results of this survey to improve influenza vaccination programs in LMICs, which is a critical component of global pandemic preparedness for influenza and other pathogens such as coronaviruses. Additionally, strategies to improve global influenza vaccination coverage should be tailored to country income level and geographic location.

    • Informatics
      • Detection of Emerging Drugs Involved in Overdose via Diachronic Word Embeddings of Substances Discussed on Social Mediaexternal icon
        Wright AP, Jones CM, Horng Chau D, Matthew Gladden R, Sumner SA.
        J Biomed Inform. 2021 May 25:103824.
        Substances involved in overdose deaths have shifted over time and continue to undergo transition. Early detection of emerging drugs involved in overdose is a major challenge for traditional public health data systems. While novel social media data have shown promise, there is a continued need for robust natural language processing approaches that can identify emerging substances. Consequently, we developed a new metric, the relative similarity ratio, based on diachronic word embeddings to measure movement in the semantic proximity of individual substance words to 'overdose' over time. Our analysis of 64,420,376 drug-related posts made between January 2011 and December 2018 on Reddit, the largest online forum site, reveals that this approach successfully identified fentanyl, the most significant emerging substance in the overdose epidemic, >1 year earlier than traditional public health data systems. Use of diachronic word embeddings may enable improved identification of emerging substances involved in drug overdose, thereby improving the timeliness of prevention and treatment activities.

    • Injury and Violence
    • Laboratory Sciences
      • The idea of specimen self-collection or self-STI testing is not new. In 2019, the World Health Organization (WHO) published the "WHO Consolidated Guideline on Self-Care Interventions for Health" as a first installment in a planned series for various diseases (8). The first document focused on "Sexual and Reproductive Health and Rights". Self-care including self-testing has the readily apparent benefits of privacy, confidentiality, speed, convenience, and access if the price is affordable. It is "people-centered" (9) and enables active participation in one's own health. It is also a health system approach as it can reduce burden on stretched systems with world-wide shortages in medical personnel or other barriers to health care access. Potential risks include: low specimen return rates, uncertain follow-up (linkage to care including treatment, repeat testing including test of cure, partner notification, counseling on risk reduction), unintended/unnecessary use (resulting in false positives with their own set of associated problems), incorrect use, lack of understanding of window periods (resulting in false negatives), lack of surveillance data generation, among other issues (9). The WHO systematically reviewed evidence for self-testing or specimen self-collection for GC, CT and syphilis, including US studies, and published a meta-analysis of available evidence (9). Programs offering self-collection of samples increased overall uptake of STI testing services (RR: 2.941, 95% CI 1.188 to 7.281) and case finding (RR: 2.166, 95% CI1.043 to 4.498), prior to the pandemic (9). U. S. laboratory research on the equivalence and/or superiority of self-collected versus provider-collected specimens for test sensitivity was reported by Gaydos et al (summarized or referenced in (10)). Based on this evidence, WHO issued a new recommendation in 2019 "Self-collection of samples for Neisseria gonorrhoeae and Chlamydia trachomatis should be made available as an additional approach to deliver STI testing services for individuals using STI testing services" (8). In addition, WHO issued a new and conditional recommendation: "Self-collection of samples for Treponema pallidum (syphilis) and Trichomonas vaginalis may be considered as an additional approach to deliver STI testing services for Individuals using STI testing services" (8). Thus, even before the COVID-19 pandemic, substantial expert agreement existed concerning benefits of this approach.

    • Occupational Safety and Health
      • Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" productsexternal icon
        Lindberg JE, Quinn MM, Gore RJ, Galligan CJ, Sama SR, Sheikh NN, Markkanen PK, Parker-Vega A, Karlsson ND, LeBouf RF, Virji MA.
        J Occup Environ Hyg. 2021 May 18:1-12.
        Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

    • Parasitic Diseases
      • Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case dataexternal icon
        Cameron E, Young AJ, Twohig KA, Pothin E, Bhavnani D, Dismer A, Merilien JB, Hamre K, Meyer P, Le Menach A, Cohen JM, Marseille S, Lemoine JF, Telfort MA, Chang MA, Won K, Knipes A, Rogier E, Amratia P, Weiss DJ, Gething PW, Battle KE.
        Elife. 2021 Jun 1;10.
        Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand'Anse Department in South-Western Haiti.

    • Substance Use and Abuse
      • Clinician Beliefs and Practices Related to Cannabisexternal icon
        Schauer GL, Njai R, Grant AM.
        Cannabis Cannabinoid Res. 2021 Apr 26.
        Introduction: Medical cannabis (marijuana) use is legal in 33 U.S. states and the District of Columbia. Clinicians can play an important role in helping patients access and weigh potential benefits and risks of medicinal cannabis. Accordingly, this study aimed to assess clinician beliefs and practices related to cannabis. Methods: Data are from 1506 family practice doctors, internists, nurse practitioners, and oncologists who responded to the 2018 DocStyles, a web-based panel survey of clinicians. Questions assessed medicinal uses for and practices related to cannabis and assessed clinicians' knowledge of cannabis legality in their state. Logistic regression was used to assess multivariable correlates of asking about, assessing, and recommending cannabis. Results: Over two-thirds (68.9%) of clinicians surveyed believe that cannabis has medicinal uses and just over a quarter (26.6%) had ever recommended cannabis to a patient. Clinicians who believed cannabis had medicinal uses had 5.9 times the adjusted odds (95% confidence interval 3.9-8.9) of recommending cannabis to patients. Beliefs about conditions for medical cannabis use did not necessarily align with the current scientific evidence. Nearly two-thirds (60.0%) of clinicians surveyed incorrectly reported the legal status of cannabis in their state. Discussion: Findings suggest that while clinicians believe that cannabis has medicinal uses, they may not have a full understanding of the scientific evidence and may not accurately understand their state-based policies for cannabis legalization and use. Given that clinicians are responsible for recommending medicinal cannabis in most states that have legalized it, ongoing education about the health effects of cannabis is warranted.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Dietary Factors and Prevention: Risk of End-Stage Kidney Disease by Fruit and Vegetable Consumptionexternal icon
        Banerjee T, Carrero JJ, McCulloch C, Burrows NR, Siegel KR, Morgenstern H, Saran R, Powe NR.
        Am J Nephrol. 2021 May 27:1-12.
        BACKGROUND: The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. METHODS: We used data from the Third National Health and Nutrition Examination Survey (1988-1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. RESULTS: 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for <2 times/day (1.45 [1.24-1.68], 2 to <3 times/day (1.40 [1.18-1.61]), 3 to <4 times/day (1.25 [1.04-1.46]), and 4 to <6 times/day (1.14 [0.97-1.31]). There was suggestion of heterogeneity (p for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1-4 (n = 5,346) and specifically in those with CKD stages 3-4 (n = 1,084). CONCLUSIONS: Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.

      2. A population study of screening history and diagnostic outcomes of women with invasive cervical cancerexternal icon
        Benard VB, Jackson JE, Greek A, Senkomago V, Huh WK, Thomas CC, Richardson LC.
        Cancer Med. 2021 May 21.
        BACKGROUND: Despite advances to prevent and detect cervical cancer, national targets for screening have not been met in the United States. Previous studies suggested that approximately half of women who developed cervical cancer were not adequately screened. This study aimed to provide an updated examination of women's screening and diagnostic practices five years prior to an invasive cervical cancer diagnosis. METHODS: The study included women age 21 years and older diagnosed with invasive cervical cancer in 2013-2016 from three population-based state cancer registries in the United States. Medical records abstraction identified screening history and diagnostic follow-up. A mailed survey provided sociodemographic data. Screening was a Pap or human papillomavirus (HPV) test between 6 months and 5 years before diagnosis. Adequate follow-up was defined per management guidelines. RESULTS: Of the 376 women, 60% (n = 228) had not been screened. Among women who received an abnormal screening result (n = 122), 67% (n = 82) had adequate follow-up. Predictors of: (a) being screened were younger age, having a higher income, and having insurance; (b) adequate follow-up were having a higher income, and (c) stage 1 cervical cancer were being screened and younger age. CONCLUSION: Unlike other cancer patterns of care studies, this study uses data obtained from medical records supplemented with self-report information to understand a woman's path to diagnosis, her follow-up care, and the stage of her cervical cancer diagnosis. This study provides findings that could be used to reach more unscreened or under screened women and to continue lowering cervical cancer incidence in the United States.

      3. INTRODUCTION: The 2015 Sustainable Development Goals include the objective of reducing premature mortality from major non-communicable diseases (NCDs) by one-third by 2030. Accomplishing this objective has demographic implications with relevance for countries' health systems and costs. However, evidence on the system-wide implications of NCD targets is limited. METHODS: We developed a cohort-component model to estimate demographic change based on user-defined disease-specific mortality trajectories. The model accounts for ageing over 101 annual age cohorts, disaggregated by sex and projects changes in the size and structure of the population. We applied this model to the context of Bangladesh, using the model to simulate demographic outlooks for Bangladesh for 2015-2030 using three mortality scenarios. The 'status quo' scenario entails that the disease-specific mortality profile observed in 2015 applies throughout 2015-2030. The 'trend' scenario adopts age-specific, sex-specific and disease-specific mortality rate trajectories projected by WHO for the region. The 'target' scenario entails a one-third reduction in the mortality rates of cardiovascular disease, cancer, diabetes and chronic respiratory diseases between age 30 and 70 by 2030. RESULTS: The status quo, trend and target scenarios projected 178.9, 179.7 and 180.2 million population in 2030, respectively. The cumulative number of deaths during 2015-2030 was estimated at 17.4, 16.2 and 15.6 million for each scenario, respectively. During 2015-2030, the target scenario would avert a cumulative 1.73 million and 584 000 all-cause deaths compared with the status quo and trend scenarios, respectively. Male life expectancy was estimated to increase from 71.10 to 73.47 years in the trend scenario and to 74.38 years in the target scenario; female life expectancy was estimated to increase from 73.68 to 75.34 years and 76.39 years in the trend and target scenarios, respectively. CONCLUSION: The model describes the demographic implications of NCD prevention and control targets, estimating the potential increase in life expectancy associated with achieving key NCD reduction targets. The results can be used to inform future health system needs and to support planning for increased healthcare coverage in countries.

      4. Facilitators to referrals to CDC's National Diabetes Prevention Program in primary care practices and pharmacies: DocStyles 2016-2017external icon
        Nhim K, Khan T, Gruss S, Wozniak G, Kirley K, Schumacher P, Albright A.
        Prev Med. 2021 May 11;149:106614.
        Despite evidence of the effectiveness of behavioral change interventions for type 2 diabetes prevention, health care provider referrals to organizations offering the National Diabetes Prevention Program (National DPP) lifestyle change program (LCP) remain suboptimal. This study examined facilitators of LCP referrals among primary care providers and pharmacists (providers). We analyzed data on 1956 providers from 2016 to 2017 DocStyles web-based surveys. Pearson chi-square or Fisher's exact tests were used for bivariate associations between facilitators, provider characteristics, and their self-reported referral and bi-directional referral (where they received patient status updates back from the LCPs) to an LCP. Multiple logistic regressions were used to estimate the effects of facilitators to referral practices, controlling for providers' characteristics. Geocoding was done at the street level for in-person, public LCP class locations and at the zip code level for survey respondents to create a density measure for LCP availability within 10 miles. Overall, 21% of providers referred their patients with prediabetes to LCPs, and 6.4% engaged in bi-directional referral. Provider practices that established clinical-community linkages (CCLs) with LCPs (AOR = 4.88), used electronic health records (EHRs) to manage patients (AOR = 2.94), or practiced within 10 miles of an in-person, public LCP class location (AOR = 1.49) were more likely to refer. Establishing CCLs with LCPs (AOR = 8.59) and using EHRs (AOR = 1.86) were also facilitators of bi-directional referral. This study highlights the importance of establishing CCLs between provider settings and organizations offering the National DPP LCP, increasing use of EHRs to manage patients, and increasing availability of in-person LCP class locations near provider practices.

      5. Evidence-Based Interventions and Colorectal Cancer Screening Rates: The Colorectal Cancer Screening Program, 2015-2017external icon
        Sharma KP, DeGroff A, Maxwell AE, Cole AM, Escoffery NC, Hannon PA.
        Am J Prev Med. 2021 May 14.
        INTRODUCTION: The Centers for Disease Control and Prevention administers the Colorectal Cancer Control Program to increase colorectal cancer screening rates among people aged 50-75 years in areas where rates are lower than state or national levels. The aim of this study is to better understand the effectiveness of specific Colorectal Cancer Control Program components. METHODS: The study population included clinics enrolled in the Colorectal Cancer Control Program during Years 1 and 2. Clinic data collected by the Centers for Disease Control and Prevention annually from 2015 to 2017 for program evaluation were used. The outcome variable was screening rate change through Program Year 2, and predictor variables were a new implementation or enhancement of evidence-based interventions and other program components. The analysis, conducted in 2020, used ordinary least square and generalized estimating equations regressions and first difference models to estimate the associations of independent variables with the outcome. RESULTS: Of the total 336 clinics, 50%-70% newly implemented or enhanced different evidence-based interventions. Among these, client reminders were most highly associated with the increase in screening rates (8.0 percentage points). Provider reminder was not significantly associated with any change in screening rates. Among all program components, having a colorectal cancer screening champion was most highly (8.4 percentage points) associated with screening rate change. Results from different models were slightly different but in agreement. CONCLUSIONS: Client reminders, provider assessment and feedback, and colorectal cancer screening champions were associated with increased clinic-level colorectal cancer screening rates. Universal implementation of these strategies can substantially increase colorectal cancer screening rates in the U.S.

      6. INTRODUCTION: The Patient Protection and Affordable Care Act requires many health insurance plans to cover certain clinical preventive services in network with no cost sharing. This study describes the utilization trends of 8 clinical preventive services by insurance status and analyzes utilization disparities. METHODS: Data were collected from 2011 to 2019 through the Behavioral Risk Factor Surveillance System and were analyzed in 2021. Logistic regression and generalized linear modeling were fitted to calculate the absolute and relative differences by insurance status, respectively. Annual percentage point change was applied to assess the trends in utilization and the relative difference. RESULTS: Trends in utilization ranged from an annual percentage point change high with zoster vaccination of 8.03 (p<0.01) and a low with cervical cancer screening of -1.01 (p<0.01). Trends (except for HIV testing) were consistently substantially lower among the uninsured. Utilization among all participants increased for 4 clinical preventive services, although larger increases were observed among the uninsured for breast and colon cancer screenings. The utilization of cervical cancer screening decreased, and the utilization of the other 3 services did not change significantly. The relative difference between the insured and the uninsured decreased modestly with the greatest reductions observed for breast cancer screening and zoster vaccination, whereas increases were observed for HIV testing. CONCLUSIONS: Despite the reduction of cost barriers for the insured, there were larger increases in utilization among the uninsured, and a narrowed gap was observed over time for some services. Ongoing efforts to monitor the trends in clinical preventive services utilization may help identify and evaluate the strategies designed to increase their use.

      7. The Centers for Disease Control and Prevention (CDC) created a health communication marketing and promotion support system (support system) to help 10 CDC-funded national organizations (recipients) grow enrollment of underserved populations in the National Diabetes Prevention Program. This article describes the creation of a successful support system to increase the use of effective marketing approaches and key messaging. The support system was developed using a systematic approach. It included a needs assessment, audience research, marketing strategy identification, expert panel review, materials development, and dissemination guidance. Hands-on, individualized, and group end-user training and technical assistance was also included. Recipients received culturally and linguistically tailored marketing materials to support their specific priority audiences, as well as corresponding training on recommended dissemination methods. In in-depth key-informant interviews, staff from six recipients reported increased knowledge of local communities and audiences, efficacy and skills to conduct media interviews, capacity to identify and train champions and influencers, and greater community partner investments. With marketing support, 90% of recipients reported increased enrollment, of which 40% exceeded self-set targets and another 40% doubled or tripled their enrollment numbers. These findings indicate that a customized strategic health communication marketing and promotion support system presents a significant opportunity to help recipients increase enrollment in evidence-based interventions. Practitioners disseminating evidence-based interventions may consider a support system to increase program uptake.

    • Communicable Diseases
      1. High Pgp3 Chlamydia trachomatis seropositivity, pelvic inflammatory disease and infertility among women, National Health and Nutrition Examination Survey, United States, 2013-2016external icon
        Anyalechi GE, Hong J, Danavall DC, Martin DL, Gwyn SE, Horner PJ, Raphael BH, Kirkcaldy RD, Kersh EN, Bernstein KT.
        Clin Infect Dis. 2021 May 29.
        BACKGROUND: Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Pgp3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA). METHODS: We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI ≥ 50,000; low-positive was MFI > 551-<50,000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (95% CI) were compared for women with chlamydial infection, self-reported PID, and infertility. RESULTS: Of 2,339 women aged 18-39 years, 1,725 (73.7%) had sera and 1,425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had low positive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]).Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab. CONCLUSIONS: High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection.

      2. Salmonella Bloodstream Infections in Hospitalized Children with Acute Febrile Illness-Uganda, 2016-2019external icon
        Appiah GD, Mpimbaza A, Lamorde M, Freeman M, Kajumbula H, Salah Z, Kugeler K, Mikoleit M, White PB, Kapisi J, Borchert J, Sserwanga A, Van Dyne S, Mead P, Kim S, Lauer AC, Winstead A, Manabe YC, Flick RJ, Mintz E.
        Am J Trop Med Hyg. 2021 May 17.
        Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.

      3. Substantial Need for Preexposure Prophylaxis Among Men Who Have Sex With Men in Hanoi, Vietnamexternal icon
        Bhatia R, Le Minh G, An LT, Thai TT, Bui H, Ngoc LB, Vu D, Abdul-Quader A.
        Sex Transm Dis. 2021 May 1;48(5):e56-e58.
        We used data from the Health in Men-Hanoi cohort to determine the proportion of HIV-negative men who have sex with men with PrEP indications in Hanoi. Among 717 men who have sex with men, 537 (72.2% [66.6%-77.3%]) had ≥1 PrEP indication, signaling a substantial need for PrEP scale-up. Condomless anal intercourse was the most frequent indication (68.7% [60.3%-76.1%]), followed by previous/current sexually transmitted infection (59.4% [51.0%-67.2%]).

      4. Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021external icon
        Borchering RK, Viboud C, Howerton E, Smith CP, Truelove S, Runge MC, Reich NG, Contamin L, Levander J, Salerno J, van Panhuis W, Kinsey M, Tallaksen K, Obrecht RF, Asher L, Costello C, Kelbaugh M, Wilson S, Shin L, Gallagher ME, Mullany LC, Rainwater-Lovett K, Lemaitre JC, Dent J, Grantz KH, Kaminsky J, Lauer SA, Lee EC, Meredith HR, Perez-Saez J, Keegan LT, Karlen D, Chinazzi M, Davis JT, Mu K, Xiong X, Pastore YP, Vespignani A, Srivastava A, Porebski P, Venkatramanan S, Adiga A, Lewis B, Klahn B, Outten J, Schlitt J, Corbett P, Telionis PA, Wang L, Peddireddy AS, Hurt B, Chen J, Vullikanti A, Marathe M, Healy JM, Slayton RB, Biggerstaff M, Johansson MA, Shea K, Lessler J.
        MMWR Morb Mortal Wkly Rep. 2021 May 14;70(19):719-724.
        After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

      5. Estimated Annual Number of HIV Infections ─ United States, 1981-2019external icon
        Bosh KA, Hall HI, Eastham L, Daskalakis DC, Mermin JH.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 4;70(22):801-806.
        The first cases of Pneumocystis carinii (jirovecii) pneumonia among young men, which were subsequently linked to HIV infection, were reported in the MMWR on June 5, 1981 (1). At year-end 2019, an estimated 1.2 million persons in the United States were living with HIV infection (2). Using data reported to the National HIV Surveillance System, CDC estimated the annual number of new HIV infections (incidence) among persons aged ≥13 years in the United States during 1981-2019. Estimated annual HIV incidence increased from 20,000 infections in 1981 to a peak of 130,400 infections in 1984 and 1985. Incidence was relatively stable during 1991-2007, with approximately 50,000-58,000 infections annually, and then decreased in recent years to 34,800 infections in 2019. The majority of infections continue to be attributable to male-to-male sexual contact (63% in 1981 and 66% in 2019). Over time, the proportion of HIV infections has increased among Black/African American (Black) persons (from 29% in 1981 to 41% in 2019) and among Hispanic/Latino persons (from 16% in 1981 to 29% in 2019). Despite the lack of a cure or a vaccine, today's HIV prevention tools, including HIV testing, prompt and sustained treatment, preexposure prophylaxis, and comprehensive syringe service programs, provide an opportunity to substantially decrease new HIV infections. Intensifying efforts to implement these strategies equitably could accelerate declines in HIV transmission, morbidity, and mortality and reduce disparities.

      6. Etiology of acute meningitis and encephalitis from hospital-based surveillance in South Kazakhstan oblast, February 2017-January 2018external icon
        Bumburidi Y, Utepbergenova G, Yerezhepov B, Berdiyarova N, Kulzhanova K, Head J, Moffett D, Singer D, Angra P, Whistler T, Sejvar J.
        PLoS One. 2021 ;16(5):e0251494.
        Encephalitis and meningitis (EM) are severe infections of the central nervous system associated with high morbidity and mortality. The etiology of EM in Kazakhstan is not clearly defined, so from February 1, 2017 to January 31, 2018 we conducted hospital-based syndromic surveillance for EM at the Shymkent City Hospital, in the South Kazakhstan region. All consenting inpatients meeting a standard case definition were enrolled. Blood and cerebrospinal fluid (CSF) samples were collected for bacterial culture, and CSF samples were additionally tested by PCR for four bacterial species and three viruses using a cascading algorithm. We enrolled 556 patients. Of these, 494 were of viral etiology (including 4 probable rabies cases), 37 were of bacterial etiology, 19 were of unknown etiology and 6 were not tested. The most commonly identified pathogens included enterovirus (73%, n = 406 cases), herpes simplex virus (12.8%, n = 71), and Neisseria meningitidis (3.8%, n = 21). The incidence rates (IRs) for enteroviral and meningococcal EM were found to be 14.5 and 0.7 per 100,000 persons, respectively. The IR for bacterial EM using both PCR and culture results was 3-5 times higher compared to culture-only results. Antibacterial medicines were used to treat 97.2% (480/494) of virus-associated EM. Incorporation of PCR into routine laboratory diagnostics of EM improves diagnosis, pathogen identification, ensures IRs are not underestimated, and can help avoid unnecessary antibacterial treatment.

      7. Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritisexternal icon
        Cannon JL, Bonifacio J, Bucardo F, Buesa J, Bruggink L, Chan MC, Fumian TM, Giri S, Gonzalez MD, Hewitt J, Lin JH, Mans J, Muñoz C, Pan CY, Pang XL, Pietsch C, Rahman M, Sakon N, Selvarangan R, Browne H, Barclay L, Vinjé J.
        Emerg Infect Dis. 2021 May;27(5):1438-1445.
        Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

      8. COVID-19 Vaccine Breakthrough Infections Reported to CDC - United States, January 1-April 30, 2021external icon
        CDC COVID-19 Vaccine Breakthrough Case Investigations Team .
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):792-793.
        COVID-19 vaccines are a critical tool for controlling the ongoing global pandemic. The Food and Drug Administration (FDA) has issued Emergency Use Authorizations for three COVID-19 vaccines for use in the United States.* In large, randomized-controlled trials, each vaccine was found to be safe and efficacious in preventing symptomatic, laboratory-confirmed COVID-19 (1-3). Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons (i.e. received all recommended doses of an FDA-authorized COVID-19 vaccine) will develop symptomatic or asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19 (2-8).

      9. Morbidity and Mortality among Adults Experiencing Homelessness Hospitalized with COVID-19external icon
        Cha S, Henry A, Montgomery MP, Laws RL, Pham H, Wortham J, Garg S, Kim L, Mosites E.
        J Infect Dis. 2021 May 16.
        People experiencing homelessness (PEH) are at higher risk for chronic health conditions, but clinical characteristics and outcomes for PEH hospitalized with COVID-19 are not known. We analyzed population-based surveillance data of COVID-19-associated hospitalizations during March 1-May 31, 2020. Two percent of the people hospitalized with COVID-19 for whom a housing status was recorded were homeless. Of 199 cases in the analytic sample, most were of racial/ethnic minority groups, and had underlying health conditions. Clinical outcomes such as ICU admission, respiratory support including mechanical ventilation, and deaths were documented. Hispanic and Non-Hispanic Black persons accounted for most mechanical ventilation and deaths. Severe illness was common among persons experiencing homelessness who were hospitalized with COVID-19.

      10. COVID-19 Severity and COVID-19-Associated Deaths Among Hospitalized Patients with HIV Infection - Zambia, March-December 2020external icon
        Chanda D, Minchella PA, Kampamba D, Itoh M, Hines JZ, Fwoloshi S, Boyd MA, Hamusonde K, Chirwa L, Nikoi K, Chirwa R, Siwingwa M, Sivile S, Zyambo KD, Mweemba A, Mbewe N, Mutengo KH, Malama K, Agolory S, Mulenga LB.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 4;70(22):807-810.
        The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

      11. Practices and Activities Among Healthcare Personnel with SARS-CoV-2 Infection Working in Different Healthcare Settings-10 Emerging Infections Program Sites, April-November 2020external icon
        Chea N, Eure T, Penna AR, Brown CJ, Nadle J, Godine D, Frank L, Czaja CA, Johnston H, Barter D, Miller BF, Angell K, Marshall K, Meek J, Brackney M, Carswell S, Thomas S, Wilson LE, Perlmutter R, Marceaux-Galli K, Fell A, Lim S, Lynfield R, Davis SS, Phipps EC, Sievers M, Dumyati G, Concannon C, McCullough K, Woods A, Seshadri S, Myers C, Pierce R, Ocampo VL, Guzman-Cottrill JA, Escutia G, Samper M, Pena SA, Adre C, Groenewold M, Thompson ND, Magill SS.
        Infect Control Hosp Epidemiol. 2021 Jun 2:1-17.
        Healthcare personnel with SARS-CoV-2 infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

      12. Global Seasonal Influenza Mortality Estimates: A Comparison of 3 Different Approachesexternal icon
        Cozza V, Campbell H, Chang HH, Iuliano AD, Paget J, Patel NN, Reiner RC, Troeger C, Viboud C, Bresee JS, Fitzner J.
        Am J Epidemiol. 2021 May 4;190(5):718-727.
        Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research's Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.

      13. Administration of Bamlanivimab to Skilled Nursing Facility Residents During a COVID-19 Outbreak, January-February 2021, Arizonaexternal icon
        Dale AP, Hudson M, Cullen T, Ellingson K, Davis K, Armenta D, Friebus H, Currie C, Bhattarai R, Brady S, Komatsu K, Stone N, Uyeki T, Slifka KJ, Perez-Velez C, Keaton A.
        J Am Med Dir Assoc. 2021 May 4.

      14. Respiratory Viral Infections and Infection Prevention Practices among Women with Acute Respiratory Illness during Delivery Hospitalizations during the 2019-2020 Influenza Seasonexternal icon
        Dawood FS, Varner M, Munoz F, Stockwell MS, Suyama J, Li DK, Tita A, Mathias L, Shakib JH, Piedra PA, Gyamfi-Bannerman C, Weissman A, Ferber J, Battarbee AN, Wesley MG, Vorwaller K, Powers E, Gibson M, Bond N, Santarcangelo P, Avadhanula V, Newes-Adeyi G, Hunt DR, Subramaniam A, Sanusi A, Boone A, Ogokeh C, Macio I, Odouli R, Thind P, Vargas CY, Almonte C, Galang R, Shapiro-Mendoza C, Campbell AP.
        J Infect Dis. 2021 May 25.
        We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations in influenza season to describe clinical testing for respiratory viruses and infection prevention practices. Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. Based on clinical and study testing combined, 41/91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17/91, 19%); 53% (9/17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. Peripartum respiratory infections may be underrecognized.

      15. Multidrug-resistant tuberculosis imported into low-incidence countries-a GeoSentinel analysis, 2008-2020external icon
        Eimer J, Patimeteeporn C, Jensenius M, Gkrania-Klotsas E, Duvignaud A, Barnett ED, Hochberg NS, Chen LH, Trigo-Esteban E, Gertler M, Greenaway C, Grobusch MP, Angelo KM, Hamer DH, Caumes E, Asgeirsson H.
        J Travel Med. 2021 May 12.
        BACKGROUND: Early detection of imported multidrug-resistant tuberculosis (MDR-TB) is crucial, but knowledge gaps remain about migration- and travel-associated MDR-TB epidemiology. The aim was to describe epidemiologic characteristics among international travelers and migrants with MDR-TB. METHODS: Clinician-determined and microbiologically confirmed MDR-TB diagnoses deemed to be related to travel or migration were extracted from GeoSentinel, a global surveillance network of travel and tropical medicine clinics, from January 2008 through December 2020. MDR-TB was defined as resistance to both isoniazid and rifampicin. Additional resistance to either a fluoroquinolone or a second-line injectable drug was categorized as pre-extensively drug-resistant (pre-XDR) TB, and as extensively drug-resistant (XDR) TB when resistance was detected for both. Sub-analyses were performed based on degree of resistance and country of origin. RESULTS: Of 201 patients, 136 had MDR-TB (67.7%), 25 had XDR-TB (12.4%), 23 had pre-XDR TB (11.4%), and 17 had unspecified MDR- or XDR-TB (8.5%); 196 (97.5%) were immigrants, of which 92 (45.8%) originated from the former Soviet Union. The median interval from arrival to presentation was 154 days (interquartile range [IQR]: 10-751 days); 34.3% of patients presented within 1 month after immigration, 30.9% between 1 and 12 months, and 34.9% after ≥1 year. Pre-XDR- and XDR-TB patients from the former Soviet Union other than Georgia presented earlier than those with MDR-TB (26 days [IQR: 8-522] vs. 369 days [IQR: 84-827]) while patients from Georgia presented very early, irrespectively of the level of resistance (8 days [IQR: 2-18] vs. 2 days [IQR: 1-17]). CONCLUSIONS: MDR-TB is uncommon in traditional travellers. Purposeful medical migration may partly explain differences in time to presentation among different groups. Public health resources are needed to better understand factors contributing to cross-border MDR-TB spread and to develop strategies to optimize care of TB-infected patients in their home countries before migration.

      16. Disparities in HIV clinical stages progression of patients at outpatient clinics in Democratic Republic of Congoexternal icon
        Ewetola R, Shah GH, Maluantesa L, Etheredge G, Waterfield K, Mulenga A, Kilundu A.
        Int J Environ Res Public Health. 2021 ;18(10).
        Context: In this era of patient-centered care, it is increasingly important for HIV/AIDS care and treatment programs to customize their services according to patients' clinical stage progression and other risk assessments. To enable such customization of HIV care and treatment de-livery, the research evidence explaining factors associated with patients' clinical stages is needed. Objective(s): The primary objective of this study was to produce such scientific evidence by analyzing the most recent data for patients at outpatient clinics in the provinces of Kinshasa and Haut-Katanga and to examine the patient characteristics associated with WHO stages of disease progression. Method(s): Using a quantitative retrospective cohort study design, we analyzed data from 49,460 people living with HIV (PLHIV) on antiretroviral therapy (ART) from 241 HIV/AIDS clinics located in Haut-Katanga and Kinshasa provinces of the Democratic Republic of Congo. We performed Chi-square and multinomial logistic regression analyses. Result(s): A small proportion (i.e., 4.4%) of PLHIV were at WHO's clinical progression stage 4, whereas 30.7% were at clinical stage 3, another 22.9% at stage 2, and the remaining 41.9% were at stage 1, the least severe stage. After controlling for other demographic and clinical factors included in the model, the likelihood of being at stage 1 rather than stage 3 or 4 was significantly higher (at p <= 0.05) for patients with no tuberculosis (TB) than those with TB co-infection (adjusted odds ratio or AOR, 5.73; confidence interval or CI, 4.98- 6.59). The odds of being at stage 1 were significantly higher for female patients (AOR, 1.35; CI, 1.29- 1.42), and those with the shorter duration on ART (vs. greater than 40.37 months). Patents in rural health zones (AOR, 0.32) and semi-rural health zones (AOR, 0.79) were less likely to be at stage 1, compared to patients in urban health zones. Conclusion(s): Our study showed that TB co-infection raised the risk for PLHIV to be at the severe stages of clinical progression of HIV. Such variation supports the thesis that customized HIV management approaches and clinical regimens may be imperative for this high-risk population. We also found significant variation in HIV clinical progression stages by geographic location and demographic characteristics. Such variation points to the need for more targeted efforts to address the disparities, as the programs attempt to improve the effectiveness of HIV care and treatment. The intersectionality of vulnerabilities from HIV, TB, and COVID-19-related hardships has elevated the need for customized care and treatment even more in the COVID-19 era.

      17. HIV detection by an emergency department HIV screening program during a regional outbreak among people who inject drugsexternal icon
        Faryar KA, Ancona RM, Reau Z, Lyss SB, Braun RS, Rademaker T, Sickles RK, Lyons MS.
        PLoS One. 2021 ;16(5):e0251756.
        OBJECTIVE: Multiple HIV outbreaks among persons who inject drugs (PWID) have occurred in the US since 2015. Emergency departments (EDs), recognized as essential venues for HIV screening, may play a unique role in identifying undiagnosed HIV among PWID, who frequently present for complications of injection drug use (IDU). Our objective was to describe changes in HIV diagnoses among PWID detected by an ED HIV screening program and estimate the program's contribution to HIV diagnoses among PWID county-wide during the emergence of a regional HIV outbreak. METHODS: This was a retrospective study of electronically queried clinical records from an urban, safety-net ED's HIV screening program and publicly available HIV surveillance data for its surrounding county, Hamilton County, Ohio. Outcomes included the change in number of HIV diagnoses and the ED's contribution to case identification county-wide, overall and for PWID during 2014-2018. RESULTS: During 2014-2018, the annual number of HIV diagnoses made by the ED program increased from 20 to 42 overall, and from 1 to 18 for PWID. We estimated that the ED contributed 18% of HIV diagnoses in the county and 22% of diagnoses among PWID. CONCLUSIONS: The ED program contributed 1 in 5 new HIV diagnoses among PWID county-wide, further illustrating the importance of ED HIV screening programs in identifying undiagnosed HIV infections. In areas experiencing increasing IDU, HIV screening in EDs can provide an early indication of increasing HIV diagnoses among PWID and can substantially contribute to case-finding during an HIV outbreak.

      18. Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 22 state, local, and territorial health departments, March 29, 2020 -March 5, 2021external icon
        Galang RR, Newton SM, Woodworth KR, Griffin I, Oduyebo T, Sancken CL, Olsen EO, Aveni K, Wingate H, Shephard H, Fussman C, Alaali ZS, Silcox K, Siebman S, Halai UA, Lopez CD, Lush M, Sokale A, Barton J, Chaudhary I, Patrick PH, Schlosser L, Reynolds B, Gaarenstroom N, Chicchelly S, Read JS, de Wilde L, Mbotha D, Azziz-Baumgartner E, Hall AJ, Tong VT, Ellington S, Gilboa SM.
        Clin Infect Dis. 2021 May 22.
        BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection. METHODS: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-March 5, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. RESULTS: Among 7,950 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 25 years and older, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. CONCLUSIONS: Older age and having underlying medical conditions were associated with increased risk of moderate-to-severe or critical COVID-19 illness among pregnant women. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.

      19. Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools - Georgia, November 16-December 11, 2020external icon
        Gettings J, Czarnik M, Morris E, Haller E, Thompson-Paul AM, Rasberry C, Lanzieri TM, Smith-Grant J, Aholou TM, Thomas E, Drenzek C, MacKellar D.
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):779-784.
        To meet the educational, physical, social, and emotional needs of children, many U.S. schools opened for in-person learning during fall 2020 by implementing strategies to prevent transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). To date, there have been no U.S. studies comparing COVID-19 incidence in schools that varied in implementing recommended prevention strategies, including mask requirements and ventilation improvements* (2). Using data from Georgia kindergarten through grade 5 (K-5) schools that opened for in-person learning during fall 2020, CDC and the Georgia Department of Public Health (GDPH) assessed the impact of school-level prevention strategies on incidence of COVID-19 among students and staff members before the availability of COVID-19 vaccines.(†) Among 169 K-5 schools that participated in a survey on prevention strategies and reported COVID-19 cases during November 16-December 11, 2020, COVID-19 incidence was 3.08 cases among students and staff members per 500 enrolled students.(§) Adjusting for county-level incidence, COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks, and 39% lower in schools that improved ventilation, compared with schools that did not use these prevention strategies. Ventilation strategies associated with lower school incidence included methods to dilute airborne particles alone by opening windows, opening doors, or using fans (35% lower incidence), or in combination with methods to filter airborne particles with high-efficiency particulate absorbing (HEPA) filtration with or without purification with ultraviolet germicidal irradiation (UVGI) (48% lower incidence). Multiple strategies should be implemented to prevent transmission of SARS-CoV-2 in schools (2); mask requirements for teachers and staff members and improved ventilation are important strategies that elementary schools could implement as part of a multicomponent approach to provide safer, in-person learning environments. Universal and correct mask use is still recommended by CDC for adults and children in schools regardless of vaccination status (2).

      20. Acute Respiratory Illnesses in Children in the SARS-CoV-2 Pandemic: Prospective Multicenter Studyexternal icon
        Haddadin Z, Schuster JE, Spieker AJ, Rahman H, Blozinski A, Stewart L, Campbell AP, Lively JY, Michaels MG, Williams JV, Boom JA, Sahni LC, Staat M, McNeal M, Selvarangan R, Harrison CJ, Weinberg GA, Szilagyi PG, Englund JA, Klein EJ, Curns AT, Rha B, Langley GE, Hall AJ, Patel MM, Halasa NB.
        Pediatrics. 2021 May 13.

      21. SARS-CoV-2 Infections and Viral Isolations among Serially Tested Cats and Dogs in Households with Infected Owners in Texas, USAexternal icon
        Hamer SA, Pauvolid-Corrêa A, Zecca IB, Davila E, Auckland LD, Roundy CM, Tang W, Torchetti MK, Killian ML, Jenkins-Moore M, Mozingo K, Akpalu Y, Ghai RR, Spengler JR, Barton Behravesh C, Fischer RS, Hamer GL.
        Viruses. 2021 May 19;13(5).
        Understanding the ecological and epidemiological roles of pets in the transmission of SARS-CoV-2 is critical for animal and human health, identifying household reservoirs, and predicting the potential enzootic maintenance of the virus. We conducted a longitudinal household transmission study of 76 dogs and cats living with at least one SARS-CoV-2-infected human in Texas and found that 17 pets from 25.6% of 39 households met the national case definition for SARS-CoV-2 infections in animals. This includes three out of seventeen (17.6%) cats and one out of fifty-nine (1.7%) dogs that were positive by RT-PCR and sequencing, with the virus successfully isolated from the respiratory swabs of one cat and one dog. Whole-genome sequences of SARS-CoV-2 obtained from all four PCR-positive animals were unique variants grouping with genomes circulating among people with COVID-19 in Texas. Re-sampling showed persistence of viral RNA for at least 25 d-post initial test. Additionally, seven out of sixteen (43.8%) cats and seven out of fifty-nine (11.9%) dogs harbored SARS-CoV-2 neutralizing antibodies upon initial sampling, with relatively stable or increasing titers over the 2-3 months of follow-up and no evidence of seroreversion. The majority (82.4%) of infected pets were asymptomatic. 'Reverse zoonotic' transmission of SARS-CoV-2 from infected people to animals may occur more frequently than recognized.

      22. Racial and Ethnic Disparities in Incidence of SARS-CoV-2 Infection, 22 US States and DC, January 1-October 1, 2020external icon
        Hollis ND, Li W, Van Dyke ME, Njie GJ, Scobie HM, Parker EM, Penman-Aguilar A, Clarke KE.
        Emerg Infect Dis. 2021 ;27(5):1477-1481.
        We examined disparities in cumulative incidence of severe acute respiratory syndrome coronavirus 2 by race/ethnicity, age, and sex in the United States during January 1-October 1, 2020. Hispanic/Latino and non-Hispanic Black, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander persons had a substantially higher incidence of infection than non-Hispanic White persons.

      23. Characteristics of COVID-19 Cases and Outbreaks at Child Care Facilities - District of Columbia, July-December 2020external icon
        Kim C, McGee S, Khuntia S, Elnour A, Johnson-Clarke F, Mangla A, Iyengar P, Nesbitt L.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):744-748.
        The occurrence of cases of COVID-19 reported by child care facilities among children, teachers, and staff members is correlated with the level of community spread (1,2). To describe characteristics of COVID-19 cases at child care facilities and facility adherence to guidance and recommendations, the District of Columbia (DC) Department of Health (DC Health) and CDC reviewed COVID-19 case reports associated with child care facilities submitted to DC Health and publicly available data from the DC Office of the State Superintendent of Education (OSSE) during July 1-December 31, 2020. Among 469 licensed child care facilities, 112 (23.9%) submitted 269 reports documenting 316 laboratory-confirmed cases and three additional cases identified through DC Health's contact tracers. Outbreaks associated with child care facilities,(†) defined as two or more laboratory-confirmed and epidemiologically linked cases at a facility within a 14-day period (3), occurred in 27 (5.8%) facilities and accounted for nearly one half (156; 48.9%) of total cases. Among the 319 total cases, 180 (56.4%) were among teachers or staff members. The majority (56.4%) of facilities reported cases to DC Health on the same day that they were notified of a positive test result for SARS-CoV-2, the virus that causes COVID-19, by staff members or parents.(§) Facilities were at increased risk for an outbreak if they had been operating for <3 years, if symptomatic persons sought testing ≥3 days after symptom onset, or if persons with asymptomatic COVID-19 were at the facility. The number of outbreaks associated with child care facilities was limited. Continued implementation and maintenance of multiple prevention strategies, including vaccination, masking, physical distancing, cohorting, screening, and reporting, are important to reduce transmission of SARS-CoV-2 in child care facilities and to facilitate a timely public health response to prevent outbreaks.(¶).

      24. A cross-sectional study measuring contact patterns using diaries in an urban and a rural community in South Africa, 2018external icon
        Kleynhans J, Tempia S, McMorrow ML, von Gottberg A, Martinson NA, Kahn K, Moyes J, Mkhencele T, Lebina L, Gómez-Olivé FX, Wafawanaka F, Mathunjwa A, Cohen C.
        BMC Public Health. 2021 Jun 3;21(1):1055.
        BACKGROUND: Describing contact patterns is crucial to understanding infectious disease transmission dynamics and guiding targeted transmission mitigation interventions. Data on contact patterns in Africa, especially South Africa, are limited. We measured and compared contact patterns in a rural and urban community, South Africa. We assessed participant and contact characteristics associated with differences in contact rates. METHODS: We conducted a cross-sectional study nested in a prospective household cohort study. We interviewed participants to collect information on persons in contact with for one day. We described self-reported contact rates as median number people contacted per day, assessed differences in contact rates based on participant characteristics using quantile regression, and used a Poisson model to assess differences in contact rates based on contact characteristics within age groups. We also calculated cumulative person hours in contact within age groups at different locations. RESULTS: We conducted 535 interviews (269 rural, 266 urban), with 17,252 contacts reported. The overall contact rate was 14 (interquartile range (IQR) 9-33) contacts per day. Those ≤18 years had higher contact rates at the rural site (coefficient 17, 95% confidence interval (95%CI) 10-23) compared to the urban site, for those aged 14-18 years (13, 95%CI 3-23) compared to < 7 years. No differences were observed for adults. There was a strong age-based mixing, with age groups interacting more with similar age groups, but also interaction of participants of all ages with adults. Children aged 14-18 years had the highest cumulative person hours in contact (116.3 rural and 76.4 urban). CONCLUSIONS: Age played an important role in the number and duration of contact events, with children at the rural site having almost double the contact rate compared to the urban site. These contact rates can be utilized in mathematical models to assess transmission dynamics of infectious diseases in similar communities.

      25. INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare services worldwide. However, little has been reported regarding the impact on blood utilization. We quantified the impact of COVID-19 on blood utilization and discards among facilities reporting to the National Healthcare Safety Network Hemovigilance Module. METHODS: Facilities continuously reporting data, during January 2016-June 2020, on transfused and discarded blood components, stratified by component type (red blood cells [RBC], platelets and plasma), were included. Interrupted time-series analysis with generalized estimating equations, adjusting for facility surgical volume and seasonality, was used to quantify changes in blood utilization and discards relative to a Centers for Medicare & Medicaid Services notification delaying non-essential medical procedures (March 2020). RESULTS: Seventy-two facilities included in the analyses, on average, transfused 44,548 and discarded 2202 blood components monthly. Following the March 2020 notification and after multivariable adjustment, RBC and platelet utilization declined, -14.8% (p < 0.001) and - 16.6% (p = 0.017) respectively. Discards increased for RBCs (49.0%, p = 0.013) and platelets (60.4%, p = 0.002). No statistically significant change in plasma was found. Following these abrupt changes, blood utilization and discards rebounded towards baseline with RBC use increasing by 5.7% (p < 0.001), and platelet and RBC discards decreasing -16.4% (<0.001) and - 12.7 (p = 0.001), respectively. CONCLUSION: Following notification delaying elective surgical procedures, blood utilization declined substantially while blood discards increased, resulting in substantial wastage of blood products. Ongoing and future pandemic response efforts should consider the impact of interventions on blood supply and demand to ensure blood availability. This article is protected by copyright. All rights reserved.

      26. Using the 2013-2017 National Survey of Family Growth, 37.6% of women with ≥1 anal sex partner in the last 12 months reported chlamydia testing at unspecified anatomic sites in the past 12 months. Women whose medical provider asked about type of sex (i.e., vaginal, oral, anal), compared with those whose provider did not, reported higher chlamydia testing.

      27. COVID-19 Testing to Sustain In-Person Instruction and Extracurricular Activities in High Schools - Utah, November 2020-March 2021external icon
        Lanier WA, Babitz KD, Collingwood A, Graul MF, Dickson S, Cunningham L, Dunn AC, MacKellar D, Hersh AL.
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):785-791.
        Cessation of kindergarten through grade 12 in-person instruction and extracurricular activities, which has often occurred during the COVID-19 pandemic, can have negative social, emotional, and educational consequences for children (1,2). Although preventive measures such as masking, physical distancing, hand hygiene, and improved ventilation are commonly used in schools to reduce transmission of SARS-CoV-2, the virus that causes COVID-19, and support in-person instruction (3-6), routine school-based COVID-19 testing has not been as widely implemented. In addition to these types of standard preventive measures, Utah health and school partners implemented two high school testing programs to sustain extracurricular activities and in-person instruction and help identify SARS-CoV-2 infections: 1) Test to Play,* in which testing every 14 days was mandated for participation in extracurricular activities; and 2) Test to Stay,(†) which involved school-wide testing to continue in-person instruction as an alternative to transitioning to remote instruction if a school crossed a defined outbreak threshold (3). During November 30, 2020-March 20, 2021, among 59,552 students tested through these programs, 1,886 (3.2%) received a positive result. Test to Play was implemented at 127 (66%) of Utah's 193 public high schools and facilitated completion of approximately 95% of scheduled high school extracurricular winter athletics competition events.(§) Test to Stay was conducted at 13 high schools, saving an estimated 109,752 in-person instruction student-days.(¶) School-based COVID-19 testing should be considered as part of a comprehensive prevention strategy to help identify SARS-CoV-2 infections in schools and sustain in-person instruction and extracurricular activities.

      28. COVID-19 Case Investigation and Contact Tracing in the US, 2020external icon
        Lash RR, Moonan PK, Byers BL, Bonacci RA, Bonner KE, Donahue M, Donovan CV, Grome HN, Janssen JM, Magleby R, McLaughlin HP, Miller JS, Pratt CQ, Steinberg J, Varela K, Anschuetz GL, Cieslak PR, Fialkowski V, Fleischauer AT, Goddard C, Johnson SJ, Morris M, Moses J, Newman A, Prinzing L, Sulka AC, Va P, Willis M, Oeltmann JE.
        JAMA Netw Open. 2021 Jun 1;4(6):e2115850.
        IMPORTANCE: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19. OBJECTIVE: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020. MAIN OUTCOMES AND MEASURES: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks. RESULTS: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts.

      29. HIV Viral Load Monitoring Among Patients Receiving Antiretroviral Therapy - Eight Sub-Saharan Africa Countries, 2013-2018external icon
        Lecher SL, Fonjungo P, Ellenberger D, Toure CA, Alemnji G, Bowen N, Basiye F, Beukes A, Carmona S, de Klerk M, Diallo K, Dziuban E, Kiyaga C, Mbah H, Mengistu J, Mots'oane T, Mwangi C, Mwangi JW, Mwasekaga M, N'Tale J, Naluguza M, Ssewanyana I, Stevens W, Zungu I, Bhairavabhotla R, Chun H, Gaffga N, Jadczak S, Lloyd S, Nguyen S, Pati R, Sleeman K, Zeh C, Zhang G, Alexander H.
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):775-778.
        One component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) goal to end the HIV/AIDS epidemic by 2030, is that 95% of all persons receiving antiretroviral therapy (ART) achieve viral suppression.(†) Thus, testing all HIV-positive persons for viral load (number of copies of viral RNA per mL) is a global health priority (1). CDC and other U.S. government agencies, as part of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), together with other stakeholders, have provided technical assistance and supported the cost for multiple countries in sub-Saharan Africa to expand viral load testing as the preferred monitoring strategy for clinical response to ART. The individual and population-level benefits of ART are well understood (2). Persons receiving ART who achieve and sustain an undetectable viral load do not transmit HIV to their sex partners, thereby disrupting onward transmission (2,3). Viral load testing is a cost-effective and sustainable programmatic approach for monitoring treatment success, allowing reduced frequency of health care visits for patients who are virally suppressed (4). Viral load monitoring enables early and accurate detection of treatment failure before immunologic decline. This report describes progress on the scale-up of viral load testing in eight sub-Saharan African countries from 2013 to 2018 and examines the trajectory of improvement with viral load testing scale-up that has paralleled government commitments, sustained technical assistance, and financial resources from international donors. Viral load testing in low- and middle-income countries enables monitoring of viral load suppression at the individual and population level, which is necessary to achieve global epidemic control. Although there has been substantial achievement in improving viral load coverage for all patients receiving ART, continued engagement is needed to reach global targets.

      30. Notes from the Field: Impact of the COVID-19 Response on Scale-Up of HIV Viral Load Testing - PEPFAR-Supported Countries, January-June 2020external icon
        Lecher SL, Naluguza M, Mwangi C, N'Tale J, Edgil D, Alemnji G, Alexander H.
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):794-795.

      31. We assessed STD/HIV service availability at the primary STD safety net clinic by Phase I EHE jurisdiction status. HIV testing was >90%. In EHE jurisdictions, 22% of primary safety net clinics initiated and/or provided PrEP, 46.6% provided PrEP education or referral only and 29.9% did not provide any PrEP services.

      32. Disease intervention specialists (DIS) conduct partner notification for STD and HIV to interrupt the transmission of STD/HIV. In 2016, we collected information from health departments in the United States of America to determine the number of DIS and whether this number was sufficient for STD/HIV prevention. We identified 1610 STD/HIV DIS positions in the USA and 379 DIS supervisory positions. Of DIS positions, 85% were filled indicating potential issues with turnover. Using nationally reportable data from 2016, we found that states with more primary and secondary syphilis cases had more DIS. DIS participated in public health emergencies in 57% of states. Most USA states indicated that the DIS workforce was not sufficient for STD/HIV prevention. Knowledge of information about DIS workload (e.g. number of STD/HIV cases assigned per DIS) would be helpful.

      33. Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Medical Masks with Maintenance of Integrity and Fitexternal icon
        Lendvay TS, Chen J, Harcourt BH, Scholte FE, Lin YL, Kilinc-Balci FS, Lamb MM, Homdayjanakul K, Cui Y, Price A, Heyne B, Sahni J, Kabra KB, Lin YC, Evans D, Mores CN, Page K, Chu LF, Haubruge E, Thiry E, Ludwig-Begall LF, Wielick C, Clark T, Wagner T, Timm E, Gallagher T, Faris P, Macia N, Mackie CJ, Simmons SM, Reader S, Malott R, Hope K, Davies JM, Tritsch SR, Dams L, Nauwynck H, Willaert JF, De Jaeger S, Liao L, Zhao M, Laperre J, Jolois O, Smit SJ, Patel AN, Mayo M, Parker R, Molloy-Simard V, Lemyre JL, Chu S, Conly JM, Chu MC.
        Infect Control Hosp Epidemiol. 2021 May 21:1-83.
        OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 µM MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings.

      34. BACKGROUND: Patterns of human papillomavirus (HPV) prevalence by age differ by sex. To further the descriptive epidemiology of genital HPV, we analyzed prevalence by age for non-vaccine-(non-4vHPV)-type and vaccine-(4vHPV)-type HPV by sex using 2013-2016 National Health and Nutrition Examination Survey data, the first 4 years of national data from both sexes. METHODS: Penile and cervicovaginal swabs were self-collected from 15-59-year-olds and tested for 37 HPV types. 4vHPV-type (6/11/16/18) and non-4vHPV-type (any of 33 other types) prevalences were estimated by 3-year age group and participant characteristics. Average percent changes (APC) in prevalence were estimated using segmented log-binomial regression. RESULTS: Among females, a positive relationship between non-4vHPV-type prevalence and age was seen from 15-17 to 21-23 years (APC: 56.5), followed by a negative relationship through 30-32 years (APC: -13.2); thereafter, prevalence was not related to age. 4vHPV-type prevalence was positively related to age through 24-26 years (APC: 56.9), then negatively related through 57-59 years (APC: -6.0). Among males, non-4vHPV-type prevalence had a positive relationship with age through 21-23 years (APC: 102.4) with a smaller positive relationship through 57-59 years (APC: 1.4). For both sexes, modeled joinpoints for 4vHPV-type prevalence occurred at older ages compared to joinpoints for non-4vHPV-type prevalence. CONCLUSIONS: Sex differences in age-specific non-vaccine-type HPV prevalence may reflect natural history and sexual behavior. Differences in vaccine-type and non-vaccine-type modeling results suggest vaccine impact as joinpoints occur in mid-late-20s for vaccine-type HPV but early-20s for non-vaccine-types. These data can assist in refining HPV vaccination models and inform HPV vaccination practices and policy.

      35. Evaluating the Presence of Replication-Competent SARS-CoV-2 from Nursing Home Residents with Persistently Positive RT-PCR Resultsexternal icon
        Lutgring JD, Tobolowsky FA, Hatfield KM, Lehnertz NB, Sullivan MM, Martin KG, Keaton A, Sexton DJ, Tamin A, Harcourt JL, Thornburg NJ, Reddy SC, Jernigan JA.
        Clin Infect Dis. 2021 May 14.
        Replication-competent virus has not been detected in individuals with mild to moderate COVID-19 more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

      36. COVID-19 Infection, Reinfection, and Vaccine Effectiveness in a Prospective Cohort of Arizona Frontline/Essential Workers: The AZ HEROES Research Protocolexternal icon
        Lutrick K, Ellingson KD, Baccam Z, Rivers P, Beitel S, Parker J, Hollister J, Sun X, Gerald JK, Komatsu K, Kim E, LaFleur B, Grant L, Yoo YM, Kumar A, Mayo Lamberte J, Cowling BJ, Cobey S, Thornburg NJ, Meece JK, Kutty P, Nikolich-Zugich J, Thompson MG, Burgess JL.
        JMIR Res Protoc. 2021 May 26.
        BACKGROUND: The Arizona Healthcare, Emergency Response, and Other Essential workers Study (AZ HEROES) aims to examine the epidemiology of SARS-CoV-2 infection and COVID-19 illness among adults with high occupational exposure risk. OBJECTIVE: Study objectives include estimating incidence of SARS-CoV-2 infection in essential workers by symptom presentation and demographic factors, determining independent effects of occupational and community exposures on incidence of SARS-CoV-2 infection, establishing molecular and immunologic characteristics of SARS-CoV-2 infection in essential workers, describing the duration and patterns of rRT-PCR-positivity, and examining post-vaccine immunologic response. METHODS: Eligible participants include Arizona residents aged 18-85 years who work at least 20 hours per week in an occupation involving regular direct contact (within three feet) with others. Recruitment goals are stratified by demographic characteristics (50% aged 40 or older, 50% women, and 50% Hispanic or American Indian), by occupation (40% healthcare personnel, 30% first responders, and 30% other essential workers), and by prior SARS-CoV-2 infection (with up to 50% seropositive at baseline). Information on sociodemographics, health and medical history, vaccination status, exposures to individuals with suspected or confirmed SARS-CoV-2 infection, use of personal protective equipment, and perceived risks are collected at enrollment and updated through quarterly surveys. Every week, participants complete active surveillance for COVID-19-like illness (CLI) and self-collect nasal swabs. Additional self-collected nasal swab and saliva specimens are collected in the event of CLI onset. Respiratory specimens are sent to Marshfield Laboratories and tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR) assay. CLI symptoms and impact on work and productivity are followed through illness resolution. Serum specimens are collected every 3 months and additional sera are collected following incident rRT-PCR positivity and after each COVID-19 vaccine dose. Incidence of SARS-CoV-2 infections will be calculated by person-weeks at risk and compared by occupation and demographic characteristics and by seropositivity status and infection and vaccination history. RESULTS: The AZ HEROES study was funded by the Centers for Disease Control and Prevention. Enrollment began July 27, 2020 and as of May 1, 2021 a total of 3,165 participants have been enrolled in the study. CONCLUSIONS: AZ HEROES is unique in aiming to recruit a diverse sample of essential workers and prospectively following strata of SARS-CoV-2 seronegative and seropositive adults. Survey results combined with active surveillance data on exposure, CLI, weekly molecular diagnostic testing, and periodic serology will be used to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, assess the intensity and durability of immune responses to natural infection and COVID-19 vaccination, and contribute to the evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/28925.

      37. Insti-based initial antiretroviral therapy in adults with HIV, The HIV Outpatient Study, 2007-2018external icon
        Mayer S, Rayeed N, Novak RM, Li J, Palella FJ, Buchacz K.
        AIDS Res Hum Retroviruses. 2021 May 25.
        BACKGROUND: We evaluated treatment duration and viral suppression (VS) outcomes with integrase strand transfer inhibitor (INSTI)-based regimens versus other contemporary regimens among adults in routine HIV care. METHODS: Eligible participants were seen during January 1, 2007 to June 30, 2018 at nine U.S. HIV clinics, initiated antiretroviral therapy (ART) (baseline date), and had ≥2 clinic visits thereafter. We assessed the probability of remaining on a regimen and achieving HIV RNA < 200 copies/mL on initial INSTI versus non-INSTI ART by Kaplan-Meier analyses and their correlates by Cox regression. RESULTS: Among 1005 patients, 335 (33.3%) were prescribed an INSTI-containing regimen and 670 (66.7%) a non-INSTI regimen, which may have included non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other agents. In both groups, most patients were male, non-white, and aged <50 years. Comparing the INSTI with non-INSTI group, the median baseline log10 HIV viral load (copies/mL) was 4.6 vs. 4.5 and the median CD4+ cell count (cells/mm3) was 352 vs. 314. In Kaplan-Meier analysis, the estimated probabilities of remaining on initial regimens at 2 and 4 years were 58% and 40% for INSTI and 51% and 33% for non-INSTI group, respectively (log-rank test p = 0.003. In multivariable models, treatment with an INSTI (vs. non-INSTI) ART was negatively associated with a regimen switch (Hazard Ratio [HR], 0.67, 95% Confidence Interval [CI] 0.56, 0.81, p < 0.001), and was positively associated with achieving viral suppression (HR 1.52; CI 1.29, 1.79, p < 0.001), both irrespective of baseline viral load levels. CONCLUSIONS: Initial INSTI-based regimens were associated with longer durations and better viral suppression than non-INSTI regimens. Results support INSTI regimens as the initial therapy in U.S. treatment guidelines.

      38. Seroprevalence of SARS-CoV-2 antibodies in Seattle, Washington: October 2019-April 2020external icon
        McCulloch DJ, Jackson ML, Hughes JP, Lester S, Mills L, Freeman B, Rasheed MA, Thornburg NJ, Chu HY.
        PLoS One. 2021 ;16(5):e0252235.
        BACKGROUND: The first US case of SARS-CoV-2 infection was detected on January 20, 2020. However, some serology studies suggest SARS-CoV-2 may have been present in the United States prior to that, as early as December 2019. The extent of domestic COVID-19 detection prior to 2020 has not been well-characterized. OBJECTIVES: To estimate the prevalence of SARS-CoV-2 antibody among healthcare users in the greater Seattle, Washington area from October 2019 through early April 2020. STUDY DESIGN: We tested residual samples from 766 Seattle-area adults for SARS-CoV-2 antibodies utilizing an ELISA against prefusion-stabilized Spike (S) protein. RESULTS: No antibody-positive samples were found between October 2, 2019 and March 13, 2020. Prevalence rose to 1.2% in late March and early April 2020. CONCLUSIONS: The absence of SARS-CoV-2 antibody-positive samples in October 2019 through mid-March, 2020, provides evidence against widespread circulation of COVID-19 among healthcare users in the Seattle area during that time. A small proportion of this metropolitan-area cohort had been infected with SARS-CoV-2 by spring of 2020.

      39. Disease surveillance for the COVID-19 era: time for bold changesexternal icon
        Morgan OW, Aguilera X, Ammon A, Amuasi J, Fall IS, Frieden T, Heymann D, Ihekweazu C, Jeong EK, Leung GM, Mahon B, Nkengasong J, Qamar FN, Schuchat A, Wieler LH, Dowell SF.
        Lancet. 2021 May 14.

      40. Opportunistic Illnesses in Children With HIV Infection in the United States, 1997-2016external icon
        Nesheim SR, Balaji A, Hu X, Lampe M, Dominguez KL.
        Pediatr Infect Dis J. 2021 Apr 21.
        BACKGROUND: Among children with HIV infection, opportunistic illness (OI) rates decreased after introduction of highly active antiretroviral therapy (ART) in 1997. We evaluated whether such decreases have continued. METHODS: Data from the Centers for Disease Control and Prevention's National HIV Surveillance System for children with HIV living in the US during 1997-2016 was used to enumerate infants experiencing the first OI by birth year and OIs among all children <13 years of age (stratified by natality). We calculated the time to first OI among infants using Kaplan-Meier methods. RESULTS: Among infants born during 1997-2016, 711 first OIs were diagnosed. The percentage of the first OIs diagnosed in successive 5-year birth periods was: 60.0% (1997-2001), 24.6% (2002-2006), 11.3% (2007-2011), and 3.4% (2012-2016). For every OI, the number of first cases decreased nearly annually. Time to first OI increased in successive birth periods. Among children <13 years of age, 2083 OI were diagnosed, including Pneumocystis jiroveci pneumonia, candidiasis, recurrent bacterial infection, wasting syndrome, cytomegalovirus, lymphocytic interstitial pneumonitis, tuberculosis, nontuberculous mycobacteriosis and herpes simplex virus. The rate (#/1000 person-years) decreased overall (60-7.2) and for all individual OIs. Earlier during 1997-2016, rates for all OIs were higher among foreign-born than US-born children but later became similar for all OIs except tuberculosis. CONCLUSIONS: Among children with HIV in the US, numbers and rates of all OIs decreased during 1997-2016. Earlier, OI rates were highest among non-US-born children but were later comparable to those among US-born children for all OIs except tuberculosis.

      41. Epidemiologic Findings from Case Investigations and Contact Tracing for First 200 Cases of Coronavirus Disease, Santa Clara County, California, USAexternal icon
        Ortiz N, Villarino E, Lee JT, Bajema KL, Ricaldi JN, Smith S, Lin W, Cortese M, Barskey AE, Da Silva JF, Bonin BJ, Rudman S, Han GS, Fischer M, Chai SJ, Cody SH.
        Emerg Infect Dis. 2021 May;27(5):1301-1308.
        In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic [86%] and Filipino [100%]); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control.

      42. The CDC HIV Outbreak Coordination Unit: Developing a Standardized, Collaborative Approach to HIV Outbreak Assessment and Responseexternal icon
        Oster AM, France AM, McClung RP, Buchacz K, Lyss SB, Peters PJ, Weidle PJ, Switzer WM, Phillip SA, Brooks JT, Hernandez AL.
        Public Health Rep. 2021 May 28:333549211018678.
        The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017-December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative.

      43. Coronavirus Disease 2019 (COVID-19) in Americans Aboard the Diamond Princess Cruise Shipexternal icon
        Plucinski MM, Wallace M, Uehara A, Kurbatova EV, Tobolowsky FA, Schneider ZD, Ishizumi A, Bozio CH, Kobayashi M, Toda M, Stewart A, Wagner RL, Moriarty LF, Murray R, Queen K, Tao Y, Paden C, Mauldin MR, Zhang J, Li Y, Elkins CA, Lu X, Herzig CT, Novak R, Bower W, Medley AM, Acosta AM, Knust B, Cantey PT, Pesik NT, Halsey ES, Cetron MS, Tong S, Marston BJ, Friedman CR.
        Clin Infect Dis. 2021 May 18;72(10):e448-e457.
        BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.

      44. Using video-analysis technology to estimate social mixing and simulate influenza transmission at a mass gatheringexternal icon
        Rainey JJ, Koch DB, Chen YH, Yuan J, Cheriyadat A.
        Epidemics. 2021 May 12;36:100466.
        Mass gatherings create settings conducive to infectious disease transmission. Empirical data to model infectious disease transmission at mass gatherings are limited. Video-analysis technology could be used to generate data on social mixing patterns needed for simulating influenza transmission at mass gatherings. We analyzed short video recordings of persons attending the GameFest event at a university in Troy, New York, in April 2013 to demonstrate the feasibility of this approach. Attendees were identified and tracked during three randomly selected time periods using an object-tracking algorithm. Tracks were analyzed to calculate the number and duration of unique pairwise contacts. A contact occurred each time two attendees were within 2 m of each other. We built and tested an agent-based stochastic influenza simulation model assuming two scenarios of mixing patterns in a geospatially accurate representation of the event venue -one calibrated to the mean cumulative contact duration estimated from GameFest video recordings and the other using a uniform mixing pattern. We compared one-hour attack rates (i.e., becoming infected) generated from these two scenarios following the introduction of a single infectious seed. Across the video recordings, 278 attendees were identified and tracked, resulting in 1,247 unique pairwise contacts with a cumulative mean contact duration of 74.76 s (SD: 80.71). The one-hour simulated mean attack rates were 2.17 % (95 % CI:1.45 - 2.82) and 0.21 % (95 % CI: 0.14 - 0.28) in the calibrated and uniform mixing model scenarios, respectively. We simulated influenza transmission at the GameFest event using social mixing data objectively captured through video-analysis technology. Microlevel geospatially accurate simulations can be used to assess the layout of event venues on social mixing and disease transmission. Future work can expand on this demonstration project to larger spatial and temporal scenes in more diverse settings.

      45. Changing Molecular Epidemiology of Hepatitis A Virus Infection, United States, 1996-2019external icon
        Ramachandran S, Xia GL, Dimitrova Z, Lin Y, Montgomery M, Augustine R, Kamili S, Khudyakov Y.
        Emerg Infect Dis. 2021 Jun;27(6):1742-1745.
        Hepatitis A virus (HAV) genotype IA was most common among strains tested in US outbreak investigations and surveillance during 1996-2015. However, HAV genotype IB gained prominence during 2016-2019 person-to-person multistate outbreaks. Detection of previously uncommon strains highlights the changing molecular epidemiology of HAV infection in the United States.

      46. Multifaceted Public Health Response to a COVID-19 Outbreak Among Meat-Processing Workers, Utah, March-June 2020external icon
        Rogers TM, Robinson SJ, Reynolds LE, Ladva CN, Burgos-Garay M, Whiteman A, Budge H, Soto N, Thompson M, Hunt E, Barson T, Boyd AT.
        J Public Health Manag Pract. 2021 Jun 1.
        OBJECTIVE: To identify potential strategies to mitigate COVID-19 transmission in a Utah meat-processing facility and surrounding community. DESIGN/SETTING: During March-June 2020, 502 workers at a Utah meat-processing facility (facility A) tested positive for SARS-CoV-2. Using merged data from the state disease surveillance system and facility A, we analyzed the relationship between SARS-CoV-2 positivity and worker demographics, work section, and geospatial data on worker residence. We analyzed worker survey responses to questions regarding COVID-19 knowledge, beliefs, and behaviors at work and home. PARTICIPANTS: (1) Facility A workers (n = 1373) with specimen collection dates and SARS-CoV-2 RT-PCR test results; (2) residential addresses of all persons (workers and nonworkers) with a SARS-CoV-2 diagnostic test (n = 1036), living within the 3 counties included in the health department catchment area; and (3) facility A workers (n = 64) who agreed to participate in the knowledge, attitudes, and practices survey. MAIN OUTCOME MEASURES: New cases over time, COVID-19 attack rates, worker characteristics by SARS-CoV-2 test results, geospatially clustered cases, space-time proximity of cases among workers and nonworkers; frequency of quantitative responses, crude prevalence ratios, and counts and frequency of coded responses to open-ended questions from the COVID-19 knowledge, attitudes, and practices survey. RESULTS: Statistically significant differences in race (P = .01), linguistic group (P < .001), and work section (P < .001) were found between workers with positive and negative SARS-CoV-2 test results. Geographically, only 6% of cases were within statistically significant spatiotemporal case clusters. Workers reported using handwashing (57%) and social distancing (21%) as mitigation strategies outside work but reported apprehension with taking COVID-19-associated sick leave. CONCLUSIONS: Mitigating COVID-19 outbreaks among workers in congregate settings requires a multifaceted public health response that is tailored to the workforce. IMPLICATIONS FOR POLICY AND PRACTICE: Tailored, multifaceted mitigation strategies are crucial for reducing COVID-19-associated health disparities among disproportionately affected populations.

      47. Distribution and Clonality of drug-resistant tuberculosis in South Africaexternal icon
        Said H, Ratabane J, Erasmus L, Gardee Y, Omar S, Dreyer A, Ismail F, Bhyat Z, Lebaka T, van der Meulen M, Gwala T, Adelekan A, Diallo K, Ismail N.
        BMC Microbiol. 2021 May 28;21(1):157.
        BACKGROUND: Studies have shown that drug-resistant tuberculosis (DR-TB) in South Africa (SA) is clonal and is caused mostly by transmission. Identifying transmission chains is important in controlling DR-TB. This study reports on the sentinel molecular surveillance data of Rifampicin-Resistant (RR) TB in SA, aiming to describe the RR-TB strain population and the estimated transmission of RR-TB cases. METHOD: RR-TB isolates collected between 2014 and 2018 from eight provinces were genotyped using combination of spoligotyping and 24-loci mycobacterial interspersed repetitive-units-variable-number tandem repeats (MIRU-VNTR) typing. RESULTS: Of the 3007 isolates genotyped, 301 clusters were identified. Cluster size ranged between 2 and 270 cases. Most of the clusters (247/301; 82.0%) were small in size (< 5 cases), 12.0% (37/301) were medium sized (5-10 cases), 3.3% (10/301) were large (11-25 cases) and 2.3% (7/301) were very large with 26-270 cases. The Beijing genotype was responsible for majority of RR-TB cases in Western and Eastern Cape, while the East-African-Indian-Somalian (EAI1_SOM) genotype accounted for a third of RR-TB cases in Mpumalanga. The overall proportion of RR-TB cases estimated to be due to transmission was 42%, with the highest transmission-rate in Western Cape (64%) and the lowest in Northern Cape (9%). CONCLUSION: Large clusters contribute to the burden of RR-TB in specific geographic areas such as Western Cape, Eastern Cape and Mpumalanga, highlighting the need for community-wide interventions. Most of the clusters identified in the study were small, suggesting close contact transmission events, emphasizing the importance of contact investigations and infection control as the primary interventions in SA.

      48. Proposal for Human Respiratory Syncytial Virus Nomenclature below the Species Levelexternal icon
        Salimi V, Viegas M, Trento A, Agoti CN, Anderson LJ, Avadhanula V, Bahl J, Bont L, Brister JR, Cane PA, Galiano M, Graham BS, Hatcher EL, Hellferscee O, Henke DM, Hirve S, Jackson S, Keyaerts E, Kragten-Tabatabaie L, Lindstrom S, Nauwelaers I, Nokes DJ, Openshaw PJ, Peret TC, Piedra PA, Ramaekers K, Rector A, Trovão NS, von Gottberg A, Zambon M, Zhang W, Williams TC, Barr IG, Buchholz UJ.
        Emerg Infect Dis. 2021 Jun;27(6):1-9.
        Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory disease, and lifelong reinfections are common. Its 2 major subgroups, A and B, exhibit some antigenic variability, enabling HRSV to circulate annually. Globally, research has increased the number of HRSV genomic sequences available. To ensure accurate molecular epidemiology analyses, we propose a uniform nomenclature for HRSV-positive samples and isolates, and HRSV sequences, namely: HRSV/subgroup identifier/geographic identifier/unique sequence identifier/year of sampling. We also propose a template for submitting associated metadata. Universal nomenclature would help researchers retrieve and analyze sequence data to better understand the evolution of this virus.

      49. Reduced sensitivity of SARS-CoV-2 PCR testing with single-nostril nasal swabsexternal icon
        Salvatore PP, Bhattacharyya S, Christensen K, Tate JE, Kirking HL.
        J Clin Virol. 2021 May 9;140:104852.

      50. Proposed Framework for Considering SARS-CoV-2 Antigen Testing of Unexposed Asymptomatic Workers in Selected Workplacesexternal icon
        Schulte PA, Piacentino JD, Weissman DN, de Perio MA, Chiu SK, Radonovich LJ, Trout D, Beezhold D, Hearl FJ, Howard J.
        J Occup Environ Med. 2021 May 19.
        OBJECTIVES: To propose a framework for considering SARS-CoV-2 antigen testing of unexposed asymptomatic workers in selected workplaces. METHODS: This is a commentary based on established occupational safety and health principles, published articles, and other pertinent literature, including non-peer-reviewed preprints in prior to April 16, 2021. RESULTS: Not applicable to this commentary/viewpoint article. CONCLUSION: Antigen testing is a rapidly evolving and useful public health tool that can be used to guide measures to reduce spread of SARS-CoV-2 in the community and in selected workplaces. This commentary provides a proposed framework for occupational safety and health practitioners and employers for considering antigen testing as a method to screen asymptomatic workers in selected non-healthcare settings. When applied selectively, antigen testing can be a useful, effective part of a comprehensive workplace program for COVID-19 prevention and control.

      51. Recent Trends in the Epidemiology of Fungal Infectionsexternal icon
        Seagle EE, Williams SL, Chiller TM.
        Infect Dis Clin North Am. 2021 Jun;35(2):237-260.
        The breadth of fungi causing human disease and the spectrum of clinical presentations associated with these infections has widened. Epidemiologic trends display dramatic shifts with expanding geographic ranges, identification of new at-risk groups, increasing prevalence of resistant infections, and emergence of novel multidrug-resistant pathogenic fungi. Certain fungi have been transmitted between patients in clinical settings. Major health events not typically associated with mycoses resulted in larger proportions of the population susceptible to secondary fungal infections. Many health care-related, environmental, and socioeconomic factors have influenced these epidemiologic shifts. This review summarizes updates to clinically significant fungal pathogens in North America.

      52. Risk Factors for TB/HIV Coinfection and Consequences for Patient Outcomes: Evidence from 241 Clinics in the Democratic Republic of Congoexternal icon
        Shah GH, Ewetola R, Etheredge G, Maluantesa L, Waterfield K, Engetele E, Kilundu A.
        Int J Environ Res Public Health. 2021 May 13;18(10).
        (1) Background: In resource-limited countries, patients with tuberculosis (TB)/HIV coinfection commonly face economic, sociocultural, and behavioral barriers to effective treatment. These barriers manifest from low treatment literacy, poverty, gender inequality, malnutrition, societal stigmas regarding HIV, and an absence of available care. It is critical for intervention programs to understand and assist in overcoming these barriers and any additional risks encountered by patients with TB/HIV coinfection. This study analyzes variation in TB/HIV coinfection and risks of negative outcomes among patients with TB/HIV coinfection compared to those without coinfection. (2) Methods: This quantitative study used data from 49,460 patients receiving ART from 241 HIV/AIDS clinics in Haut-Katanga and Kinshasa, two provinces in the Democratic Republic of Congo. Chi-square and logistic regression analysis were performed. (3) Results: Significantly higher proportions of patients with TB/HIV coinfection were men (4.5%; women, 3.3%), were new patients (3.7%; transferred-in, 1.6%), resided in the Kinshasa province (4.0%; Haut-Katanga, 2.7%), and were in an urban health zone (3.9%) or semi-rural health zone (3.1%; rural, 1.2%). Logistic regression analysis showed that after controlling for demographic and clinical variables, TB/HIV coinfection increased the risk of death (adjusted odds ratio (AOR), 2.26 (95% confidence interval (CI): 1.94-2.64)) and LTFU (AOR, 2.06 (95% CI: 1.82-2.34)). TB/HIV coinfection decreased the odds of viral load suppression (AOR, 0.58 (95% CI: 0.46-0.74)). (4) Conclusions: TB/HIV coinfection raises the risk of negative outcomes such as death, LTFU, and lack of viral load suppression. Our findings can help HIV clinics in Democratic Republic of Congo and other African countries to customize their interventions to improve HIV care and reduce care disparities among patients.

      53. Comparing the ecological niches of chlamydial and gonococcal infections in Winnipeg, Canada: 2007-2016external icon
        Shaw SY, Elliott LJ, Nowicki DL, Green C, Ross CP, Reimer JN, Wylie JL, Plourde PJ, Aral SO, Becker ML, Blanchard JF.
        Sex Transm Dis. 2021 Apr 23.
        BACKGROUND: Previous studies have shown substantial differences in geographic clustering of sexually transmitted infections (STI), such as chlamydia (CT) and gonorrhea (NG), conditional on epidemic phase. CT and NG have recently shown resurgent epidemiology in the northern hemisphere. This study describes the recent epidemiology of CT and NG in Winnipeg, Canada, combining traditional surveillance tools with place-based analyses, and comparing the ecological niches of CT and NG, in the context of their evolving epidemiology. METHODS: Data were collected as part of routine public health surveillance between 2007 and 2016. Secular trends for CT and NG, and CT/NG co-infection were examined. Gini coefficients and population attributable fractions explored the distribution, and concentration of infections over time and space. RESULTS: Rates of CT increased from 394.9/100,000 population to 476.2/100,000 population from 2007 to 2016. NG rates increased from 78.0/100,000 population to 143.5/100,000 population during the same time period. Each pathogen had its own ecological niche: CT was widespread geographically and socio-demographically, while NG was clustered in Winnipeg's inner-core. CT/NG co-infections had the narrowest space and age distribution. NG was shown to be undergoing a growth phase, with clear signs of geographic dispersion. The expansion of NG resembled the geographic distribution of CT. CONCLUSIONS: We demonstrated that NG was experiencing a growth phase, confirming theoretical predictions of geographic dispersion during a growth phase. During this phase, NG occupied similar geographic spaces as CT. Knowledge of different ecological niches could lead to better targeting of resources for sub-populations vulnerable to STIs.

      54. Granulomatous Dermatitis Associated With Rubella Virus Infection in an Adult With Immunodeficiencyexternal icon
        Shields BE, Perelygina L, Samimi S, Haun P, Leung T, Abernathy E, Chen MH, Hao L, Icenogle J, Drolet B, Wilson B, Bryer JS, England R, Blumberg E, Wanat KA, Sullivan K, Rosenbach M.
        JAMA Dermatol. 2021 May 26.
        IMPORTANCE: Immunodeficiency-related, vaccine-derived rubella virus (RuV) as an antigenic trigger of cutaneous and visceral granulomas is a rare, recently described phenomenon in children and young adults treated with immunosuppressant agents. OBJECTIVE: To perform a comprehensive clinical, histologic, immunologic, molecular, and genomic evaluation to elucidate the potential cause of an adult patient's atypical cutaneous granulomas. DESIGN, SETTING, AND PARTICIPANTS: A prospective evaluation of skin biopsies, nasopharyngeal swabs, and serum samples submitted to the Centers for Disease Control and Prevention was conducted to assess for RuV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and viral genomic sequencing. The samples were obtained from a man in his 70s with extensive cutaneous granulomas mimicking both cutaneous sarcoidosis (clinically) and CD8+ granulomatous cutaneous T-cell lymphoma (histopathologically). The study was conducted from September 2019 to February 2021. MAIN OUTCOMES AND MEASURES: Identification and genotyping of a novel immunodeficiency-related RuV-associated granulomatous dermatitis. RESULTS: Immunohistochemistry for RuV capsid protein and RT-PCR testing for RuV RNA revealed RuV in 4 discrete skin biopsies from different body sites. In addition, RuV RNA was detected in the patient's nasopharyngeal swabs by RT-PCR. The full viral genome was sequenced from the patient's skin biopsy (RVs/Philadelphia.PA.USA/46.19/GR, GenBank Accession #MT249313). The patient was ultimately diagnosed with a novel RuV-associated granulomatous dermatitis. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that clinicians and pathologists may consider RuV-associated granulomatous dermatitis during evaluation of a patient because it might have implications for the diagnosis of cutaneous sarcoidosis, with RuV serving as a potential antigenic trigger, and for the diagnosis of granulomatous cutaneous T-cell lymphoma, with histopathologic features that may prompt an evaluation for immunodeficiency and/or RuV.

      55. Impact of Policy and Funding Decisions on COVID-19 Surveillance Operations and Case Reports - South Sudan, April 2020-February 2021external icon
        Shragai T, Summers A, Olushayo O, Rumunu J, Mize V, Laku R, Bunga S.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 4;70(22):811-817.
        Early models predicted substantial COVID-19-associated morbidity and mortality across Africa (1-3). However, as of March 2021, countries in Africa are among those with the lowest reported incidence of COVID-19 worldwide (4). Whether this reflects effective mitigation, outbreak response, or demographic characteristics, (5) or indicates limitations in disease surveillance capacity is unclear (6). As countries implemented changes in funding, national policies, and testing strategies in response to the COVID-19 pandemic, surveillance capacity might have been adversely affected. This study assessed whether changes in surveillance operations affected reporting in South Sudan; testing and case numbers reported during April 6, 2020-February 21, 2021, were analyzed relative to the timing of funding, policy, and strategy changes.* South Sudan, with a population of approximately 11 million, began COVID-19 surveillance in February 2020 and reported 6,931 cases through February 21, 2021. Surveillance data analyzed were from point of entry screening, testing of symptomatic persons who contacted an alert hotline, contact tracing, sentinel surveillance, and outbound travel screening. After travel restrictions were relaxed in early May 2020, international land and air travel resumed and mandatory requirements for negative pretravel test results were initiated. The percentage of all testing accounted for by travel screening increased >300%, from 21.1% to 91.0% during the analysis period, despite yielding the lowest percentage of positive tests among all sources. Although testing of symptomatic persons and contact tracing yielded the highest percentage of COVID-19 cases, the percentage of all testing from these sources decreased 88%, from 52.6% to 6.3% after support for these activities was reduced. Collectively, testing increased over the project period, but shifted toward sources least likely to yield positive results, possibly resulting in underreporting of cases. Policy, funding, and strategy decisions related to the COVID-19 pandemic response, such as those implemented in South Sudan, are important issues to consider when interpreting the epidemiology of COVID-19 outbreaks.

      56. Experiences and Views of Domestic Summer Travelers During the COVID-19 Pandemic: Findings from a National Surveyexternal icon
        SteelFisher GK, McMurtry CL, Caporello HL, McGowan E, Schafer TJ, Lubell KM, Friedman AL, Allen J, Shockey C, Grady A, Ben-Porath EN.
        Health Secur. 2021 May 24.
        Domestic travel creates a serious risk of spreading COVID-19, including novel strains of the virus. Motivating potential travelers to take precautions is critical, especially for those at higher risk for severe illness. To provide an evidence base for communication efforts, we examined the experiences and views of travelers during the summer of 2020 through a telephone survey of 1,968 US adults, conducted in English and Spanish, July 2 through July 16, 2020. The survey found that more than one-quarter (28%) of adults had traveled domestically in the prior 30 days, most commonly for "vacation" (43%), and less than half wore masks (46%) or practiced social distancing (47%) "all of the time." Although high-risk adults were significantly less likely to travel than non-high-risk adults (23% vs 31%; P < .001), they were no more likely to take precautions. Many travelers did not wear a mask or practice social distancing because they felt such actions were unnecessary (eg, they were outside or with friends and family). Although a substantial share of travelers (43% to 53%) trusted public health agencies "a great deal" for information about reducing risks while traveling, more travelers (73%) trusted their own healthcare providers. Findings suggest that outreach may be improved by partnering with providers to emphasize the benefits of layering precautions and provide targeted education to high-risk individuals. Messages that are empathetic to the need to reduce stress and convey how precautions can protect loved ones may be particularly resonant after more than a year of pandemic-related restrictions.

      57. Coronavirus disease 2019 (COVID-19) Versus Influenza in Hospitalized Adult Patients in the United States: Differences in Demographic and Severity Indicatorsexternal icon
        Talbot HK, Martin ET, Gaglani M, Middleton DB, Ghamande S, Silveira FP, Murthy K, Zimmerman RK, Trabue CH, Olson SM, Petrie JG, Ferdinands JM, Patel MM, Monto AS.
        Clin Infect Dis. 2021 May 29.
        BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. METHODS: Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016-2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. RESULTS: Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). CONCLUSIONS: While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths.

      58. Approximately 90% of tuberculosis (TB) cases among non-US-born persons in the United States are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated whether birthplace is associated with time to disease progression among non-US-born persons in whom TB disease developed. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 birth regions, adjusting for sex, birth year, and age at entry. After adjusting for age at entry and birth year, the median time to TB diagnosis was lowest among persons from Middle Africa, 128 months (95% CI 116-146 months) for male persons and 121 months (95% CI 108-136 months) for female persons. We found time to TB diagnosis among non-US-born persons varied by birth region, which represents a prognostic indicator for progression of latent TB infection to TB disease.

      59. BACKGROUND: Estimates in the research literature on the health-related quality of life (QOL) associated with pneumococcal disease exhibit variation. It complicates the selection of estimates in modeling projects that evaluate the health impact and economic value of the prevention and treatment. This study reviewed the literature and developed pooled QOL estimates associated with pneumococcal disease states. METHODS: We searched peer-reviewed literature for studies that reported pneumococcal disease-related QOL estimates. For each study, we extracted QOL estimates and categorized by age group and disease state. QOL estimates were converted to quality-adjusted life-years (QALYs). Pooled QALY estimates were calculated using simple average, sample-size weighting and inverse-variance weighting. RESULTS: From 18 studies, we organized QOL estimates into 20 groups based on age and disease state. We observed the largest within-disease state variations of QALY estimates in meningitis-related disease states compared to other disease states. Across all age-disease state categories, the pooled QALY estimates ranged from 0.39 for meningitis with long-term sequelae among 0- to 18-year-olds, to 1.00 for non-inpatient pneumonia among 0- to 18-year-olds. CONCLUSIONS: Our results indicated disparities in QOL estimates associated with pneumococcal disease from the literature. Pooled estimates provided a source of consistency that can be used in future modeling efforts.

      60. Outcomes of Reflex Cryptococcal Antigen (CrAg) Screening in Human Immunodeficiency Virus (HIV)-Positive Patients With CD4 Counts of 100-200 Cells/µL in Botswanaexternal icon
        Tenforde MW, Milton T, Rulaganyang I, Muthoga C, Tawe L, Chiller T, Greene G, Jordan A, Williams CG, Owen L, Leeme TB, Boose A, Ngidi J, Mine M, Jarvis JN.
        Clin Infect Dis. 2021 May 4;72(9):1635-1638.
        Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101-200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101-200 cells/µL.

      61. Influenza Activity in the US During the 2020-2021 Seasonexternal icon
        Uyeki TM, Wentworth DE, Jernigan DB.
        Jama. 2021 May 24.

      62. Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Virusesexternal icon
        Wang L, Fan X, Bonenfant G, Cui D, Hossain J, Jiang N, Larson G, Currier M, Liddell J, Wilson M, Tamin A, Harcourt J, Ciomperlik-Patton J, Pang H, Dybdahl-Sissoko N, Campagnoli R, Shi PY, Barnes J, Thornburg NJ, Wentworth DE, Zhou B.
        Emerg Infect Dis. 2021 May;27(5):1380-1392.
        Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.

      63. HIV drug resistance among adults initiating antiretroviral therapy in Ugandaexternal icon
        Watera C, Ssemwanga D, Namayanja G, Asio J, Lutalo T, Namale A, Sanyu G, Ssewanyana I, Gonzalez-Salazar JF, Nazziwa J, Nanyonjo M, Raizes E, Kabuga U, Mwangi C, Kirungi W, Musinguzi J, Mugagga K, Mbidde EK, Kaleebu P.
        J Antimicrob Chemother. 2021 May 15.
        BACKGROUND: WHO revised their HIV drug resistance (HIVDR) monitoring strategy in 2014, enabling countries to generate nationally representative HIVDR prevalence estimates from surveys conducted using this methodology. In 2016, we adopted this strategy in Uganda and conducted an HIVDR survey among adults initiating or reinitiating ART. METHODS: A cross-sectional survey of adults aged ≥18 years initiating or reinitiating ART was conducted at 23 sites using a two-stage cluster design sampling method. Participants provided written informed consent prior to enrolment. Whole blood collected in EDTA vacutainer tubes was used for preparation of dried blood spot (DBS) specimens or plasma. Samples were shipped from the sites to the Central Public Health Laboratory (CPHL) for temporary storage before transfer to the Uganda Virus Research Institute (UVRI) for genotyping. Prevalence of HIVDR among adults initiating or reinitiating ART was determined. RESULTS: Specimens from 491 participants (median age 32 years and 61.5% female) were collected between August and December 2016. Specimens from 351 participants were successfully genotyped. Forty-nine had drug resistance mutations, yielding an overall weighted HIVDR prevalence of 18.2% with the highest noted for NNRTIs at 14.1%. CONCLUSIONS: We observed a high HIVDR prevalence for NNRTIs among adults prior to initiating or reinitiating ART in Uganda. This is above WHO's recommended threshold of 10% when countries should consider changing from NNRTI- to dolutegravir-based first-line regimens. This recommendation was adopted in the revised Ugandan ART guidelines. Dolutegravir-containing ART regimens are preferred for first- and second-line ART regimens.

      64. Changes in the Number of Intensive Care Unit Beds in U.S. Hospitals During the Early Months of the COVID-19 Pandemic, as reported to the National Healthcare Safety Network's COVID-19 Moduleexternal icon
        Weiner-Lastinger LM, Dudeck MA, Allen-Bridson K, Dantes R, Gross C, Nkwata A, Tejedor SC, Pollock D, Benin A.
        Infect Control Hosp Epidemiol. 2021 Jun 3:1-12.
        Using data from the National Healthcare Safety Network (NHSN), we assessed changes to intensive care unit (ICU) bed capacity during the early months of the COVID-19 pandemic. Changes in capacity varied by hospital type and size. ICU beds increased by 36%, highlighting the pressure placed on hospitals during the pandemic.

      65. Intersecting Paths of Emerging and Reemerging Infectious Diseasesexternal icon
        Wilson TM, Paddock CD, Reagan-Steiner S, Bhatnagar J, Martines RB, Wiens AL, Madsen M, Komatsu KK, Venkat H, Zaki SR.
        Emerg Infect Dis. 2021 May;27(5):1517-1519.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic.

      66. Infective Endocarditis Among Persons Aged 18-64 Years Living with Human Immunodeficiency Virus, Hepatitis C Infection, or Opioid Use Disorder, United States, 2007-2017external icon
        Wong CY, Zhu W, Aurigemma GP, Furukawa N, Teshale EH, Huang YA, Peters PJ, Hoover KW.
        Clin Infect Dis. 2021 May 18;72(10):1767-1781.
        BACKGROUND: Infective endocarditis (IE) is a life-threatening bacterial infection of the heart valves, most often diagnosed in older persons and persons with prior cardiac surgery. It is also associated with injection drug use, a behavior that has increased in recent years along with the US opioid crisis. METHODS: We conducted a retrospective cohort analysis of commercial and Medicaid health insurance databases to estimate incident cases of IE in the United States in 2017, stratified by persons living with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and opioid use disorder (OUD). We also estimated annual percentage changes (EAPCs) in IE from 2007-2017 among persons with commercial insurance. RESULTS: The weighted incidence rate of IE was 13.8 cases per 100 000 persons among persons with commercial insurance, and 78.7 among those with Medicaid. The incidence rate of IE among commercially insured persons increased slightly from 2007-2017 (EAPC, 1.0%). It decreased among commercially insured persons living with HIV, from 148.0 in 2007 to 112.1 in 2017 (EAPC, -4.3%), and increased among those with HCV infection, from 172.4 in 2007 to 238.6 in 2017 (EAPC, 3.2%). Among persons aged 18-29 years with HCV infection, IE increased from 322.3 in 2007 to 1007.1 in 2017 (EAPC, 16.3%), and among those with OUD it increased from 156.4 in 2007 to 642.9 in 2017 (EAPC, 14.8%). CONCLUSIONS: The incidence rate of IE increased markedly among young persons with HCV infections or OUD. This increase appears to parallel the ongoing national opioid crisis. Harm reduction with syringe services programs, medications for opioid use disorder, and safe injection practices can prevent the spread of HIV, HCV, and IE.

      67. Burden and etiology of moderate and severe diarrhea in children less than 5 years of age living in north and south of China: Prospective, population-based surveillanceexternal icon
        Zhou HL, Bessey T, Wang SM, Mo ZJ, Barclay L, Wang JX, Zhang CJ, Ma JC, Qiu C, Zhao G, Li RC, Zhao YL, Jiang B, Wang XY.
        Gut Pathog. 2021 May 24;13(1):33.
        BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.

    • Disaster Control and Emergency Services
      1. The Pandemic Influenza Preparedness (PIP) Framework: strengthening laboratory and surveillance capacities in the Western Pacific Region, 2014-2017external icon
        Chugh H, Samaan G, Resnikoff T, Bergeri I, Barragan J, Dueger E.
        Western Pac Surveill Response J. 2020 Oct-Dec;11(4):32-35.

    • Environmental Health
      1. Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys?external icon
        Chin HB, Kelly A, Adgent MA, Patchel SA, James K, Vesper HW, Botelho JC, Chandler DW, Zemel BS, Schall JI, Ford EG, Darge K, Stallings VA, Baird DD, Rogan WJ, Umbach DM.
        J Clin Endocrinol Metab. 2021 May 20.
        CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. DESIGN: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow-milk formula, or breastmilk feeding during study follow-up. Reproductive hormone concentrations and male anatomical measurements were longitudinally assessed from birth to 28 weeks. SETTING: Clinic-based cohort. PARTICIPANTS: 147 mother-infant boy pairs. INTERVENTIONS: not applicable. MAIN OUTCOME MEASURE: Serum testosterone and luteinizing hormone (LH) concentrations, stretched penile length, anogenital distance, and testis volume. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks [176 ng/dL (quartiles:124, 232)] and remained in this range until 12 weeks, in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n=55) and boys fed cow-milk formula (n=54). Compared with breastfed boys (n=38), soy-formula-fed boys had a more rapid increase in penile length (p=0.004) and slower initial lengthening of AGD (p=0.03), but no differences in hormone trajectories. CONCLUSIONS: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow-milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

      2. Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) studyexternal icon
        Colicino E, de Water E, Just AC, Navarro E, Pedretti NF, McRae N, Braun JM, Schnaas L, Rodríguez-Carmona Y, Hernández C, Tamayo-Ortiz M, M. Téllez-Rojo M, Deierlein AL, Calafat AM, Baccarelli A, Wright RO, Horton MK.
        Environ Res. 2021 May 26:111338.
        BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log(2)-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß =0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.

      3. Strengthening Aquatic Health and Safety: How a Pilot Program Supported Local Health Departments in Updating Pool Codesexternal icon
        D'Angelo EK, Galan DI, Laco JP, Fink T, Skaggs JM, Kunsman C, Warren E.
        J Public Health Manag Pract. 2021 Jul-Aug 01;27(4):428-431.

      4. Outbreaks Associated with Treated Recreational Water - United States, 2015-2019external icon
        Hlavsa MC, Aluko SK, Miller AD, Person J, Gerdes ME, Lee S, Laco JP, Hannapel EJ, Hill VR.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):733-738.
        Outbreaks associated with treated recreational water can be caused by pathogens or chemicals in aquatic venues such as pools, hot tubs, water playgrounds, or other artificially constructed structures that are intended for recreational or therapeutic purposes. For the pseriod 2015-2019, public health officials from 36 states and the District of Columbia (DC) voluntarily reported 208 outbreaks associated with treated recreational water. Almost all (199; 96%) of the outbreaks were associated with public (nonbackyard) pools, hot tubs, or water playgrounds. These outbreaks resulted in at least 3,646 cases of illness, 286 hospitalizations, and 13 deaths. Among the 155 (75%) outbreaks with a confirmed infectious etiology, 76 (49%) were caused by Cryptosporidium (which causes cryptosporidiosis, a gastrointestinal illness) and 65 (42%) by Legionella (which causes Legionnaires' disease, a severe pneumonia, and Pontiac fever, a milder illness with flu-like symptoms). Cryptosporidium accounted for 2,492 (84%) of 2,953 cases resulting from the 155 outbreaks with a confirmed etiology. All 13 deaths occurred in persons affected by a Legionnaires' disease outbreak. Among the 208 outbreaks, 71 (34%) were associated with a hotel (i.e., hotel, motel, lodge, or inn) or a resort, and 107 (51%) started during June-August. Implementing recommendations in CDC's Model Aquatic Health Code (MAHC) (1) can help prevent outbreaks associated with treated recreational water in public aquatic venues.

    • Epidemiology and Surveillance
      1. US nationwide assessment of school health policies and practices using state-level dataexternal icon
        Bryan LN, Brener N, Barker L, Lo A, Underwood JM.
        Health Educ J. 2021 .
        Objective: After the discontinuation of School Health Policies and Practices Study (SHPPS) in 2016, the US Centers for Disease Control and Prevention (CDC) began exploring innovative ways to gather school health information using existing surveillance systems. School Health Profiles (Profiles) is a school-based system of surveys that monitors school health policies and practices in states and other jurisdictions. The objective of this study was to assess whether prevalence estimates calculated using nationally representative SHPPS as an established benchmark were similar to estimates using aggregated Profiles data. Method: Nationwide 2014 Profiles estimates were calculated from data across all 50 US states and the District of Columbia and compared to national 2014 SHPPS estimates. Fifty-seven questions were identical between the data sources. Equivalence tests were used to determine similarity between data sources. Results: Overall, the median difference between 2014 SHPPS and 2014 Profiles estimate was one percentage point and distribution-free 95% confidence intervals were (−0.8, 3.1). Of the 57 school health policy and practice indicators examined in this study, 38 (66.7%) were found to be equivalent. Of these equivalent indicators, the median percentage point difference between data sources was 0.8 (−0.8, 2.5). A nonparametric sign test showed that none of the medians of the estimate differences examined were significantly different from zero. Conclusion: This study demonstrates the expanded utility of state-level data to meet public health surveillance needs. This study found that aggregated, state-level Profiles data can be used to calculate nationwide prevalence estimates that are reasonably consistent with results from a nationally representative survey. © The Author(s) 2021.

    • Genetics and Genomics
      1. Whole gene analysis of a genotype G29P[6] human rotavirus strain identified in Central African Republicexternal icon
        Banga-Mingo V, Esona MD, Betrapally NS, Gautam R, Jaimes J, Katz E, Waku-Kouomou D, Bowen MD, Gouandjika-Vasilache I.
        BMC Res Notes. 2021 May 31;14(1):218.
        OBJECTIVE: Rotavirus A (RVA) remains the main causative agent of gastroenteritis in young children and the young of many mammalian and avian species. In this study we describe a RVA strain detected from a 6-month-old child from Central African Republic (CAR). RESULTS: We report the 11 open reading frame sequences of a G29-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 rotavirus strain, RVA/Human-wt/CAR/CAR91/2014/G29P[6]. Nine genes (VP1-VP3, VP6, NSP1-NSP5) shared 90-100% sequence similarities with genogroup 2 rotaviruses. Phylogenetically, backbone genes, except for VP3 and NSP4 genes, were linked with cognate gene sequences of human DS-1-like genogroup 2, hence their genetic origin. The VP3 and NSP4 genes, clustered genetically with both human and animal strains, an indication genetic reassortment human and animal RVA strains has taken place. The VP7 gene shared nucleotide (93-94%) and amino acid (95.5-96.7%) identities with Kenyan and Belgian human G29 strains, as well as to buffalo G29 strain from South Africa, while the VP4 gene most closely resembled P[6]-lineage I strains from Africa and Bangladesh (97%).

      2. Framing Bacterial Genomics for Public Health(care)external icon
        Halpin AL, McDonald LC, Elkins CA.
        J Clin Microbiol. 2021 Jun 2:Jcm0013521.
        Advancements in comparative genomics have generated significant interest in defining applications for healthcare-associated pathogens. Clinical microbiology, however, relies on increasingly automated platforms to quickly identify pathogens, resistance mechanisms, and therapy options within CLIA- and FDA-approved frameworks. Additionally, and most notably, healthcare-associated pathogens, especially those that are resistant to antibiotics, represent a diverse spectrum of genera harboring complex genetic targets including antibiotic, biocide, and virulence determinants that can be highly transmissible and, at least for antibiotic resistance, serve as potential targets for containment efforts. U.S. public health investments have focused on rapidly detecting outbreaks and emerging resistance in healthcare-associated pathogens using reference, culture-based, and molecular methods that are distributed, for example, across national laboratory network infrastructures. Herein we describe the public health applications of genomic science that are built from the top-down for broad surveillance, as well as the bottom-up, starting with identification of infections and infectious clusters. For healthcare-associated, including antimicrobial-resistant, pathogens, we propose a combination of top-down and bottom-up genomic approaches leveraged across the public health spectrum, from local infection control, to regional and national containment efforts, to national surveillance for understanding emerging strain ecology and fitness of healthcare pathogens.

      3. Genomic analysis of the predominant strains and antimicrobial resistance determinants within 1479 Neisseria gonorrhoeae isolates from the U.S. Gonococcal Isolate Surveillance Project in 2018external icon
        Reimche JL, Chivukula VL, Schmerer MW, Joseph SJ, Pham CD, Schlanger K, St Cyr SB, Weinstock HS, Raphael BH, Kersh EN, Gernert KM.
        Sex Transm Dis. 2021 May 14.
        BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring.

      4. Using Neisseria meningitidis genomic diversity to inform outbreak strain identificationexternal icon
        Retchless AC, Chen A, Chang HY, Blain AE, McNamara LA, Mustapha MM, Harrison LH, Wang X.
        PLoS Pathog. 2021 May 18;17(5):e1009586.
        Meningococcal disease is a life-threatening illness caused by the human-restricted bacterium Neisseria meningitidis. Outbreaks in the USA involve at least two cases in an organization or community caused by the same serogroup within three months. Genome comparisons, including phylogenetic analysis and quantification of genome distances can provide confirmatory evidence of pathogen transmission during an outbreak. Interpreting genome distances depends on understanding their distribution both among isolates from outbreaks and among those not from outbreaks. Here, we identify outbreak strains based on phylogenetic relationships among 141 N. meningitidis isolates collected from 28 outbreaks in the USA during 2010-2017 and 1516 non-outbreak isolates collected through contemporaneous meningococcal surveillance. We show that genome distance thresholds based on the maximum SNPs and allele distances among isolates in the phylogenetically defined outbreak strains are sufficient to separate most pairs of non-outbreak isolates into separate strains. Non-outbreak isolate pairs that could not be distinguished from each other based on genetic distances were concentrated in the clonal complexes CC11, CC103, and CC32. Within each of these clonal complexes, phylodynamic analysis identified a group of isolates with extremely low diversity, collected over several years and multiple states. Clusters of isolates with low genetic diversity could indicate increased pathogen transmission, potentially resulting in local outbreaks or nationwide clonal expansions.

      5. Comparative neurotranscriptomics reveal widespread species differences associated with bondingexternal icon
        Tripp JA, Berrio A, McGraw LA, Matz MV, Davis JK, Inoue K, Thomas JW, Young LJ, Phelps SM.
        BMC Genomics. 2021 May 31;22(1):399.
        BACKGROUND: Pair bonding with a reproductive partner is rare among mammals but is an important feature of human social behavior. Decades of research on monogamous prairie voles (Microtus ochrogaster), along with comparative studies using the related non-bonding meadow vole (M. pennsylvanicus), have revealed many of the neural and molecular mechanisms necessary for pair-bond formation in that species. However, these studies have largely focused on just a few neuromodulatory systems. To test the hypothesis that neural gene expression differences underlie differential capacities to bond, we performed RNA-sequencing on tissue from three brain regions important for bonding and other social behaviors across bond-forming prairie voles and non-bonding meadow voles. We examined gene expression in the amygdala, hypothalamus, and combined ventral pallidum/nucleus accumbens in virgins and at three time points after mating to understand species differences in gene expression at baseline, in response to mating, and during bond formation. RESULTS: We first identified species and brain region as the factors most strongly associated with gene expression in our samples. Next, we found gene categories related to cell structure, translation, and metabolism that differed in expression across species in virgins, as well as categories associated with cell structure, synaptic and neuroendocrine signaling, and transcription and translation that varied among the focal regions in our study. Additionally, we identified genes that were differentially expressed across species after mating in each of our regions of interest. These include genes involved in regulating transcription, neuron structure, and synaptic plasticity. Finally, we identified modules of co-regulated genes that were strongly correlated with brain region in both species, and modules that were correlated with post-mating time points in prairie voles but not meadow voles. CONCLUSIONS: These results reinforce the importance of pre-mating differences that confer the ability to form pair bonds in prairie voles but not promiscuous species such as meadow voles. Gene ontology analysis supports the hypothesis that pair-bond formation involves transcriptional regulation, and changes in neuronal structure. Together, our results expand knowledge of the genes involved in the pair bonding process and open new avenues of research in the molecular mechanisms of bond formation.

      6. Tuberculosis Genotype Clusters and Transmission in the U.S., 2009-2018external icon
        Wortham JM, Li R, Althomsons SP, Kammerer S, Haddad MB, Powell KM.
        Am J Prev Med. 2021 May 12.
        INTRODUCTION: In the U.S., universal genotyping of culture-confirmed tuberculosis cases facilitates cluster detection. Early recognition of the small clusters more likely to become outbreaks can help prioritize public health resources for immediate interventions. METHODS: This study used national surveillance data reported during 2009-2018 to describe incident clusters (≥3 tuberculosis cases with matching genotypes not previously reported in the same county); data were analyzed during 2020. Cox proportional hazards regression models were used to examine the patient characteristics associated with clusters doubling in size to ≥6 cases. RESULTS: During 2009-2018, a total of 1,516 incident clusters (comprising 6,577 cases) occurred in 47 U.S. states; 231 clusters had ≥6 cases. Clusters of ≥6 cases disproportionately included patients who used substances, who had recently experienced homelessness, who were incarcerated, who were U.S. born, or who self-identified as being of American Indian or Alaska Native race or of Black race. A median of 54 months elapsed between the first and the third cases in clusters that remained at 3-5 cases compared with a median of 9.5 months in clusters that grew to ≥6 cases. The longer time between the first and third cases and the presence of ≥1 patient aged ≥65 years among the first 3 cases predicted a lower hazard for accumulating ≥6 cases. CONCLUSIONS: Clusters accumulating ≥3 cases within a year should be prioritized for intervention. Effective response strategies should include plans for targeted outreach to U.S.-born individuals, incarcerated people, those experiencing homelessness, people using substances, and individuals self-identifying as being of American Indian or Alaska Native race or of Black race.

    • Global Health
      1. Health of Asylees Compared to Refugees in the United States Using Domestic Medical Examination Data, 2014-2016: A Cross-Sectional Analysisexternal icon
        Kumar GS, Pezzi C, Payton C, Mamo B, Urban K, Scott K, Montour J, Cabanting N, Aguirre J, Ford R, Hughes SE, Kawasaki B, Kennedy L, Jentes ES.
        Clin Infect Dis. 2021 May 27.
        BACKGROUND: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. METHODS: We conducted a retrospective cross-sectional analysis of domestic medical examination data from nine US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C, and select sexually transmitted infections and parasites by refugee or asylee visa status. RESULTS: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (Prevalence Ratio [PR]=0.8), hepatitis B (0.7), hepatitis C (0.5) and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. CONCLUSIONS: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention's Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination.

    • Health Disparities
      1. Racial disparities in invasive Haemophilus influenzae disease - United States, 2008-2017external icon
        Brown NE, Blain AE, Burzlaff K, Harrison LH, Petit S, Schaffner W, Smelser C, Thomas A, Triden L, Watt JP, Pondo T, Whaley MJ, Hu F, Wang X, Oliver S, Soeters HM.
        Clin Infect Dis. 2021 May 16.
        BACKGROUND: Since the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease (Hi) epidemiology has changed and racial disparities have not been recently described. METHODS: Active population- and laboratory-based surveillance for Hi was conducted through Active Bacterial Core surveillance (ABCs) at 10 U.S. sites. Data from 2008-2017 was used to estimate projected nationwide annual incidence in cases/100,000. RESULTS: During 2008-2017, ABCs identified 7379 Hi cases. Of 6705 (90.9%) patients with reported race, 76.2% were White, 18.6% were Black, 2.8% were Asian/Pacific Islander (PI), and 2.4% were American Indian and Alaska Native (AI/AN). Nationwide annual incidence was 1.8 cases/100,000. By race, incidence was highest among AI/AN populations (3.1) and lowest among Asian/PI populations (0.8). Nontypeable Hi (NTHi) caused the largest incidence within all races (1.3), with no striking disparities identified. Among AI/AN children aged <5 years, incidence of Hi serotype a (Hia) was 16.7 times higher and Hib incidence was 22.4 times higher than among White children. Though Hia incidence was lower among White and Black populations compared to AI/AN, Hia incidence increased 13.6% annually among White children and 40.4% annually among Black children aged <5 years. CONCLUSIONS: While NTHi causes the largest Hi burden overall, AI/AN populations experience disproportionately high rates of Hia and Hib, with the greatest disparity among AI/AN children aged <5 years. Prevention tools are needed to reduce disparities affecting AI/AN children and address increasing Hia incidence in other communities.

      2. Racial and Ethnic Disparities in Breastfeeding Initiation ─ United States, 2019external icon
        Chiang KV, Li R, Anstey EH, Perrine CG.
        MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):769-774.
        Breastfeeding is the optimal source of nutrition for most infants (1). Although breastfeeding rates in the United States have increased during the past decade, racial/ethnic disparities persist (2). Breastfeeding surveillance typically focuses on disparities at the national level, because small sample sizes limit examination of disparities at the state or territorial level. However, birth certificate data allow for assessment of breastfeeding initiation among nearly all newborn infants in the United States both nationally and at the state and territorial levels. To describe breastfeeding initiation by maternal race/ethnicity,* CDC analyzed 2019 National Vital Statistics System (NVSS) birth certificate data for 3,129,646 births from 48 of the 50 states (all except California and Michigan(†)), the District of Columbia (DC), and three U.S. territories (Guam, Northern Mariana Islands, and Puerto Rico). The prevalence of breastfeeding initiation was 84.1% overall and varied by maternal race/ethnicity, ranging from 90.3% among infants of Asian mothers to 73.6% among infants of Black mothers, a difference of 16.7 percentage points. Across states, the magnitude of disparity between the highest and lowest breastfeeding rates by racial/ethnic groups varied, ranging from 6.6 percentage points in Vermont to 37.6 percentage points in North Dakota, as did the specific racial/ethnic groups with the highest and lowest rates. These state/territory-specific data highlight the variation that exists in breastfeeding disparities across the United States and can help public health practitioners and health departments identify groups on which to focus efforts. Targeting breastfeeding promotion programs on populations with lower breastfeeding rates might help reduce racial/ethnic disparities in breastfeeding initiation and improve infant nutrition and health.

      3. Finding "Bright Spots": Using Multiple Measures to Examine Local-Area Racial Equity in Cancer Mortality Outcomesexternal icon
        Scott LC, Bartley S, Dowling NF, Richardson LC.
        Am J Epidemiol. 2021 Apr 6;190(4):673-680.
        In this article, we present a variety of measures that quantify equity in cancer mortality outcomes, demonstrate how the measures perform with various cancer types, and identify counties, or "bright spots," that meet the criteria of those measures. Using county-level age-adjusted mortality rates for 2007-2016 from the National Center for Health Statistics, we identified counties that had both equitable and optimal outcomes for Black and White death rates across 5 types of cancer: cancers of the lung/bronchus, prostate, female breast, colorectum, and liver. The number of counties that met the criteria ranged from 0 to 442, depending on cancer type and measure used. Prostate cancer and male liver cancer consistently had the lowest number of "bright spots," with a maximum of 3 counties meeting the most lenient criteria. This paper presents several ways to examine equity, using rate ratios and standard error measures, in cancer mortality outcomes. It highlights areas with positive progress toward equity and areas with a potential need for equity-focused cancer-control planning. Examining local areas of positive deviance can inform cancer-control programming and planning around health equity.

      4. Purpose: Little is known regarding the health care utilization patterns of refugees resettled in the United States. We analyzed the Annual Survey of Refugees (ASR), a nationally representative survey of recently resettled refugees, to assess these patterns. Methods: Anonymized 2016 ASR data were examined for refugees 16 years old who arrived from 2011 to 2014. Results: Refugees most often used private physicians (34%), health clinics (19%), and emergency rooms (14%). Approximately 15% reported no regular source of care, and 34% had health insurance for 1 month of the prior year. Conclusion: Results indicate differing health care use and coverage, revealing opportunities for educational interventions.

      5. The disproportionate impact of COVID-19 and associated disparities among Hispanic, non-Hispanic Black, and non-Hispanic American Indian/Alaska Native children and teenagers has been documented. Reducing these disparities along with overcoming unintended negative consequences of the pandemic, such as the disruption of in-person schooling, calls for broad community-based collaborations and nuanced approaches. Based on national survey data, children from some racial and ethnic minority groups have a higher prevalence of obesity, asthma, type 2 diabetes, and hypertension; were diagnosed more frequently with COVID-19; and had more severe outcomes compared with their non-Hispanic White (NHW) counterparts. Furthermore, a higher proportion of children from some racial and ethnic minority groups lived in families with incomes less than 200% of the federal poverty level or in households lacking secure employment compared with NHW children. Children from some racial and ethnic minority groups were also more likely to attend school via online learning compared with NHW counterparts. Because the root causes of these disparities are complex and multifactorial, an organized community-based approach is needed to achieve greater proactive and sustained collaborations between local health departments, local school systems, and other public and private organizations to pursue health equity. This article provides a summary of potential community-based health promotion strategies to address racial and ethnic disparities in COVID-19 outcomes and educational inequities among children and teens, specifically in the implementation of strategic partnerships, including initial collective work, outcomes-based activities, and communication. These collaborations can facilitate policy, systems, and environmental changes in school systems that support emergency preparedness, recovery, and resilience when faced with public health crises.

    • Health Economics
      1. The Impact of Covid-19 State Closure Orders on Consumer Spending, Employment, and Business Revenueexternal icon
        Dunphy C, Miller GF, Rice K, Vo L, Sunshine G, McCord R, Howard-Williams M, Coronado F.
        J Public Health Manag Pract. 2021 May 13.
        CONTEXT: In response to the COVID-19 pandemic, states across the United States implemented various strategies to mitigate transmission of SARS-CoV-2 (the virus that causes COVID-19). OBJECTIVE: To examine the effect of COVID-19-related state closures on consumer spending, business revenue, and employment, while controlling for changes in COVID-19 incidence and death. DESIGN: The analysis estimated a difference-in-difference model, utilizing temporal and geographic variation in state closure orders to analyze their impact on the economy, while controlling for COVID-19 incidence and death. PARTICIPANTS: State-level data on economic outcomes from the Opportunity Insights data tracker and COVID-19 cases and death data from INTERVENTIONS: The mitigation strategy analyzed within this study was COVID-19-related state closure orders. Data on these orders were obtained from state government Web sites containing executive or administrative orders. MAIN OUTCOME MEASURES: Outcomes include state-level estimates of consumer spending, business revenue, and employment levels. RESULTS: Analyses showed that although state closures led to a decrease in consumer spending, business revenue, and employment, they accounted for only a small portion of the observed decreases in these outcomes over the first wave of COVID-19. CONCLUSIONS: The impact of COVID-19 on economic activity likely reflects a combination of factors, in addition to state closures, such as individuals' perceptions of risk related to COVID-19 incidence, which may play significant roles in impacting economic activity.

      2. Modeling the Cost-Effectiveness of Express Multi-Site Gonorrhea Screening among Men Who Have Sex with Men in the United Statesexternal icon
        Earnest R, Rönn MM, Bellerose M, Menon-Johansson AS, Berruti AA, Chesson HW, Gift TL, Hsu KK, Testa C, Zhu L, Malyuta Y, Menzies NA, Salomon JA.
        Sex Transm Dis. 2021 May 14.
        BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in U.S. MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical exam and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over five years, labor and material costs, and incremental cost effectiveness ratios (ICER) for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multi-site anatomic screening among U.S. MSM.

      3. BACKGROUND: New cases of COVID-19 continue to occur daily in the United States, and the need for medical treatments continues to grow. Knowledge of the direct medical costs of COVID-19 treatments is limited. OBJECTIVE: To examine the characteristics of older adults with COVID-19 and their costs for COVID-19-related medical care. DESIGN: Retrospective observational study. SETTING: Medical claims for Medicare fee-for-service (FFS) beneficiaries. PATIENTS: Medicare FFS beneficiaries aged 65 years or older who had a COVID-19-related medical encounter during April through December 2020. MEASUREMENTS: Patient characteristics and direct medical costs of COVID-19-related hospitalizations and outpatient visits. RESULTS: Among 28.1 million Medicare FFS beneficiaries, 1 181 127 (4.2%) sought COVID-19-related medical care. Among these patients, 23.0% had an inpatient stay and 4.2% died during hospitalization. The majority of the patients were female (57.0%), non-Hispanic White (79.6%), and residents of an urban county (77.2%). Medicare FFS costs for COVID-19-related medical care were $6.3 billion; 92.6% of costs were for hospitalizations. The mean hospitalization cost was $21 752, and the mean length of stay was 9.2 days; hospitalization cost and length of stay were higher if the patient needed a ventilator ($49 441 and 17.1 days) or died ($32 015 and 11.3 days). The mean cost per outpatient visit was $164. Patients aged 75 years or older were more likely to be hospitalized, but their hospitalizations were associated with lower costs than for younger patients. Male sex and non-White race/ethnicity were associated with higher probability of being hospitalized and higher medical costs. LIMITATION: Results are based on Medicare FFS patients. CONCLUSION: The COVID-19 pandemic has resulted in substantial disease and economic burden among older Americans, particularly those of non-White race/ethnicity. PRIMARY FUNDING SOURCE: None.

      4. BACKGROUND: Outreach screening is a common strategy for detecting cases of syphilis in high-risk populations. New rapid syphilis tests allow for quicker response times and may alter the costs of detecting and treating syphilis in non-clinical settings. METHODS: Between May and October of 2017, we collected detailed retrospective cost data from two outreach screening programs engaging people experiencing homelessness and LGBTQ populations. Comprehensive and retrospective cost information, disaggregated by cost category, programmatic activity, and source of support, was collected during and after the testing period. RESULTS: Across all sites, rapid syphilis tests were conducted on 595 people at an average cost of $213 per person. Twenty-three cases of syphilis were confirmed and treated for an average cost of $5,517 per case, ranging from $3,604 at a rehabilitation facility to $13,140 at LGBTQ venues served by a mobile clinic. Personnel contributed the most to total costs (56.4%), followed by supplies (12.8%) and the use of buildings (10.4%). Expenditures by programmatic activity varied substantially across sites. CONCLUSIONS: Testing costs varied between venues, reflecting differences in the models used and intensity of services provided. While staff costs are the major driver, buildings and supplies costs are also significant. Our findings suggest that outreach screenings using rapid syphilis tests may be a feasible and cost-effective tool for health departments when targeting known high-prevalence areas and hard to reach populations.

    • Healthcare Associated Infections
      1. Aztreonam-Avibactam Susceptibility Testing Program for Metallo-beta-lactamase-producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019-December 2020external icon
        Bhatnagar A, Boyd S, Sabour S, Bodnar J, Nazarian E, Peinovich N, Wagner C, Craft B, Vagnone PS, Simpson J, Stone VN, Therrien M, Bateman A, Lower D, Huang JY, Gumbis S, Lonsway D, Lutgring JD, Karlsson M, Brown AC.
        Antimicrob Agents Chemother. 2021 Jun 1:Aac0048621.
        Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC(50) and MIC(90) of aztreonam-avibactam were 0.5/4 μg/mL and 8/4 μg/mL, respectively. Aztreonam-avibactam displayed potent in vitro activity against the MBL-producing Enterobacterales tested.

      2. Azithromycin and Ciprofloxacin Treatment Outcomes During an Outbreak of Multidrug-Resistant Shigella sonnei Infections in a Retirement Community-Vermont, 2018external icon
        Gharpure R, Friedman CR, Fialkowski V, Collins JP, Strysko J, Marsh ZA, Chen JC, Meservey EH, Adediran AA, Schroeder MN, Wadhwa A, Fullerton KE, Watkins LF.
        Clin Infect Dis. 2021 May 16.
        BACKGROUND: In 2018, CDC and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin. METHODS: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms. RESULTS: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, four were treated with azithromycin; all had clinical treatment failure and two also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; two patients failed treatment with ciprofloxacin. CONCLUSIONS: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

      3. Treatment Practices for Adults with Candidemia at Nine Active Surveillance Sites - United States, 2017-2018external icon
        Gold JA, Seagle EE, Nadle J, Barter DM, Czaja CA, Johnston H, Farley MM, Thomas S, Harrison LH, Fischer J, Pattee B, Mody RK, Phipps EC, Shrum Davis S, Tesini BL, Zhang AY, Markus TM, Schaffner W, Lockhart SR, Vallabhaneni S, Jackson BR, Lyman M.
        Clin Infect Dis. 2021 Jun 3.
        BACKGROUND: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. METHODS: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at nine U.S. sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. RESULTS: Among 1,835 patients who received antifungal treatment, 1,258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06, 95% confidence interval: 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). Over half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. CONCLUSIONS: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for non-adherence to IDSA guidelines should be evaluated, and clinician education is needed.

      4. Implementation of core elements of antibiotic stewardship in nursing homes-National Healthcare Safety Network, 2016-2018external icon
        Gouin KA, Kabbani S, Anttila A, Mak J, Mungai E, McCray TT, Bell J, Hicks LA, Stone ND.
        Infect Control Hosp Epidemiol. 2021 May 26:1-5.
        OBJECTIVE: To assess the national uptake of the Centers for Disease Control and Prevention's (CDC) core elements of antibiotic stewardship in nursing homes from 2016 to 2018 and the effect of infection prevention and control (IPC) hours on the implementation of the core elements. DESIGN: Retrospective, repeated cross-sectional analysis. SETTING: US nursing homes. METHODS: We used the National Healthcare Safety Network (NHSN) Long-Term Care Facility Component annual surveys from 2016 to 2018 to assess nursing home characteristics and percent implementation of the core elements. We used log-binomial regression models to estimate the association between weekly IPC hours and the implementation of all 7 core elements while controlling for confounding by facility characteristics. RESULTS: We included 7,506 surveys from 2016 to 2018. In 2018, 71% of nursing homes reported implementation of all 7 core elements, a 28% increase from 2016. The greatest increases in implementation from 2016 to 2018 were in education (19%), reporting (18%), and drug expertise (15%). In 2018, 71% of nursing homes reported pharmacist involvement in improving antibiotic use, an increase of 27% since 2016. Nursing homes that reported at least 20 hours of IPC activity per week were 14% (95% confidence interval, 7%-20%) more likely to implement all 7 core elements when controlling for facility ownership and affiliation. CONCLUSIONS: Nursing homes reported substantial progress in antibiotic stewardship implementation from 2016 to 2018. Improvements in access to drug expertise, education, and reporting antibiotic use may reflect increased stewardship awareness and resource use among nursing home providers under new regulatory requirements. Nursing home stewardship programs may benefit from increased IPC staff hours.

      5. OBJECTIVES: Most patients with Campylobacter infections do not require antibiotics; however, they are indicated in severe cases. Clinical breakpoints for many antibiotics have not yet been established by the Clinical and Laboratory Standards Institute, making antibiotic selection for resistant infections challenging. During an outbreak of pet store puppy-associated extensively drug resistant (XDR) Campylobacter jejuni infections resistant to seven classes of antibiotics, several patients required antibiotics. The aims of this study were to describe the minimal inhibitory concentrations (MICs) of the outbreak strain for various antibiotics and the successful treatment of two patients using imipenem-cilastatin, a drug not traditionally used to treat Campylobacter infections. METHODS: We used whole genome multi-locus sequence typing (wgMLST) to determine the genetic relatedness of Campylobacter isolates collected from two human patients' stool samples with the outbreak strain. We performed extended antimicrobial susceptibility testing on 14 outbreak isolates and 6 control strains to determine MICs for 30 antibiotics from 14 classes. RESULTS: Isolates from both patients were found to be highly related to the outbreak strain by wgMLST. MICs indicated resistance of outbreak strain to most antibiotic classes; exceptions included phenicols, glycylcyclines, and carbapenems. Due to potential side effects of phenicols and safety issues precluding use of glycylcyclines like tigecycline when alternatives agents are available, we used carbapenems to treat patients who got severely ill from the outbreak strain infections. CONCLUSIONS: Stewardship and clinical vigilance are warranted when deciding whether and how to treat patients with suspected C. jejuni diarrhea with antibiotics. Clinicians should maintain a high index of suspicion for XDR Campylobacter when patients fail to improve and consider use of carbapenems in such settings.

      6. Increased Incidence of Antimicrobial-Resistant Nontyphoidal Salmonella Infections, United States, 2004-2016external icon
        Medalla F, Gu W, Friedman CR, Judd M, Folster J, Griffin PM, Hoekstra RM.
        Emerg Infect Dis. 2021 Jun;27(6):1662-1672.
        Salmonella is a major cause of foodborne illness in the United States, and antimicrobial-resistant strains pose a serious threat to public health. We used Bayesian hierarchical models of culture-confirmed infections during 2004-2016 from 2 Centers for Disease Control and Prevention surveillance systems to estimate changes in the national incidence of resistant nontyphoidal Salmonella infections. Extrapolating to the United States population and accounting for unreported infections, we estimated a 40% increase in the annual incidence of infections with clinically important resistance (resistance to ampicillin or ceftriaxone or nonsusceptibility to ciprofloxacin) during 2015-2016 (≈222,000 infections) compared with 2004-2008 (≈159,000 infections). Changes in the incidence of resistance varied by serotype. Serotypes I 4,[5],12:i:- and Enteritidis were responsible for two thirds of the increased incidence of clinically important resistance during 2015-2016. Ciprofloxacin-nonsusceptible infections accounted for more than half of the increase. These estimates can help in setting targets and priorities for prevention.

      7. Human Adenovirus 11 in 2 Renal Transplant Recipients: Suspected Donor-Derived Infectionexternal icon
        Sherman AC, Lu X, Schneider E, Langston A, Ellis CL, Pastan S, Bhatnagar J, Reagan-Steiner S, Annambhotla P, Lindstrom S, Mehta A, Pouch SM, Sexton ME.
        Open Forum Infect Dis. 2021 ;8(3).
        Background: Human adenovirus (HAdV) infections can lead to high mortality in solid organ transplant (SOT) recipients, with rare reports of donor-derived infection. Methods: Two renal transplant recipients with HAdV-11 infection who received kidneys from the same donor are described. Whole-genome sequencing (WGS) was performed. Results: WGS showed 100% nucleotide sequence identity for the 2 HAdV-11 isolates. The patients presented with distinct clinical syndromes, and both were treated with brincidofovir. Conclusions: Donor-derived HAdV infection is presumed to be low; however, disseminated HAdV in SOT recipients can be severe, and clinicians should be aware of the clinical course and treatment options. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

    • Immune System Disorders

    • Immunity and Immunization
      1. Response to Poliovirus Outbreaks in the Lake Chad Sub-Region: A GIS Mapping Approachexternal icon
        Ajiri A, Okeibunor J, Aiyeoribe S, Ntezayabo B, Mailhot M, Nzioki M, Traore A, Khalid A, Diallo M, Ilboudo M, Mikeyas BM, Samba D, Mulunda T, De Medeiros N, Rabenarivo B, Diomande F, Okiror S.
        J Immunol Sci. 2021 Apr 12;Spec Issue(2):1115.
        The geographic information system (GIS) mapping was used to improve the efficiency of vaccination teams. This paper documents the process in the deployment of geographical information system in response to polio eradication in Chad. It started with a careful review of government official documents as well as review of literature and online resources on Chad, which confirmed that official boundaries existed at two levels, namely Regions and Districts. All settlement locations in the target Districts were identified by manual feature extraction of high-resolution, recent satellite imagery, and map layers created for the following categories: hamlets, hamlet areas, small settlements, and built-up areas (BUAs). This clearly improved microplanning and provided valuable feedback in identifying missed settlements, leading to increased coverage and fewer missed children.

      2. Patterns in COVID-19 Vaccination Coverage, by Social Vulnerability and Urbanicity - United States, December 14, 2020-May 1, 2021external icon
        Barry V, Dasgupta S, Weller DL, Kriss JL, Cadwell BL, Rose C, Pingali C, Musial T, Sharpe JD, Flores SA, Greenlund KJ, Patel A, Stewart A, Qualters JR, Harris L, Barbour KE, Black CL.
        MMWR Morb Mortal Wkly Rep. 2021 Jun 4;70(22):818-824.
        Disparities in vaccination coverage by social vulnerability, defined as social and structural factors associated with adverse health outcomes, were noted during the first 2.5 months of the U.S. COVID-19 vaccination campaign, which began during mid-December 2020 (1). As vaccine eligibility and availability continue to expand, assuring equitable coverage for disproportionately affected communities remains a priority. CDC examined COVID-19 vaccine administration and 2018 CDC social vulnerability index (SVI) data to ascertain whether inequities in COVID-19 vaccination coverage with respect to county-level SVI have persisted, overall and by urbanicity. Vaccination coverage was defined as the number of persons aged ≥18 years (adults) who had received ≥1 dose of any Food and Drug Administration (FDA)-authorized COVID-19 vaccine divided by the total adult population in a specified SVI category.(†) SVI was examined overall and by its four themes (socioeconomic status, household composition and disability, racial/ethnic minority status and language, and housing type and transportation). Counties were categorized into SVI quartiles, in which quartile 1 (Q1) represented the lowest level of vulnerability and quartile 4 (Q4), the highest. Trends in vaccination coverage were assessed by SVI quartile and urbanicity, which was categorized as large central metropolitan, large fringe metropolitan (areas surrounding large cities, e.g., suburban), medium and small metropolitan, and nonmetropolitan counties.(§) During December 14, 2020-May 1, 2021, disparities in vaccination coverage by SVI increased, especially in large fringe metropolitan (e.g., suburban) and nonmetropolitan counties. By May 1, 2021, vaccination coverage was lower among adults living in counties with the highest overall SVI; differences were most pronounced in large fringe metropolitan (Q4 coverage = 45.0% versus Q1 coverage = 61.7%) and nonmetropolitan (Q4 = 40.6% versus Q1 = 52.9%) counties. Vaccination coverage disparities were largest for two SVI themes: socioeconomic status (Q4 = 44.3% versus Q1 = 61.0%) and household composition and disability (Q4 = 42.0% versus Q1 = 60.1%). Outreach efforts, including expanding public health messaging tailored to local populations and increasing vaccination access, could help increase vaccination coverage in high-SVI counties.

      3. Sample size considerations for mid-season estimates from a large influenza vaccine effectiveness network in the United Statesexternal icon
        Chung JR, Flannery B, Kim SS, Gaglani M, Raiyani C, Belongia EA, McLean HQ, Nowalk MP, Zimmerman RK, Jackson ML, Jackson LA, Martin ET, Monto AS, Patel M.
        Vaccine. 2021 May 13.
        INTRODUCTION: Mid-season influenza vaccine effectiveness (VE) estimates are a useful tool to help guide annual influenza vaccine strain selection, vaccine policy, and public health messaging. We propose using a sample size-driven approach with data-driven inputs for publication of mid-season influenza VE. METHODS: We used pooled inputs for VE by (sub)type and average vaccine coverage by age groups using data from eight seasons of the US Influenza VE Network to calculate sample sizes needed to estimate mid-season VE. RESULTS: We estimate that 135 influenza-positive cases would be needed to detect an overall VE of 40% with 55% vaccine coverage among test-negative controls. Larger sample sizes would be required to produce reliable estimates specifically against influenza A/H3N2 and for older age groups. CONCLUSION: Using an existing network, most of the recent influenza seasons in the US would facilitate valid mid-season VE estimates using the proposed sample sizes for broad age groupings.

      4. Vaccine safety issues at the turn of the 21st centuryexternal icon
        Conklin L, Hviid A, Orenstein WA, Pollard AJ, Wharton M, Zuber P.
        BMJ Glob Health. 2021 May;6(Suppl 2).
        Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO's Global Advisory Committee for Vaccine Safety (GACVS) during 1999-2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations.

      5. A systems map of the economic considerations for vaccination: Application to hard-to-reach populationsexternal icon
        Cox SN, Wedlock PT, Pallas SW, Mitgang EA, Yemeke TT, Bartsch SM, Abimbola T, Sigemund SS, Wallace A, Ozawa S, Lee BY.
        Vaccine. 2021 May 24.
        BACKGROUND: Understanding the economics of vaccination is essential to developing immunization strategies that can be employed successfully with limited resources, especially when vaccinating populations that are hard-to-reach. METHODS: Based on the input from interviews with 24 global experts on immunization economics, we developed a systems map of the mechanisms (i.e., necessary steps or components) involved in vaccination, and associated costs and benefits, focused at the service delivery level. We used this to identify the mechanisms that may be different for hard-to-reach populations. RESULTS: The systems map shows different mechanisms that determine whether a person may or may not get vaccinated and the potential health and economic impacts of doing so. The map is divided into two parts: 1) the costs of vaccination, representing each of the mechanisms involved in getting vaccinated (n = 23 vaccination mechanisms), their associated direct vaccination costs (n = 18 vaccination costs), and opportunity costs (n = 5 opportunity costs), 2) the impact of vaccination, representing mechanisms after vaccine delivery (n = 13 impact mechanisms), their associated health effects (n = 10 health effects for beneficiary and others), and economic benefits (n = 13 immediate and secondary economic benefits and costs). Mechanisms that, when interrupted or delayed, can result in populations becoming hard-to-reach include getting vaccines and key stakeholders (e.g., beneficiaries/caregivers, vaccinators) to a vaccination site, as well as vaccine administration at the site. CONCLUSION: Decision-makers can use this systems map to understand where steps in the vaccination process may be interrupted or weak and identify where gaps exist in the understanding of the economics of vaccination. With improved understanding of system-wide effects, this map can help decision-makers inform targeted interventions and policies to increase vaccination coverage in hard-to-reach populations.

      6. Modeling the impacts of clinical influenza testing on influenza vaccine effectiveness estimatesexternal icon
        Feldstein LR, Ferdinands JM, Self WH, Randolph AG, Aboodi M, Baughman AH, Brown SM, Exline MC, Files DC, Gibbs K, Ginde AA, Gong MN, Grijalva CG, Halasa N, Khan A, Lindsell CJ, Newhams M, Peltan ID, Prekker ME, Rice TW, Shapiro NI, Steingrub J, Talbot HK, Halloran ME, Patel M.
        J Infect Dis. 2021 May 20.
        BACKGROUND: Test-negative design studies for evaluating influenza vaccine effectiveness (VE) enroll patients with acute respiratory infection. Enrollment typically occurs before influenza status is determined, resulting in over-enrollment of influenza-negative patients. With availability of rapid and accurate molecular clinical testing, influenza status could be ascertained prior to enrollment, thus improving study efficiency. We estimate potential biases in VE when using clinical testing. METHODS: We simulate data assuming 60% vaccinated, 25% of those vaccinated are influenza positive, and VE of 50%. We show the effect on VE in five scenarios. RESULTS: VE is affected only when clinical testing preferentially targets patients based on both vaccination and influenza status. VE is overestimated by 10% if non-testing occurs in 39% of vaccinated influenza-positive patients and 24% of others; and if non-testing occurs in 8% of unvaccinated influenza-positive patients and 27% of others. VE is underestimated by 10% if non-testing occurs in 32% of unvaccinated influenza-negative patients and 18% of others. CONCLUSIONS: Although differential clinical testing by vaccine receipt and influenza positivity may produce errors in estimated VE, bias in testing would have to be substantial and overall proportion of patients tested would have to be small to result in a meaningful difference in VE.

      7. Influenza Vaccine Effectiveness for Prevention of Severe Influenza-Associated Illness among Adults in the United States, 2019-2020: A test-negative studyexternal icon
        Grijalva CG, Feldstein LR, Talbot HK, Aboodi M, Baughman AH, Brown SM, Casey JD, Erickson HL, Exline MC, Files DC, Gibbs KW, Ginde AA, Gong MN, Halasa N, Khan A, Lindsell CJ, Nwosu SK, Peltan ID, Prekker ME, Rice TW, Shapiro NI, Steingrub J, Stubblefield WB, Tenforde MW, Patel M, Self WH.
        Clin Infect Dis. 2021 May 20.
        BACKGROUND: Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized. METHODS: We conducted a test-negative study in an intensive care unit (ICU) network at 10 United States hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019-2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders. RESULTS: Among 638 patients, the median (interquartile) age was 57 (44-68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2 to 53%), including 28% (-9% to 52%) against influenza A, and 52% (13% to 74%) against influenza B. VE was higher in adults 18-49 years old (62%; 95% CI: 27% to 81%) than those 50-64 years old (20%, -48% to 57%) and ≥65 years old (-3%; 95% CI: -97% to 46%) (p=0.0789 for interaction). VE was significantly higher against influenza-associated death (80%, 95% CI: 4% to 96%) than non-fatal influenza illness. CONCLUSIONS: During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.

      8. Physician survey regarding updated PCV13 vaccine recommendations for adults ≥65 yearsexternal icon
        Hurley LP, O'Leary ST, Kobayashi M, Crane LA, Cataldi J, Brtnikova M, Beaty BL, Gorman C, Lindley MC, Kempe A.
        J Am Geriatr Soc. 2021 May 14.
        BACKGROUND: In June 2019, the Advisory Committee on Immunization Practices recommended discontinuing the routine use of the pneumococcal conjugate vaccine (PCV13) among adults aged ≥65 years and instead recommended PCV13 be used based on shared clinical decision making (SCDM). OBJECTIVES: We wanted to assess among primary care physicians (1) knowledge and attitudes regarding the new SCDM PCV13 recommendation and (2) how the new recommendation will affect their likelihood of recommending PCV13 to adults aged ≥65 years. DESIGN: This was done by mail and internet-based survey, which was conducted October 2019 through January 2020. The study was carried out on a nationally representative sample of general internists (GIMs) and family physicians (FPs). RESULTS: The response rate was 64% (617/968, GIM 57%, FP 71%). Only 41% of respondents were aware of the SCDM PCV13 recommendation in adults aged ≥65 years; 76% agreed (37% "Strongly," 39% "Somewhat") that their patients aged ≥65 years will get confused by having a SCDM recommendation for PCV13 and a routine recommendation for the pneumococcal polysaccharide vaccine (PPSV23); 60% agreed (18% "Strongly," 42% "Somewhat") that they were unsure of what points to emphasize when having a SCDM conversation with an adult aged ≥65 years about receiving PCV13. Just over 50% reported they would be less likely to recommend PCV13 for adults aged ≥65 years as a result of the new recommendation, but 42% reported that their recommendation for PCV13 would not change. CONCLUSIONS: Word of the new ACIP recommendation for PCV13 for adults aged ≥65 years needs to be further disseminated. Investigation into why some physicians do not plan to change their recommendations is warranted.

      9. Using immunisation caregiver journey interviews to understand and optimise vaccination uptake: lessons from Sierra Leoneexternal icon
        Jalloh MF, Hickler B, Parmley LE, Sutton R, Kulkarni S, Mansaray A, Eleeza O, Patel P, Wilhelm E, Conklin L, Akinjeji A, Toure M, Wolff B, Prybylski D, Wallace AS, Lahuerta M.
        BMJ Glob Health. 2021 May;6(5).
        Quantitative and qualitative assessments have revealed diverse factors that influence the uptake of childhood immunisation services and shed light on reasons for vaccination delays and refusals. UNICEF and partner organisations developed the Immunisation Caregiver Journey Framework as a novel way to understand caregiver experiences in accessing and receiving immunisation services for children. This framework aims to help immunisation programmes identify vaccination barriers and opportunities to improve vaccination uptake by enhancing the overall caregiver journey in a systems-focused manner, using human-centred design principles. In this paper, we adapt the framework into a flexible qualitative inquiry approach with theoretical guidance from interpretative phenomenology. We draw from the implementation experiences in Sierra Leone to inform methodological guidance on how to design and implement the Immunisation Caregiver Journey Interviews (ICJI) to understand the lived experiences of caregivers as they navigate immunisation services for their children. Practical guidance is provided on sampling techniques, conducting interviews, data management, data analysis and the use of data to inform programmatic actions. When properly implemented, the ICJI approach generates a rich qualitative understanding of how caregivers navigate household and community dynamics, as well as primary healthcare delivery systems. We argue that understanding and improving the caregiver journey will enhance essential immunisation outcomes, such as the completion of the recommended vaccination schedule, timeliness of vaccination visits and reduction in dropouts between vaccine doses.

      10. Serotype 2 oral poliovirus vaccine (OPV2) choices and the consequences of delaying outbreak responseexternal icon
        Kalkowska DA, Pallansch MA, Wassilak SG, Cochi SL, Thompson KM.
        Vaccine. 2021 May 13.
        The Global Polio Eradication Initiative (GPEI) faces substantial challenges with managing outbreaks of serotype 2 circulating vaccine-derived polioviruses (cVDPV2s) in 2021. A full five years after the globally coordinated removal of serotype 2 oral poliovirus vaccine (OPV2) from trivalent oral poliovirus vaccine (tOPV) for use in national immunization programs, cVDPV2s did not die out. Since OPV2 cessation, responses to outbreaks caused by cVDPV2s mainly used serotype 2 monovalent OPV (mOPV2) from a stockpile. A novel vaccine developed from a genetically stabilized OPV2 strain (nOPV2) promises to potentially facilitate outbreak response with lower prospective risks, although its availability and properties in the field remain uncertain. Using an established global poliovirus transmission model and building on a related analysis that characterized the impacts of disruptions in GPEI activities caused by the COVID-19 pandemic, we explore the implications of trade-offs associated with delaying outbreak response to avoid using mOPV2 by waiting for nOPV2 availability (or equivalently, delayed responses waiting for national validation of meeting the criteria for nOPV2 initial use). Consistent with prior modeling, responding as quickly as possible with available mOPV2 promises to reduce the expected burden of disease in the outbreak population and to reduce the chances for the outbreak virus to spread to other areas. Delaying cVDPV2 outbreak response (e.g., modeled as no response January-June 2021) to wait for nOPV2 can considerably increase the total expected cases (e.g., by as many as 1,300 cVDPV2 cases in the African region during 2021-2023) and increases the likelihood of triggering the need to restart widescale preventive use of an OPV2-containing vaccine in national immunization programs that use OPV. Countries should respond to any cVDPV2 outbreaks quickly with rounds that achieve high coverage using any available OPV2, and plan to use nOPV2, if needed, once it becomes widely available based on evidence that it is as effective but safer in populations than mOPV2.

      11. Theoretical Framework for Retrospective Studies of the Effectiveness of SARS-CoV-2 Vaccinesexternal icon
        Lewnard JA, Patel MM, Jewell NP, Verani JR, Kobayashi M, Tenforde MW, Dean NE, Cowling BJ, Lopman BA.
        Epidemiology. 2021 Jul 1;32(4):508-517.
        Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. Such studies are now underway amid the ongoing rollout of SARS-CoV-2 vaccines globally. Although traditional case-control and test-negative design studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here, we review the theoretical basis for estimation of vaccine direct effects under traditional case-control and test-negative design frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, nonspecific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The traditional case-control design may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The test-negative design reduces but may not eliminate this confounding, for instance, if individuals who receive vaccination seek care or testing for less-severe illness. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.

      12. Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccinationexternal icon
        Liles E, Irving SA, Dandamudi P, Belongia EA, Daley MF, DeStefano F, Jackson LA, Jacobsen SJ, Kharbanda E, Klein NP, Weintraub E, Naleway AL.
        Vaccine. 2021 May 26.
        BACKGROUND: Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS: Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS: Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS: Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

      13. Baseline Asymptomatic Malaria Infection and Immunogenicity of rVSVΔG-ZEBOV-GP Vaccine: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)external icon
        Mahon BE, Simon J, Widdowson MA, Samai M, Rogier E, Legardy-Williams J, Liu K, Schiffer J, Lange J, DeByle C, Pinner R, Schuchat A, Slutsker L, Goldstein S.
        J Infect Dis. 2021 May 20.
        BACKGROUND: The effect of malaria infection on rVSVΔG-ZEBOV-GP (ERVEBO®) immunogenicity is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-6 Ebola epidemic. In STRIVE's immunogenicity sub-study, participants provided blood samples at baseline, 1, 6, and 9-12 months. Anti-glycoprotein (GP) binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by PCR. RESULTS: Overall, 506 participants enrolled in the immunogenicity sub-study and had ≥1 post-vaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73(14.6%). All GP-ELISA and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants seroresponded by GP-ELISA (≥2-fold rise AND ≥200 EU/ml), while 81.5% seroresponded by PRNT (≥4-fold rise) at ≥1 post-vaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with and without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower.

      14. Genetic Diversity of Meningococcal Serogroup B Vaccine Antigens among Carriage Isolates Collected from Students at Three Universities in the United States, 2015-2016external icon
        Marjuki H, Chang HY, Topaz N, Whaley MJ, Vuong J, Chen A, Jenkins LT, Hu F, Schmink S, Retchless AC, Thomas JD, Acosta AM, McNamara LA, Soeters HM, Mbaeyi S, Wang X.
        mBio. 2021 May 18;12(3).
        Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.IMPORTANCE The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact fHbp genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities.

      15. Stopping a polio outbreak in the midst of war: Lessons from Syriaexternal icon
        Mbaeyi C, Moran T, Wadood Z, Ather F, Sykes E, Nikulin J, Al Safadi M, Stehling-Ariza T, Zomahoun L, Ismaili A, Abourshaid N, Asghar H, Korukluoglu G, Duizer E, Ehrhardt D, Burns CC, Sharaf M.
        Vaccine. 2021 May 27.
        BACKGROUND: Outbreaks of circulating vaccine-derived polioviruses (cVDPVs) pose a threat to the eventual eradication of all polioviruses. In 2017, an outbreak of cVDPV type 2 (cVDPV2) occurred in the midst of a war in Syria. We describe vaccination-based risk factors for and the successful response to the outbreak. METHODS: We performed a descriptive analysis of cVDPV2 cases and key indicators of poliovirus surveillance and vaccination activities during 2016-2018. In the absence of reliable subnational coverage data, we used the caregiver-reported vaccination status of children with non-polio acute flaccid paralysis (AFP) as a proxy for vaccination coverage. We then estimated the relative odds of being unvaccinated against polio, comparing children in areas affected by the outbreak to children in other parts of Syria in order to establish the presence of poliovirus immunity gaps in outbreak affected areas. FINDINGS: A total of 74 cVDPV2 cases were reported, with paralysis onset ranging from 3 March to 21 September 2017. All but three cases were reported from Deir-ez-Zor governorate and 84% had received < 3 doses of oral poliovirus vaccine (OPV). After adjusting for age and sex, non-polio AFP case-patients aged 6-59 months in outbreak-affected areas had 2.5 (95% CI: 1.1-5.7) increased odds of being unvaccinated with OPV compared with non-polio AFP case-patients in the same age group in other parts of Syria. Three outbreak response rounds of monovalent OPV type 2 (mOPV2) vaccination were conducted, with governorate-level coverage mostly exceeding 80%. INTERPRETATION: Significant declines in both national and subnational polio vaccination coverage, precipitated by war and a humanitarian crisis, led to a cVDPV2 outbreak in Syria that was successfully contained following three rounds of mOPV2 vaccination.

      16. Disparities in COVID-19 Vaccination Coverage Between Urban and Rural Counties - United States, December 14, 2020-April 10, 2021external icon
        Murthy BP, Sterrett N, Weller D, Zell E, Reynolds L, Toblin RL, Murthy N, Kriss J, Rose C, Cadwell B, Wang A, Ritchey MD, Gibbs-Scharf L, Qualters JR, Shaw L, Brookmeyer KA, Clayton H, Eke P, Adams L, Zajac J, Patel A, Fox K, Williams C, Stokley S, Flores S, Barbour KE, Harris LQ.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):759-764.
        Approximately 60 million persons in the United States live in rural counties, representing almost one fifth (19.3%) of the population.* In September 2020, COVID-19 incidence (cases per 100,000 population) in rural counties surpassed that in urban counties (1). Rural communities often have a higher proportion of residents who lack health insurance, live with comorbidities or disabilities, are aged ≥65 years, and have limited access to health care facilities with intensive care capabilities, which places these residents at increased risk for COVID-19-associated morbidity and mortality (2,3). To better understand COVID-19 vaccination disparities across the urban-rural continuum, CDC analyzed county-level vaccine administration data among adults aged ≥18 years who received their first dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine, or a single dose of the Janssen COVID-19 vaccine (Johnson & Johnson) during December 14, 2020-April 10, 2021 in 50 U.S. jurisdictions (49 states and the District of Columbia [DC]). Adult COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%) overall and among adults aged 18-64 years (29.1% rural, 37.7% urban), those aged ≥65 years (67.6% rural, 76.1% urban), women (41.7% rural, 48.4% urban), and men (35.3% rural, 41.9% urban). Vaccination coverage varied among jurisdictions: 36 jurisdictions had higher coverage in urban counties, five had higher coverage in rural counties, and five had similar coverage (i.e., within 1%) in urban and rural counties; in four jurisdictions with no rural counties, the urban-rural comparison could not be assessed. A larger proportion of persons in the most rural counties (14.6%) traveled for vaccination to nonadjacent counties (i.e., farther from their county of residence) compared with persons in the most urban counties (10.3%). As availability of COVID-19 vaccines expands, public health practitioners should continue collaborating with health care providers, pharmacies, employers, faith leaders, and other community partners to identify and address barriers to COVID-19 vaccination in rural areas (2).

      17. Rotavirus vaccination likely to be cost saving to society in the United Statesexternal icon
        Newall AT, Leong RN, Reyes JF, Curns AT, Rudd J, Tate J, Macartney K, Parashar U.
        Clin Infect Dis. 2021 May 26.
        BACKGROUND: Following the introduction of rotavirus immunization in 2006 in the United States (US) there were substantial declines in the domestic rotavirus disease burden. In this study we assess the value for money achieved by the program in the decade following vaccine introduction. METHODS: We applied an age-specific static multi-cohort compartmental model to examine the impact and cost-effectiveness of the US rotavirus immunization program in children <5 years of age using healthcare utilization data from 2001-2015 inclusive. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained from both a healthcare system and societal perspective. RESULTS: Declines in healthcare utilization associated with the rotavirus and acute gastroenteritis occurred from 2006 and continued to grow before stabilizing from 2010-2011. From 2011-2015, an estimated annual average of approximately 118,000 hospitalizations, 86,000 emergency department presentations and 460,000 outpatient and physician office visits were prevented. From a societal perspective during this same period the program was estimated to be cost saving in the base case model and in >90% of probabilistic sensitivity analysis simulations and from a healthcare system perspective >98% of simulations found an ICER below $100,000 per QALY gained. CONCLUSIONS: After the program stabilized, we found the rotavirus immunization in the US was likely to have been cost saving to society. The greater than expected healthcare and productivity savings reflect the success of the rotavirus immunization program in the US.

      18. Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel - 33 U.S. Sites, January-March 2021external icon
        Pilishvili T, Fleming-Dutra KE, Farrar JL, Gierke R, Mohr NM, Talan DA, Krishnadasan A, Harland KK, Smithline HA, Hou PC, Lee LC, Lim SC, Moran GJ, Krebs E, Steele M, Beiser DG, Faine B, Haran JP, Nandi U, Schrading WA, Chinnock B, Henning DJ, LoVecchio F, Nadle J, Barter D, Brackney M, Britton A, Marceaux-Galli K, Lim S, Phipps EC, Dumyati G, Pierce R, Markus TM, Anderson DJ, Debes AK, Lin M, Mayer J, Babcock HM, Safdar N, Fischer M, Singleton R, Chea N, Magill SS, Verani J, Schrag S.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):753-758.
        Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

      19. Novel vaccine safety issues and areas that would benefit from further researchexternal icon
        Salmon DA, Lambert PH, Nohynek HM, Gee J, Parashar UD, Tate JE, Wilder-Smith A, Hartigan-Go KY, Smith PG, Zuber PL.
        BMJ Glob Health. 2021 May;6(Suppl 2).
        Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables continual assessment to ensure the benefits outweigh the risks and, when safety problems arise, they are quickly identified, characterised and further problems prevented when possible. We review five vaccine safety case studies: (1) dengue vaccine and enhanced dengue disease, (2) pandemic influenza vaccine and narcolepsy, (3) rotavirus vaccine and intussusception, (4) human papillomavirus vaccine and postural orthostatic tachycardia syndrome and complex regional pain syndrome, and (5) RTS,S/adjuvant system 01 malaria vaccine and meningitis, cerebral malaria, female mortality and rebound severe malaria. These case studies were selected because they are recent and varied in the vaccine safety challenges they elucidate. Bringing these case studies together, we develop lessons learned that can be useful for addressing some of the potential safety issues that will inevitably arise with new vaccines.

      20. CONTEXT: Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of age receiving the vaccine for the first time. OBJECTIVE: To systematically review studies comparing vaccine effectiveness (VE) and immunogenicity after 1 or 2 doses of inactivated influenza vaccine (IIV) in children. DATA SOURCES: Data sources included Medline, Embase, and Cochrane Library databases. STUDY SELECTION: We included studies published in a peer reviewed journal up to April 2, 2019, with available abstracts, written in English, and with children aged 6 months through 8 years. DATA EXTRACTION: VE among fully and partially vaccinated children was compared with that of unvaccinated children. We extracted geometric mean titers of serum hemagglutination inhibition (HAI) antibodies against influenza A(H1N1), A(H3N2), and B-lineage vaccine antigens after 1 and 2 IIV doses. Outcomes were evaluated by age, timing of doses, vaccine composition, and prevaccination titers. RESULTS: A total of 10 VE and 16 immunogenicity studies were included. VE was higher for fully vaccinated groups than partially vaccinated groups, especially for children aged 6-23 months. Our findings show increased HAI titers after 2 doses, compared with 1. Older children and groups with prevaccination antibodies have robust HAI titers after 1 dose. Similar vaccine strains across doses, not the timing of doses, positively affects immune response. LIMITATIONS: Few studies focused on older children. Researchers typically administered one-half the standard dose of IIV. HAI antibodies are an imperfect correlate of protection. CONCLUSIONS: Findings support policies recommending 2 IIV doses in children to provide optimal protection against influenza.

      21. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Adolescents Aged 12-15 Years - United States, May 2021external icon
        Wallace M, Woodworth KR, Gargano JW, Scobie HM, Blain AE, Moulia D, Chamberland M, Reisman N, Hadler SC, MacNeil JR, Campos-Outcalt D, Morgan RL, Daley MF, Romero JR, Talbot HK, Lee GM, Bell BP, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):749-752.
        The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, Inc; Philadelphia, Pennsylvania) in persons aged ≥16 years (1); on December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the vaccine in the same age group (2). As of May 12, 2021, approximately 141.6 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥16 years.* On May 10, 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years (1). On May 12, 2021, ACIP issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(§) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥12 years under an EUA is interim and will be updated as additional information becomes available.

    • Injury and Violence
      1. Bullying Victimization and Perpetration Among US Children with and Without Tourette Syndromeexternal icon
        Charania SN, Danielson ML, Claussen AH, Lebrun-Harris LA, Kaminski JW, Bitsko RH.
        J Dev Behav Pediatr. 2021 May 26.
        OBJECTIVE: Tourette syndrome (TS) and co-occurring mental, behavioral, and developmental disorders (MBDDs) have been shown to affect peer relationships. This study provides nationally representative estimates of diagnosed TS prevalence and the prevalence of parent-reported bullying victimization and perpetration among US children with and without TS. METHODS: This study included 2016-2017 National Survey of Children's Health data on children aged 6 to 17 years (N = 51,001) with parent-reported responses about TS diagnosis and their child's experiences with bullying victimization and perpetration. We calculated weighted prevalence estimates of diagnosed TS and of bullying indicators among children ever diagnosed with TS compared with peers without TS. We conducted a logistic regression analysis to estimate adjusted prevalence ratios of bullying involvement by TS status, controlling for age, sex, and co-occurring MBDDs. RESULTS: By parent report, 0.3% of US children had ever received a diagnosis of TS; most children with a TS diagnosis (83.2%) had a co-occurring MBDD. Among children with TS, 56.1% experienced bullying victimization, 20.7% experienced bullying perpetration, and 15.9% experienced both, compared with 21.6%, 6.0%, and 4.1% for children without TS, respectively. After adjusting for age, sex, and co-occurring MBDDs, only the association between TS and bullying victimization remained statistically significant. CONCLUSION: Compared with children without TS, children with TS overall experience more bullying victimization and perpetration. Health care professionals treating children with TS could assess challenges with peer relationships and co-occurring disorders to provide targeted support and referral.

      2. Engaging Communities in Youth Violence Prevention: Introduction and Contentsexternal icon
        D'Inverno AS, Bartholow BN.
        Am J Public Health. 2021 May;111(S1):S10-s16.

      3. Conflict-related violence and mental health among self-settled Democratic Republic of Congo female refugees in Kampala, Uganda - a respondent driven sampling surveyexternal icon
        Familiar I, Muniina PN, Dolan C, Ogwal M, Serwadda D, Kiyingi H, Bahinduka CS, Sande E, Hladik W.
        Confl Health. 2021 May 26;15(1):42.
        BACKGROUND: Violence and traumatic events are highly prevalent among refugees, but less is known about the impact of these experiences among self-settled refugees in the country of asylum. We evaluated the association between traumatic experiences and PTSD and depression symptoms among female Democratic Republic of Congo (DRC) refugees living in Kampala, Uganda. METHODS: Participants were recruited using respondent driven sampling in one refugee service center in Kampala, Uganda. Eligibility criteria included: Congolese nationality, age 18+ years, self-settled in Kampala for at least 6 months, refugee status or documentation of application for refugee status. Only data from female participants were included in this analysis. Depression symptoms were screened with the Patient Health Questionnaire-2, and symptom criteria for PTSD and traumatic experiences were evaluated with the Harvard Trauma Questionnaire. Logistic regression models were performed to separately assess associations between mental health outcomes (PTSD and depression), rape and non-sexual violence. RESULTS: Five hundred eighty women with a mean age of 33 years were interviewed. Among participants, 73% (95% CI:67-78%) met symptom criteria for PTSD, 57% (95% CI: 51-63%) for depression, and 65% reported thoughts of ending one's life. 79% of women reported experience of rape, for over half (54%) it occurred more than once, and 82% were gang raped. Crude and adjusted odds ratios (ORs) show that PTSD was most strongly associated with being raped (OR = 2.43, p < 0.01), lacking shelter (OR = 2.86, p < 0.01), lacking food or water (OR = 2.53, p = 0.02), lacking access to health care (OR = 2.84, p < 0.01), forced labor (OR = 2.6, p < 0.01), extortion and/or robbery (OR = 3.08, p < 0.01), experiencing the disappearance/kidnapping of a family member or friend (OR = 2.72, p < 0.01), and witnessing the killing or murder of other people (OR = 3.28, p < 0.01). Depression was significantly associated with several traumatic experiences including rape (OR = 2.3, p = 0.01), and experiencing the disappearance/kidnapping of a child or spouse (OR = 1.99, p = 0.01). CONCLUSIONS: Refugee women self-settled in Kampala reported high lifetime experiences of violence and traumatic events including rape, as well as high rates of PTSD and depression. Future programming addressing self-settled refugees and their settlement in host countries may benefit from including local and national integration strategies.

      4. A Model for Effective Community-Academic Partnerships for Youth Violence Preventionexternal icon
        Gorman-Smith D, Bechhoefer D, Cosey-Gay FN, Kingston BE, Nation MA, Vagi KJ, Villamar JA, Zimmerman MA.
        Am J Public Health. 2021 May;111(S1):S25-s27.

      5. Youth Voices in Violence Preventionexternal icon
        Jones G, Jackson T, Ahmed H, Brown Q, Dantzler T, Ford N, Lawrence S, Neely T, Olivas B, Palencia A, Pinder J, Pinder N, Raggs A, Ray C, Robinson Q, Rousseau A, Sims J, Stowe R, Teeples WT, Thomas E, Williams T, Mercado MC.
        Am J Public Health. 2021 May;111(S1):S17-s19.

      6. Developing and Implementing Community-Level Strategies for Preventing Youth Violence in the United Statesexternal icon
        Kingston BE, Zimmerman MA, Wendel ML, Gorman-Smith D, Wright-Kelly E, Mattson SA, Trudeau AT.
        Am J Public Health. 2021 May;111(S1):S20-s24.

      7. Youths and Violence: Changing the Narrativeexternal icon
        Metzler M, Jackson T, Trudeau A.
        Am J Public Health. 2021 May;111(S1):S35-s37.

      8. Social and Structural Determinants of Health and Youth Violence: Shifting the Paradigm of Youth Violence Preventionexternal icon
        Nation M, Chapman DA, Edmonds T, Cosey-Gay FN, Jackson T, Marshall KJ, Gorman-Smith D, Sullivan T, Trudeau AT.
        Am J Public Health. 2021 May;111(S1):S28-s31.

      9. Emergency Department Visits for Bicycle-Related Traumatic Brain Injuries Among Children and Adults - United States, 2009-2018external icon
        Sarmiento K, Haileyesus T, Waltzman D, Daugherty J.
        MMWR Morb Mortal Wkly Rep. 2021 May 14;70(19):693-697.
        Bicycling leads to the highest number of sport and recreation-related emergency department (ED) visits for traumatic brain injuries (TBIs) in the United States (1). Because bicycling continues to grow in popularity,* primarily among U.S. adults, examining the strategies that mitigate the risk for TBI is important. CDC analyzed data from the National Electronic Injury Sursveillance System-All Injury Program (NEISS-AIP) to determine the incidence of EDs for bicycle-related TBIs during 2009-2018. An estimated 596,972 ED visits for bicycle-related TBIs occurred in the United States during the study period. Rates of ED visits were highest among adult males (aged ≥18 years) and among children and adolescents aged 10-14 years during 2009-2018. Overall, the rate of ED visits for bicycle-related TBIs decreased by approximately one half (48.7%) among children and by 5.5% among adults. As the number of persons riding bicycles increases, expansion of comprehensive bicycling safety interventions for bicyclists and drivers by states and local communities, such as interventions to increase driver compliance with traffic laws and helmet use among riders, improvements in bicycling infrastructure, and customized interventions for males and other groups at high risk might help reduce bicycle-related injuries.

      10. Differences in Head Impact Exposures Between Youth Tackle and Flag Football Games and Practices: Potential Implications for Prevention Strategiesexternal icon
        Sarmiento K, Waltzman D, Devine O, Zhang X, DePadilla L, Kresnow MJ, Borradaile K, Hurwitz A, Jones D, Goyal R, Breiding MJ.
        Am J Sports Med. 2021 May 17:3635465211011754.
        BACKGROUND: Interventions designed to reduce the risk for head impacts and concussion in youth football have increased over the past decade; however, understanding of the role of regular game play on head impact exposure among youth tackle and flag football athletes is currently limited. PURPOSE: To explore head impact exposure among youth tackle and flag football athletes (age range, 6-14 years) during both practices and games. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Using the Vector MouthGuard sensor, the authors collected head impact data from 524 tackle and flag youth football athletes over the course of a football season. Quantities of interest were estimated from regression models using Bayesian methods. RESULTS: For impacts ≥10g, a tackle football athlete had an estimated 17.55 (95% CI, 10.78-28.96) times more head impacts per practice compared with a flag football athlete (6.85 [95% CI, 6.05-7.76] and 0.39 [95% CI, 0.24-0.62] head impacts, respectively). Additionally, a tackle football athlete had an estimated 19.48 (95% CI, 12.74-29.98) times more head impacts per game compared with a flag football athlete (13.59 [95% CI, 11.97-15.41] and 0.70 [95% CI, 0.46-1.05] head impacts, respectively). Among tackle football athletes, the estimated average impact rate was 6.51 (95% CI, 5.75-7.37) head impacts during a practice and 12.97 (95% CI, 11.36-14.73) impacts during a game, resulting in 2.00 (95% CI, 1.74-2.29) times more ≥10g head impacts in games versus practices. Tackle football athletes had 2.06 (95% CI, 1.80-2.34) times more high-magnitude head impacts (≥40g) during a game than during a practice. On average, flag football athletes experienced an estimated 0.37 (95% CI, 0.20-0.60) head impacts during a practice and 0.77 (95% CI, 0.53-1.06) impacts during a game, resulting in 2.06 (95% CI, 1.29-3.58) times more ≥10g head impacts in games versus practices. Because of model instability caused by a large number of zero impacts for flag football athletes, a comparison of high-magnitude head impacts is not reported for practices or games. CONCLUSION: This study provides a characterization of the head impact exposure of practices and games among a large population of youth tackle and flag football athletes aged 6 to 14 years. These findings suggest that a greater focus on game-based interventions, such as fair play interventions and strict officiating, may be beneficial to reduce head impact exposures for youth football athletes.

    • Laboratory Sciences
      1. Amylin, Aβ42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cellsexternal icon
        Bubak AN, Beseler C, Como CN, Coughlan CM, Johnson NR, Hassell JE, Burnet AM, Mescher T, Schmid DS, Coleman C, Mahalingam R, Cohrs RJ, Boyd TD, Potter H, Shilleh AH, Russ HA, Nagel MA.
        J Infect Dis. 2021 Apr 8;223(7):1284-1294.
        BACKGROUND: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. METHODS: Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. RESULTS: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. CONCLUSIONS: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

      2. Method for Accurate Quantitation of Volatile Organic Compounds in Urine Using Point of Collection Internal Standard Additionexternal icon
        Chambers DM, Edwards KC, Sanchez E, Reese CM, Fernandez AT, Blount BC, De Jesús VR.
        ACS Omega. 2021 May 18;6(19):12684-12690.
        A method to achieve accurate measurement of unmetabolized volatile organic compounds (VOCs) in urine was developed and characterized. The method incorporates a novel preanalytical approach of adding isotopically labeled internal standard (ISTD) analogues directly to the collection container at the point of collection to compensate for analyte loss to the headspace and the collection container surfaces. Using this approach, 45 toxic VOCs ranging in water solubility and boiling point were evaluated and analyzed by headspace solid-phase microextraction/gas chromatography-mass spectrometry. Results show that urine VOCs could be equally lost to the container headspace as to the container surface suggesting similarity of these two regions as partition phases. Surface adsorption loss was found to trend with compound water solubility. In particular, with no headspace, more nonpolar VOCs experienced substantial losses (e.g., 48% for hexane) in a standard 120 mL urine cup at concentrations in the low- and sub-ppb range. The most polar VOCs evaluated (e.g., tetrahydrofuran) showed no significant loss. Other commonly practiced methods for urine sample collection and analysis such as aliquoting, specimen freezing, and use of surrogate ISTD were found to significantly bias results. With this method, we achieved errors ranging from -8.0 to 4.8% of spiked urine specimens. Paired urine and blood specimens from cigarette smokers were compared to assess this method.

      3. The frequency of lymphogranuloma venereum (LGV) or invasive Chlamydia trachomatis (CT) infection with serovar L1, L2 or L3 is unknown in the United States. While no diagnostic test is commercially available, we used a laboratory-developed test and detected LGV-associated serovar L2 in 14% of 132 remnant CT-positive rectal swabs.

      4. In Vitro Activity of Novel Antifungal Olorofim against Filamentous Fungi and Comparison to Eight Other Antifungal Agentsexternal icon
        Georgacopoulos O, Nunnally NS, Ransom EM, Law D, Birch M, Lockhart SR, Berkow EL.
        J Fungi (Basel). 2021 May 12;7(5).
        Olorofim is a novel antifungal drug that belongs to the orotomide drug class which inhibits fungal dihydroorotate dehydrogenase (DHODH), thus halting pyrimidine biosynthesis and ultimately DNA synthesis, cell growth and division. It is being developed at a time when many invasive fungal infections exhibit antifungal resistance or have limited treatment options. The goal of this study was to evaluate the in vitro effectiveness of olorofim against a large collection of recently isolated, clinically relevant American mold isolates. In vitro antifungal activity was determined for 246 azole-susceptible Aspergillus fumigatus isolates, five A. fumigatus with TR(34)/L98H-mediated resistance, 19 Rhizopus species isolates, 21 Fusarium species isolates, and one isolate each of six other species of molds. Olorofim minimum inhibitory concentrations (MICs) were compared to antifungal susceptibility testing profiles for amphotericin B, anidulafungin, caspofungin, isavuconazole, itraconazole, micafungin, posaconazole, and voriconazole. Olorofim MICs were significantly lower than those of the echinocandin and azole drug classes and amphotericin B. A. fumigatus wild type and resistant isolates shared the same MIC50 = 0.008 μg/mL. In non-Aspergillus susceptible isolates (MIC ≤ 2 μg/mL), the geometric mean (GM) MIC to olorofim was 0.54 μg/mL with a range of 0.015-2 μg/mL. Olorofim had no antifungal activity (MIC ≥ 2 μg/mL) against 10% of the collection (31 in 297), including some isolates from Rhizopus spp. and Fusarium spp. Olorofim showed promising activity against A. fumigatus and other molds regardless of acquired azole resistance.

      5. The polysaccharide capsule is a key virulence factor of Streptococcus pneumoniae There are numerous epidemiologically important pneumococcal capsular serotypes, and recent findings have demonstrated that several of them are commonly found among nonpathogenic commensal species. Here, we describe 9 nonpneumococcal strains carrying close homologs of pneumococcal capsular biosynthetic (cps) loci that were discovered during recent pneumococcal carriage studies of adults in the United States and Kenya. Two distinct Streptococcus infantis strains cross-reactive with pneumococcal serotype 4 and carrying cps4-like capsular biosynthetic (cps) loci were recovered. Opsonophagocytic killing assays employing rabbit antisera raised against S. infantis US67cps4 revealed serotype 4-specific killing of both pneumococcal and nonpneumococcal strains. An S. infantis strain and two Streptococcus oralis strains, all carrying cps9A-like loci, were cross-reactive with pneumococcal serogroup 9 strains in immunodiffusion assays. Antiserum raised against S. infantis US64cps9A specifically promoted killing of serotype 9A and 9V pneumococcal strains as well as S. oralis serotype 9A strains. Serotype-specific PCR of oropharyngeal specimens from a recent adult carriage study in the United States indicated that such nonpneumococcal strains were much more common in this population than serotype 4 and serogroup 9 pneumococci. We also describe S. oralis and S. infantis strains expressing serotypes identical or highly related to serotypes 2, 13, and 23A. This study has expanded the known overlap of pneumococcal capsular serotypes with related commensal species. The frequent occurrence of nonpneumococcal strains in the upper respiratory tract that share vaccine and nonvaccine capsular serotypes with pneumococci could affect population immunity to circulating pneumococcal strains.IMPORTANCE The distributions and frequencies of individual pneumococcal capsular serotypes among nonpneumococcal strains in the upper respiratory tract are unknown and potentially affect pneumococcal serotype distributions among the population and immunity to circulating pneumococcal strains. Repeated demonstration that these nonpneumococcal strains expressing so-called pneumococcal serotypes are readily recovered from current carriage specimens is likely to be relevant to pneumococcal epidemiology, niche biology, and even to potential strategies of employing commensal live vaccines. Here, we describe multiple distinct nonpneumococcal counterparts for each of the pneumococcal conjugate vaccine (PCV) serotypes 4 and 9V. Additional data from contemporary commensal isolates expressing serotypes 2, 13, and 23A further demonstrate the ubiquity of such strains. Increased focus upon this serological overlap between S. pneumoniae and its close relatives may eventually prove that most, or possibly all, pneumococcal serotypes have counterparts expressed by the common upper respiratory tract commensal species Streptococcus mitis, Streptococcus oralis, and Streptococcus infantis.

      6. Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal developmentexternal icon
        Goldberg M, Ciesielski Jones AJ, McGrath JA, Barker-Cummings C, Cousins DS, Kipling LM, Meadows JW, Kesner JS, Marcus M, Monteilh C, Sandler DP.
        PLoS One. 2021 ;16(5):e0251598.
        BACKGROUND: Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. OBJECTIVE: Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. METHODS: Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007-2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. RESULTS: Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. CONCLUSIONS: Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

      7. Improving laboratory quality and capacity through leadership and management training: Lessons from Zambia 2016-2018external icon
        Gopolang F, Zulu-Mwamba F, Nsama D, Kruuner A, Nsofwa D, Kasvosve I, Gomo R, Motlhabane T, Chohan B, Soge O, Osterhage D, Campbell N, Noble M, Downer A, Flandin JF, Nartker A, Koehn C, Nonde LK, Shibemba A, Ndongmo CB, Steinau M, Perrone LA.
        Afr J Lab Med. 2021 ;10(1):1225.
        BACKGROUND: Competent leadership and management are imperative for delivering quality laboratory services; however, few laboratory managers receive job-specific training in organisational management and leadership. OBJECTIVE: To develop and evaluate participants' competencies in organisational leadership and management as measured through learner and laboratory quality improvement assessments. METHODS: This professional development programme employed a mentored, blended learning approach, utilising in-person didactic and online training, with the practical application of a capstone project in the laboratories. Programme impact was evaluated through a series of pre- and post-laboartory assessments using the Stepwise Laboratory Improvement Process Towards Accreditation checklist, as well as learner-competency assessments through online quizzes and discussions. RESULTS: From 2016 to 2018, 31 managers and quality officers from 16 individual laboratories graduated from the programme having completed capstone projects addressing areas in the entire laboratory testing process. Laboratories increased their compliance with the International Organization for Standardization 15189 standard and all but two laboratories significantly increased their accreditation scores. Two laboratories gained three stars, two laboratories gained two stars, and five laboratories gained one star. Five laboratories subsequently achieved International Organization for Standardization 15189 accreditation in 2019. CONCLUSION: This programme taught leadership theory to laboratory managers and allowed them to implement leadership and management practices in the laboratory setting. Programmes such as this complement existing laboratory quality management training programmes such as Strengthening Laboratory Management Toward Accreditation.

      8. Antiretroviral drug exposure in urethral and glans surface sampling of the penisexternal icon
        Haaland RE, Fountain J, Dinh C, Lupo LD, Martin A, Conway-Washington C, Hall L, Kelley CF, Garcia-Lerma JG, Heneine W.
        J Antimicrob Chemother. 2021 May 19.
        BACKGROUND: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab, <LOD-328 ng/swab; darunavir 6 ng/swab, <LOD-149 ng/swab). Estimated peak urethral secretion emtricitabine and darunavir concentrations are between 10 and 20 μg/mL, similar to rectal secretions, 4-fold greater than in plasma, but 2-fold lower than in urine. Tenofovir and elvitegravir were detected on less than 20% of urethral or glans swabs collected within 24 h of dosing. CONCLUSIONS: We document ARV dosing in the urethra and on the glans surface with high drug concentrations noted for emtricitabine and darunavir and lower tenofovir and elvitegravir concentrations. Data suggest a potential protective role of urethral emtricitabine or darunavir against penile HIV acquisition.

      9. Evaluation of Loopamp™ Leishmania Detection Kit and Leishmania Antigen ELISA for Post-Elimination Detection and Management of Visceral Leishmaniasis in Bangladeshexternal icon
        Hossain F, Picado A, Owen SI, Ghosh P, Chowdhury R, Maruf S, Khan MA, Rashid MU, Nath R, Baker J, Ghosh D, Adams ER, Duthie MS, Hossain MS, Basher A, Nath P, Aktar F, Cruz I, Mondal D.
        Front Cell Infect Microbiol. 2021 ;11:670759.
        With reduced prevalence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), direct and field deployable diagnostic tests are needed to implement an effective diagnostic and surveillance algorithm for post-elimination VL control. In this regard, here we investigated the diagnostic efficacies of a loop-mediated isothermal amplification (LAMP) assay (Loopamp™ Leishmania Detection Kit, Eiken Chemical CO., Ltd, Japan), a real-time quantitative PCR assay (qPCR) and the Leishmania antigen ELISA (CLIN-TECH, UK) with different sampling techniques and evaluated their prospect to incorporate into post-elimination VL control strategies. Eighty clinically and rK39 rapid diagnostic test confirmed VL cases and 80 endemic healthy controls were enrolled in the study. Peripheral blood and dried blood spots (DBS) were collected from all the participants at the time of diagnosis. DNA was extracted from whole blood (WB) and DBS via silica columns (QIAGEN) and boil & spin (B&S) methods and tested with qPCR and Loopamp. Urine was collected from all participants at the time of diagnosis and was directly subjected to the Leishmania antigen ELISA. 41 patients were followed up and urine samples were collected at day 30 and day 180 after treatment and ELISA was performed. The sensitivities of the Loopamp-WB(B&S) and Loopamp-WB(QIA) were 96.2% (95% CI 89·43-99·22) and 95% (95% CI 87·69-98·62) respectively. The sensitivity of Loopamp-DBS(QIA) was 85% (95% CI 75·26- 92·00). The sensitivities of the qPCR-WB(QIA) and qPCR-DBS(QIA) were 93.8% (95% CI 86·01-97·94) and 72.5% (95% CI 61·38-81·90) respectively. The specificity of all molecular assays was 100%. The sensitivity and specificity of the Leishmania antigen ELISA were 97.5% (95% CI 91·47-99·70) and 91.95% (95% CI 84·12-96·70) respectively. The Leishmania antigen ELISA depicted clinical cure at day 180 in all the followed-up cases. Efficacy and sustainability identify the Loopamp-WB(B&S) and the Leishmania antigen ELISA as promising and minimally invasive VL diagnostic tools to support VL diagnostic and surveillance activities respectively in the post-elimination era.

      10. Diagnostic Utility of Serum and Urinary Metabolite Analysis in Patients with Interstitial Cystitis/Painful Bladder Syndromeexternal icon
        Kim J, De Hoedt A, Wiggins E, Haywood K, Jin P, Greenwood B, Narain NR, Tolstikov V, Bussberg V, Barbour KE, Kiebish MA, Freedland S, Anger JT.
        Urology. 2021 May 16.
        OBJECTIVE: To identify the potential biomarkers of interstitial cystitis/painful bladder syndrome (IC), a chronic syndrome of bladder-centric pain with unknown etiology that has an adverse impact on quality of life, we analyzed the urine and serum metabolomes of a cohort of IC patients and non-disease controls (NC). METHODS: Home collection of serum and urine samples was obtained from 19 IC and 20 NC females in the Veterans Affairs (VA) Health Care System. IC was diagnosed independently by thorough review of medical records using established criteria. Biostatistics and bioinformatics analyses, including univariate analysis, unsupervised clustering, random forest analysis, and metabolite set enrichment analysis (MSEA), were then utilized to identify potential IC biomarkers. RESULTS: Metabolomics profiling revealed distinct expression patterns between NC and IC. Random forest analysis of urine samples suggested discriminators specific to IC; these include phenylalanine, purine, 5-oxoproline, and 5-hydroxyindoleacetic acid. When these urinary metabolomics-based analytes were combined into a single model, the AUC was 0.92, suggesting strong potential clinical value as a diagnostic signature. Serum-based metabolomics did not provide potential IC discriminators. CONCLUSIONS: Analysis of serum and urine revealed that women with IC have distinct metabolomes, highlighting key metabolic pathways that may provide insight into the pathophysiology of IC. The findings from this pilot study suggest that integrated analyses of urinary metabolites, purine, phenylalanine, 5-oxoproline, and 5-HIAA, can lead to promising IC biomarkers for pathophysiology of IC. Validation of these results using a larger dataset is currently underway.

      11. Genomic features of humoral immunity support tolerance model in Egyptian rousette batsexternal icon
        Larson PA, Bartlett ML, Garcia K, Chitty J, Balkema-Buschmann A, Towner J, Kugelman J, Palacios G, Sanchez-Lockhart M.
        Cell Rep. 2021 May 18;35(7):109140.
        Bats asymptomatically harbor many viruses that can cause severe human diseases. The Egyptian rousette bat (ERB) is the only known reservoir for Marburgviruses and Sosuga virus, making it an exceptional animal model to study antiviral mechanisms in an asymptomatic host. With this goal in mind, we constructed and annotated the immunoglobulin heavy chain locus, finding an expansion on immunoglobulin variable genes associated with protective human antibodies to different viruses. We also annotated two functional and distinct immunoglobulin epsilon genes and four distinctive functional immunoglobulin gamma genes. We described the Fc receptor repertoire in ERBs, including features that may affect activation potential, and discovered the lack of evolutionary conserved short pentraxins. These findings reinforce the hypothesis that a differential threshold of regulation and/or absence of key immune mediators may promote tolerance and decrease inflammation in ERBs.

      12. Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetesexternal icon
        Lundstig A, McDonald SL, Maziarz M, Weldon WC, Vaziri-Sani F, Lernmark Å, Nilsson AL.
        J Gen Virol. 2021 May;102(5).
        Ljungan virus (LV), a Parechovirus of the Picornavirus family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87-012 LV isolate. The goal was to determine NLVA titres in incident 0-18 years old newly diagnosed type 1 diabetes patients (n=67) and school children controls (n=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (P=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (P=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.

      13. MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathologyexternal icon
        Lundy SR, Abney K, Ellerson D, Igietseme JU, Carroll D, Eko FO, Omosun YO.
        Pathogens. 2021 May 7;10(5).
        Genital Chlamydia trachomatis infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including Chlamydia infection. Among the miRNAs involved in regulating host responses and pathologic outcome of Chlamydia infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of Chlamydia infection. We developed miR-378b knockout mice (miR-378b(-/-)) using Crispr/Cas and infected them along with their wild-type (WT) control with Chlamydia to compare the infectivity and reproductive pathologies. The results showed that miR-378b(-/-) mice were unable to clear the infection compared to WT mice; also, miR-378b(-/-) mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b(-/-) mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b(-/-) mice showed protection from Chlamydia-induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease.

      14. Influenza Virus-Induced Novel miRNAs Regulate the STAT Pathwayexternal icon
        Othumpangat S, Beezhold DH, Umbright CM, Noti JD.
        Viruses. 2021 May 23;13(6).
        MicroRNAs (miRNAs) are essential regulators of gene expression in humans and can control pathogenesis and host-virus interactions. Notably, the role of specific host miRNAs during influenza virus infections are still ill-defined. The central goal of this study was to identify novel miRNAs and their target genes in response to influenza virus infections in airway epithelium. Human airway epithelial cells exposed to influenza A virus (IAV) induced several novel miRNAs that were identified using next-generation sequencing (NGS) and their target genes by biochemical methods. NGS analysis predicted forty-two RNA sequences as possible miRNAs based on computational algorithms. The expression patterns of these putative miRNAs were further confirmed using RT-PCR in human bronchial epithelial cells exposed to H1N1, H9N1(1P10), and H9N1 (1WF10) strains of influenza virus. A time-course study showed significant downregulation of put-miR-34 in H1N1 and put-miR-35 in H9N1(1P10)-infected cells, which is consistent with the NGS data. Additionally, put-miR-34 and put-miR-35 showed a high fold enrichment in an argonaute-immunoprecipitation assay compared to the controls, indicating their ability to form a complex with argonaute protein and RNA-induced silencing complex (RISC), which is a typical mode of action found with miRNAs. Our earlier studies have shown that the replication and survival of influenza virus is modulated by certain transcription factors such as NF-ĸB. To identify the target(s) of these putative miRNAs, we screened 84 transcription factors that have a role in viral pathogenesis. Cells transfected with mimic of the put-miR-34 showed a significant decrease in the expression of Signal Transducers and Activators of Transcription 3 (STAT3), whereas the inhibitor of put-miR-34 showed a significant increase in STAT3 expression and its phosphorylation. In addition, put-miR-34 had 76% homology to the untranslated region of STAT3. NGS and PCR array data submitted to the Gene Ontology project also predicted the role of transcription factors modulated by put-miR-34. Our data suggest that put-miR-34 may be a good target for antiviral therapy.

      15. Pharmacogenetic (PGx) testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials (RMs) are currently available for many of the variants that are tested. The Association for Molecular Pathology PGx Work Group has published a series of papers recommending alleles for inclusion in clinical testing. Several of the alleles were not considered for Tier 1 due to a lack of reference materials. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention (CDC) based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 18 DNA samples derived from Coriell cell lines. DNA samples were distributed to five volunteer testing laboratories for genotyping using three commercially available and laboratory developed tests. Several Tier 2 variants including CYP2C9*13, CYP2C19*35, the CYP2C cluster variant (rs12777823), two variants in VKORC1 (rs61742245 and rs72547529) related to warfarin resistance and two variants in GGCX (rs12714145 and rs11676382) related to clotting factor activation were identified among these samples. These publicly available materials complement the pharmacogenetic reference materials previously characterized by GeT-RM and will support the quality assurance and quality control programs of clinical laboratories performing pharmacogenetic testing.

      16. New methylene blue derivatives suggest novel anti-orthopoxviral strategiesexternal icon
        Priyamvada L, Burgado J, Baker-Wagner M, Kitaygorodskyy A, Olson V, Lingappa VR, Satheshkumar PS.
        Antiviral Res. 2021 May 13;191:105086.
        Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives.

      17. Serotype-Switch Variant of Multidrug-Resistant Streptococcus pneumoniae Sequence Type 271external icon
        Scherer EM, Beall B, Metcalf B.
        Emerg Infect Dis. 2021 Jun;27(6):1689-1692.
        We discovered 3 invasive, multidrug-resistant Streptococcus pneumoniae isolates of vaccine-refractory capsular serotype 3 that recently arose within the successful sequence type 271 complex through a serotype switch recombination event. Mapping genomic recombination sites within the serotype 3/sequence type 271 progeny revealed a 55.9-kb donated fragment that encompassed cps3, pbp1a, and additional virulence factors.

      18. On the robustness of latent class models for diagnostic testing with no gold standardexternal icon
        Schofield MR, Maze MJ, Crump JA, Rubach MP, Galloway R, Sharples KJ.
        Stat Med. 2021 May 14.
        It is difficult to estimate sensitivity and specificity of diagnostic tests when there is no gold standard. Latent class models have been proposed as a potential solution as they provide estimates without the need for a gold standard. Using a motivating example of the evaluation of point of care tests for leptospirosis in Tanzania, we show how a realistic violation of assumptions underpinning the latent class model can lead directly to substantial bias in the estimates of the parameters of interest. In particular, we consider the robustness of estimates of sensitivity, specificity, and prevalence, to the presence of additional latent states when fitting a two-state latent class model. The violation is minor in the sense that it cannot be routinely detected with goodness-of-fit procedures, but is major with regard to the resulting bias.

      19. Viral replicon particles protect IFNAR(-/-) mice against lethal Crimean-Congo hemorrhagic fever virus challenge three days after vaccinationexternal icon
        Spengler JR, Welch SR, Scholte FE, Rodriguez SE, Harmon JR, Coleman-McCray JD, Nichol ST, Montgomery JM, Bergeron É, Spiropoulou CF.
        Antiviral Res. 2021 May 24:105090.
        Crimean-Congo hemorrhagic fever virus (CCHFV) causes mild to severe and fatal disease in humans. Person-to-person transmission is common, necessitating the availability of rapidly deliverable therapeutic and prophylactic interventions to mitigate CCHFV spread. Previously, we showed complete protection using one dose of a viral replicon particle (VRP) vaccine administered 28 days before CCHFV challenge. In order to determine the utility of the VRP vaccine for rapid vaccination protocols, we assessed the efficacy of such vaccination administered at various intervals relative to challenge in IFNAR(-/-) mice. Unvaccinated mice uniformly succumbed to disease by 8 days post infection (dpi). All mice vaccinated 14, 7, or 3 days prior to CCHFV challenge survived infection. Mice vaccinated -14 or -7 dpi were fully protected from clinical disease, whereas mice inoculated -3 dpi developed signs of disease prior to recovering to baseline values 5-9 dpi. These data support the utility of the VRP vaccine for modified short course vaccination protocols to protect against disease and severe outcomes.

      20. Chromosome-Level Genome Sequence of Leishmania (Leishmania) tropica Strain CDC216-162, Isolated from an Afghanistan Clinical Caseexternal icon
        Unoarumhi Y, Batra D, Sheth M, Narayanan V, Lin W, Zheng Y, Rowe LA, Pohl J, de Almeida M.
        Microbiol Resour Announc. 2021 May 20;10(20).
        PacBio and Illumina MiSeq platforms were used for genomic sequencing of a Leishmania (Leishmania) tropica strain isolated from a patient infected in Pakistan. PacBio assemblies were generated using Flye v2.4 and polished with MiSeq data. The results represent a considerable improvement of the currently available genome sequences in the GenBank database.

      21. Isolation and characterization of novel reassortant mammalian orthoreovirus from pigs in the United Statesexternal icon
        Wang L, Li Y, Walsh T, Shen Z, Li Y, Nath ND, Lee J, Zheng B, Tao Y, Paden CR, Queen K, Zhang S, Tong S, Ma W.
        Emerg Microbes Infect. 2021 May 21:1-43.
        Mammalian orthoreovirus (MRV) infects multiple mammalian species including humans. A United States Midwest swine farm with approximately one thousand 3-month-old pigs experienced an event, in which more than 300 pigs showed neurological signs, like "down and peddling", with approximately 40% mortality. A novel MRV was isolated from the diseased pigs. Sequence and phylogenetic analysis revealed that the isolate was a reassortant virus containing viral gene segments from three MRV serotypes that infect human, bovine and swine. The M2 and S1 segment of the isolate showed 94% and 92% nucleotide similarity to the M2 of the MRV2 D5/Jones and the S1 of the MRV1 C/bovine/Indiana/MRV00304/2014, respectively; the remaining eight segments displayed 93%-94% nucleotide similarity to those of the MRV3 FS-03/Porcine/USA/2014. Pig studies showed that both MRV-infected and native contact pigs displayed fever, diarrhea and nasal discharge. MRV RNA was detected in different intestinal locations of both infected and contact pigs, indicating that the MRV isolate is pathogenic and transmissible in pigs. Seroconversion was also observed in experimentally infected pigs. A prevalence study on more than 180 swine serum samples collected from two states without disease revealed 40-52% positive to MRV. All results warrant the necessity to monitor MRV epidemiology and reassortment as the MRV could be an important pathogen for the swine industry and a novel MRV might emerge to threaten animal and public health.

    • Maternal and Child Health
      1. Does Early Identification of Central Congenital Hypothyroidism Result in Improved Outcomes?external icon
        Donaldson MD, Grosse SD.
        J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2373-e2375.

      2. Intrapartum group B Streptococcal prophylaxis and childhood weight gainexternal icon
        Mukhopadhyay S, Bryan M, Dhudasia MB, Quarshie W, Gerber JS, Grundmeier RW, Koebnick C, Sidell MA, Getahun D, Sharma AJ, Spiller MW, Schrag SJ, Puopolo KM.
        Arch Dis Child Fetal Neonatal Ed. 2021 May 6.
        OBJECTIVE: To determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP). DESIGN: Retrospective cohort study of 13 804 infants. SETTING: Two perinatal centres and a primary paediatric care network in Philadelphia. PARTICIPANTS: Term infants born 2007-2012, followed longitudinally from birth to 5 years of age. EXPOSURES: GBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure. OUTCOMES: Difference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates. RESULTS: GBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children. CONCLUSION: GBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies.

      3. Prevalence, serotype and antibiotic susceptibility of Group B Streptococcus isolated from pregnant women in Jakarta, Indonesiaexternal icon
        Safari D, Gultom SM, Tafroji W, Azzahidah A, Soesanti F, Khoeri MM, Prayitno A, Pimenta FC, da Gloria Carvalho M, Uiterwaal C, Putri ND.
        PLoS One. 2021 ;16(5):e0252328.
        Group B Streptococcus (GBS) is a bacterial pathogen which is a leading cause of neonatal infection. Currently, there are limited GBS data available from the Indonesian population. In this study, GBS colonization, serotype distribution and antimicrobial susceptibility profile of isolates were investigated among pregnant women in Jakarta, Indonesia. Demographics data, clinical characteristics and vaginal swabs were collected from 177 pregnant women (mean aged: 28.7 years old) at 29-40 weeks of gestation. Bacterial culture identification tests and latex agglutination were performed for GBS. Serotyping was done by conventional multiplex PCR and antibiotic susceptibility testing by broth microdilution. GBS colonization was found in 53 (30%) pregnant women. Serotype II was the most common serotype (30%) followed by serotype III (23%), Ia and IV (13% each), VI (8%), Ib and V (6% each), and one non-typeable strain. All isolates were susceptible to vancomycin, penicillin, ampicillin, cefotaxime, daptomycin and linezolid. The majority of GBS were resistant to tetracycline (89%) followed by clindamycin (21%), erythromycin (19%), and levofloxacin (6%). The serotype III was more resistant to erythromycin, clindamycin, and levofloxacin and these isolates were more likely to be multidrug resistant (6 out of 10) compared to other serotypes. This report provides demographics of GBS colonization and isolate characterization in pregnant women in Indonesia. The results may facilitate preventive strategies to reduce neonatal GBS infection and improve its treatment.

      4. Urodynamic characteristics of neurogenic bladder in newborns with myelomeningocele and refinement of the definition of bladder hostility: Findings from the UMPIRE multi-center studyexternal icon
        Tanaka ST, Yerkes EB, Routh JC, Tu DD, Austin JC, Wiener JS, Vasquez E, Joseph DB, Ahn JJ, Wallis MC, Williams T, Rose C, Baum MA, Cheng EY.
        J Pediatr Urol. 2021 May 1.
        INTRODUCTION: Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration. OBJECTIVE: To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization. STUDY DESIGN: The UMPIRE protocol follows a cohort of newborns with myelomeningocele at nine children's hospitals in the United States. Infants are started on clean intermittent catheterization shortly after birth. If residual volumes are low and there is no or mild hydronephrosis, catheterization is discontinued. Baseline urodynamics are obtained at or before 3 months of age to determine further management. Based on protocol-specific definitions, urodynamic studies were reviewed by the clinical site in addition to a central review team; and if necessary, by all site urologists to achieve 100% concurrence. RESULTS: We reviewed 157 newborn urodynamic studies performed between May 2015 and September 2017. Of these 157 infants, 54.8% were boys (86/157). Myelomeningocele closure was performed in-utero in 18.4% (29/157) and postnatally in 81.5% (128/157) of newborns. After primary review, reviewers agreed on overall bladder categorization in 50% (79/157) of studies. Concurrence ultimately reached 100% with further standardization of interpretation. We found that it was not possible to reliably differentiate a bladder contraction due to detrusor overactivity from a volitional voiding contraction in an infant. We revised our categorization system to group the "normal" and "safe" categories together as "low risk". Additionally, diagnosis of detrusor sphincter dyssynergia (DSD) with surface patch electrodes could not be supported by other elements of the urodynamics study. We excluded DSD from our revised high risk category. The final categorizations were high risk in 15% (23/157); intermediate risk in 61% (96/157); and low risk in 24% (38/157). CONCLUSION: We found pitfalls with our original categorization for bladder hostility. Notably, DSD could not be reliably measured with surface patch of electrodes. The effect of this change on future renal outcomes remains to be defined.

      5. Newborn screening is an important public health program and a triumph of preventive medicine. Economic analyses show that the benefits of newborn screening clearly outweigh the costs for certain diseases, but not necessarily for other ones. This is due to the great diversity of the natural history of the diseases detected, to the fact that each of these diseases considered individually is rare, and to differences in the effectiveness of interventions. In addition, the benefit-cost ratio of screening for a particular disorder may differ between countries, specifically between high-income and low- and middle-income countries. The burden of a disorder may also be alleviated by increased clinical awareness and effective clinical services, even in the absence of newborn screening. In this article, we focus on economic analyses of newborn screening for primary congenital hypothyroidism, which has been in place in high-income countries for roughly 40 years, and for classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Screening for the latter is not yet universal, even in high-income countries, although the lack of universal implementation may reflect factors other than economic considerations.

    • Medicine
      1. A national level estimation of population need for blood in Indiaexternal icon
        Mammen JJ, Asirvatham ES, Lakshmanan J, Sarman CJ, Mani T, Charles B, Upadhyaya S, Rajan S.
        Transfusion. 2021 May 15.
        BACKGROUND: The population need for blood is the total volume required to transfuse all the individuals who need transfusion in a defined population over a defined period. The clinical demand will arise when people with a disease or condition who require transfusion, access healthcare services, and subsequently the clinicians request blood. Essentially, the conversion of need to demand must be maximum to avoid preventable mortality and morbidity. The study estimated the population need for blood in India. METHODS: The methodology included a comprehensive literature review to determine the diseases and conditions requiring transfusion, the population at risk, and prevalence or incidence; and Delphi method to estimate the percentage of people requiring transfusion, and the quantum. RESULTS: The estimated annual population need was 26.2 million units (95% CI; 17.9-38.0) of whole blood to address the need for red cells and other components after the separation process. The need for medical conditions was 11.0 million units (95% CI:8.7-14.7), followed by surgery 6.6 million (95% CI:3.8-10.0), pediatrics 5.0 million (95% CI:3.5-7.0), and obstetrics and gynecology 3.6 million units (95% CI:1.9-6.2). The gap between need and demand which depends upon the access and efficiency of healthcare service provision was estimated at 13 million units. CONCLUSION: The study brings evidence to highlight the gap between need and demand and the importance of addressing it. It cannot be just the responsibility of blood transfusion or health systems, it requires a multi-sectoral approach to address the barriers affecting the conversion of need to clinical demand for blood.

    • Mining
      1. Assessing Longwall Gateroad Ground Response and Support Alternativesexternal icon
        Esterhuizen GS, Klemetti T, Sears MM, Zhang P, van Dyke M, Dougherty H, Tulu IB.
        Min Metall Explor. 2021 .
        Ground falls in longwall gateroad entries remain a concern in modern longwall operations. The gateroads are subject to changing horizontal and vertical ground stress induced by longwall extraction. These stress changes can result in failure of the strata around an entry leading to large deformations of the entry roof, floor, and ribs. The gateroad support systems are required to control the failed strata while maintaining safe access to the longwall face and unimpeded ventilation. This paper presents research that was conducted to better understand the stability issues in gateroad excavations and to develop procedures for evaluating support and layout alternatives for longwall gateroads. Using the results of a field-monitoring program and numerical model analysis of case histories, a conceptual model of gateroad support needs was developed. The conceptual model formed the basis for developing a set of equations that can be used to estimate likely roof sag and support loading for given roof geology and longwall-induced loading conditions. The developed equations were used to compare predicted gateroad stability to field study results, showing satisfactory agreement. The calculation procedures are used to demonstrate their application in assessing support alternatives at a case study mine. It is concluded that the developed analysis procedures provide realistic assessments of likely ground stability and can be used to evaluate alternative gateroad support systems at operating longwall mines. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

    • Nutritional Sciences
      1. OBJECTIVE: To examine whether the density of neighbourhood restaurants affected the frequency of eating restaurant meals and subsequently affected diet quality. DESIGN: Cross-sectional and longitudinal designs. Structural equation models assessed the indirect relationship between restaurant density (≤3 miles (4.8 km) of participant addresses) and dietary quality (Healthy Eating Index 2010 (HEI)) via the frequency of eating restaurant meals, after adjustment for sociodemographics, select health conditions, region, residence duration and area-level income. SETTING: Urbanised areas in multiple regions of the USA, years 2000-2002 and 2010-2012. PARTICIPANTS: Participants aged 45-84 years were followed for 10 years (n 3567). RESULTS: Median HEI (out of 100) was 59 at baseline and 62 at follow-up. Cross-sectional analysis found residing in areas with a high density of restaurants (highest ranked quartile) was associated with 52% higher odds of frequently eating restaurant meals (≥3 times/week, odds ratio [OR]:1.52, 95% confidence interval [CI] 1.18-1.98) and 3% higher odds of having lower dietary quality (HEI lowest quartile<54, OR:1.03,CI:1.01-1.06); associations were not sustained in longitudinal analyses. Cross-sectional analysis found 34% higher odds of having lower dietary quality for those who frequently ate at restaurants (OR:1.34,CI:1.12-1.61); and more restaurant meals (over time increase ≥1 times/week) was associated with higher odds of having worse dietary quality at follow-up (OR:1.21,CI:1.00-1.46). CONCLUSIONS: Restaurant density was associated with frequently eating out in cross-sectional and longitudinal analyses but was associated with the lower dietary quality only in cross-sectional analyses. Frequent restaurant meals were negatively related to dietary quality. Interventions that encourage less frequent eating out may improve population dietary quality.

      2. Anemia and Vitamin B-12 and Folate Status in Women of Reproductive Age in Southern India: Estimating Population-Based Risk of Neural Tube Defectsexternal icon
        Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar S, Zhang M, Pfeiffer CM, Qi YP, Rose CE, Williams JL, Bonam W, Crider KS.
        Curr Dev Nutr. 2021 May;5(5):nzab069.
        BACKGROUND: Women of reproductive age (WRA) are a high-risk population for anemia and micronutrient deficiencies. However, there are few representative population-level data from India, which could help inform evidence-based recommendations and policy. OBJECTIVE: To conduct a population-based biomarker survey of anemia and vitamin B-12 and folate status in WRA as part of a periconceptional surveillance program in southern India. METHODS: Participants were WRA (15-40 y) who were not pregnant or lactating. Whole blood (n = 979) was analyzed for hemoglobin via a Coulter counter (Coulter HMX). Plasma, serum, and RBCs were processed and stored at -80°C or less until batch analysis. Vitamin B-12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were evaluated via microbiological assay. Anemia and severe anemia were defined as hemoglobin <12.0 g/dL and <8.0 g/dL, respectively. Vitamin B-12 deficiency and insufficiency were defined as total vitamin B-12 <148 pmol/L and <221 pmol/L, respectively. Folate deficiency and insufficiency were defined as RBC folate <305 nmol/L and <748 nmol/L. A previously developed Bayesian model was used to predict neural tube defect (NTD) prevalence per 10,000 births. RESULTS: A total of 41.5% of WRA had anemia and 3.0% had severe anemia. A total of 48.3% of WRA had vitamin B-12 deficiency and 74.3% had vitamin B-12 insufficiency. The prevalence of RBC folate deficiency was 7.6%, and 79.3% of WRA had RBC folate <748 nmol/L, the threshold for optimal NTD prevention. Predicted NTD prevalence per 10,000 births based on RBC folate concentrations was 20.6 (95% uncertainty interval: 16.5-25.5). CONCLUSIONS: The substantial burden of anemia, vitamin B-12 deficiency, and RBC folate insufficiency in WRA in this setting suggests an opportunity for anemia and birth defects prevention. Findings will directly inform the development of a randomized trial for anemia and birth defects prevention in southern India.This study was registered at as NCT04048330.

      3. Dietary Sources of Plasma trans Fatty Acids among Adults in the United States: NHANES 2009-2010external icon
        Li C, Richter P, Cobb LK, Kuiper HC, Seymour J, Vesper HW.
        Curr Dev Nutr. 2021 May;5(5):nzab063.
        BACKGROUND: Intake of trans fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations. OBJECTIVE: The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009-2010 in the United States. METHODS: Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables. RESULTS: Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (P < 0.001 for palmitelaidic acid, elaidic acid, vaccenic acid, and sumTFAs); cakes, cookies, pastries, and pies (P < 0.001 for elaidic acid, vaccenic acid, and sumTFAs; P < 0.05 for linolelaidic acid); milk and milk desserts (P < 0.01 for palmitelaidic acid and vaccenic acid; P < 0.05 for linolelaidic acid and sumTFAs); beef/veal, lamb/goat, and venison/deer (P < 0.01 for vaccenic acid; P < 0.05 for sumTFAs); and butters (P < 0.001 for palmitelaidic acid and vaccenic acid; P < 0.05 for sumTFAs). CONCLUSIONS: The findings suggest that the above 5 food groups/subgroups could be the main dietary sources of plasma TFAs among adults in the United States in 2009-2010.

      4. Supplemental Vitamin D Increased Serum Total 25-Hydroxyvitamin D in the US Adult Population During 2007-2014external icon
        Schleicher RL, Sternberg MR, Potischman N, Gahche JJ, Storandt RJ, Maw KL, Pfeiffer CM.
        J Nutr. 2021 May 24.
        BACKGROUND: Data from the 2007-2010 NHANES suggested that vitamin D supplements contributed to increased serum concentrations of 25-hydroxyvitamin D [25(OH)D] in the US population. OBJECTIVES: We sought to determine whether 25(OH)D continued to increase during NHANES 2011-2014 and whether associations of 25(OH)D with preselected covariates differed across time periods. METHODS: For this study, 25(OH)D was measured in adults (≥20 y) using LC-MS/MS. Descriptive and regression analyses were stratified by survey period to investigate the effects of age, race-Hispanic origin, sex, season, BMI, dietary vitamin D, and vitamin D-containing supplements. A multiple linear regression model was used to assess 25(OH)D changes between two 4-y survey periods, namely 2007-2010 and 2011-2014. RESULTS: We observed several significant concomitant increases between 2007-2010 and 2011-2014: unadjusted mean 25(OH)D increased by 2.7 nmol/L (95% CI: 0, 5.4 nmol/L; P = 0.048), the percentage of persons taking any vitamin D-containing supplements increased 2.9% (95% CI: 0.03, 5.5%; P = 0.0314), and the percentage of persons taking high-dose (≥1000 IU/d) vitamin D-containing supplements increased 8.6% (95% CI: 6.9, 9.9%; P < 0.0001). With covariate adjustment, the increase in 25(OH)D from 2007-2010 to 2011-2014 was no longer statistically significant [1.4 nmol/L (95% CI: -3.0, 0.23 nmol/L; P = 0.09)]. After adjustments, several large differences in 25(OH)D remained, namely non-Hispanic blacks had 25(OH)D 22 nmol/L lower than that of non-Hispanic whites, and users of vitamin D-containing supplements ≥1000 IU/d had 25(OH)D 31 nmol/L higher than that of nonusers. CONCLUSIONS: After adjusting for vitamin D supplement dose, the overall adjusted increase in 25(OH)D was no longer statistically significant, suggesting that changes in US adults' 25(OH)D concentrations between NHANES periods 2007-2010 and 2011-2014 may primarily be associated with changes in vitamin D supplementation.

      5. Systematic Process Framework for Conducting Implementation Science Research in Food Fortification Programsexternal icon
        Teachout E, Rowe LA, Pachon H, Tsang BL, Yeung LF, Rosenthal J, Razzaghi H, Moore M, Panagides D, Milani P, Cannon MJ.
        Glob Health Sci Pract. 2021 May 25.
        Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention.

    • Obituary
      1. The Lasting Contribution of Dr. Saba Masho on Youth Violence Preventionexternal icon
        Chapman DA, Sullivan TN, Edmonds T, Adera T, Marshall KJ.
        Am J Public Health. 2021 May;111(S1):S6-s7.

    • Occupational Safety and Health
      1. BACKGROUND: The landscaping services industry is one of the more dangerous in the United States, with higher rates of both fatal and nonfatal injuries than the all-industry average. This study uses claims from the Ohio Bureau of Workers' Compensation (OHBWC) database to identify high rates of occupational injuries and illnesses in this industry in Ohio. The causes of those illnesses and injuries are highlighted to identify common factors. METHODS: The OHBWC database includes injured-worker industry identification, occupation, business size, demographics, diagnoses, and free-text descriptions of injury circumstances. We identified landscaping service industry claims from 2001 to 2017, and describe annual claim counts and rates. RESULTS: Over the 17-year period, 18,037 claims were accepted, with "Struck by object or equipment" and "Overexertion involving outside sources" being the most common events or exposures. Sprains and fractures were the most prevalent of the more serious lost-time (LT) injuries. Free-text descriptions of claims indicate that arborist work and loading/unloading of work vehicles and trailers are particularly hazardous. Younger and shorter-tenured workers were injured most frequently, although the average workers' age was higher for LT claims. The total cost of claims to the OHBWC from the landscaping services industry for 2001-2017 was over $226,000,000. Almost $214,000,000, or 94.4%, was for LT injuries and illnesses, even though LT claims comprise only 18% of total claims. CONCLUSIONS: Targeted improvements in landscaper safety could come from controlling events leading to LT claims. Engineering controls and improved training are strongly recommended to reduce falls, overexertion, and struck-by injuries.

      2. Occupational exposure to high-level disinfectants and risk of miscarriage among nursesexternal icon
        Ding M, Lawson C, Johnson C, Rich-Edwards J, Gaskins AJ, Boiano J, Henn S, Rocheleau C, Chavarro JE.
        Occup Environ Med. 2021 May 26.
        OBJECTIVES: To examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses. METHODS: Our study included women who enrolled in the Nurses' Health Study 3 (2010-2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs. RESULTS: Our study included 2579 nurses with a median of 5.6 years of follow-up (range: 1-9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93). CONCLUSIONS: We observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously.

      3. How Will the Future of Work Shape OSH Research and Practice? A Workshop Summaryexternal icon
        Felknor SA, Streit JM, McDaniel M, Schulte PA, Chosewood LC, Delclos GL.
        Int J Environ Res Public Health. 2021 May 26;18(11).
        Growth of the information economy and globalization of labor markets will be marked by exponential growth in emerging technologies that will cause considerable disruption of the social and economic sectors that drive the global job market. These disruptions will alter the way we work, where we work, and will be further affected by the changing demographic characteristics and level of training of the available workforce. These changes will likely result in scenarios where existing workplace hazards are exacerbated and new hazards with unknown health effects are created. The pace of these changes heralds an urgent need for a proactive approach to understand the potential effects new and emerging workplace hazards will have on worker health, safety, and well-being. As employers increasingly rely on non-standard work arrangements, research is needed to better understand the work organization and employment models that best support decent work and improved worker health, safety, and well-being. This need has been made more acute by the SARS-CoV-2 global pandemic that has resulted in dramatic changes in employment patterns, millions of lost jobs, an erosion of many economic sectors, and widespread disparities which further challenge occupational safety and health (OSH) systems to ensure a healthy and productive workplace. To help identify new research approaches to address OSH challenges in the future, a virtual workshop was organized in June 2020 with leading experts in the fields of OSH, well-being, research methods, mental health, economics, and life-course analysis. A paradigm shift will be needed for OSH research in the future of work that embraces key stakeholders and thinks differently about research that will improve lives of workers and enhance enterprise success. A more transdisciplinary approach to research will be needed that integrates the skills of traditional and non-traditional OSH research disciplines, as well as broader research methods that support the transdisciplinary character of an expanded OSH paradigm. This article provides a summary of the presentations, discussion, and recommendations that will inform the agenda of the Expanded Focus for Occupational Safety and Health (Ex4OSH) International Conference, planned for December 2021.

      4. Needs and Procedures for a National Anthropometry Study of Law Enforcement Officersexternal icon
        Hsiao H, Whisler R, Bradtmiller B.
        Hum Factors. 2021 Jun 2:187208211019157.
        OBJECTIVES: This research aims to determine the need and extent for a national anthropometry survey of law enforcement officers (LEOs) via an exploratory investigation of anthropometric changes of LEOs in four decades and comparisons of the LEO data with three existing military and civilian anthropometry sources. BACKGROUND: The best available anthropometric dataset of LEOs is 45 years old and has largely become outdated due to demographic changes. Assessing the extent of anthropometric changes of LEOs through a sample and evaluating the differences of the sample against existing anthropometric datasets is a step toward ascertaining the necessity for a national LEO anthropometry study. METHOD: Thirty-two body dimensions of 67 regional male LEOs and seven female LEOs were measured, and the data of males were compared with the best available LEO anthropometry data from 1975 and three recent non-LEO anthropometry databases. RESULTS: Anthropometric dimensions were significantly different between this LEO study and existing data sources, especially in chest circumference and body weight. Most of the significant differences are important differences for LEO protective gear and vehicle design. CONCLUSION: The study confirmed that the existing 45-year-old LEO dataset and recent Army and civilian datasets would not be suitable for armor and equipment design for the current LEO population. APPLICATION: The study results are useful in supporting the decision of investing in a national LEO anthropometry survey and for equipment manufacturers to recognize the distinctiveness of LEO anthropometry from other populations and the magnitude of anthropometry changes of LEOs over the past 45 years.

      5. Acrylamide (ACM) is a high-volume industrial chemical with diverse uses in manufacturing, construction and laboratory research. ACM is a well-established neurotoxic agent causing peripheral neuropathy with impairment in the arms and legs of exposed workers, most thoroughly studied in Swedish tunnel workers exposed to ACM grouting. A quantitative risk assessment was performed to assess ACM risk to workers. Using data from a published paper investigating peripheral neuropathies in Chinese chemical workers, estimates of exposure response for vibration perception threshold and nerve conduction velocities were calculated, based on hemoglobin adducts and air concentrations as exposure metrics. The benchmark dose procedure was applied in order to calculate excess risks of impairment, defined as adverse performance exceeding the 95(th) percentile in unexposed populations, at various concentrations of airborne ACM exposure. Under the assumptions in this risk assessment, after three years of inhalation exposure at 0.3 mg/m(3), the excess attributable impairment manifest in vibration perception and nerve conduction velocity is estimated to occur in 1-2% of workers. For 10 years at 0.3 mg/m(3) ACM inhalation (equivalent to 3 years at 1.0 mg/m(3)) the excess prevalence of impairment would be 2-14% of workers, assuming the effect continues to accrue linearly in time. Using published data, the risks of impairment from peripheral neuropathy attributable to exclusively airborne ACM exposure can be predicted for exposure periods less than 10 years. The risks associated with dermal and airborne ACM exposures can be estimated by characterizing working process environments using ACM Hb-adduct levels and possibly monitored with urinary biomarkers.

      6. Evaluation of total inward leakage for NIOSH-approved elastomeric half-facepiece, full-facepiece, and powered air-purifying respirators using sodium chloride and corn oil aerosolsexternal icon
        Rengasamy S, Zhuang Z, Lawrence RB, Boutin B, Yorio P, Horvatin M, McClain C, Harris JR, Coffey C.
        J Occup Environ Hyg. 2021 May 26:1-9.
        Recently, total inward leakage (TIL) for filtering facepiece and elastomeric half-mask respirators (EHRs) was measured according to the International Organization for Standardization (ISO) test method standard 16900-1:2014 that showed larger TIL for corn oil aerosol than for NaCl aerosol. Comparison of TIL measured for different aerosols for higher protection level respirators is lacking. The objective of this study was to determine TIL for EHRs, full-facepiece respirators, and loose-fitting and tight-fitting powered air-purifying respirators (PAPRs) using NaCl and corn oil aerosols to compare. TIL was measured for two models each of EHRs, full-facepiece respirators, and loose-fitting and tight-fitting PAPRs. After fit testing with a PortaCount (TSI, St. Paul, MN) using the Occupational Safety and Health Administration (OSHA) protocol, eight subjects were tested in the NaCl aerosol chamber first and then in the corn oil aerosol chamber, while another eight subjects tested in the reverse order. Subjects were randomly assigned to one of the two groups. TIL was measured as a ratio of mass-based aerosol concentrations inside the mask to the test chamber while the subjects performed ISO 16900-1-defined exercises using continuous sampling methods. The concentration of corn oil aerosol was measured with one light scattering photometer, alternately, and NaCl aerosol was measured using two flame photometers. Results showed the geometric mean TIL for EHR was significantly (p < 0.05) larger for corn oil aerosol than for NaCl aerosol. EHR models equipped with P100 filters showed relatively smaller TIL values than the same models with N95 filters showing that TIL was inversely related to filter efficiency. Interestingly, TIL was significantly (p < 0.05) larger for NaCl aerosol than for corn oil aerosol for PAPRs, but not for full-facepiece respirators. TIL was inversely related to fit factors of respirator types. Overall, filter efficiency and faceseal leakage determine TIL. The relative trends in TIL for the two aerosols' test methods differ between respirator types indicating that generalization of TIL for respirator types may not be appropriate when using different test agents.

      7. An investigation of the effectiveness of vibration-reducing gloves for controlling vibration exposures during grinding handheld workpiecesexternal icon
        Xu XS, Welcome DE, McDowell TW, Warren C, Service S, Lin H, Chen Q, Dong RG.
        Appl Ergon. 2021 May 12;95:103454.
        Prolonged and intensive vibration exposures during the grinding of handheld workpieces may cause hand-arm vibration syndrome. The objectives of this study are to develop an on-the-hand method for evaluating vibration-reducing (VR) gloves, and to determine whether VR gloves can significantly reduce the vibration exposures. A worker holding and pressing a typical workpiece (golf club head) against a grinding wheel or belt in order to shape the workpiece was simulated, and the input vibration and those on the workpiece and hand-arm system were measured. Ten human subjects participated in the experiment. The results demonstrate that VR gloves significantly reduced the vibrations at the palm, hand dorsum, and wrist. The grinding interface condition and hand feed force did not substantially affect glove effectiveness. The use of gloves slightly increased the workpiece resonant response, but the resonant response did not significantly affect glove effectiveness. This study concluded that the use of VR gloves can help control vibration exposures of workers performing grinding of handheld workpieces.

    • Parasitic Diseases

      1. Evaluation of the durability of long-lasting insecticidal nets in Guatemalaexternal icon
        Castellanos ME, Rodas S, Juárez JG, Lol JC, Chanquin S, Morales Z, Vizcaino L, Smith SC, Vanden Eng J, Woldu HG, Lenhart A, Padilla N.
        Malar J. 2021 May 14;20(1):219.
        BACKGROUND: Insecticide-treated bed nets (ITNs) are widely used for the prevention and control of malaria. In Guatemala, since 2006, ITNs have been distributed free of charge in the highest risk malaria-endemic areas and constitute one of the primary vector control measures in the country. Despite relying on ITNs for almost 15 years, there is a lack of data to inform the timely replacement of ITNs whose effectiveness becomes diminished by routine use. METHODS: The survivorship, physical integrity, insecticide content and bio-efficacy of ITNs were assessed through cross-sectional surveys conducted at 18, 24 and 32 months after a 2012 distribution of PermaNet® 2.0 in a malaria focus in Guatemala. A working definition of 'LLIN providing adequate protection' was developed based on the combination of the previous parameters and usage of the net. A total of 988 ITNs were analysed (290 at 18 months, 349 at 24 months and 349 at 32 months). RESULTS: The functional survivorship of bed nets decreased over time, from 92% at 18 months, to 81% at 24 months and 69% at 32 months. Independent of the time of the survey, less than 80% of the bed nets that were still present in the household were reported to have been used the night before. The proportion of bed nets categorized as "in good condition" per World Health Organization (WHO) guidelines of the total hole surface area, diminished from 77% to 18 months to 58% at 32 months. The portion of ITNs with deltamethrin concentration less than 10 mg/m(2) increased over time. Among the bed nets for which bioassays were conducted, the percentage that met WHO criteria for efficacy dropped from 90% to 18 months to 52% at 32 months. The proportion of long-lasting insecticidal nets (LLINs) providing adequate protection was 38% at 24 months and 21% at 32 months. CONCLUSIONS: At 32 months, only one in five of the LLINs distributed in the campaign provided adequate protection in terms of survivorship, physical integrity, bio-efficacy and usage. Efforts to encourage the community to retain, use, and properly care for the LLINs may improve their impact. Durability assessments should be included in future campaigns.

      2. Cutaneous Leishmaniasis Caused by an Unknown Leishmania Strain, Arizona, USAexternal icon
        de Almeida M, Zheng Y, Nascimento FS, Bishop H, Cama VA, Batra D, Unoarumhi Y, Afghan AK, Shi VY, LeBoit PE, Liu EW, Donovan FM.
        Emerg Infect Dis. 2021 Jun;27(6):1714-1717.
        We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.

      3. Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015-2016external icon
        Diarra Y, Koné O, Sangaré L, Doumbia L, Haidara DB, Diallo M, Maiga A, Sango HA, Sidibé H, Mihigo J, Nace D, Ljolje D, Talundzic E, Udhayakumar V, Eckert E, Woodfill CJ, Moriarty LF, Lim P, Krogstad DJ, Halsey ES, Lucchi NW, Koita OA.
        Malar J. 2021 May 25;20(1):235.
        BACKGROUND: The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. METHODS: Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2000-200,000 asexual parasites/μL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42. were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. RESULTS: A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI 78.5-88.4%) in the AL arm and 93.1% (95% CI 89.7-96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0-95.9%) in the AL arm and 97.1% (93.6-100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. CONCLUSIONS: The findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

      4. The Immediate Effects of a Combined Mass Drug Administration and Indoor Residual Spraying Campaign to Accelerate Progress towards Malaria Elimination in Grande-Anse, Haitiexternal icon
        Druetz T, Stresman G, Ashton RA, Joseph V, van den Hoogen L, Worges M, Hamre KE, Fayette C, Monestime F, Impoinvil D, Rogier E, Chang MA, Lemoine JF, Drakeley C, Eisele TP.
        J Infect Dis. 2021 May 16.
        BACKGROUND: Haiti is planning targeted interventions to accelerate progress towards malaria elimination. In the most affected Department (Grande-Anse), a combined mass drug administration (MDA) and indoor residual spraying (IRS) campaign was launched in October 2018. This study assessed the intervention effectiveness in reducing P. falciparum prevalence. METHODS: An ecological quasi-experimental study was designed, using a pre- and post-test with nonrandomized control group. Surveys were conducted in November 2017 in a panel of easy access groups (25 schools and 16 clinics), and were repeated 2-6 weeks after the campaign, in November 2018. Single-dose sulfadoxine-pyrimethamine and primaquine was used for MDA, and primiphos methyl as insecticide for IRS. RESULTS: A total of 10,006 participants were recruited. 52% of the population in the intervention area reported having received MDA. Prevalence diminished between 2017 and 2018 in both areas, but the reduction was significantly larger in the intervention area (ratio of adjusted risk ratios = 0.32, 95% confidence interval [0.104 - 0.998]). CONCLUSIONS: Despite a moderate coverage, the campaign was effective in reducing P. falciparum prevalence immediately after one round. Targeted MDA+IRS are useful in pre-elimination settings to rapidly decrease the parasite reservoir, an encouraging step to accelerate progress towards malaria elimination.

      5. Chagas Disease: Implementation of Screening to Benefit Mother and Infantexternal icon
        Edwards MS, Montgomery SP.
        Clin Perinatol. 2021 Jun;48(2):331-342.
        Pregnancy-based screening would identify women with Chagas disease, allowing for treatment of Trypanosoma cruzi-infected women and infants to prevent potentially fatal Chagas cardiomyopathy.

      6. Surveillance of Human Guinea Worm in Chad, 2010-2018external icon
        Guagliardo SA, Ruiz-Tiben E, Hopkins DR, Weiss AJ, Ouakou PT, Zirimwabagabo H, Unterwegner K, Tindall D, Cama VA, Bishop H, Sapp SG, Roy SL.
        Am J Trop Med Hyg. 2021 May 24.
        The total number of Guinea worm cases has been reduced by 99.9% since the mid-1980s when the eradication campaign began. Today, the greatest number of cases is reported from Chad. In this report, we use surveillance data collected by the Chad Guinea Worm Eradication Program to describe trends in human epidemiology. In total, 114 human cases were reported during the years 2010-2018, with highest rates of containment (i.e., water contamination prevented) in the years 2013, 2014, 2016, and 2017 (P < 0.0001). Approximately half of case-patients were female, and 65.8% of case-patients were aged 30 years or younger (mean: 26.4 years). About 34.2% of case-patients were farmers. Cases were distributed across many ethnicities, with a plurality of individuals being of the Sara Kaba ethnicity (21.3%). Most cases occurred between the end of June and the end of August and were clustered in the Chari Baguirmi (35.9%) and Moyen Chari regions (30.1%). Cases in the northern Chari River area peaked in April and in August, with no clear pattern in the southern Chari River area. History of travel within Chad was reported in 7.0% of cases, and male subjects (12.5%) were more likely than female subjects (1.7%) to have reported a history of travel (P = 0.03). Our findings confirm that human Guinea worm is geographically disperse and rare. Although the proportion of case-patients with travel history is relatively small, this finding highlights an additional challenge of surveillance in mobile populations in the final stages of the global eradication campaign.

      7. The identification and characterization of proteins produced during human infection with Plasmodium spp. have guided the malaria community in research, diagnosis, epidemiology, and other efforts. Recently developed methods for the detection of these proteins (antigens) in the laboratory have provided new types of data that can inform the evaluation of malaria diagnostics, epidemiological investigations, and overall malaria control strategies. Here, the focus is primarily on antigens that are currently known to be detectable in human specimens and on their impact on the understanding of malaria in human populations. We highlight historical and contemporary laboratory assays for malaria antigen detection, the concept of an antigen profile for a biospecimen, and ways in which binary results for a panel of antigens could be interpreted and utilized for different analyses. Particular emphasis is given to the direct comparison of field-level malaria diagnostics and laboratory antigen detection for the development of an external evaluation scheme. The current limitations of laboratory antigen detection are considered, and the future of this developing field is discussed.

      8. Malaria prevention and treatment in migrant agricultural workers in Dangur district, Benishangul-Gumuz, Ethiopia: social and behavioural aspectsexternal icon
        Tadesse Y, Irish SR, Chibsa S, Dugassa S, Lorenz LM, Gebreyohannes A, Teka H, Solomon H, Gezahegn E, Petros Y, Haile M, Eshetu M, Murphy M.
        Malar J. 2021 May 19;20(1):224.
        BACKGROUND: Sixty percent of the Ethiopia population is at risk of malaria, with the highest prevalence reported in Gambella (6%) and Benishangul-Gumuz (3%) regions. Within these regions are large agricultural developments with high numbers of seasonal migrant workers. The migrant workers are believed to be at increased risk for malaria infection due to their poor living conditions and outdoor activities, but there is little information on their specific behaviours and health risks. This study was conducted to address this gap. METHODS: Quantitative observations were conducted from September to December 2017 in the Benishangul-Gumuz Region. The nightly routines of mobile migrant workers were observed every month for 4 consecutive months. The study team collected quantitative data including nocturnal behavioural observations of worker living conditions, malaria prevention efforts, and work activities and surveys of worker representatives. Qualitative data was collected from migrant workers, farm managers and local health providers using focus group discussions and semi-structured interviews. RESULTS: Migrant workers arrived in the study area during the peak malaria transmission season and the workers in focus groups reported repeated cases of malaria during their stay on the farms. Overall, less than a quarter of the migrant workers were sleeping under a mosquito net by midnight in all 4 observation months. Some work activities also took place outdoors at night. The study additionally found a lack of access to malaria prevention and treatment at the farms and challenges in utilizing local public health facilities. CONCLUSIONS: There is a need to better address malaria prevention and treatment needs among migrant workers in Ethiopia through outreach from existing healthcare infrastructure and within the farms themselves. This will help prevent malaria transmission both within this population and prevent transmission of malaria back to home communities in lower burden areas in Ethiopia.

      9. Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoniexternal icon
        Wiegand RE, Secor WE, Fleming FM, French MD, King CH, Deol AK, Montgomery SP, Evans D, Utzinger J, Vounatsou P, de Vlas SJ.
        PLoS Negl Trop Dis. 2021 May 25;15(5):e0009444.
        BACKGROUND: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. METHODOLOGY: A total of 22,488 children aged 6-15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003-2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. PRINCIPAL FINDINGS: S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. CONCLUSIONS/SIGNIFICANCE: Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual's intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

    • Program Evaluation
      1. In 2012, the Centers for Disease Control and Prevention (CDC) established the Achieving Public Health Impact through Research (APHIR) contract mechanism. APHIR provides CDC's Centers, Institute, and Offices (CIOs) a mechanism that supports multiyear, high impact public health research. Awarded projects supported research on a wide range of topics (e.g., cancer surveillance, HIV education programs, development of biological assays, and evaluation of traumatic brain injury prevention programs) and achieved diverse outcomes (e.g., contribution to the body of knowledge in their field, changes in practice and health service delivery, and capacity building). This article describes how existing impact frameworks and a variety of methods and tools (key informant interviews, online survey, bibliometric analysis, Altmetric and document reviews) were used to identify the outcomes achieved by awarded projects. The approach discussed in this paper can be used to evaluate projects that involve a diversity of activities and outcomes.

    • Public Health Leadership and Management
      1. BACKGROUND: A recent systematic review evaluated the effectiveness of strategies to improve healthcare provider (HCP) performance in low-income and middle-income countries. The review identified strategies with varying effects, including in-service training, supervision and group problem-solving. However, whether their effectiveness changed over time remained unclear. In particular, understanding whether effects decay over time is crucial to improve sustainability. METHODS: We conducted a secondary analysis of data from the aforementioned review to explore associations between time and effectiveness. We calculated effect sizes (defined as percentage-point (%-point) changes) for HCP practice outcomes (eg, percentage of patients correctly treated) at each follow-up time point after the strategy was implemented. We estimated the association between time and effectiveness using random-intercept linear regression models with time-specific effect sizes clustered within studies and adjusted for baseline performance. RESULTS: The primary analysis included 37 studies, and a sensitivity analysis included 77 additional studies. For training, every additional month of follow-up was associated with a 0.19 %-point decrease in effectiveness (95% CI: -0.36 to -0.03). For training combined with supervision, every additional month was associated with a 0.40 %-point decrease in effectiveness (95% CI: -0.68 to -0.12). Time trend results for supervision were inconclusive. For group problem-solving alone, time was positively associated with effectiveness, with a 0.50 %-point increase in effect per month (95% CI: 0.37 to 0.64). Group problem-solving combined with training was associated with large improvements, and its effect was not associated with time. CONCLUSIONS: Time trends in the effectiveness of different strategies to improve HCP practices vary among strategies. Programmes relying solely on in-service training might need periodical refresher training or, better still, consider combining training with group problem-solving. Although more high-quality research is needed, these results, which are important for decision-makers as they choose which strategies to use, underscore the utility of studies with multiple post-implementation measurements so sustainability of the impact on HCP practices can be assessed.

      2. How can we strengthen the Joint External Evaluation?external icon
        Stowell D, Garfield R.
        BMJ Glob Health. 2021 May;6(5).

    • Reproductive Health
      1. The safety of asthma medications during pregnancy and lactation: Clinical management and research prioritiesexternal icon
        Chambers CD, Krishnan JA, Alba L, Albano JD, Bryant AS, Carver M, Cohen LS, Gorodetsky E, Hernandez-Diaz S, Honein MA, Jones BL, Murray RK, Namazy JA, Sahin L, Spong CY, Vasisht KP, Watt K, Wurst KE, Yao L, Schatz M.
        J Allergy Clin Immunol. 2021 Jun;147(6):2009-2020.
        Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.

      2. Update to U.S. Selected Practice Recommendations for Contraceptive Use: Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetateexternal icon
        Curtis KM, Nguyen A, Reeves JA, Clark EA, Folger SG, Whiteman MK.
        MMWR Morb Mortal Wkly Rep. 2021 May 21;70(20):739-743.
        U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), adapted by CDC from global guidance developed by the World Health Organization (WHO), provides evidence-based guidance on contraceptive use for U.S. health care providers (1). During January-February, 2021, CDC evaluated the 2019 WHO recommendation on self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (2). CDC adopted the WHO recommendation on the basis of moderate-certainty evidence that self-administered DMPA-SC is safe and effective, and has higher continuation rates compared with provider-administered DMPA. The new U.S. SPR recommendation states that self-administered DMPA-SC should be made available as an additional approach to deliver injectable contraception. Provider-administered DMPA should remain available. Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be offered in a noncoercive manner through a shared decision-making process between patients and their health care providers, with a focus on patient preferences and equitable access to the full range of contraceptive methods.

      3. COVID-19 and family planning service delivery: Findings from a survey of U.S. physiciansexternal icon
        Zapata LB, Curtis KM, Steiner RJ, Reeves JA, Nguyen AT, Miele K, Whiteman MK.
        Prev Med. 2021 May 31:106664.
        Equitable access to contraception is critical for reproductive autonomy. Using cross-sectional data from the DocStyles survey administered September-October 2020 (68% response rate), we compared changes in family planning-related clinical services and healthcare delivery strategies before and during the COVID-19 pandemic and assessed service provision issues among 1063 U.S. physicians whose practice provided family planning services just before the pandemic. About one-fifth of those whose practices provided the following services or strategies just before the pandemic discontinued these services during the pandemic: long-acting reversible contraception (LARC) placement (16%); LARC removal (17%); providing or prescribing emergency contraceptive pills (ECPs) in advance (18%); and reminding patients about contraception injections or LARC removal or replacement (20%). Many practices not providing the following services or strategies just before the pandemic initiated these services during the pandemic: telehealth for contraception initiation (43%); telehealth for contraception continuation (48%); and renewing contraception prescriptions without requiring an office visit (36%). While a smaller proportion of physicians reported service provision issues in the month before survey completion than at any point during the pandemic, about one-third still reported fewer adult females seeking care (37%) and technical challenges with telehealth (32%). Discontinuation of key family planning services during the COVID-19 pandemic may limit contraception access and impede reproductive autonomy. Implementing healthcare service delivery strategies that reduce the need for in-person visits (e.g., telehealth for contraception, providing or prescribing ECPs in advance) may decrease disruptions in care. Resources exist for public health and clinical efforts to ensure contraception access during the pandemic.

    • Substance Use and Abuse
      1. Drugs and Drug Classes Involved in Overdose Deaths Among Females, United States: 1999-2017external icon
        Carmichael AE, Schier JG, Mack KA.
        J Womens Health (Larchmt). 2021 May 20.
        Background: Drug overdose deaths among U.S. women have risen steadily from 1999 to 2017, especially among certain ages. Various studies report involvement of drugs and drug classes in overdose deaths. Less is known, however, regarding the combinations that are most often indicated on death certificates, particularly among females. Analyzing mutually, exclusive drug/drug class combinations listed on death certificates of females are the objective of this study. Materials and Methods: Mortality data for U.S. female residents were obtained from the 1999 to 2017 National Vital Statistics System (n = 260,782). Analyses included deaths with an underlying cause of death based on International Classification of Diseases, 10th Revision (ICD-10) codes for drug overdoses. The drug/drug class involved included individual 4-digit ICD-10 codes in the range T36.0-T50.9, including poisoning deaths due to all drugs, excluding alcohol. Years from 1999 to 2017 were grouped in six 3-year categories with the most recent year (2017) left separate for analysis. All drug overdose deaths were analyzed in mutually exclusive categories. Results: From 1999 to 2017, the top-listed drug/drug class overall and by year grouping was solely "other and unspecified drugs, medicaments and biological substances"; however, that listing dropped from 25.8% from the 1999 to 2001 period to 14.1% in 2017. Overall, the next most frequent single drug/drug class mentions were "natural and semisynthetic opioids" (20,951; 8.0%) and "cocaine" (10,882; 4.2%). Two of the top five drug/drug class combinations included benzodiazepines ("natural and semisynthetic opioids"/"benzodiazepines" and "methadone"/"benzodiazepines"). Conclusions: Analyzing trends in drugs and drug classes involved in female drug overdose deaths is a critical foundation for developing gender-responsive public health interventions. Reducing high-risk drug use by improving prescribing practices, preventing drug use initiation, and addressing use of multiple drugs can help prevent overdose deaths.

      2. Do out-of-pocket costs influence retention and adherence to medications for opioid use disorder?external icon
        Dunphy C, Peterson C, Zhang K, Jones CM.
        Drug Alcohol Depend. 2021 May 21;225:108784.
        BACKGROUND: Availability of medications for opioid use disorder (MOUD) has increased during the past two decades but treatment retention and adherence remain low. This study aimed to measure the impact of out-of-pocket buprenorphine cost on treatment retention and adherence among US commercially insured patients. METHODS: Medical payment records from IBM MarketScan were analyzed for 6,439 adults age 18-64 years with commercial insurance who initiated buprenorphine treatment during January 1, 2016 to June 30, 2017. Regression models analyzed the relationship between patients' average daily out-of-pocket buprenorphine cost and buprenorphine retention (at least 80 % days covered by buprenorphine) at three different thresholds (180, 360, and 540 days) and adherence (the number of days of buprenorphine coverage) within each retention threshold. Models controlled for patient demographic and clinical characteristics including age, sex, presence of other substance use disorders, psychiatric and pain diagnoses, and receipt of prescription medications. RESULTS: A one dollar increase in daily out-of-pocket buprenorphine cost was associated with a 12-14 % decrease in the odds of retention and a 5-8 % increase in the number of days without buprenorphine coverage during each analyzed retention threshold. CONCLUSION: Recent policies have attempted to address supply-side barriers to MOUD treatment. This study highlights patient cost-sharing as a demand-side barrier to MOUD. While the average out-of-pocket buprenorphine cost is lower than two decades ago, this study suggests even at current levels such costs decrease retention and adherence among commercially insured patients. Efforts to address demand-side barriers could help maximize the health and social benefits of buprenorphine-based MOUD.

      3. BACKGROUND: To determine how clinicians with a DATA waiver to prescribe buprenorphine for opioid use disorder (OUD) adapted during the COVID-19 pandemic to emergency authorities, including use of telehealth to prescribe buprenorphine, the challenges faced by clinicians, and strategies employed by them to manage patients with OUD. METHODS: From June 23, 2020 to August 19, 2020, we conducted an electronic survey of U.S. DATA-waivered clinicians. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Among 10,238 respondents, 68 % were physicians, 25 % nursing-related providers, and 6% physician assistants; 28 % reported never prescribing or not prescribing in the 12 months prior to the survey. Among the 72 % of clinicians who reported past 12-month buprenorphine prescribing (i.e. active practitioners during the pandemic) 30 % reported their practice setting closed to in-person visits during COVID-19; 33 % reported remote prescribing to new patients without an in-person examination. The strongest predictors of remote buprenorphine prescribing to new patients were prescribing buprenorphine to larger numbers of patients in an average month in the past year and closure of the practice setting during the pandemic; previous experience with remote prescribing to established patients prior to COVID-19 also was a significant predictor. Among clinicians prescribing to new patients without an in-person examination, 5.5 % reported difficulties with buprenorphine induction, most commonly withdrawal symptoms. CONCLUSIONS: Telehealth practices and prescribing to new patients without an in-person examination were adopted by DATA-waivered clinicians during the first six months of COVID-19. Permanent adoption of these authorities may enable expanded access to buprenorphine treatment.

      4. Characteristics of Adults Who Use Both Marijuana and E-Cigarette, or Vaping, Products : A Cross-Sectional Study, Utah, 2018external icon
        Lewis NM, Friedrichs M, Wagstaff SS, Nakashima AK, Dunn AC.
        Public Health Rep. 2021 May 26:333549211018679.
        OBJECTIVES: Among young people, dual use of marijuana and e-cigarette, or vaping, products (EVPs) is linked with using more inhalant substances and other substances, and poorer mental health. To understand antecedents and potential risks of dual use in adults, we analyzed a representative adult population in Utah. METHODS: We used data from the 2018 Utah Behavioral Risk Factor Surveillance System (n = 10 380) and multivariable logistic regression to evaluate differences in sociodemographic characteristics, comorbidities, and risk factors among adults aged ≥18 who reported currently using both EVPs (any substance) and marijuana (any intake mode), compared with a referent group of adults who used either or neither. RESULTS: Compared with the referent group, adults using EVPs and marijuana had greater odds of being aged 18-29 (adjusted odds ratio [aOR] = 12.44; 95% CI, 6.15-25.14) or 30-39 (aOR = 3.75; 95% CI, 1.73-8.12) versus ≥40, being male (aOR = 3.29; 95% CI, 1.82-5.96) versus female, reporting ≥14 days of poor mental health in previous 30 days (aOR = 2.30; 95% CI, 1.23-4.32) versus <14 days, and reporting asthma (aOR = 2.09; 95% CI, 1.02-4.31), chronic obstructive pulmonary disorder (aOR = 2.94; 95% CI, 1.19-7.93), currently smoking cigarettes (aOR = 4.56; 95% CI, 2.63-7.93), or past-year use of prescribed chronic pain medications (aOR = 2.13; 95% CI, 1.06-4.30), all versus not. CONCLUSIONS: Clinicians and health promotion specialists working with adults using both EVPs and marijuana should assess risk factors and comorbidities that could contribute to dual use or associated outcomes and tailor prevention messaging accordingly.

      5. Congruence of opioid prescriptions and dispensing using electronic records and claims dataexternal icon
        Nataraj N, Zhang K, Strahan AE, Guy GP.
        Health Serv Res. 2021 May 18.
        OBJECTIVE: To quantify discrepancies between opioid prescribing and dispensing via the percentage of patients with Electronic Medical Record (EMR) prescriptions who subsequently filled the prescription within 90 days, defined as congruence, and compared opioid congruence with related medications. DATA SOURCES: Deidentified data from the IBM MarketScan Explorys Claims-EMR Dataset. STUDY DESIGN: In this retrospective, observational study, we examined congruence for commonly prescribed controlled substances-opioids, stimulants, and benzodiazepines. Congruence was stratified by age group and sex. DATA COLLECTION/EXTRACTION METHODS: Continuously enrolled adults aged 18-64 years with an EMR encounter (excluding inpatient settings) and ≥ 1 prescription for selected classes between 1/1/2016 and 10/2/2017. PRINCIPAL FINDINGS: During the study period, 1,353,478 adults had ≥1 EMR encounter. Patients with stimulants prescriptions had the highest congruence (83%) corresponding to 7151 claims for 8,635 EMR prescriptions, followed by opioids (66%; 62,766/95,690) and benzodiazepines (64%; 30,181/47,408). Chi-square testing showed congruence differed by age group within opioids (P < .0001) and benzodiazepines (P < .0001) and was higher among females within benzodiazepines (P < .0001). CONCLUSIONS: These findings demonstrate that relying on claims data alone for opioid prescribing measures might underestimate actual prescribing magnitude by as much as one-third in these data. Combined EMR and claims data can help future research better understand characteristics associated with congruence or incongruence between prescribing and dispensing.

      6. Is the severity of the Great Recession's aftershocks correlated with changes in access to the combined prevention environment among people who inject drugs?external icon
        Wise A, Kianian B, Chang HH, Linton S, Wolfe ME, Smith J, Tempalski B, Jarlais DD, Ross Z, Semaan S, Wejnert C, Broz D, Cooper HL.
        Int J Drug Policy. 2021 May 11;95:103264.
        BACKGROUND: The 2008 Recession was a global event that led to funding cuts for programs and services in the United States; though this recession officially ended in 2009, its aftershocks continued through 2012. We evaluated the relationship between the severity of the Great Recession's aftermath and spatial access to combined prevention services (i.e. HIV testing, syringe service programs, substance use disorder treatment program) for people who inject drugs (PWID) living in 19 metropolitan statistical areas (MSAs) in the United States. METHODS: The unit of analysis was the ZIP code; we sampled ZIP codes in these 19 MSAs where ≥1 PWID lived in 2009 and 2012, according to the CDC's National HIV Behavioral Surveillance. We used administrative data to describe the combined prevention environment (i.e., spatial access to HIV testing) for each ZIP code, and measured the severity of the recession's aftermath in each ZIP code, and in the counties and MSAs where these ZIP codes were located. Multilevel modeling estimated associations between changes in the aftermath of the Great Recession and ZIP code-level changes in spatial access to combined prevention services from 2009 to 2012. RESULTS: 675 ZIP codes located in 36 counties and 19 MSAs were included in this analysis. From 2009 to 2012, 21% of ZIP code areas lost access to combined prevention services and 14% gained access. ZIP codes with higher poverty rates relative to their respective MSAs were less likely to lose access (aOR: 0.91; 95% CI: 0.88, 0.95) and more likely to gain access (aOR: 1.05; 95% CI: 1.01, 1.09); there is some evidence to suggest the former association was attenuated for ZIP codes with higher percentages of non-Hispanic white residents. CONCLUSION: Combined prevention services for PWID living in these 675 ZIP codes demonstrated resilience in the aftermath of the Great Recession. Future research should explore whether community-based and federal HIV prevention initiatives contributed to this resilience, particularly in areas with higher concentrations of people of color.

    • Zoonotic and Vectorborne Diseases
      1. Findings the graves: SLED Family Reunification Program: SLED Family Reunification Programexternal icon
        Bensyl D, Bangura B, Cundy S, Gegbai F, Gorina Y, Harding JD, Hersey S, Jambai A, Kamara AS, Kargbo A, Kamara MA, Lansana P, Otieno D, Redd JT, Samba TT, Singh T, Vandi MA.
        Ann Epidemiol. 2021 May 28.
        In 2015, the Sierra Leone Ministry of Health and Sanitation (MoHS) and the Centers for Disease Control and Prevention (CDC) agreed to consolidate data recorded by MoHS and international partners during the Ebola epidemic and create the Sierra Leone Ebola Database (SLED). The primary objectives were helping families to identify the location of graves of their loved ones who died from any cause at the time of the Ebola epidemic and creating a data source for epidemiological research. The Family Reunification Program fulfils the first SLED objective. The purpose of this paper is to describe the Family Reunification Program (Program) development, functioning and results. The MoHS, CDC, SLED Team, and Concern Worldwide developed, tested, and implemented methodology and tools to conduct the Program. Family liaisons were trained in protection of the personally identifiable information. The SLED Family Reunification Program allows families in Sierra Leone, who did not know the final resting place of their loved ones, to be reunited with their graves and to bring them relief and closure. Continuing family requests in search of the burial place of loved ones five years after the end of the epidemic shows that the emotional burden of losing a family member and not knowing the place of burial does not diminish with time. As of February 2021, the Program continues and is described to allow its replication for other emergency events including COVID-19 and new Ebola outbreaks.

      2. Multisectoral cost analysis of a human and livestock anthrax outbreak in Songwe Region, Tanzania (December 2018-January 2019), using a novel Outbreak Costing Toolexternal icon
        Bodenham RF, Mtui-Malamsha N, Gatei W, Woldetsadik MA, Cassell CH, Salyer SJ, Halliday JE, Nonga HE, Swai ES, Makungu S, Mwakapeje E, Bernard J, Bebay C, Makonnen YJ, Fasina FO.
        One Health. 2021 Dec;13:100259.
        OBJECTIVES: We applied a novel Outbreak Costing Tool (OCT), developed by the US Centers for Disease Control and Prevention (CDC), to estimate the costs of investigating and responding to an anthrax outbreak in Tanzania. We also evaluated the OCT's overall utility in its application to a multisectoral outbreak response. METHODS: We collected data on direct costs associated with a human and animal anthrax outbreak in Songwe Region (December 2018 to January 2019) using structured questionnaires from key-informants. We performed a cost analysis by entering direct costs data into the OCT, grouped into seven cost categories: labor, office, travel and transport, communication, laboratory support, medical countermeasures, and consultancies. RESULTS: The total cost for investigating and responding to this outbreak was estimated at 102,232 United States dollars (USD), with travel and transport identified as the highest cost category (62,536 USD) and communication and consultancies as the lowest, with no expenditure, for the combined human and animal health sectors. CONCLUSIONS: Multisectoral investigation and response may become complex due to coordination challenges, thus allowing escalation of public health impacts. A standardized framework for collecting and analysing cost data is vital to understanding the nature of outbreaks, in anticipatory planning, in outbreak investigation and in reducing time to intervention. Pre-emptive use of the OCT will also reduce overall and specific (response period) intervention costs for the disease. Additional aggregation of the costs by government ministries, departments and tiers will improve the use of the tool to enhance sectoral budget planning for disease outbreaks in a multisectoral response.

      3. Rabies post-exposure healthcare-seeking behaviors and perceptions: Results from a knowledge, attitudes, and practices survey, Uganda, 2013external icon
        Bonaparte SC, Adams L, Bakamutumaho B, Barbosa Costa G, Cleaton JM, Gilbert AT, Osinubi M, Pieracci EG, Recuenco S, Tugumizemu V, Wamala J, Wallace RM.
        PLoS One. 2021 ;16(6):e0251702.
        BACKGROUND: Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination. METHODOLOGY: A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents. RESULTS: A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event. CONCLUSIONS: There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.

      4. Characterizing Areas with Increased Burden of West Nile Virus Disease in California, 2009-2018external icon
        Danforth ME, Fischer M, Snyder RE, Lindsey NP, Martin SW, Kramer VL.
        Vector Borne Zoonotic Dis. 2021 Jun 2.
        West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe neurological disease in humans, for which there is no treatment or vaccine. From 2009 to 2018, California has reported more human disease cases than any other state in the United States. We sought to identify smaller geographic areas within the 10 California counties with the highest number of WNV cases that accounted for disproportionately large numbers of human cases from 2009 to 2018. Eleven areas, consisting of groups of high-burden ZIP codes, were identified in nine counties within southern California and California's Central Valley. Despite containing only 2% of California's area and 17% of the state's population, these high-burden ZIP codes accounted for 44% of WNV cases reported and had a mean annual incidence that was 2.4 times the annual state incidence. Focusing mosquito control and public education efforts in these areas would lower WNV disease burden.

      5. Case Series of Laboratory-Associated Zika Virus Disease, United States, 2016-2019external icon
        Hills SL, Morrison A, Stuck S, Sandhu K, Mason KL, Stanek D, Gabel J, Osborne MA, Schroeder BA, Rico E, Drenzek CL, Gallagher GR, Fiddner J, Heberlein-Larson LA, Brown CM, Fischer M.
        Emerg Infect Dis. 2021 May;27(5):1296-1300.
        Zika virus diagnostic testing and laboratory research increased considerably when Zika virus began spreading through the Americas in 2015, increasing the risk for potential Zika virus exposure of laboratory workers and biomedical researchers. We report 4 cases of laboratory-associated Zika virus disease in the United States during 2016-2019. Of these, 2 were associated with needlestick injuries; for the other 2 cases, the route of transmission was undetermined. In laboratories in which work with Zika virus is performed, good laboratory biosafety practices must be implemented and practiced to reduce the risk for infection among laboratory personnel.

      6. Prevention of Lyme and other tickborne diseases using a rodent-targeted approach: A randomized controlled trial in Connecticutexternal icon
        Hinckley AF, Niesobecki SA, Connally NP, Hook SA, Biggerstaff BJ, Horiuchi KA, Hojgaard A, Mead PS, Meek JI.
        Zoonoses Public Health. 2021 May 28.
        Tickborne diseases are an increasing public health problem in the northeastern USA. Bait boxes that apply acaricide to rodents have been shown in small field studies to significantly reduce abundance of Ixodes scapularis ticks as well as their pathogen infection rates in treated areas. The effectiveness of this intervention for preventing human tickborne diseases (TBDs) has not been demonstrated. During 2012-2016, TickNET collaborators conducted a randomized, blinded, placebo-controlled trial among 622 Connecticut households. Each household received active (containing fipronil wick) or placebo (empty) bait boxes in their yards over two consecutive years. Information on tick encounters and TBDs among household members was collected through biannual surveys. Nymphal ticks were collected from a subset of 100 properties during spring at baseline, during treatment, and in the year post-intervention. Demographic and property characteristics did not differ between treatment groups. There were no significant differences post-intervention between treatment groups with respect to tick density or pathogen infection rates, nor for tick encounters or TBDs among household members. We found no evidence that rodent-targeted bait boxes disrupt pathogen transmission cycles or significantly reduce household risk of tick exposure or TBDs. The effectiveness of this intervention may depend on scale of use or local enzootic cycles.

      7. OBJECTIVES: To understand the barriers contributing to the more than threefold decline in the number of deaths (of all causes) reported to a national toll free telephone line (1-1-7) after the 2014-2016 Ebola outbreak ended in Sierra Leone and explore opportunities for improving routine death reporting as part of a nationwide mortality surveillance system. DESIGN: An exploratory qualitative assessment comprising 32 in-depth interviews (16 in Kenema district and 16 in Western Area). All interviews were audio-recorded, transcribed and analysed using qualitative content analysis to identify themes. SETTING: Participants were selected from urban and rural communities in two districts that experienced varying levels of Ebola cases during the outbreak. All interviews were conducted in August 2017 in the post-Ebola-outbreak context in Sierra Leone when the Sierra Leone Ministry of Health and Sanitation was continuing to mandate reporting of all deaths. PARTICIPANTS: Family members of deceased persons whose deaths were not reported to the 1-1-7 system. RESULTS: Death reporting barriers were driven by the lack of awareness to report all deaths, lack of services linked to reporting, negative experiences from the Ebola outbreak including prohibition of traditional burial rituals, perception that inevitable deaths do not need to be reported and situations where prompt burials may be needed. Facilitators of future willingness to report deaths were largely influenced by the perceived communicability and severity of the disease, unexplained circumstances of the death that need investigation and the potential to leverage existing death notification practices through local leaders. CONCLUSIONS: Social mobilisation and risk communication efforts are needed to help the public understand the importance and benefits of sustained and ongoing death reporting after an Ebola outbreak. Localised practices for informal death notification through community leaders could be integrated into the formal reporting system to capture community-based deaths that may otherwise be missed.

      8. Evaluating Differences in Whole Blood, Serum, and Urine Screening Tests for Zika Virus, Puerto Rico, USA, 2016external icon
        Rosinger AY, Olson SM, Ellington SR, Perez-Padilla J, Simeone RM, Pedati CS, Schroeder BA, Santiago GA, Medina FA, Muñoz-Jordán JL, Adams LE, Galang RR, Valencia-Prado M, Bakkour S, Colón C, Goodwin M, Meaney-Delman D, Read JS, Petersen LR, Jamieson DJ, Deseda CC, Honein MA, Rivera-García B, Shapiro-Mendoza CK.
        Emerg Infect Dis. 2021 May;27(5):1505-1508.
        We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015-2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.

      9. Rocky Mountain Spotted Fever in a Large Metropolitan Center, Mexico-United States Border, 2009-2019external icon
        Zazueta OE, Armstrong PA, Márquez-Elguea A, Hernández Milán NS, Peterson AE, Ovalle-Marroquín DF, Fierro M, Arroyo-Machado R, Rodriguez-Lomeli M, Trejo-Dozal G, Paddock CD.
        Emerg Infect Dis. 2021 Jun;27(6).

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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