Issue 34, September 21, 2021

CDC Science Clips: Volume 13, Issue 34, September 21, 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
      • BACKGROUND: Early onset colorectal cancer (CRC) incidence is rising under age 50, with a birth cohort effect for increasing incidence among individuals born 1950 and later. It is unclear whether increasing incidence trends will confer increased risk beyond age 50, the previously most commonly recommended age to initiate screening, when screening availability might modify incidence trends. AIM: Evaluate US trends in colorectal cancer (CRC) for ages 40-59 years. METHODS: We analyzed counts and incidence rates for CRC, including by anatomic subsite, using the US Cancer Statistics dataset covering 100% of the population 2003-2017. Joinpoint regression was used to quantify Average Annual Percent Change (AAPC) in cancer incidence by age subgroup. RESULTS: 470,458 CRC cases were observed age 40-59, with absolute numbers of rectal (n = 4173) and distal cases (n = 3327) per year for age 50-54 approaching age 55-59 cases for rectal (n = 4566) and distal (n = 3682) cancer by 2017. Increasing early onset rectal cancer incidence per 100,000 occuring under age 50 was observed to extend to age 50-54, from 4.9 to 6.3 for age 40-44 (AAPC 2.1; 95% CI 1.5-2.7), 9.3 to 12.0 for age 45-49 (AAPC 1.5; 95% CI 1.1-1.4), and from 16.7 to 19.5 for age 50-54 (AAPC 1.0; 95% CI 0.7-1.3). CONCLUSIONS: CRC trends suggest observed increased risks under age 50 are also present after age 50, despite prior availability of screening for this group. Recent CRC trends support initiation of screening earlier than age 50, and promotion of "on-time" screening initiation.

    • Disaster Control and Emergency Services
    • Health Disparities
      • BACKGROUND: Drug overdose deaths involving stimulants, including cocaine and psychostimulants with abuse potential (e.g., methamphetamine), have been increasing, partly because of co-involvement with opioids. Stimulant-involved overdose deaths have disproportionately increased among non-Hispanic Black (Black) and non-Hispanic American Indian/Alaskan Native (AI/AN) persons; however, the role of opioids in exacerbating disproportionate stimulant-involved death rates is unclear. METHODS: Analysis of National Vital Statistics System multiple cause-of-death mortality files examined age-adjusted cocaine- and psychostimulant-involved death rates. Analyses of death rates stratified by racial and ethnic group and opioid co-involvement included: 1) Joinpoint regression of 2004-2019 trends, 2) changes in rates from 2018 to 2019, and 3) demographic and geographic characteristics of 2019 deaths. RESULTS: From 2004 to 2019, cocaine and psychostimulant-involved death rates were higher for Black and AI/AN persons, respectively. Among all groups, increases in cocaine-involved overdose rates were largely driven by opioid co-involvement, particularly after 2013. From 2004 to 2019, rates for psychostimulant-involved deaths increased with and without opioid co-involvement. Rates for overdoses co-involving cocaine and synthetic opioids increased from 2018 to 2019 for Hispanic, non-Hispanic White (White), and Black persons. Psychostimulant-involved overdose rates with and without synthetic opioid co-involvement increased among Hispanic, White, and Black persons. In 2019, Black and AI/AN persons continued to experience higher cocaine- and psychostimulant-involved death rates, respectively. CONCLUSIONS: Stimulant-involved deaths continue to increase, and the role of opioids in driving these deaths varies by race and ethnicity. Ensuring equitable access to proven prevention and treatment interventions and incorporating social determinants of health into future research around effective pharmacotherapies may help reduce stimulant-involved overdose deaths.

    • Health Economics
      • We examine the relationship credit access has had with the U.S. agricultural productivity and residual returns to resources. Our theoretical analysis suggests that limited credit access can be sufficient to prevent a representative farmer from maximizing both short-And long-run profits. Empirical results show that increased credit access is positively associated with both productivity and residual returns to resources. Our findings imply that one way to stimulate the U.S. agricultural productivity growth is to increase credit access. They also provide strong empirical support for the productivity-stimulating value of programs such as the Farm Service Agency's Farm Loan Program. © The Author(s), 2021. Published by Cambridge University Press on behalf of the Southern Agricultural Economics Association.

    • Healthcare Associated Infections
      • The effect of disinfectants on the microbial community on environmental healthcare surfaces using next generation sequencingexternal icon
        Perry-Dow KA, de Man T, Halpin AL, Shams AM, Rose LJ, Noble-Wang JA.
        Am J Infect Control. 2021 Sep 2.
        BACKGROUND: Healthcare-associated infections (HAIs) are a significant economic burden and cause of avoidable morbidity and mortality within healthcare systems. The contribution of environmental contamination to HAI transmission has been recognized, but the mechanisms by which transmission occurs are still being investigated. The objective of this study was to characterize the microbial communities of disinfected, non-critical healthcare surfaces using next generation sequencing technology. METHODS: Composite environmental surface samples were from high-touch surfaces in rooms of patients isolated for infections with multidrug-resistant organisms during their hospitalization. Information on the disinfectant product used and cleaning type (routine or terminal) was collected. 16S rRNA gene amplicon sequencing and analysis were performed. Community analysis was conducted to determine the bacterial composition and compare the detection of target pathogens by culture from 94 Contact Precaution rooms. RESULTS: Overall percent agreement between culture and sequence methods ranged from 52% to 88%. A significant difference was observed in bacterial composition between rooms cleaned with bleach and those cleaned with a quaternary ammonium compound (QAC) for composite 2 (overbed table, intravenous pole, and inner room door handle) (ANOSIM R2 = 0.66, p = 0.005) but not composite 1 (bed rails, television remote control unit, call buttons, and telephone). CONCLUSIONS: Surfaces in bleach-cleaned rooms contained a higher proportion of gram-positive microbiota, whereas rooms cleaned with QAC contained a higher proportion of gram-negative microbiota, suggesting disinfectant products may impact the healthcare environment microbiome.

    • Immunity and Immunization
      • Surveillance for adverse events after COVID-19 mRNA vaccinationexternal icon
        Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, Donahue JG, Kharbanda EO, Naleway A, Nelson JC, Xu S, Yih WK, Glanz JM, Williams JT, Hambidge SJ, Lewin BJ, Shimabukuro TT, DeStefano F, Weintraub ES.
        Jama. 2021 Sep 3.
        IMPORTANCE: Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. OBJECTIVES: To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. DESIGN, SETTING, AND PARTICIPANTS: This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. EXPOSURES: Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. MAIN OUTCOMES AND MEASURES: Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted. RESULTS: A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. CONCLUSIONS AND RELEVANCE: In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

    • Informatics
      • MicrobeTrace: Retooling molecular epidemiology for rapid public health responseexternal icon
        Campbell EM, Boyles A, Shankar A, Kim J, Knyazev S, Cintron R, Switzer WM.
        PLoS Comput Biol. 2021 Sep 7;17(9):e1009300.
        Outbreak investigations use data from interviews, healthcare providers, laboratories and surveillance systems. However, integrated use of data from multiple sources requires a patchwork of software that present challenges in usability, interoperability, confidentiality, and cost. Rapid integration, visualization and analysis of data from multiple sources can guide effective public health interventions. We developed MicrobeTrace to facilitate rapid public health responses by overcoming barriers to data integration and exploration in molecular epidemiology. MicrobeTrace is a web-based, client-side, JavaScript application ( that runs in Chromium-based browsers and remains fully operational without an internet connection. Using publicly available data, we demonstrate the analysis of viral genetic distance networks and introduce a novel approach to minimum spanning trees that simplifies results. We also illustrate the potential utility of MicrobeTrace in support of contact tracing by analyzing and displaying data from an outbreak of SARS-CoV-2 in South Korea in early 2020. MicrobeTrace is developed and actively maintained by the Centers for Disease Control and Prevention. Users can email for support. The source code is available at

    • Injury and Violence
      • Measurement of adverse childhood experiences: It mattersexternal icon
        Reidy DE, Niolon PH, Estefan LF, Kearns MC, D'Inverno AS, Marker CC, Merrick MT.
        Am J Prev Med. 2021 Sep 3.
        INTRODUCTION: Alternative measurement approaches for adverse childhood experiences (i.e., count score versus individual adverse childhood experiences measured dichotomously versus individual adverse childhood experiences measured ordinally) can alter the association between adverse childhood experiences and adverse outcomes. This could significantly impact the interpretation of adverse childhood experiences research. METHODS: Data were collected in 2018 (analyzed in 2020) via Amazon's Mechanical Turk and from people incarcerated in 4 correctional facilities (N=1,451). Included adverse childhood experience questions measured the following: physical, emotional, and sexual abuse; physical and emotional neglect; household mental illness, substance use, domestic violence, and incarceration; and exposure to community violence before age 18 years. A total of 19 measured outcomes spanned 4 domains of functioning: general functioning, substance use, psychopathology, and criminal behavior. RESULTS: Regression models using the count score explained the least amount of variance in outcomes, whereas multivariable regression models assessing adverse childhood experiences on a continuum explained the most variance. In many instances, the explained variance increased by 2-5 times across the predictive models. When comparing regression coefficients for multivariable regression models that measured adverse childhood experiences as binary versus ordinal, there were notable differences in the effect sizes and in which adverse childhood experiences predicted outcomes. Disparities in results were most pronounced among high-risk populations that experience a disproportionate amount of adverse childhood experiences. CONCLUSIONS: Alternative methods of measuring adverse childhood experiences can influence understanding of their true impact. These findings suggest that the deleterious effects of imprecise measurement methods may be most pronounced in the populations most at risk of adverse childhood experiences. For the sake of prevention, the measurement of adverse childhood experiences must evolve.

    • Laboratory Sciences
      • Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort studyexternal icon
        Ho CS, Feng PI, Narita M, Stout JE, Chen M, Pascopella L, Garfein R, Reves R, Katz DJ.
        Lancet Infect Dis. 2021 Sep 6.
        BACKGROUND: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. METHODS: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at, NCT01622140. FINDINGS: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (p(trend)<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years. INTERPRETATION: Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA. FUNDING: US Centers for Disease Control and Prevention.

    • Occupational Safety and Health
      • Exposure to particulate matter and estimation of volatile organic compounds across wildland firefighter job tasksexternal icon
        Navarro KM, West MR, O'Dell K, Sen P, Chen IC, Fischer EV, Hornbrook RS, Apel EC, Hills AJ, Jarnot A, DeMott P, Domitrovich JW.
        Environ Sci Technol. 2021 Sep 7;55(17):11795-11804.
        Wildland firefighters are exposed to smoke-containing particulate matter (PM) and volatile organic compounds (VOCs) while suppressing wildfires. From 2015 to 2017, the U.S. Forest Service conducted a field study collecting breathing zone measurements of PM(4) (particulate matter with aerodynamic diameter ≤4 μm) on wildland firefighters from different crew types and while performing various fire suppression tasks on wildfires. Emission ratios of VOC (parts per billion; ppb): PM(1) (particulate matter with aerodynamic diameter ≤1 μm; mg/m(3)) were calculated using data from a separate field study conducted in summer 2018, the Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption, and Nitrogen (WE-CAN) Campaign. These emission ratios were used to estimate wildland firefighter exposure to acrolein, benzene, and formaldehyde. Results of this field sampling campaign reported that exposure to PM(4) and VOC varied across wildland firefighter crew type and job task. Type 1 crews had greater exposures to both PM(4) and VOCs than type 2 or type 2 initial attack crews, and wildland firefighters performing direct suppression had statistically higher exposures than those performing staging and other tasks (mean differences = 0.82 and 0.75 mg/m(3); 95% confidence intervals = 0.38-1.26 and 0.41-1.08 mg/m(3), respectively). Of the 81 personal exposure samples collected, 19% of measured PM(4) exposures exceeded the recommended National Wildland Fire Coordinating Group occupational exposure limit (0.7 mg/m(3)). Wildland fire management should continue to find strategies to reduce smoke exposures for wildland firefighters.

    • Physical Activity
      • Steps per day and all-cause mortality in middle-aged adults in the Coronary Artery Risk Development in Young Adults Studyexternal icon
        Paluch AE, Gabriel KP, Fulton JE, Lewis CE, Schreiner PJ, Sternfeld B, Sidney S, Siddique J, Whitaker KM, Carnethon MR.
        JAMA Netw Open. 2021 Sep 1;4(9):e2124516.
        IMPORTANCE: Steps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality. OBJECTIVE: To estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021. EXPOSURE: Daily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more. MAIN OUTCOMES AND MEASURES: All-cause mortality. RESULTS: A total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality. CONCLUSIONS AND RELEVANCE: This cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.

    • Zoonotic and Vectorborne Diseases
      • U.S. dog importations during the COVID-19 pandemic: Do we have an erupting problem?external icon
        Pieracci EG, Williams CE, Wallace RM, Kalapura CR, Brown CM.
        PLoS One. 2021 ;16(9):e0254287.
        Dog importation data from 2018-2020 were evaluated to ascertain whether the dog importation patterns in the United States changed during the COVID-19 pandemic, specifically with regard to denial of entry. Dog denial of entry reports from January 1, 2018, to December 31, 2020, stored within the Centers for Disease Control and Prevention (CDC) Quarantine Activity Reporting System (QARS), were reviewed. Basic descriptive statistics were used to analyze the data. Reason for denial, country of origin, and month of importation were all examined to determine which countries of origin resulted in the largest number of denials, and whether there was a seasonal change in importations during the COVID-19 pandemic (2020), compared to previous years (2018 and 2019). During 2020, CDC denied entry to 458 dogs. This represents a 52% increase in dogs denied entry compared to the averages in 2018 and 2019. Dogs were primarily denied entry for falsified rabies vaccination certificates (56%). Three countries exported 74% of all dogs denied entry into the United States, suggesting that targeted interventions may be needed for certain countries. Increased attempts to import inadequately vaccinated dogs from countries with canine rabies in 2020 may have been due to the increased demand for domestic pets during the COVID-19 pandemic. Educational messaging should highlight the risk of rabies and the importance of making informed pet purchases from foreign entities to protect pet owners, their families, and the public.

  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. Background: Presentation with mild symptoms is a common reason for intravenous thrombolysis (IVT) nonuse among acute ischemic stroke (AIS) patients. We examined the impact of IVT on the outcomes of mild AIS over time. Methods: Using the Paul Coverdell National Stroke Program data, we examined trends in IVT utilization from 2010 to 2019 among AIS patients presenting with National Institutes of Health Stroke Scale (NIHSS) scores ≤5. Outcomes adjudicated included rates of discharge to home and ability to ambulate independently at discharge. We used generalized estimating equation models to examine the effect of IVT on outcomes of AIS patients presenting with mild symptoms and calculated adjusted odds ratio (AOR) with 95% confidence intervals (CI). Results: During the study period, 346,762 patients presented with mild AIS symptoms. Approximately 6.2% were treated with IVT. IVT utilization trends increased from 3.7% in 2010 to 7.7% in 2019 (p < 0.001). Patients treated with IVT had higher median NIHSS scores upon presentation (IVT 3 [2, 4] vs. no IVT 2 [0, 3]). Rates of discharge to home (AOR 2.06, 95% CI: 1.99-2.13) and ability to ambulate at time of discharge (AOR 1.82, 95% CI: 1.76-1.89) were higher among those treated with IVT. Conclusion: There was an increased trend in IVT utilization among AIS patients presenting with mild symptoms. Utilization of IVT increased the odds of being discharged to home and the ability to ambulate at discharge independently in patients with mild stroke. © 2021 The Author(s). Published by S. Karger AG, Basel.

      2. Influence of asthma and obesity on respiratory symptoms, work ability and lung function: findings from a cross-sectional Norwegian population studyexternal icon
        Klepaker G, Henneberger PK, Hertel JK, Holla Ø L, Kongerud J, Fell AK.
        BMJ Open Respir Res. 2021 Sep;8(1).
        BACKGROUND: Although asthma and obesity are each associated with adverse respiratory outcomes, a possible interaction between them is less studied. This study assessed the extent to which asthma and overweight/obese status were independently associated with respiratory symptoms, lung function, Work Ability Score (WAS) and sick leave; and whether there was an interaction between asthma and body mass index (BMI) ≥25 kg/m(2) regarding these outcomes. METHODS: In a cross-sectional study, 626 participants with physician-diagnosed asthma and 691 without asthma were examined. All participants completed a questionnaire and performed spirometry. The association of outcome variables with asthma and BMI category were assessed using regression models adjusted for age, sex, smoking status and education. RESULTS: Asthma was associated with reduced WAS (OR=1.9 (95% CI 1.4 to 2.5)), increased sick leave in the last 12 months (OR=1.4 (95% CI 1.1 to 1.8)) and increased symptom score (OR=7.3 (95% CI 5.5 to 9.7)). Obesity was associated with an increased symptom score (OR=1.7 (95% CI 1.2 to 2.4)). Asthma was associated with reduced prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV(1)) (β=-6.6 (95% CI -8.2 to -5.1) and -5.2 (95% CI -6.7 to -3.4), respectively) and prebronchodilator forced vital capacity (FVC) (β=-2.3 (95% CI -3.6 to -0.96)). Obesity was associated with reduced prebronchodilator and postbronchodilator FEV(1) (β=-2.9 (95% CI -5.1 to -0.7) and -2.8 (95% CI -4.9 to -0.7), respectively) and FVC (-5.2 (95% CI -7.0 to -3.4) and -4.2 (95% CI -6.1 to -2.3), respectively). The only significant interaction was between asthma and overweight status for prebronchodilator FVC (β=-3.6 (95% CI -6.6 to -0.6)). CONCLUSIONS: Asthma and obesity had independent associations with increased symptom scores, reduced prebronchodilator and postbronchodilator FEV(1) and reduced prebronchodilator FVC. Reduced WAS and higher odds of sick leave in the last 12 months were associated with asthma, but not with increased BMI. Besides a possible association with reduced FVC, we found no interactions between asthma and increased BMI.

      3. Trends in office visits during which opioids were prescribed for adults with arthritis in the US, 2006-2015external icon
        Santo L, Schappert SM, Hootman JM, Helmick CG.
        Arthritis Care Res (Hoboken). 2020 Sep 16.
        OBJECTIVE: To analyze trends for visits to office-based physicians at which opioids were prescribed among adults with arthritis in the US, from 2006 to 2015. METHODS: We analyzed nationally representative data on patient visits to office-based physicians from 2006 to 2015 from the National Ambulatory Medical Care Survey (NAMCS). Visit percentages for first- and any-listed diagnosis of arthritis by age groups and sex were reported. Time points were grouped into 2-year intervals to increase the reliability of estimates. Annual percentage point change and 95% confidence intervals (95% CIs) were reported from linear regression models. RESULTS: From 2006 to 2015, the percentage of visits to office-based physicians by adults with a first-listed diagnosis of arthritis increased from 4.1% (95% CI 3.5%, 4.7%) in 2006-2007 to 5.1% (95% CI 3.9%, 6.6%) in 2014-2015 (P = 0.033). Among these visits, the percentage of visits with opioids prescribed increased from 16.5% (95% CI 13.1%, 20.5%) in 2006-2007 to 25.6% (95% CI 17.9%, 34.6%) in 2014-2015 (P = 0.017). The percentage of visits with any-listed diagnosis of arthritis increased from 6.6% (95% CI 5.9%, 7.4%) in 2006-2007 to 8.4% (95% CI 7.0%, 10.0%) in 2014-2015 (P = 0.001). Among these visits, the percentage of visits with opioids prescribed increased from 17.4% (95% CI 14.6%, 20.4%) in 2006-2007 to 25.0% (95% CI 19.7%, 30.8%) in 2014-2015 (P = 0.004). CONCLUSION: From 2006 to 2015, the percentage of visits to office-based physicians by adults with arthritis increased and the percentage of opioids prescribed at these visits also increased. NAMCS data will allow continued monitoring of these trends after the implementation of the 2016 Centers for Disease Control and Prevention Guideline for prescribing opioids for chronic pain.

      4. Learning from cervical cancer survivors: An examination of barriers and facilitators to cervical cancer screening among women in the United Statesexternal icon
        Senkomago V, Greek A, Jackson JE, Thomas CC, Richardson LC, Benard VB.
        J Prim Care Community Health. 2021 Jan-Dec;12.
        BACKGROUND: Screening and timely follow-up have lowered cervical cancer incidence in the US; however, screening coverage, incidence, and death rates have remained fairly stable in recent years. Studies suggest that half of women diagnosed with cervical cancer don't receive appropriate screening prior to diagnosis; cervical cancer survivors can provide crucial insight into barriers and facilitators to screening. METHODS: Participants were cervical cancer survivors ≥21 years, identified through population-based central cancer registries (CR) in 3 US states or a social network (SN), Cervivor. CR participants completed a mailed survey on screening history, barriers, and facilitators to screening and sociodemographic data. SN participants completed the same survey online. RESULTS: CR participants (N = 480) were older, with a lower proportion of non-Hispanic white, married, and insured women compared to SN participants (N = 148). Fifty percent of CR and 79% of SN participants were screened 5 years prior to their diagnoses. Of those screened, 28% in both groups reported not following-up on abnormal results. For both groups, the most frequently identified screening barrier was that participants never imagined they would develop cervical cancer (percent agree CR = 76%; SN = 86%), and the facilitator was wanting to take care of their bodies (CR = 95%; SN = 94%). CONCLUSION: Addressing key barriers to obtaining screening and timely follow-up related to lack of knowledge of cervical cancer risk and screening tests and addressing insurance coverage in the design or modification of interventions may increase cervical cancer screening and lower cervical cancer incidence in the US.

    • Communicable Diseases
      1. Sporadic Creutzfeldt-Jakob disease in a very young personexternal icon
        Appleby BS, Maddox R, Schonberger LB, Cali I, Hammett T, Cohen M, Belay E.
        Neurology. 2021 Sep 8.
        OBJECTIVES: Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in mid-to-late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of young cases of sCJD that are not associated with a genetic mutation or acquired prion disease risk factors. METHODS: We describe the clinical presentation, diagnostic work-up, and post-mortem examination of a 22-year-old man with sCJD. RESULTS: The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. Cerebrospinal (CSF) real time quaking induced conversion (RT-QuIC) was indeterminate, and brain magnetic resonance imaging (MRI) was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD. DISCUSSION: Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Post-mortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.

      2. Derivation and external validation of a risk score for predicting HIV-associated tuberculosis to support case finding and preventive therapy scale-up: A cohort studyexternal icon
        Auld AF, Kerkhoff AD, Hanifa Y, Wood R, Charalambous S, Liu Y, Agizew T, Mathoma A, Boyd R, Date A, Shiraishi RW, Bicego G, Mathebula-Modongo U, Alexander H, Serumola C, Rankgoane-Pono G, Pono P, Finlay A, Shepherd JC, Ellerbrock TV, Grant AD, Fielding K.
        PLoS Med. 2021 Sep 7;18(9):e1003739.
        BACKGROUND: Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV-TB care. METHODS AND FINDINGS: We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/μL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/μL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) <18.5kg/m2 (2 points), and severe anemia (hemoglobin <8g/dL) (3 points). Sensitivity using WHO 4-symptom TB screen was 73%, 80%, 94%, and 94% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, but increased to 88%, 87%, 97%, and 97%, when a clinical score of ≥2 was used. Negative predictive value (NPV) also increased 1%, 0.3%, 1.6%, and 1.7% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, when the clinical score of ≥2 replaced WHO 4-symptom TB screen. Categorizing risk scores into low (<2), moderate (2 to 10), and high-risk categories (>10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings. CONCLUSIONS: The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV-TB care to maximize impact of available resources.

      3. BACKGROUND: Recent increases in high-risk substance use (HRSU) (i.e., injection drug use, heroin, methamphetamine, crack/cocaine) have coincided with rising primary and secondary (P&S) syphilis rates. To further understand these trends, we examined sexual risk behaviors among women, men who have sex with women only (MSW) and men who have sex with men (MSM) who were diagnosed with P&S syphilis in 2018 and reported HRSU. METHODS: Data on HRSU and sexual risk behaviors among persons with P&S syphilis were drawn from syphilis case reports in 2018 from the National Notifiable Diseases Surveillance System. Persons with P&S syphilis were asked about sexual risk behaviors in the past 12 months including exchange sex for drugs/money; sex while intoxicated and/or high on drugs; sex with a person who injects drugs (PWID); sex with an anonymous partner; and number of sex partners. We describe percentages and adjusted prevalence ratios for women, MSW and MSM reporting these behaviors by age, race/Hispanic ethnicity, type of drug used, and incarceration history (both in past 12 months). RESULTS: Among 19,634 persons diagnosed with P&S syphilis in 2018 with information on HRSU, 29.3% of women, 22.7% of MSW and 12.4% of MSM reported HRSU. Among those reporting HRSU, percentages reporting exchange sex ranged from 17%-35% (highest for women), while reports of anonymous sex ranged from 44%-71% (highest for MSM). In this population, sexual risk behaviors were more commonly reported among those with recent incarceration history than those without such history. Among those reporting injection drug use or heroin use, percentages reporting sex with a PWID ranged from 51%-77%. In adjusted models, HRSU was significantly associated with one or more sexual risk behaviors for women (aPR, 2.63 (95% CI, 2.39-2.90); MSW aPR, 1.38 (95% CI, 1.31-1.46); and MSM aPR, 1.30 (95% CI, 1.26-1.34). CONCLUSIONS: Collaborative partnerships across the US public health system could help address barriers to timely clinical care among persons diagnosed with P&S syphilis who report HRSU.

      4. Hospitalizations associated with COVID-19 among children and adolescents - COVID-NET, 14 states, March 1, 2020-August 14, 2021external icon
        Delahoy MJ, Ujamaa D, Whitaker M, O'Halloran A, Anglin O, Burns E, Cummings C, Holstein R, Kambhampati AK, Milucky J, Patel K, Pham H, Taylor CA, Chai SJ, Reingold A, Alden NB, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Openo KP, Teno K, Weigel A, Kim S, Leegwater L, Bye E, Como-Sabetti K, Ropp S, Rudin D, Muse A, Spina N, Bennett NM, Popham K, Billing LM, Shiltz E, Sutton M, Thomas A, Schaffner W, Talbot HK, Crossland MT, McCaffrey K, Hall AJ, Fry AM, McMorrow M, Reed C, Garg S, Havers FP.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 10;70(36):1255-1260.
        Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,(†) COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.(§) Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)(¶) data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,(††) and quarantining as recommended after exposure to persons with COVID-19.(§§).

      5. PrEP for key populations: results from the first PrEP demonstration project in the Democratic Republic of the Congoexternal icon
        Franks J, Teasdale C, Olsen H, Wang C, Mushimebele N, Tenda Mazala R, Tchissambou T, Malele Bazola F, Bingham T, Djomand G, Mukinda E, Ewetola R, Abrams E, Reidy W.
        AIDS Care. 2021 Sep 8:1-4.
        Oral pre-exposure prophylaxis (PrEP) is recommended for persons at substantial risk for HIV, including female sex workers (FSW), men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW). We report on a PrEP demonstration project at seven clinics in the Democratic Republic of the Congo. Routinely collected data were abstracted to assess PrEP uptake, scheduled visit attendance, and self-reported adherence. Between February and May 2018, 469 eligible clients were offered daily oral PrEP; 75.1% accepted: 78.7% FSW, 20.5% MSM, and 0.9% TGW. Two percent also identified as PWID. Attendance was 64.5% at one-month visits; 82.1% at three-month visits; and among 47.7% of clients who initiated PrEP at least six months before data abstraction, 85.8% at six-month visits. Among 66.3% of clients with at least one adherence assessment, 39% self-reported low adherence. Results demonstrate the acceptability of PrEP delivered in healthcare settings serving FSW, MSM, PWID, and TGW.

      6. Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescentsexternal icon
        Geva A, Patel MM, Newhams MM, Young CC, Son MB, Kong M, Maddux AB, Hall MW, Riggs BJ, Singh AR, Giuliano JS, Hobbs CV, Loftis LL, McLaughlin GE, Schwartz SP, Schuster JE, Babbitt CJ, Halasa NB, Gertz SJ, Doymaz S, Hume JR, Bradford TT, Irby K, Carroll CL, McGuire JK, Tarquinio KM, Rowan CM, Mack EH, Cvijanovich NZ, Fitzgerald JC, Spinella PC, Staat MA, Clouser KN, Soma VL, Dapul H, Maamari M, Bowens C, Havlin KM, Mourani PM, Heidemann SM, Horwitz SM, Feldstein LR, Tenforde MW, Newburger JW, Mandl KD, Randolph AG.
        EClinicalMedicine. 2021 Oct;40:101112.
        BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. METHODS: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. FINDINGS: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. INTERPRETATION: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.

      7. New Mexico Department of Health (NMDOH) conducted a matched case-control study to compare 315 persons (cases) with and 945 persons (controls) without SARS-CoV-2 secondary detection (i.e., positive SARS-CoV-2 test ≥90 days after first detection as of December 10, 2020). Compared with controls, cases had greater odds of higher SARS-CoV-2 testing frequency (adjusted odds ratio [aOR] = 1.2), being female (aOR = 1.6), being non-Hispanic American Indian/Alaska Native (aOR = 2.3), having diabetes mellitus (aOR = 1.8), and residing/working in detention/correctional facilities (aOR = 4.7). Diagnostic tools evaluating infectiousness at secondary detection are urgently needed to inform infection control practices.

      8. Sustained transmission of Neisseria gonorrhoeae with high-level resistance to azithromycin, in Indianapolis, Indiana, 2017-2018external icon
        Holderman JL, Thomas JC, Schlanger K, Black JM, Town K, St Cyr SB, Pham CD, Kirkcaldy RD.
        Clin Infect Dis. 2021 Sep 7;73(5):808-815.
        BACKGROUND: Since 2014, Neisseria gonorrhoeae azithromycin (AZM) susceptibility has declined in the United States, but high-level AZM resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 N. gonorrhoeae isolates with HL-AZMR identified in Indianapolis over 13 months. METHODS: N. gonorrhoeae culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) using Etest. AZM minimum inhibitory concentrations ≥256 µg/mL were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. RESULTS: During 2017-2018, AST was performed in 1016 N. gonorrhoeae isolates collected at the Bell Flower Clinic. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin susceptible. Of the 12 men, 9 were white and reported male sex partners. Nine of the men were able to be retested; all were cured with 250-mg ceftriaxone plus 1-g AZM. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic-mtrR promoter along with 23S ribosomal RNA mutations that appear to have emerged from circulating strains. CONCLUSIONS: The close genetic relatedness with limited epidemiologic linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multipronged approach to understanding an outbreak of sexually transmitted disease.

      9. Beyond disease intervention: Exploring an expanded role for partner services in the MATRix-NC Demonstration Projectexternal icon
        Hurt CB, Morrison AS, Guy J, Mobley VL, Dennis AM, Barrington C, Samoff E, Hightow-Weidman LB, McNeil CJ, Carry MG, Hogben M, Seña AC.
        Sex Transm Dis. 2021 Aug 31.
        BACKGROUND: Disease intervention specialists (DIS) provide partner services (PS) for sexually transmitted infections (STI). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. METHODS: Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in four urban North Carolina (NC) counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for pre-exposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1 month, and 3 month computerized surveys. RESULTS: Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. CONCLUSIONS: Chain-referral sampling from PS clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

      10. Using wastewater surveillance data to support the COVID-19 response - United States, 2020-2021external icon
        Kirby AE, Walters MS, Jennings WC, Fugitt R, LaCross N, Mattioli M, Marsh ZA, Roberts VA, Mercante JW, Yoder J, Hill VR.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 10;70(36):1242-1244.
        Wastewater surveillance, the measurement of pathogen levels in wastewater, is used to evaluate community-level infection trends, augment traditional surveillance that leverages clinical tests and services (e.g., case reporting), and monitor public health interventions (1). Approximately 40% of persons infected with SARS-CoV-2, the virus that causes COVID-19, shed virus RNA in their stool (2); therefore, community-level trends in SARS-CoV-2 infections, both symptomatic and asymptomatic (2) can be tracked through wastewater testing (3-6). CDC launched the National Wastewater Surveillance System (NWSS) in September 2020 to coordinate wastewater surveillance programs implemented by state, tribal, local, and territorial health departments to support the COVID-19 pandemic response. In the United States, wastewater surveillance was not previously implemented at the national level. As of August 2021, NWSS includes 37 states, four cities, and two territories. This report summarizes NWSS activities and describes innovative applications of wastewater surveillance data by two states, which have included generating alerts to local jurisdictions, allocating mobile testing resources, evaluating irregularities in traditional surveillance, refining health messaging, and forecasting clinical resource needs. NWSS complements traditional surveillance and enables health departments to intervene earlier with focused support in communities experiencing increasing concentrations of SARS-CoV-2 in wastewater. The ability to conduct wastewater surveillance is not affected by access to health care or the clinical testing capacity in the community. Robust, sustainable implementation of wastewater surveillance requires public health capacity for wastewater testing, analysis, and interpretation. Partnerships between wastewater utilities and public health departments are needed to leverage wastewater surveillance data for the COVID-19 response for rapid assessment of emerging threats and preparedness for future pandemics.

      11. High seroprevalence of SARS-CoV-2 but low infection fatality ratio eight months after introduction in Nairobi, Kenyaexternal icon
        Ngere I, Dawa J, Hunsperger E, Otieno N, Masika M, Amoth P, Makayotto L, Nasimiyu C, Gunn BM, Nyawanda B, Oluga O, Ngunu C, Mirieri H, Gachohi J, Marwanga D, Munywoki PK, Odhiambo D, Alando MD, Breiman RF, Anzala O, Njenga MK, Bulterys M, Herman-Roloff A, Osoro E.
        Int J Infect Dis. 2021 Sep 2.
        BACKGROUND: The lower-than-expected COVID-19 morbidity and mortality in Africa has been attributed to multiple factors, including weak surveillance. We estimated the burden of SARS-CoV-2 infections eight months into the epidemic in Nairobi, Kenya. METHODS: We conducted a population-based cross-sectional survey using multi-stage random sampling to select households within Nairobi in November 2020. Sera from consenting household members were tested for antibodies to SARS-CoV-2. Seroprevalence was estimated after adjusting for population structure and test performance. Infection fatality ratios (IFRs) were calculated by comparing study estimates to reported cases and deaths. RESULTS: Among 1,164 individuals, the adjusted seroprevalence was 34.7% (95%CI 31.8-37.6). Half the enrolled households had at least one positive participant. Seropositivity increased in more densely populated areas (spearman's r=0.63; p=0.009). Individuals aged 20-59 years had at least 2-fold higher seropositivity than those aged 0-9 years. The IFR was 40 per 100,000 infections, with individuals ≥60 years old having higher IFRs. CONCLUSION: Over one-third of Nairobi residents had been exposed to SARS-CoV-2 by November 2020, indicating extensive transmission. However, the IFR was >10-fold lower than that reported in Europe and the United States, supporting the perceived lower morbidity and mortality in sub-Saharan Africa.

      12. Antimicrobial susceptibility of urogenital and extragenital neisseria gonorrhoeae isolates among men who have sex with men - SURRG and eGISP, 2018-2019external icon
        Quilter LA, St Cyr SB, Hong J, Asbel L, Bautista I, Carter B, Casimir Y, Denny M, Ervin M, Gomez R, Harvey A, Holderman JL, Johnson K, Kohn RP, Learner ER, Mauk K, Menza T, Mettenbrink C, Nettleton WD, Nicosia KR, Pham CD, Ried C, Schlanger K, Schneider A, Soge OO, Tabidze I, Taylor SN, Tilghman W, Toler C, Weinstock H, Torrone EA.
        Sex Transm Dis. 2021 Aug 31.
        BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through CDC's enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). METHODS: During January 1, 2018-December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p < 0.05). CONCLUSIONS: Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

      13. Strengthening the U.S. Response to Resistant Gonorrhea (SURRG): An overview of a multi-site program to enhance local response capacity for antibiotic-resistant Neisseria gonorrhoeaeexternal icon
        Schlanger K, Learner ER, Pham CD, Mauk K, Golden M, Wendel KA, Amsterdam L, McNeil CJ, Johnson K, Nguyen TQ, Holderman JL, Hasty GL, St Cyr SB, Town K, Nash EE, Kirkcaldy RD.
        Sex Transm Dis. 2021 Aug 31.
        BACKGROUND: In 2016, CDC initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies. METHODS: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in STD and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin. RESULTS: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018-2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% (3,412) and 8.9% (4,883) of local reported cases in 2018 and 2019 respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts. CONCLUSIONS: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed.

      14. Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0-17 years - United States, August 2020-August 2021external icon
        Siegel DA, Reses HE, Cool AJ, Shapiro CN, Hsu J, Boehmer TK, Cornwell CR, Gray EB, Henley SJ, Lochner K, Suthar AB, Lyons BC, Mattocks L, Hartnett K, Adjemian J, van Santen KL, Sheppard M, Soetebier KA, Logan P, Martin M, Idubor O, Natarajan P, Sircar K, Oyegun E, Dalton J, Perrine CG, Peacock G, Schweitzer B, Morris SB, Raizes E.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 10;70(36):1249-1254.
        Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,(†) causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.

      15. Long-term symptoms among adults tested for SARS-CoV-2 - United States, January 2020-April 2021external icon
        Wanga V, Chevinsky JR, Dimitrov LV, Gerdes ME, Whitfield GP, Bonacci RA, Nji MA, Hernandez-Romieu AC, Rogers-Brown JS, McLeod T, Rushmore J, Lutfy C, Bushman D, Koumans E, Saydah S, Goodman AB, Coleman King SM, Jackson BR, Cope JR.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 10;70(36):1235-1241.
        Long-term symptoms often associated with COVID-19 (post-COVID conditions or long COVID) are an emerging public health concern that is not well understood. Prevalence of post-COVID conditions has been reported among persons who have had COVID-19 (range = 5%-80%), with differences possibly related to different study populations, case definitions, and data sources (1). Few studies of post-COVID conditions have comparisons with the general population of adults with negative test results for SARS-CoV-2, the virus that causes COVID-19, limiting ability to assess background symptom prevalence (1). CDC used a nonprobability-based Internet panel established by Porter Novelli Public Services* to administer a survey to a nationwide sample of U.S. adults aged ≥18 years to compare the prevalence of long-term symptoms (those lasting >4 weeks since onset) among persons who self-reported ever receiving a positive SARS-CoV-2 test result with the prevalence of similar symptoms among persons who reported always receiving a negative test result. The weighted prevalence of ever testing positive for SARS-CoV-2 was 22.2% (95% confidence interval [CI] = 20.6%-23.8%). Approximately two thirds of respondents who had received a positive test result experienced long-term symptoms often associated with SARS-CoV-2 infection. Compared with respondents who received a negative test result, those who received a positive test result reported a significantly higher prevalence of any long-term symptom (65.9% versus 42.9%), fatigue (22.5% versus 12.0%), change in sense of smell or taste (17.3% versus 1.7%), shortness of breath (15.5% versus 5.2%), cough (14.5% versus 4.9%), headache (13.8% versus 9.9%), and persistence (>4 weeks) of at least one initially occurring symptom (76.2% versus 69.6%). Compared with respondents who received a negative test result, a larger proportion of those who received a positive test result reported believing that receiving a COVID-19 vaccine made their long-term symptoms better (28.7% versus 15.7%). Efforts to address post-COVID conditions should include helping health care professionals recognize the most common post-COVID conditions and optimize care for patients with persisting symptoms, including messaging on potential benefits of COVID-19 vaccination.

      16. Enteric illness outbreaks reported through the National Outbreak Reporting System, United States, 2009-19external icon
        Wikswo ME, Roberts V, Marsh Z, Manikonda K, Gleason B, Kambhampati A, Mattison C, Calderwood L, Balachandran N, Cardemil C, Hall AJ.
        Clin Infect Dis. 2021 Sep 8.
        BACKGROUND: The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. The aim of this study is to describe enteric illness outbreaks reported during 11 years of surveillance. METHODS: We extracted finalized reports from NORS for outbreaks occurring during 2009-2019. Outbreaks were included if they were caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. RESULTS: A total of 38,395 outbreaks met inclusion criteria, increasing from 1,932 in 2009 to 3,889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n=23,812, 62%) and contaminated food (n=9,234, 24%). Norovirus was the most commonly reported etiology, reported in 22,820 (59%) outbreaks, followed by Salmonella (n=2,449, 6%) and Shigella (n=1,171, 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (p<0.0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and E. coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). The case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). CONCLUSIONS: Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.

    • Community Health Services
      1. Every school healthy: Policy, research, and actionexternal icon
        Howley NL, Hunt H.
        J Sch Health. 2020 Dec;90(12):903-906.

      2. The Health Education Teacher Instructional Competency Framework: A conceptual guide for quality instruction in school healthexternal icon
        Szucs LE, Andrzejewski JD, Robin L, Telljohann S, Pitt Barnes S, Hunt P.
        J Sch Health. 2021 Oct;91(10):774-787.
        BACKGROUND: Teacher instructional competency, the set of essential knowledge and skills needed to guide teaching practice, is critical to the successful implementation of school health education. The purpose of this paper is to introduce the Health Education Teacher Instructional Competency (HETIC) framework, a new conceptualization describing teacher characteristics, essential knowledge, and essential skills, which can influence instructional practice and improve student learning outcomes in health education. METHODS: Data from 17 publicly available guidance documents, professional standards, published reports, and empirical studies relevant to the fields of public education, school health education, and sexual health education were abstracted and analyzed using qualitative thematic content analysis. RESULTS: The framework describes 3 domains: personal characteristics, essential knowledge, and essential skills, which are believed to contribute to teachers' instructional competencies in delivering health education. The knowledge domain asserts 5 key categories, while the essential skills domain includes 3 categories (learning environments, content and delivery, and collaboration and learning) and contains 11 unique skills. Collectively, these domains are influenced by the learner, school/community, and policy-level factors that shape health education curriculum and instruction. CONCLUSIONS: The HETIC framework presents a conceptual roadmap to guide quality health education preparation, job-embedded training, and delivery. Improving teachers' instructional competencies strengthens learning and prosocial environments that are inclusive, responsive, and affirming of students' health and learning needs. Teacher who demonstrate instructional competency can help students to achieve desired education and health outcomes, specifically acquiring the knowledge and skills needed to adapt, practice, and maintain healthy behaviors throughout their lifetime.

    • Disaster Control and Emergency Services
      1. World Trade Center Health Program - United States, 2012-2020external icon
        Azofeifa A, Martin GR, Santiago-Colón A, Reissman DB, Howard J.
        MMWR Surveill Summ. 2021 Sep 10;70(4):1-21.
        PROBLEM/CONDITION: After the September 11, 2001, terrorist attacks on the United States, approximately 400,000 persons were exposed to toxic contaminants and other factors that increased their risk for certain physical and mental health conditions. Shortly thereafter, both federal and nonfederal funds were provided to support various postdisaster activities, including medical monitoring and treatment. In 2011, as authorized by the James Zadroga 9/11 Health and Compensation Act of 2010, the CDC World Trade Center (WTC) Health Program began providing medical screening, monitoring, and treatment of 9/11-related health conditions for WTC responders (i.e., persons who were involved in rescue, response, recovery, cleanup, and related support activities after the September 11, 2001, terrorist attacks) and affected WTC survivors (i.e., persons who were present in the dust or dust cloud on 9/11 or who worked, lived, or attended school, child care centers, or adult day care centers in the New York City disaster area). REPORTING PERIOD COVERED: 2012-2020. DESCRIPTION OF SYSTEM: The U.S. Department of Health and Human Services WTC Health Program is administered by the director of CDC's National Institute for Occupational Safety and Health. The WTC Health Program uses a multilayer administrative claims system to process members' authorized program health benefits. Administrative claims data are primarily generated by clinical providers in New York and New Jersey at the Clinical Centers of Excellence and outside those states by clinical providers in the Nationwide Provider Network. This report describes WTC Health Program trends for selected indicators during 2012-2020. RESULTS: In 2020, a total of 104,223 members were enrolled in the WTC Health Program, of which 73.4% (n = 76,543) were responders and 26.6% (n = 27,680) were survivors. WTC Health Program members are predominantly male (78.5%). The median age of members was 51 years (interquartile range [IQR]: 44-57) in 2012 and 59 years (IQR: 52-66) in 2020. During 2012-2020, enrollment and number of certifications of WTC-related health conditions increased among members, with the greatest changes observed among survivors. Overall, at enrollment, most WTC Health Program members lived in New York (71.7%), New Jersey (9.3%), and Florida (5.7%). In 2020, the total numbers of cancer and noncancer WTC-related certifications among members were 20,612 and 50,611, respectively. Skin cancer, male genital system cancers, and in situ neoplasms (e.g., skin and breast) are the most common WTC-related certified cancer conditions. The most commonly certified noncancer conditions are in the aerodigestive and mental health categories. The average number of WTC-related certified conditions per certified member is 2.7. In 2020, a total of 40,666 WTC Health Program members received annual monitoring and screening examinations (with an annual average per calendar year of 35,245). In 2020, the total number of WTC Health Program members who received treatment was 41,387 (with an annual average per calendar year of 32,458). INTERPRETATION: Since 2011, the WTC Health Program has provided health care for a limited number of 9/11-related health conditions both for responders and survivors of the terrorist attacks. Over the study period, program enrollment and WTC certification increased, particularly among survivors. As the members age, increased use of health services and costs within the WTC Health Program are expected; chronic diseases, comorbidities, and other health-related conditions unrelated to WTC exposures are more common in older populations, which might complicate the clinical management of WTC-related health conditions. PUBLIC HEALTH ACTION: Analysis of administrative claims data in the context of WTC research findings can better clarify the health care use patterns of WTC Health Program members. This information guides programmatic decision-making and might also help guide future disaster preparedness and response health care efforts. Strengthening the WTC Health Program health informatics infrastructure is warranted for timely programmatic and research decision-making.

    • Disease Reservoirs and Vectors
      1. The host range restriction of bat-associated no-known-vector flaviviruses occurs post-entryexternal icon
        Charles J, Tangudu CS, Nunez-Avellaneda D, Brault AC, Blitvich BJ.
        J Gen Virol. 2021 Sep;102(9).
        Most flaviviruses are transmitted horizontally between vertebrate hosts by haematophagous arthropods. Others exhibit host ranges restricted to vertebrates or arthropods. Vertebrate-specific flaviviruses are commonly referred to as no-known-vector (NKV) flaviviruses and can be separated into bat- and rodent-associated NKV flaviviruses. Rio Bravo virus (RBV) is one of eight recognized bat-associated NKV (B-NKV) flaviviruses. Studies designed to identify the genetic determinants that condition the host range restriction of B-NKV flaviviruses have never been performed. To investigate whether the host range restriction occurs at the level of attachment or entry, chimeric flaviviruses were created by inserting the pre-membrane and envelope protein genes of RBV into the genetic backbones of yellow fever virus (YFV) and Zika virus (ZIKV), two mosquito-borne flaviviruses associated with human disease. The chimeric viruses infected both vertebrate and mosquito cells. In vertebrate cells, all viruses produced similar mean peak titres, but the chimeric viruses grew more slowly than their parental viruses during early infection. In mosquito cells, the chimeric virus of YFV and RBV grew more slowly than YFV at early post-inoculation time points, but reached a similar mean peak titre. In contrast, the chimeric virus of ZIKV and RBV produced a mean peak titre that was approximately 10-fold lower than ZIKV. The chimeric virus of YFV and RBV produced an intermediate plaque phenotype, while the chimeric virus of ZIKV and RBV produced smaller plaques than both parental viruses. To conclude, we provide evidence that the structural glycoproteins of RBV permit entry into both mosquito and vertebrate cells, indicating that the host range restriction of B-NKV flaviviruses is mediated by a post-attachment/entry event.

    • Environmental Health
      1. Polycyclic aromatic hydrocarbons in Houston parks after Hurricane Harveyexternal icon
        Casillas GA, Johnson NM, Chiu WA, Ramirez J, McDonald TJ, Horney JA.
        Environ Justice. 2021 Aug 1;14(4):277-287.
        Unprecedented inland precipitation and catastrophic flooding associated with Hurricane Harvey potentially redistributed contaminants from industrial sites and transportation infrastructure to recreational areas that make up networks of green infrastructure, creeks, and waterways used for flood control throughout the Greater Houston Area. Sediment samples were collected in parks located near the Buffalo Bayou watershed 1 week after Hurricane Harvey made landfall and again 7 weeks later. Total concentrations of the U.S. Environmental Protection Agency's (EPA's) 16 priority polycyclic aromatic hydrocarbons (PAHs) were measured in each sample at both time points. Diagnostic ratios were calculated to improve understanding of potential sources of PAHs after flooding. Diagnostic ratios suggest vehicular traffic to be a potential source for PAHs in parks. Although the concentrations of PAHs in all samples were below EPA actionable levels, given that no background values were available for comparison, it is difficult to quantify the impact flooding from Hurricane Harvey had on PAH concentrations in Houston parks. However, given the high frequency of flooding in Houston, and the concentration of industrial facilities and transportation infrastructure adjacent to recreation areas, these data demonstrate that PAHs were still present after unprecedented flooding. This study may also serve as a baseline for future efforts to understand the environmental health impacts of disasters.

    • Epidemiology and Surveillance
      1. Predicting virologically confirmed influenza using school absences in Allegheny County, Pennsylvania, USA during the 2007-2015 influenza seasonsexternal icon
        Quandelacy TM, Zimmer S, Lessler J, Vukotich C, Bieltz R, Grantz KH, Galloway D, Read JM, Zheteyeva Y, Gao H, Uzicanin A, Cummings DA.
        Influenza Other Respir Viruses. 2021 Sep 3.
        BACKGROUND: Children are important in community-level influenza transmission. School-based monitoring may inform influenza surveillance. METHODS: We used reported weekly confirmed influenza in Allegheny County during the 2007 and 2010-2015 influenza seasons using Pennsylvania's Allegheny County Health Department all-age influenza cases from health facilities, and all-cause and influenza-like illness (ILI)-specific absences from nine county school districts. Negative binomial regression predicted influenza cases using all-cause and illness-specific absence rates, calendar week, average weekly temperature, and relative humidity, using four cross-validations. RESULTS: School districts reported 2 184 220 all-cause absences (2010-2015). Three one-season studies reported 19 577 all-cause and 3012 ILI-related absences (2007, 2012, 2015). Over seven seasons, 11 946 confirmed influenza cases were reported. Absences improved seasonal model fits and predictions. Multivariate models using elementary school absences outperformed middle and high school models (relative mean absolute error (relMAE) = 0.94, 0.98, 0.99). K-5 grade-specific absence models had lowest mean absolute errors (MAE) in cross-validations. ILI-specific absences performed marginally better than all-cause absences in two years, adjusting for other covariates, but markedly worse one year. CONCLUSIONS: Our findings suggest seasonal models including K-5th grade absences predict all-age-confirmed influenza and may serve as a useful surveillance tool.

    • Genetics and Genomics
      1. Streptococcus pneumoniae genomic datasets from an Indian population describing pre-vaccine evolutionary epidemiology using a whole genome sequencing approachexternal icon
        Nagaraj G, Govindan V, Ganaie F, Venkatesha VT, Hawkins PA, Gladstone RA, McGee L, Breiman RF, Bentley SD, Klugman KP, Lo SW, Ravikumar KL.
        Microb Genom. 2021 Sep;7(9).
        Globally, India has a high burden of pneumococcal disease, and pneumococcal conjugate vaccine (PCV) has been rolled out in different phases across the country since May 2017 in the national infant immunization programme (NIP). To provide a baseline for assessing the impact of the vaccine on circulating pneumococci in India, genetic characterization of pneumococcal isolates detected prior to introduction of PCV would be helpful. Here we present a population genomic study of 480 Streptococcus pneumoniae isolates collected across India and from all age groups before vaccine introduction (2009-2017), including 294 isolates from pneumococcal disease and 186 collected through nasopharyngeal surveys. Population genetic structure, serotype and antimicrobial susceptibility profile were characterized and predicted from whole-genome sequencing data. Our findings revealed high levels of genetic diversity represented by 110 Global Pneumococcal Sequence Clusters (GPSCs) and 54 serotypes. Serotype 19F and GPSC1 (CC320) was the most common serotype and pneumococcal lineage, respectively. Coverage of PCV13 (Pfizer) and 10-valent Pneumosil (Serum Institute of India) serotypes in age groups of ≤2 and 3-5 years were 63-75 % and 60-69 %, respectively. Coverage of PPV23 (Merck) serotypes in age groups of ≥50 years was 62 % (98/158). Among the top five lineages causing disease, GPSC10 (CC230), which ranked second, is the only lineage that expressed both PCV13 (serotypes 3, 6A, 14, 19A and 19F) and non-PCV13 (7B, 13, 10A, 11A, 13, 15B/C, 22F, 24F) serotypes. It exhibited multidrug resistance and was the largest contributor (17 %, 18/103) of NVTs in the disease-causing population. Overall, 42 % (202/480) of isolates were penicillin-resistant (minimum inhibitory concentration ≥0.12 µg ml(-1)) and 45 % (217/480) were multidrug-resistant. Nine GPSCs (GPSC1, 6, 9, 10, 13, 16, 43, 91, 376) were penicillin-resistant and among them six were multidrug-resistant. Pneumococci expressing PCV13 serotypes had a higher prevalence of antibiotic resistance. Sequencing of pneumococcal genomes has significantly improved our understanding of the biology of these bacteria. This study, describing the pneumococcal disease and carriage epidemiology pre-PCV introduction, demonstrates that 60-75 % of pneumococcal serotypes in children ≤5 years are covered by PCV13 and Pneumosil. Vaccination against pneumococci is very likely to reduce antibiotic resistance. A multidrug-resistant pneumococcal lineage, GPSC10 (CC230), is a high-risk clone that could mediate serotype replacement.

    • Health Disparities
      1. Disparities in breast-conserving therapy for non-Hispanic American Indian/Alaska native women compared with non-Hispanic white womenexternal icon
        Erdrich J, Cordova-Marks F, Monetathchi AR, Wu M, White A, Melkonian S.
        Ann Surg Oncol. 2021 Sep 6.
        BACKGROUND: Little is known about the surgical patterns of American Indian/Alaska Native (AI/AN) breast cancer patients. The purpose of this study is to determine whether there are disparities in breast cancer surgery and radiation therapy between non-Hispanic AI/AN (NH-AI/AN) women and non-Hispanic White (NHW) women. METHODS: Data from the National Program of Cancer Registries of the Centers for Disease Control and Surveillance, Epidemiology, and End Results were used for this cross-sectional study. Female patients with invasive breast cancer diagnosed 2010-2015 were stratified by race/ethnicity, surgical procedure, radiation, and region. Percentage distributions of mastectomy and lumpectomy were compared overall and by region and stage. RESULTS: From 2010 to 2015 there were 3292 NH-AI/AN women and 165,225 NHW women diagnosed with breast cancer. For early stage (AJCC stage 1 and 2), NH-AI/AN women had overall significantly higher percentage of mastectomy (41% vs 34.4%, p < 0.001) and significantly lower percentage of lumpectomy (59% vs 65.6%) compared with NHW women, without significant differences in post-lumpectomy radiation (71% vs 70%). There were regional variations, notably in the Northern Plains, where the percentage of mastectomy for early-stage disease was 48.9% for NH-AI/AN women versus 35.9% for NHW women, and in Alaska with 47% for NH-AI/AN women versus 33.3% for NHW women (p < 0.001). There were no overall significant differences in type of surgery or radiation for late-stage disease between groups. CONCLUSION: This is the first study to show disparities in surgical management of NH-AI/AN women with breast cancer. For early-stage disease, NH-AI/AN women undergo a higher percentage of mastectomy. Future clinical directions could focus on the factors that drive awareness, decision-making, and access to breast conservation.

      2. Social vulnerability and county stay-at-home behavior during COVID-19 stay-at-home orders, United States, April 7-April 20, 2020external icon
        Fletcher KM, Espey J, Grossman M, Sharpe JD, Curriero FC, Wilt GE, Sunshine G, Moreland A, Howard-Williams M, Ramos JG, Giuffrida D, García MC, Harnett WM, Foster S.
        Ann Epidemiol. 2021 Sep 6.
        PURPOSE: Early COVID-19 mitigation relied on people staying home except for essential trips. The ability to stay home may differ by sociodemographic factors. We analyzed how factors related to social vulnerability impact a community's ability to stay home during a stay-at-home order. METHODS: Using generalized, linear mixed models stratified by stay-at-home order (mandatory or not mandatory), we analyzed county-level stay-at-home behavior (inferred from mobile devices) during a period when a majority of United States counties had stay-at-home orders (April 7 to April 20, 2020) with the Centers for Disease Control and Prevention Social Vulnerability Index. RESULTS: Counties with higher percentages of single-parent households, mobile homes, and persons with lower educational attainment were associated with lower stay-at-home behavior compared with counties with lower respective percentages. Counties with higher unemployment, higher percentages of limited-English-language speakers, and more multi-unit housing were associated with increases in stay-at-home behavior compared with counties with lower respective percentages. Stronger effects were found in counties with mandatory orders. CONCLUSIONS: Sociodemographic factors impact a community's ability to stay home during COVID-19 stay-at-home orders. Communities with higher social vulnerability may have more essential workers without work-from-home options or fewer resources to stay home for extended periods, which may increase risk for COVID-19. Results are useful for tailoring messaging, COVID-19 vaccine delivery, and responses to future outbreaks.

      3. Sexual and reproductive health information: Disparities across sexual orientation groups in two cohorts of U.S. womenexternal icon
        Tabaac AR, Haneuse S, Johns M, Tan AS, Austin SB, Potter J, Lindberg L, Charlton BM.
        Sex Res Social Policy. 2021 Sep;18(3):612-620.
        INTRODUCTION: Limited research exists about how receiving/seeking sexual and reproductive health (SRH) information differs by sexual orientation. Our goal was to identify how sources and topics of SRH information differed by sexual orientation during adolescence in a sample of U.S. women. METHODS: A sample of 8,541 U.S. women ages 22-35 years from two cohorts of the Growing Up Today Study completed a 2016 questionnaire measure about receiving/seeking SRH information before age 18 years. Adjusted log-linear models assessed differences in SRH information topics and sources by reported sexual orientation (completely heterosexual with no same-sex partners [reference]; completely heterosexual with same-sex partners; mostly heterosexual; bisexual; lesbian). RESULTS: Compared to the referent, most sexual minority subgroups were more likely to receive/seek information from peers, media, and other sources (e.g., community centers). With the exception of lesbians, sexual minority subgroups were more likely to receive/seek information about contraception, and mostly heterosexual and bisexual women were more likely to receive information about sexually transmitted infections. Conclusions: Findings indicate women of diverse sexual orientations need access to SRH information from sources like schools, peers, and media. Sexual minority women receive/seek information about many SRH topics, which indicates that opportunities to tailor educational resources within and outside of schools are needed so SRH benefits to these populations are maximized. POLICY IMPLICATIONS: Specifying sexual minority-sensitive educational materials in sex education policy can meet information needs and aid sexual minority women in making informed sexual health decisions.

    • Health Economics
      1. Dance of dollars: State funding effects on local health department expendituresexternal icon
        Viall AH, Bekemeier B, Yeager V, Carton T.
        J Public Health Manag Pract. 2021 Sep 1.
        OBJECTIVE: We examined changes in total local health department (LHD) expenditures in the state of Washington following introduction of a new state funding program to support core public health services and infrastructure. METHODS: We used a pre/posttest design regression model to evaluate changes in LHD expenditures 1, 2, and 6 years into the new state program. To address potential endogeneity in the model, we repeated all 3 analyses using 2-stage least squares regression. RESULTS: In the base case, overall spending among LHDs significantly increased with receipt of the new state funds in the first years of the program (2008 and 2009). However, those increases were not sustained over the longer term (2013). In subpopulation analyses, total LHD spending increased more among larger LHDs. CONCLUSIONS: Between 2006 and 2013, new state investments in core public health functions increased Washington State LHD expenditures in the short term, but those increases did not persist over time. For public health financial modernization efforts to translate into public health infrastructure modernization successes, the way new investments are structured may be as important as the amount of funding added.

    • Healthcare Associated Infections
      1. Rapid assessment and containment of Candida auris transmission in postacute care settings-Orange County, California, 2019external icon
        Karmarkar EN, O'Donnell K, Prestel C, Forsberg K, Gade L, Jain S, Schan D, Chow N, McDermott D, Rossow J, Toda M, Ruiz R, Hun S, Dale JL, Gross A, Maruca T, Glowicz J, Brooks R, Bagheri H, Nelson T, Gualandi N, Khwaja Z, Horwich-Scholefield S, Jacobs J, Cheung M, Walters M, Jacobs-Slifka K, Stone ND, Mikhail L, Chaturvedi S, Klein L, Vagnone PS, Schneider E, Berkow EL, Jackson BR, Vallabhaneni S, Zahn M, Epson E.
        Ann Intern Med. 2021 Sep 7.
        BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

      2. Notes from the field: Tuberculosis outbreak linked to a contaminated bone graft product used in spinal surgery - Delaware, March-June 2021external icon
        Li R, Wilson WW, Schwartz NG, Hernandez-Romieu AC, Glowicz J, Hanlin E, Taylor M, Pelkey H, Briody CA, Gireesh L, Eskander M, Lingenfelter K, Althomsons SP, Stewart RJ, Free R, Annambhotla P, Basavaraju SV, Wortham JM, Morris SB, Benowitz I, Haddad MB, Hong R, Drees M.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 10;70(36):1261-1263.

    • Immunity and Immunization
      1. Ecological analysis of the decline in incidence rates of COVID-19 among nursing home residents associated with vaccination, United States, December 2020-January 2021external icon
        Benin AL, Soe MM, Edwards JR, Bagchi S, Link-Gelles R, Schrag SJ, Herzer K, Verani JR, Budnitz D, Nanduri S, Jernigan J, Edens C, Gharpure R, Patel A, Wu H, Golshir BC, Jaffe A, Li Q, Srinivasan A, Shulman E, Ling SM, Moody-Williams J, Fleisher LA, Pollock DA, Bell J.
        J Am Med Dir Assoc. 2021 Aug 13.
        OBJECTIVE: To evaluate if facility-level vaccination after an initial vaccination clinic was independently associated with COVID-19 incidence adjusted for other factors in January 2021 among nursing home residents. DESIGN: Ecological analysis of data from the CDC's National Healthcare Safety Network (NHSN) and from the CDC's Pharmacy Partnership for Long-Term Care Program. SETTING AND PARTICIPANTS: CMS-certified nursing homes participating in both NHSN and the Pharmacy Partnership for Long-Term Care Program. METHODS: A multivariable, random intercepts, negative binomial model was applied to contrast COVID-19 incidence rates among residents living in facilities with an initial vaccination clinic during the week ending January 3, 2021 (n = 2843), vs those living in facilities with no vaccination clinic reported up to and including the week ending January 10, 2021 (n = 3216). Model covariates included bed size, resident SARS-CoV-2 testing, staff with COVID-19, cumulative COVID-19 among residents, residents admitted with COVID-19, community county incidence, and county social vulnerability index (SVI). RESULTS: In December 2020 and January 2021, incidence of COVID-19 among nursing home residents declined to the lowest point since reporting began in May, diverged from the pattern in community cases, and began dropping before vaccination occurred. Comparing week 3 following an initial vaccination clinic vs week 2, the adjusted reduction in COVID-19 rate in vaccinated facilities was 27% greater than the reduction in facilities where vaccination clinics had not yet occurred (95% confidence interval: 14%-38%, P < .05). CONCLUSIONS AND IMPLICATIONS: Vaccination of residents contributed to the decline in COVID-19 incidence in nursing homes; however, other factors also contributed. The decline in COVID-19 was evident prior to widespread vaccination, highlighting the benefit of a multifaced approach to prevention including continued use of recommended screening, testing, and infection prevention practices as well as vaccination to keep residents in nursing homes safe.

      2. Rotavirus vaccines: progress and new developmentsexternal icon
        Cates J, Tate JE, Parashar U.
        Expert Opin Biol Ther. 2021 Sep 6.
        INTRODUCTION: Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths annually. There are six licensed oral, live-attenuated rotavirus vaccines, including four vaccines pre-qualified for global use by WHO, and two country-specific vaccines. Successful expansion of rotavirus vaccines into national immunization programs worldwide has led to a 59% decrease in rotavirus hospitalizations and 36% decrease in diarrhea deaths due to rotavirus in vaccine-introducing countries. AREAS COVERED: This review describes the current rotavirus vaccines in use, global coverage, vaccine efficacy from clinical trials, and vaccine effectiveness and impact from post-licensure evaluations. Vaccine safety, particularly as it relates to the risk of intussusception, is also summarized. Additionally, an overview of candidate vaccines in the pipeline is provided. EXPERT OPINION: Considerable evidence over the past decade has demonstrated high effectiveness (80-90%) of rotavirus vaccines at preventing severe rotavirus disease in high-income countries, although the effectiveness has been lower (40-70%) in low-to-middle-income countries. Surveillance and research should continue to explore modifiable factors that influence vaccine effectiveness, strengthen data to better evaluate newer rotavirus vaccines, and aid in the development of future vaccines that can overcome the limitations of current vaccines.

      3. Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversityexternal icon
        Davis EH, Beck AS, Li L, White MM, Greenberg MB, Thompson JK, Widen SG, Barrett AD, Bourne N.
        NPJ Vaccines. 2021 Sep 2;6(1):112.
        Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA14-5-3 and SA14-2-8 were derived from SA14. Both were shown to be attenuated but lacked sufficient immunogenicity to be considered effective vaccines. To better contrast the SA14-14-2 vaccine with its less-immunogenic counterparts, genetic diversity, ribavirin sensitivity, mouse virulence and mouse immunogenicity of the three vaccines were investigated. Next generation sequencing demonstrated that SA14-14-2 was significantly more diverse than both SA14-5-3 and SA14-2-8, and was slightly less diverse than WT SA14. Notably, WT SA14 had unpredictable levels of diversity across its genome whereas SA14-14-2 is highly diverse, but genetic diversity is not random, rather the virus only tolerates variability at certain residues. Using Ribavirin sensitivity in vitro, it was found that SA14-14-2 has a lower fidelity replication complex compared to SA14-5-3 and SA14-2-8. Mouse virulence studies showed that SA14-2-8 was the most virulent of the three vaccine strains while SA14-14-2 had the most favorable combination of safety (virulence) and immunogenicity for all vaccines tested. SA14-14-2 contains genetic diversity and sensitivity to the antiviral Ribavirin similar to WT parent SA14, and this genetic diversity likely explains the (1) differences in genomic sequences reported for SA14-14-2 and (2) the encoding of major attenuation determinants by the viral E protein.

      4. Why aren't we achieving high vaccination rates for rotavirus vaccine in the United States?external icon
        Kempe A, O'Leary ST, Cortese MM, Crane LA, Cataldi JR, Brtnikova M, Beaty BL, Hurley LP, Gorman C, Tate JE, St Pierre JL, Lindley MC.
        Acad Pediatr. 2021 Jul 10.
        BACKGROUND: Rotavirus vaccine (RV) coverage levels for US infants are <80%. METHODS: We surveyed nationally representative networks of pediatricians by internet/mail from April to June, 2019. Multivariable regression assessed factors associated with difficulty administering the first RV dose (RV#1) by the maximum age. RESULTS: Response rate was 68% (303/448). Ninety-nine percent of providers reported strongly recommending RV. The most common barriers to RV delivery overall (definite/somewhat of a barrier) were: parental concerns about vaccine safety overall (27%), parents wanting to defer (25%), parents not thinking RV was necessary (12%), and parent concerns about RV safety (6%). The most commonly reported reasons for nonreceipt of RV#1 by 4 to 5 months (often/always) were parental vaccine refusal (9%), hospitals not giving RV at discharge from nursery (7%), infants past the maximum age when discharged from neonatal intensive care unit/nursery (6%), and infant not seen before maximum age for well care visit (3%) or seen but no vaccine given (4%). Among respondents 4% strongly agreed and 25% somewhat agreed that they sometimes have difficulty giving RV#1 before the maximum age. Higher percentage of State Child Health Insurance Program/Medicaid-insured children in the practice and reporting that recommendations for timing of RV doses are too complicated were associated with reporting difficulty delivering the RV#1 by the maximum age. CONCLUSIONS: US pediatricians identified multiple, actionable issues that may contribute to suboptimal RV immunization rates including lack of vaccination prior to leaving nurseries after prolonged stays, infants not being seen for well care visits by the maximum age, missed opportunities at visits and parents refusing/deferring.

      5. mRNA vaccine effectiveness against COVID-19 among symptomatic outpatients aged ≥16 years in the United States, February - May 2021external icon
        Kim SS, Chung JR, Belongia EA, McLean HQ, King JP, Nowalk MP, Zimmerman RK, Balasubramani GK, Martin ET, Monto AS, Lamerato LE, Gaglani M, Smith ME, Dunnigan KM, Jackson ML, Jackson LA, Tenforde MW, Verani JR, Kobayashi M, Schrag S, Patel MM, Flannery B.
        J Infect Dis. 2021 Sep 8.
        Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

      6. Effectiveness of COVID-19 vaccines in ambulatory and inpatient care settingsexternal icon
        Thompson MG, Stenehjem E, Grannis S, Ball SW, Naleway AL, Ong TC, DeSilva MB, Natarajan K, Bozio CH, Lewis N, Dascomb K, Dixon BE, Birch RJ, Irving SA, Rao S, Kharbanda E, Han J, Reynolds S, Goddard K, Grisel N, Fadel WF, Levy ME, Ferdinands J, Fireman B, Arndorfer J, Valvi NR, Rowley EA, Patel P, Zerbo O, Griggs EP, Porter RM, Demarco M, Blanton L, Steffens A, Zhuang Y, Olson N, Barron M, Shifflett P, Schrag SJ, Verani JR, Fry A, Gaglani M, Azziz-Baumgartner E, Klein NP.
        N Engl J Med. 2021 Sep 8.
        BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 85 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

      7. Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation, an open label, phase IV, randomized controlled trialexternal icon
        Zaman K, Kovacs SD, Vanderende K, Aziz A, Yunus M, Khan S, Snider CJ, An Q, Estivariz CF, Oberste MS, Pallansch MA, Anand A.
        Vaccine. 2021 Sep 1.
        BACKGROUND: After global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. METHODS: We conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. FINDINGS: Of the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77-81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98-99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. INTERPRETATION: Results support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.

      8. Receipt of mRNA Covid-19 vaccines and risk of spontaneous abortionexternal icon
        Zauche LH, Wallace B, Smoots AN, Olson CK, Oduyebo T, Kim SY, Petersen EE, Ju J, Beauregard J, Wilcox AJ, Rose CE, Meaney-Delman DM, Ellington SR.
        N Engl J Med. 2021 Sep 8.

    • Informatics
      1. High real-time reporting of domestic and wild animal diseases following rollout of mobile phone reporting system in Kenyaexternal icon
        Njenga MK, Kemunto N, Kahariri S, Holmstrom L, Oyas H, Biggers K, Riddle A, Gachohi J, Muturi M, Mwatondo A, Gakuya F, Lekolool I, Sitawa R, Apamaku M, Osoro E, Widdowson MA, Munyua P.
        PLoS One. 2021 ;16(9):e0244119.
        BACKGROUND: To improve early detection of emerging infectious diseases in sub-Saharan Africa (SSA), many of them zoonotic, numerous electronic animal disease-reporting systems have been piloted but not implemented because of cost, lack of user friendliness, and data insecurity. In Kenya, we developed and rolled out an open-source mobile phone-based domestic and wild animal disease reporting system and collected data over two years to investigate its robustness and ability to track disease trends. METHODS: The Kenya Animal Biosurveillance System (KABS) application was built on the Java® platform, freely downloadable for android compatible mobile phones, and supported by web-based account management, form editing and data monitoring. The application was integrated into the surveillance systems of Kenya's domestic and wild animal sectors by adopting their existing data collection tools, and targeting disease syndromes prioritized by national, regional and international animal and human health agencies. Smartphone-owning government and private domestic and wild animal health officers were recruited and trained on the application, and reports received and analyzed by Kenya Directorate of Veterinary Services. The KABS application performed automatic basic analyses (frequencies, spatial distribution), which were immediately relayed to reporting officers as feedback. RESULTS: Of 697 trained domestic animal officers, 662 (95%) downloaded the application, and >72% of them started reporting using the application within three months. Introduction of the application resulted in 2- to 14-fold increase in number of disease reports when compared to the previous year (relative risk = 14, CI 13.8-14.2, p<0.001), and reports were more widely distributed. Among domestic animals, food animals (cattle, sheep, goats, camels, and chicken) accounted for >90% of the reports, with respiratory, gastrointestinal and skin diseases constituting >85% of the reports. Herbivore wildlife (zebra, buffalo, elephant, giraffe, antelopes) accounted for >60% of the wildlife disease reports, followed by carnivores (lions, cheetah, hyenas, jackals, and wild dogs). Deaths, traumatic injuries, and skin diseases were most reported in wildlife. CONCLUSIONS: This open-source system was user friendly and secure, ideal for rolling out in other countries in SSA to improve disease reporting and enhance preparedness for epidemics of zoonotic diseases.

    • Injury and Violence
      1. Symptom profile of affirmative responses to a self-report concussion question, United States 2019external icon
        Daugherty J, Sarmiento K, Womack LS, Breiding M.
        Brain Inj. 2021 Sep 6:1-5.
        Information is limited about signs and symptoms experienced by individuals who self-report a concussion within surveys. The objective of this study was to assess the number and types of signs/symptoms adults experienced and whether or not medical attention was reported after sustaining a self-reported concussion in the past year. A sample of 3,624 adults responded to the web-based 2019 FallStyles survey. Respondents were asked if they had sustained a concussion in the past 12 months and if so, which (if any) signs/symptoms they experienced following the injury. The frequency and percentages of symptoms were calculated. Approximately 2.9% of respondents reported a concussion in the past year. Approximately two-thirds of respondents who reported sustaining a recent concussion stated that they experienced two or more signs/symptoms; the remaining one-third reported zero or one symptom. The findings suggest self-report concussion questions need additional improvement, particularly those that capture concussion using a single question, to improve the validity of self-reports.

      2. Introduction: Teen motor vehicle crash fatality rates differ by geographic location. Studies assessing teen transportation risk behaviors by location are inconclusive. Therefore, we explored the role of census region and metropolitan status for driving prevalence and four transportation risk behaviors among U.S. public high school students. Methods: Data from 2015 and 2017 national Youth Risk Behavior Surveys were combined and analyzed. Multivariable models controlled for sex, age, race/ethnicity, grades in school, and school socioeconomic status. Results: Overall, 41% of students did not always wear a seat belt. Students attending schools in the Northeast were 40% more likely than those in the Midwest to not always wear a seat belt. Among the 75% of students aged ≥16 years who had driven during the past 30 days, 47% texted/e-mailed while driving. Students in the Northeast were 20% less likely than those in the Midwest to text/e-mail while driving, and students attending suburban or town schools were more likely to text/e-mail while driving (20% and 30%, respectively) than students attending urban schools. Nineteen percent of students rode with a driver who had been drinking alcohol, and 7% of drivers aged ≥16 years drove when they had been drinking alcohol, with no significant differences by location for either alcohol-related behavior. Conclusions: We found few differences in teen transportation risk behaviors by census region or metropolitan status. Age at licensure, time since licensure, driving experience, and the policy and physical driving environment might contribute more to variation in teen fatal crashes by location than differences in transportation risk behaviors. Regardless of location, teen transportation risk behaviors remain high. Future research could address developing effective strategies to reduce teen cell phone use while driving and enhancing community implementation of existing, effective strategies to improve seat belt use and reduce alcohol consumption and driving after drinking alcohol. © 2021

    • Laboratory Sciences
      1. A randomized, double blind, placebo-controlled, phase 1 safety and pharmacokinetic study of dapivirine gel (0.05%) administered rectally to HIV-1 seronegative adults (MTN-026)external icon
        Cranston RD, Brown E, Bauermeister J, Dunne EF, Hoesley C, Ho K, Johnson S, Lucas J, Dominguez-Islas C, Gundacker H, Peda M, Jacobson CE, Kramzer L, Singh D, Dezzutti CS, Kunjara Na Ayudhya RP, Brand RM, Wang L, Marzinke MA, Piper J, Devlin B, Nuttall J, McGowan I, Hendrix CW.
        AIDS Res Hum Retroviruses. 2021 Sep 9.
        INTRODUCTION: Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, formulated as rectal gel, for safety, pharmacokinetics, and acceptability. METHODS: HIV-uninfected men and women aged 18-45 years were enrolled at United States and Thailand sites and randomized 2:1 to receive DPV 0.05% or placebo gel via rectal applicator. A single dose phase was followed by 7 observed daily doses. Plasma, and fluid and tissue from both rectum and cervix were collected at baseline and after the final dose over 72 hours for pharmacokinetics, ex-vivo HIV-1 biopsy challenge, histology, and flow cytometry. RESULTS: 28 participants were randomized; 2 terminated early; 9 were female and 19 male; 12 were white, 11 Asian, 4 black and 1 other race/ethnicity. Mean age was 28.5 and 34.2 years in the DPV and placebo arms, respectively. Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations (median [interquartile range]) 0.5-1 and 2 hours after a single dose were 256 ng/gm (below limit of quantitation [BLQ], 666) and BLQ (BLQ, 600), respectively, then BLQ (BLQ, BLQ) from 24-72 hours; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15, 0.48) after one dose and 0.40 (0.33, 0.49) after seven doses. CONCLUSIONS: The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.

      2. A novel UHPLC-MS/MS method for measuring 8-iso-prostaglandin F(2α) in bronchoalveolar lavage fluidexternal icon
        Holder C, Adams A, Allison C, Cote O, Lippens R, Blount BC, Wang L.
        Front Chem. 2021 ;9:695940.
        In August 2019, the Centers for Disease Control and Prevention (CDC) received the first reports of lung injuries that were eventually termed e-cigarette, or vaping, product use-associated lung injury (EVALI). As part of the investigation, CDC laboratories rapidly developed assays for analyzing substances in bronchoalveolar lavage (BAL) fluid collected from EVALI case patients. This report describes the development and validation of a high-throughput isotope dilution UHPLC-MS/MS method for measuring a major oxidative stress biomarker, 8-iso-prostaglandin F(2α) (8-isoprostane), in BAL fluid samples. The method showed good sensitivity, 17.6 pg/ml LOD, and requires only 50 μl of sample volume. The method had high throughput with an analytical run time of 11 min. The within-day and between-day coefficient of variation (CV) were below 2%. Accuracy, calculated from spiked recovery, at three spiking levels, ranged from 95.5-101.8%. This novel UHPLC-MS/MS method characterizes oxidative stress in lung epithelial tissue and thus helps to elucidate potential pathologic processes.

      3. Ricin is a toxic protein derived from the castor bean plant (Ricinus communis) and has potential for bioterrorism or criminal use. Therefore, sensitive and rapid analytical methods are needed for its confirmatory detection in environmental samples. Our laboratory previously reported on the development of a confirmatory method to detect ricin involving antibody capture of ricin followed by mass spectrometric detection of ricin's enzymatic activity and of tryptic fragments unique to ricin. Here, we describe a novel ricin capture method of magnetic beads coated with 4-aminophenyl-1-thiol-β-galactopyranoside, using ricin's lectin characteristics. The assay has been adapted for use on a simple, benchtop MALDI-TOF MS mass spectrometer common in clinical microbiology laboratories. Validation of the novel assay includes establishment of a limit of detection, and an examination of assay selectivity. The limit of detection of the enzymatic activity method is 8 ng/mL and 500 ng/mL for the confirmatory tryptic fragment assay. The assay is highly selective with no cross-reactivity from near neighbors and highly specific with a panel of 19 cultivars all testing positive. Additionally, there were no interferences found during testing of a panel of white powders. This allows for a confirmatory detection method for ricin in laboratories lacking expensive, sophisticated mass spectrometers.

      4. As part of the Centers for Disease Control and Prevention’s post-radiological/nuclear incident response mission, we developed rapid bioassay analytical methods to assess possible human exposure to radionuclides and internal contamination. Liquid scintillation counting (LSC) is a valuable analytical tool for the rapid detection and quantification of gross alpha/beta-emitting radionuclides in urine samples. A key characteristic of this type of bioassay method is its detection sensitivity for the priority threat radionuclides. We evaluated the limit of detection of selected LSC instruments to determine which instrument can be used when low-dose measurement is important. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

      5. Delivery of double-stranded RNAs (dsRNAs) produced by Escherichia coli HT115(DE3) for nontransgenic RNAi-based insect pest managementexternal icon
        Taracena ML, Garcia Caffaro I, Paiva-Silva GO, Oliveira PL, Rendon PA, Dotson EM, Pennington PM.
        Methods Mol Biol. 2022 ;2360:279-294.
        RNA interference (RNAi) is a powerful mechanism that can be exploited not only for physiology research but also for designing insect pest management approaches. Some insects cause harm by vectoring diseases dangerous to humans, livestock, or plants or by damaging crops. For at least a decade now, different insect control strategies that induce RNAi by delivering double stranded RNA (dsRNA) targeting essential genes have been proposed. Here, we focus on nontransgenic RNAi-based approaches that use oral delivery of dsRNA through feeding of inactivated bacteria to produce RNAi in disease vectors and in a crop pest. This potential pest management method could be easily adapted to target different genes or similar organisms.

      6. Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from SHIV acquisition by long-acting cabotegravir in macaquesexternal icon
        Vishwanathan SA, Zhao C, Luthra R, Khalil GK, Morris MM, Dinh C, Gary MJ, Mitchell J, Spreen WR, Pereira LE, Heneine W, García-Lerma JG, McNicholl JM.
        Aids. 2021 Aug 20.
        OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STI) that are known to increase HIV susceptibility in women. DESIGN: Two macaque models of increasing vaginal STI severity were used for efficacy assessment. METHODS: The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV). Six animals were CAB-LA treated and 5 were controls. The second study (n = 9) included a triple STI model with repeated exposures to CT, TV and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared to untreated controls over time. RESULTS: All 6 CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges while the untreated animals became SHIV-infected after a median of 2 challenges (log-rank p < 0.001) or 1 challenge (log-rank p = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers and seroconversion. CONCLUSION: In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.

      7. Pulmonary delivery of the broad-spectrum matrix metalloproteinase inhibitor marimastat diminishes multiwalled carbon nanotube-induced circulating bioactivity without reducing pulmonary inflammationexternal icon
        Young TL, Mostovenko E, Denson JL, Begay JG, Lucas SN, Herbert G, Zychowski K, Hunter R, Salazar R, Wang T, Fraser K, Erdely A, Ottens AK, Campen MJ.
        Part Fibre Toxicol. 2021 Sep 8;18(1):34.
        BACKGROUND: Multiwalled carbon nanotubes (MWCNT) are an increasingly utilized engineered nanomaterial that pose the potential for significant risk of exposure-related health outcomes. The mechanism(s) underlying MWCNT-induced toxicity to extrapulmonary sites are still being defined. MWCNT-induced serum-borne bioactivity appears to dysregulate systemic endothelial cell function. The serum compositional changes after MWCNT exposure have been identified as a surge of fragmented endogenous peptides, likely derived from matrix metalloproteinase (MMP) activity. In the present study, we utilize a broad-spectrum MMP inhibitor, Marimastat, along with a previously described oropharyngeal aspiration model of MWCNT administration to investigate the role of MMPs in MWCNT-derived serum peptide generation and endothelial bioactivity. RESULTS: C57BL/6 mice were treated with Marimastat or vehicle by oropharyngeal aspiration 1 h prior to MWCNT treatment. Pulmonary neutrophil infiltration and total bronchoalveolar lavage fluid protein increased independent of MMP blockade. The lung cytokine profile similarly increased following MWCNT exposure for major inflammatory markers (IL-1β, IL-6, and TNF-α), with minimal impact from MMP inhibition. However, serum peptidomic analysis revealed differential peptide compositional profiles, with MMP blockade abrogating MWCNT-derived serum peptide fragments. The serum, in turn, exhibited differential potency in terms of inflammatory bioactivity when incubated with primary murine cerebrovascular endothelial cells. Serum from MWCNT-treated mice led to inflammatory responses in endothelial cells that were significantly blunted with serum from Marimastat-treated mice. CONCLUSIONS: Thus, MWCNT exposure induced pulmonary inflammation that was largely independent of MMP activity but generated circulating bioactive peptides through predominantly MMP-dependent pathways. This MWCNT-induced lung-derived bioactivity caused pathological consequences of endothelial inflammation and barrier disruption.

    • Medicine
      1. Women and girls with haemophilia receiving care at specialized haemophilia treatment centres in the United Statesexternal icon
        Miller CH, Soucie JM, Byams VR, Payne AB, Sidonio RF, Buckner TW, Bean CJ.
        Haemophilia. 2021 Sep 4.
        INTRODUCTION: Females may have haemophilia with the same factor VIII (FVIII) or factor IX (FIX) levels as affected males. Characterization of females with haemophilia would be useful for health care planning to meet their unique needs. Federally-funded haemophilia treatment centres (HTCs) in the United States contribute data on all individuals with bleeding disorders receiving care to the Population Profile (HTC PP) component of the Community Counts Public Health Surveillance of Bleeding Disorders project. AIMS: To estimate the number of females with haemophilia receiving care at HTCs in the United States and compare their characteristics with those of males with haemophilia. METHODS: HTC PP data collected on people receiving care at an HTC from January 2012 through September 2020 with haemophilia A and B were evaluated by sex for demographic and clinical characteristics. RESULTS: A factor level < 40% was reported for 23,196 males (97.8%) and 1667 females (47.6%) attending HTCs; 51 (.48%) severe, 79 (1.4%) moderate, and 1537 (17.9%) mild haemophilia patients were female. Females were older, more often White, and less often non-Hispanic than males. Females were less likely to have history of HIV or HCV infection, even among those with severe disease, but twice as likely to have infection status unknown. Females with mild haemophilia were more often uninsured than males. CONCLUSIONS: Females with severe or moderate haemophilia are uncommon, even in specialized care centres; however, almost one in five patients with mild haemophilia was female, indicating needs for specialized care based on factor level and history for affected females.

    • Occupational Safety and Health
      1. Aging and the future of decent workexternal icon
        Fischer FM, Martinez MC, Alfredo CH, Silva-Junior JS, Oakman J, Cotrim T, Fisher D, Popkin S, Petery GA, Schulte PA.
        Int J Environ Res Public Health. 2021 Aug 24;18(17).
        The United Nations identified decent work and economic growth as a sustainable development goal for 2030. Decent work is a term that sums up aspirations for people in their working lives. One of the factors that influences the achievement of decent work is aging. This article examines how aspects of aging and organizational factors affect work ability across the lifespan and throughout one's work career. Additionally, the critical issue of worker physical mobility was also addressed as a practical limitation to functional aging. Through our investigation, we identified gaps in the literature where research and interventions should be promoted. These include early disability studies; population dashboards of workers' health metrics; intervention and cost effectiveness in health promotion and prevention of early functional aging at work; policies for tailoring demands to individual needs and abilities; and inequities of social protection for aging workers.

      2. OBJECTIVE Diabetes affects nearly 12.2% of U.S. adults. Comorbid depressive symptoms among U.S. workers with diabetes are associated with increased unemployment and reduced work performance. This study examined the age-group-specific prevalence of depression among U.S. workers with self-reported diabetes and identified factors associated with depression. METHODS Data from the 2014-2018 Behavioral Risk Factor Surveillance System were used to examine the prevalence of depression among adult workers with diabetes in the United States. Relationships between depression prevalence and diabetes and demographic, physical, and behavioral risk factors were examined through bivariate and multivariable analyses. Age was categorized into four groups: 18-34, 35-54, 55-64, and &gt;=65 years. RESULTS The overall prevalence of self-reported depression among U.S. workers with diabetes was 17.4%-30% higher than among those without diabetes. Workers with diabetes aged 18-34 years had the highest depression prevalence (28.7%) compared with other age-groups. Female workers with diabetes were significantly more likely than male workers to report depression in all age-groups. Young adult workers with diabetes who had another chronic disease were nearly three times more likely to report depression than those without another chronic condition. There were no overlapping patterns of prevalence of diabetes and depression by state. CONCLUSION Workers with diabetes are at an increased risk of depression, which can affect their overall health and productivity. These findings indicate that, among those with diabetes, young adult workers and women are most likely to have depression. Employee wellness programs may address the specific needs of individuals with diabetes and depression.

      3. Nano- and microplastics in the workplaceexternal icon
        Murashov V, Geraci CL, Schulte PA, Howard J.
        J Occup Environ Hyg. 2021 Sep 3:1-9.

      4. Fiber-cement can contain as much as 50% crystalline silica and cutting this material has shown to cause excessive exposures to respirable crystalline silica. We conducted this study to evaluate different saw blades for cutting fiber-cement siding, aiming at identifying blade design features that lead to lower dust release. Through laboratory evaluations of 22 saw blades, the releasing rate of respirable dust, i.e., GAPS, was analyzed and compared with and without engineering control measures. Two on-tool passive control measures were specifically evaluated. First, a dust-collecting box with a capped exhaust port was attached to the circular saw. Second, the dust-collecting box was connected to a passive dust collector, which includes a cyclone dust collector and an air filter. Both control measures help collect a portion of the dust with the aid of the induced airflow from the fast-spinning blade. The GAPS generally increased with the number of teeth and the kerf width of the blades. However, the number of teeth seems to have a reduced effect on GAPS for the conditions with the two control measures, possibly due to a higher airflow rate induced by more blade teeth, which results in more dust captured by the dust collectors. The 4-tooth Hitachi blade had the lowest GAPS under all three testing conditions, likely due to fewer teeth, thinner kerf, and its specific design characteristics of a “smooth” gullet optimizing induced airflow and dust transporting into the dust collectors. The control measure with the added passive dust collector provided a dust collection efficiency as high as 66%. The gullet design of the blade seems to play an important role in affecting the amount of dust releasing as well as the collection efficiency of the passive dust controls. Copyright: U.S. Government work.

    • Parasitic Diseases
      1. Therapeutic efficacy of artemisinin-based combination therapies in Democratic Republic of the Congo and investigation of molecular markers of antimalarial resistanceexternal icon
        Moriarty LF, Nkoli PM, Likwela JL, Mulopo PM, Sompwe EM, Rika JM, Mavoko HM, Svigel SS, Jones S, Ntamabyaliro NY, Kaputu AK, Lucchi N, Subramaniam G, Niang M, Sadou A, Ngoyi DM, Muyembe Tamfum JJ, Schmedes SE, Plucinski MM, Chowell-Puente G, Halsey ES, Kahunu GM.
        Am J Trop Med Hyg. 2021 Sep 7.
        Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

    • Reproductive Health
      1. Characteristics of Women with Urinary Tract Infection in Pregnancyexternal icon
        Johnson CY, Rocheleau CM, Howley MM, Chiu SK, Arnold KE, Ailes EC.
        J Womens Health (Larchmt). 2021 Sep 1.
        Background: Urinary tract infection (UTI) is the most common bacterial infection in pregnancy. Known risk factors for UTI in pregnancy include diabetes and certain urologic conditions. Other maternal characteristics might also be associated with risk and could provide clues to the etiology of UTI in pregnancy. Our objective was to identify maternal characteristics associated with UTI in pregnancy. Materials and Methods: We used data from pregnant women participating in the National Birth Defects Prevention Study, a population-based study of risk factors for major structural birth defects in 10 U.S. sites, from 1997 to 2011. In cross-sectional analyses, we used multivariable log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations between self-reported maternal characteristics and UTI in pregnancy. Results: In our sample of 41,869 women, the overall prevalence of reported UTI in pregnancy was 18%, but ranged from 11% to 26% between study sites. In adjusted models, diabetes was moderately associated with higher UTI prevalence (PR 1.39, 95% CI: 1.24-1.57). Higher UTI prevalence was associated even more strongly with low educational attainment (PR 2.06, 95% CI: 1.77-2.40 for some high school vs. graduate school), low household income (PR 1.64, 95% CI: 1.46-1.84 for <$10,000 vs. ≥$50,000), and race/ethnicity (PR 1.45, 95% CI: 1.13-1.80 for American Indian or Alaska Native vs. White women). Conclusions: About one in six women reported UTI in pregnancy but the prevalence varied markedly by geography and maternal characteristics. This variability could provide clues to the causes of UTI in pregnancy.

    • Substance Use and Abuse
      1. Characterizing opioid-involved overdose risk in local communities: An opioid overdose vulnerability assessment across Indiana, 2017external icon
        Sawyer JL, Shrestha S, Pustz JC, Gottlieb R, Nichols D, Van Handel M, Lingwall C, Stopka TJ.
        Preventive Medicine Reports. 2021 ;24.
        The objective of this initiative was to conduct a comprehensive opioid overdose vulnerability assessment in Indiana and evaluate spatial accessibility to opioid use disorder treatment, harm reduction services, and opioid response programs. We compiled 2017 county-level (n = 92) data on opioid-related and socioeconomic indicators from publicly available state and federal sources. First, we assessed the spatial distribution of opioid-related indicators in a geographic information system (GIS). Next, we used a novel regression-weighted ranking approach with mean standardized covariates and an opioid-involved overdose mortality outcome to calculate county-level vulnerability scores. Finally, we examined accessibility to opioid use disorder treatment services and opioid response programs at the census tract-level (n = 1511) using two-step floating catchment area analysis. Opioid-related emergency department visit rate, opioid-related arrest rate, chronic hepatitis C virus infection rate, opioid prescription rate, unemployment rate, and percent of female-led households were independently and positively associated with opioid-involved overdose mortality (p < 0.05). We identified high-risk counties across the rural–urban continuum and primarily in east central Indiana. We found that only one of the 19 most vulnerable counties was in the top quintile for treatment services and had naloxone provider accessibility in all of its census tracts. Findings from our vulnerability assessment provide local-level context and evidence to support and inform future public health policies and targeted interventions in Indiana in areas with high opioid overdose vulnerability and low service accessibility. Our approach can be replicated in other state and local public health jurisdictions to assess opioid-involved public health vulnerabilities. © 2021 The Author(s)

    • Zoonotic and Vectorborne Diseases
      1. Identification and characterization of Rift Valley fever virus-specific T cells reveals a dependence on CD40/CD40L interactions for prevention of encephalitisexternal icon
        Barbeau DJ, Cartwright HN, Harmon JR, Spengler JR, Spiropoulou CF, Sidney J, Sette A, McElroy AK.
        J Virol. 2021 Sep 8:Jvi0150621.
        Rift Valley fever virus (RVFV) is an arbovirus found throughout Africa. It causes disease that is typically mild and self-limiting; however, some infected individuals experience severe manifestations, including hepatitis, encephalitis, or even death. Reports of RVFV encephalitis are notable amongst immunosuppressed individuals, suggesting a role for adaptive immunity in preventing this severe complication. This phenomenon has been modeled in C57BL/6 mice depleted of CD4 T cells prior to infection with DelNSs RVFV (RVFV containing a deletion of NSs), resulting in late-onset encephalitis accompanied by high levels of viral RNA in the brain in 30% of animals. In this study, we sought to define the specific type(s) of CD4 T cells that mediate protection from RVFV encephalitis. The viral epitopes targeted by CD4 and CD8 T cells were defined in C57BL/6 mice, and tetramers for both CD4 and CD8 T cells were generated. RVFV-specific CD8 T cells were expanded and of a cytotoxic and proliferating phenotype in the liver following infection. RVFV-specific CD4 T cells were identified in the liver and spleen following infection and phenotyped as largely Th1 or Tfh subtypes. Knock-out mice lacking various aspects of pathways important in Th1 and Tfh development and function were used to demonstrate that T-bet, CD40, CD40L, and MHCII mediated protection from RVFV encephalitis, while IFN-γ and IL-12 were dispensable. Virus-specific antibody responses correlated with protection from encephalitis in all mouse strains, suggesting that Tfh-B cell interactions modulate clinical outcome in this model. Importance: The prevention of RVFV encephalitis requires intact adaptive immunity. In this study we develop reagents to detect RVFV-specific T cells and provide evidence for Tfh cells and CD40/CD40L interactions as critical mediators of this protection.

      2. Clinical and neurodevelopmental outcomes based on brain imaging studies in a Colombian cohort of children with probable antenatal Zika virus exposureexternal icon
        Daza M, Mercado M, Moore CA, Valencia D, Lengua MF, Newton S, Rodríguez B, Tong VT, Acevedo P, Gilboa SM, Ospina ML, Mulkey SB.
        Birth Defects Res. 2021 Sep 7.
        BACKGROUND: Our aim was to describe the neuroimaging and clinical evaluations of children with antenatal Zika-virus (ZIKV) exposure. METHODS: The Colombian National Institute of Health performed serial clinical evaluations of children with probable antenatal ZIKV exposure (i.e., born to ZIKV symptomatic mothers or born with birth defects compatible with ZIKV infection, regardless of laboratory results) over 2 years that included head circumference (HC), eye examination, and neurodevelopmental assessments. Clinical neuroimaging studies (head computed tomography and/or brain magnetic resonance imaging) were analyzed for abnormalities, two-dimensional measurements were made of the right and left frontal and occipital cortical thickness. Two abnormal patterns were defined: Pattern 1 (sum of four areas of cortex <6 cm) and Pattern 2 (sum of four areas of cortex ≥6 cm and < 10 cm). RESULTS: Thirty-one children had a neuroimaging study; in 24, cortical thickness was measured. The median age at the first visit was 8 (range: 6-9) months and 22 (range: 19-42) months at the last evaluation. In the 24 cases with cortical measurements, three were normal, 12 were in Pattern 1, and nine were in Pattern 2. Children within Pattern 1 had lower mean HC at birth and in follow-up (both p < .05) and a higher frequency of structural eye abnormalities (p < .01). A trend towards poorer neuromotor development was seen in Pattern 1, although not statistically significant (p = .06). CONCLUSION: Brain imaging classification based on cortical measurements correlate with ophthalmologic abnormalities and HC. Cortical thickness may be a marker for clinical outcomes in children with congenital ZIKV infection.

      3. Bite injuries among vaccination staff participating in a mass canine rabies vaccination campaign, Haiti 2016-2017external icon
        Kirkhope RT, Gibson AD, Augustin PD, Crowdis K, Fénelon N, MacLeod ET, Vigilato MA, Pieracci EG, Wallace RM.
        Am J Trop Med Hyg. 2021 Sep 7.
        Elimination of dog-transmitted human rabies worldwide will require large-scale dog vaccination campaigns. However, this places participating vaccinators at increased risk. Data from the 2016-2017 Haitian mass rabies vaccination campaign was analyzed to determine dog bite incidence among vaccinators. A survey was then developed for completion by all identifiable bitten vaccinators covering demographics; experience and training; bite episode details; attitudes toward dogs and rabies; and medical care. A parallel group of unbitten vaccinators was also surveyed. Dog bite incidence was 0.03% (43/127,000) of all dogs vaccinated. The capture, vaccinate, and release method of vaccination carried a significantly higher risk of dog bite (0.35%, 6/1,739 vaccinations) than other methods (P < 0.001). Twenty-seven bitten vaccinators, and 54 control vaccinators were included in the survey analysis. No differences were found between groups in demographics, experience, or training. However, bitten vaccinators were significantly more likely than the control group to have experienced a dog bite before the study period (P < 0.001). This may be associated with a lesser appreciation of dogs, and/or a poorer ability to interpret dog behavioral signals within this group. Although 98% of the control group indicated they would seek medical care for a dog bite, only 35% of bitten vaccinators sought such care. On a yearly basis, for the Haitian campaign, a full series of postexposure rabies vaccinations for all bite victims would prove more cost-effective than preexposure vaccination of all vaccinators. These findings may prove useful for the planning and safety of future mass dog vaccination campaigns.

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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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