Issue 28, August 10, 2021

CDC Science Clips: Volume 13, Issue 28, August 10, 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
      • A pilot study of integration of medical and dental care in 6 statesexternal icon
        Linabarger M, Brown M, Patel N.
        Prev Chronic Dis. 2021 Jul 22;18:E72.
        INTRODUCTION: Poor oral health affects overall health. Chronic diseases and related risk factors such as tobacco use or consuming sugar-sweetened beverages can also increase a person's risk of periodontitis. Given the linkages between oral health and certain chronic diseases, we conducted a pilot study to facilitate intradepartmental collaborations between state chronic disease and oral health programs. METHODS: State health departments in 6 states (Alaska, Colorado, Georgia, Maryland, Minnesota, and New York) collaborated to develop and implement projects that addressed oral health and the following chronic diseases or risk factors: obesity, diabetes, heart disease, stroke, and tobacco use. States developed various projects, including media campaigns, clinical education, and screening and referrals. We used a mixed-methods approach to understand barriers to and facilitators of states' increasing collaboration and implementation of pilot projects. In-depth interviews were conducted with 12 staff (1 from oral health and 1 from chronic disease for each state). We also reviewed state-submitted documents and performance measures. RESULTS: All 6 states increased collaboration between their oral health and chronic disease programs and successfully implemented pilot projects. Collaboration was facilitated by investing in relationships, championing medical-dental integration, and meeting and communicating frequently. Barriers to collaboration included the perception of oral health in chronic disease programs as separate and distinct from other chronic diseases and the structure of funding. The pilot projects were facilitated by partner support, providing technical assistance to clinics, and working early on referral networks. Barriers to implementing the pilot projects included gaining clinician buy-in and establishing referral networks. CONCLUSION: This pilot study demonstrated that by fostering collaboration, state health departments are able to train dental and medical clinicians, deliver clinical preventive education to patients, implement referral systems, and deliver impressions via media campaigns.

    • Communicable Diseases
      • Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: A modelling studyexternal icon
        Hillis SD, Unwin HJ, Chen Y, Cluver L, Sherr L, Goldman PS, Ratmann O, Donnelly CA, Bhatt S, Villaveces A, Butchart A, Bachman G, Rawlings L, Green P, Nelson CA, Flaxman S.
        Lancet. 2021 Jul 20;398(10298):391-402.
        BACKGROUND: The COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation. METHODS: We used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60-84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection-fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers. FINDINGS: Globally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000-1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000-1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15-50 years. Between two and five times more children had deceased fathers than deceased mothers. INTERPRETATION: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

    • Environmental Health
      • Long-term pollen trends and associations between pollen phenology and seasonal climate in Atlanta, Georgia (1992-2018)external icon
        Manangan A, Brown C, Saha S, Bell J, Hess J, Uejio C, Fineman S, Schramm P.
        Ann Allergy Asthma Immunol. 2021 Jul 23.
        BACKGROUND: Previous research has shown airborne pollen concentrations and phenology in allergenic plants are changing. Additionally, variations in seasonal climate are known to affect pollen phenology in trees, weeds, and grasses. OBJECTIVE: We investigated localized trends in pollen concentrations and pollen phenology over time, and the effect of seasonal climate variations. METHODS: We used daily pollen count concentrations from a National Allergy Bureau (NAB) pollen counting station located in metropolitan Atlanta, Georgia, U.S. for 13 allergenic taxa. To examine long-term trends over time, we developed linear regression models for six pollen measures. To examine the effect of seasonal climate on phenology, we developed regression models using seasonal climate measures as independent variables, and pollen measures as dependent variables. RESULTS: For several tree pollen taxa, pollen concentrations increased over time, including oak and juniper pollen. In multiple species, pollen seasons trended toward an earlier release throughout the 27-year period. Variations in seasonal climate did have an effect on pollen counts and the timing of pollen release but varied by taxa. Generally, warmer spring temperatures were associated with an earlier pollen release. Additionally, precipitation from the preceding fall and winter were associated with increased pollen concentration in the spring months. CONCLUSION: Allergenic pollen concentrations for several types of pollen are increasing and trending toward an earlier pollen release in Atlanta, GA. Warmer temperatures preceding the pollen season were associated with the earlier pollen release.

      • Exposure to endocrine disrupting chemicals (edcs) and cardiometabolic indices during pregnancy: The HOME Studyexternal icon
        Vuong AM, Braun JM, Sjödin A, Calafat AM, Yolton K, Lanphear BP, Chen A.
        Environment International. 2021 ;156.
        Background: Toxicology studies have identified pregnancy as a window of susceptibility for endocrine disrupting chemicals (EDCs) and cardiometabolic indices in women. No study in humans, however, has examined EDC mixtures and cardiometabolic indices during pregnancy. Methods: We used the Health Outcomes and Measures of the Environment (HOME) Study to examine whether bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFAS), and phthalates are associated with blood pressure, glucose, and lipids in 388 pregnant women. We measured PBDEs and PFAS in serum at 16 weeks gestation, while BPA and phthalate metabolites were quantified in urine at 16 and 26 weeks gestation. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate covariate-adjusted associations of individual EDCs and their mixtures with cardiometabolic indices during pregnancy. Results: A 10-fold increase in BDE-28 was associated with a 13.1 mg/dL increase in glucose (95% Confidence Interval [CI] 2.9, 23.2) in linear regression. The BKMR model also identified BDE-28 as having a positive association with glucose. BDE-28, BDE-47, and BDE-99 were positively associated with total cholesterol in both single- and multi-pollutant models, whereas a suggestive negative association was noted with BDE-153. Mono-n-butyl phthalate (MBP) (β = -7.9 mg/dL, 95% CI −12.9, −3.0) and monobenzyl phthalate (MBzP) (β = −6.3 mg/dL, 95% CI −10.6, −2.0) were both associated with significant decreases in cholesterol in linear regression, but only MBzP was identified as an important contributor in the BKMR model. Conclusion: Overall, we observed positive associations between PBDEs with glucose and cholesterol levels during pregnancy, while negative associations were found between some phthalate biomarkers and cholesterol. No relationship was noted for BPA or PFAS with cardiometabolic indices during pregnancy across both models. © 2021 The Author(s)

    • Food Safety
      • Restaurant date-marking practices concerning ready-to-eat food requiring time and temperature control for safetyexternal icon
        Brown LG, Ebrahim-Zadeh SD, Hoover ER, DiPrete L, Matis B, Viveiros B, Irving DJ, Copeland D, Nicholas D, Hedeen N, Tuttle J, Williams L, Liggans G, Kramer A.
        Foodborne Pathog Dis. 2021 Jul 27.
        Certain foods are more vulnerable to foodborne pathogen growth and formation of toxins than others. Lack of time and temperature control for these foods can result in the growth of pathogens, such as Listeria monocytogenes, and lead to foodborne outbreaks. The Food and Drug Administration's (FDA) Food Code classifies these foods as time/temperature control for safety (TCS) foods and details safe cooking, holding, and storing temperatures for these foods. The FDA Food Code also includes a date-marking provision for ready-to-eat TCS foods that are held for >24 h. The provision states that these foods should not be held in refrigeration for >7 days and should be marked with the date or day by which the food should be "consumed on the premises, sold, or discarded." To learn more about restaurants' date-marking practices, the Centers for Disease Control and Prevention's Environmental Health Specialists Network (EHS-Net) conducted observations and manager interviews in 359 restaurants in 8 EHS-Net jurisdictions. Managers reported that they date marked ready-to-eat TCS foods more often than data collectors observed this practice (91% vs. 77%). Observation data showed almost a quarter of study restaurants did not date-mark ready-to-eat TCS foods. In addition, restaurants with an internal date-marking policy date marked 1.25 times more often than restaurants without such a policy and chain restaurants date marked 5.02 times more often than independently owned restaurants. These findings suggest that regulators and the retail food industry may improve food safety and lower the burden of foodborne illness in the United States if they target interventions to independent restaurants and encourage strong date-marking policies.

    • Health Behavior and Risk
      • School-level poverty and rurality associated with differences in sexual risk behaviors among U.S. public high school studentsexternal icon
        Underwood JM, Pampati S, Everett Jones S, Bryan LN, Demissie Z, Cavalier Y, Rasberry CN.
        J Adolesc Health. 2021 Jul 19.
        PURPOSE: This study examined associations between student sexual behaviors and both school-level socioeconomic status and metropolitan status. METHODS: National Youth Risk Behavior Survey data from 2017 (N = 14,765, response rate = 60%) and 2019 (N = 13,677, 60%) were combined. School-level socioeconomic status (low-, mid-, and high-poverty based on the percentage of students eligible for free or reduced-price meals) and metropolitan status (urban, suburban/town, or rural) were identified for students attending public high schools. Sexual behaviors included currently sexually active, four or more lifetime sexual partners, condom use during the last sexual intercourse, hormonal birth control use during the last sexual intercourse, condom and hormonal birth control use during the last sexual intercourse, and drank alcohol or used drugs before the last sexual intercourse. Adjusted prevalence ratios were calculated using logistic regression models, controlling for sex, race/ethnicity, and grade. RESULTS: Compared to students attending low-poverty schools, high-poverty school students were significantly more likely to be currently sexually active (adjusted prevalence ratio = 1.4 [95% confidence interval = 1.1-1.8]) and have four or more lifetime sexual partners (1.6 [1.0-2.5]), but were significantly less likely to have drank alcohol or used drugs before the last sexual intercourse (.7 [.5-.9]) and have used hormonal birth control during the last sexual intercourse (.7 [.6-1.0]). Compared to students attending rural schools, urban school students were significantly less likely to be currently sexually active (.8 [.7-.9]) and have four or more lifetime sexual partners (.7 [.5-.9]). CONCLUSIONS: School-level socioeconomic status and metropolitan status were associated with differential risk in sexual behaviors.

    • Health Disparities
      • OBJECTIVES: To reduce the number of new HIV infections and improve HIV health care outcomes, the social conditions in which people live and work should be assessed. The objective of this study was to describe linkage to HIV medical care by selected demographic characteristics and social determinants of health (SDH) among US adults with HIV at the county level. METHODS: We used National HIV Surveillance System data from 42 US jurisdictions and data from the American Community Survey to describe differences in linkage to HIV medical care among adults aged ≥18 with HIV infection diagnosed in 2017. We categorized SDH variables into higher or lower levels of poverty (where <13% or ≥13% of the population lived below the federal poverty level), education (where <13% or ≥13% of the population had <high school diploma), and health insurance coverage (where <12% or ≥12% of the population lacked health insurance). We calculated prevalence ratios (PRs) and 95% CIs. RESULTS: Of 33 204 adults with HIV infection diagnosed in 2017, 78.4% were linked to HIV medical care ≤1 month after diagnosis. Overall, rates of linkage to care were significantly lower among men and women living in counties with higher versus lower poverty (PR = 0.96; 95% CI, 0.94-0.97), with lower versus higher health insurance coverage (PR = 0.93; 95% CI, 0.92-0.94), and with lower versus higher education levels (PR = 0.97; 95% CI, 0.96-0.98). CONCLUSIONS: Increasing health insurance coverage and addressing economic and educational disparities would likely lead to better HIV care outcomes in these areas.

    • Immunity and Immunization
      • Modeling poliovirus surveillance and immunization campaign quality monitoring costs for Pakistan and Afghanistan for 2019-2023external icon
        Kalkowska DA, Pallansch MA, Cochi SL, Thompson KM.
        Open Forum Infect Dis. 2021 Jul;8(7):ofab264.
        BACKGROUND: The Global Polio Eradication Initiative (GPEI) Strategic Plan for 2019-2023 includes commitments to monitor the quality of immunization campaigns using lot quality assurance sampling surveys (LQAS) and to support poliovirus surveillance in Pakistan and Afghanistan. METHODS: We analyzed LQAS and poliovirus surveillance data between 2016 and 2020, which included both acute flaccid paralysis (AFP) case-based detection and the continued expansion of environmental surveillance (ES). Using updated estimates for unit costs, we explore the costs of different options for future poliovirus monitoring and surveillance for Pakistan and Afghanistan. RESULTS: The relative value of the information provided by campaign quality monitoring and surveillance remains uncertain and depends on the design, implementation, and performance of the systems. Prospective immunization campaign quality monitoring (through LQAS) and poliovirus surveillance will require tens of millions of dollars each year for the foreseeable future for Pakistan and Afghanistan. CONCLUSIONS: LQAS campaign monitoring as currently implemented in Pakistan and Afghanistan provides limited and potentially misleading information about immunization quality. AFP surveillance in Pakistan and Afghanistan provides the most reliable evidence of transmission, whereas ES provides valuable supplementary information about the extent of transmission in the catchment areas represented at the time of sample collection.

    • Nutritional Sciences
      • Background: Returning to work can impact breastfeeding duration; limited data exist on how this may impact a lower income population. Methods: Data from U.S. Department of Agriculture's longitudinal study WIC Infant and Toddler Feeding Practices Study-2 were used to assess breastfeeding duration (<12 versus ≥12 months) by age of the baby when women first returned to work and work status (full time and part time). Multivariable logistic regression was used to determine the association of the timing of return to work, work status, and the combination (timing and work status) with breastfeeding duration. Results: Among women who had worked prenatally and initiated breastfeeding, 20.2% breastfed for ≥12 months. Compared to women who did not return to work, fewer women breastfed for ≥12 months if they returned full time or part time (34.1%, 12.0%, and 20.0%, respectively, p < 0.0001). Work status negatively impacted breastfeeding for ≥12 months (full-time adjusted odds ratio [aOR]: 0.24; 95% confidence interval [CI]: 0.13, 0.44 and part-time aOR: 0.51; 95% CI: 0.31, 0.83). Compared to women who did not return, those who returned full time within 3 months or returned part time >1 to 3 months after birth had lower odds of breastfeeding ≥12 months. Conclusions: Returning to work within 3 months after birth had a negative impact on breastfeeding for ≥12 months, particularly for those who returned full time. Efforts to support maternity leave and flexible work schedules could prolong breastfeeding durations among a low-income population. This study was a registered study at (NCT02031978).

    • Occupational Safety and Health
      • Exposures to dust, vapors, or fumes (DVF) are associated with chronic bronchitis (CB) and emphysema. The 2007-2012 National Health and Nutrition Examination Survey data were used to estimate age-standardized prevalence of CB and emphysema among ever-employed adults by exposure status and industry and occupation groups. Age-standardized CB and emphysema prevalence were 2.3% and 1.9%, respectively. Of the estimated 111 million U.S. workers exposed to DVF, 2.7% reported CB and 2.8% reported emphysema. Workers in the "accommodation, food services" industry and "food preparation, serving related" occupations were more likely to report CB and emphysema. Current findings indicate that workplace exposures may be associated with high prevalence of CB and emphysema in certain industry and occupational groups. Early diagnosis and identifying associated workplace exposures are important steps in CB and emphysema prevention efforts.

    • Parasitic Diseases
      • BACKGROUND: Severe malaria can be deadly and requires treatment with intravenous artesunate (IVAS). The Centers for Disease Control and Prevention provided IVAS starting April 1, 2019 for all patients with severe malaria in the United States. This study describes the safety and effectiveness of IVAS in these patients. METHODS: Patients meeting criteria for severe malaria April 2019-December 2020 who received IVAS were included. Demographic, clinical, laboratory, adverse event, and outcome information were collected. Clinical presentation, time to reach 1% and 0% parasitemia, adverse events, and death were described using proportions, medians, interquartile range (IQR), and tests of significance for differences in proportions. RESULTS: Of 280 patients included, the majority were male (61.4%), Black/African American (75.0%), with a median age of 35 years (IQR 15.8-53.9). Most had P. falciparum (83.6%) with median parasitemia of 8.0% (IQR 4.6-13.2). Of 170 patients with information, 159 (93.5%) reached ≤1% parasitemia by the third IVAS dose with a median time of 17.6 hours (IQR 10.8-28.8), and 0% parasitemia in a median of 37.2 hours (IQR: 27.2-55.2). Patients with parasite densities >10% and those requiring adjunct therapy had significantly higher parasite clearance times. Adverse events associated with IVAS were reported in 4.8% (n=13 of 271). Eight patients had post-artesunate delayed hemolysis that resolved. There were five (1.8%) deaths, all attributable to severe malaria. CONCLUSIONS: IVAS is a safe and effective drug for the treatment of severe malaria in the United States; timely administration can be lifesaving.

    • Physical Activity
      • Cardiovascular responses to physical activity during work and leisureexternal icon
        Quinn TD, Kline CE, Nagle E, Radonovich LJ, Alansare A, Barone Gibbs B.
        Occup Environ Med. 2021 Jul 28.
        OBJECTIVES: Recent evidence suggests that occupational physical activity (OPA) is associated with adverse cardiovascular health, whereas leisure time physical activity is protective. This study explored explanatory physiological mechanisms. METHODS: Nineteen males (68% white, age=46.6±7.9 years, body mass index=27.9±5.1 kg/m(2)) with high self-reported OPA wore activity (ActiGraph and activPAL) and heart rate (HR) monitors for 7 days and an ambulatory blood pressure (BP) monitor on one workday and one non-workday. Mixed effects models compared cardiovascular variables (24-hour, nocturnal, waking and non-work time HR and BP) and nocturnal HR variability (HRV) on workdays versus non-workdays. Additional models examined associations of daily activity (steps, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA)) with cardiovascular variables. Workday by daily activity interactions were examined. RESULTS: 24-hour and waking HR and diastolic BP as well as non-work diastolic BP were significantly higher on workdays versus non-workdays (p<0.05 for all). However, no difference in systolic BP or nocturnal HR or BP was observed between work and non-workdays (p>0.05 for all). Low-frequency and high-frequency power indices of nocturnal HRV were lower on workdays (p<0.05 for both). Daily steps and LPA were positively associated with 24-hour and waking HR on work and non-workdays. Significant interactions suggested MVPA increases HR and lowers nocturnal HRV during workdays, with the opposite effect on non-workdays. CONCLUSIONS: Cardiovascular load was higher on workdays versus non-workdays with no compensatory hypotensive response following workdays. Daily MVPA may differentially affect ambulatory cardiovascular load and nocturnal HRV on workdays versus non-workdays, supporting the physical activity health paradox hypothesis.

  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. Examination of sleep and obesity in children and adolescents in the United Statesexternal icon
        Chehal PK, Shafer L, Cunningham SA.
        Am J Health Promot. 2021 Jul 12.
        PURPOSE: This study contributes to the growing literature on the association between sleep and obesity by examining the associations between hours of sleep, consistency of bedtime, and obesity among children in the US. DESIGN: Analysis of a nationally representative sample of non-institutionalized children from the 2016-17 National Survey of Children's Health. SETTING: US, national. SUBJECTS: Children ages 10-17 years (n = 34,640). MEASURES: Parent reported weeknight average hours of sleep and consistency of bedtime. Body mass index classified as underweight, normal, overweight or obesity using parent-reported child height and weight information, classified using CDC BMI-for-Age Growth Charts. ANALYSIS: Multivariate logistic regression models were used to estimate associations between measures of sleep and body mass index weight category adjusting for individual, household and neighborhood characteristics. RESULTS: An additional hour of sleep was associated with 10.8% lower odds of obesity, net of consistency in bedtime. After controlling for sleep duration, children who usually went to bed at the same time on weeknights had lower odds of obesity (24.8%) relative to children who always went to bed at the same time. CONCLUSION: Sleep duration is predictive of lower odds of obesity in US children and adolescents. Some variability in weeknight bedtime is associated with lower odds of obesity, though there were no additional benefits to extensive variability in bedtime.

      2. BACKGROUND AND PURPOSE: Emergency department visits and hospitalizations for stroke declined significantly following declaration of coronavirus disease 2019 (COVID-19) as a national emergency on March 13, 2020, in the United States. This study examined trends in hospitalizations for stroke among Medicare fee-for-service beneficiaries aged ≥65 years and compared characteristics of stroke patients during COVID-19 pandemic to comparable weeks in the preceding year (2019). METHODS: For trend analysis, we examined stroke hospitalizations from week 1 in 2019 through week 44 in 2020. For comparison of patient characteristics, we estimated percent reduction in weekly stroke hospitalizations from 2019 to 2020 during weeks 10 through 23 and during weeks 24 through 44 by age, sex, race/ethnicity, and state. RESULTS: Compared to weekly numbers of hospitalizations for stroke reported during 2019, stroke hospitalizations in 2020 decreased sharply during weeks 10 through 15 (March 1-April 11), began increasing during weeks 16 through 23, and remained at a level lower than the same weeks in 2019 from weeks 24 through 44 (June 7-October 31). During weeks 10 through 23, stroke hospitalizations decreased by 22.3% (95% CI, 21.4%-23.1%) in 2020 compared with same period in 2019; during weeks 24 through 44, they decreased by 12.1% (95% CI, 11.2%-12.9%). The magnitude of reduction increased with age but similar between men and women and among different race/ethnicity groups. Reductions in stroke hospitalizations between weeks 10 through 23 varied by state ranging from 0.0% (95% CI, -16.0%-1.7%) in New Hampshire to 36.2% (95% CI, 24.8%-46.7%) in Montana. CONCLUSIONS: One-in-5 fewer stroke hospitalizations among Medicare fee-for-service beneficiaries occurred during initial weeks of the COVID-19 pandemic (March 1-June 6) and weekly stroke hospitalizations remained at a lower than expected level from June 7 to October 31 in 2020 compared with 2019. Changes in stroke hospitalizations varied substantially by state.

    • Communicable Diseases
      1. Incidence rates of influenza illness during pregnancy in Suzhou, China, 2015-2018external icon
        Chen L, Zhou S, Bao L, Millman AJ, Zhang Z, Wang Y, Tan Y, Song Y, Cui P, Pang Y, Liu C, Qin J, Zhang P, Thompson MG, Iuliano AD, Zhang R, Greene CM, Zhang J.
        Influenza Other Respir Viruses. 2021 Jul 29.
        BACKGROUND: Data on influenza incidence during pregnancy in China are limited. METHODS: From October 2015 to September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. RESULTS: In total, we enrolled 18 724 pregnant women median aged 28 years old, 37% in first trimester, 48% in second trimester, and 15% in third trimester, with seven self-reported influenza vaccination during pregnancy. In the 18-week epidemic period during October 2015 to September 2016, influenza incidence was 0.7/100 person-months (95% CI: 0.5-0.9). In the cumulative 29-week-long epidemic during October 2016 to September 2017, influenza incidence was 1.0/100 person-months (95% CI: 0.8-1.2). In the 11-week epidemic period during October 2017 to September 2018, influenza incidence was 2.1/100 person-months (95% CI: 1.9-2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. CONCLUSIONS: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.

      2. Guidance for implementing COVID-19 prevention strategies in the context of varying community transmission levels and vaccination coverageexternal icon
        Christie A, Brooks JT, Hicks LA, Sauber-Schatz EK, Yoder JS, Honein MA.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 27;70(30):1044-1047.
        COVID-19 vaccination remains the most effective means to achieve control of the pandemic. In the United States, COVID-19 cases and deaths have markedly declined since their peak in early January 2021, due in part to increased vaccination coverage (1). However, during June 19-July 23, 2021, COVID-19 cases increased approximately 300% nationally, followed by increases in hospitalizations and deaths, driven by the highly transmissible B.1.617.2 (Delta) variant* of SARS-CoV-2, the virus that causes COVID-19. Available data indicate that the vaccines authorized in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) offer high levels of protection against severe illness and death from infection with the Delta variant and other currently circulating variants of the virus (2). Despite widespread availability, vaccine uptake has slowed nationally with wide variation in coverage by state (range = 33.9%-67.2%) and by county (range = 8.8%-89.0%).(†) Unvaccinated persons, as well as persons with certain immunocompromising conditions (3), remain at substantial risk for infection, severe illness, and death, especially in areas where the level of SARS-CoV-2 community transmission is high. The Delta variant is more than two times as transmissible as the original strains circulating at the start of the pandemic and is causing large, rapid increases in infections, which could compromise the capacity of some local and regional health care systems to provide medical care for the communities they serve. Until vaccination coverage is high and community transmission is low, public health practitioners, as well as schools, businesses, and institutions (organizations) need to regularly assess the need for prevention strategies to avoid stressing health care capacity and imperiling adequate care for both COVID-19 and other non-COVID-19 conditions. CDC recommends five critical factors be considered to inform local decision-making: 1) level of SARS-CoV-2 community transmission; 2) health system capacity; 3) COVID-19 vaccination coverage; 4) capacity for early detection of increases in COVID-19 cases; and 5) populations at increased risk for severe outcomes from COVID-19. Among strategies to prevent COVID-19, CDC recommends all unvaccinated persons wear masks in public indoor settings. Based on emerging evidence on the Delta variant (2), CDC also recommends that fully vaccinated persons wear masks in public indoor settings in areas of substantial or high transmission. Fully vaccinated persons might consider wearing a mask in public indoor settings, regardless of transmission level, if they or someone in their household is immunocompromised or is at increased risk for severe disease, or if someone in their household is unvaccinated (including children aged <12 years who are currently ineligible for vaccination).

      3. Cohort profile: A prospective household cohort study of influenza, respiratory syncytial virus and other respiratory pathogens community burden and transmission dynamics in South Africa, 2016-2018external icon
        Cohen C, McMorrow ML, Martinson NA, Kahn K, Treurnicht FK, Moyes J, Mkhencele T, Hellferscee O, Lebina L, Moroe M, Motlhaoleng K, Gómez-Olivé FX, Wagner R, Tollman S, Wafawanaka F, Ngobeni S, Kleynhans J, Mathunjwa A, Buys A, Maake L, Wolter N, Carrim M, Piketh S, Language B, Mathee A, von Gottberg A, Tempia S.
        Influenza Other Respir Viruses. 2021 Jul 23.
        PURPOSE: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission. PARTICIPANTS: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year. Participants were sampled with nasopharyngeal swabs twice-weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually. FINDINGS TO DATE: There were 122 113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR-confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case. FUTURE PLANS: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.

      4. Effectiveness of syphilis partner notification after adjusting for treatment dates, 7 jurisdictionsexternal icon
        Cope AB, Bernstein KT, Matthias J, Rahman M, Diesel JC, Pugsley RA, Schillinger JA, Chew Ng RA, Klingler EJ, Mobley VL, Samoff E, Peterman TA.
        Sex Transm Dis. 2021 Jul 24.
        INTRODUCTION: Disease intervention specialists (DIS) prevent syphilis by assuring treatment for patients' sex partners through partner notification (PN). Different interpretations of how to measure partners treated due to DIS efforts complicates PN evaluation. We measured PN impact by counting partners treated for syphilis after DIS interviewed the patient. METHODS: We reviewed data from early syphilis cases reported during 2015-2017 in seven jurisdictions. We compared infected partners brought to treatment using: 1) DIS-assigned disposition codes or 2) all infected partners treated 0-90 days after the patient's interview (adjusted treatment estimate). Stratified analyses assessed patient characteristics associated with the adjusted treatment estimate. RESULTS: DIS interviewed 23,613 patients who reported 20,890 partners with locating information. Many of the 3,569 (17.1%) partners classified by DIS as brought to treatment were treated before the patient was interviewed. There were 2,359 (11.3%) partners treated 0-90 days after the patient's interview. Treatment estimates were more consistent between programs when measured using our adjusted estimates (range 6.1%-14.8% per patient interviewed) compared to DIS-assigned disposition (range 6.1%-28.3%). Treatment of >1 partner occurred after 9.0% of interviews and was more likely if the patient was a woman (17.9%), aged <25 years (12.6%), interviewed ≤7 days from diagnosis (13.9%), HIV negative (12.6%), or had no reported history of syphilis (9.8%). CONCLUSIONS: Counting infected partners treated 0-90 days after interview reduced variability in reporting and facilitates quality assurance. Identifying programs and DIS who are particularly good at finding and treating partners could improve program impact.

      5. CD4 cell count: A critical tool in the HIV responseexternal icon
        Ford N, Chiller T.
        Clin Infect Dis. 2021 Jul 26.

      6. Use, safety assessment, and implementation of two point-of-care tests for COVID-19 testingexternal icon
        Hahn M, Olsen A, Stokes K, Fowler RC, Gu R, Semple-Lytch S, DeVito A, Kurpiel P, Hughes S, Rakeman JL.
        Am J Clin Pathol. 2021 Jul 24.
        OBJECTIVES: The Abbot ID NOW COVID-19 assay and Quidel Sofia 2 SARS Antigen FIA are point-of-care assays that offer rapid testing for severe acute respiratory syndrome coronavirus 2 viral RNA and nucleocapsid protein, respectively. Given the utility of these devices in the field, we investigated the feasibility and safety of using the ID NOW and Sofia assays in the public health response to the coronavirus disease 2019 pandemic and in future public health emergencies. METHODS: A combination of utilization and contamination testing in addition to a review of instrument workflows was conducted. RESULTS: Utilization testing demonstrated that both tests are intuitive, associated with high user test success (85%) in our study, and could be implemented by staff after minimal training. Contamination tests revealed potential biosafety concerns due to the open design of the ID NOW instrument and the transfer mechanisms with the Sofia. When comparing the workflow of the ID NOW and the Sofia, we found that the ID NOW was more user-friendly and that the transfer technology reduces the chance of contamination. CONCLUSIONS: The ID NOW, Sofia, and other emerging point-of-care tests should be used only after careful consideration of testing workflow, biosafety risk mitigations, and appropriate staff training.

      7. Progress toward the 90-90-90 HIV targets in Zimbabwe and identifying those left behindexternal icon
        Hakim AJ, Tippett Barr BA, Kinchen S, Musuka G, Manjengwa J, Munyati S, Gwanzura L, Mugurungi O, Ncube G, Saito S, Parekh BS, Patel H, Duong YT, Gonese E, Sleeman K, Ruangtragool L, Justman J, Herman-Roloff A, Radin E.
        J Acquir Immune Defic Syndr. 2021 Jul 24.
        OBJECTIVE: We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. DESIGN: We conducted a cross-sectional household survey. METHODS: Consenting adults and children in the household were eligible to participate in ZIMPHIA (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. VLS was defined as HIV RNA <1,000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15-64 years. RESULTS: We enrolled 11,098 men and 14,033 women aged 15-64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9-78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1-89.7) were receiving ART, and of these people, 85.3% (95% CI: 83.4-87.1) had VLS. Male sex age 15-34 years and having one or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS. CONCLUSIONS: Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged<35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets.

      8. Influenza-like illness among personnel responding to U.S. quarantine of cruise ship passengers exposed to SARS-CoV-2external icon
        Harvey RR, Nett RJ, McNamara K, McClung RP, Pieracci EG, Mayer O, Labar KA, Xu K, Facey J, Honein MA.
        J Occup Environ Med. 2021 Jul 22.
        OBJECTIVES: Before community transmission of COVID-19 was recognized in the United States, cruise ship passengers with high risk for exposure to SARS-CoV-2 were repatriated and quarantined. We describe cases of influenza-like illness (ILI) among responders. METHODS: We reviewed situation reports and responder illness reports to characterize ill responders, including illness onset date, symptoms, fever, diagnostic tests, potential breaches in PPE use, and return to work status. RESULTS: Among 339 responders, nine (3%) reported ILI. No breaches in PPE were reported. Three responders with ILI were tested for both SARS-CoV-2 infection and influenza A; none tested positive for SARS-CoV-2 infection and two tested positive for influenza A. CONCLUSIONS: Despite an outbreak of ILI among responders, none were diagnosed with COVID-19, suggesting preventive measures in place might have been sufficient to prevent responders from SARS-CoV-2 exposure.

      9. Progress toward hepatitis B control - World Health Organization European Region, 2016-2019external icon
        Khetsuriani N, Mosina L, Van Damme P, Mozalevskis A, Datta S, Tohme RA.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 30;70(30):1029-1035.
        In 2019, an estimated 14 million persons in the World Health Organization (WHO) European Region* (EUR) were chronically infected with hepatitis B virus (HBV), and approximately 43,000 of these persons died from complications of chronic HBV infection (1). In 2016, the WHO Regional Office for Europe set hepatitis B control program targets for 2020, including 1) ≥90% coverage with 3 doses of hepatitis B vaccine (HepB3), 2) ≥90% coverage with interventions to prevent mother-to-child transmission (MTCT) of HBV,(†) and 3) ≤0.5% prevalence of HBV surface antigen (HBsAg)(§) in age groups eligible for vaccination with hepatitis B vaccine (HepB) (2-4). This report describes the progress made toward hepatitis B control in EUR during 2016-2019. By December 2019, 50 (94%) of 53 countries in EUR provided routine vaccination with HepB to all infants or children aged 1-12 years (universal HepB), including 23 (43%) countries that offered hepatitis B birth dose (HepB-BD) to all newborns. In addition, 35 (73%) of the 48 countries with universal infant HepB vaccination reached ≥90% HepB3 coverage annually during 2017-2019, and 19 (83%) of the 23 countries with universal birth dose administration achieved ≥90% timely HepB-BD coverage(¶) annually during that period. Antenatal hepatitis B screening coverage was ≥90% in 17 (57%) of 30 countries that selectively provided HepB-BD to infants born to mothers with positive HBsAg test results. In January 2020, Italy and the Netherlands became the first counties in EUR to be validated to have achieved the regional hepatitis B control targets. Countries can accelerate progress toward hepatitis B control by improving coverage with HepB and interventions to prevent MTCT and documenting achievement of the HBsAg seroprevalence target through representative serosurveys or, in low-endemicity countries, antenatal screening.

      10. BACKGROUND: Following many years of decline, HIV diagnoses attributed to injection drug use (IDU) in the United States increased in 2015, the year of a large outbreak among persons who inject drugs (PWID) in Indiana. We assessed trends in HIV diagnoses among PWID across the urban-rural continuum. METHODS: We conducted national and county-level analyses of diagnoses among persons aged ≥13 years with HIV attributed to IDU only and reported to the National HIV Surveillance System through December 2019; county of residence at diagnosis was classified according to CDC's National Center for Health Statistics Urban-Rural Classification Scheme. National trends for diagnoses occurring during 2010-2014 and 2014-2018 were assessed by estimated annual percentage change (EAPC). Counties were considered to have an "alert," (i.e., an increase above baseline) if the number of 2019 diagnoses among PWID was >2 standard deviations and >2 diagnoses greater than the mean of annual diagnoses during 2016-2018. RESULTS: Nationally, HIV diagnoses among PWID declined 33% during 2010-2014 from 3314 to 2220 (EAPC: -9.7%; 95% confidence interval [CI]: -10.8 to -8.6); EAPCs declined significantly in five of six urban-rural strata. During 2014-2018, diagnoses increased 11% to 2465 (EAPC: 2.4%; 95%CI: 1.1 to 3.8); EAPCs were >0 for all urban-rural strata, though most were nonsignificant. Alerts were detected in 23 counties, representing five urban-rural strata. CONCLUSIONS: Vigilance is needed for increases in HIV among PWID in counties across the urban-rural continuum, particularly those with indicators of increased drug use. Prompt detection, investigation, and response are critical for stemming transmission.

      11. High HIV prevalence among decedents received by two high-volume mortuaries in Kisumu, western Kenya, 2019external icon
        Onyango DO, van der Sande MA, Musingila P, Kinywa E, Opollo V, Oyaro B, Nyakeriga E, Waruru A, Waruiru W, Mwangome M, Macharia T, Young PW, Junghae M, Ngugi C, De Cock KM, Rutherford GW.
        PLoS One. 2021 ;16(7):e0253516.
        BACKGROUND: Accurate data on HIV-related mortality are necessary to evaluate the impact of HIV interventions. In low- and middle-income countries (LMIC), mortality data obtained through civil registration are often of poor quality. Though not commonly conducted, mortuary surveillance is a potential complementary source of data on HIV-associated mortality. METHODS: During April-July 2019, we assessed HIV prevalence, the attributable fraction among the exposed, and the population attributable fraction among decedents received by two high-volume mortuaries in Kisumu County, Kenya, where HIV prevalence in the adult population was estimated at 18% in 2019 with high ART coverage (76%). Stillbirths were excluded. The two mortuaries receive 70% of deaths notified to the Kisumu East civil death registry; this registry captures 45% of deaths notified in Kisumu County. We conducted hospital chart reviews to determine the HIV status of decedents. Decedents without documented HIV status, including those dead on arrival, were tested using HIV antibody tests or polymerase chain reaction (PCR) consistent with national HIV testing guidelines. Decedents aged less than 15 years were defined as children. We estimated annual county deaths by applying weights that incorporated the study period, coverage of deaths, and mortality rates observed in the study. RESULTS: The two mortuaries received a total of 1,004 decedents during the study period, of which 95.1% (955/1004) were available for study; 89.1% (851/955) of available decedents were enrolled of whom 99.4% (846/851) had their HIV status available from medical records and post-mortem testing. The overall population-based, age- and sex-adjusted mortality rate was 12.4 per 1,000 population. The unadjusted HIV prevalence among decedents was 28.5% (95% confidence interval (CI): 25.5-31.6). The age- and sex-adjusted mortality rate in the HIV-infected population (40.7/1000 population) was four times higher than in the HIV-uninfected population (10.2/1000 population). Overall, the attributable fraction among the HIV-exposed was 0.71 (95% CI: 0.66-0.76) while the HIV population attributable fraction was 0.17 (95% CI: 0.14-0.20). In children the attributable fraction among the exposed and population attributable fraction were 0.92 (95% CI: 0.89-0.94) and 0.11 (95% CI: 0.08-0.15), respectively. CONCLUSIONS: Over one quarter (28.5%) of decedents received by high-volume mortuaries in western Kenya were HIV-positive; overall, HIV was considered the cause of death in 17% of the population (19% of adults and 11% of children). Despite substantial scale-up of HIV services, HIV disease remains a leading cause of death in western Kenya. Despite progress, increased efforts remain necessary to prevent and treat HIV infection and disease.

      12. Human immunodeficiency virus (HIV) drug resistance, phylogenetic analysis, and superinfection among men who have sex with men and transgender women in sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 studyexternal icon
        Sivay MV, Palumbo PJ, Zhang Y, Cummings V, Guo X, Hamilton EL, McKinstry L, Ogendo A, Kayange N, Panchia R, Dominguez K, Chen YQ, Sandfort TG, Eshleman SH.
        Clin Infect Dis. 2021 Jul 1;73(1):60-67.
        BACKGROUND: The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075. METHODS: HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing. RESULTS: HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort. CONCLUSIONS: This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.

      13. Effects of patient characteristics on diagnostic performance of self-collected samples for SARS-CoV-2 testingexternal icon
        Smith-Jeffcoat SE, Koh M, Hoffman A, Rebolledo PA, Schechter MC, Miller HK, Sleweon S, Rossetti R, Kasinathan V, Shragai T, O'Laughlin K, Espinosa CC, Khalil GM, Adeyemo AO, Moorman A, Bauman BL, Joseph K, O'Hegarty M, Kamal N, Atallah H, Moore BL, Bohannon CD, Bankamp B, Hartloge C, Bowen MD, Paulick A, Gargis AS, Elkins C, Stewart RJ, da Silva J, Biedron C, Tate JE, Wang YF, Kirking HL.
        Emerg Infect Dis. 2021 ;27(8):2081-2089.
        We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.

      14. COVID-19 outbreak associated with a fitness center - Minnesota, September-November 2020external icon
        Suhs T, Gerlach D, Garfin J, Lorentz A, Firestone M, Sherden M, Hackman K, Gray T, Siebman S, Wienkes H, Vilen K, Wang X, Como-Sabetti K, Danila R, Smith K, Medus C.
        Clin Infect Dis. 2021 Jul 23.
        The Minnesota Department of Health investigated a COVID-19 outbreak at a fitness center in Olmsted County, Minnesota. Twenty-three SARS-CoV-2 infections (five employees and 18 members) were identified. An epidemiological investigation supported by whole genome sequencing demonstrated that transmission of SARS-CoV-2 occurred at the fitness center despite following recommended prevention strategies.

      15. Shiga toxin-producing Escherichia coli outbreaks in the United States, 2010–2017external icon
        Tack DM, Kisselburgh HM, Richardson LC, Geissler A, Griffin PM, Payne DC, Gleason BL.
        Microorganisms. 2021 ;9(7).
        Shiga toxin-producing Escherichia coli (STEC) cause illnesses ranging from mild diarrhea to ischemic colitis and hemolytic uremic syndrome (HUS); serogroup O157 is the most common cause. We describe the epidemiology and transmission routes for U.S. STEC outbreaks during 2010– 2017. Health departments reported 466 STEC outbreaks affecting 4769 persons; 459 outbreaks had a serogroup identified (330 O157, 124 non-O157, 5 both). Among these, 361 (77%) had a known transmission route: 200 foodborne (44% of O157 outbreaks, 41% of non-O157 outbreaks), 87 person-toperson (16%, 24%), 49 animal contact (11%, 9%), 20 water (4%, 5%), and 5 environmental contamination (2%, 0%). The most common food category implicated was vegetable row crops. The distribution of O157 and non-O157 outbreaks varied by age, sex, and severity. A significantly higher percentage of STEC O157 than non-O157 outbreaks were transmitted by beef (p = 0.02). STEC O157 outbreaks also had significantly higher rates of hospitalization and HUS (p < 0.001). © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      16. Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020external icon
        Tempia S, Walaza S, Bhiman JN, McMorrow ML, Moyes J, Mkhencele T, Meiring S, Quan V, Bishop K, McAnerney JM, von Gottberg A, Wolter N, Du Plessis M, Treurnicht FK, Hellferscee O, Dawood H, Naby F, Variava E, Siwele C, Baute N, Nel J, Reubenson G, Zar HJ, Cohen C.
        Euro Surveill. 2021 Jul;26(29).
        BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.

      17. Exploring and comparing the structure of sexual networks affected by Neisseria gonorrhoeae using sexual partner services investigation and genomic dataexternal icon
        Town K, Learner ER, Chivukula VL, Mauk K, Reimche JL, Schmerer MW, Black J, Pathela P, Bhattacharyya S, Kerani RP, Gieseker KE, Fukuda A, Sankaran M, McNeil CJ, Spicknall IH, Raphael BH, St Cyr SB, Bernstein K, Kersh EN, Kirkcaldy RD, Schlanger K, Gernert KM.
        Sex Transm Dis. 2021 Jul 23.
        BACKGROUND: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). METHODS: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. RESULTS: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. CONCLUSIONS: Combining PSI and WGS data improves our understanding of sexual network connectivity.

      18. Comparison of the SARS-CoV-2 spike protein elisa and the Abbott Architect SARS-CoV-2 IgG nucleocapsid protein assays for detection of antibodiesexternal icon
        Wadhwa A, Yin S, Freeman B, Hershow RB, Killerby M, Yousaf AR, Lester S, Mills L, Buono SA, Pomeroy M, Owusu D, Chu VT, Tate JE, Bhattacharyya S, Hall P, Thornburg NJ, Kirking HL.
        PLoS One. 2021 ;16(7):e0255208.
        Serologic assays developed for SARS-CoV-2 detect different antibody subtypes and are based on different target antigens. Comparison of the performance of a SARS-CoV-2 Spike-Protein ELISA and the nucleocapsid-based Abbott ArchitectTM SARS-CoV-2 IgG assay indicated that the assays had high concordance, with rare paired discordant tests results.

    • Disease Reservoirs and Vectors
      1. Characterization of resistance profile (intensity and mechanisms) of Anopheles gambiae in three communes of northern Benin, West Africaexternal icon
        Kpanou CD, Sagbohan HW, Dagnon F, Padonou GG, Ossè R, Salako AS, Sidick A, Sewadé W, Sominahouin A, Condo P, Ahmed SH, Impoinvil D, Akogbéto M.
        Malar J. 2021 Jul 27;20(1):328.
        BACKGROUND: The selection and the spread of insecticide resistance in malaria vectors to the main classes of insecticides used in vector control tools are a major and ongoing challenge to malaria vector control programmes. This study aimed to determine the intensity of vector resistance to insecticides in three regions of Benin with different agro-ecological characteristics. METHODS: Larvae of Anopheles gambiae sensu lato (s.l.) were collected from September to November 2017 in different larval sites in three northern Benin communes: Parakou, Kandi and Malanville. Two to five-day-old, non-blood-fed, female mosquitoes were exposed to papers impregnated with deltamethrin, permethrin and bendiocarb at dosages of 1 × the diagnostic dose, 5 × and 10 × to determine the intensity of resistance in these vectors. Molecular frequencies of the kdr L1014F and ace-1R G119S insecticide resistance mutations and levels of detoxification enzymes were determined for mosquitoes sampled at each study site. RESULTS: Resistance to pyrethroids (permethrin and deltamethrin) was recorded in all three communes with mortality rates below 60% using the diagnostic dose (1x). The results obtained after exposure of An. gambiae to permethrin 10 × were 99% in Kandi, 98% in Malanville and 99% in Parakou. With deltamethrin 10x, mortality rates were 100% in Kandi, 96% in Malanville and 73% in Parakou. For the diagnostic dose of bendiocarb, suspected resistance was recorded in the communes of Malanville (97%) and Kandi (94%) while sensitivity was observed in Parakou (98%).Using the 10 × dose, mortality was 98% in Kandi, 100% in Malanville and 99% in Parakou. The frequencies of the kdr L1014F allele varied between 59 and 83% depending on the sites and species of the An. gambiae complex, while the frequency of the ace-1R G119S gene varied between 0 and 5%. Biochemical tests showed high levels of oxidase and esterase activity compared to the susceptible colony strain of An. gambiae sensu stricto (Kisumu strain). CONCLUSION: Anopheles gambiae showed a generalized loss of susceptibility to permethrin and deltamethrin but also showed moderate to high intensity of resistance in different regions of Benin. This high intensity of resistance is a potential threat to the effectiveness of vector control.

    • Genetics and Genomics
      1. Using genomics to examine the persistence of streptococcus pneumoniae serotype 19a in Ireland and the emergence of a sub-clade associated with vaccine failuresexternal icon
        Corcoran M, Mereckiene J, Cotter S, Murchan S, Lo SW, McGee L, Breiman RF, Cunney R, Humphreys H, Bentley SD, Gladstone RA.
        Vaccine. 2021 Jul 20.
        BACKGROUND: Streptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children. METHODS: Invasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007-08 and 2017-18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC). RESULTS: Expansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995-2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25). CONCLUSIONS: The identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies.

    • Health Disparities
      1. Trends, mechanisms, and racial/ethnic differences of tuberculosis incidence in the US-born population aged 50 years or older in the United Statesexternal icon
        Kim S, Cohen T, Horsburgh CR, Miller JW, Hill AN, Marks SM, Li R, Kammerer JS, Salomon JA, Menzies NA.
        Clin Infect Dis. 2021 Jul 29.
        BACKGROUND: Older age is a risk factor for TB in low incidence settings. Using data from the U.S. National TB Surveillance System and American Community Survey, we estimated trends and racial/ethnic differences in TB incidence among US-born cohorts aged ≥50 years. METHODS: 42,000 TB cases among US-born persons ≥50 years were reported during 2001-2019. We used generalized additive regression models to decompose the effects of birth cohort and age on TB incidence rates, stratified by sex and race/ethnicity. Using genotype-based estimates of recent transmission (available 2011-2019), we implemented additional models to decompose incidence trends by estimated recent versus remote infection. RESULTS: Estimated incidence rates declined with age, for the overall cohort and most sex and race/ethnicity strata. Average annual percentage declines flattened for older individuals, from 8.80% (95% confidence interval 8.34-9.23) in 51-year-olds to 4.51% (3.87-5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (6.13-11.26) on average between successive cohort years. Incidence rates were substantially higher for racial/ethnic minorities, and these inequalities persisted across all birth cohorts. Rates from recent infection declined at approximately 10% per year as individuals aged. Rates from remote infection declined more slowly with age, and this annual percentage decline approached zero for the oldest individuals. CONCLUSIONS: TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection.

    • Health Economics
      1. Cost-effectiveness of dengue vaccination in Puerto Ricoexternal icon
        España G, Leidner AJ, Waterman SH, Perkins TA.
        PLoS Negl Trop Dis. 2021 Jul 26;15(7):e0009606.
        An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045-0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13-24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.

    • Immunity and Immunization
      1. Vaccine effectiveness against acute respiratory illness hospitalizations for influenza-associated pneumonia during the 2015-2016 to 2017-2018 seasons, US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)external icon
        Ghamande S, Shaver C, Murthy K, Raiyani C, White HD, Lat T, Arroliga AC, Wyatt D, Talbot HK, Martin ET, Monto AS, Zimmerman RK, Middleton DB, Silveira FP, Ferdinands JM, Patel MM, Gaglani M.
        Clin Infect Dis. 2021 Jul 28.
        BACKGROUND: Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). METHODS: Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of 'definite/probable pneumonia'. We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing RT-PCR confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. RESULTS: Of 4,843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had 'definite/probable pneumonia' and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI]): 17%-53%); by type/subtype, it was 74% (95% CI: 52%-87%), influenza A (H1N1)pdm09; 25% (-15% to 50%), A (H3N2); and 23% (95% CI: -32% to 54%), influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19%-77%). CONCLUSIONS: Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B.

      2. Disparities in COVID-19 vaccination coverage among health care personnel working in long-term care facilities, by job category, National Healthcare Safety Network - United States, March 2021external icon
        Lee JT, Althomsons SP, Wu H, Budnitz DS, Kalayil EJ, Lindley MC, Pingali C, Bridges CB, Geller AI, Fiebelkorn AP, Graitcer SB, Singleton JA, Patel SA.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 30;70(30):1036-1039.
        Residents of long-term care facilities (LTCFs) and health care personnel (HCP) working in these facilities are at high risk for COVID-19-associated mortality. As of March 2021, deaths among LTCF residents and HCP have accounted for almost one third (approximately 182,000) of COVID-19-associated deaths in the United States (1). Accordingly, LTCF residents and HCP were prioritized for early receipt of COVID-19 vaccination and were targeted for on-site vaccination through the federal Pharmacy Partnership for Long-Term Care Program (2). In December 2020, CDC's National Healthcare Safety Network (NHSN) launched COVID-19 vaccination modules, which allow U.S. LTCFs to voluntarily submit weekly facility-level COVID-19 vaccination data.* CDC analyzed data submitted during March 1-April 4, 2021, to describe COVID-19 vaccination coverage among a convenience sample of HCP working in LTCFs, by job category, and compare HCP vaccination coverage rates with social vulnerability metrics of the surrounding community using zip code tabulation area (zip code area) estimates. Through April 4, 2021, a total of 300 LTCFs nationwide, representing approximately 1.8% of LTCFs enrolled in NHSN, reported that 22,825 (56.8%) of 40,212 HCP completed COVID-19 vaccination.(†) Vaccination coverage was highest among physicians and advanced practice providers (75.1%) and lowest among nurses (56.7%) and aides (45.6%). Among aides (including certified nursing assistants, nurse aides, medication aides, and medication assistants), coverage was lower in facilities located in zip code areas with higher social vulnerability (social and structural factors associated with adverse health outcomes), corresponding to vaccination disparities present in the wider community (3). Additional efforts are needed to improve LTCF immunization policies and practices, build confidence in COVID-19 vaccines, and promote COVID-19 vaccination. CDC and partners have prepared education and training resources to help educate HCP and promote COVID-19 vaccination coverage among LTCF staff members.(§).

      3. Hepatitis B vaccination among adults with diabetes mellitus, U.S., 2018external icon
        Lu PJ, Hung MC, Srivastav A, Williams WW, Harris AM.
        Am J Prev Med. 2021 Jul 19.
        INTRODUCTION: Hepatitis B vaccination is routinely recommended for adults with diabetes mellitus aged <60 years and for those aged ≥60 years at the discretion of their healthcare provider. The purpose of this study is to assess hepatitis B vaccination coverage among adults with and without diabetes mellitus. METHODS: Data from the 2014-2018 National Health Interview Survey were analyzed in 2020 to determine hepatitis B vaccination series completion (≥3 doses) among adults aged 18-59 and ≥60 years with diabetes mellitus. Multivariable logistic regression analysis was conducted to identify the factors independently associated with hepatitis B vaccination among adults aged 18-59 and ≥60 years with diabetes mellitus. RESULTS: In 2018, among adults aged 18-59 years with diabetes mellitus, 33.2% had received hepatitis B vaccination (≥3 doses), an increase of 9.7 percentage points from 2014 (p<0.05). Among adults aged ≥60 years with diabetes mellitus, coverage was 15.3% in 2018 and did not increase during 2014-2018. Coverage was not significantly different among adults with diabetes mellitus compared with those without diabetes mellitus, even after controlling for the assessed factors. Among adults with diabetes mellitus aged 18-59 and ≥60 years, younger age, having some college or college education, having been tested for HIV, being healthcare personnel, or having traveled to hepatitis B virus-endemic areas were independently associated with an increased likelihood of vaccination. CONCLUSIONS: Self-reported hepatitis B vaccination coverage among adults with diabetes mellitus remains suboptimal. Healthcare providers should assess patients' diabetes status, recommend and offer needed vaccinations to patients, or refer them to alternate sites for vaccination.

      4. Achieving high poliovirus antibody seroprevalence in areas at risk of vaccine-derived poliovirus transmission-Niger experienceexternal icon
        Ousmane S, Ibrahim DD, Goel A, Hendley WS, Mainou BA, Palmer T, Diaha A, Greene SA, Mach O.
        Open Forum Infect Dis. 2021 Jul;8(7):ofab210.
        BACKGROUND: Outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across Africa. We conducted a serological survey of polio antibodies in high-polio risk areas of Niger to assess risk of poliovirus outbreaks. METHODS: Children between 1 and 5 years of age were enrolled from structures randomly selected using satellite imaging enumeration in Diffa Province, Niger, in July 2019. After obtaining informed consent, dried blood spot cards were collected. Neutralizing antibodies against 3 poliovirus serotypes were detected using microneutralization assay at the Centers for Disease Control and Prevention. RESULTS: We obtained analyzable data from 309/322 (95.9%) enrolled children. Seroprevalence of polio antibodies was 290/309 (93.9%), 272/309 (88.0%), and 254/309 (82.2%) for serotypes 1, 2, and 3, respectively. For serotypes 1 and 2, the seroprevalence did not significantly change with age (P = .09 and P = .44, respectively); for serotype 3, it increased with age (from 65% in 1-2-year-olds to 91.1% in 4-5-year olds; P < .001). We did not identify any risk factors for type 2 seronegativity. CONCLUSIONS: With type 2 seroprevalence close to 90%, the risk of emergence of new cVDPV2 outbreaks in Niger is low; however, the risk of cVDPV2 importations from neighboring countries leading to local transmission persists. Niger should maintain its outbreak response readiness capacity and further strengthen its routine immunization.

      5. Effectiveness of human papillomavirus (HPV) vaccination against penile HPV infection in men who have sex with men and transgender womenexternal icon
        Winer RL, Lin J, Querec TD, Unger ER, Stern JE, Rudd JM, Golden MR, Swanson F, Markowitz LE, Meites E.
        J Infect Dis. 2021 Jul 28.
        BACKGROUND: In the United States, HPV vaccination has been recommended since 2011 for males aged 11-12 years, with catch-up vaccination recommended through age 26 years for previously unvaccinated men who have sex with men (MSM). METHODS: During 2016-2018, a cross-sectional study enrolled MSM and transgender women aged 18-26 years in Seattle, Washington. Participants submitted self-collected penile swab specimens for HPV genotyping. HPV vaccination history was self-reported. We compared HPV prevalence among vaccinated participants versus participants with no/unknown vaccination history using log-binomial regression to estimate adjusted prevalence ratios (aPR) and confidence intervals (CI). RESULTS: Among 687 participants, 348 (50.7%) self-reported ever receiving ≥1 HPV vaccine dose; median age at first HPV vaccination was 21 years and median age at first sex was 17 years. Overall, prevalence of penile quadrivalent HPV vaccine (4vHPV)-type HPV was similar in vaccinated participants (12.1%) and participants with no/unknown vaccination (15.6%) (aPR=0.69, 95%CI:0.47-1.01). However, prevalence was significantly lower in participants vaccinated at age ≤18 years than in participants with no/unknown vaccination (aPR=0.15, 95%CI:0.04-0.62), corresponding to a vaccine effectiveness of 85% against 4vHPV-type HPV. CONCLUSIONS: Results suggest HPV vaccination is effective in preventing penile HPV infections in young MSM when administered at age ≤18 years.

    • Laboratory Sciences
      1. Assessment and utility of 2 Chlamydia trachomatis Pgp3 serological assays for seroprevalence studies among women in the United Statesexternal icon
        Danavall DC, Gwyn S, Anyalechi GE, Bowden KE, Hong J, Kirkcaldy RD, Bernstein KT, Kersh EN, Martin D, Raphael BH.
        Diagn Microbiol Infect Dis. 2021 Jul 8;101(2):115480.
        Two plasmid gene protein (Pgp3)-based serological assays, the Pgp3-ELISA and multiplex bead assay (Pgp3-MBA), were compared and used to estimate seropositivity of Chlamydia trachomatis (CT) among females 14 to 39 years old participating in the National Health and Nutrition Examination Survey between 2013-2016. Of the 2,201 specimens tested, 502 (29.5%, 95% CI 27.6-31.5) were positive using Pgp3-ELISA and 624 (28.4%, 95% CI 26.5-30.3) were positive using Pgp3-MBA. The overall agreement between the assays was 87.7%. Corresponding nucleic acid amplification test (NAAT) results were available for 1,725 specimens (from women 18-39 years old); of these, 42 (2.4%, 95% CI 1.8-3.3) were CT NAAT-positive. Most of the CT NAAT-positive specimens had corresponding positive serological assay results; 33 (78.6%, 95% CI 62.8-89.2) were Pgp3-ELISA-positive and 36 (85.7%, 95% CI 70.8-94.1) were Pgp3-MBA-positive. Although Pgp3-ELISA and Pgp3-MBA demonstrated equivalent performance in this study, an advantage of the Pgp3-MBA over Pgp3-ELISA is that it is well suited for high sample throughput applications.

      2. Apolipoprotein A-I modulates HDL particle size in the absence of apolipoprotein A-IIexternal icon
        Melchior JT, Street SE, Vaisar T, Hart R, Jerome J, Kuklenyik Z, Clouet-Foraison N, Thornock C, Bedi S, Shah AS, Segrest JP, Heinecke JW, Davidson WS.
        J Lipid Res. 2021 Jul 26:100099.
        Human high-density lipoproteins (HDL) are a complex mixture of structurally-related nanoparticles that perform distinct physiological functions. We previously showed human HDL containing apolipoprotein A-I (APOA1) but not apolipoprotein A-II (APOA2), designated LpA-I, is composed primarily of two discretely sized populations. Here, we isolated these particles directly from human plasma by antibody affinity chromatography, separated them by high-resolution size exclusion chromatography and performed a deep molecular characterization of each species. The large and small LpA-I populations were spherical with mean diameters of 109 Å and 91 Å, respectively. Unexpectedly, isotope dilution MS/MS with [(15)N]-APOA1 in concert with quantitation of particle concentration by calibrated ion mobility analysis demonstrated that the large particles contained fewer APOA1 molecules than the small particles; the stoichiometries were 3.0 and 3.7 molecules of APOA1 per particle, respectively. MS/MS experiments showed that the protein cargo of large LpA-I particles was more diverse. Human HDL and isolated particles containing both APOA1 and APOA2 exhibit a much wider range and variation of particle sizes than LpA-I, indicating that APOA2 is likely the major contributor to HDL size heterogeneity. We propose a ratchet model based on the trefoil structure of APOA1 whereby the helical cage maintaining particle structure has two 'settings' - large and small - that accounts for these findings. This understanding of the determinants of HDL particle size and protein cargo distribution serves as a basis for determining the roles of HDL subpopulations in metabolism and disease states.

      3. Characterization of reference materials with an Association for Molecular Pathology Pharmacogenetics Working Group tier 2 status: CYP2C9, CYP2C19, VKORC1, CYP2C cluster variant, and GGCX: A GeT-RM Collaborative Projectexternal icon
        Pratt VM, Turner A, Broeckel U, Dawson DB, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Requesens D, Vetrini F, Kalman LV.
        J Mol Diagn. 2021 Aug;23(8):952-958.
        Pharmacogenetic testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials are currently available for many of the variants that are tested. The Association for Molecular Pathology Pharmacogenetic Work Group has published a series of papers recommending alleles for inclusion in clinical testing. Several of the alleles were not considered for tier 1 because of a lack of reference materials. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention-based Genetic Testing Reference Material (GeT-RM) program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 18 DNA samples derived from Coriell cell lines. DNA samples were distributed to five volunteer testing laboratories for genotyping using three commercially available and laboratory developed tests. Several tier 2 variants, including CYP2C9∗13, CYP2C19∗35, the CYP2C cluster variant (rs12777823), two variants in VKORC1 (rs61742245 and rs72547529) related to warfarin resistance, and two variants in GGCX (rs12714145 and rs11676382) related to clotting factor activation, were identified among these samples. These publicly available materials complement the pharmacogenetic reference materials previously characterized by the GeT-RM program and will support the quality assurance and quality control programs of clinical laboratories that perform pharmacogenetic testing.

      4. Borrelia mayonii - a cause of Lyme borreliosis that can be visualized by microscopy of thin blood filmsexternal icon
        Pritt BS, Fernholz EC, Replogle AJ, Kingry LC, Sciotto MP, Petersen JM.
        Clin Microbiol Infect. 2021 Jul 26.

    • Maternal and Child Health
      1. Maternal exposure to hydroxychloroquine and birth defectsexternal icon
        Howley MM, Werler MM, Fisher SC, Van Zutphen AR, Carmichael SL, Broussard CS, Heinke D, Ailes EC, Pruitt SM, Reefhuis J, Mitchell AA, Browne ML.
        Birth Defects Res. 2021 Jul 23.
        BACKGROUND: Hydroxychloroquine is a treatment for rheumatic disease and considered safe during pregnancy. Interest in hydroxychloroquine has increased as it is being examined as a potential treatment and prophylaxis for coronavirus disease 2019. Data on the risks of specific birth defects associated with hydroxychloroquine use are sparse. METHODS: Using data from two case-control studies (National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study), we described women who reported hydroxychloroquine use in pregnancy and the presence of specific major birth defects in their offspring. Cases had at least one major birth defect and controls were live-born healthy infants. Women self-reported medication use information in the few months before pregnancy through delivery. RESULTS: In total, 0.06% (19/31,468) of case and 0.04% (5/11,614) of control mothers in National Birth Defects Prevention Study, and 0.04% (11/29,838) of case and 0.05% (7/12,868) of control mothers in Birth Defects Study reported hydroxychloroquine use. Hydroxychloroquine users had complicated medical histories and frequent medication use for a variety of conditions. The observed birth defects among women taking hydroxychloroquine were varied and included nine oral cleft cases; the elevated observed:expected ratios for specific oral cleft phenotypes and for oral clefts overall had 95% confidence intervals that included 1.0. CONCLUSION: While teratogens typically produce a specific pattern of birth defects, the observed birth defects among the hydroxychloroquine-exposed women did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects. The number of exposed cases is small; results should be interpreted cautiously.

    • Nutritional Sciences
      1. Micronutrient powders and diarrhoea risk in infants and young childrenexternal icon
        Suchdev PS, Jefferds ME, Dewey KG, Zlotkin S, Aguayo VM, de Pee S, Kraemer K, Greig A, Arabi M, De-Regil LM.
        Lancet Child Adolesc Health. 2021 Aug;5(8):e28-e29.

    • Occupational Safety and Health
      1. Sleep quality and dietary patterns in an occupational cohort of police officersexternal icon
        Velazquez-Kronen R, Millen AE, Ochs-Balcom HM, Mnatsakanova A, Gu JK, Andrew M, Violanti J.
        Behav Sleep Med. 2021 Jul 25:1-13.
        We examined the association between self-reported sleep quality, sleep duration, and dietary patterns among police officers in the Buffalo Cardio-Metabolic Occupational Stress (BCOPS) study.422 police officers aged 21-74 (2004-2009).We used a cross-sectional study design and obtained sleep quality and duration from responses to the 19-item Pittsburgh Sleep Quality Index. Using 46 energy-adjusted food groups derived from a 125-item food frequency questionnaire, we identified dietary patterns using exploratory factor analysis. Multiple linear regression analysis was used to examine the associations of sleep quality and duration with the derived dietary patterns.We identified major dietary patterns: fruits and vegetables (FV), dairy products, starches and fried foods, and meat and eggs. Individuals with poor sleep quality had a lower average FV score than those with optimal sleep (β [SE] = -0.32 [0.13]; p = .01). Significant interactions were observed between sex and the FV and dairy products dietary patterns, where women with poor sleep quality had a lower mean FV score compared to women with optimal sleep quality (β [SE] = -0.81 [0.29]; p = .01). Women with < 6 hours sleep duration had a lower mean dairy score compared to women with ≥ 7 hours sleep duration (β [SE] = -0.69 [0.29]; p = .02). We did not observe these associations among men.Among women, good sleep quality and long sleep duration were associated with a dietary pattern high in consumption of both fruits and vegetables and dairy products.Abbreviations: BCOPS: Buffalo Cardio-Metabolic Occupational Stress study; BMI: body mass index; FFQ: food frequency questionnaire; FV: fruits and vegetables; KMO: Kaiser-Meyer-Olkin test; MET: metabolic equivalent of task score; PSQI: Pittsburgh Sleep Quality Index questionnaire.

    • Parasitic Diseases
      1. Linked surveillance and genetic data uncovers programmatically relevant geographic scale of Guinea worm transmission in Chadexternal icon
        Ribado JV, Li N, Thiele E, Lyons H, Cotton JA, Weiss A, Tchindebet Ouakou P, Moundai T, Zirimwabagabo H, Guagliardo SA, Chabot-Couture G, Proctor JL.
        PLoS Negl Trop Dis. 2021 Jul 26;15(7):e0009609.
        BACKGROUND: Guinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten-year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission. METHODOLOGY/PRINCIPAL FINDINGS: We coupled genomic and surveillance case data from 2012-2018 to investigate the modes of transmission between dog and human hosts and the geographic connectivity of worms. Eighty-six variants across four genes in the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling revealed worms with the same genotype ('genetically identical') were within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms varied in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm was surrounded by five to ten genetically distinct worms within a 50 kilometer radius. As expected, we observed a change in the genetic similarity distribution between pairs of worms using variants across the complete mitochondrial genome in an independent population. CONCLUSIONS/SIGNIFICANCE: In the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic identity and modeling can facilitate the understanding of local transmission. The co-occurrence of genetically non-identical worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between pairs of worms from variants identified across the complete mitochondrial genome suggests that expanding the number of genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination.

      2. Control and elimination of schistosomiasis as a public health problem: Thresholds fail to differentiate schistosomiasis morbidity prevalence in childrenexternal icon
        Wiegand RE, Secor WE, Fleming FM, French MD, King CH, Montgomery SP, Evans D, Utzinger J, Vounatsou P, de Vlas SJ.
        Open Forum Infect Dis. 2021 Jul;8(7):ofab179.
        BACKGROUND: Current World Health Organization guidelines utilize prevalence of heavy-intensity infections (PHIs), that is, ≥50 eggs per 10 mL of urine for Schistosoma haematobium and ≥400 eggs per gram of stool for S. mansoni, to determine whether a targeted area has controlled schistosomiasis morbidity or eliminated schistosomiasis as a public health problem. The relationship between these PHI categories and morbidity is not well understood. METHODS: School-age participants enrolled in schistosomiasis monitoring and evaluation cohorts from 2003 to 2008 in Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia were surveyed for infection and morbidity at baseline and after 1 and 2 rounds of preventive chemotherapy. Logistic regression was used to compare morbidity prevalence among participants based on their school's PHI category. RESULTS: Microhematuria levels were associated with the S. haematobium PHI categories at all 3 time points. For any other S. haematobium or S. mansoni morbidity that was measured, PHI categories did not differentiate morbidity prevalence levels consistently. CONCLUSIONS: These analyses suggest that current PHI categorizations do not differentiate the prevalence of standard morbidity markers. A reevaluation of the criteria for schistosomiasis control is warranted.

    • Physical Activity
      1. Sedentary behavior in United States adults: Fall 2019external icon
        Matthews CE, Carlson SA, Saint-Maurice PF, Patel S, Salerno E, Loftfield E, Troiano RP, Fulton JE, Sampson JN, Tribby C, Keadle S, Berrigan D.
        Med Sci Sports Exerc. 2021 Jul 23.
        PURPOSE: Higher levels of sedentary behavior are associated with early mortality, but the distribution of sedentary time by classes of behavior and demographic groups is poorly described in United States (US) adults. To quantify the amount and sources of sedentary time in US adults we conducted a nationwide survey using a novel validated self-administerd previous-day recall method and compare these values with a commonly used sitting time question. METHODS: Participants from the AmeriSpeak panel aged 20 to 75 years (N = 2,640) completed up to two Activities Completed over Time in 24 Hours (ACT24) previous day recalls. Recalls were conducted on randomly selected days in October and November 2019. Survey sample design were applied to reflect the US population. RESULTS: Mean age was 45.3 years, 51% were female, 67% non-Hispanic white, and 37% had a body mass index of ≥30 kg/m2. US adults reported a mean 9.5 hrs/d of sedentary time (95% confidence interval [CI] 9.4, 9.7 hrs/d), which was 34% more than reported using a common surveillance measure (p < 0.01). Most daily sedentary time was accumulated in the leisure and work life domains, with leisure accounting for 47% (4.3 hrs/d [95%CI 4.2, 4.5 hrs/d]) of the total sedentary time. Eighty-two percent of leisure time was spent sedentary, mainly watching television/videos or engaged in internet/computer use. CONCLUSIONS: US adults appear to spend more time in sedentary behavior than previously thought and the majority of this time is accumulated at work and in leisure-time. Reducing sedentary screen-time during leisure in favor of physically active could be an important intervention target in the effort to increase physical activity in US adults.

    • Reproductive Health
      1. COVID-19 and sexual and reproductive health care: Findings from primary care providers who serve adolescentsexternal icon
        Steiner RJ, Zapata LB, Curtis KM, Whiteman MK, Brittain AW, Tromble E, Keys KR, Fasula AM.
        J Adolesc Health. 2021 Jul 20.
        PURPOSE: Among U.S. primary care physicians who delivered sexual and reproductive health (SRH) services to adolescents before the COVID-19 pandemic, we examine (1) changes in availability of in-person SRH services; (2) changes in accessibility and utilization of SRH services; and (3) use of strategies to support provision of SRH services during the pandemic. METHODS: Data were from the DocStyles provider survey administered September-October 2020. Descriptive analyses were restricted to family practitioners, internists, and pediatricians whose main work setting was outpatient and whose practice provided family planning or sexually transmitted infection services to ≥ one patient aged 15-19 years per week just before the COVID-19 pandemic (n = 791). RESULTS: Among physicians whose practices provided intrauterine device/implant placement/removal or clinic-based sexually transmitted infection testing before the COVID-19 pandemic, 51% and 36% indicated disruption of these services during the pandemic, respectively. Some physicians also reported reductions in walk-in hours (38%), evening/weekend hours (31%), and adolescents seeking care (43%) in the past month. At any point during the pandemic, 61% provided contraception initiation/continuation and 44% provided sexually transmitted infection services via telehealth. Among these physicians, about one-quarter reported confidentiality concerns with telehealth in the past month. There were small increases or no changes in other strategies to support contraceptive care. CONCLUSIONS: Findings suggest disruption of certain SRH services and issues with access because of the pandemic among primary care providers who serve adolescents. There are opportunities to enhance implementation of confidential telehealth services and other service delivery strategies that could help promote adolescent SRH in the United States.

    • Statistics as Topic
      1. Evaluating nonresponse weighting adjustment for the population-based HIV impact assessment surveys on incorporating survey outcomesexternal icon
        Lin TH, Cervantes FI, Saito S, Bain R.
        J Acquir Immune Defic Syndr. 2021 Aug 1;87(Suppl 1):S52-s56.
        BACKGROUND: The nonresponse weighting adjustment of the Population-based HIV Impact Assessment (PHIA) surveys uses the weighting class method in combination with a tree analysis to identify predictors significant to response propensity. Variable selection for this type of nonresponse adjustment identifies auxiliary variables correlated with response propensity alone and produces 1 set of weights applicable for all analyses of the survey data. An alternative approach identifies auxiliary variables correlated to both the response probability and selected key outcome variables. This approach may identify a different set of variables for the nonresponse adjustments and may produce more efficient estimates for the key outcome variables. SETTING: The PHIA surveys from 2016 to 2017. METHODS: Weighting class, joint-classification, and two-step modeling. RESULTS: There was little difference among estimates produced by the alternative weighting methods and the PHIA estimates. The joint-classification method produced more efficient estimates (ie, smaller design effects) compared with the PHIA method, while the two-step method was inconclusive. CONCLUSIONS: The efficiency of the estimates produced by the PHIA weighting method closely resembles those specifically targeted at key survey outcomes and serves well as a multipurpose weight.

    • Substance Use and Abuse
      1. Epidemiology, outcomes, and trends of patients with sepsis and opioid-related hospitalizations in U.S. hospitalsexternal icon
        Alrawashdeh M, Klompas M, Kimmel S, Larochelle MR, Gokhale RH, Dantes RB, Hoots B, Hatfield KM, Reddy SC, Fiore AE, Septimus EJ, Kadri SS, Poland R, Sands K, Rhee C.
        Crit Care Med. 2021 Jun 23.
        OBJECTIVES: Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN: Retrospective cohort study. SETTING: About 373 U.S. hospitals. PATIENTS: Adults hospitalized between January 2009 and September 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness. The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS: Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

      2. Implementation of the Uttarakhand Tobacco Free Initiative in schools, India, 2016external icon
        Garcia de Quevedo I, Arrazola RA, Yadav R, Soura BD, Ahluwalia IB.
        Prev Chronic Dis. 2021 Jul 29;18:E74.
        PURPOSE AND OBJECTIVES: A process evaluation, the Uttarakhand Tobacco Free Initiative (UTFI), was conducted in 49 public high schools and colleges in the state of Uttarakhand, India, to measure program implementation, provide feedback to school administrators, and identify barriers to tobacco control. INTERVENTION APPROACH: UTFI aims to 1) raise awareness and provide education and tools for teachers and school administrators about the dangers of tobacco use and secondhand smoke, 2) encourage participation in student-led activities to promote tobacco-free initiatives, and 3) enforce tobacco-free school policies in the state of Uttarakhand. EVALUATION METHODS: We used the CDC evaluation framework to document key components and lessons learned from the UTFI. We distributed questionnaires to 71 teachers and principals in December 2016, to assess awareness of school activities and policies related to the initiative. Descriptive statistics were computed for quantitative data, and a thematic content analysis was used for qualitative data. RESULTS: Of the 71 participants, 66 (92.9%) were aware of tobacco use policies in schools, and 63 (88.7%) agreed policies were enforced. Sixty-six participants (93.0%) said that they taught tobacco prevention-related topics, and 41 of 70 respondents (58.6%) reported that a student-led group helped to enforce tobacco-free policies in their schools. Of 69 respondents, almost all (n = 66) reported satisfaction with UTFI implementation. Challenges identified were related to tobacco products being readily accessible near school premises, lack of tobacco prevention materials, and tobacco use by school staff. IMPLICATIONS FOR PUBLIC HEALTH: Successes of UTFI were documented by measuring different components of the process, including implementation of program activities and teacher and principal satisfaction. Results might help enhance key processes for the initiative and highlight some barriers to implementation, such as enforcing tobacco control policy off school premises. Continued efforts are needed to prevent tobacco use among young people.

      3. Prevalence of self-reported prescription opioid use and illicit drug use among U.S. adults: NHANES 2005-2016external icon
        Gu JK, Allison P, Trotter AG, Charles LE, Ma CC, Groenewold M, Andrew ME, Luckhaupt SE.
        J Occup Environ Med. 2021 Jul 22.
        OBJECTIVE: To estimate the self-reported prevalence of prescription opioid use and illicit drug use in the U.S. METHODS: Self-reported prescription opioid use and illicit drug use (mostly non-opioid) were obtained for adults and adult workers (NHANES 2005-2016). RESULTS: Prevalence (95% CI) of prescription opioid use was 6.5% (6.0-7.0) (adults) and 4.1% (3.7-4.5) (workers). Prevalence of illicit drug use was 9.5% (8.8-10.1) (adults) and 10.2% (9.4-11.1) (workers). Among occupations, prevalence of prescription opioid use was highest in personal care (6.5%; 4.1-10.4) and healthcare practitioners (5.9%; 3.8-9.0); for illicit drug use, construction/extraction (18.0%; 15.1-21.3) and food preparation (15.8%; 12.5-19.7). CONCLUSION: The prevalence of prescription opioid use was elevated among some occupations. Judicious prescription strategies and targeted interventions are both needed. The prevalence of illicit drug use among certain occupational groups suggests the need to ensure access to therapy.

      4. BACKGROUND AND OBJECTIVES: Hospital discharge records remain a common data source for tracking the opioid crisis among pregnant women and infants. The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) transition from the International Classification of Diseases, Ninth Revision, Clinical Modification may have affected surveillance. Our aim was to evaluate this transition on rates of neonatal abstinence syndrome (NAS), maternal opioid use disorder (OUD), and opioid-related diagnoses (OUD with ICD-10-CM codes for long-term use of opioid analgesics and unspecified opioid use). METHODS: Data from the 2013-2017 Healthcare Cost and Utilization Project's National Inpatient Sample were used to conduct, interrupted time series analysis and log-binomial segmented regression to assess whether quarterly rates differed across the transition. RESULTS: From 2013 to 2017, an estimated 18.8 million birth and delivery hospitalizations were represented. The ICD-10-CM transition was not associated with NAS rates (rate ratio [RR]: 0.99; 95% confidence interval [CI]: 0.90-1.08; P = .79) but was associated with 11% lower OUD rates (RR: 0.89; 95% CI: 0.80-0.98; P = .02) and a decrease in the quarterly trend (RR: 0.98; 95% CI: 0.96-1.00; P = .04). The transition was not associated with maternal OUD plus long-term use rates (RR: 0.98; 95% CI: 0.89-1.09; P = .76) but was associated with a 20% overall increase in opioid-related diagnosis rates including long-term and unspecified use (RR: 1.20; 95% CI: 1.09-1.32; P < .001). CONCLUSIONS: The ICD-10-CM transition did not appear to affect NAS. However, coding of maternal OUD alone may not capture the same population across the transition, which confounds the interpretation of trend data spanning this time period.

    • Zoonotic and Vectorborne Diseases
      1. Stability of Zika virus antibodies in specimens from a retrospective serological studyexternal icon
        Sasmono RT, Johar E, Yohan B, Ma'roef CN, Soebandrio A, Myint KS, Pronyk P, Hadinegoro SR, Soepardi EJ, Bouckenooghe A, Hawley W, Rosenberg R, Powers AM.
        Am J Trop Med Hyg. 2021 Jul 26.

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