Issue 12, April 6, 2021

CDC Science Clips: Volume 13, Issue 12, April 6, 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
      • The histology of brain tumours for 67,331 children and 671,085 adults diagnosed in 60 countries during 2000-2014: a global, population-based study (CONCORD-3)external icon
        Girardi F, Rous B, Stiller CA, Gatta G, Fersht N, Storm HH, Rodrigues JR, Herrmann C, Marcos-Gragera R, Peris-Bonet R, Valkov M, Weir HK, Woods RR, You H, Cueva PA, De P, Di Carlo V, Johannesen TB, Lima CA, Lynch CF, Coleman MP, Allemani C.
        Neuro Oncol. 2021 Mar 19.
        INTRODUCTION: Global variations in survival for brain tumours are very wide when all histological types are considered together. Appraisal of international differences should be informed by the distribution of histology, but little is known beyond Europe and North America. PATIENTS AND METHODS: The source for the analysis was the CONCORD data base, a programme of global surveillance of cancer survival trends, which includes the tumour records of individual patients from more than 300 population-based cancer registries. We considered all patients aged 0-99 years who were diagnosed with a primary brain tumour during 2000-2014, whether malignant or non-malignant. We presented the histology distribution of these tumours, for patients diagnosed during 2000-2004, 2005-2009, and 2010-2014. RESULTS: Records were submitted from 60 countries on five continents, 67,331 for children and 671,085 for adults. After exclusion of irrelevant morphology codes, the final study population comprised 60,783 children and 602,112 adults. Only 59 of 60 countries covered in CONCORD-3 were included, because none of the Mexican records were eligible. We defined 12 histology groups for children, and 11 histology groups for adults. In children (0-14 years), the proportion of low-grade astrocytomas ranged between 6% and 50%. Medulloblastoma was the most common sub-type in countries where low-grade astrocytoma was less commonly reported. In adults (15-99 years), the proportion of glioblastomas varied between 9% and 69%. International comparisons were made difficult by wide differences in the proportion of tumours with unspecified histology, which accounted for up to 52% of diagnoses in children and up to 65% in adults. CONCLUSIONS: To our knowledge, this is the first account of the global histology distribution of brain tumours, in children and adults. Our findings provide insights into the practices and the quality of cancer registration worldwide.

    • Communicable Diseases
      • Lessons from co-production of evidence and policy in Nigeria's COVID-19 responseexternal icon
        Abubakar I, Dalglish SL, Ihekweazu CA, Bolu O, Aliyu SH.
        BMJ Glob Health. 2021 Mar;6(3).
        In February 2020, Nigeria faced a potentially catastrophic COVID-19 outbreak due to multiple introductions, high population density in urban slums, prevalence of other infectious diseases and poor health infrastructure. As in other countries, Nigerian policymakers had to make rapid and consequential decisions with limited understanding of transmission dynamics and the efficacy of available control measures. We present an account of the Nigerian COVID-19 response based on co-production of evidence between political decision-makers, health policymakers and academics from Nigerian and foreign institutions, an approach that allowed a multidisciplinary group to collaborate on issues arising in real time. Key aspects of the process were the central role of policymakers in determining priority areas and the coordination of multiple, sometime conflicting inputs from stakeholders to write briefing papers and inform effective national decision making. However, the co-production approach met with some challenges, including limited transparency, bureaucratic obstacles and an overly epidemiological focus on numbers of cases and deaths, arguably to the detriment of addressing social and economic effects of response measures. Larger systemic obstacles included a complex multitiered health system, fragmented decision-making structures and limited funding for implementation. Going forward, Nigeria should strengthen the integration of the national response within existing health decision bodies and implement strategies to mitigate the social and economic impact, particularly on the poorest Nigerians. The co-production of evidence examining the broader public health impact, with synthesis by multidisciplinary teams, is essential to meeting the social and public health challenges posed by the COVID-19 pandemic in Nigeria and other countries.

      • Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021external icon
        Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, Olsho LE, Caban-Martinez AJ, Fowlkes A, Lutrick K, Kuntz JL, Dunnigan K, Odean MJ, Hegmann KT, Stefanski E, Edwards LJ, Schaefer-Solle N, Grant L, Ellingson K, Groom HC, Zunie T, Thiese MS, Ivacic L, Wesley MG, Lamberte JM, Sun X, Smith ME, Phillips AL, Groover KD, Yoo YM, Gerald J, Brown RT, Herring MK, Joseph G, Beitel S, Morrill TC, Mak J, Rivers P, Harris KM, Hunt DR, Arvay ML, Kutty P, Fry AM, Gaglani M.
        MMWR Morb Mortal Wkly Rep. 2021 Apr 2;70(13):495-500.
        Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.(†) Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.(§) In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

    • Environmental Health
      • Plasma Concentrations of Per- and Polyfluoroalkyl Substances and Body Composition from Mid-childhood to Early Adolescenceexternal icon
        Janis JA, Rifas-Shiman SL, Seshasayee SM, Sagiv S, Calafat AM, Gold DR, Coull BA, Rosen CJ, Oken E, Fleisch AF.
        J Clin Endocrinol Metab. 2021 Mar 19.
        CONTEXT: Per- and polyfluoroalkyl substances (PFAS) may alter body composition by lowering anabolic hormones and increasing inflammation, but data are limited, particularly in adolescence when body composition is rapidly changing. OBJECTIVE: To evaluate associations of PFAS plasma concentrations in childhood with change in body composition through early adolescence. DESIGN, SETTING, AND PARTICIPANTS: 537 children in the Boston-area Project Viva cohort. METHODS: We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to examine associations of plasma concentrations of six PFAS, quantified by mass spectrometry, in mid-childhood (mean age 7.9 years; 2007-2010) with change in body composition measured by dual-energy X-ray absorptiometry from mid-childhood to early adolescence (mean age 13.1 years). RESULTS: In single PFAS linear regression models, children with higher concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoate (PFDA), and perfluorohexane sulfonate (PFHxS) had less accrual of lean mass (e.g., -0.33 [95% CI: -0.52, -0.13] kg/m 2 per doubling of PFOA). Children with higher PFOS and PFHxS had less accrual of total and truncal fat mass (e.g., -0.32 [95% CI: -0.54, -0.11] kg/m 2 total fat mass per doubling of PFOS), particularly subcutaneous fat mass (e.g., -17.26 [95% CI -32.25, -2.27] g/m 2 per doubling of PFOS). Children with higher PFDA and perfluorononanoate (PFNA) had greater accrual of visceral fat mass (e.g., 0.44 [95% CI: 0.13, 0.75] g/m 2 per doubling of PFDA). Results from BKMR mixture models were consistent with linear regression analyses. CONCLUSIONS: Early life exposure to some but not all PFAS may be associated with adverse changes in body composition.

      • Chemical Mixture Exposures During Pregnancy and Cognitive Abilities in School-Aged Childrenexternal icon
        Kalloo G, Wellenius GA, McCandless L, Calafat AM, Sjodin A, Sullivan AJ, Romano ME, Karagas MR, Chen A, Yolton K, Lanphear BP, Braun JM.
        Environ Res. 2021 Mar 17:111027.
        INTRODUCTION: Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities. METHODS: In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003-2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scores ]=cross clusters, and with increasing PC scores and individual biomarker concentrations. RESULTS: Geometric mean biomarker concentrations were generally highest, intermediate, and lowest among women in clusters 1, 2, and 3, respectively. Children born to women in clusters 1 and 2 had 5.1 (95% CI:-9.4,-0.8) and 2.0 (95% CI:-5.5, 1,4) lower performance IQ scores compared to children in cluster 3, respectively. PC scores and individual chemical biomarker concentrations were not associated with cognitive abilities. CONCLUSIONS: In this cohort, combined prenatal exposure to phenols, certain phthalates, pesticides, and perfluoroalkyl substances was inversely associated with children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects.

    • Genetics and Genomics
      • Improving reporting standards for polygenic scores in risk prediction studiesexternal icon
        Wand H, Lambert SA, Tamburro C, Iacocca MA, O'Sullivan JW, Sillari C, Kullo IJ, Rowley R, Dron JS, Brockman D, Venner E, McCarthy MI, Antoniou AC, Easton DF, Hegele RA, Khera AV, Chatterjee N, Kooperberg C, Edwards K, Vlessis K, Kinnear K, Danesh JN, Parkinson H, Ramos EM, Roberts MC, Ormond KE, Khoury MJ, Janssens A, Goddard KA, Kraft P, MacArthur JA, Inouye M, Wojcik GL.
        Nature. 2021 Mar;591(7849):211-219.
        Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.

    • Health Communication and Education
    • Health Disparities
      • Relationship between neighborhood census-tract level socioeconomic status and respiratory syncytial virus-associated hospitalizations in U.S. adults, 2015-2017external icon
        Holmen JE, Kim L, Cikesh B, Kirley PD, Chai SJ, Bennett NM, Felsen CB, Ryan P, Monroe M, Anderson EJ, Openo KP, Como-Sabetti K, Bye E, Talbot HK, Schaffner W, Muse A, Barney GR, Whitaker M, Ahern J, Rowe C, Langley G, Reingold A.
        BMC Infect Dis. 2021 Mar 23;21(1):293.
        BACKGROUND: Respiratory syncytial virus (RSV) infection causes substantial morbidity and mortality in children and adults. Socioeconomic status (SES) is known to influence many health outcomes, but there have been few studies of the relationship between RSV-associated illness and SES, particularly in adults. Understanding this association is important in order to identify and address disparities and to prioritize resources for prevention. METHODS: Adults hospitalized with a laboratory-confirmed RSV infection were identified through population-based surveillance at multiple sites in the U.S. The incidence of RSV-associated hospitalizations was calculated by census-tract (CT) poverty and crowding, adjusted for age. Log binomial regression was used to evaluate the association between Intensive Care Unit (ICU) admission or death and CT poverty and crowding. RESULTS: Among the 1713 cases, RSV-associated hospitalization correlated with increased CT level poverty and crowding. The incidence rate of RSV-associated hospitalization was 2.58 (CI 2.23, 2.98) times higher in CTs with the highest as compared to the lowest percentages of individuals living below the poverty level (≥ 20 and < 5%, respectively). The incidence rate of RSV-associated hospitalization was 1.52 (CI 1.33, 1.73) times higher in CTs with the highest as compared to the lowest levels of crowding (≥5 and < 1% of households with > 1 occupant/room, respectively). Neither CT level poverty nor crowding had a correlation with ICU admission or death. CONCLUSIONS: Poverty and crowding at CT level were associated with increased incidence of RSV-associated hospitalization, but not with more severe RSV disease. Efforts to reduce the incidence of RSV disease should consider SES.

    • Health Economics
      • Work flexibility and work-related well-beingexternal icon
        Ray TK, Pana-Cryan R.
        Int J Environ Res Public Health. 2021 ;18(6):1-17.
        Work organization practices, including work flexibility, are changing and can affect worker well-being. Common work flexibility types include working at home, taking time off when needed, and changing one’s work schedule. Given the changes in and the importance of work flexibility, the study assesses its prevalence and association with worker well-being in the United States. We used 2002–2018 General Social Survey—Quality of Worklife (GSS-QWL) data, descriptive statistics, and regression analyses to assess the reported likelihood of job stress, job satisfaction, healthy days, and days with activity limitations among workers reporting work flexibility. The prevalence of work flexibility remained relatively stable during the period examined. Working at home increased the likelihood of job stress by 22% and job satisfaction by 65%. Taking time off decreased the likelihood of job stress by 56% and days with activity limitations by 24%, and more than doubled the likelihood of job satisfaction. Changing one’s schedule decreased the likelihood of job stress by 20% and increased the likelihood of job satisfaction by 62%. This study used all the available data from GSS-QWL and demonstrated the ongoing importance of work flexibility for well-being.

    • Injury and Violence
      • Factors associated with concussion-symptom knowledge and attitudes toward concussion care seeking in a national survey of parents of middle-school children in the USexternal icon
        Kerr ZY, Nedimyer AK, Kay MC, Chandran A, Gildner P, Byrd KH, Haarbauer-Krupa JK, Register-Mihalik JK.
        J Sport Health Sci. 2021 Mar;10(2):113-121.
        BACKGROUND: Developing appropriate concussion prevention and management paradigms in middle school (MS) settings requires understanding parents' general levels of concussion-related knowledge and attitudes. This study examined factors associated with concussion-symptom knowledge and care-seeking attitudes among parents of MS children (aged 10-15 years). METHODS: A panel of 1224 randomly selected U.S. residents, aged ≥ 18 years and identifying as parents of MS children, completed an online questionnaire capturing parental and child characteristics. The parents' concussion-symptom knowledge was measured using 25 questions, with possible answers being "yes", "maybe", and "no". Correct answers earned 2 points, "maybe" answers earned 1 point, and incorrect answers earned 0 point (range: 0-50; higher scores = better knowledge). Concussion care-seeking attitudes were also collected using five 7-point scale items (range: 5-35; higher scores = more positive attitudes). Multivariable ordinal logistic regression models identified predictors of higher scores. Models met proportional odds assumptions. Adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs) (excluding 1.00) were deemed statistically significant. RESULTS: Median scores were 39 (interquartile range: 32-44) for symptom knowledge and 32 (interquartile range: 28-35) for care-seeking attitude. In multivariable models, odds of better symptom knowledge were higher in women vs. men (aOR = 2.28; 95%CI: 1.71-3.05), white/non-Hispanics vs. other racial or ethnic groups (aOR = 1.88; 95%CI: 1.42-2.49), higher parental age (10-year-increase aOR = 1.47; 95%CI: 1.26-1.71), and greater competitiveness (10%-scale-increase aOR = 1.24; 95%CI: 1.13-1.36). Odds of more positive care-seeking attitudes were higher in white/non-Hispanics vs. other racial or ethnic groups (aOR = 1.45; 95%CI: 1.06-1.99) and in older parental age (10-year-increase aOR = 1.24; 95%CI: 1.05-1.47). CONCLUSION: Characteristics of middle school children's parents (e.g., sex, race or ethnicity, age) are associated with their concussion-symptom knowledge and care-seeking attitudes. Parents' variations in concussion knowledge and attitudes warrant tailored concussion education and prevention.

    • Occupational Safety and Health
      • Occupational physical activity and cardiovascular disease in the United Statesexternal icon
        Quinn TD, Yorio PL, Smith PM, Seo Y, Whitfield GP, Barone Gibbs B.
        Occup Environ Med. 2021 Mar 18.
        BACKGROUND: Emerging evidence, predominately from European and Asian countries, describes opposing effects of occupational physical activity (OPA) and leisure-time physical activity (LTPA) on cardiovascular health. This analysis examined cardiovascular disease (CVD) prevalence associated with OPA and LTPA. METHODS: This cross-sectional analysis of 2015 National Health Interview Survey data (n=16 974) employed logistic regression to estimate odds (OR) of self-reported CVD (coronary heart disease, heart attack, stroke or angina) with self-reported total occupational activity (TOA), occupational exertion (OE), occupational standing and walking (OSW) and LTPA. OPA was measured using two questions: 'How often does your job involve…' (1) 'repeated lifting, pushing, pulling or bending?' (OE) and (2) 'standing or walking around?' (OSW) with responses on a 5-item Likert scale (0=never, 4=always). TOA was categorised similarly after summing OE and OSW scores. LTPA was defined as 0, 1-149 or ≥150 min/week of moderate-to-vigorous activity. All models adjusted for common socioeconomic variables and additional analyses were stratified by sex, smoking status and LTPA. RESULTS: Odds for CVD were higher when 'always' performing TOA (OR 1.99 95% CI 1.12 to 3.53), OE (OR 2.15, 95% CI 1.45 to 3.19) or OSW (OR 1.84, 95% CI 1.07 to 3.17) compared with 'never'. When restricting to never-smokers, odds for CVD were higher when 'always' performing TOA (OR 3.00, 95% CI 1.38 to 6.51) and OE (OR 3.00, 95% CI 1.80 to 5.02) versus 'never'. CONCLUSION: Associations of high OPA with CVD were equally apparent across sexes, stronger in lower LTPA levels and stronger in never-smokers. While uncontrolled confounding is still possible, even after extensive adjustment, the seemingly paradoxical adverse associations with OPA and CVD should be investigated further.

    • Substance Use and Abuse
      • Alcohol testing and alcohol involvement among violent deaths by state, 2014-2016external icon
        Greene N, Tomedi LE, Cox ME, Mello E, Esser MB.
        Prev Med. 2021 Mar 18:106527.
        Blood alcohol concentration (BAC) testing rates vary across states, potentially biasing estimates of alcohol involvement in violent deaths. The National Violent Death Reporting System (NVDRS) collects information on violent deaths, including decedents' BACs. This study assessed characteristics of violent deaths by BAC testing status, and the proportion of decedents with a positive BAC or BAC ≥ 0.08 g/dL. NVDRS data from 2014 to 2016 (2014: 18 states; 2015: 27 states; 2016: 32 states) were analyzed to assess BAC testing (tested, not tested, unknown/missing) by state, decedent characteristics, and death investigation system (e.g., state medical examiner, coroners), in 2019. The proportion of violent deaths with a BAC > 0.0 or ≥ 0.08 g/dL was also assessed. Among 95,390 violent death decedents, 57.1% had a BAC test (range: 9.5% in Georgia to 95.8% in Utah), 2.3% were not tested, and 40.6% had an unknown/missing BAC testing status (range: 1.3% in Alaska to 78.0% in Georgia). Decedents who were 21-44 years, American Indian/Alaska Native or Hispanic, died by poisoning, died by undetermined intent, or were investigated by a state medical examiner were most likely to receive BAC testing. Among the violent deaths with a reported BAC, 41.1% had a positive BAC and 27.7% had a BAC ≥ 0.08 g/dL. About 2 in 5 violent deaths were missing data on alcohol testing. Increased testing and reporting of alcohol among violent deaths could inform the development and use of evidence-based prevention strategies (e.g., increasing alcohol taxes, regulating alcohol outlet density) for reducing violent deaths.

  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. Prevalence and Correlates of Hypertension Unawareness among Lebanese Adults: The Need to Target Those "left Behind"external icon
        Ghaddar F, Hammad L, Tohme RA, Kabakian-Khasholian T, Hwalla N, Sibai AM.
        Int J Hypertens. 2021 ;2021.
        Introduction. Hypertension unawareness is context-specific, and our understanding of factors associated with it has implications on primary healthcare practices locally and contributes to achieving cardiovascular disease (CVD) targets, globally. In this study, we examine the prevalence and correlates of hypertension unawareness among adult Lebanese population. Methods. The study sample included a nationally representative sample of 2214 adults ≥25 years of age from the Noncommunicable Disease (NCD) Risk Factor WHO-STEPS cross-sectional survey conducted in Lebanon. In the first step, hypertension was assessed based on reported morbidity using face-To-face interviews, and in the second step, based on blood pressure (BP) measurement. We defined hypertension prevalence as systolic/diastolic blood pressure ≥140/90 mmHg and/or ongoing treatment for hypertension. Hypertension unawareness was described as lack of prior knowledge of hypertensive status. Those responding negatively to the face-To-face interview question "whether they had ever been told by a health worker that they have hypertension"were labelled as "apparently healthy."Results. Overall prevalence of hypertension was 30.7%. A total of 369 subjects were unaware of their condition, representing 51.8% of all hypertensives and 15.9% of the apparently healthy. Multivariable analysis controlling for a number of confounders showed that, among apparently healthy participants, insurance coverage and contact with healthcare services were not associated with higher likelihood for hypertension awareness. Among all hypertensives, hypertension unawareness was significantly higher in the young, those with BMI <25 kg/m2 (adjusted OR (aOR): 2.52; 95% CI: 1.35-4.69), no CVD (aOR: 3.30; 95% CI: 1.74-6.29), and participants with no reported family history of hypertension (aOR: 4.87; 95% CI: 2.89-8.22), compared to their counterparts. Conclusion. In Lebanon, unawareness of hypertension occurred in those clinically least perceived to be at risk. These findings are key for optimizing current screening practices and informing NCD prevention efforts in the country and contribute to achieving global targets of the SDGs of "leaving no one behind."

      2. Mapping stages, barriers and facilitators to the implementation of HEARTS in the Americas initiative in 12 countries: A qualitative studyexternal icon
        Giraldo GP, Joseph KT, Angell SY, Campbell NR, Connell K, DiPette DJ, Escobar MC, Valdés-Gonzalez Y, Jaffe MG, Malcolm T, Maldonado J, Lopez-Jaramillo P, Olsen MH, Ordunez P.
        J Clin Hypertens (Greenwich). 2021 Mar 18.
        The World Health Organization (WHO) Global Hearts Initiative offers technical packages to reduce the burden of cardiovascular diseases through population-wide and targeted health services interventions. The Pan American Health Organization (PAHO) has led implementation of the HEARTS in the Americas Initiative since 2016. The authors mapped the developmental stages, barriers, and facilitators to implementation among the 371 primary health care centers in the participating 12 countries. The authors used the qualitative method of document review to examine cumulative country reports, technical meeting notes, and reports to regional stakeholders. Common implementation barriers include segmentation of health systems, overcoming health care professionals' scope of practice legal restrictions, and lack of health information systems limiting operational evaluation and quality improvement mechanisms. Main implementation facilitators include political support from ministries of health and leading scientific societies, PAHO's role as a regional catalyst to implementation, stakeholder endorsement demonstrated by incorporating HEARTS into official documents, and having a health system oriented to primary health care. Key lessons include the need for political commitment and cultivating on-the-ground leadership to initiate a shift in hypertension care delivery, accompanied by specific progress in the development of standardized treatment protocols and a set of high-quality medicines. By systematizing an implementation strategy to ease integration of interventions into delivery processes, the program strengthened technical leadership and ensured sustainability. These study findings will aid the regional approach by providing a staged planning model that incorporates lessons learned. A systematic approach to implementation will enhance equity, efficiency, scale-up, and sustainability, and ultimately improve population hypertension control.

      3. OBJECTIVE: To assess the prevalence of migraine or severe headache among US adults by inflammatory bowel disease (IBD) status. BACKGROUND: Emerging evidence in clinical settings suggests a higher prevalence of migraine among patients with IBD than those without IBD. METHODS: Data from 60,436 US adults aged ≥18 years participating in the 2015 and 2016 National Health Interview Survey (NHIS) were analyzed. The relationship between IBD status and migraine or severe headache was assessed overall and stratified by levels of selected characteristics including sex, age, race/ethnicity, education, poverty status, marital status, smoking status, obesity status, serious psychological distress, and major chronic condition status. RESULTS: Overall, the age-adjusted prevalence of migraine or severe headache was 15.4% (n = 9062) and of IBD was 1.2% (n = 862). A higher age-adjusted migraine or severe headache prevalence was reported among participants with IBD than those without IBD (28.1% vs. 15.2%, p < 0.0001). The association of migraine or severe headache with IBD remained significant overall [adjusted prevalence ratio (95% CI) = 1.59 (1.35-1.86)] and within the levels of most other selected characteristics after controlling for all other covariates. CONCLUSIONS: Our results confirmed a higher prevalence of migraine or severe headache among US adults with IBD than those without. Healthcare providers might assess migraine or severe headache among patients with IBD to improve management and quality of life.

      4. Human papillomavirus oral-and sero-positivity in fanconi anemiaexternal icon
        Sauter SL, Zhang X, Romick-Rosendale L, Wells SI, Myers KC, Brusadelli MG, Poff CB, Brown DR, Panicker G, Unger ER, Mehta PA, Bleesing J, Davies SM, Kovacic MB.
        Cancers. 2021 ;13(6):1-18.
        High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predis-position to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96–11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.

    • Communicable Diseases
      1. Short-Term Effects of the COVID-19 Pandemic on HIV Care Utilization, Service Delivery, and Continuity of HIV Antiretroviral Treatment (ART) in Haitiexternal icon
        Celestin K, Allorant A, Virgin M, Marinho E, Francois K, Honoré JG, White C, Valles JS, Perrin G, De Kerorguen N, Flowers J, Balan JG, Koama JB, Barnhart S, Puttkammer N.
        AIDS Behav. 2021 Mar 18:1-7.
        INTRODUCTION: Our study describes changes in HIV care service delivery and continuity of HIV antiretroviral therapy (ART) for people living with HIV (PLHIV) during the 8 weeks before and after diagnosis of the first coronavirus disease 2019 (COVID-19) cases in Haiti on March 19, 2020. METHODS: Using data from 96 out of 167 health facilities offering ART services, we compared four ART program indicators: (1) count of HIV visits; (2) proportion of ART dispenses in community-based settings (DAC); (3) proportion of multi-month dispensing of ART medications > 6 months (> 6 m MMD); and (4) proportion of timely ART refills. We used uncontrolled interrupted time series (ITS) models to estimate slope and level changes in each indicator with the arrival of COVID-19. RESULTS AND DISCUSSION: From week 1 to week 16, the average number of HIV visits fell from 121.5 to 92.5 visits, the proportion of DAC rose from 22.7% to 36.7%, the proportion of > 6 m MMD rose from 29.4% to 48.4%, and the proportion of timely ART refills fell from 51.9% to 43.8%. The ITS models estimated abrupt increases of 36% in > 6 m MMD (p < 0.001) and 37% in DAC (p < 0.001) at the time of COVID-19 arrival, and no change after arrival of COVID-19. The was an abrupt decline of 18% in timely ART refills with the arrival of COVID-19 and a decline of 1% per week thereafter, both non-statistically significant changes. CONCLUSIONS: The sudden changes in HIV service utilization represent dramatic adaptations needed to mitigate primary and secondary effects of the COVID-19 pandemic on PLHIV. This study underscores the urgency of optimizing ART delivery models in Haiti and beyond, in order to maintain progress toward HIV epidemic control.

      2. Pilot Investigation of SARS-CoV-2 Secondary Transmission in Kindergarten Through Grade 12 Schools Implementing Mitigation Strategies - St. Louis County and City of Springfield, Missouri, December 2020external icon
        Dawson P, Worrell MC, Malone S, Tinker SC, Fritz S, Maricque B, Junaidi S, Purnell G, Lai AM, Neidich JA, Lee JS, Orscheln RC, Charney R, Rebmann T, Mooney J, Yoon N, Petit M, Schmidt S, Grabeel J, Neill LA, Barrios LC, Vallabhaneni S, Williams RW, Goddard C, Newland JG, Neatherlin JC, Salzer JS.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):449-455.
        Many kindergarten through grade 12 (K-12) schools offering in-person learning have adopted strategies to limit the spread of SARS-CoV-2, the virus that causes COVID-19 (1). These measures include mandating use of face masks, physical distancing in classrooms, increasing ventilation with outdoor air, identification of close contacts,* and following CDC isolation and quarantine guidance(†) (2). A 2-week pilot investigation was conducted to investigate occurrences of SARS-CoV-2 secondary transmission in K-12 schools in the city of Springfield, Missouri, and in St. Louis County, Missouri, during December 7-18, 2020. Schools in both locations implemented COVID-19 mitigation strategies; however, Springfield implemented a modified quarantine policy permitting student close contacts aged ≤18 years who had school-associated contact with a person with COVID-19 and met masking requirements during their exposure to continue in-person learning.(§) Participating students, teachers, and staff members with COVID-19 (37) from 22 schools and their school-based close contacts (contacts) (156) were interviewed, and contacts were offered SARS-CoV-2 testing. Among 102 school-based contacts who received testing, two (2%) had positive test results indicating probable school-based SARS-CoV-2 secondary transmission. Both contacts were in Springfield and did not meet criteria to participate in the modified quarantine. In Springfield, 42 student contacts were permitted to continue in-person learning under the modified quarantine; among the 30 who were interviewed, 21 were tested, and none received a positive test result. Despite high community transmission, SARS-CoV-2 transmission in schools implementing COVID-19 mitigation strategies was lower than that in the community. Until additional data are available, K-12 schools should continue implementing CDC-recommended mitigation measures (2) and follow CDC isolation and quarantine guidance to minimize secondary transmission in schools offering in-person learning.

      3. Tuberculosis - United States, 2020external icon
        Deutsch-Feldman M, Pratt RH, Price SF, Tsang CA, Self JL.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):409-414.
        Tuberculosis (TB) disease incidence has decreased steadily since 1993 (1), a result of decades of work by local TB programs to detect, treat, and prevent TB disease and transmission. During 2020, a total of 7,163 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC), a relative reduction of 20%, compared with the number of cases reported during 2019.* TB incidence per 100,000 persons was 2.2 during 2020, compared with 2.7 during 2019. Since 2010, TB incidence has decreased by an average of 2%-3% annually (1). Pandemic mitigation efforts and reduced travel might have contributed to the reported decrease. The magnitude and breadth of the decrease suggest potentially missed or delayed TB diagnoses. Health care providers should consider TB disease when evaluating patients with signs and symptoms consistent with TB (e.g., cough of >2 weeks in duration, unintentional weight loss, and hemoptysis), especially when diagnostic tests are negative for SARS-CoV-2, the virus that causes COVID-19. In addition, members of the public should be encouraged to follow up with their health care providers for any respiratory illness that persists or returns after initial treatment. The steep, unexpected decline in TB cases raises concerns of missed cases, and further work is in progress to better understand factors associated with the decline.

      4. Rapid Scale-up of an Antiretroviral Therapy Program Before and During the COVID-19 Pandemic - Nine States, Nigeria, March 31, 2019-September 30, 2020external icon
        Dirlikov E, Jahun I, Odafe SF, Obinna O, Onyenuobi C, Ifunanya M, Efuntoye TA, Tingir N, Ene U, Fagbemi A, Meribe C, Bassey O, Ayo A, Fagbamigbe OJ, Amafah J, Bamidele M, Alagi M, Oladipo A, Dalhatu I, Okoye M, Onotu D, Gwamna J, Abrams WA, Conner DA, Nwaohiri A, Carpenter D, Ijeoma UC, Shah S, Tison LI, Shah M, Chun H, Williams-Sherlock M, Boyd AT, Bachanas P, Ikpeazu A, Aliyu GG, Ellerbrock T, Swaminathan M.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):421-426.
        In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.

      5. Risk factors for measles deaths among children during a Nationwide measles outbreak - Romania, 2016-2018external icon
        Donadel M, Stanescu A, Pistol A, Stewart B, Butu C, Jankovic D, Paunescu B, Zimmerman L.
        BMC Infect Dis. 2021 Mar 19;21(1):279.
        BACKGROUND: Case fatality ratio (CFR) among all age groups during the 2016-2018 measles outbreak in Romania was increased compared with previous outbreaks. To identify risk factors for measles death, we conducted a case-control study among infants and children hospitalized for measles. METHODS: National surveillance data were used to identify hospitalized cases of laboratory-confirmed or epidemiologically linked measles in infants and children aged < 59 months with rash onset from January 2016 to July 2018. We abstracted medical records of 50 fatal cases ("cases") and 250 non-fatal cases ("controls") matched by age, sex, district of residence, and urban/rural place of residence. We calculated univariable and multivariable matched odds ratios (OR) and 95% confidence intervals (CIs) for risk factors. RESULTS: Ninety-three percent of case-patients and controls had not received a valid dose of a measles-containing vaccine; only 5 % received Vitamin A supplementation once diagnosed with measles. In the univariable analysis, cases were more likely than controls to have had a healthcare-related exposure to measles manifesting as inpatient admission for pneumonia during the 7 to 21 day measles incubation period (OR: 3.0; 95% CI [1.2, 7.2]), to have had a history of malnutrition (OR: 3.4; 95% CI [1.1, 9.9]), and to have had pneumonia as a complication of measles (OR:7.1; 95% CI [2.0-24.8]). In the multivariable analysis, pneumonia as a measles complication remained a risk for death (OR: 7.1; 95% CI [1.4-35.3]). CONCLUSIONS: Implementing infection prevention and control practices, ensuring immunization of healthcare workers, and hospitalizing only severe measles cases may minimize the risk of nosocomial measles transmission. Implementing World Health Organization (WHO) recommendations for Vitamin A supplementation, improving immunization of children to prevent influenza, pneumococcal, and other bacterial respiratory diseases may decrease complications and deaths due to measles in Romania.

      6. COVID-19 in Primary and Secondary School Settings During the First Semester of School Reopening - Florida, August-December 2020external icon
        Doyle T, Kendrick K, Troelstrup T, Gumke M, Edwards J, Chapman S, Propper R, Rivkees SA, Blackmore C.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):437-441.
        After detection of cases of COVID-19 in Florida in March 2020, the governor declared a state of emergency on March 9,* and all school districts in the state suspended in-person instruction by March 20. Most kindergarten through grade 12 (K-12) public and private schools in Florida reopened for in-person learning during August 2020, with varying options for remote learning offered by school districts. During August 10-December 21, 2020, a total of 63,654 COVID-19 cases were reported in school-aged children; an estimated 60% of these cases were not school-related. Fewer than 1% of registered students were identified as having school-related COVID-19 and <11% of K-12 schools reported outbreaks. District incidences among students correlated with the background disease incidence in the county; resumption of in-person education was not associated with a proportionate increase in COVID-19 among school-aged children. Higher rates among students were observed in smaller districts, districts without mandatory mask-use policies, and districts with a lower proportion of students participating in remote learning. These findings highlight the importance of implementing both community-level and school-based strategies to reduce the spread of COVID-19 and suggest that school reopening can be achieved without resulting in widespread illness among students in K-12 school settings.

      7. Epidemiology of Tuberculosis and Progress Toward Meeting Global Targets - Worldwide, 2019external icon
        Fukunaga R, Glaziou P, Harris JB, Date A, Floyd K, Kasaeva T.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):427-430.
        Although tuberculosis (TB) is curable and preventable, in 2019, TB remained the leading cause of death from a single infectious agent worldwide and the leading cause of death among persons living with HIV infection (1). The World Health Organization's (WHO's) End TB Strategy set ambitious targets for 2020, including a 20% reduction in TB incidence and a 35% reduction in the number of TB deaths compared with 2015, as well as zero TB-affected households facing catastrophic costs (defined as costs exceeding 20% of annual household income) (2). In addition, during the 2018 United Nations High-Level Meeting on TB (UNHLM-TB), all member states committed to setting 2018-2022 targets that included provision of TB treatment to 40 million persons and TB preventive treatment (TPT) to 30 million persons, including 6 million persons living with HIV infection and 24 million household contacts of patients with confirmed TB (4 million aged <5 years and 20 million aged ≥5 years) (3,4). Annual data reported to WHO by 215 countries and territories, supplemented by surveys assessing TB prevalence and patient costs in some countries, were used to estimate TB incidence, the number of persons accessing TB curative and preventive treatment, and the percentage of TB-affected households facing catastrophic costs (1). Globally, TB illness developed in an estimated 10 million persons in 2019, representing a decline in incidence of 2.3% from 2018 and 9% since 2015. An estimated 1.4 million TB-related deaths occurred, a decline of 7% from 2018 and 14% since 2015. Although progress has been made, the world is not on track to achieve the 2020 End TB Strategy incidence and mortality targets (1). Efforts to expand access to TB curative and preventive treatment need to be substantially amplified for UNHLM-TB 2022 targets to be met.

      8. BACKGROUND: Early infant diagnosis (EID) of HIV, followed by effective care including antiretroviral therapy (ART), reduces infant mortality by 76% and HIV progression by 75%. In 2015, 50% of 1.2 million HIV-exposed infants (HEI) in 21 priority countries received a virologic test within the recommended 2 months of birth. We sought to identify factors associated with timely uptake of virologic EID among HEI and gain insight into missed opportunities. METHODS: This was a cross-sectional study that used de-identified data from electronic medical records of 54 health facilities within the Christian Health Association of Kenya (CHAK) HIV Project database. All HEI who had their first HIV virologic test done between January 2015 and December 2017 were included in the study and categorized as either having the test within or after 8 weeks of birth. Multivariate linear mixed effects regression model was used to determine factors associated with uptake of the first HIV EID polymerase chain reaction (PCR). Predictor variables studied include sex, birth weight, the entry point into care, provision of ART prophylaxis for the infant, maternal ART at time of EID, mode of delivery, and place of delivery. RESULTS: We included 2020 HEI of whom 1018 (50.4%) were female. A majority, 1596 (79.0%) had their first HIV PCR within 2 months of birth at a median age of 6.4 weeks (interquartile range 6-7.4). Overall, HIV positivity rate at initial test among this cohort was 1.2%. Delayed HIV PCR testing for EID was more likely to yield a positive result [adjusted odds ratio (aOR) = 1.29 (95% confidence interval (CI) 1.09-1.52) p = 0.003]. Infants of mothers not on ART at the time of HIV PCR test and infants who had not received prophylaxis to prevent vertical HIV transmission had significant increased odds of a delayed initial test [aOR = 1.27 (95% CI = 1.18-1.37) p = < 0.0001] and [aOR = 1.43 (95% CI 1.27-1.61) p = < 0.001] respectively. CONCLUSION: An initial HIV PCR test done after 8 weeks of birth is likely to yield a positive result. Barriers to accessing ART for treatment among HIV-infected pregnant and breastfeeding women, and prophylaxis for the HEI were associated with delayed EID. In order to ensure timely EID, programs need to incorporate both facility and community strategy interventions to ensure all pregnant women seek antenatal care and deliver within health facilities.

      9. Acute diarrheal disease outbreak in Muzaffarpur Village, Chandauli District, Uttar Pradesh, Indiaexternal icon
        Gupta G, Singh A, Dikid T, Saroha E, Sodha SV.
        Indian J Public Health. 2021 Jan;65(Supplement):S34-s40.
        BACKGROUND: Acute diarrheal disease (ADD) outbreaks frequently occur in the Gangetic plains of Uttar Pradesh, India. In August 2017, Muzaffarpur village, Uttar Pradesh, reported an ADD outbreak. OBJECTIVES: Outbreak investigation was conducted to find out the epidemiology and to identify the risk factors. METHODS: A 1:1 area-matched case-control study was conducted. Suspected ADD case was defined as ≥3 loose stools or vomiting within 24 h in a Muzaffarpur resident between August 7 and September 9, 2017. A control was defined as an absence of loose stools and vomiting in a resident between August 7 and September 9, 2017. A matched odds ratio (mOR) with 95% confidence intervals (CIs) was calculated. Drinking water was assessed to test for the presence of any contamination. Stool specimens were tested for Vibrio cholerae, and water samples were also tested for any fecal contamination and residual chlorine. RESULTS: Among 70 cases (female = 60%; median age = 12 years, range = 3 months-70 years), two cases died and 35 cases were hospitalized. Area-A in Muzaffarpur had the highest attack rate (8%). The index case washed soiled clothes at well - A1 1 week before other cases occurred. Among 67 case-control pairs, water consumption from well-A1 (mOR: 43.00; 95% CI: 2.60-709.88) and not washing hands with soap (mOR: 2.87; 95% CI: 1.28-6.42) were associated with illness. All seven stool specimens tested negative for V. cholerae. All six water samples, including one from well-A1, tested positive for fecal contamination with <0.2 ppm of residual chlorine. CONCLUSION: This outbreak was associated with consumption of contaminated well water and hand hygiene. We recommended safe water provision, covering wells, handwashing with soap, access to toilets, and improved laboratory capacity for testing diarrheal pathogens.

      10. Low SARS-CoV-2 Transmission in Elementary Schools - Salt Lake County, Utah, December 3, 2020-January 31, 2021external icon
        Hershow RB, Wu K, Lewis NM, Milne AT, Currie D, Smith AR, Lloyd S, Orleans B, Young EL, Freeman B, Schwartz N, Bryant B, Espinosa C, Nakazawa Y, Garza E, Almendares O, Abara WE, Ehlman DC, Waters K, Hill M, Risk I, Oakeson K, Tate JE, Kirking HL, Dunn A, Vallabhaneni S, Hersh AL, Chu VT.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):442-448.
        School closures affected more than 55 million students across the United States when implemented as a strategy to prevent the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Reopening schools requires balancing the risks for SARS-CoV-2 infection to students and staff members against the benefits of in-person learning (2). During December 3, 2020-January 31, 2021, CDC investigated SARS-CoV-2 transmission in 20 elementary schools (kindergarten through grade 6) that had reopened in Salt Lake County, Utah. The 7-day cumulative number of new COVID-19 cases in Salt Lake County during this time ranged from 290 to 670 cases per 100,000 persons.(†) Susceptible(§) school contacts(¶) (students and staff members exposed to SARS-CoV-2 in school) of 51 index patients** (40 students and 11 staff members) were offered SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing. Among 1,041 susceptible school contacts, 735 (70.6%) were tested, and five of 12 cases identified were classified as school-associated; the secondary attack rate among tested susceptible school contacts was 0.7%. Mask use among students was high (86%), and the median distance between students' seats in classrooms was 3 ft. Despite high community incidence and an inability to maintain ≥6 ft of distance between students at all times, SARS-CoV-2 transmission was low in these elementary schools. The results from this investigation add to the increasing evidence that in-person learning can be achieved with minimal SARS-CoV-2 transmission risk when multiple measures to prevent transmission are implemented (3,4).

      11. HIV incidence by male circumcision status from the population-based HIV impact assessment (PHIA) surveys-eight sub-Saharan African countries, 2015-2017external icon
        Hines JZ, Sachathep K, Pals S, Davis SM, Toledo C, Bronson M, Parekh B, Carrasco M, Xaba S, Mandisarisa J, Kamobyi R, Chituwo O, Kirungi WL, Alamo S, Kabuye G, Awor AC, Mmbando S, Simbeye D, Aupokolo MA, Zemburuka B, Nyirenda R, Msungama W, Tarumbiswa T, Manda R, Nuwagaba-Biribonwoha H, Kiggundu V, Thomas AG, Watts H, Voetsch AC, Williams DB.
        J Acquir Immune Defic Syndr. 2021 Mar 16.
        BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually-acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally-representative samples. Data from the Population-based HIV Impact Assessments (PHIAs) were used to compare incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from PHIAs conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia and Zimbabwe from 2015-2017. Incidence was measured using a recent infection testing algorithm, and analyzed by self-reported MC status distinguishing between medical and non-medical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random effects logistic regression model using pooled survey weights. Analyses were age-stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men (0.04% [95% CI: 0.00, 0.10%] versus 0.34% [95% CI: 0.10, 0.57%], respectively; p-value = 0.01); whereas among men 35-59 years, there was no significant incidence difference (1.36% [95% CI: 0.32, 2.39%] versus 0.55% [95% CI: 0.14, 0.67%], respectively; p-value = 0.14). DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally-representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa.

      12. Cholera outbreak in an informal settlement at Shahpur huts, Panchkula District, Haryana State, India, 2019external icon
        Jain A, Choudhary S, Saroha E, Bhatnagar P, Harvey P.
        Indian J Public Health. 2021 Jan;65(Supplement):S51-s54.
        In September 2019, after a reported death due to acute diarrheal disease in Shahpur village, Panchkula district, Haryana state, India, we conducted an outbreak investigation to identify the etiological agent, estimate the burden of disease, and make recommendations to prevent future outbreaks. The suspected cholera case was a resident of Shahpur huts, ≥1 year of age having ≥3 loose stools within a 24-h period between September 1 and 28, 2019 and a laboratory-confirmed cholera case, whose stool specimen tested positive for Vibrio cholerae. We identified 196 suspected cholera cases with a median age of 18 years (range: 1-65 years); 54% (106) being female. The overall attack rate was 8% (196/2,602), and the case fatality rate was 1% (2/196). Tested samples of water from tanks (n = 6), sewage effluent (n = 2), and 22% (4/18) of stool specimens collected from suspected cases were positive for V. cholerae. Strengthening surveillance, improving water, and sanitation systems are recommended to prevent future cholera outbreaks.

      13. Measles outbreak among children ≤15 years old, Jaintia Hills District, Meghalaya, India, 2017external icon
        Lowang D, Dhuria M, Yadav R, Mylliem P, Sodha SV, Khasnobis P.
        Indian J Public Health. 2021 Jan;65(Supplement):S5-s9.
        BACKGROUND: Of 1115 measles outbreaks during 2015 in India, 61,255 suspected measles cases were reported. In 2016, a measles outbreak was reported at East and West Jaintia Hills districts in Meghalaya State, India. OBJECTIVES: The outbreak was investigated to describe the epidemiology, estimate vaccination coverage and vaccine effectiveness (VE), determine risk factors for the disease, and recommend control and prevention measures. METHODS: A measles case was defined as new-onset fever with maculopapular rash occurring between May 1, 2016, and January 21, 2017, in a resident of East and West Jaintia Hills. Cases were identified by active and passive surveillance. Serum and urine samples were collected from cases with laboratory diagnosis for confirmation. A retrospective cohort study was conducted to estimate vaccination coverage, VE, and risk factors for the disease. RESULTS: We identified 382 cases (51% female). The attack rate was 24% with three deaths. The case fatality rate was <1%. The median age was 4 years (range: 3 months-12 years). Among children 12-60 months, 128 (56%) received measles-containing-vaccine first-dose (MCV1), 85 (37%) received measles-containing-vaccine second-dose (MCV2), and 80 (35%) received Vitamin A. VE for MCV1 was 78% and for MCV2 94%. Being unvaccinated for MCV1 (relative risk [RR] = 9.7, 95% confidence interval [CI] = 4.6-20.5) and MCV2 (RR = 17.4, 95% CI = 4.3-69.4) were both strongly associated with illness. CONCLUSIONS: Poor vaccination coverage led to the measles outbreak in East and West Jaintia Hills districts of Meghalaya. Strengthening the routine immunization systems and improving Vitamin A uptake is essential to prevent further outbreaks.

      14. Establishment of Isolation and Noncongregate Hotels During COVID-19 and Symptom Evolution Among People Experiencing Homelessness-Atlanta, Georgia, 2020external icon
        Montgomery MP, Paulin HN, Morris A, Cotton A, Speers A, Boyd AT, Buff AM, Mathews D, Wells A, Marchman C, Gaffga N, Bamrah Morris S, Cavanaugh SS.
        J Public Health Manag Pract. 2021 May-Jun 01;27(3):285-294.
        CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

      15. BACKGROUND: Transgender persons are at high risk for HIV infection. Testing is a key component of the national effort to end the HIV epidemic in the United States. SETTING: Sixty-one local and state health departments and 150 community-based organizations funded by the Centers for Disease Control and Prevention to conduct HIV testing programs. METHODS: We analyzed HIV testing data submitted to the Centers for Disease Control and Prevention by funded health departments and community-based organizations during 2012-2017. Descriptive analysis examined patterns of HIV testing and key outcomes (diagnosis of HIV infection, linkage to HIV medical care, and interview for partner services) among transgender persons. Multivariate robust Poisson regression was used to assess associations between HIV testing outcomes and demographic characteristics, census region, and test setting. RESULTS: A total of 82,818 HIV tests were provided to transgender persons. Of these, 2280 (2.8%) transgender persons were diagnosed with HIV infection; 1556 (1.9%) received a new and 724 (0.9%) a previous diagnosis with HIV infection. The highest percentage of new HIV diagnosis was found among persons tested in correctional settings (4.6%), non-Hispanic Blacks (3.5%) and transgender women (2.4%). Among newly diagnosed persons, 85.0% were linked to HIV medical care ≤90 days after diagnosis and 63.5% were interviewed for partner services. CONCLUSIONS: HIV positivity was high, and the delivery of partner services was low, among transgender persons. HIV testing outcomes among transgender persons varied significantly by demographic characteristics and test setting. HIV prevention programs that are responsive to the needs of transgender persons may address gender-related disparities in HIV testing outcomes.

      16. Underlying cardiopulmonary conditions as a risk factor for influenza and respiratory syncytial virus infection among community-dwelling adults aged ≥ 65 years in Thailand: Findings from a two-year prospective cohort studyexternal icon
        Praphasiri P, Shrestha M, Patumanond J, Nakphook S, Chawalchitiporn S, Ditsungnoen D, Dawood FS, Mott JA, Prasert K.
        Influenza Other Respir Viruses. 2021 Mar 25.
        BACKGROUND: Adults with cardiopulmonary conditions may be at increased risk of influenza and respiratory syncytial virus (RSV) infection, but it is not well-established and few data are available from middle-income countries. METHODS: Using data from a prospective cohort study of influenza vaccine effectiveness, we estimated and compared the incidences of influenza and RSV between community-dwelling Thai adults aged ≥ 65 years with and without cardiopulmonary conditions. During May 2015-May 2017, older adults in a rural province in Thailand were followed-up with weekly surveillance for acute respiratory illness (ARI), defined broadly as new onset or worsening of cough with or without fever, and hospitalized ARI. When ill, nasal self-swabs and/or nasopharyngeal swabs were collected for reverse-transcription polymerase chain reaction testing. We used Poisson regression to calculate incidence rate ratios (IRR), adjusting for age, sex, current smoking, number of hospital visits, weekly influenza activity, and influenza vaccination. RESULTS: Overall, 3220 adults with a median age of 71 years (IQR 68-76) were enrolled; 1324 (41.1%) were male; and 313 (9.7%) had ≥1 underlying cardiopulmonary condition, most commonly chronic obstructive pulmonary disease (131; 41.2%) or asthma (73; 23.3%). Participants with cardiopulmonary conditions had higher incidences of ARI, influenza, and RSV than those without (Adjusted IRR: 1.84, 95% CI 1.64-2.07; 1.86, 95% CI 1.07-3.26; 2.04, 95% CI 1.11-3.76, respectively). CONCLUSION: Older adults in rural Thailand with cardiopulmonary conditions have increased rates of ARI, influenza, and RSV infections. Our findings support efforts to ensure this population has access to influenza vaccines and other respiratory illness prevention measures.

      17. Influenza and other respiratory viral infections associated with absence from school among schoolchildren in Pittsburgh, Pennsylvania, USA: a cohort studyexternal icon
        Read JM, Zimmer S, Vukotich C, Schweizer ML, Galloway D, Lingle C, Yearwood G, Calderone P, Noble E, Quadelacy T, Grantz K, Rinaldo C, Gao H, Rainey J, Uzicanin A, Cummings DA.
        BMC Infect Dis. 2021 Mar 22;21(1):291.
        BACKGROUND: Information on the etiology and age-specific burden of respiratory viral infections among school-aged children remains limited. Though school aged children are often recognized as driving the transmission of influenza as well as other respiratory viruses, little detailed information is available on the distribution of respiratory infections among children of different ages within this group. Factors other than age including gender and time spent in school may also be important in determining risk of infection but have been little studied in this age group. METHODS: We conducted a cohort study to determine the etiology of influenza like illness (ILI) among 2519 K-12 students during the 2012-13 influenza season. We obtained nasal swabs from students with ILI-related absences. Generalized linear mixed-effect regressions determined associations of outcomes, including ILI and laboratory-confirmed respiratory virus infection, with school grade and other covariates. RESULTS: Overall, 459 swabs were obtained from 552 ILI-related absences. Respiratory viruses were found in 292 (63.6%) samples. Influenza was found in 189 (41.2%) samples. With influenza B found in 134 (70.9%). Rates of influenza B were significantly higher in grades 1 (10.1, 95% CI 6.8-14.4%), 2 (9.7, 6.6-13.6%), 3 (9.3, 6.3-13.2%), and 4 (9.9, 6.8-13.8%) than in kindergarteners (3.2, 1.5-6.0%). After accounting for grade, sex and self-reported vaccination status, influenza B infection risk was lower among kindergarteners in half-day programs compared to kindergarteners in full-day programs (OR = 0.19; 95% CI 0.08-0.45). CONCLUSIONS: ILI and influenza infection is concentrated in younger schoolchildren. Reduced infection by respiratory viruses is associated with a truncated school day for kindergarteners but this finding requires further investigation in other grades and populations.

      18. Sociodemographic, Ecological, and Spatiotemporal Factors Associated with Human Immunodeficiency Virus Drug Resistance in Florida: A Retrospective Analysisexternal icon
        Rich SN, Poschman K, Hu H, Mavian C, Cook RL, Salemi M, Spencer EC, Prosperi M.
        J Infect Dis. 2021 Mar 3;223(5):866-875.
        BACKGROUND: Persons living with human immunodeficiency virus (HIV) with resistance to antiretroviral therapy are vulnerable to adverse HIV-related health outcomes and can contribute to transmission of HIV drug resistance (HIVDR) when nonvirally suppressed. The degree to which HIVDR contributes to disease burden in Florida-the US state with the highest HIV incidence- is unknown. METHODS: We explored sociodemographic, ecological, and spatiotemporal associations of HIVDR. HIV-1 sequences (n = 34 447) collected during 2012-2017 were obtained from the Florida Department of Health. HIVDR was categorized by resistance class, including resistance to nucleoside reverse-transcriptase , nonnucleoside reverse-transcriptase , protease , and integrase inhibitors. Multidrug resistance and transmitted drug resistance were also evaluated. Multivariable fixed-effects logistic regression models were fitted to associate individual- and county-level sociodemographic and ecological health indicators with HIVDR. RESULTS: The HIVDR prevalence was 19.2% (nucleoside reverse-transcriptase inhibitor resistance), 29.7% (nonnucleoside reverse-transcriptase inhibitor resistance), 6.6% (protease inhibitor resistance), 23.5% (transmitted drug resistance), 13.2% (multidrug resistance), and 8.2% (integrase strand transfer inhibitor resistance), with significant variation by Florida county. Individuals who were older, black, or acquired HIV through mother-to-child transmission had significantly higher odds of HIVDR. HIVDR was linked to counties with lower socioeconomic status, higher rates of unemployment, and poor mental health. CONCLUSIONS: Our findings indicate that HIVDR prevalence is higher in Florida than aggregate North American estimates with significant geographic and socioecological heterogeneity.

      19. Comparison of common acute respiratory infection case definitions for identification of hospitalized influenza cases at a population-based surveillance site in Egyptexternal icon
        Rowlinson E, Peters L, Mansour A, Mansour H, Azazzy N, Said M, Samy S, Abbas E, Abu Elsood H, Fahim M, Eid A, Reaves E, Van Beneden C, Hamid S, Olsen S, Fitzner J, Dueger E.
        PLoS One. 2021 ;16(3):e0248563.
        BACKGROUND: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases. METHODS: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia. RESULTS: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only). CONCLUSIONS: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.

      20. Treatment outcomes of isoniazid-resistant (Rifampicin susceptible) tuberculosis patients in Uzbekistan, 2017–2018external icon
        Sayfutdinov Z, Kumar A, Nabirova D, Gadoev J, Turaev L, Sultanov S, Alaverdyan S, Parpieva N.
        Int J Environ Res Public Health. 2021 ;18(6):1-8.
        Tuberculosis patients “resistant to isoniazid and susceptible to rifampicin (Hr-TB)” remain neglected, despite a high burden and poor outcomes. The World Health Organization (WHO) recommends a 6 month regimen consisting of levofloxacin, rifampicin, ethambutol, and pyrazinamide (LRZE) to treat Hr-TB. In contrast, Uzbekistan uses a 9 month regimen (LRZE plus a second-line injectable in the first 3 months). We aimed to assess the treatment outcomes of this novel regimen among Hr-TB patients treated in two regions of Uzbekistan (Fergana and Bukhara) in 2017–2018. We conducted a cohort study involving secondary analysis of routine surveillance data. Of 132 Hr-TB patients, 105 (80%) were successfully treated. Death was the predominant unsuccessful outcome (13, 10%) followed by “treatment failure” (10, 8%) and “lost to follow-up” (4, 2%). High treatment success is an indicator of the potential effectiveness of the novel regimen and adds to the limited global evidence on this issue. However, the sample size was small and there was no comparison group. Since the study was conducted in two regions of Uzbekistan only, the findings have limited generalizability. We recommend future research using an adequate sample size and an appropriate study design (randomized controlled trial or prospective cohort with a control group receiving the WHO-recommended regimen).

      21. Key Factors for Successful Implementation of HIV Prevention Services by THRIVE Community Collaborativesexternal icon
        Tanner MR, Iqbal K, Dominguez KL, Zhu W, Obi J, Hoover KW.
        Public Health Rep. 2021 Mar 25:333549211005793.
        OBJECTIVE: The Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project created collaboratives of health departments, community-based organizations, and clinical partners to improve HIV prevention services for men who have sex with men (MSM) and transgender women (TGW) of color. We administered an online survey from September 2018 through February 2019 to assess the collaboratives. METHODS: We used a Likert scale to measure agreement on collaborative characteristics. We used Fisher exact tests to compare success ratings by health department employment and funding status. We created a radar chart to compare the percentage agreement on key characteristics of the most and least successful collaboratives. We used a general inductive approach in the qualitative analysis of open-ended question responses. RESULTS: Of 262 survey recipients, 133 responded (51%); 49 (37%) respondents were from health departments. Most respondents (≥70%) agreed that their collaborative is diverse, cooperates, meets regularly, has realistic goals, has effective leadership, and has effective communication. Most respondents (87%) rated their collaborative as successful in implementing HIV prevention services for MSM and TGW of color. Comparison of the most and least successful collaborative found the greatest difference in respondent agreement in the presence of effective leadership, communication, and adequate resources. The most commonly cited challenge in the open-ended questions was inadequate resources. The most commonly cited success was increased provision of services, particularly preexposure prophylaxis. CONCLUSIONS: Community collaboratives were considered successful by most collaborative members and may be an effective part of HIV prevention strategies.

      22. Universal access to Xpert MTB/RIF testing for diagnosis of tuberculosis in Uzbekistan: How well are we doing?external icon
        Turaev L, Kumar A, Nabirova D, Alaverdyan S, Parpieva N, Abdusamatova B.
        Int J Environ Res Public Health. 2021 ;18(6):1-13.
        As per national guidelines in Uzbekistan, all presumptive tuberculosis patients should be tested using the Xpert MTB/RIF assay for diagnosing tuberculosis. There is no published evidence how well this is being implemented. In this paper, we report on the Xpert coverage among presumptive tuberculosis patients in 2018 and 2019, factors associated with non-testing and delays involved. Analysis of national aggregate data indicated that Xpert testing increased from 24% in 2018 to 46% in 2019, with variation among the regions: 21% in Tashkent region to 100% in Karakalpakstan. In a cohort (January–March 2019) constituted of 40 randomly selected health facilities in Tashkent city and Bukhara region, there were 1940 patients of whom 832 (43%, 95% confidence interval (CI): 41–45%) were not Xpert-tested. Non-testing was significantly higher in Bukhara region (73%) compared to Tashkent city (28%). In multivariable analysis, patient’s age, distance between primary health centre (PHC) and Xpert laboratory, diagnostic capacity and site of PHC were associated with non-testing. The median (interquartile range) duration from date of initial visit to PHC to receiving results was 1 (1–2) day in Tashkent city compared to 3 (1–6) days in Bukhara region (p-value <0.001). While there is commendable progress, universal access to Xpert testing is not a reality yet.

      23. Whole-genome sequencing of SARS-CoV-2 reveals the detection of G614 variant in Pakistanexternal icon
        Umair M, Ikram A, Salman M, Khurshid A, Alam M, Badar N, Suleman R, Tahir F, Sharif S, Montgomery J, Whitmer S, Klena J.
        PLoS One. 2021 ;16(3):e0248371.
        Since its emergence in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide including Pakistan. During the pandemic, whole genome sequencing has played an important role in understanding the evolution and genomic diversity of SARS-CoV-2. Although an unprecedented number of SARS-CoV-2 full genomes have been submitted in GISAID and NCBI, data from Pakistan is scarce. We report the sequencing, genomic characterization, and phylogenetic analysis of five SARS-CoV-2 strains isolated from patients in Pakistan. The oropharyngeal swabs of patients that were confirmed positive for SARS-CoV-2 through real-time RT-PCR at National Institute of Health, Pakistan, were selected for whole-genome sequencing. Sequencing was performed using NEBNext Ultra II Directional RNA Library Prep kit for Illumina (NEW ENGLAND BioLabs Inc., MA, US) and Illumina iSeq 100 instrument (Illumina, San Diego, US). Based on whole-genome analysis, three Pakistani SARS-CoV-2 strains clustered into the 20A (GH) clade along with the strains from Oman, Slovakia, United States, and Pakistani strain EPI_ISL_513925. The two 19B (S)-clade strains were closely related to viruses from India and Oman. Overall, twenty-nine amino acid mutations were detected in the current study genome sequences, including fifteen missense and four novel mutations. Notably, we have found a D614G (aspartic acid to glycine) mutation in spike protein of the sequences from the GH clade. The G614 variant carrying the characteristic D614G mutation has been shown to be more infectious that lead to its rapid spread worldwide. This report highlights the detection of GH and S clade strains and G614 variant from Pakistan warranting large-scale whole-genome sequencing of strains prevalent in different regions to understand virus evolution and to explore their genetic diversity.

      24. Update on Hepatitis A Managementexternal icon
        Weng MK, Harris AM, Nelson NP.
        Jama. 2021 Jan 26;325(4):401.

    • Disease Reservoirs and Vectors
      1. Preventing the cross-border spread of zoonotic diseases: Multisectoral community engagement to characterize animal mobility-Uganda, 2020external icon
        Medley AM, Gasanani J, Nyolimati CA, McIntyre E, Ward S, Okuyo B, Kabiito D, Bender C, Jafari Z, LaMorde M, Babigumira PA, Nakiire L, Agwang C, Merrill R, Ndumu D, Doris K.
        Zoonoses Public Health. 2021 Mar 21.
        In Uganda, the borders are highly porous to animal movement, which may contribute to zoonotic disease spread. We piloted an animal adaptation of an existing human-focused toolkit to collect data on animal movement patterns and interactions to inform One Health programs. During January 2020, we conducted focus group discussions and key informant interviews with participatory mapping of 2 national-level One Health stakeholders and 2 local-level abattoir representatives from Kampala. Zoonotic disease hotspots changed in 2020 compared with reports from 2017-2019. In contrast to local-level participants, national-level participants highlighted districts rather than specific locations. Everyone discussed livestock species; only national-level participants mentioned wildlife. Participants described seasonality differently. Stakeholders used the results to identify locations for zoonotic disease interventions and sites for future data collection. This implementation of an animal-adapted population mobility mapping exercise highlights the importance of multisectoral initiatives to promote One Health border health approaches.

    • Environmental Health
      1. The biomonitoring of Great Lakes populations-iii program: The Milwaukee Angler Projectexternal icon
        Li Z, Serio T, Meiman J, He X, Ragin-Wilson A.
        J Environ Health. 2021 ;83(6):40-43.

      2. The 2018 ATSDR mixture framework recommends three approaches including the hazard index (HI) for environmental mixture toxicity assessment. Per- and polyfluoroalkyls (PFAS) are found in our environment and general populations. Recent experimental mixture toxicity studies of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and an assessment of 17 PFAS indicate the use of additivity for their joint toxicity assessment. The aim of this investigation was to detail the stepwise procedures and examine the extent and use of the HI approach for PFAS mixture assessment. Using estimated general public lifetime exposures (high, medium, and low), binary mixtures of PFOS and PFOA yielded, respectively, hazard indices (HIs) of 30.67, 8.33, and 3.63 for developmental toxicity; 10.67, 5.04, and 2.34 for immunological toxicity; 3.57, 1.68, and 0.78 for endocrine toxicity; 4.51, 1.73, and 0.79 for hepatic toxicity; and 15.08, 2.29, and 0.88 for reproductive toxicity. A heterogeneous mixture of PFOA, PFAS, dioxin (CDD), and polybrominated compounds (PBDE) for high exposure scenario yielded HIs of 30.99 for developmental, 10.77 for immunological, 3.64 for endocrine, 4.61 for hepatic, and 17.36 for reproductive effects. The HI values are used as a screening tool; the potential concern for exposures rises as HI values increase. For HI values >1, a follow-up including further analysis of specific exposures, use of internal dosimetry, and uncertainty factors is conducted before recommending appropriate actions. The HI approach appears suitable to address present-day PFAS public health concerns for initial assessment of multiple health effects, until further insights are gained into their mechanistic toxicology.The findings and conclusions in this article are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

      3. Bayesian toxicokinetic modeling of cadmium exposure in Chinese populationexternal icon
        Qing Y, Yang J, Zhang Q, Zhu Y, Ruiz P, Wu M, Zhao G, Zhao Q, Liu H, Cai H, Qin L, Zheng W, He G.
        J Hazard Mater. 2021 ;413.
        Cadmium (Cd) is a toxic heavy metal widely present in the environment. Estimating its internal levels for a given external exposure using toxicokinetic (TK) models is key to the human health risk assessment of Cd. In this study, existing Cd TK models were adapted to develop a one-compartment TK model and a multi-compartment physiologically based toxicokinetic (PBTK) model by estimating the characteristics of Cd kinetics based on Cd exposure data from 814 Chinese residents. Both models not only considered the effect of gender difference on Cd kinetics, but also described the model parameters in terms of distributions to reflect individual variability. For both models, the posterior distributions of sensitive parameters were estimated using the Markov chain-Monte Carlo method (MCMC) and the approximate Bayesian computation-MCMC algorithm (ABC-MCMC). Validation with the test dataset showed 1.4–22.5% improvement in the root mean square error (RMSE) over the original models. After a systematic literature search, the optimized models showed acceptable prediction on other Chinese datasets. The study provides a method for parameter optimization of TK models under different exposure environment, and the validated models can serve as new quantitative assessment tools for the risk assessment of Cd in the Chinese population.

      4. Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Womenexternal icon
        Reeves KW, Vieyra G, Grimes NP, Meliker J, Jackson RD, Wactawski-Wende J, Wallace R, Zoeller RT, Bigelow C, Hankinson SE, Manson JE, Cauley JA, Calafat AM.
        J Clin Endocrinol Metab. 2021 Mar 23.
        BACKGROUND: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI). METHODS: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N=1255). We measured thirteen phthalate biomarkers and creatinine in 2-3 urine samples per participant collected over 3 years, when all participants were cancer-free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. RESULTS: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT non-users, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT non-users and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%, 95% CI -2.81 - -0.78%) or mono-carboxynonyl phthalate (-1.84%, 95% CI -2.80 - -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. DISCUSSION: Certain phthalate biomarkers are associated with greater percent decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.

    • Food Safety
      1. Ability of whole-genome sequencing to refine a salmonella i 4,[5],12:I:-cluster in New York state and detect a multistate outbreak linked to raw poultryexternal icon
        Huth P, Wirth SE, Baker D, Nicholas DC, Douris A, Freiman J, Kline KE, Devinney K, Gläsker S, Schwensohn C.
        Food Prot Trends. 2021 ;41(2):239-245.
        Whole-genome sequencing (WGS) has proven to be a more powerful tool than pulsed-field gel electrophoresis for foodborne illness cluster definition because of improved resolution. Between November 2017 and May 2018, the New York State (NYS) Dept. of Health investigated 10 cases of Salmonella I 4,[5],12:i:-with pulsed-field gel electrophoresis pattern JPXX01.0621; comparison of case exposures did not identify a common source of infection. In June 2018, the NYS Dept. of Health’s Wadsworth Center analyzed the isolates using WGS and defined a subcluster of five isolates related within zero to six single-nucleotide polymorphisms. The National Center for Biotechnology Information Pathogen Detection browser advanced this investigation by identifying additional clinical and food (chicken) isolates related within zero to eight single-nucleotide polymorphisms to the original subcluster. Comparison of WGS-related isolates would support the hypothesis that illness was associated with exposure to a kosher poultry product. This outbreak ultimately consisted of 25 cases from six states. Of 20 cases interviewed, all reported chicken consumption, and of those able to recall brand information, 83% cited a brand produced at a facility linked to the WGS-related chicken isolates. This paper demonstrates how WGS was able to refine a Salmonella I 4,[5],12:i:-cluster in NYS to uncover a multistate outbreak linked to raw poultry.

      2. Outbreak investigation of foodborne illness among political rally attendees, Cuddalore, Tamil Nadu, Indiaexternal icon
        Patil AA, Velayudhan A, Durairaj GK, Khasnobis P, Sodha SV.
        Indian J Public Health. 2021 Jan;65(Supplement):S55-s58.
        In July 2015, we investigated a foodborne illness outbreak in Sithalikuppam and Verupachi villages, Cuddalore district, Tamil Nadu, among the political rally attendees to determine the risk factors for illness. We conducted a retrospective cohort study, calculated risk ratio for the food exposures, and cultured stool specimens. Of 55 rally attendees, we identified 36 (65%) case patients; 32 (89%) had diarrhea and 20 (56%) had vomiting. Median incubation period was 14 h. Eighty-nine percent (32/36) of those who ate lemon rice at dinner had illness compared to 21% (4/19) of those who did not (RR 4.2). Of the six nonattendees who ate leftovers on July 25, all ate only lemon rice and became ill. Stool cultures were negative for Salmonella, Shigella, and Vibrio species. Lemon rice was probably contaminated with enterotoxins such as from Bacillus cereus. Our findings highlighted need for community food safety education and importance of thorough outbreak investigations.

      3. Foodborne Disease outbreak associated with eating Gaajar Halwa at a Wedding - Palghar District, Maharashtra, India, 2018external icon
        Vardhan V, Dikid T, Yadav R, Patil R, Awate P.
        Indian J Public Health. 2021 Jan;65(Supplement):S10-s13.
        BACKGROUND: A foodborne disease outbreak among wedding attendees from Makunsar village, Palghar district, Maharashtra state, India, was reported on February 18, 2018. OBJECTIVES: The outbreak investigation was conducted to find out the epidemiology of the outbreak and to identify the etiologic agent and risk factors. METHODS: A case-control study was carried out, where cases (patients), controls, and food handlers were interviewed and leftover foods were collected for culture. A case was defined as a person having vomiting or diarrhea (i.e., ≥3 loose stools within 24 h) who attended the wedding ceremony at Makunsar village, Palghar district, Maharashtra, on February 18, 2018. Attack rate and odds ratio (OR) were calculated with 95% confidence intervals (CIs). RESULTS: Out of 75 cases, 63% were female. Altogether, forty-two (56%) cases were hospitalized, and later on, all of them were discharged from hospital without any mortality. About 93%, 68%, 43%, and 41% of the cases reported with vomiting, nausea, abdominal pain, and diarrhea, respectively. The median incubation period was found to be 4 h (range: 2-8 h). Eating gaajar halwa (carrot pudding) was significantly associated with illness (OR: 12.8; 95% CI: 3.5-46). Gaajar halwa is prepared with khoa, a perishable milk product. The gaajar halwa culture yielded no growth. CONCLUSION: The case-patients' clinical presentation and incubation period were consistent with enterotoxin-producing Staphylococcus aureus as the probable etiologic agent. The epidemiologic investigation identified the probable etiologic agent and food source in a low-resource community setting. Community food handlers were educated on food preparation hygiene and safe storage measures to prevent future outbreaks.

      4. Shellfish poisoning outbreaks in Cuddalore District, Tamil Nadu, Indiaexternal icon
        Velayudhan A, Nayak J, Murhekar MV, Dikid T, Sodha SV.
        Indian J Public Health. 2021 Jan;65(Supplement):S29-s33.
        BACKGROUND: Two suspected shellfish poisoning events were reported in Cuddalore District in Tamil Nadu, India, between January and April 2015. OBJECTIVES: The study was conducted to confirm the outbreaks and to identify the source and risk factors. METHODS: For both outbreaks, a case was defined as a person with nausea, vomiting, or dizziness. Sociodemographic details and symptoms were noted down. Data were also collected in a standard 3-day food frequency questionnaire, along with a collection of clam samples. A case-control study was initiated in the April outbreak. Stool samples were collected from cases, and clam vendors were interviewed. RESULTS: In an outbreak that happened in January, all the twenty people reported to be consumed clams were diagnosed as cases (100% attack rate, 100% exposure rate). In the April outbreak, we identified 199 cases (95% attack rate). In both outbreaks, the clams were identified as genus Meretrix meretrix. The most common reported symptoms were dizziness and vomiting. The clams heated and consumed within 30-60 min. No heavy metals or chemicals were detected in the clams, but assays for testing shellfish toxins were unavailable. All 64 selected cases reported clam consumption (100% exposure rate) as did 11 controls (17% exposure rate). Illness was associated with a history of eating of clams (odds ratio = 314, 95% confidence interval = 39-512). Of the six stool samples tested, all were culture negative for Salmonella, Shigella, and Vibrio cholerae. The water at both sites was contaminated with garbage and sewage. CONCLUSION: Coordinated and timely efforts by a multidisciplinary team of epidemiologists, marine biologists, and food safety officers led to the outbreaks' containment.

    • Health Disparities
      1. Homelessness is associated with a multitude of poor health outcomes. However, the full extent of the risks associated with homelessness are not possible to quantify without reliable population data. Here, we outline three federal, publicly-available data sources available to estimate the number of people experiencing homelessness in the United States. We describe the appropriate uses and limitations of each data source in the context of infectious disease epidemiology. These data sources provide an opportunity to expand current research and develop actionable analyses.

    • Health Economics
      1. Objective: To assess healthcare utilization, lost work days, and bed days among workers with chronic obstructive pulmonary disease (COPD) by industry and occupation. Methods: The 2014-2018 National Health Interview Survey (NHIS) data were analyzed. Results: Among workers with COPD the highest odds of reporting an emergency room (ER) visit and lost work days were observed among workers aged &gt;=65 years, females, those with no health insurance, and current combustible tobacco users. Workers with COPD in the information industry and computer and mathematical occupation reported highest odds of an ER visit and utilities industry workers reported highest odds for lost work days. Conclusions: The high healthcare utilization and lost work days among workers with COPD in certain industries and occupations underscores the importance of continued surveillance and tailored interventions to reduce disease burden and improve worker health.

      2. Cost-effectiveness of pediatric norovirus vaccination in daycare settingsexternal icon
        Steimle LN, Havumaki J, Eisenberg MC, Eisenberg JN, Prosser LA, Pike J, Ortega-Sanchez IR, Mattison CP, Hall AJ, Steele MK, Lopman BA, Hutton DW.
        Vaccine. 2021 Mar 16.
        OBJECTIVE: Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. METHODS: We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. RESULTS: A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. CONCLUSION: Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.

      3. Health insurance coverage has increased overtime. This study examined the associations between health insurance status and adoption of health-related behaviors among US adults. Using data collected through the 2017 Behavioral Risk Factor Surveillance System on health insurance coverage and type of insurance, we examined four health-related behaviors (i.e., no tobacco use, nondrinking or moderate drinking, meeting aerobic physical activity recommendations, and having a healthy body weight) and their associations with health insurance status. We conducted log-linear regression analyses to assess the associations with adjusting for potential confounders. Results showed the percentages of adults who reported no tobacco use or meeting physical activity recommendations were significantly higher, and the percentages of adults with a healthy body weight were significantly lower among those who were insured versus uninsured, or among adults with private insurance versus uninsured. Adults with health insurance also had a higher prevalence of reporting all 4 health-related behaviors than those uninsured. These patterns persisted after multivariable adjustment for potential confounders including sociodemographics, routine checkup, and number of chronic diseases. Adults with public insurance were 7% more likely to report no tobacco use than adults who were uninsured. Additionally, adults with private insurance were 8% and 7% more likely to report no tobacco use and meeting physical activity recommendations, respectively, but 10% less likely to report nondrinking or moderate drinking than adults with public insurance. In conclusion, we found significant associations existed between having health insurance coverage and engaging in some health-related behaviors among US adults.

    • Healthcare Associated Infections
      1. Chlorhexidine gluconate (CHG) is an antiseptic that is widely used in healthcare due to its excellent safety profile and wide spectrum of activity. Daily bathing with CHG has proven to be effective in the prevention of healthcare-associated infections and multidrug-resistant pathogen decolonization. Despite the proven benefits of CHG use, there remain concerns and unanswered questions about the potential for unintended microbial consequences of routine CHG bathing. This review aims to explore some of these questions.

      2. Salmonella Infantis, a common contaminant of poultry products, is known to harbor mobile genetic elements that confer multi-drug resistance (MDR) and have been detected in many continents. Here, we report four MDR S. Infantis strains recovered from poultry house environments in Santa Cruz Island of the Galapagos showing extended-spectrum β-lactamase (ESBL) resistance and reduced fluoroquinolone susceptibility. Whole-genome sequencing (WGS) revealed the presence of the ESBL-conferring blaCTX-M-65 gene in an IncFIB-like plasmid in three S. Infantis isolates. Multi-locus sequence typing (MLST) and single nucleotide variant/polymorphism (SNP) SNVPhyl analysis showed that the S. Infantis isolates belong to sequence type ST32, likely share a common ancestor, and are closely related (1–3 SNP difference) to blaCTX-M-65-containing clinical and veterinary S. Infantis isolates from the United States and Latin America. Furthermore, phylogenetic analysis of SNPs following core-genome alignment (i.e., ParSNP) inferred close relatedness between the S. Infantis isolates from Galapagos and the United States. Prophage typing confirmed the close relationship among the Galapagos S. Infantis and was useful in distinguishing them from the United States isolates. This is the first report of MDR blaCTX-M-65-containing S. Infantis in the Galapagos Islands and highlights the need for increased monitoring and surveillance programs to determine prevalence, sources, and reservoirs of MDR pathogens.

      3. A Learning Collaborative to Improve Antibiotic Prescribing in Primary Care Pediatric Practicesexternal icon
        Norlin C, Fleming-Dutra K, Mapp J, Monti J, Shaw A, Bartoces M, Barger K, Emmer S, Dolins JC.
        Clin Pediatr (Phila). 2021 Mar 25:99228211001623.
        An American Academy of Pediatrics State Chapter organized a 6-month, mostly online quality improvement learning collaborative to improve antibiotic prescribing and patient education for upper respiratory infection (URI) and acute otitis media (AOM). Practices submitted data on quality measures at baseline, monthly, and 4 months post-project. Fifty-three clinicians from 6 independent, private primary care pediatric practices participated. Use of first-line antibiotics for AOM increased from 63.5% at baseline to 80.4% 4 months post-project. Use of safety-net antibiotic prescriptions (SNAP) for AOM increased from 4.5% to 16.9%. Educating patients about management for URI increased from 66.1% to 88.0% and for AOM from 20.4% to 85.6%. Practices maintained high performance for not prescribing antibiotics for URI (94.4% to 96.2%). Leveraging local relationships and national resources, this replicable antibiotic stewardship project engaged independent private practices to improve patient education for URI and AOM and prescribing and use of SNAP for AOM.

      4. Real-Time Virtual Infection Prevention and Control Assessments in Skilled Nursing Homes, New York, March 2020 - A Pilot Projectexternal icon
        Ostrowsky B, Weil LM, Olaisen R, Stricof R, Adams E, Tsivitis M, Eramo A, Giardina R, Erazo R, Southwick K, Greenko J, Lutterloh E, Blog D, Green C, Carrasco K, Fernandez R, Vallabhaneni S, Quinn M, Kogut S, Bennett J, Chico D, Luzinas M.
        Infect Control Hosp Epidemiol. 2021 Mar 19:1-27.
        OBJECTIVE: to describe a pilot infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal two-week period when the region became the nation's epicenter for COVID-19. DESIGN: a telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity. PARTICIPANTS: SNFs in 14 NYS counties including New York City. INTERVENTION: a three-component remote IPC assessment: 1) screening tool; 2) telephone IPC checklist; and 3) COVID-19 video IPC assessment ("COVIDeo"). RESULTS: 92 SNFs completed the IPC screening tool and checklist; 52/92 (57%) were conducted as part COVID-19 investigations, and 40/92 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14/40 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26/92 (28%) of assessments and provided observations that other tools would have missed including: PPE (personal protective equipment) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took approximately one hour each, reached an estimated four times as many SNFs as onsite visits in a similar timeframe. CONCLUSIONS: Remote IPC assessments by telephone and video provided a timely and feasible method to assess the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across NYS and in various healthcare facility types. Similar methods have been adapted nationally through CDC.

      5. Antimicrobial Susceptibility Profiles to Predict the Presence of Carbapenemase Genes among Carbapenem-Resistant Pseudomonas aeruginosaexternal icon
        Vallabhaneni S, Huang JY, Grass JE, Bhatnagar A, Sabour S, Lutgring JD, Campbell D, Karlsson M, Kallen AJ, Nazarian E, Snavely EA, Morris S, Wang C, Lee R, Koag M, Lewis R, Garcia B, Brown AC, Walters MS.
        J Clin Microbiol. 2021 Mar 24.
        Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) with carbapenamase-producing (CP) genes is critical for preventing transmission. Our objective was to assess whether certain antimicrobial susceptibility testing (AST) profiles can efficiently identify CP-CRPA.Methods: We defined CRPA as P. aeruginosa with imipenem or meropenem MICs of ≥8μg/ml; CP-CRPA were CRPA with CP genes (bla (KPC)/bla (IMP)/bla (NDM)/bla (VIM)). We assessed the sensitivity and specificity of AST profiles to detect CP-CRPA among CRPA collected by CDC's Antibiotic Resistance Laboratory Network (AR Lab Network) and the Emerging Infections Program (EIP) during 2017-2019.Results: Three percent (195/6192) of AR Lab Network CRPA were CP-CRPA. Among CRPA, adding not susceptible (NS) to cefepime or ceftazidime to the definition had 91% sensitivity and 50% specificity for identifying CP-CRPA; NS to ceftolozane-tazobactam had 100% sensitivity and 86% specificity. Of 965 EIP CRPA evaluated for CP genes, seven CP-CRPA were identified; 6 of 7 were NS to cefepime and ceftazidime, and all 7 were NS to ceftolozane-tazobactam. Among 4182 EIP isolates, clinical laboratory AST results were available for 96% for cefepime, 80% for ceftazidime, and 4% for ceftolozane-tazobactam. The number of CRPA needed to test (NNT) to identify one CP-CRPA decreased from 138 to 64 if the definition of NS to cefepime or ceftazidime was used and to 7 with NS to ceftolozane-tazobactam.Conclusion: Adding not susceptible to cefepime or ceftazidime to CRPA carbapenemase testing criteria would reduce the NNT by half and can be implemented in most clinical laboratories; adding not susceptible to ceftolozane-tazobactam could be even more predictive once AST for this drug is more widely available.

    • Immunity and Immunization
      1. Commentary: Addressing vaccine hesitancy in the age of COVID-19external icon
        Fisher A, Mbaeyi S, Cohn A.
        Acad Pediatr. 2021 Mar 19.

      2. INTRODUCTION: In 2006 and 2008, two live, oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), were introduced into the routine immunization program in the United States. A previous rotavirus vaccine, RotaShield, was associated with an increased risk of intussusception, with data suggesting an age-dependent variation in risk. Advisory Committee on Immunization Practices (ACIP) currently recommends that RV5 or RV1 immunization be initiated by age 14 weeks and 6 days and completed by 8 months 0 days. METHODS: We searched for U.S. VAERS reports of RV5, RV1, or unknown rotavirus vaccine brand among individuals aged ≥8 months. We analyzed reports by 2 age groups (individuals aged ≥8 months-≤5 years and ≥6 years), vaccine brand name, adverse event (AE) reported, classification of seriousness (death, non-death serious, and non-serious) and mode of exposure (direct vs. indirect exposure). For serious reports we reviewed available medical records and assigned a primary diagnosis. RESULTS: VAERS received a total of 344 U.S. reports following rotavirus vaccination among individuals ≥8 months of age, 32 (9.3%) were serious. In the younger age-group, 307 (99%) of 309 reports followed direct vaccination of the child. In contrast, in individuals aged ≥6 years, 21 (60%) of 35 reports were via potential indirect exposure to a vaccinated child. The frequently reported AEs in the younger age-group were inappropriate schedule of drug administration 104 (34%) and drug administered to patient of inappropriate age 45 (15%); in the older group these were accidental exposure 9 (26%) and eye irritation 7 (20%). No difference in the safety profile was observed between RV1 and RV5. CONCLUSIONS: We did not identify any unexpected AEs for RV vaccines among individuals aged ≥8 months. Health care providers should adhere to the ACIP recommended schedule and older individuals should apply necessary precautions to prevent potential secondary exposure from vaccinated children.

      3. County-Level COVID-19 Vaccination Coverage and Social Vulnerability - United States, December 14, 2020-March 1, 2021external icon
        Hughes MM, Wang A, Grossman MK, Pun E, Whiteman A, Deng L, Hallisey E, Sharpe JD, Ussery EN, Stokley S, Musial T, Weller DL, Murthy BP, Reynolds L, Gibbs-Scharf L, Harris L, Ritchey MD, Toblin RL.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):431-436.
        The U.S. COVID-19 vaccination program began in December 2020, and ensuring equitable COVID-19 vaccine access remains a national priority.* COVID-19 has disproportionately affected racial/ethnic minority groups and those who are economically and socially disadvantaged (1,2). Thus, achieving not just vaccine equality (i.e., similar allocation of vaccine supply proportional to its population across jurisdictions) but equity (i.e., preferential access and administra-tion to those who have been most affected by COVID-19 disease) is an important goal. The CDC social vulnerability index (SVI) uses 15 indicators grouped into four themes that comprise an overall SVI measure, resulting in 20 metrics, each of which has national and state-specific county rankings. The 20 metric-specific rankings were each divided into lowest to highest tertiles to categorize counties as low, moderate, or high social vulnerability counties. These tertiles were combined with vaccine administration data for 49,264,338 U.S. residents in 49 states and the District of Columbia (DC) who received at least one COVID-19 vaccine dose during December 14, 2020-March 1, 2021. Nationally, for the overall SVI measure, vaccination coverage was higher (15.8%) in low social vulnerability counties than in high social vulnerability counties (13.9%), with the largest coverage disparity in the socioeconomic status theme (2.5 percentage points higher coverage in low than in high vulnerability counties). Wide state variations in equity across SVI metrics were found. Whereas in the majority of states, vaccination coverage was higher in low vulnerability counties, some states had equitable coverage at the county level. CDC, state, and local jurisdictions should continue to monitor vaccination coverage by SVI metrics to focus public health interventions to achieve equitable coverage with COVID-19 vaccine.

      4. Declines in Prevalence of Human Papillomavirus Vaccine-Type Infection Among Females after Introduction of Vaccine - United States, 2003-2018external icon
        Rosenblum HG, Lewis RM, Gargano JW, Querec TD, Unger ER, Markowitz LE.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 26;70(12):415-420.
        Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (1). Although most infections resolve without clinical sequalae, persistent HPV infection can cause cervical, other anogenital, and oropharyngeal cancers and anogenital warts. HPV vaccination has been recommended in the United States at age 11-12 years since 2006 for females and since 2011 for males. Catch-up vaccination is recommended through age 26 years.* A quadrivalent vaccine (4vHPV) targeting types 6, 11, 16, and 18 was mainly used until 2015, when a 9-valent vaccine (9vHPV), targeting the same four types as 4vHPV and five additional types (31, 33, 45, 52, and 58), was introduced; 9vHPV has been the only vaccine available in the United States since the end of 2016 (2). HPV vaccination coverage has increased but remains lower than that of other vaccinations recommended for adolescents (3). A decrease in prevalence of 4vHPV types detected in cervicovaginal swabs among young females from the prevaccine era (2003-2006) to 2007-2010 in the National Health and Nutrition Examination Survey (NHANES) was an early indicator of vaccine impact (2) and was also observed in later periods (4,5). NHANES data from 2017-2018 were included in this analysis to update HPV prevalence estimates among females aged 14-34 years. From the prevaccine era to 2015-2018, significant decreases in 4vHPV-type prevalence occurred among females aged 14-19 years (88%) and 20-24 years (81%). In sexually experienced females, 4vHPV-type prevalence decreased in those who reported receiving ≥1 HPV vaccine dose (97% among those aged 14-19 years, 86% among those aged 20-24 years) and in those who reported no vaccination (87% among those aged 14-19 years, 65% among those aged 20-24 years). Significant declines among unvaccinated females suggest herd effects. These data show increasing impact of HPV vaccination in the United States. HPV vaccination is a critical prevention tool against HPV infection, anogenital warts, and HPV-attributable precancers and cancers. HPV vaccination is highly effective and is recommended routinely at age 11-12 years and through 26 years for persons not already vaccinated.

      5. Comparative antibody responses to the live-attenuated and recombinant herpes zoster vaccinesexternal icon
        Schmid DS, Miao C, Leung J, Johnson M, Weinberg A, Levin MJ.
        J Virol. 2021 Mar 24.
        Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): 1) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV), and 2) recombinant adjuvanted vaccine (RZV) containing recombinant VZV glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status.VZV T cell-mediated immunity (CMI), but not humoral immunity, are considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination [19 and 12 avidity index units (AIU), respectively]. RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost: 47 AIU versus 22 AIU; mean neutralizing antibody boost: 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r=0.5) and moderately with gp avidity increases (r=0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCEThese observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity, neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Finally, combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development could benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.

      6. Effect of maternal Tdap on infant antibody response to a primary vaccination series with whole cell pertussis vaccine in São Paulo, Brazilexternal icon
        Vaz-de-Lima LR, Sato AP, Pawloski LC, Fernandes EG, Rajam G, Sato HK, Patel D, Li H, de Castilho EA, Tondella ML, Schiffer J.
        Vaccine: X. 2021 ;7.
        Background: Maternal Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination provides antibody transfer to newborn infants and may affect their antibody response to the primary vaccination series. This study aimed to assess the effect of Tdap vaccination during pregnancy on infant antibody response to the whole cell pertussis (DTwP) primary series. Methods: Plasma from 318 pregnant women (243 Tdap-vaccinated and 75 unvaccinated) and their infants (cord blood) was collected at delivery; infant blood was again collected at 2 and 7 months, before and after their primary DTwP series. Anti-pertussis toxin (PT), pertactin (PRN), filamentous hemagglutinin (FHA), fimbriae 2/3 (FIM) and adenylate cyclase toxin (ACT) IgG antibodies were quantified by a microsphere-based multiplex antibody capture assay and anti-PT neutralizing antibodies by the Real Time Cell analysis system. Results: Infant geometric mean concentrations (GMCs) of IgG anti-Tdap antigens were significantly higher (p < 0.001) among the Tdap-vaccinated (PT: 57.22 IU/mL; PRN: 464.86 IU/mL; FHA: 424.0 IU/mL), versus the unvaccinated group (4 IU/mL, 15.43 IU/mL, 31.99 IU/mL, respectively) at delivery. Anti-FIM and ACT GMCs were similar between the two groups. At 2 months of age, anti-PT, PRN, and FHA GMCs remained higher (p < 0.001) in the Tdap-vaccinated group (12.64 IU/mL; 108.76 IU/mL; 87.41 IU/mL, respectively) than the unvaccinated group (1.02 IU/mL; 4.46 IU/mL; 6.89 IU/mL). However, at 7 months, after receiving the third DTwP dose, the anti-PT GMC was higher (p = 0.016) in the unvaccinated group (7.91 IU/mL) compared to the vaccinated group (2.27 IU/mL), but without differences for anti-PRN, FHA, FIM and ACT GMCs. Conclusion: Elevated antibody levels suggest that maternal Tdap vaccination might protect infants until 2 months of age. Reduced anti-PT levels at 7 months indicate potential blunting of immune response in infants. Surveillance would help determine if blunting alters vaccine immunity and impacts pertussis prevention in infants.

    • Informatics
      1. Challenges of and Solutions for Developing Tailored Video Interventions That Integrate Multiple Digital Assets to Promote Engagement and Improve Health Outcomes: Tutorialexternal icon
        Harshbarger C, Burrus O, Rangarajan S, Bollenbacher J, Zulkiewicz B, Verma R, Galindo CA, Lewis MA.
        JMIR Mhealth Uhealth. 2021 Mar 23;9(3):e21128.
        BACKGROUND: Video is a versatile and popular medium for digital health interventions. As mobile device and app technology advances, it is likely that video-based interventions will become increasingly common. Although clinic waiting rooms are complex and busy environments, they offer the opportunity to facilitate engagement with video-based digital interventions as patients wait to see their providers. However, to increase efficiency in public health, leverage the scalability and low cost of implementing digital interventions, and keep up with rapidly advancing technology and user needs, more design and development guidance is needed for video-based tailored interventions. OBJECTIVE: We provide a tutorial for digital intervention researchers and developers to efficiently design and develop video-based tailored digital health interventions. We describe the challenges and solutions encountered with Positive Health Check (PHC), a hybrid app used to deliver a brief, interactive, individually tailored video-based HIV behavioral counseling intervention. PHC uses video clips and multimedia digital assets to deliver intervention content, including interactive tailored messages and graphics, a repurposed animated video, and patient and provider handouts generated in real time by PHC. METHODS: We chronicle multiple challenges and solutions for the following: (1) using video as a medium to enhance user engagement, (2) navigating the complexity of linking a database of video clips with other digital assets, and (3) identifying the main steps involved in building an app that will seamlessly deliver to users individually tailored messages, graphics, and handouts. RESULTS: We leveraged video to enhance user engagement by featuring "video doctors," full-screen video, storyboards, and streamlined scripts. We developed an approach to link the database of video clips with other digital assets through script coding and flow diagrams of algorithms to deliver a tailored user experience. We identified the steps to app development by using keyframes to design the integration of video and digital assets, using agile development methods to gather iterative feedback from multidisciplinary teams, and creating an intelligent data-driven back-end solution to tailor message delivery to individual users. CONCLUSIONS: Video-based digital health interventions will continue to play an important role in the future of HIV prevention and treatment, as well as other clinical health practices. However, facilitating the adoption of an HIV video intervention in HIV clinical settings is a work in progress. Our experience in designing and developing PHC presented unique challenges due to the extensive use of a large database of videos tailored individually to each user. Although PHC focuses on promoting the health and well-being of persons with HIV, the challenges and solutions presented in this tutorial are transferable to the design and development of video-based digital health interventions focused on other areas of health.

    • Injury and Violence
      1. Compared to young men, Ugandan young women are disproportionately impacted by HIV. Childhood transactional sex may contribute to this disparity. Using data from the 2015 Uganda Violence Against Children Survey, we used logistic regression models to assess the association between childhood transactional sex and negative outcomes. Among 18-24-year-old young women who had sex prior to 18 (n = 982), those who ever engaged in transactional sex had 5.9 times [adjusted odds ratio (AOR); confidence interval (CI): 1.6-22.2] higher odds of having multiple sexual partners in the past year; 5.2 times (AOR; CI: 2.1-12.9) higher odds of infrequent condom use in the past year; 3.0 times (AOR; CI: 1.2-7.9) higher odds of hurting themselves intentionally; and 3.2 times (AOR; CI: 1.3-7.7) higher odds of having attitudes justifying spousal abuse than young women who never engaged in transactional sex. Interventions for transactional sex and HIV in Uganda should consider prioritizing prevention, harm-reduction and continued investment in adolescent girls' and young women's futures.

    • Laboratory Sciences
      1. Smartphone-based sound level measurement apps: Evaluation of directional responseexternal icon
        Celestina M, Kardous CA, Trost A.
        Applied Acoustics. 2021 ;171.
        Smartphones have evolved into powerful devices with computing capabilities that rival the power of personal computers. Any smartphone can now be turned into a sound-measuring device because of its built-in microphone. Many sound measuring apps exist on the market for various mobile platforms. In our earlier research, we showed that a smart device with an adequate app can achieve compliance with most of the Class 2 requirements for periodic testing. In this paper, we present the methods and results of measuring directional response of a sound level meter consisting of a smartphone and one commercially available sound level meter app in the horizontal plane. We used both the built-in smartphone microphone and an external microphone according to relevant IEC [International Electrotechnical Commission] and ANSI [American National Standards Institute] sound level meter standards. The results show that the sound level meter app and an external microphone can achieve compliance with the requirements for Class 2 of IEC 61672/ANSI S1.4–2014 standard in the horizontal plane.

      2. Bias Correction in Estimating Proportions by Imperfect Pooled Testingexternal icon
        Hepworth G, Biggerstaff BJ.
        J Agric Biol Environ Stat. 2021 ;26(1):90-104.
        In the estimation of proportions by pooled testing, the MLE is biased. Hepworth and Biggerstaff (JABES, 22:602–614, 2017) proposed an estimator based on the bias correction method of Firth (Biometrika 80:27–38, 1993) and showed that it is almost unbiased across a range of pooled testing problems involving no misclassification. We now extend their work to allow for imperfect testing. We derive the estimator, provide a Newton–Raphson iterative formula for its computation and test it in situations involving equal or unequal pool sizes, drawing on problems encountered in plant disease assessment and prevalence estimation of mosquito-borne viruses. Our estimator is highly effective at reducing the bias for prevalences consistent with the pooled testing procedure employed.

      3. Liquid chromatography-tandem mass spectrometry method for measuring vitamin E acetate in bronchoalveolar lavage fluidexternal icon
        Morel Espinosa M, Blount BC, Valentin-Blasini L.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Feb 27;1171:122607.
        We investigated the suitability of isotope-dilution liquid chromatography coupled with tandem mass spectrometry for identifying vitamin E acetate (VEA) in bronchoalveolar lavage (BAL) fluid. This new method demonstrates high accuracy, selectivity, and sensitivity, with mean recoveries higher than 90%, coefficients of variation ranging from 1.5% to 4.5%, and a limit of detection of 1.10 ng/mL. Calibration curves were linear (R(2) > 0.99). The linear range and detection limit of the method were adequate for identifying VEA in 48 of 51 BAL fluid samples collected from people with lung injury resulting from e-cigarettes, or vaping, product use. We conclude that this method is an effective tool for studying VEA accumulation in lungs caused by using e-cigarettes, or vaping, products that contain VEA.

      4. DNA mismatch repair (MMR) relies on MutS and MutL ATPases for mismatch recognition and strand-specific nuclease recruitment to remove mispaired bases in daughter strands. However, whether the MutS-MutL complex coordinates MMR by ATP-dependent sliding on DNA or protein-protein interactions between the mismatch and strand discrimination signal is ambiguous. Using functional MMR assays and systems preventing proteins from sliding, we show that sliding of human MutSα is required not for MMR initiation, but for final mismatch removal. MutSα recruits MutLα to form a mismatch-bound complex, which initiates MMR by nicking the daughter strand 5' to the mismatch. Exonuclease 1 (Exo1) is then recruited to the nick and conducts 5' → 3' excision. ATP-dependent MutSα dissociation from the mismatch is necessary for Exo1 to remove the mispaired base when the excision reaches the mismatch. Therefore, our study has resolved a long-standing puzzle, and provided new insights into the mechanism of MMR initiation and mispair removal.

      5. Radioactive strontium is a nuclear fission decay product found in industrial products and nuclear waste and is released during nuclear accidents. Current urine radiostrontium separation methods often are based on the use of Sr resin columns or cartridges (Eichrom Technologies). Most of these analytical methods use stable Sr as a tracer, with subsequent Sr recovery. The gravimetric recovery method requires 120 times more stable Sr than does the inductively coupled plasma mass spectrometry method described here. This difference can affect cartridge performance especially with aging cartridges.

      6. The importance of binomial nomenclature for the identification of pollen aeroallergensexternal icon
        Ramon GD, Green BJ, Levetin E, Makra L, Bielory L.
        J Allergy Clin Immunol Pract. 2021 Mar 16.
        The diagnosis and treatment of atopic disorders associated with specific aerobiological triggers require basic botanical training. However, the identification of specific pollen can often be confounded by broad naming conventions that range from categorized colloquial, to scientific names based on either higher taxonomic levels, or in some cases binomial nomenclature. Physicians specializing in allergy often lack a comprehensive understanding with respect to plant taxonomy and botanical nomenclature that are critical skills required for clinical practice and research programs evaluating pollen and airborne fungal spores. In addition, binomial and current family designation and synonyms, including author citation are often misused, causing a misinterpretation of existing plants species or pollen types. It is critical that the correct botanical name is linked to a validated specimen, and scientific naming conventions are used where possible by the clinician and researcher. In relation to pollen identification, we propose that clinicians and researchers should provide the currently accepted binomial nomenclature, offer relevant synonyms, and use the Angiosperm Phylogeny Group names.

      7. Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnosticsexternal icon
        Smith T, Masciotra S, Luo W, Sullivan V, Switzer WM, Johnson JA, Heneine W.
        Aids. 2021 Mar 22.
        OBJECTIVE: Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach ∼1 mg/mL and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products. DESIGN METHODS: The anti-gp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074, and N6 and anti-gp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV 1/2 assays, and the supplemental Geenius and HIV-1 Western blot assays. RESULTS: At 1 mg/mL, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4, and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity. CONCLUSION: We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.

    • Nutritional Sciences
      1. A School-Based Weekly Iron and Folic Acid Supplementation Program Effectively Reduces Anemia in a Prospective Cohort of Ghanaian Adolescent Girlsexternal icon
        Gosdin L, Sharma AJ, Tripp K, Amoaful EF, Mahama AB, Selenje L, Jefferds ME, Martorell R, Ramakrishnan U, Addo OY.
        J Nutr. 2021 Mar 23.
        BACKGROUND: School-based iron and folic acid (IFA) supplementation is recommended for adolescent girls in countries with high burdens of anemia. OBJECTIVES: We aimed to evaluate the context-specific effectiveness of a school-based, integrated anemia control program with IFA supplementation in Ghana. METHODS: Using data from a pre-post, longitudinal program evaluation, we evaluated the effectiveness of school-based weekly IFA supplementation in reducing the burden of anemia and increasing hemoglobin concentrations (Hb; primary outcomes) in 2 regions of Ghana. Generalized linear mixed effects models with schools (clusters) as random effects were used to quantify the change in the anemia prevalence and the mean Hb associated with cumulative IFA tablet consumption over 1 school year (30-36 weeks), controlling for participant-level potential confounders. A cut point for minimum effective cumulative IFA consumption that is reflective of adequate Hb was derived following logistic regression. This cut point was verified by a restricted cubic spline model of IFA consumption and Hb. RESULTS: The analytical sample included 60 schools and 1387 girls ages 10-19 years. The prevalence of anemia declined during 1 school year of the intervention, from 25.1% to 19.6% (P = 0.001). Students consumed a mean of 16.4 IFA tablets (range, 0-36). IFA consumption was positively associated with Hb and negatively associated with anemia. Each additional IFA tablet consumed over the school year was associated with a 5% (95% CI, 1-10%) reduction in the adjusted odds of anemia at follow-up, though the relationship is nonlinear. The cut point for minimum effective consumption was 26.7 tablets over a 30-36-week school year, with tablets provided weekly. CONCLUSIONS: School-based weekly IFA supplementation is effective in improving Hb and reducing the anemia prevalence among schoolgirls in Ghana, though most participants consumed fewer than the minimum effective number of IFA tablets. Increasing intake adherence may further improve anemia outcomes in this population.

      2. Vitamin A deficiency has declined in Malawi, but with evidence of elevated vitamin A in childrenexternal icon
        Williams AM, Tanumihardjo SA, Rhodes EC, Mapango C, Kazembe B, Phiri F, Kang'ombe DD, Sheftel J, Orchardson V, Tripp K, Suchdev PS.
        Am J Clin Nutr. 2021 Mar 5.
        BACKGROUND: Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS). OBJECTIVE: We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey. METHODS: Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design. RESULTS: We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables. CONCLUSIONS: Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification.

    • Occupational Safety and Health
      1. Shift work and overtime across a career in law enforcement: a 15-year studyexternal icon
        Riedy SM, Fekedulegn D, Vila B, Andrew M, Violanti JM.
        Policing. 2021 ;44(2):200-212.
        Purpose: To characterize changes in work hours across a career in law enforcement. Design/methodology/approach: N = 113 police officers enrolled in the BCOPS cohort were studied. The police officers started their careers in law enforcement between 1994 and 2001 at a mid-sized, unionized police department in northwestern New York and continued to work at this police department for at least 15 years. Day-by-day work history records were obtained from the payroll department. Work hours, leave hours and other pay types were summarized for each calendar year across their first 15 years of employment. Linear mixed-effects models with a random intercept over subject were used to determine if there were significant changes in pay types over time. Findings: A total of 1,617 individual-years of data were analyzed. As the police officers gained seniority at the department, they worked fewer hours and fewer night shifts. Total paid hours did not significantly change due to seniority-based increases in vacation time. Night shift work was increasingly in the form of overtime as officers gained seniority. Overtime was more prevalent at the beginning of a career and after a promotion from police officer to detective. Originality/value: Shiftwork and long work hours have negative effects on sleep and increase the likelihood of on-duty fatigue and performance impairment. The results suggest that there are different points within a career in law enforcement where issues surrounding shiftwork and long work hours may be more prevalent. This has important implications for predicting fatigue, developing effective countermeasures and measuring fatigue-related costs.

    • Parasitic Diseases
      1. Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congoexternal icon
        Parr JB, Kieto E, Phanzu F, Mansiangi P, Mwandagalirwa K, Mvuama N, Landela A, Atibu J, Efundu SU, Olenga JW, Thwai KL, Morgan CE, Denton M, Poffley A, Juliano JJ, Mungala P, Likwela JL, Sompwe EM, Rogier E, Tshefu AK, N'Siala A, Kalonji A.
        Sci Rep. 2021 Mar 22;11(1):6495.
        The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen's kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.

      2. Framework for Characterizing Longitudinal Antibody Response in Children After Plasmodium falciparum Infectionexternal icon
        Rogier E, Nace D, Dimbu PR, Wakeman B, Pohl J, Beeson JG, Drakeley C, Tetteh K, Plucinski M.
        Front Immunol. 2021 ;12:617951.
        Human Plasmodium infection produces a robust adaptive immune response. Time courses for 104 children followed for 42 days after initiation of Plasmodium falciparum chemotherapy were assayed for antibody levels to the five isotypes of human immunoglobulins (Ig) and 4 subclasses of IgG for 32 P. falciparum antigens encompassing all 4 parasite stages of human infection. IgD and IgE against these antigens were undetectable at 1:100 serum concentration, but other Ig isotypes and IgG subclasses were consistently observed against all antigens. Five quantitative parameters were developed to directly compare Ig response among isotypes and antigens: C(max), maximum antibody level; Δ(C), difference between C(max) and the antibody level at Day 0; t(max), time in days to reach C(max); t(1/2), Ig signal half-life in days; t(neg), estimated number of days until complete loss of Ig signal. Classical Ig patterns for a bloodborne pathogen were seen with IgM showing early t(max) and IgG production highest among Ig isotypes. However, some unexpected trends were observed such as IgA showing a biphasic pattern for many antigens. Variability among these dynamics of Ig acquisition and loss was noted for different P. falciparum antigens and able to be compared both quantitatively and statistically. This parametrization methodology allows direct comparison of Ig isotypes produced against various Plasmodium antigens following malaria infection, and the same methodology could be applied to other longitudinal serologic studies from P. falciparum or different pathogens. Specifically for P. falciparum seroepidemiological studies, reliable and quantitative estimates regarding the IgG dynamics in human populations can better optimize modeling efforts for serological outputs.

      3. Human infection with an unknown species of Dracunculus in Vietnamexternal icon
        Thach PN, van Doorn HR, Bishop HS, Fox MS, Sapp SG, Cama VA, Van Duyet L.
        Int J Infect Dis. 2021 Mar 15.
        Guinea worm (GW) disease, caused by Dracunculus medinensis, is an almost eradicated waterborne zoonotic disease. The World Health Organization currently lists GW as endemic in only 5 African countries. In July 2020 the Vietnamese public health surveillance system detected a hanging worm in a 23-year -old male patient, who did not report any travel to Africa or any country previously endemic for GW. The patient was hospitalized with symptoms of fatigue, anorexia, muscle aches, and abscesses with worms hanging out of the skin in the lower limbs. The worms were retrieved from the lesions and microscopically examined in Vietnam, identifying structures compatible with Dracunculus spp. and L1-type larvae. A section of this parasite was sent to CDC Atlanta for confirmatory diagnosis of GW. The adult worm had cuticle structures compatible with Dracunculus parasites, although the length of L1 larvae was about 339 µm, substantially shorter than D. medinensis. The DNA sequence analysis of the 18S small subunit rRNA gene confirmed that this parasite was not GW, and determined that the sample belonged to a Dracunculus sp not previously reported in GenBank that clustered with the animal-infective D. insignis and D. lutrae, located in a different clade than D. medinensis. This study highlights the importance of effective public health surveillance systems and the collaborative work of local public health authorities from Vietnam with WHO and CDC in the efforts to achieve the eradication of GW.

    • Public Health Leadership and Management
      1. Building public health capacity through India epidemic intelligence service and field epidemiology training programs in Indiaexternal icon
        Singh SK, Murhekar M, Gupta S, Minh NN, Sodha SV.
        Indian J Public Health. 2021 Jan;65(Supplement):S1-s4.

    • Reproductive Health
      1. Motivations to use hormonal contraceptive methods and condoms among HIV-positive and negative women randomized to a progestin contraceptive in Malawi: a qualitative studyexternal icon
        Bula AK, Hatfield-Timajchy K, Chapola J, Chinula L, Hurst SA, Kourtis AP, Tang JH.
        BMC Womens Health. 2021 Mar 20;21(1):114.
        BACKGROUND: Although many countries have been promoting hormonal contraceptives to prevent unintended pregnancy and condom use to prevent HIV transmission, little is known about how women targeted by these messages have interpreted and internalized them. We describe HIV-positive and negative women's understanding of the benefits of contraception and condoms and their motivations to use them. METHODS: This is a qualitative sub-study from a clinical trial evaluating the effects of progestin contraception on HIV-positive and negative women aged 18-45 years randomly assigned to depot medroxyprogesterone acetate (DMPA) injection or levonorgestrel (LNG) implant. We purposively recruited 41 women to participate in in-depth interviews (IDIs) and focus group discussions (FGDs) after randomization into the main study. We conducted a total of 30 IDIs and 6 FGDs comprised of 4-7 women (N = 32). All women were counselled about potential risks for HIV acquisition/transmission with progestin-only contraception, drug-drug interactions between the implant and efavirenz-based ART, and the need to use condoms with their assigned contraceptive to help prevent pregnancy and HIV acquisition and transmission. RESULTS: All women understood that HIV is transmitted through unprotected sex and that HIV transmission can be prevented through condom use but not DMPA injection or LNG implant use. Nearly all HIV-positive women knew or suspected that their partners were also HIV-positive and were most interested in using condoms to prevent infection with a drug-resistant HIV strain to keep their HIV viral load low. Almost all reported that their partners agreed to condom use, but few used them consistently. Most women believed that condoms were effective at preventing both HIV and pregnancy if used consistently. Nearly all women considered contraception and condom use as important in preventing unintended pregnancy and HIV because partner disclosure of HIV status is low. CONCLUSION: Our results showed that both HIV-positive and negative women understood modes of HIV transmission and prevention and were aware that hormonal contraceptives are only effective for preventing pregnancy and not HIV. Although both HIV-negative and positive women were motivated to use condoms to prevent both HIV acquisition and infection with other HIV strains respectively, they all faced challenges from their partners in using condoms consistently.

      2. Patient feedback surveys among pregnant women in Eswatini to improve antenatal care retentionexternal icon
        Teasdale CA, Geller A, Shongwe S, Mafukidze A, Choy M, Magaula B, Yuengling K, King K, De Gusmao EP, Ryan C, Ao T, Callahan T, Modi S, Abrams EJ.
        PLoS One. 2021 ;16(3):e0248685.
        BACKGROUND: Uptake and retention in antenatal care (ANC) is critical for preventing adverse pregnancy outcomes for both mothers and infants. METHODS: We implemented a rapid quality improvement project to improve ANC retention at seven health facilities in Eswatini (October-December 2017). All pregnant women attending ANC visits were eligible to participate in anonymous tablet-based audio assisted computer self-interview (ACASI) surveys. The 24-question survey asked about women's interactions with health facility staff (HFS) (nurses, mentor mothers, receptionists and lab workers) with a three-level symbolic response options (agree/happy, neutral, disagree/sad). Women were asked to self-report HIV status. Survey results were shared with HFS at monthly quality improvement sessions. Chi-square tests were used to assess differences in responses between months one and three, and between HIV-positive and negative women. Routine medical record data were used to compare retention among pregnant women newly enrolled in ANC two periods, January-February 2017 ('pre-period') and January-February 2018 ('post-period') at two of the participating health facilities. Proportions of women retained at 3 and 6 months were compared using Cochran-Mantel-Haenszel and Wilcoxon tests. RESULTS: A total of 1,483 surveys were completed by pregnant women attending ANC, of whom 508 (34.3%) self-reported to be HIV-positive. The only significant change in responses from month one to three was whether nurses listened with agreement increasing from 88.3% to 94.8% (p<0.01). Overall, WLHIV had significantly higher proportions of reported satisfaction with HFS interactions compared to HIV-negative women. A total of 680 pregnant women were included in the retention analysis; 454 (66.8%) HIV-negative and 226 (33.2%) WLHIV. In the pre- and post-periods, 59.4% and 64.6%, respectively, attended at least four ANC visits (p = 0.16). The proportion of women retained at six months increased from 60.9% in the pre-period to 72.7% in the post-period (p = 0.03). For HIV-negative women, pre- and post-period six-month retention significantly increased from 56.6% to 71.6% (p = 0.02); however, the increase in WLHIV retained at six months from 70.7% (pre-period) to 75.0% (post-period) was not statistically significant (p = 0.64). CONCLUSION: The type of rapid quality improvement intervention we implemented may be useful in improving patient-provider relationships although whether it can improve retention remains unclear.

    • Substance Use and Abuse
      1. Concentrations of cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in US non-daily cigarette smokersexternal icon
        Gutiérrez-Torres DS, Wang L, Blount BC, Xia B, Sosnoff CS, Shiels MS, Inoue-Choi M, Etemadi A, Freedman ND.
        Cancer Epidemiol Biomarkers Prev. 2021 Mar 18.
        BACKGROUND: Accumulating evidence suggests that non-daily smokers have higher disease and mortality risks than never smokers. Yet, the accuracy of self-reported non-daily cigarette smoking is poorly understood. METHODS: We examined the concordance between self-reported non-daily smoking and serum cotinine in 18,835 adult participants (20 years or older) of the 2007-2014 National Health and Nutrition Examination Surveys, in comparison with daily smokers and non-smokers. We also analyzed concentrations of the urinary biomarker 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by smoking status. RESULTS: In the study sample, 77.8% (14,660) reported currently not smoking (non-smokers), 18.3% (3,446) smoked every day (daily smokers) and 3.9% (729) smoked on some days of the past month (non-daily smokers). Just 2.1% of non-smokers had cotinine concentrations in the active smoking range (>10 ng/mL), compared to 70.4% of non-daily and 98.8% of daily smokers. Non-daily smokers reported smoking a median of 24 cigarettes per month (interquartile range (IQR): 9-60) and had substantially higher concentrations of NNAL (Median: 72.5, IQR: 14.8-211.0 pg/mL) than non-smokers (Median: 0.4, IQR: 0.4-2.1 pg/mL), though lower than daily smokers (Median: 294.0, IQR: 148.0-542.0 pg/mL). Among non-daily smokers, concentrations of cotinine and NNAL were positively correlated with days and cigarettes smoked per month (P<0.001). CONCLUSIONS: We observed excellent concordance between self-reported non-daily cigarette smoking and concentrations of serum cotinine. IMPACT: These results provide evidence for the validity of self-reported non-daily smoking and indicate that non-daily smokers are exposed to substantial concentrations of carcinogenic nitrosamines regardless of the low number of cigarettes they smoke per month.

      2. Toxicology of flavoring- and cannabis-containing e-liquids used in electronic delivery systemsexternal icon
        Stefaniak AB, LeBouf RF, Ranpara AC, Leonard SS.
        Pharmacol Ther. 2021 Mar 18;224:107838.
        Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.

    • Zoonotic and Vectorborne Diseases
      1. Geographic distribution and genetic characterization of poxviruses from human infections in Georgia, 2009-2014external icon
        Khmaladze E, Mauldin MR, Tsaguria D, Gavashelidze M, Sidamonidze K, Tevdoradze T, Li Y, Reynolds MG, Imnadze P, Nakazawa Y.
        Arch Virol. 2021 Mar 21.
        Anthrax is endemic in Georgia, as are multiple zoonotic poxviruses. Poxvirus-associated infections share some clinical manifestations and exposure risks with anthrax, and so it is important to distinguish between the two. With this in mind, an archived collection of anthrax-negative DNA samples was retrospectively screened for poxviruses, and of the 148 human samples tested, 64 were positive. Sequence analysis confirmed the presence of orf virus, bovine papular stomatitis virus, and pseudocowpox virus. This study provides evidence of previously unrecognized poxvirus infections in Georgia and highlights the benefit of the timely identification of such infections by improving laboratory capacity.

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

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