Issue 29, August 17, 2021

CDC Science Clips: Volume 13, Issue 29, August 17, 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.
    • Communicable Diseases
      • Suspected SARS-CoV-2 reinfections: Incidence, predictors, and healthcare use among patients at 238 U.S. healthcare facilities, June 1, 2020- February 28, 2021external icon
        Lawandi A, Warner S, Sun J, Demirkale CY, Danner RL, Klompas M, Gundlapalli A, Datta D, Harris AM, Morris SB, Natarajan P, Kadri SS.
        Clin Infect Dis. 2021 Aug 5.
        In a retrospective cohort study, among 131,773 patients with previous COVID19, reinfection with SARS-CoV-2 was suspected in 253(0.2%) patients at 238 U.S. healthcare facilities between June 1, 2020- February 28, 2021. Women displayed a higher cumulative reinfection risk. Healthcare burden and illness severity were similar between index and reinfection encounters.

      • Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: A collaborative pooled analysis of 64 studiesexternal icon
        Wei F, Gaisa MM, D'Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Donà MG, Goldstone SE, Schim van der Loeff MF, Neukam K, Meites E, Poynten IM, Dai J, Combes JD, Wieland U, Burgos J, Wilkin TJ, Hernandez AL, Iribarren Díaz M, Hidalgo-Tenorio C, Valencia Arredondo M, Nyitray AG, Wentzensen N, Chow EP, Smelov V, Nowak RG, Phanuphak N, Woo YL, Choi Y, Hu Y, Schofield AM, Woestenberg PJ, Chikandiwa AT, Hickey AC, de Pokomandy A, Murenzi G, Péré H, Del Pino M, Ortiz AP, Charnot-Katsikas A, Liu X, Chariyalertsak S, Strong C, Ong JJ, Yunihastuti E, Etienney I, Ferré VM, Zou H, Segondy M, Chinyowa S, Alberts CJ, Clifford GM.
        Lancet HIV. 2021 Jul 30.
        BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p(trend)=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p(trend)<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p(trend)=0·0076); the prevalence plateaued thereafter (p(trend)=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

    • Environmental Health
      • Co-occurrence of metal contaminants in United States public water systems in 2013-2015external icon
        Thompson AK, Monti MM, Gribble MO.
        Int J Environ Res Public Health. 2021 ;18(15).
        The United States Environmental Protection Agency monitors contaminants in drinking water and consolidates these results in the National Contaminant Occurrence Database. Our objective was to assess the co-occurrence of metal contaminants (total chromium, hexavalent chromium, molybdenum, vanadium, cobalt, and strontium) over the years 2013-2015. We used multilevel Tobit regression models with state and water system-level random intercepts to predict the geometric mean of each contaminant occurring in each public water system, and estimated the pairwise correlations of predicted water system-specific geometric means across contaminants. We found that the geometric means of vanadium and total chromium were positively correlated both in large public water systems (r = 0.45, p < 0.01) and in small public water systems (r = 0.47, p < 0.01). Further research may address the cumulative human health impacts of ingesting more than one contaminant in drinking water. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Food Safety
      • Foodborne botulism outbreaks in the United States, 2001-2017external icon
        Lúquez C, Edwards L, Griffin C, Sobel J.
        Front Microbiol. 2021 ;12:713101.
        Foodborne botulism is an intoxication caused by ingestion of food containing botulinum neurotoxin. Cases of foodborne botulism are usually sporadic (single, unrelated) but outbreaks of two or more cases occur. In this mini-review we will examine the following for the period 2001-2017, in the United States: botulism surveillance data, outbreaks of botulism affecting 10 or more people, and the public health preparedness and response approach.

    • Health Disparities
      • BACKGROUND: American Indian and Alaska Native (AI/AN) populations have experienced regional variation and disparities in colorectal cancer incidence rates. METHODS: We examined colorectal cancer (CRC) incidence (2013-2017) and CRC incidence trends (1999-2017) among American Indian and Alaska Native (AI/AN) persons. Incidence data were linked to Indian Health Service enrollment records, and analyses were restricted to Purchased/Referred Care Delivery Areas. Incidence rates of CRC among AI/AN and White persons were analyzed in 6 geographic regions; Hispanic persons were excluded. Incidence trends were analyzed using linear modeling. RESULTS: During 2013-2017, CRC incidence was 41% higher among AI/AN than among White persons. AI/AN incidence rates per 100,000 varied regionally from 34.4 in the East to 96.1 in Alaska. Compared to White persons, AI/AN persons had higher CRC incidence rates among all age strata and were more likely to have late-stage diagnoses. Incidence rate trends indicated significant increases among both AI/AN and White persons aged <50 years and among AI/AN persons aged 50-64 years. The CRC incidence rate trend increased among AI/AN persons in the Southwest. CONCLUSIONS: The disparity of CRC incidence rates between AI/AN and White persons has widened since 2005-2009. AI/AN populations have higher CRC incidence compared to White populations, especially in the Alaska region. IMPACT: Our finding of increased CRC incidence disparities suggests that enhanced screening efforts and culturally appropriate clinical and public health interventions are needed among AI/AN persons overall, and especially in regions and age groups in which CRC rates are increasing.

    • Health Economics
    • Healthcare Associated Infections
      • Advancing diagnostic stewardship for healthcare associated infections, antibiotic resistance, and sepsisexternal icon
        Curren EJ, Lutgring JD, Kabbani S, Diekema DJ, Gitterman S, Lautenbach E, Morgan DJ, Rock C, Salerno RM, McDonald LC.
        Clin Infect Dis. 2021 Aug 4.
        Diagnostic stewardship means ordering the right tests, for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance, and treatment of sepsis. CDC's Division of Healthcare Quality Promotion (DHQP) hosted a meeting on improving patient safety through diagnostic stewardship with a focus on the use of the laboratory. The meeting identified emerging issues in the field of diagnostic stewardship, raised awareness of these issues among stakeholders, and discussed strategies and interventions to address the issues-all with an emphasis on improved outcomes and patient safety. This white paper summarizes the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.

    • Immunity and Immunization
      • Progress towards rubella elimination - WHO European Region, 2005-2019pdf iconexternal icon
        O'Connor P, Jankovic D, Zimmerman L, Mamou MB, Reef S.
        Weekly Epidemiological Record. 2021 ;96(24):229-240.
        This study reports the elimination of rubella across Europe, focusing on (1) immunisation activities, (2) surveillance activities, (3) Rubella incidence and genotypes, and (4) regional verification commission and progress towards elimination. Substantial progress towards rubella elimination has been made in the WHO European Region. Verification of elimination is nearly complete, which would make the European Region the second WHO region to achieve rubella elimination, after the Region of the Americas. Sustaining regional rubella elimination will require maintaining high coverage with RCVs through routine immunisation programmes at national and subnational levels, offering supplementary rubella vaccination to susceptible adults, maintaining high-quality laboratory-supported rubella and CRS surveillance for outbreak detection and response and a fully functioning Regional Verification Commission. Because of the COVID-19 pandemic, additional efforts might be needed to strengthen surveillance systems and fill in the immunity gaps.

    • Informatics
      • Building an interactive geospatial visualization application for national health care-associated infection surveillance: Development studyexternal icon
        Zheng S, Edwards JR, Dudeck MA, Patel PR, Wattenmaker L, Mirza M, Tejedor SC, Lemoine K, Benin AL, Pollock DA.
        JMIR Public Health Surveill. 2021 Jul 30;7(7):e23528.
        BACKGROUND: The Centers for Disease Control and Prevention's (CDC's) National Healthcare Safety Network (NHSN) is the most widely used health care-associated infection (HAI) and antimicrobial use and resistance surveillance program in the United States. Over 37,000 health care facilities participate in the program and submit a large volume of surveillance data. These data are used by the facilities themselves, the CDC, and other agencies and organizations for a variety of purposes, including infection prevention, antimicrobial stewardship, and clinical quality measurement. Among the summary metrics made available by the NHSN are standardized infection ratios, which are used to identify HAI prevention needs and measure progress at the national, regional, state, and local levels. OBJECTIVE: To extend the use of geospatial methods and tools to NHSN data, and in turn to promote and inspire new uses of the rendered data for analysis and prevention purposes, we developed a web-enabled system that enables integrated visualization of HAI metrics and supporting data. METHODS: We leveraged geocoding and visualization technologies that are readily available and in current use to develop a web-enabled system designed to support visualization and interpretation of data submitted to the NHSN from geographically dispersed sites. The server-client model-based system enables users to access the application via a web browser. RESULTS: We integrated multiple data sets into a single-page dashboard designed to enable users to navigate across different HAI event types, choose specific health care facility or geographic locations for data displays, and scale across time units within identified periods. We launched the system for internal CDC use in January 2019. CONCLUSIONS: CDC NHSN statisticians, data analysts, and subject matter experts identified opportunities to extend the use of geospatial methods and tools to NHSN data and provided the impetus to develop NHSNViz. The development effort proceeded iteratively, with the developer adding or enhancing functionality and including additional data sets in a series of prototype versions, each of which incorporated user feedback. The initial production version of NHSNViz provides a new geospatial analytic resource built in accordance with CDC user requirements and extensible to additional users and uses in subsequent versions.

    • Laboratory Sciences
      • Laboratory capacity assessments in 25 African countries at high risk of yellow fever, August-December 2018external icon
        Johnson BW, Demanou M, Fall G, Betoulle JL, Obiekea C, Basile AJ, Domingo C, Goodman C, Mossel E, Reusken C, Staples E, de Morais JF, Neto Z, Paixao P, Denon YE, Glitho M, Mahinou J, Kagone T, Nakoune E, Gamougam K, Simbu EP, Ahuka S, Mombouli JV, Goma-Nkoua C, Adjogoua EV, Tayachew A, Beyene B, Sanneh B, Jarju ML, Mendy A, Amelor DK, Ofosu-Appiah L, Opare D, Antwi L, Adade R, Magassouba N, Gomes SF, Limbaso S, Lutomiah J, Gbelee B, Dogba J, Cisse I, Idde Z, Ihekweazu C, Mba N, Faye O, Sall AA, Koroma Z, Juma MA, Maror JA, Eldigail M, Elduma AH, Elageb R, Badziklou K, Komla KA, Kayiwa J, Lutwama JJ, Hampton L, Mulders MN.
        Pan African Medical Journal. 2021 ;38.
        Introduction: accurate and timely laboratory diagnosis of yellow fever (YF) is critical to the Eliminate Yellow Fever Epidemics (EYE) strategy. Gavi, the Vaccine Alliance recognized the need to support and build capacity in the national and regional laboratories in the Global YF Laboratory Network (GYFLN) as part of this strategy. Method(s): to better understand current capacity, gaps and needs of the GYFLN laboratories in Africa, assessments were carried out in national and regional reference laboratories in the 25 African countries at high risk for YF outbreaks that were eligible for new financial support from Gavi. Result(s): the assessments found that the GYFLN in Africa has high capacity but 21% of specimens were not tested due to lack of testing kits or reagents and approximately 50% of presumptive YF cases were not confirmed at the regional reference laboratory due to problems with shipping. Conclusion(s): the laboratory assessments helped to document the baseline capacities of these laboratories prior to Gavi funding to support strengthening YF laboratories. Copyright © Barbara Wilmot Johnson et al.

    • Maternal and Child Health
      • Maternal prepregnancy weight and gestational weight gain in association with autism and developmental disorders in offspringexternal icon
        Matias SL, Pearl M, Lyall K, Croen LA, Kral TV, Fallin D, Lee LC, Bradley CB, Schieve LA, Windham GC.
        Obesity (Silver Spring). 2021 Aug 4.
        OBJECTIVE: Maternal prepregnancy BMI and gestational weight gain (GWG) are examined in relation to autism spectrum disorder (ASD) and other developmental disorders (DD) in offspring in a multisite case-control study. METHODS: Maternal prepregnancy BMI, obtained from medical records or self-report, was categorized as underweight, normal weight, overweight, obesity Class 1, or obesity Class 2/3. GWG was standardized for gestational age (GWG z score), and the rate (pounds/week) was categorized per adherence with clinical recommendations. Logistic regression models, adjusting for demographic factors, were used to assess associations with ASD (n = 1,159) and DD (n = 1,617), versus control children (n = 1,633). RESULTS: Maternal obesity Class 2/3 was associated with ASD (adjusted odds ratio [AOR] = 1.87, 95% CI: 1.40-2.51) and DD (AOR = 1.61, 95% CI: 1.22-2.13). GWG z score was not associated with DD (AOR = 1.14, 95% CI: 0.95-1.36), but the GWG z score highest tertile was associated with higher odds of ASD, particularly among male children (AOR = 1.47, 95% CI: 1.15-1.88). CONCLUSIONS: Results indicate that maternal prepregnancy severe obesity increases risk of ASD and DD in children and suggest high gestational-age-adjusted GWG is a risk factor for ASD in male children. Because maternal BMI and GWG are routinely measured and potentially modifiable, these findings could inform early interventions for high-risk mother-child dyads.

    • Zoonotic and Vectorborne Diseases
      • Development and implementation of the Ebola exposure window calculator: A tool for Ebola virus disease outbreak field investigationsexternal icon
        Whitesell A, Bustamante ND, Stewart M, Freeman J, Dismer AM, Alarcon W, Kofman A, Ben Hamida A, Nichol ST, Damon I, Haberling DL, Keita M, Mbuyi G, Armstrong G, Juang D, Dana J, Choi MJ.
        PLoS One. 2021 ;16(8):e0255631.
        During an Ebola virus disease (EVD) outbreak, calculating the exposure window of a confirmed case can assist field investigators in identifying the source of infection and establishing chains of transmission. However, field investigators often have difficulty calculating this window. We developed a bilingual (English/French), smartphone-based field application to assist field investigators in determining the exposure window of an EVD case. The calculator only requires the reported date of symptoms onset and the type of symptoms present at onset or the date of death. Prior to the release of this application, there was no similar electronic capability to enable consistent calculation of EVD exposure windows for field investigators. The Democratic Republic of the Congo Ministry of Health endorsed the application and incorporated it into trainings for field staff. Available for Apple and Android devices, the calculator continues to be downloaded even as the eastern DRC outbreak resolved. We rapidly developed and implemented a smartphone application to estimate the exposure window for EVD cases in an outbreak setting.

  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. Lifetime risk of developing diabetes and years of life lost among those with diabetes in Brazilexternal icon
        Bracco PA, Gregg EW, Rolka DB, Schmidt MI, Barreto SM, Lotufo PA, Bensenor I, Duncan BB.
        J Glob Health. 2021 ;11:04041.
        BACKGROUND: Given the paucity of studies for low- or middle-income countries, we aim to provide the first ever estimations of lifetime risk of diabetes, years of life spent and lost among those with diabetes for Brazilians. Estimates of Brazil´s diabetes burden consist essentially of reports of diabetes prevalence from national surveys and mortality data. However, these additional metrics are at times more meaningful ways to characterize this burden. METHODS: We joined data on incidence of physician-diagnosed diabetes from the Brazilian risk factor surveillance system, all-cause mortality from national statistics, and diabetes mortality rate ratios from ELSA-Brasil, an ongoing cohort study. To calculate lifetime risk of developing diabetes, we applied an illness-death state model. To calculate years of life lost for those with diabetes and years lived with the disease, we additionally calculated the mortality rates for those with diabetes. RESULTS: A 35-year-old white adult had a 23.4% (95% CI = 22.5%-25.5%) lifetime risk of developing diabetes by age 80 while a same-aged black/brown adult had a 30.8% risk (95% confidence interval (CI) = 29.6%-33.2%). Men diagnosed with diabetes at age 35 would live 32.9 (95% CI = 32.4-33.2) years with diabetes and lose 5.5 (95% CI = 5.1-6.1) years of life. Similarly-aged women would live 38.8 (95% CI = 38.3-38.9) years with diabetes and lose 2.1 (95% CI = 1.9-2.6) years of life. CONCLUSIONS: Assuming maintenance of current rates, one-quarter of young Brazilians will develop diabetes over their lifetimes, with this number reaching almost one-third among young, black/brown women. Those developing diabetes will suffer a decrease in life expectancy and will generate a considerable cost in terms of medical care.

      2. Blood from a stone: Funding hypertension prevention, treatment, and care in low- and middle-income countriesexternal icon
        Cohn J, Kostova D, Moran AE, Cobb LK, Pathni AK, Bisrat D.
        J Hum Hypertens. 2021 Jul 30.

      3. Demographic differences and disparities in the misdiagnosis of interstitial cystitis/bladder pain syndrome in a national cohort of VA patientsexternal icon
        Dallas KB, Bresee C, De Hoedt A, Senechal JF, Barbour KE, Kim J, Freedland SJ, Anger JT.
        Urology. 2021 Aug 1.
        OBJECTIVES: To explore association between misdiagnosis of IC/BPS and demographics. Interstitial cystitis/bladder pain syndrome (IC/BPS) is associated with significant diagnostic uncertainty, resulting in frequent misdiagnosis as there is little known about the potential impact of key demographic factors. METHODS: All patients in the VA system between 1999-2016 were identified by ICD-9/10 codes for IC/BPS (595.1/N30.10) (n=9,503). ICD code accuracy for true IC/BPS (by strict criteria) was assessed by in-depth chart abstraction (n= 2,400). Associations were explored between rates of misdiagnosis and demographics. RESULTS: IC/BPS criteria were met in only 651 (48.8%) of the 1,334 charts with an ICD code for IC/BPS reviewed in depth. There were no differences in the misdiagnosis rate by race (p=0.27) or by ethnicity (p=0.97), after adjusting for differences in age and gender. In IC/BPS-confirmed cases, female patients were diagnosed at a younger age than males (41.9 vs. 58.2 years, p<0.001). Black and Hispanic patients were diagnosed at a younger age compared to White (41.9 vs. 50.2 years, p<0.001) and non-Hispanic patients, respectively (41.1 vs. 49.1 years, p=0.002). CONCLUSION: There was a high rate of misdiagnosis of IC/BPS overall, with only 48.8% of patients with an ICD code for IC/BPS meeting diagnostic criteria. There were no significant associations between diagnostic accuracy and race/ethnicity. Black and Hispanic patients were more likely to receive a diagnosis of IC/BPS at a younger age, suggesting there may be differing natural histories or presentation patterns of IC/BPS between racial/ethnic groups.

      4. Hypertension in women: The role of adolescent childbearingexternal icon
        Datta BK, Husain MJ, Kostova D.
        BMC Public Health. 2021 Jul 29;21(1):1481.
        BACKGROUND: Adolescent childbearing is associated with various health risks to the mother and child, and potentially with adverse socioeconomic outcomes. However, little is known about the role of adolescent childbearing in maternal health outcomes in adulthood. This study investigates the link between childbirth in adolescence and later-life risk of hypertension among women in India. METHODS: We obtained nationally representative data on demographic and health outcomes for 442,845 women aged 25 to 49 from the India National Family Health Survey (NFHS) 2015-16. We assessed the difference in hypertension prevalence between women who gave birth in adolescence (age 10 to 19) and those who did not, for the full sample and various sub-samples, using linear probability models with controls for individual characteristics, hypertension risk factors, and geographic fixed effects. RESULTS: Nearly 40% of the women in the sample gave birth in adolescence. The adjusted probability of being hypertensive in adulthood was 2.3 percentage points higher for this group compared to women who did not give childbirth in adolescence. This added probability was larger for women who gave birth earlier in adolescence (4.8 percentage points) and for women who gave birth more than once in adolescence (3.4 percentage points). CONCLUSIONS: Adolescent childbearing was strongly associated with a higher probability of adult female hypertension in India. This finding illustrates the intertemporal relationship between health risk factors during the life cycle, informing the importance of addressing adverse early life events (e.g. child marriage and adolescent childbirth) for hypertension outcomes among women in India.

      5. Assessing national cervical cancer screening guidelines: Results from an HIV testing clinic also screening for cervical cancer and HPV in Soweto, South Africaexternal icon
        Hopkins KL, Jaffer M, Hlongwane KE, Otwombe K, Dietrich J, Cheyip M, Olivier J, Doherty T, Gray GE.
        PLoS One. 2021 ;16(7):e0255124.
        OBJECTIVE: A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women. METHODS: This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18-29, 30+ years), HIV status, Pap smear results and tested for statistical significance. RESULTS: Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear. CONCLUSION: South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women <30 years, both populations found to have high prevalence of HR-HPV. HPV-based primary screening from 25 years could improve outcomes.

    • Communicable Diseases
      1. Seasonal influenza during the COVID-19 pandemic in Bangladeshexternal icon
        Akhtar Z, Chowdhury F, Rahman M, Ghosh PK, Ahmmed MK, Islam MA, Mott JA, Davis W.
        PLoS One. 2021 ;16(8):e0255646.
        INTRODUCTION: During the 2019 novel coronavirus infectious disease (COVID-19) pandemic in 2020, limited data from several countries suggested reduced seasonal influenza viruses' circulation. This was due to community mitigation measures implemented to control the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used sentinel surveillance data to identify changes in the 2020 influenza season compared with previous seasons in Bangladesh. METHODS: We used hospital-based influenza surveillance (HBIS) data of Bangladesh that are generated year-round and are population-representative severe acute respiratory infection (SARI) data for all age groups from seven public and two private tertiary care level hospitals data from 2016 to 2019. We applied the moving epidemic method (MEM) by using R language (v4.0.3), and MEM web applications (v2.14) on influenza-positive rates of SARI cases collected weekly to estimate an average seasonal influenza curve and establish epidemic thresholds. RESULTS: The 2016-2019 average season started on epi week 18 (95% CI: 15-25) and lasted 12.5 weeks (95% CI: 12-14 weeks) until week 30.5. The 2020 influenza season started on epi week 36 and ended at epi week 41, lasting for only five weeks. Therefore, influenza epidemic started 18 weeks later, was 7.5 weeks shorter, and was less intense than the average epidemic of the four previous years. The 2020 influenza season started on the same week when COVID-19 control measures were halted, and 13 weeks after the measures were relaxed. CONCLUSION: Our findings suggest that seasonal influenza circulation in Bangladesh was delayed and less intense in 2020 than in previous years. Community mitigation measures may have contributed to this reduction of seasonal influenza transmission. These findings contribute to a limited but growing body of evidence that influenza seasons were altered globally in 2020.

      2. Detection of dengue virus serotype 1 in central nervous system of a child in Bandung, West Java: A case reportexternal icon
        Alisjahbana DH, Nurmawati S, Hakim DD, Milanti M, Dewi YP, Johar E, Myint KS, Lederman JP, Powers AM, Alisjahbana B, Antonjaya U.
        SAGE Open Med Case Reports. 2021 ;9.
        Central nervous system involvement of dengue virus is increasingly reported from endemic areas. This study describes the clinical characteristics and laboratory features of a pediatric patient enrolled in a central nervous system illness study conducted in 2017–2018 to identify viral and bacterial etiologies in Indonesian children. Dengue diagnostics including molecular and serological testing were performed on an encephalitis patient who presented with both classical dengue and neurological clinical symptoms. Dengue virus serotype 1 RNA was detected in both cerebrospinal fluid and serum by serotype-specific reverse transcription polymerase chain reaction, and the E gene was successfully sequenced. Anti-dengue virus immunoglobulin M was detected in both admission and discharge sera, whereas anti-dengue virus immunoglobulin G was identified only in the discharge serum. This study describes the central nervous system complications in a case with dengue virus infection in West Java, Indonesia, and highlights the potential for dengue virus serotype 1, a serotype rarely associated with neurotropism, to cause encephalitis. © The Author(s) 2021.

      3. Incident bone fracture and mortality in a large HIV cohort outpatient study, 2000-2017, USAexternal icon
        Battalora L, Armon C, Palella F, Li J, Overton ET, Hammer J, Fuhrer J, Novak RM, Carlson K, Spear JR, Buchacz K.
        Arch Osteoporos. 2021 Aug 2;16(1):117.
        We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. PURPOSE/INTRODUCTION: Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. METHODS: We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. RESULTS: Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000-2004 to 1.9 during 2013-2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15-1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. CONCLUSIONS: Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care.

      4. Improving pandemic response: Employing mathematical modeling to confront COVID-19external icon
        Biggerstaff M, Slayton RB, Johansson MA, Butler JC.
        Clin Infect Dis. 2021 Aug 3.
        Modeling complements surveillance data to inform COVID-19 public health decision making and policy development. This includes the use of modeling to improve situational awareness, to assess epidemiological characteristics, and to inform the evidence base for prevention strategies. To enhance modeling utility in future public health emergencies, the Centers for Disease Control and Prevention (CDC) launched the Infectious Disease Modeling and Analytics Initiative. The initiative objectives are to: (1) strengthen leadership in infectious disease modeling, epidemic forecasting, and advanced analytic work; (2) build and cultivate a community of skilled modeling and analytics practitioners and consumers across CDC; (3) strengthen and support internal and external applied modeling and analytic work; and, (4) working with partners, coordinate government-wide advanced data modeling and analytics for infectious diseases. These efforts are critical to help prepare CDC, the country, and the world to respond effectively to present and future infectious disease threats.

      5. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings - Barnstable County, Massachusetts, July 2021external icon
        Brown CM, Vostok J, Johnson H, Burns M, Gharpure R, Sami S, Sabo RT, Hall N, Foreman A, Schubert PL, Gallagher GR, Fink T, Madoff LC, Gabriel SB, MacInnis B, Park DJ, Siddle KJ, Harik V, Arvidson D, Brock-Fisher T, Dunn M, Kearns A, Laney AS.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 6;70(31):1059-1062.
        During July 2021, 469 cases of COVID-19 associated with multiple summer events and large public gatherings in a town in Barnstable County, Massachusetts, were identified among Massachusetts residents; vaccination coverage among eligible Massachusetts residents was 69%. Approximately three quarters (346; 74%) of cases occurred in fully vaccinated persons (those who had completed a 2-dose course of mRNA vaccine [Pfizer-BioNTech or Moderna] or had received a single dose of Janssen [Johnson & Johnson] vaccine ≥14 days before exposure). Genomic sequencing of specimens from 133 patients identified the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, in 119 (89%) and the Delta AY.3 sublineage in one (1%). Overall, 274 (79%) vaccinated patients with breakthrough infection were symptomatic. Among five COVID-19 patients who were hospitalized, four were fully vaccinated; no deaths were reported. Real-time reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold (Ct) values in specimens from 127 vaccinated persons with breakthrough cases were similar to those from 84 persons who were unvaccinated, not fully vaccinated, or whose vaccination status was unknown (median = 22.77 and 21.54, respectively). The Delta variant of SARS-CoV-2 is highly transmissible (1); vaccination is the most important strategy to prevent severe illness and death. On July 27, CDC recommended that all persons, including those who are fully vaccinated, should wear masks in indoor public settings in areas where COVID-19 transmission is high or substantial.* Findings from this investigation suggest that even jurisdictions without substantial or high COVID-19 transmission might consider expanding prevention strategies, including masking in indoor public settings regardless of vaccination status, given the potential risk of infection during attendance at large public gatherings that include travelers from many areas with differing levels of transmission.

      6. IMPORTANCE: Persistence of cervical high-risk human papillomavirus (hrHPV) after treatment for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) has not been compared between cryotherapy and loop electrosurgical excision procedure (LEEP) among HIV-positive women. OBJECTIVE: To evaluate whether cryotherapy or LEEP is more effective at clearing hrHPV and whether persistent hrHPV is associated with CIN2+ recurrence among HIV-positive women. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a randomized clinical trial conducted among women with HIV, hrHPV, and CIN2+ in Nairobi, Kenya. From June 2011 to September 2016, 354 HIV-positive women with CIN2+ disease had hrHPV cervical samples collected before and after treatment with cryotherapy or LEEP. Data were analyzed from September 2018 to January 2021. INTERVENTIONS: Women were randomized 1:1 to receive cryotherapy or LEEP and were followed up every 6 months for 24 months with hrHPV cervical swab and Papanicolaou test with confirmatory biopsy. MAIN OUTCOMES AND MEASURES: The main outcomes of this analysis were hrHPV positivity defined as having 1 of 12 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and disease recurrence defined as CIN grade 2 or higher as determined with cervical biopsy. RESULTS: A total of 354 HIV-positive women with CIN2+ were included in the study; mean (SD) age was 37 (8) years in the cryotherapy arm and 38 (9) years in the LEEP arm. Baseline hrHPV prevalence was 90% (160 of 177) in the cryotherapy arm and 94% (166 of 177) in the LEEP arm (P = .24), and the most common hrHPV types detected were 16 (87 of 326 [27%]), 58 (87 of 326 [27%]), 35 (86 of 326 [26%]), 52 (66 of 326 [20%]), and 18 (56 of 325 [17%]). Over 24 months, clearance of hrHPV was significantly higher among those who underwent LEEP compared with cryotherapy (hazard ratio, 1.40; 95% CI, 1.03-1.90; P = .03). In multivariable analysis, hrHPV type-specific persistence at 12-month follow-up was significantly associated with CIN2+ recurrence from 12 months to 24 months (adjusted hazard ratio, 4.70; 95% CI, 2.47-8.95; P < .001). Performance of hrHPV testing at 12 months for recurrent CIN2+ was 93% sensitivity, 46% specificity, 38% positive predictive value, and 95% negative predictive value. CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, HIV-positive women who received LEEP were more likely to clear hrHPV infection compared with those undergoing cryotherapy, reinforcing the efficacy of LEEP in this population. Persistent hrHPV was significantly associated with recurrent CIN2+, suggesting that LEEP's benefits may be related in part to its ability to clear hrHPV infection. Screening for hrHPV infection after treatment among HIV-positive women may be used to rule out recurrent CIN disease given its high sensitivity and negative predictive value. TRIAL REGISTRATION: Identifier: NCT01298596.

      7. SARS-CoV-2 prevalence among outpatients during community transmission, Zambia, July 2020external icon
        Hines JZ, Fwoloshi S, Kampamba D, Barradas DT, Banda D, Zulu JE, Wolkon A, Yingst S, Boyd MA, Siwingwa M, Chirwa L, Kapina M, Sinyange N, Mukonka V, Malama K, Mulenga LB, Agolory S.
        Emerg Infect Dis. 2021 Aug;27(8):2166-2168.
        During the July 2020 first wave of severe acute respiratory syndrome coronavirus 2 in Zambia, PCR-measured prevalence was 13.4% among outpatients at health facilities, an absolute difference of 5.7% compared with prevalence among community members. This finding suggests that facility testing might be an effective strategy during high community transmission.

      8. Improved detection and management of advanced HIV disease through a community adult TB-contact tracing intervention with same-day provision of the WHO-recommended package of care including art initiation in a rural district of Mozambiqueexternal icon
        Izco S, Murias-Closas A, Jordan AM, Greene G, Catorze N, Chiconela H, Garcia JI, Blanco-Arevalo A, Febrer A, Casellas A, Saavedra B, Chiller T, Nhampossa T, Garcia-Basteiro A, Letang E.
        J Int AIDS Soc. 2021 Aug;24(8):e25775.
        INTRODUCTION: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. METHODS: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/μL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. RESULTS: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. CONCLUSIONS: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.

      9. Transmission dynamics of severe acute respiratory syndrome coronavirus 2 in high-density settings, Minnesota, USA, March-June 2020external icon
        Lehnertz NB, Wang X, Garfin J, Taylor J, Zipprich J, VonBank B, Martin K, Eikmeier D, Medus C, Wiedinmyer B, Bernu C, Plumb M, Pung K, Honein MA, Carter R, MacCannell D, Smith KE, Como-Sabetti K, Ehresmann K, Danila R, Lynfield R.
        Emerg Infect Dis. 2021 Aug;27(8):2052-2063.
        Coronavirus disease has disproportionately affected persons in congregate settings and high-density workplaces. To determine more about the transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in these settings, we performed whole-genome sequencing and phylogenetic analysis on 319 (14.4%) samples from 2,222 SARS-CoV-2-positive persons associated with 8 outbreaks in Minnesota, USA, during March-June 2020. Sequencing indicated that virus spread in 3 long-term care facilities and 2 correctional facilities was associated with a single genetic sequence and that in a fourth long-term care facility, outbreak cases were associated with 2 distinct sequences. In contrast, cases associated with outbreaks in 2 meat-processing plants were associated with multiple SARS-CoV-2 sequences. These results suggest that a single introduction of SARS-CoV-2 into a facility can result in a widespread outbreak. Early identification and cohorting (segregating) of virus-positive persons in these settings, along with continued vigilance with infection prevention and control measures, is imperative.

      10. Estimating the effect of increasing dispensing intervals on retention in care for people with HIV in Haitiexternal icon
        Parrish C, Basu A, Fishman P, Koama JB, Robin E, Francois K, Honore JG, Van Onacker JD, Puttkammer N.
        EClinicalMedicine. 2021 August;38.
        Background: Multi-month dispensing (MMD) for antiretroviral therapy (ART) is a promising care strategy to improve HIV treatment adherence. The effectiveness of MMD in routine settings has not yet been evaluated within a causal inference framework. We analyzed data from a robust clinical data system to evaluate MMD in Haiti. Method(s): We assessed 1-year retention in care among 21,880 ART-naive HIV-positive persons who started ART on or after January 1, 2017, up until November 1, 2018. We used an instrumental variable analysis to estimate the causal impact of MMD. This approach was used to address potential selection into specific dispensing intervals because MMD is not randomly applied to individuals. Finding(s): We found that extending ART dispensing intervals increased the probability of retention at 12 months after ART initiation, with up to a 24.2%-point increase (95%CI: 21.9, 26.5) in the likelihood of retention with extending dispenses by 30 days for those receiving one-month dispenses. We observed statistically significant gains to retention with MMD with up to an approximately 4-month supply of ART; +5.1%-points (95%CI: 2.4,7.8). Increasing dispensing lengths for those already receiving >=5-month supply of ART had a potentially negative effect on retention. Interpretation(s): MMD for ART is an effective service delivery strategy that improves care retention for new ART recipients. There is a potentially negative effect of increasing prescription lengths for those new ART recipients already receiving longer ART supplies, though more research is needed to characterize this effect given medication supplies of this length are not common for newer ART recipients. Copyright © 2021 The Author(s)

      11. Adherence to daily oral TDF/FTC for PrEP in community health center populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Studyexternal icon
        Smith DK, Rawlings MK, Glick N, Mena L, Coleman M, Houlberg M, McCallister S, Wiener J.
        AIDS Behav. 2021 Aug 4.
        The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0-1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0-1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09-2.34) or "Other" race (RR 1.62, CI 0.99-2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33-4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level.

    • Environmental Health
      1. Temporal trends of concentrations of per- and polyfluoroalkyl substances among adults with overweight and obesity in the United States: Results from the Diabetes Prevention Program and NHANESexternal icon
        Lin PD, Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Calafat AM, Webster TF, Horton ES, Oken E.
        Environ Int. 2021 Jul 29;157:106789.
        BACKGROUND: Understanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S. OBJECTIVES: Determine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age. METHODS: We described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m(2)). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model. RESULTS: Longitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS. DISCUSSION: We observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.

    • Epidemiology and Surveillance
      1. Participatory surveillance of COVID-19 in Lesotho via weekly calls: Protocol for cell phone data collectionexternal icon
        Greenleaf A, Mwima G, Lethoko M, Conkling M, Keefer G, Chang C, McLeod N, Maruyama H, Chen Q, Farley S, Low A.
        JMIR Res Protoc. 2021 Aug 1.
        BACKGROUND: The increase in cell phone ownership in low- and middle- income countries (LMIC) has created an opportunity for low-cost, rapid turnaround data collection by calling participants on their cell phones. Cell phones can be mobilized for myriad data collection purposes, including surveillance. In LMIC, cell phone-based surveillance has been used to track Ebola, measles, acute flaccid paralysis, and diarrheal disease, as well as non-communicable diseases. Phone-based surveillance in LMIC is a particularly pertinent, burgeoning approach in the context of the COVID-19 pandemic. Participatory surveillance via cell phone could allow governments to assess burden of disease and complements existing surveillance systems. OBJECTIVE: We describe the protocol for the LeCellPHIA project, a cell phone surveillance system that collects weekly population-based data on influenza-like illness (ILI) in Lesotho by calling a representative sample of a recent face-to-face survey. METHODS: We established a phone-based surveillance system to collect ILI symptoms from approximately 1700 participants who had participated in a recent face-to-face survey in Lesotho, the Population-based HIV Impact Assessment (PHIA) Survey. Of the 15,267 PHIA participants who were over 18, 11,975 (78.44%) consented to future research and provided a valid phone number. We followed the PHIA sample design and included 342 primary sampling units from 10 districts. We randomly selected 5 households from each primary sampling unit that had an eligible participant and sampled one person per household. We oversampled the elderly, as they are more likely to be affected by COVID-19. A three-day Zoom training was conducted in June 2020 to train LeCellPHIA interviewers. RESULTS: The surveillance system launched July 1, 2020, beginning with a two-week enrollment period followed by weekly calls that will continue until September 30, 2021. Of the 11,975 phone numbers that were in the sample frame, 3,020 were sampled and 1,778 were enrolled. CONCLUSIONS: The surveillance system will track COVID-19 in a resource-limited setting. The novel approach of a weekly cell phone-based surveillance system can be used to track other health outcomes and this protocol provides information about how to implement such a system.

      2. Use of SMS-linked electronic surveys for COVID-19 case investigation and contact tracing - Marin County, CA, USAexternal icon
        Janssen JM, McGrath A, Ereman R, Moonan PK, Oeltmann JE, Willis M, McCurdy SA.
        Public Health Pract (Oxf). 2021 Nov;2:100170.
        OBJECTIVES: We sought to quantify the proportion of contacts reported by persons with COVID-19 through a short message service (SMS)-linked survey in comparison to the proportion of contacts reported during a follow-up phone-interview. We also sought to assess improvement in contact tracing timeliness associated with sending SMS-linked surveys. STUDY DESIGN: During December 4-15, 2020, persons identified as COVID-19 cases whose data was entered into Marin County's contact tracing database on even days received a SMS-linked survey and persons whose data was entered on odd days did not; all were called for case investigation and contact tracing. Chi-square test and Fisher's exact test were used to compare demographic data. Chi-square test was used to contrast categorical outcomes, and Wilcoxon's rank-sum test was used for continuous outcomes. RESULTS: Among 350 SMS-linked survey recipients, 85 (24%) responded and 4 (1%) reported contacts using the survey; an additional 303 contacts were reported during phone interviews. Without phone interviews, 99% of reported contacts would have been missed. There was no meaningful difference between study arms in the proportion of contacts notified within 48 h. CONCLUSIONS: This SMS-linked survey had low participation and was not useful for identifying contacts. Phone interviews remained crucial for COVID-19 contact tracing.

    • Genetics and Genomics
      1. Three cases of infant botulism were reported in a small Colorado town between 1981 and 1984. The first two cases occurred in 1981, 6 months apart, and the third case occurred in 1984. Clostridium botulinum type A was isolated from stool of all three case patients and from environmental samples of the patient's homes. An epidemiological investigation and follow-up study were conducted from 1981 to 1986 and concluded the cases were likely related. In this study, we sought to determine whether the C. botulinum type A clinical isolates were related to each other and to isolates obtained from environmental samples. We performed whole genome sequencing (WGS) for 17 isolates associated with this potential cluster of infant botulism. Fifteen isolates were confirmed to be C. botulinum type A(B) and contained botulinum toxin gene subtypes A1 and B5 by WGS; these strains formed a monophyletic cluster in a phylogeny and were considered closely related to each other (0-18 high-quality single-nucleotide polymorphisms), but distinct from other C. botulinum type A(B) in Colorado and elsewhere in the United States. Results of our study suggest that the three infant botulism cases could have represented a cluster due to a C. botulinum type A(B) strain present in the environment.

      2. COPLA, a taxonomic classifier of plasmidsexternal icon
        Redondo-Salvo S, Bartomeus-Peñalver R, Vielva L, Tagg KA, Webb HE, Fernández-López R, de la Cruz F.
        BMC Bioinformatics. 2021 Jul 31;22(1):390.
        BACKGROUND: Plasmids are mobile genetic elements, key in the dissemination of antibiotic resistance, virulence determinants and other adaptive traits in bacteria. Obtaining a robust method for plasmid classification is necessary to better understand the genetics and epidemiology of many pathogens. Until now, plasmid classification systems focused on specific traits, which limited their precision and universality. The definition of plasmid taxonomic units (PTUs), based on average nucleotide identity metrics, allows the generation of a universal plasmid classification scheme, applicable to all bacterial taxa. Here we present COPLA, a software able to assign plasmids to known and novel PTUs, based on their genomic sequence. RESULTS: We implemented an automated pipeline able to assign a given plasmid DNA sequence to its cognate PTU, and assessed its performance using a sample of 1000 unclassified plasmids. Overall, 41% of the samples could be assigned to a previously defined PTU, a number that reached 63% in well-known taxa such as the Enterobacterales order. The remaining plasmids represent novel PTUs, indicating that a large fraction of plasmid backbones is still uncharacterized. CONCLUSIONS: COPLA is a bioinformatic tool for universal, species-independent, plasmid classification. Offered both as an automatable pipeline and an open web service, COPLA will help bacterial geneticists and clinical microbiologists to quickly classify plasmids.

    • Health Disparities
      1. Racial disparity in potential occupational exposure to COVID-19external icon
        Asfaw A.
        J Racial Ethn Health Disparities. 2021 Aug 5.
        BACKGROUND: Nationwide, as of 20 June 2021, COVID-19 has claimed more than 599,000 lives and infected nearly 33 million people. Studies have shown that COVID-19 disproportionately affects some racial and ethnic minority groups. This study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high COVID-19 exposure risks, relative to their share in the total workforce. The study incorporates white collar workers, who to date have not gotten as much attention in terms of workers safety. METHODS: Using the March and April 2020 Current Population Survey and O*Net data, this study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high risk of exposure to COVID-19 (exposure to disease and infection at work, inability to maintain physical distancing at work, and inability to work from home) relative to their share in the total workforce. RESULTS: The results showed that Black workers were overrepresented in occupations with high potential risk of exposure to disease and infection at work and inability to maintain physical distancing at work. Hispanic workers were overrepresented in occupations where potential risk of inability to work from home was the highest. CONCLUSION: Occupation can be one of the risk factors for the current disproportionately high COVID-19 infection rates among Black and Hispanic workers. COVID-19-related prevention measures at high risk occupations, including providing adequate personal protective equipment, training, working space, and vaccinations, could help to reduce not only the spread of COVID-19 and infectious diseases but also their disproportionately high impact in certain minority racial and ethnic groups.

      2. Subjective cognitive decline higher among sexual and gender minorities in the United States, 2015-2018external icon
        Flatt JD, Cicero EC, Lambrou NH, Wharton W, Anderson JG, Bouldin ED, McGuire LC, Taylor CA.
        Alzheimers Dement (N Y). 2021 ;7(1):e12197.
        INTRODUCTION: Subjective cognitive decline (SCD) represents self-reported problems with memory, a possible early sign of dementia. Little is known about SCD among sexual and gender minority (SGM) adults who identify as lesbian, gay, bisexual, and/or transgender or gender non-binary. METHODS: Data were weighted to represent population estimates from 25 states' 2015-2018 Behavioral Risk Factor Surveillance System to describe SCD in adults ≥45 years by SGM status. Logistic regression tested associations between demographic and health conditions. RESULTS: SCD prevalence was higher in SGM (15.7%; 95% confidence interval [CI]:13.1-18.2) than in non-SGM adults (10.5%; 95% CI:10.1-10.9; P < .0001). SGM adults with SCD were also more likely to report functional limitations due to SCD than non-SGM adults with SCD, 60.8% versus 47.8%, P = .0048. Differences in SCD by SGM status were attenuated after accounting for depression. DISCUSSION: Higher prevalence of SCD in SGM adults highlights the importance of ensuring inclusive screenings, interventions, care services, and resources for SGM adults.

      3. Association of community socioeconomic deprivation with evidence of reduced kidney function at time of type 2 diabetes diagnosisexternal icon
        Hirsch AG, Nordberg CM, Chang A, Poulsen MN, Moon KA, Siegel KR, Rolka DB, Schwartz BS.
        SSM - Population Health. 2021 September;15.
        Background: While there are known individual-level risk factors for kidney disease at time of type 2 diabetes diagnosis, little is known regarding the role of community context. We evaluated the association of community socioeconomic deprivation (CSD) and community type with estimated glomerular filtration rate (eGFR) when type 2 diabetes is diagnosed. Method(s): This was a retrospective cohort study of 13,144 adults with newly diagnosed type 2 diabetes in Pennsylvania. The outcome was the closest eGFR measurement within one year prior to and two weeks after type 2 diabetes diagnosis, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation. We used adjusted multinomial regression models to estimate associations of CSD (quartile 1, least deprivation) and community type (township, borough, city) with eGFR and used adjusted generalized estimating equation models to evaluate whether community features were associated with the absence of diabetes screening in the years prior to type 2 diabetes diagnosis. Result(s): Of the participants, 1279 (9.7%) had hyperfiltration and 1377 (10.5%) had reduced eGFR. Women were less likely to have hyperfiltration and more likely to have reduced eGFR. Black (versus White) race was positively associated with hyperfiltration when the eGFR calculation was corrected for race but inversely associated without the correction. Medical Assistance (ever versus never) was positively associated with reduced eGFR. Higher CSD and living in a city were each positively associated (odds ratio [95% confidence interval]) with reduced eGFR (CSD quartiles 3 and 4 versus quartile 1, 1.23 [1.04, 1.46], 1.32 [1.11, 1.58], respectively; city versus township, 1.38 [1.15, 1.65]). These features were also positively associated with the absence of a type 2 diabetes screening measure. Conclusion(s): In a population-based sample, more than twenty percent had hyperfiltration or reduced eGFR at time of type 2 diabetes diagnosis. Individual- and community-level factors were associated with these outcomes. Copyright © 2021 The Authors

      4. Majority African-American neighborhoods on the edges of North Carolina municipalities are less likely than white peri-urban neighborhoods to be served by a community system regulated under the Safe Drinking Water Act. These households rely on unregulated private wells, which are at much higher risk of contamination than neighboring community water supplies. Yet, risk awareness of consuming well water is low, and no prior research has tested risk communication interventions for these communities. We present a randomized-controlled trial of an oversized postcard to promote water testing among this audience. The postcard design followed the mental models approach to risk communication. To our knowledge, this is the first U.S. randomized-controlled trial of a mailed communication to promote water testing in any audience and one of few trials of the mental models approach. We evaluated the postcard's effects on self-reported water testing with and without a free water test offer (vs. no-intervention control) via a survey mailed one month after the interventions. The combined communication and free test doubled the odds of self-reported water testing, compared to the control group (p = 0.046). It increased the odds of testing by 65%, compared to the free test alone. Recall of receiving a postcard about water testing increased the odds of self-reported testing twelve-fold (p < 0.001). Although these results suggest that targeted risk information delivered by mail can promote water testing when paired with a free test, the mechanism remains unclear. Additional research on beliefs influencing perceptions about well water may yield interventions that are even more effective.

    • Health Economics
      1. Insurance reimbursements for recombinant zoster vaccine in the private sectorexternal icon
        Leidner AJ, Tang Z, Guo A, Anderson TC, Tsai Y.
        Vaccine. 2021 Aug 2.
        A two-dose series of the recombinant zoster vaccine (RZV, Shingrix) was licensed by the Food and Drug Administration in 2017 and recommended by the Advisory Committee on Immunization Practices in 2018 for adults in the United States age 50 years and older. Despite the health benefits of shingles vaccination, coverage has remained low, with financial barriers among healthcare providers identified as one potential factor. This study estimates the reimbursement levels for RZV among a large sample of privately insured individuals in the US from the 2018 IBM® MarketScan® Commercial Claims and Encounters database. Of 198,534 claims for an RZV dose, the mean reimbursement was $149. Most claims (83%) exceeded $140, which was the private sector vaccine price reported on the CDC vaccine price list in April 2018. These results can be useful for providers considering procuring RZV and for state immunization programs considering ways to improve vaccination coverage.

    • Healthcare Associated Infections
      1. Skin metagenomic sequence analysis of early Candida auris outbreaks in U.S. nursing homesexternal icon
        Huang X, Welsh RM, Deming C, Proctor DM, Thomas PJ, Gussin GM, Huang SS, Kong HH, Bentz ML, Vallabhaneni S, Chiller T, Jackson BR, Forsberg K, Conlan S, Litvintseva AP, Segre JA.
        mSphere. 2021 Aug 4:e0028721.
        Candida auris is a human fungal pathogen classified as an urgent threat to the delivery of health care due to its extensive antimicrobial resistance and the high mortality rates associated with invasive infections. Global outbreaks have occurred in health care facilities, particularly, long-term care hospitals and nursing homes. Skin is the primary site of colonization for C. auris. To accelerate research studies, we developed microbiome sequencing protocols, including amplicon and metagenomic sequencing, directly from patient samples at health care facilities with ongoing C. auris outbreaks. We characterized the skin mycobiome with a database optimized to classify Candida species and C. auris to the clade level. While Malassezia species were the predominant skin-associated fungi, nursing home residents also harbored Candida species, including C. albicans, and C. parapsilosis. Amplicon sequencing was concordant with culturing studies to identify C. auris-colonized patients and provided further resolution that distinct clades of C. auris are colonizing facilities in New York and Illinois. Shotgun metagenomic sequencing from a clinical sample with a high fungal bioburden generated a skin-associated profile of the C. auris genome. Future larger scale clinical studies are warranted to more systematically investigate the effects of commensal microbes and patient risk factors on the colonization and transmission of C. auris. IMPORTANCE Candida auris is a human pathogen of high concern due to its extensive antifungal drug resistance and high mortality rates associated with invasive infections. Candida auris skin colonization and persistence on environmental surfaces make this pathogen difficult to control once it enters a health care facility. Residents in long-term care hospitals and nursing homes are especially vulnerable. In this study, we developed microbiome sequencing protocols directly from surveillance samples, including amplicon and metagenomic sequencing, demonstrating concordance between sequencing results and culturing.

      2. Supplemental findings of the 2019 National Blood Collection and Utilization Surveyexternal icon
        Mowla SJ, Sapiano MR, Jones JM, Berger JJ, Basavaraju SV.
        Transfusion. 2021 Aug 1.
        INTRODUCTION: Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). METHODS: National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. RESULTS: Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. CONCLUSION: Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.

      3. Donor-derived ehrlichiosis: Two clusters following solid organ transplantationexternal icon
        Saha A, Browning C, Dandamudi R, Barton K, Graepel K, Cullity M, Abusalah W, Christine D, Rossi C, Drexler N, Basavaraju S, Annambhotia P, Guillamet RV, Eid AJ, Maliakkal J, Miller A, Hugge C, Dharnidharka VR, Kandula P, Moritz MJ.
        Clin Infect Dis. 2021 Jul 30.
        Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor derived clusters of ehrlichiosis are described here. During the summer of 2020, two cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis (HLH). Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All three were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization (OPO) and the OPTN for further investigation by public health authorities.

    • Immunity and Immunization
      1. COVID-19 vaccine safety in adolescents aged 12-17 years - United States, December 14, 2020-July 16, 2021external icon
        Hause AM, Gee J, Baggs J, Abara WE, Marquez P, Thompson D, Su JR, Licata C, Rosenblum HG, Myers TR, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 6;70(31):1053-1058.
        As of July 30, 2021, among the three COVID-19 vaccines authorized for use in the United States, only the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine is authorized for adolescents aged 12-17 years. The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech vaccine for use in persons aged ≥16 years on December 11, 2020 (1); the EUA was expanded to include adolescents aged 12-15 years on May 10, 2021 (2), based on results from a Phase 3 clinical trial (3). Beginning in June 2021, cases of myocarditis and myopericarditis (hereafter, myocarditis) after receipt of Pfizer-BioNTech vaccine began to be reported, primarily among young males after receipt of the second dose (4,5). On June 23, 2021, CDC's Advisory Committee on Immunization Practices (ACIP) reviewed available data and concluded that the benefits of COVID-19 vaccination to individual persons and the population outweigh the risks for myocarditis and recommended continued use of the vaccine in persons aged ≥12 years (6). To further characterize safety of the vaccine, adverse events after receipt of Pfizer-BioNTech vaccine reported to the Vaccine Adverse Event Reporting System (VAERS) and adverse events and health impact assessments reported in v-safe (a smartphone-based safety surveillance system) were reviewed for U.S. adolescents aged 12-17 years during December 14, 2020-July 16, 2021. As of July 16, 2021, approximately 8.9 million U.S. adolescents aged 12-17 years had received Pfizer-BioNTech vaccine.* VAERS received 9,246 reports after Pfizer-BioNTech vaccination in this age group; 90.7% of these were for nonserious adverse events and 9.3% were for serious adverse events, including myocarditis (4.3%). Approximately 129,000 U.S. adolescents aged 12-17 years enrolled in v-safe after Pfizer-BioNTech vaccination; they reported local (63.4%) and systemic (48.9%) reactions with a frequency similar to that reported in preauthorization clinical trials. Systemic reactions were more common after dose 2. CDC and FDA continue to monitor vaccine safety and provide data to ACIP to guide COVID-19 vaccine recommendations.

      2. Environmental surveillance for risk assessment in the context of a phase 2 clinical trial of type 2 novel oral polio vaccine in Panamaexternal icon
        Rojas-Bonilla M, Coulliette-Salmond A, Belgasmi H, Wong K, Sayyad L, Vega E, Grimoldi F, Oberste MS, Ruttimann R.
        Viruses. 2021 ;13(7).
        Environmental surveillance was recommended for risk mitigation in a novel oral polio vaccine-2 (nOPV2) clinical trial (M5-ABMG) to monitor excretion, potential circulation, and loss of attenuation of the two nOPV2 candidates. The nOPV2 candidates were developed to address the risk of poliovirus (PV) type 2 circulating vaccine-derived poliovirus (cVDPV) as part of the global eradication strategy. Between November 2018 and January 2020, an environmental surveillance study for the clinical trial was conducted in parallel to the M5-ABMG clinical trial at five locations in Panama. The collection sites were located upstream from local treatment plant inlets, to capture the excreta from trial participants and their community. Laboratory analyses of 49 environmental samples were conducted using the two-phase separation method. Novel OPV2 strains were not detected in sewage samples collected during the study period. However, six samples were positive for Sabin-like type 3 PV, two samples were positive for Sabin-like type 1 PV, and non-polio entero-viruses NPEVs were detected in 27 samples. One of the nOPV2 candidates has been granted Emergency Use Listing by the World Health Organization and initial use started in March 2021. This environmental surveillance study provided valuable risk mitigation information to support the Emergency Use Listing application. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      3. Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introductionexternal icon
        Senghore M, Tientcheu PE, Worwui AK, Jarju S, Okoi C, Suso SM, Foster-Nyarko E, Ebruke C, Sonko M, Kourna MH, Agossou J, Tsolenyanu E, Renner LA, Ansong D, Sanneh B, Cisse CB, Boula A, Miwanda B, Lo SW, Gladstone RA, Schwartz S, Hawkins P, McGee L, Klugman KP, Breiman RF, Bentley SD, Mwenda JM, Kwambana-Adams BA, Antonio M.
        Microb Genom. 2021 Jul;7(7).
        Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

      4. Impact of mandatory vaccination of healthcare personnel on rates of influenza and other viral respiratory pathogensexternal icon
        Simberkoff MS, Rattigan SM, Gaydos CA, Gibert CL, Gorse GJ, Nyquist AC, Price CS, Reich N, Rodriguez-Barradas MC, Bessesen M, Brown A, Cummings DA, Radonovich LJ, Perl TM.
        Infect Control Hosp Epidemiol. 2021 Aug 5:1-5.
        OBJECTIVE: The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings. SETTING: Four Veterans' Affairs (VA) health systems and three non-VA medical centers. METHODS: We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies. RESULTS: Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13-0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02-1.57). CONCLUSIONS: Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%-53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.

      5. Assessment of genetic changes and neurovirulence of shed sabin and novel type 2 oral polio vaccine virusesexternal icon
        Wahid R, Mercer L, Macadam A, Carlyle S, Stephens L, Martin J, Chumakov K, Laassri M, Petrovskaya S, Smits SL, Stittelaar KJ, Gast C, Weldon WC, Konopka-Anstadt JL, Oberste MS, Van Damme P, De Coster I, Rüttimann R, Bandyopadhyay A, Konz J.
        NPJ Vaccines. 2021 Jul 29;6(1):94.
        Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.

    • Laboratory Sciences
      1. This study evaluated the ability of the MALDI-ToF MS from Bruker Daltonics to identify clinical Mitis-Group-Streptococcus isolates with a focus on Streptococcus pseudopneumoniae. The results were analyzed using the standard log(score) and the previously published list(score). Importantly, using the log(score) no misidentifications occurred and 27 of 29 (93%) S. pneumoniae and 27 of 30 (90%) S. oralis strains were identified, but only 1 of 31 (3%) S. pseudopneumoniae and 1 of 13 (8%) S. mitis strains were identified. However, our results show that 30 of 31 S. pseudopneumoniae strains had a S. pseudopneumoniae Main Spectral Profiles within the 3 best matches. Using the list(score) all S. oralis and S. pneumoniae strains were identified correctly, but list(score) misidentified 10 S. pseudopneumoniae and 5 S. mitis. We propose to use the log(score) for identification of S. pneumoniae, S. pseudopneumoniae, S. mitis and S. oralis, but for some strains additional testing may be needed.

      2. Quantification of SARS-CoV-2 spike and nucleocapsid proteins using isotope dilution tandem mass spectrometryexternal icon
        Pierce-Ruiz C, Santana WI, Sutton WJ, Fischler DA, Cooper HC, Marc LR, Barr JR, Williams TL.
        Vaccine. 2021 Jul 24.
        The emergence and subsequent global outbreak of the novel coronavirus SARS-CoV-2 prompted our laboratory to launch efforts to develop methods for SARS-CoV-2 antigen detection and quantification. We present an isotope dilution mass spectrometry method (IDMS) for rapid and accurate quantification of the primary antigens, spike and nucleocapsid proteins. This IDMS method utilizes liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze sample tryptic digests for detection and quantification of selected conserved peptides of SARS-CoV-2 spike and nucleocapsid proteins. The IDMS method has the necessary attributes to be successfully utilized for accurate quantification in SARS-CoV-2 protein-based vaccines and as targets of rapid diagnostic tests. Absolute quantification was achieved by quantifying and averaging 5 peptides for spike protein (3 peptides in the S1 subunit and 2 peptides in the S2 subunit) and 4 peptides for nucleocapsid protein. The overall relative standard deviation of the method was 3.67% for spike protein and 5.11% for nucleocapsid protein. IDMS offers speed (5 h total analysis time), sensitivity (LOQ; 10 fmol/µL) and precision for quantification of SARS-CoV-2 spike and nucleocapsid proteins.

      3. Characterization of the first carbapenem-resistant Pseudomonas aeruginosa clinical isolate harboring bla(sim-1) from the United Statesexternal icon
        Prussing C, Canulla T, Singh N, McAuley P, Gosciminski M, King E, Bandy U, Machado MJ, Karlsson M, Musser KA, Huard RC, Nazarian EJ.
        Antimicrob Agents Chemother. 2021 Aug 2:Aac0106621.
        The emergence and transmission of metallo-β-lactamases are significant public health concerns that threaten the utility of antimicrobial therapy (1, 2).….

    • Maternal and Child Health
      1. Periconceptional nonsteroidal anti-inflammatory drug use, folic acid intake, and the risk of spina bifidaexternal icon
        Esposito DB, Parker SE, Mitchell AA, Tinker SC, Werler MM.
        Birth Defects Res. 2021 Aug 3.
        BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy may increase risk for neural tube defects (NTDs), including spina bifida. Folic acid intake can prevent NTDs, but it is not known whether it modifies any risks associated with NSAID use. OBJECTIVES: To assess the impact of periconceptional NSAID use on the risk of spina bifida overall and stratified by folic acid intake. STUDY DESIGN: We analyzed 1998-2015 data from the Slone Epidemiology Center Birth Defects Study, a multi-site, case-control study. Mothers were interviewed to identify sociodemographic factors, behaviors, and exposures during pregnancy. Periconceptional NSAID use was defined as use of aspirin, ibuprofen, naproxen, or COX2 inhibitors within the month before or after the last menstrual period. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for NSAID use, adjusted for study center and race/ethnicity stratified by average daily folic acid intake above ("high FA") or below ("low FA") 400 mcg/day. RESULTS: We compared mothers of 267 infants with spina bifida to mothers of 6,233 nonmalformed controls. Among control mothers, 20% used NSAIDS periconceptionally (16% ibuprofen, 4% aspirin, 3% naproxen, and <1% COX-2 inhibitors). For any NSAID use, the aORs among low FA and high FA women were 1.70 (95% CI [1.13, 2.57]) and 1.09 (95% CI [0.69, 1.71]), respectively. CONCLUSIONS: We observed a small increase in the risk for spina bifida among infants born to women who used NSAIDs periconceptionally, but this risk was limited to those who had inadequate folic acid intake.

    • Nutritional Sciences
      1. A qualitative analysis of program fidelity and perspectives of educators and parents after two years of the girls' iron-folate tablet supplementation (GIFTS) program in Ghanaian secondary schoolsexternal icon
        Gosdin L, Amoaful EF, Sharma D, Sharma AJ, Addo OY, Ashigbi X, Mumuni B, Situma R, Ramakrishnan U, Martorell R, Jefferds ME.
        Curr Dev Nutr. 2021 Jul;5(7):nzab094.
        BACKGROUND: To address the burden of anemia in adolescent girls in Ghana, the Girls' Iron-Folate Tablet Supplementation (GIFTS) program was established in 2017. An evaluation found that although iron and folic acid (IFA) supplementation reached nearly all adolescent girls in schools during year 1, most girls received fewer than the minimum effective number of tablets over the school year. Barrier analyses highlighted schools as drivers of adherence, though information was incomplete on the reasons for the disparities among schools. Information was also lacking on the implementation of health and nutrition education. OBJECTIVES: At the start of year 3 of an integrated adolescent anemia prevention program with IFA supplementation, the present study sought to illuminate differences in program fidelity among schools and across time and potential factors that drive such differences. METHODS: After stratifying by school level, size, geographic location, and intake adherence during year 1, 16 schools were purposively selected. For each school, semistructured key informant interviews were conducted with 1 coordinator at the district level, 3 educators at the school level, and 1 parent leader. Following thematic analysis methods, recorded and transcribed interviews were coded and organized into deductive and inductive themes. RESULTS: Limited training, challenges during distribution of IFA, lack of incentives, and inconsistent health and nutrition education diminished program fidelity. Strong supply chain, widespread awareness promotion, improved acceptability, and intrinsically motivated educators improved program fidelity. After 2 y of implementation, schools had made program adaptations, and widespread changes in attitudes and beliefs about the IFA tablets had improved their acceptability. However, limitations remained related to supply chain, program ownership, communication between health and education sectors, training, motivation, and resources. CONCLUSIONS: The fidelity of Ghana's GIFTS program is strengthened by its supply chain, acceptability, and motivated stakeholders; however, training, curricula, clear communication, and incentives could improve it.

      2. BACKGROUND: Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). METHODS: In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×10(9)/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. FINDINGS: 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05). INTERPRETATION: The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. FUNDING: None.

    • Occupational Safety and Health
      1. During emergencies, areas with higher social vulnerability experience an increased risk for negative health outcomes. However, research has not extrapolated this concept to understand how the workers who respond to these areas may be affected. Researchers from the National Institute for Occupational Safety and Health (NIOSH) merged approximately 160,000 emergency response calls received from three fire departments during the COVID-19 pandemic with the CDC’s publicly available Social Vulnerability Index (SVI) to examine the utility of SVI as a leading indicator of occupational health and safety risks. Multiple regressions, binomial logit models, and relative weights analyses were used to answer the research questions. Researchers found that higher social vulnerability on household composition, minority/language, and housing/transportation increase the risk of first responders’ exposure to SARS-CoV-2. Higher socioeconomic, household, and minority vulnerability were significantly associated with response calls that required emergency treatment and transport in comparison to fire-related or other calls that are also managed by fire departments. These results have implications for more strategic emergency response planning during the COVID-19 pandemic, as well as improving Total Worker Health® and future of work initiatives at the worker and workplace levels within the fire service industry. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      2. A national overview of youth and injury trends on U.S. farms, 2001-2014external icon
        Hendricks KJ, Hendricks SA, Layne LA.
        J Agric Saf Health. 2021 Jul 9;27(3):121-134.
        HIGHLIGHTS The total number of injuries to all youth on farms consistently declined during the 14-year period from 2001 to 2014. Injuries to household farm youth, after initial declines, increased in 2012 and 2014. Although progress in farm youth safety has been made, farms continue to be hazardous places for youth. ABSTRACT. The National Institute for Occupational Safety and Health (NIOSH) conducted injury surveillance for youth on U.S. farms for two decades to measure childhood injury burden, track injury trends, and monitor hazardous injury exposures. The Childhood Agricultural Injury Survey (CAIS), a regionally stratified telephone survey, collected injury and demographic data for all youth less than 20 years of age on U.S. farms. Results from the 2014 survey are provided. Trend analyses for all survey years were conducted using a Poisson regression model with generalized estimating equations. Rate ratios with corresponding 95% confidence intervals were calculated from the model. In 2014, there were an estimated 11,942 youth farm injuries. Of these, 63% occurred to household youth. Youth between the ages of 10 and 15 incurred the most injuries, and 34% of the injuries were work-related. The total number of injuries to all youth on farms consistently declined during the 14-year period from 2001 to 2014, with annual injury rates ranging from 13.5 to 5.7 per 1,000 farms. The injury rates for household youth decreased through 2009 but increased slightly in 2012 and 2014. Farms continue to be hazardous environments for youth. Although there has been a significant decrease in the overall numbers and rates of youth farm injuries over the past decades, researchers should continue to monitor areas that remain a concern. One area that is specifically troublesome is the increase in injury rates observed for household youth in 2014.

      3. COVID-19 mortality among Amalgamated Transit Union (ATU) and Transport Workers Union (TWU) workers - March-July 2020, New York City metro areaexternal icon
        Tomasi SE, Ramirez-Cardenas A, Thiese MS, Rinsky JL, Chiu SK, Luckhaupt S, Bateman R, Burrer SL.
        Am J Ind Med. 2021 Aug 3.
        BACKGROUND: Transit workers have jobs requiring close public contact for extended periods of time, placing them at increased risk for severe acute respiratory syndrome coronavirus 2 infection and more likely to have risk factors for coronavirus disease 2019 (COVID-19)-related complications. Collecting timely occupational data can help inform public health guidance for transit workers; however, it is difficult to collect during a public health emergency. We used nontraditional epidemiological surveillance methods to report demographics and job characteristics of transit workers reported to have died from COVID-19. METHODS: We abstracted demographic and job characteristics from media scans on COVID-19 related deaths and reviewed COVID-19 memorial pages for the Amalgamated Transit Union (ATU) and Transport Workers Union (TWU). ATU and TWU provided a list of union members who died from COVID-19 between March 1-July 7, 2020 and a total count of NYC metro area union members. Peer-reviewed publications identified through a scientific literature search were used to compile comparison demographic statistics of NYC metro area transit workers. We analyzed and reported characteristics of ATU and TWU NYC metro area decedents. RESULTS: We identified 118 ATU and TWU NYC metro area transit worker COVID-19 decedents with an incidence proportion of 0.3%. Most decedents were male (83%); median age was 58 years (range: 39-71). Median professional tenure was 20 years (range: 2-41 years). Operator (46%) was the most reported job classification. More than half of the decedents (57%) worked in positions associated with close public contact. CONCLUSION: Data gathered through nontraditional epidemiological surveillance methods provided insight into risk factors among this workforce, demonstrating the need for mitigation plans for this workforce and informing transit worker COVID-19 guidance as the pandemic progressed.

    • Occupational Safety and Health - Mining
      1. Through-the-earth (TTE) communication systems are useful for post-disaster emergency communications due to their likelihood of surviving a mine disaster. The wireless channel and electromagnetic environment (EME) are two primary factors that affect the performance of a TTE system and have not been well understood in a mining environment. This paper reports our recent measurements conducted in an active coal mine to characterize the wireless channel and EME of a TTE system. TTE transmissions were successfully demonstrated in a mine location with a depth of 567 m (1,860 ft) by using ground rods installed on the surface and existing roof bolts in the underground. The results show that the EME in the mine is dominated by the 60-Hz signal and its harmonics for both surface and underground environments. The signal attenuation caused by the channel increases for frequencies greater than 90 Hz, which appears to be an optimum frequency point showing the smallest attenuation. An analytical path loss model for TTE channels is developed and validated using measurement results. This paper provides a measured data set as well as a model that an electric-field TTE system operator or system designer can reference when implementing TTE technologies in a mining environment. © 2021, Electromagnetics Academy. All rights reserved.

    • Reproductive Health
      1. The Michigan plan for appropriate tailored health care in pregnancy prenatal care recommendationsexternal icon
        Peahl AF, Zahn CM, Turrentine M, Barfield W, Blackwell SD, Roberts SJ, Powell AR, Chopra V, Bernstein SJ.
        Obstet Gynecol. 2021 Aug 5.
        OBJECTIVE: To describe MiPATH (the Michigan Plan for Appropriate Tailored Healthcare) in pregnancy panel process and key recommendations for prenatal care delivery. METHODS: We conducted an appropriateness study using the RAND Corporation and University of California Los Angeles Appropriateness Method, a modified e-Delphi process, to develop MiPATH recommendations using sequential steps: 1) definition and scope of key terms, 2) literature review and data synthesis, 3) case scenario development, 4) panel selection and scenario revisions, and 5) two rounds of panel appropriateness ratings with deliberation. Recommendations were developed for average-risk pregnant individuals (eg, individuals not requiring care by maternal-fetal medicine specialists). Because prenatal services (eg, laboratory tests, vaccinations) have robust evidence, panelists considered only how services are delivered (eg, visit frequency, telemedicine). RESULTS: The appropriateness of key aspects of prenatal care delivery across individuals with and without common medical and pregnancy complications, as well as social and structural determinants of health, was determined by the panel. Panelists agreed that a risk assessment for medical, social, and structural determinants of health should be completed as soon as individuals present for care. Additionally, the panel provided recommendations for: 1) prenatal visit schedules (care initiation, visit timing and frequency, routine pregnancy assessments), 2) integration of telemedicine (virtual visits and home devices), and 3) care individualization. Panelists recognized significant gaps in existing evidence and the need for policy changes to support equitable care with changing practices. CONCLUSION: The MiPATH recommendations offer more flexible prenatal care delivery for average-risk individuals.

    • Zoonotic and Vectorborne Diseases
      1. Notes from the field: Delays in identification and treatment of a case of septicemic plague - Navajo County, Arizona, 2020external icon
        Dale AP, Kretschmer M, Ruberto I, Wagner DM, Solomon C, Komatsu K, Venkat H.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 6;70(31):1063-1064.

      2. Clinical phenotype in infants with negative Zika virus immunoglobulin M testing born to mothers with confirmed Zika virus infection during pregnancyexternal icon
        Godfred-Cato S, Newton S, Adams L, Valencia-Prado M, Lake-Burger H, Morrison A, Jones AM, Olson SM, Roth NM, Tong VT, Gilboa SM, Meaney Delman D, Honein MA, Staples JE, Moore CA.
        Birth Defects Res. 2021 Jul 30.
        BACKGROUND: Recommended testing for both infants with Zika-associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants. METHODS: Infants from the U.S. Zika Pregnancy and Infant Registry and Zika Birth Defects Surveillance with Zika-associated birth defects and maternal and infant laboratory testing for ZIKV and two congenital infections (i.e., cytomegalovirus [CMV] and toxoplasmosis) were reviewed for phenotype and laboratory results. Infants with at least one defect considered highly specific for congenital ZIKV infection were designated as having congenital Zika syndrome (CZS) clinical phenotype for this study. RESULTS: Of 325 liveborn infants with Zika-associated birth defects and laboratory evidence of maternal ZIKV infection, 33 (10%) had CZS clinical phenotype; 171 (53%) had ZIKV IgM testing with negative or no ZIKV NAAT. ZIKV IgM was negative in the remaining 120 infants, and for 90%, testing for CMV and toxoplasmosis was missing/incomplete. Among 11 infants testing negative for ZIKV IgM, CMV, and toxoplasmosis, 2 infants had CZS clinical phenotype. CONCLUSIONS: These data add support to previous reports of negative ZIKV IgM testing in infants with clear maternal and phenotypic evidence of congenital ZIKV infection. Follow-up care consistent with the diagnosis is recommended regardless of infant ZIKV test results.

      3. BACKGROUND AND OBJECTIVES: Rocky Mountain spotted fever (RMSF) is a rapidly progressive and potentially fatal tickborne disease caused by Rickettsia rickettsii. Despite current recommendations and information on the severity of RMSF, studies show that delayed recognition and treatment continues to occur. METHODS: A literature search was performed on cases published in English between 1990-2017. The frequencies for demographic, clinical, and treatment variables was calculated. RESULTS: A total of 340 cases from 34 articles were included. Data on rash were available for 322 patients, and 261 (80%) noted rash. Mortality was 4% (2) in those who received doxycycline within the first five days of illness, and 35% (18) when treatment was delayed beyond Day five. Twenty-four (16%) reported chronic sequelae, including speech impairment (7, 5%) and ataxia (5, 3%). INTERPRETATION AND CONCLUSION: These data highlight the importance of early treatment, and add to our understanding of long-term sequelae. Early recognition by providers will facilitate appropriate treatment and reduction in morbidity and mortality.

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