Issue 39 November 3, 2020

CDC Science Clips: Volume 12, Issue 39, November 3, 2020

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. 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. Lifecourse body mass index trajectories and cardio-metabolic disease risk in Guatemalan adultsexternal icon
        Ford ND, Martorell R, Mehta NK, Perrine CG, Ramirez-Zea M, Stein AD.
        PLoS One. 2020 ;15(10):e0240904.
        Little is known about body size over the life-course and non-communicable disease risk in low- and middle-income country populations. Our study explored the role of body mass index (BMI) trajectories from infancy through mid-adulthood on cardio-metabolic disease (CMD) risk factors in a prospective cohort of Guatemalan adults. Study participants were born in Guatemala from 1962-77 and have been followed prospectively since participating in a nutrition supplementation trial as children. Sex-specific BMI latent class trajectories were derived using latent class growth modeling from up to 22 possible BMI values from age 1 month to 42 years measured between 1969 and 2004. CMD risk factors were assessed in 2015-17 (at age 37-54 years) using anthropometry, blood glucose and lipids, and blood pressure. We used logistic regression to assess the role of BMI trajectory on CMD risk factors in 510 women and 346 men (N = 856). We identified two BMI latent classes for women (low [n = 287, 56.3%] and high [n = 223, 43.7%]) and three classes for men (low [n = 141, 40.8%], medium [n = 160, 46.2%], and high [n = 45, 13.0%]). Given the small percentage of men in the high BMI latent class, we collapsed the medium and high BMI latent classes for men (n = 205, 59.1%). Among the most prevalent CMD risk factors at ages 37-54 years were abdominal obesity defined by waist-height ratio (99.6% of women and 87.3% of men), obesity defined by percent body fat (96.6% of women and 75.9% of men), low HDL-c (87.5% of women and 74.5% of men), and elevated triglycerides (78.3% of women and 73.6% of men). Except for obesity defined by BMI, we found no associations between BMI latent class and CMD risk factors in women. Among men, BMI latent class was not associated with CMD risk factors after controlling for current BMI. For the CMD risk factors we analyzed, the role of early life BMI on adult CMD appeared to be mediated by adult BMI among men-highlighting the need to establish and maintain healthy body weight over the life course.

      2. An examination of gender differences in the National Diabetes Prevention Program's Lifestyle Change Programexternal icon
        Jackson MC, Dai S, Skeete RA, Owens-Gary M, Cannon MJ, Smith BD, Jabrah R, Masalovich SE, Soler RE.
        Diabetes Educ. 2020 Oct 16.
        PURPOSE: The purpose of the study was to examine how gender was related to enrollment and number of sessions attended in the National Diabetes Prevention Program's Lifestyle Change Program (DPP LCP). METHODS: To better understand program uptake, a population of those who would be eligible for the LCP was compared to those who enrolled. Estimates of those eligible were computed using data from the National Health and Nutrition Examination Survey, whereas enrollment and sessions attended were computed using data from the Centers for Disease Control and Prevention's Diabetes Prevention Recognition Program. RESULTS: Results revealed that although similar numbers of males and females were eligible for the program, only 39 321 males versus 121 007 females had enrolled in the National DPP LCP by the end of 2017 (odds ratio = 3.20; 95% CI, 3.17-3.24). The gender differences persisted even when stratifying by age or race/ethnicity. In contrast, no significant gender differences were found between the average number of sessions attended for males (14.0) and females (13.8). DISCUSSION: Results of the study can help inform efforts to market and tailor programs to appeal more directly to men and other groups that are underrepresented in the National DPP LCP.

      3. Chronic kidney diseases in agricultural communities: report from a workshopexternal icon
        Mendley SR, Levin A, Correa-Rotter R, Joubert BR, Whelan EA, Curwin B, Koritzinsky EH, Gaughan DM, Kimmel PL, Anand S, Ordunez P, Reveiz L, Rohlman DS, Scammell MK, Wright RO, Star RA.
        Kidney Int. 2019 Nov;96(5):1071-1076.
        In June 2018, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences sponsored a workshop to identify research gaps in an increasingly common form of chronic kidney disease in agricultural communities, often termed "CKDu." The organizers invited a broad range of experts who provided diverse expertise and perspectives, many of whom had never addressed this particular epidemic. Discussion was focused around selected topics, including identifying and mitigating barriers to research in CKDu, creating a case definition, and defining common data elements. All hypotheses regarding etiology were entertained, and meeting participants discussed potential research strategies, choices in study design, and novel tools that may prove useful in this disease. Achievements of the workshop included robust cross-disciplinary discussion and preliminary planning of research goals and design. Specific challenges in implementing basic and clinical research and interventions in low- and middle-income countries were recognized. A balanced approach to leveraging local resources and capacity building without overreaching was emphasized.

      4. Assessing impact of HPV vaccination on cervical cancer incidence in women 15-29 years in the United States, 1999-2017: An ecologic studyexternal icon
        Mix JM, Van Dyne EA, Saraiya M, Hallowell BD, Thomas CC.
        Cancer Epidemiol Biomarkers Prev. 2020 Oct 20.
        BACKGROUND: To date, the human papillomavirus (HPV) vaccine impact on invasive cervical cancers in the United States has not been documented due, in part, to the time needed for cancer to develop, and to recent changes to cervical cancer screening guidelines and recommendations which complicate data interpretation. METHODS: We examined incidence rates of cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC)among women aged 15-29 years diagnosed during 1999-2017 using population-based cancer registry data covering 97.8% of the US population. Trends were stratified by age and histology. The annual percent change in cervical cancer incidence per year was calculated using Joinpoint regression. RESULTS: During 1999-2017, SCC rates decreased 7.9% per year among women aged 15-20 years, 5.5% among women aged 21-24 years, and 2.3% among women aged 25-29 years. The declines in SCC rates were largest among women aged 15-20 years from 2011 to 2017, with a decrease of 22.5% per year. Overall, AC rates decreased 4.1% per year among women aged 15-20 years, 3.6% per year among women aged 21-24 years, and 1.6% per year among women 25-29 years. AC rates declined the most among women aged 15-20 years during 2005 to 2017, decreasing 11.2% per year. CONCLUSIONS: Since HPV vaccine introduction, both SCC and AC incidence rates declined among women aged 15-20 years, a group not typically screened for cervical cancer, suggesting HPV vaccine impact. IMPACT: Timely vaccination and improved screening and follow-up among recommended age groups could result in further reductions in invasive cervical cancer.

    • Communicable Diseases
      1. BACKGROUND: Intussusception is the leading cause of acute intestinal obstruction in infants. Intussusception is mostly idiopathic, but infectious pathogens are sometimes implicated. In addition, live oral rotavirus vaccines have been associated with intussusception. METHODS: We searched the literature published between January 1, 1990, and March 16, 2020, to describe the association between intussusception among infants and young children and various pathogens, particularly adenovirus and wild rotavirus. We tallied the number of evaluations reporting a statistically significant positive association, no association and a protective association by pathogen, using any statistical method. We also calculated the median reported odds ratios (OR) of intussusception with adenovirus and rotavirus. RESULTS: We identified 3793 records on intussusception from the literature; 17 evaluations from 15 countries that evaluated 52 pathogens were included in the analysis. All 14 evaluations of adenovirus reported a statistically significant positive association with intussusception; the median OR from 9 evaluations was 3.7 (interquartile range, 3.3, 8.2). Nine of 12 evaluations assessing rotavirus found no statistically significant association, 1 found a positive association and 2 reported a protective effect; the median OR from 12 evaluations was 0.9 (interquartile range, 0.2, 1.8). No consistent relationship was observed between any other pathogens and intussusception. CONCLUSIONS: We documented a consistent association of intussusception with adenovirus, but no relationship between wild-type rotavirus and intussusception. Future research should focus on better understanding the mechanisms of intussusception with infectious pathogens, including following a rotavirus vaccination.

      2. Detection and control of fungal outbreaksexternal icon
        Caceres DH, Mohd Tap R, Alastruey-Izquierdo A, Hagen F.
        Mycopathologia. 2020 Oct 10.

      3. Potential impact of COVID-19 on recently resettled refugee populations in the United States and Canada: Perspectives of refugee healthcare providersexternal icon
        Clarke SK, Kumar GS, Sutton J, Atem J, Banerji A, Brindamour M, Geltman P, Zaaeed N.
        J Immigr Minor Health. 2020 Oct 16:1-6.
        Recently resettled refugee populations may be at greater risk for exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that causes coronavirus 2019 (COVID-19), and face unique challenges in following recommendations to protect their health. Several factors place resettled refugees at elevated risk for exposure to persons with COVID-19 or increased severity of COVID-19: being more likely to experience poverty and live in crowded housing, being employed in less protected, service-sector jobs, experiencing language and health care access barriers, and having higher rates of co-morbidities. In preparing for and managing COVID-19, resettled refugees encounter similar barriers to those of other racial or ethnic minority populations, which may then be exacerbated by unique barriers experienced from being a refugee. Key recommendations for resettlement and healthcare providers include analyzing sociodemographic data about refugee patients, documenting and resolving barriers faced by refugees, developing refugee-specific outreach plans, using culturally and linguistically appropriate resources, ensuring medical interpretation availability, and leveraging virtual platforms along with nontraditional community partners to disseminate COVID-19 messaging.

      4. Hospitalization rates and causes among persons with HIV in the US and Canada, 2005-2015external icon
        Davy-Mendez T, Napravnik S, Hogan BC, Althoff KN, Gebo KA, Moore RD, Horberg MA, Silverberg MJ, Gill MJ, Crane HM, Marconi VC, Bosch RJ, Colasanti JA, Sterling TR, Mathews WC, Mayor AM, Nanditha NG, Buchacz K, Li J, Rebeiro PF, Thorne JE, Nijhawan A, van Duin D, Wohl DA, Eron JJ, Berry SA.
        J Infect Dis. 2020 Oct 21.
        BACKGROUND: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. METHODS: In six clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV viral load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually-updated age, CD4, and VL. RESULTS: Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% CI 20.6-24.1) to 13.0 in 2015 (12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories. CONCLUSIONS: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.

      5. Does peer-navigated linkage to care work? A cross-sectional study of active linkage to care within an integrated non-communicable disease-HIV testing centre for adults in Soweto, South Africaexternal icon
        Hopkins KL, Hlongwane KE, Otwombe K, Dietrich J, Jaffer M, Cheyip M, Olivier J, van Rooyen H, Wade AN, Doherty T, Gray GE.
        PLoS One. 2020 ;15(10):e0241014.
        INTRODUCTION: South Africa is the HIV epidemic epicentre; however, non-communicable diseases (NCDs) will be the most common cause of death by 2030. To improve identification and initiation of care for HIV and NCDs, we assessed proportion of clients referred and linked to care (LTC) for abnormal/positive screening results and time to LTC and treatment initiation from a HIV Testing Services (HTS) Centre before and after integrated testing for NCDs with optional peer-navigated linkage to care. MATERIALS AND METHODS: This two-phase prospective study was conducted at an adult HTS Centre in Soweto, South Africa. Phase 1 (February-June 2018) utilised standard of care (SOC) HTS services (blood pressure [BP], HIV rapid diagnostic testing (RDT), sexually transmitted infections [STI]/Tuberculosis [TB] symptom screening) with passive referral for abnormal/positive results. Phase 2 (June 2018-March 2019) further integrated blood glucose/cholesterol/chlamydia RDT, with optional peer-navigated referral. Enrolled referred clients completed telephonic follow-up surveys confirming LTC/treatment initiation ≤3 months post-screening. Socio-demographics, screening results, time to LTC/treatment initiation, peer-navigated referral uptake were reported. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. Thematic analysis was conducted for open-ended survey responses. RESULTS: Of all 320 referrals, 40.0% were HIV-infections, 11.9% STIs, 6.6% TB, and 28.8% high/low BP. Of Phase 2-only referrals, 29.4% were for glucose and 23.5% cholesterol. Integrated NCD-HTS had significantly more clients LTC for HIV (76.7%[n = 66/86] vs 52.4%[n = 22/42], p = 0.0052) and within a shorter average time (6-8 days [Interquartile range (IQR):1-18.5] vs 8-13 days [IQR:2-32]) as compared to SOC HTS. Integrated NCD-HTS clients initiated HIV/STIs/BP treatment on average more quickly as compared to SOC HTS (5 days for STIs [IQR:1-21], 8 days for HIV/BP [IQR:5-17 and 2-13, respectively] vs 10 days for STIs [IQR: 4-32], 19.5 days for HIV [IQR:6.5-26.5], 8 days for BP [IQR:2-29)]. Participants chose passive over active referral (89.1% vs 10.9%; p<0.0001). Participants rejecting peer-navigated referral preferred to go alone (55.7% [n = 39/70]). Non-LTC was due to being busy (41.1% [n = 39/95]) and not being ready/refusing treatment (31.6% [n = 30/95]). Normalised results assessed at referral clinic (49.7% [n = 98/196]), prescribed lifestyle modification/monitoring (30.9% [n = 61/196]), and poor clinic flow/congestion and/or further testing required (10.7% [n = 21/196]) were associated with non-treatment initiation. CONCLUSION: Same-day treatment initiation is not achieved across diseases, despite peer-navigated referral. There are psychosocial and health systems barriers at entry to care/treatment initiation. Additional research may identify best strategies for rapid treatment initiation.

      6. COVID-19 mitigation behaviors by age group - United States, April-June 2020external icon
        Hutchins HJ, Wolff B, Leeb R, Ko JY, Odom E, Willey J, Friedman A, Bitsko RH.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1584-1590.
        CDC recommends a number of mitigation behaviors to prevent the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Those behaviors include 1) covering the nose and mouth with a mask to protect others from possible infection when in public settings and when around persons who live outside of one's household or around ill household members; 2) maintaining at least 6 feet (2 meters) of distance from persons who live outside one's household, and keeping oneself distant from persons who are ill; and 3) washing hands often with soap and water for at least 20 seconds, or, if soap and water are not available, using hand sanitizer containing at least 60% alcohol (1). Age has been positively associated with mask use (2), although less is known about other recommended mitigation behaviors. Monitoring mitigation behaviors over the course of the pandemic can inform targeted communication and behavior modification strategies to slow the spread of COVID-19. The Data Foundation COVID Impact Survey collected nationally representative data on reported mitigation behaviors during April-June 2020 among adults in the United States aged ≥18 years (3). Reported use of face masks increased from 78% in April, to 83% in May, and reached 89% in June; however, other reported mitigation behaviors (e.g., hand washing, social distancing, and avoiding public or crowded places) declined marginally or remained unchanged. At each time point, the prevalence of reported mitigation behaviors was lowest among younger adults (aged 18-29 years) and highest among older adults (aged ≥60 years). Lower engagement in mitigation behaviors among younger adults might be one reason for the increased incidence of confirmed COVID-19 cases in this group, which have been shown to precede increases among those >60 years (4). These findings underscore the need to prioritize clear, targeted messaging and behavior modification interventions, especially for young adults, to encourage uptake and support maintenance of recommended mitigation behaviors to prevent the spread of COVID-19.

      7. Evidence for HIV transmission across key populations: A longitudinal analysis of HIV and AIDS rates among Black people who inject drugs and Black heterosexuals in 84 large US metropolitan areas, 2008 - 2016external icon
        Ibragimov U, Beane S, Friedman SR, Tempalski B, Williams LD, McKetta S, Adimora AA, Wingood GM, Stall RD, Hall HI, Johnson AS, Cooper HL.
        Ann Epidemiol. 2020 Oct 13.
        PURPOSE: To assess cross-population linkages in HIV/AIDS epidemics, we tested the hypothesis that the number of newly diagnosed AIDS cases among Black people who inject drugs (PWID) was positively related to the natural log of the rate of newly diagnosed HIV infections among Black non-PWID heterosexuals in 84 large US metropolitan statistical areas (MSA) in 2008-2016. METHODS: We estimated a multilevel model centering the time-varying continuous exposures at baseline between the independent (Black PWID AIDS rates) and dependent (HIV diagnoses rate among Black heterosexuals) variables. RESULTS: At MSA level, baseline (standardized β=0.12) Black PWID AIDS rates and change in these rates over time (standardized β=0.11) were positively associated with the log of new HIV diagnoses rates among Black heterosexuals. Thus, MSAs with Black PWID AIDS rates that were one standard deviation higher at baseline also had rates of newly diagnosed HIV infections among Black non-PWID heterosexuals that were 10.3% higher. A one standard deviation increase in independent variable over time corresponded to 7.8% increase in dependent variable. CONCLUSIONS: Black PWID AIDS rates may predict HIV rates among non-PWID Black heterosexuals. Effective HIV programming may be predicated, in part, on addressing intertwining of HIV epidemics across populations.

      8. COVID-19-associated hospitalizations among health care personnel - COVID-NET, 13 States, March 1-May 31, 2020external icon
        Kambhampati AK, O'Halloran AC, Whitaker M, Magill SS, Chea N, Chai SJ, Daily Kirley P, Herlihy RK, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Openo KP, Monroe ML, Ryan PA, Kim S, Reeg L, Como-Sabetti K, Danila R, Davis SS, Torres S, Barney G, Spina NL, Bennett NM, Felsen CB, Billing LM, Shiltz J, Sutton M, West N, Schaffner W, Talbot HK, Chatelain R, Hill M, Brammer L, Fry AM, Hall AJ, Wortham JM, Garg S, Kim L.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1576-1583.
        Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.

      9. Evaluation of viral co-infections among patients with community-associated Clostridioides difficile infectionexternal icon
        Korhonen L, Cohen J, Gregoricus N, Farley MM, Perlmutter R, Holzbauer SM, Dumyati G, Beldavs Z, Paulick A, Vinjé J, Limbago BM, Lessa FC, Guh AY.
        PLoS One. 2020 ;15(10):e0240549.
        We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications.

      10. BACKGROUND: High-risk sexual behaviors (HRSB) are associated with sexually transmitted infections (STIs). The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend routine testing for patients with HRSB. Providers can classify patients with HRSB based on the sex of their sex partners using the International Classification of Disease Tenth Revision. We analyzed STI/human immunodeficiency virus (HIV) testing frequencies among patients with HRSB. METHODS: This study used a large US administrative outpatient medical claims data set from 2015 to 2017. Patients aged 15 to 64 years were identified with HRSB using International Classification of Disease Tenth Revision codes. An initial HRSB diagnosis in 2016 served as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing by HRSB at the index date, and 4 time intervals of 1 to 6 months, and 7 to 12 months before and after the index date. RESULTS: We identified 52,160 patients with HRSB: 90.3% were patients with opposite-sex partners, 7.7% patients with same-sex partners, and 2.1% patients with same- and opposite-sex partners. There were 77.5% and 82.1% of the patients insured 6 months before and after the index, respectively. On the index date, patients with opposite-sex partners tested most for chlamydia (65.3%) and gonorrhea (65.2%), patients with same-sex partners tested most for syphilis (51.5%) and HIV (57.8%). Among insured patients, follow-up STI/HIV testing was 89.5% during 1 to 6 months and 33.1% during 7 to 12 months after the index date. Patients tested on the index date were more likely to have an STI/HIV test within 1 to 6 months after the index date. CONCLUSIONS: The STI/HIV testing among patients with HRSB could improve. It is important for patients identified as HRSB to get tested and continue testing patients based on recommendations.

      11. Adoption of strategies to mitigate transmission of COVID-19 during a statewide primary election - Delaware, September 2020external icon
        Leidman E, Hall NB, Kirby AE, Garcia-Williams AG, Aponte J, Yoder JS, Hong R, Albence A, Coronado F, Massetti GM.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1571-1575.
        Elections occurring during the coronavirus disease 2019 (COVID-19) pandemic have been affected by notable changes in the methods of voting, the number and type of polling locations, and in-person voting procedures (1). To mitigate transmission of COVID-19 at polling locations, jurisdictions have adopted changes to protocols and procedures, informed by CDC's interim guidance, developed in collaboration with the Election Assistance Commission (2). The driving principle for this guidance is that voting practices with lower infection risk will be those which reduce the number of voters who congregate indoors in polling locations by offering a variety of methods for voting and longer voting periods. The guidance for in-person voting includes considerations for election officials, poll workers, and voters to maintain healthy environments and operations. To assess knowledge and adoption of mitigation strategies, CDC collaborated with the Delaware Department of Health and Social Services and the Delaware State Election Commission on a survey of poll workers who served during the statewide primary election on September 15, 2020. Among 522 eligible poll workers, 93% correctly answered all three survey questions about COVID-19 transmission. Respondents noted that most voters and poll workers wore masks. However, masks were not always worn correctly (i.e., covering both the nose and mouth). Responses suggest that mitigation measures recommended for both poll workers and voters were widely adopted and feasible, but also highlighted gaps in infection prevention control efforts. Strengthening of measures intended to minimize the risk of poll workers acquiring COVID-19 from ill voters, such as additional training and necessary personal protective equipment (PPE), as well as support for alternative voting options for ill voters, are needed. Adherence to mitigation measures is important not only to protect voters but also to protect poll workers, many of whom are older adults, and thus at higher risk for severe COVID-19-associated illness. Enhanced attention to reducing congregation in polling locations, correct mask use, and providing safe voting options for ill voters are critical considerations to minimize risk to voters and poll workers. Evidence from the Delaware election supports the feasibility and acceptability of implementing current CDC guidance for election officials, poll workers, and voters for mitigating COVID-19 transmission at polling locations (2).

      12. The epidemiology and estimated etiology of pathogens detected from the upper respiratory tract of adults with severe acute respiratory infections in multiple countries, 2014-2015external icon
        Milucky J, Pondo T, Gregory CJ, Iuliano D, Chaves SS, McCracken J, Mansour A, Zhang Y, Aleem MA, Wolff B, Whitaker B, Whistler T, Onyango C, Lopez MR, Liu N, Rahman MZ, Shang N, Winchell J, Chittaganpitch M, Fields B, Maldonado H, Xie Z, Lindstrom S, Sturm-Ramirez K, Montgomery J, Wu KH, Van Beneden CA.
        PLoS One. 2020 ;15(10):e0240309.
        INTRODUCTION: Etiology studies of severe acute respiratory infections (SARI) in adults are limited. We studied potential etiologies of SARI among adults in six countries using multi-pathogen diagnostics. METHODS: We enrolled both adults with SARI (acute respiratory illness onset with fever and cough requiring hospitalization) and asymptomatic adults (adults hospitalized with non-infectious illnesses, non-household members accompanying SARI patients, adults enrolled from outpatient departments, and community members) in each country. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from both SARI patients and asymptomatic adults. Specimens were tested for presence of 29 pathogens utilizing the Taqman® Array Card platform. We applied a non-parametric Bayesian regression extension of a partially latent class model approach to estimate proportions of SARI caused by specific pathogens. RESULTS: We enrolled 2,388 SARI patients and 1,135 asymptomatic adults from October 2013 through October 2015. We detected ≥1 pathogen in 76% of SARI patients and 67% of asymptomatic adults. Haemophilus influenzae and Streptococcus pneumoniae were most commonly detected (≥23% of SARI patients and asymptomatic adults). Through modeling, etiology was attributed to a pathogen in most SARI patients (range among countries: 57.3-93.2%); pathogens commonly attributed to SARI etiology included influenza A (14.4-54.4%), influenza B (1.9-19.1%), rhino/enterovirus (1.8-42.6%), and RSV (3.6-14.6%). CONCLUSIONS: Use of multi-pathogen diagnostics and modeling enabled attribution of etiology in most adult SARI patients, despite frequent detection of multiple pathogens in the upper respiratory tract. Seasonal flu vaccination and development of RSV vaccine would likely reduce the burden of SARI in these populations.

      13. COVID-19 outbreak at an overnight summer school retreat - Wisconsin, July-August 2020external icon
        Pray IW, Gibbons-Burgener SN, Rosenberg AZ, Cole D, Borenstein S, Bateman A, Pevzner E, Westergaard RP.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1600-1604.
        During July 2-August 11, 2020, an outbreak of coronavirus disease 2019 (COVID-19) occurred at a boys' overnight summer school retreat in Wisconsin. The retreat included 152 high school-aged boys, counselors, and staff members from 21 states and territories and two foreign countries. All attendees were required to provide documentation of either a positive serologic test result* within the past 3 months or a negative reverse transcription-polymerase chain reaction (RT-PCR) tests result for SARS-CoV-2 (the virus that causes COVID-19) ≤7 days before travel, to self-quarantine within their households for 7 days before travel, and to wear masks during travel. On July 15, the Wisconsin Department of Health Services (WDHS) began an investigation after being notified that two students at the retreat had received positive SARS-CoV-2 RT-PCR test results. WDHS offered RT-PCR testing to attendees on July 28 and serologic testing on August 5 and 6. Seventy-eight (51%) attendees received positive RT-PCR results (confirmed cases), and 38 (25%) met clinical criteria for COVID-19 without a positive RT-PCR result (probable cases). By the end of the retreat, 118 (78%) persons had received a positive serologic test result. Among 24 attendees with a documented positive serologic test result before the retreat, all received negative RT-PCR results. After RT-PCR testing on July 28, WDHS recommended that remaining susceptible persons (asymptomatic and with negative RT-PCR test results) quarantine from other students and staff members at the retreat. Recommended end dates for isolation or quarantine were based on established guidance (1,2) and determined in coordination with CDC. All attendees were cleared for interstate and commercial air travel to return home on August 11. This outbreak investigation documented rapid spread of SARS-CoV-2, likely from a single student, among adolescents and young adults in a congregate setting. Mitigation plans that include prearrival quarantine and testing, cohorting, symptom monitoring, early identification and isolation of cases, mask use, enhanced hygiene and disinfection practices, and maximal outdoor programming are necessary to prevent COVID-19 outbreaks in these settings (3,4).

      14. COVID-19 in a correctional facility employee following multiple brief exposures to persons with COVID-19 - Vermont, July-August 2020external icon
        Pringle JC, Leikauskas J, Ransom-Kelley S, Webster B, Santos S, Fox H, Marcoux S, Kelso P, Kwit N.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1569-1570.
        On August 11, 2020, a confirmed case of coronavirus disease 2019 (COVID-19) in a male correctional facility employee (correctional officer) aged 20 years was reported to the Vermont Department of Health (VDH). On July 28, the correctional officer had multiple brief encounters with six incarcerated or detained persons (IDPs)* while their SARS-CoV-2 test results were pending. The six asymptomatic IDPs arrived from an out-of-state correctional facility on July 28 and were housed in a quarantine unit. In accordance with Vermont Department of Corrections (VDOC) policy for state prisons, nasopharyngeal swabs were collected from the six IDPs on their arrival date and tested for SARS-CoV-2, the virus that causes COVID-19, at the Vermont Department of Health Laboratory, using real-time reverse transcription-polymerase chain reaction (RT-PCR). On July 29, all six IDPs received positive test results. VDH and VDOC conducted a contact tracing investigation(†) and used video surveillance footage to determine that the correctional officer did not meet VDH's definition of close contact (i.e., being within 6 feet of infectious persons for ≥15 consecutive minutes)(§)(,)(¶); therefore, he continued to work. At the end of his shift on August 4, he experienced loss of smell and taste, myalgia, runny nose, cough, shortness of breath, headache, loss of appetite, and gastrointestinal symptoms; beginning August 5, he stayed home from work. An August 5 nasopharyngeal specimen tested for SARS-CoV-2 by real-time RT-PCR at a commercial laboratory was reported as positive on August 11; the correctional officer identified two contacts outside of work, neither of whom developed COVID-19. On July 28, seven days preceding his illness onset, the correctional officer had multiple brief exposures to six IDPs who later tested positive for SARS-CoV-2; available data suggests that at least one of the asymptomatic IDPs transmitted SARS-CoV-2 during these brief encounters.

      15. BACKGROUND: The suppression of viremia among persons with HIV (PWH) using antiretroviral therapy has been hypothesized to reduce HIV incidence at the population level. We investigated the impact of state level viral suppression among PWH in the United States on estimated HIV incidence between 2010 and 2015. METHODS: Viral suppression data and HIV incidence estimates from the National HIV Surveillance System were available from 29 states and the District of Columbia. We assumed a one year delay for viral suppression to impact incidence. Poisson regression models were used to calculate the estimated annual percent change (EAPC) in incidence rate. We employed a multivariable mixed-effects Poisson regression model to assess the effects of state level race/ethnicity, socioeconomic status, percent men who have sex with men (MSM) and hepatitis C virus prevalence as a proxy for injection drug use on HIV incidence. FINDINGS: Fitted HIV incidence for 30 jurisdictions declined from 11.5 in 2010 to 10.0 per 100,000 population by 2015 corresponding with an EAPC of -2.67 (95% confidence interval [95%CI] -2.95, -2.38). Southern states experienced the highest estimated incidence by far throughout this period but upon adjustment for viral suppression and demographics there was a 36% lower incidence rate than Northeast states (adjusted rate ratio [aRR] 0.64; 95%CI 0.42, 0.99). For every 10 percentage point (pp) increase in viral suppression there was an adjusted 4% decline in HIV incidence rate in the subsequent year (aRR 0.96; 95%CI 0.93, 0.99). While controlling for viral suppression, HIV incidence rate increased by 42% (aRR 1.42 95%CI 1.31, 1.54) for every 5 pp increase in percent Black race and by 27% (aRR 1.27 95%CI 1.10, 1.48) for every 1 pp increase in percent MSM in states. INTERPRETATION: A decline in estimated HIV incidence from 2010 to 2015 was associated with increasing viral suppression in the United States. Race and sexual orientation were important HIV acquisition risk factors.

      16. Human prion disease surveillance in Washington state, 2006-2017external icon
        Sánchez-González L, Maddox RA, Lewis LC, Blevins JE, Harker EJ, Appleby BS, Person MK, Schonberger LB, Belay ED, DeBolt C, Lofy KH.
        JAMA Netw Open. 2020 Oct 1;3(10):e2020690.
        IMPORTANCE: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. OBJECTIVE: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. EXPOSURE: Human prion disease diagnosis. MAIN OUTCOMES AND MEASURES: The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. RESULTS: A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.

      17. Considerations in pooled testing for SARS-CoV-2 of employeesexternal icon
        Schulte PA, Weissman D, Luckhaupt SE, De Perio MA, Beezhold D, Piacentino JD, Radonovich L, Hearl FJ, Howard J.
        J Occup Environ Med. 2020 Oct:[Epub ahead of print].
        Objectives: To identify important background information on pooled tested of employees that employers workers, and health authorities should consider. Methods: This paper is a commentary based on the review by the authors of pertinent literature generally from preprints in prior to August 2020. Results: Not applicable to commentary viewpoint article. Conclusion: Pooled testing may be particularly useful to employers in communities with low prevalence of COVID-19. It can be used to reduce the number of tests and associated financial costs. For effective and efficient pooled testing employers should consider it as part of a broader, more comprehensive workplace COVID-19 prevention and control program. Pooled testing of asymptomatic employees can prevent transmission of SARS-CoV-2 and help assure employers and customers that employees are not infectious.

      18. Cytomegalovirus and Epstein-Barr virus viremia are associated with HIV DNA levels in the reservoir of Kenyan infants on antiretroviral therapyexternal icon
        Slyker JA, Guthrie B, Pankau M, Tapia K, Wamalwa D, Benki-Nugent S, Ngugi E, Huang ML, Njuguna I, Langat A, John-Stewart G, Lehman D.
        J Infect Dis. 2020 Oct 16.
        Identifying determinants of HIV reservoir levels may inform novel viral eradication strategies. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections were assessed as predictors of HIV proviral DNA level in 26 HIV RNA-suppressed Kenyan children starting antiretroviral therapy (ART) before 7 months of age. Earlier acquisition of CMV and EBV, and higher cumulative burden of systemic EBV DNA viremia were each associated with higher HIV DNA level in the reservoir after 24 months of ART, independent of HIV RNA levels over time. These data suggest delaying or containing CMV and EBV viremia may be novel strategies to limit HIV reservoir formation.

      19. Coronavirus disease among workers in food processing, food manufacturing, and agriculture workplacesexternal icon
        Waltenburg MA, Rose CE, Victoroff T, Butterfield M, Dillaha JA, Heinzerling A, Chuey M, Fierro M, Jervis RH, Fedak KM, Leapley A, Gabel JA, Feldpausch A, Dunne EM, Austin C, Pedati CS, Ahmed FS, Tubach S, Rhea C, Tonzel J, Krueger A, Crum DA, Vostok J, Moore MJ, Kempher H, Scheftel J, Turabelidze G, Stover D, Donahue M, Thomas D, Edge K, Gutierrez B, Berl E, McLafferty M, Kline KE, Martz N, Rajotte JC, Julian E, Diedhiou A, Radcliffe R, Clayton JL, Ortbahn D, Cummins J, Barbeau B, Carpenter S, Pringle JC, Murphy J, Darby B, Graff NR, Dostal TK, Pray IW, Tillman C, Rose DA, Honein MA.
        Emerg Infect Dis. 2020 Oct 19;27(1).
        We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

    • Disease Reservoirs and Vectors
      1. Ecology and management of plague in diverse communities of rodents and fleasexternal icon
        Eads DA, Biggins DE, Gage KL.
        Vector Borne Zoonotic Dis. 2020 Oct 19.
        Plague originated in Asia as a flea-borne zoonosis of mammalian hosts. Today, the disease is distributed nearly worldwide. In western United States of America, plague is maintained, transmitted, and amplified in diverse communities of rodents and fleas. We examined flea diversity on three species of prairie dogs (Cynomys spp., PDs) and six species of sympatric small rodents in Montana and Utah, United States of America. Among 2896 fleas, 19 species were identified; 13 were found on PDs and 9 were found on small rodents. In Montana, three flea species were found on PDs; the three species parasitize PDs and mice. In Utah, 12 flea species were found on PDs; the 12 species parasitize PDs, mice, voles, chipmunks, ground squirrels, rock squirrels, and marmots. Diverse flea communities and their willingness to parasitize many types of hosts, across multiple seasons and habitats, may favor plague maintenance and transmission. Flea parasitism on Peromyscus deer mice varied directly with elevation. Fleas are prone to desiccation, and might prosper at higher, mesic elevations; in addition, Peromyscus nest characteristics may vary with elevation. Effective management of plague is critical. Plague management is probably most effective when encompassing communities of rodents and fleas. Treatment of PD burrows with 0.05% deltamethrin dust, which suppressed fleas on PDs for >365 days, suppressed fleas on small rodents for at least 58 days. At one site, deltamethrin suppressed fleas on small rodents for at least 383 days. By simultaneously suppressing fleas on PDs and small rodents, deltamethrin should promote ecosystem resilience and One Health objectives.

      2. Anopheles gambiae (s.l.) is found where few are looking: assessing mosquito diversity and density outside inhabited areas using diverse sampling methodsexternal icon
        Epopa PS, Millogo AA, Collins CM, North AR, Benedict MQ, Tripet F, OʼLoughlin S, Dabiré RK, Ouédraogo GA, Diabaté A.
        Parasit Vectors. 2020 Oct 15;13(1):516.
        BACKGROUND: One of the promising current approaches to curb malaria lies in genetic vector control, the implementation of which will require an improved understanding of the movement of genetic constructs among mosquito populations. To predict potential gene flow from one area to another, it is important to begin to understand mosquito dynamics outside of the commonly-sampled village areas, and thus how genes may move between villages. This study assessed the presence and relative abundance of mosquitoes in a 6-km corridor between two villages in western Burkina Faso. METHODS: The area surrounding the villages was mapped and the road between them was used as the basis of a transect along which to sample. Five collection points were placed along this transect. To investigate both larval and adult mosquito presence, multiple sampling approaches were used surrounding each point: searching for larval sites in an area of 500 m radius, swarm sampling, human landing catches (HLC), CDC light traps and backpack aspiration catches of potential resting sites. Sampling took place twice: in September and October 2015. RESULTS: Adult mosquitoes from six species of Anopheles and three other genera were found along the whole transect. Anopheles gambiae (s.l.) was the most abundant followed by Anopheles nili and Anopheles coustani. Larvae of Anopheles spp. were found in small pools of surface water along the whole transect, though their presence increased with human proximity. HLC and aspiration were the most efficient methods of collecting adult mosquitoes along the whole transect, indicating that there are both host-seeking and resting mosquitoes well away from core village areas. In contrast, swarms of male mosquitoes, thought to be the principle mating locations of Anopheles spp. mosquitoes in West Africa, were only found close to the core village areas. CONCLUSIONS: This preliminary study indicates that Anopheles spp. mosquitoes are both present and breeding in low human-density areas along transit axes and provides both a relative evaluation of methods for use in these areas and evidence that gene flow between Sahelian population centres is likely. More robust and structured studies are nevertheless needed to come with stronger conclusions.

    • Entomology
      1. Reproductive incompatibility between Amblyomma maculatum (Acari: Ixodidae) group ticks from two disjunct geographical regions within the USAexternal icon
        Allerdice ME, Snellgrove AN, Hecht JA, Hartzer K, Jones ES, Biggerstaff BJ, Ford SL, Karpathy SE, Delgado-de la Mora J, Delgado-de la Mora D, Licona-Enriquez JD, Goddard J, Levin ML, Paddock CD.
        Exp Appl Acarol. 2020 Oct 22.
        The Amblyomma maculatum Koch group of ixodid ticks consists of three species: A. maculatum, A. triste, and A. tigrinum. However, since Koch described this group in 1844, the systematics of its members has been the subject of ongoing debate. This is especially true of A. maculatum and A. triste; recent molecular analyses reveal insufficient genetic divergence to separate these as distinct species. Further confounding this issue is the discovery in 2014 of A. maculatum group ticks in southern Arizona (AZ), USA, that share morphological characteristics with both A. triste and A. maculatum. To biologically evaluate the identity of A. maculatum group ticks from southern Arizona, we analyzed the reproductive compatibility between specimens of A. maculatum group ticks collected from Georgia (GA), USA, and southern Arizona. Female ticks from both Arizona and Georgia were mated with males from both the Georgia and Arizona Amblyomma populations, creating two homologous and two heterologous F1 cohorts of ticks: GA ♀/GA ♂, AZ ♀/AZ ♂, GA ♀/AZ ♂, and AZ ♀/GA ♂. Each cohort was maintained separately into the F2 generation with F1 females mating only with F1 males from their same cohort. Survival and fecundity parameters were measured for all developmental stages. The observed survival parameters for heterologous cohorts were comparable to those of the homologous cohorts through the F1 generation. However, the F1 heterologous females produced F2 egg clutches that did not hatch, thus indicating that the Arizona and Georgia populations of A. maculatum group ticks tested here represent different biological species.

    • Environmental Health
      1. Exposure to polychlorinated biphenyls and organochlorine pesticides and thyroid cancer in Connecticut womenexternal icon
        Deziel NC, Warren JL, Huang H, Zhou H, Sjodin A, Zhang Y.
        Environ Res. 2020 Oct 14;192:110333.
        BACKGROUND: Thyroid cancer incidence has increased substantially over the past decades, and environmental risk factors have been suggested to play a role. Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) are established thyroid hormone disruptors, but their relationship to thyroid cancer is not known. METHODS: We investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010 to 2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, age, and body mass index. Sub-analyses included stratification by tumor size (≤ and >1 cm) and birth before or during peak PCB production (born in 1960 or earlier and born after 1960), as exposures during early life may be important. We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with co-exposures to multiple PCB/OCPs. RESULTS: No PCB/OCPs were positively associated with PTC in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the those born during peak production based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. CONCLUSIONS: Our results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC, but some associations in those born during peak production suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

      2. Prenatal maternal phthalate exposures and child lipid and adipokine levels at age six: A study from the PROGRESS cohort of Mexico Cityexternal icon
        Kupsco A, Wu H, Calafat AM, Kioumourtzoglou MA, Tamayo-Ortiz M, Pantic I, Cantoral A, Tolentino M, Oken E, Braun JM, Deierlein AL, Wright RO, Téllez-Rojo MM, Baccarelli AA, Just AC.
        Environ Res. 2020 Oct 14;192:110341.
        BACKGROUND: Prenatal phthalate exposures may affect processes that underlie offspring cardiometabolic health, but findings from studies examining these associations are conflicting. We examined associations between biomarkers of phthalate exposures during pregnancy with child lipid and adipokine levels. METHODS: Data were from 463 mother-child pairs in the PROGRESS cohort of Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine samples and created an average pregnancy measure using the geometric mean. We evaluated the 15 metabolites as nine biomarkers, including four metabolite molar sums. We measured fasting serum triglycerides, non-HDL cholesterol, leptin, and adiponectin in children at the six-year follow-up visit (mean = 6.8 years). We estimated associations using linear regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) and assessed effect modification by sex. RESULTS: In BKMR and WQS models, higher concentrations of the total mixture of phthalate biomarkers were associated with lower triglycerides (β = -3.7% [-6.5, -0.78] per 1 unit increase in WQS biomarker index) and non-HDL cholesterol (β = -2.0 [-3.7, -0.25] ng/ml per increase in WQS biomarker index). Associations between individual biomarkers and child outcomes were largely null. We observed some evidence of effect modification by child sex for mono-3-carboxypropyl phthalate (β = 19.4% [1.26, 40.7] per doubling of phthalate) and monobenzyl phthalate (β = -7.6% [-14.4, -0.23]) in girls for adiponectin. CONCLUSIONS: Individual prenatal phthalate biomarkers were not associated with child lipid or adipokine levels. Contrary to our hypothesis, the total phthalate mixture was associated with lower child triglycerides and non-HDL cholesterol.

      3. Paternal mixtures of urinary concentrations of phthalate metabolites, bisphenol A and parabens in relation to pregnancy outcomes among couples attending a fertility centerexternal icon
        Mínguez-Alarcón L, Bellavia A, Gaskins AJ, Chavarro JE, Ford JB, Souter I, Calafat AM, Hauser R, Williams PL.
        Environ Int. 2020 Oct 15;146:106171.
        BACKGROUND: Few epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples' pregnancy outcomes. OBJECTIVE: We investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center. METHODS: We included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed. RESULTS: We identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores. CONCLUSION: Paternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.

    • Health Disparities
      1. The Diabetes Location, Environmental Attributes, and Disparities Network: Protocol for nested case control and cohort studies, rationale, and baseline characteristicsexternal icon
        Hirsch AG, Carson AP, Lee NL, McAlexander T, Mercado C, Siegel K, Black NC, Elbel B, Long DL, Lopez P, McClure LA, Poulsen MN, Schwartz BS, Thorpe LE.
        JMIR Res Protoc. 2020 Oct 19;9(10):e21377.
        BACKGROUND: Diabetes prevalence and incidence vary by neighborhood socioeconomic environment (NSEE) and geographic region in the United States. Identifying modifiable community factors driving type 2 diabetes disparities is essential to inform policy interventions that reduce the risk of type 2 diabetes. OBJECTIVE: This paper aims to describe the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a group funded by the Centers for Disease Control and Prevention to apply harmonized epidemiologic approaches across unique and geographically expansive data to identify community factors that contribute to type 2 diabetes risk. METHODS: The Diabetes LEAD Network is a collaboration of 3 study sites and a data coordinating center (Drexel University). The Geisinger and Johns Hopkins University study population includes 578,485 individuals receiving primary care at Geisinger, a health system serving a population representative of 37 counties in Pennsylvania. The New York University School of Medicine study population is a baseline cohort of 6,082,146 veterans who do not have diabetes and are receiving primary care through Veterans Affairs from every US county. The University of Alabama at Birmingham study population includes 11,199 participants who did not have diabetes at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study with oversampling of participants from the Stroke Belt region. RESULTS: The Network has established a shared set of aims: evaluate mediation of the association of the NSEE with type 2 diabetes onset, evaluate effect modification of the association of NSEE with type 2 diabetes onset, assess the differential item functioning of community measures by geographic region and community type, and evaluate the impact of the spatial scale used to measure community factors. The Network has developed standardized approaches for measurement. CONCLUSIONS: The Network will provide insight into the community factors driving geographical disparities in type 2 diabetes risk and disseminate findings to stakeholders, providing guidance on policies to ameliorate geographic disparities in type 2 diabetes in the United States. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21377.

      2. The purpose of this study is to present a variety of measures that quantify equity in cancer outcomes, demonstrate how the measures perform in various cancer types, and identify counties, or Bright Spots, that meet the criteria of those measures. Using county-level age adjusted death rates for 2007-2016 from the National Center for Health Statistics, we determined counties that had both equitable and optimal outcomes for the black and white death rates across five cancer types, lung/bronchus, prostate, breast, colorectal, and liver cancers. The number of counties that met the criteria ranged from 0 to 442 depending on cancer type and measure used, and prostate and male liver cancer consistently had the lowest number of Bright Spots with a maximum of 3 counties meeting the most lenient criteria. This study presents several ways to examine equity, using rate ratios and standard error measures, in cancer mortality outcomes. It highlights areas with positive progress towards equity and areas potential need for equity-focused cancer control planning. Examining local areas of positive deviance can inform cancer control programming and planning around health equity.

      3. Rural, urban, and suburban differences in influenza vaccination coverage among childrenexternal icon
        Zhai Y, Santibanez TA, Kahn KE, Srivastav A, Walker TY, Singleton JA.
        Vaccine. 2020 Oct 15.
        Influenza vaccination is the primary way to prevent influenza, yet influenza vaccination coverage remains low in the United States. Previous studies have shown that children residing in rural areas have less access to healthcare and lower vaccination coverage for some vaccines. Influenza vaccination coverage among children 6 months-17 years by rural/urban residence during the 2011-12 through 2018-19 influenza seasons was examined using National Immunization Survey-Flu data. The Council of American Survey Research Organizations response rates for National Immunization Survey-Flu ranged from 48% to 65% (2011-12 through the 2017-18 seasons) for the landline sample and 20%-39% (2011-12 through the 2018-19 seasons) for the cellular telephone sample. Children residing in rural areas had influenza vaccination coverage that ranged from 7.9 (2012-13 season) to 12.6 (2016-17 season) percentage points lower than children residing in urban areas, and ranged from 4.5 (2012-13 season) to 7.4 (2016-17 season) percentage points lower than children residing in suburban areas. The differences in influenza vaccination coverage among rural, suburban, and urban children were consistent over the eight seasons studied. Lower influenza vaccination coverage was observed among rural children regardless of child's age, mother's education, household income, or number of children under 18 years of age in the household. Rural versus urban and suburban differences in influenza vaccination coverage remained statistically significant while adjusting for selected sociodemographic characteristics. A better understanding of the reasons for lower childhood influenza vaccination coverage for children in rural and suburban areas is needed.

    • Health Economics
      1. Diarrhea hospitalization costs among children <5 years old in Madagascarexternal icon
        Burnett E, Rahajamanana VL, Raboba JL, Weldegebriel G, Vuo Masembe Y, Mwenda JM, Parashar UD, Tate JE, Robinson AL.
        Vaccine. 2020 Oct 10.
        BACKGROUND: Following a recommendation by the World Health Organization, Madagascar introduced rotavirus vaccine in 2014. Though national rotavirus vaccine coverage has remained <80%, rotavirus hospitalizations declined by 78%. Gavi, the Vaccine Alliance, has provided financial support for rotavirus vaccine, however the Malagasy government has increasing responsibility for the financial cost. METHODS: In this evaluation, we describe the direct medical, direct non-medical, and indirect cost of illness due to diarrhea among children <5 years old at a public pediatric referral hospital. A 3-part structured questionnaire was administered during and following the hospitalization and the child's hospital record was reviewed. RESULTS: In total, 96 children were included in this analysis. The median total cost of the illness was $156.00 (IQR: 104.00, 210.86) and the median direct medical cost was $107.22. Service delivery costs represented a median of 44% of the inpatient costs; medications and diagnostic tests represented a median of 28% and 20% of the total costs of the hospitalization, respectively. The median percentage of the total illness costs paid by the household was 67%. Among households with income of <$61/month, the median costs of the illness paid by the household were $78.55, representing a median of 168% of the household's monthly expenses. Among households earning >$303/month, the median costs paid by the household were $147.30, representing a median of 53% of the household's monthly expenses. Among all household income levels, caregivers commonly paid these bills from savings, borrowed money, and donations. CONCLUSIONS: Our findings will be useful in assessing the cost-effectiveness of rotavirus vaccine by decisionmakers. These results may also help hospital administrators and healthcare providers better understand the financial constraints of families.

      2. Spending on young children with autism spectrum disorder in employer-sponsored plans, 2011-2017external icon
        Grosse SD, Ji X, Nichols P, Zuvekas SH, Rice CE, Yeargin-Allsopp M.
        Psychiatr Serv. 2020 Oct 20.
        OBJECTIVE: Rapid increases in the prevalence of autism spectrum disorder (ASD) and increased access to intensive behavioral interventions have likely increased health care spending. This study estimated recent changes in spending among privately insured children with and without current ASD. METHODS: A repeated cross-sections analysis of 2011-2017 claims data from large-employer-sponsored health plans assessed changes in annual expenditures by service type for children ages 3-7 enrolled for ≥1 year and with two or more claims with ASD billing codes within a calendar year and for all other children. RESULTS: Mean spending per child with a current-year ASD diagnosis increased by 51% in 2017 U.S. dollars, from roughly $13,000 in 2011 to $20,000 in 2017. Among children who did not meet the current-year ASD case definition, per-child spending increased by 8%. Spending on children with ASD accounted for 41% of spending growth for children ages 3-7 during 2011-2017. Outpatient behavioral intervention-related spending per child with ASD increased by 376%, from $1,746 in 2011 to $8,317 in 2017; spending on all other services increased by 2%. Their share of behavioral intervention-related spending increased from 13.2% in 2011 to 41.7% in 2017. In 2011, 2.5% of children with current-year ASD diagnoses incurred ≥$20,000 in outpatient behavioral intervention-related spending, which increased to 14.4% in 2017. CONCLUSIONS: During 2011-2017, spending increased six times as much for privately insured children ages 3-7 with current-year ASD as for children without ASD, largely from increased behavioral intervention-related spending. One in seven children received at least $20,000 in services in 2017.

    • Healthcare Associated Infections
      1. Targeted gown and glove use to prevent Staphylococcus aureus acquisition in community-based nursing homes: A pilot studyexternal icon
        Lydecker AD, Osei PA, Pineles L, Johnson JK, Meisel J, Stine OC, Magder L, Gurses AP, Hebden J, Oruc C, Mody L, Jacobs Slifka K, Stone ND, Roghmann MC.
        Infect Control Hosp Epidemiol. 2020 Oct 20:1-7.
        OBJECTIVE: To test the feasibility of targeted gown and glove use by healthcare personnel caring for high-risk nursing-home residents to prevent Staphylococcus aureus acquisition in short-stay residents. DESIGN: Uncontrolled clinical trial. SETTING: This study was conducted in 2 community-based nursing homes in Maryland. PARTICIPANTS: The study included 322 residents on mixed short- and long-stay units. METHODS: During a 2-month baseline period, all residents had nose and inguinal fold swabs taken to estimate S. aureus acquisition. The intervention was iteratively developed using a participatory human factors engineering approach. During a 2-month intervention period, healthcare personnel wore gowns and gloves for high-risk care activities while caring for residents with wounds or medical devices, and S. aureus acquisition was measured again. Whole-genome sequencing was used to assess whether the acquisition represented resident-to-resident transmission. RESULTS: Among short-stay residents, the methicillin-resistant S. aureus acquisition rate decreased from 11.9% during the baseline period to 3.6% during the intervention period (odds ratio [OR], 0.28; 95% CI, 0.08-0.92; P = .026). The methicillin-susceptible S. aureus acquisition rate went from 9.1% during the baseline period to 4.0% during the intervention period (OR, 0.41; 95% CI, 0.12-1.42; P = .15). The S. aureus resident-to-resident transmission rate decreased from 5.9% during the baseline period to 0.8% during the intervention period. CONCLUSIONS: Targeted gown and glove use by healthcare personnel for high-risk care activities while caring for residents with wounds or medical devices, regardless of their S. aureus colonization status, is feasible and potentially decreases S. aureus acquisition and transmission in short-stay community-based nursing-home residents.

      2. This National Healthcare Safety Network (NHSN) surveillance case study is part of a case-study series in the American Journal of Infection Control (AJIC). These cases reflect some of the complex patient scenarios Infection Preventionists (IPs) have encountered in their daily surveillance of healthcare-associated infections (HAI) using NHSN definitions. Objectives have been previously published.

      3. Antibiotics are not indicated for the treatment of bronchitis and bronchiolitis. Using a nationally representative database from 2006-2015, we found that antibiotics were prescribed in 58% of outpatient visits for bronchitis and bronchiolitis in children, serving as a possible baseline for the expanded HEDIS 2020 measure regarding antibiotic prescribing for bronchitis.

    • Immunity and Immunization
      1. Molecular characteristics of rotavirus genotypes circulating in the south of Benin, 2016-2018external icon
        Agbla JM, Esona MD, Agbankpe AJ, Capo-Chichi A, Gautam R, Dougnon TV, Razack O, Bowen MD, Bankole HS.
        BMC Res Notes. 2020 Oct 19;13(1):485.
        OBJECTIVE: Rotavirus remains the main causative agent of gastroenteritis in young children in countries that have not yet introduced the vaccine. In Benin, rotavirus vaccine was introduced late December 2019 into the EPI. This study aims to provide pre-vaccination era rotavirus genotyping data in Benin. These data can supplement data from the surveillance system of Ministry of Health of Benin which is supported by the World Health Organization (WHO). RESULTS: Of the 420 diarrheal stool samples, actively collected in southern Benin from July 2016 through November 2018 from children under 5 years old and suffering from gastroenteritis, 167 (39.8%) samples were rotavirus EIA positive. 186 (44.3%) samples contained amplifiable rotavirus RNA detected by qRT-PCR method and were genotyped using one-step RT-PCR multiplex genotyping method. G1P[8] represents the predominant genotype (32%) followed by the G2P[4] (26%), G3P[6] (16%), G12P[8] (13%) and mixed G and P types (1%). Four samples (2%) could not be assigned both G and P type specificity.

      2. Impact of immune priming, vaccination and infection on influenza A(H3N2) antibody landscapes in childrenexternal icon
        Hinojosa M, Shepard SS, Chung JR, King JP, McLean HQ, Flannery B, Belongia EA, Levine MZ.
        J Infect Dis. 2020 Oct 22.
        BACKGROUND: Pre-existing antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination. METHODS: We enrolled 72 children (7-17 years) in 2015-16, all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014-15 with 12 became infected with A(H3N2) in 2014-15. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and post-vaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015. RESULTS: The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Post-vaccination titers were highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Pre-vaccination titers to the vaccine were the strongest predictors of post-vaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2) infected children in 2014-15 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015-16 vaccination. CONCLUSIONS: A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.

      3. Influenza vaccination policies for health workers in low-income and middle-income countries: A cross-sectional survey, January-March 2020external icon
        Maltezou HC, Theodoridou K, Tseroni M, Raftopoulos V, Bolster A, Kraigsley A, Bresee J, Lambach P.
        Vaccine. 2020 Oct 12.
        INTRODUCTION: The World Health Organization (WHO) recommends vaccination of health workers against influenza, but uptake in low-resource settings remains low. To complement routine global data collection efforts we conducted a detailed survey on influenza vaccination policies for health workers in low-income and middle-income countries (LMICs) in early 2020. METHODS: Health worker vaccination policy data were collected via a web-based survey tool sent to Expanded Programme on Immunization managers or equivalent managers of all eligible countries. High-income countries and countries with active civil war were excluded from the participation. The survey was sent by email to 109 LMICs in all WHO Regions to invite participation. Data were analyzed by World Bank income category and WHO Region. Statistical methods were applied to assess mean vaccination rates across countries. RESULTS: Sixty-eight (62%) out of 109 invited LMICs were studied. Thirty-five (51.5%) reported to have a policy for influenza vaccination of health workers. Vaccinations were voluntary in 23 countries (66%), mandatory in 4 (11%), while in 8 countries (23%) mixed vaccination policies existed. A mechanism to estimate vaccine uptake existed in 26 countries (74%). Low-income and African Region countries were less likely to have influenza vaccination policies for health workers (p-values < 0.001 and 0.009, respectively). The most common reason for not having a vaccination policy for health workers was influenza not being a priority (48.5%). CONCLUSIONS: Despite policies being in place in more than half LMICs studied, gaps remain in translating vaccination policies to action, particularly in low-income and African Region countries. To optimize the operationalization of policies, further research is needed within countries, to enable evidence-based introduction decisions, categorization of health workers for vaccination, identification of factors impacting effective service delivery, strengthening monitoring and estimation of vaccination uptake rates and ensure sustainability of funding.

      4. Postlicensure evaluation of COVID-19 vaccinesexternal icon
        Patel MM, Jackson ML, Ferdinands J.
        Jama. 2020 Oct 16.

    • Informatics
      1. BACKGROUND: Unstructured data from clinical epidemiological studies can be valuable and easy to obtain. However, it requires further extraction and processing for data analysis. Doing this manually is labor-intensive, slow and subject to error. In this study, we propose an automation framework for extracting and processing unstructured data. METHODS: The proposed automation framework consisted of two natural language processing (NLP) based tools for unstructured text data for medications and reasons for medication use. We first checked spelling using a spell-check program trained on publicly available knowledge sources and then applied NLP techniques. We mapped medication names into generic names using vocabulary from publicly available knowledge sources. We used WHO's Anatomical Therapeutic Chemical (ATC) classification system to map generic medication names to medication classes. We processed the reasons for medication with the Lancaster stemmer method and then grouped and mapped to disease classes based on organ systems. Finally, we demonstrated this automation framework on two data sources for Mylagic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): tertiary-based (n = 378) and population-based (n = 664) samples. RESULTS: A total of 8681 raw medication records were used for this demonstration. The 1266 distinct medication names (omitting supplements) were condensed to 89 ATC classification system categories. The 1432 distinct raw reasons for medication use were condensed to 65 categories via NLP. Compared to completion of the entire process manually, our automation process reduced the number of the terms requiring manual labor for mapping by 84.4% for medications and 59.4% for reasons for medication use. Additionally, this process improved the precision of the mapped results. CONCLUSIONS: Our automation framework demonstrates the usefulness of NLP strategies even when there is no established mapping database. For a less established database (e.g., reasons for medication use), the method is easily modifiable as new knowledge sources for mapping are introduced. The capability to condense large features into interpretable ones will be valuable for subsequent analytical studies involving techniques such as machine learning and data mining.

    • Laboratory Sciences
      1. High level of HIV false positives using EIA-based algorithm in survey: Importance of confirmatory testingexternal icon
        Augusto  DR, Iriemenam NC, Kohatsu L, de Sousa L, Maueia C, Hara C, Mula F, Cuamba G, Chelene I, Langa Z, Lohman N, Faife F, Giles D, Sabonete AJ, Samo Gudo E, Jani I, Parekh BS.
        PLoS One. 2020 ;15(10):e0239782.
        The Mozambique Indicators of Immunization, Malaria and HIV/AIDS (IMASIDA) survey was conducted in 2015 and used a two Enzyme Immunoassay (EIA) (Vironostika HIV-1/2 and Murex HIV-1/2) based algorithm to determine the HIV status of the consented participants. The Mozambique Ministry of Health, with support from the US Centers for Disease Control and Prevention (US CDC), added Bio-Rad Geenius™ HIV-1/2 Supplemental Assay to the IMASIDA HIV testing algorithm to confirm all specimens that were found to be reactive on one or both EIAs. In total 11690 specimens were collected to estimate the proportion of HIV positive samples. Results indicate that the proportion of HIV positive samples based on the concordant positive results of two EIA assays was 21.5% (2518/11690). The addition of the Geenius assay to the IMASIDA HIV testing algorithm demonstrated that 792 (31.5%) of 2518 specimens were false-positive and reduced the proportion of HIV positive samples to 14.7% (1722/11690), demonstrating the importance of including a highly specific HIV test to confirm HIV diagnosis. HIV surveys exclusively based on EIA testing algorithm may result in misleading high prevalence results. Our results demonstrate that more specific confirmatory testing should be added to the EIA-based algorithms to ensure accurate HIV diagnosis and correct HIV prevalence estimate in cross-sectional surveys.

      2. The ability to rapidly and effectively respond to public health emergencies, including outbreak investigations and natural disasters, is critical in a strengthened health system. In March and April 2019, the impact of tropical cyclones Idai and Kenneth in Southern Africa and subsequent flooding resulted in devastating consequences to the Mozambique health care system. In this article, we highlight the role of Mozambique's Field Epidemiology and Laboratory Training Program (FELTP) graduates as first responders during one of the most significant natural disasters on the African continent. The FELTP graduates played a key role in conducting risk assessments, active epidemiological surveillance for priority communicable diseases, and outbreak investigations and supporting the laboratory diagnosis system. The cyclone emergencies in Mozambique revealed the vulnerability of the health system. It is vital to continue the investment in increasing epidemiological capacity of health human resources, staff to adequately prepare for and respond to public health emergencies to mitigate the negative health impacts associated with those events.

      3. Pulmonary and systemic toxicity in rats following inhalation exposure of 3-D printer emissions from acrylonitrile butadiene styrene (ABS) filamentexternal icon
        Farcas MT, McKinney W, Qi C, Mandler KW, Battelli L, Friend SA, Stefaniak AB, Jackson M, Orandle M, Winn A, Kashon M, LeBouf RF, Russ KA, Hammond DR, Burns D, Ranpara A, Thomas TA, Matheson J, Qian Y.
        Inhal Toxicol. 2020 Oct 20:1-16.
        BACKGROUND: Fused filament fabrication 3-D printing with acrylonitrile butadiene styrene (ABS) filament emits ultrafine particulates (UFPs) and volatile organic compounds (VOCs). However, the toxicological implications of the emissions generated during 3-D printing have not been fully elucidated. AIM AND METHODS: The goal of this study was to investigate the in vivo toxicity of ABS-emissions from a commercial desktop 3-D printer. Male Sprague Dawley rats were exposed to a single concentration of ABS-emissions or air for 4 hours/day, 4 days/week for five exposure durations (1, 4, 8, 15, and 30 days). At 24 hours after the last exposure, rats were assessed for pulmonary injury, inflammation, and oxidative stress as well as systemic toxicity. RESULTS AND DISCUSSION: 3-D printing generated particulate with average particle mass concentration of 240 ± 90 µg/m³, with an average geometric mean particle mobility diameter of 85 nm (geometric standard deviation = 1.6). The number of macrophages increased significantly at day 15. In bronchoalveolar lavage, IFN-γ and IL-10 were significantly higher at days 1 and 4, with IL-10 levels reaching a peak at day 15 in ABS-exposed rats. Neither pulmonary oxidative stress responses nor histopathological changes of the lungs and nasal passages were found among the treatments. There was an increase in platelets and monocytes in the circulation at day 15. Several serum biomarkers of hepatic and kidney functions were significantly higher at day 1. CONCLUSIONS: At the current experimental conditions applied, it was concluded that the emissions from ABS filament caused minimal transient pulmonary and systemic toxicity.

      4. Biological effects of inhaled hydraulic fracturing sand dust. II. Particle characterization and pulmonary effects 30 d following intratracheal instillationexternal icon
        Fedan JS, Hubbs AF, Barger M, Schwegler-Berry D, Friend SA, Leonard SS, Thompson JA, Jackson MC, Snawder JE, Dozier AK, Coyle J, Kashon ML, Park JH, McKinney W, Roberts JR.
        Toxicol Appl Pharmacol. 2020 Oct 14:115282.
        Hydraulic fracturing ("fracking") is used in unconventional gas drilling to allow for the free flow of natural gas from rock. Sand in fracking fluid is pumped into the well bore under high pressure to enter and stabilize fissures in the rock. In the process of manipulating the sand on site, respirable dust (fracking sand dust, FSD) is generated. Inhalation of FSD is a potential hazard to workers inasmuch as respirable crystalline silica causes silicosis, and levels of FSD at drilling work sites have exceeded occupational exposure limits set by OSHA. In the absence of any information about its potential toxicity, a comprehensive rat animal model was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems (Fedan, J.S., Toxicol Appl Pharmacol. 00, 000-000, 2020). The present report, part of the larger investigation, describes: 1) a comparison of the physico-chemical properties of nine FSDs, collected at drilling sites, and MIN-U-SIL® 5, a reference silica dust, and 2) a comparison of the pulmonary inflammatory responses to intratracheal instillation of the nine FSDs and MIN-U-SIL® 5. Our findings indicate that, in many respects, the physico-chemical characteristics, and the biological effects of the FSDs and MIN-U-SIL® 5 after intratracheal instillation, have distinct differences.

      5. Benzene derivatives from ink lead to false positive results in neonatal hyperphenylalaninemia screening with ninhydrin fluorometric methodexternal icon
        Feng S, Mei J, Yang L, Luo P, Wang X, Wang Y, Yao J, Cui L, Pan L, Wang Z, Xin L.
        Int J Neonatal Screen. 2020 Mar;6(1):14.
        Ninhydrin-based fluorometric quantification of phenylalanine is one of the most widely used methods for hyperphenylalaninemia (HPA) screening in neonates due to its high sensitivity, high accuracy, and low cost. Here we report an increase of false positive cases in neonatal HPA screening with this method, caused by contamination of blood specimen collection devices during the printing process. Through multiple steps of verification, the contaminants were identified from ink circles printed on the collection devices to indicate the positions and sizes of blood drops. Blood specimens from HPA-negative persons collected on these contaminated collection devices showed positive results in the fluorometric tests, but negative results in tandem mass spectroscopy (MS/MS) experiments. Contaminants on the collection devices could be extracted by 80% ethanol and showed an absorption peak around 245 nm, suggesting that these contaminants may contain benzene derivatives with similar structure to phenylalanine. High-performance liquid chromatography (HPLC) analysis of the ethanol extracts from contaminated collection devices identified two prominent peaks specifically from the devices. Methyl-2-benzoylbenzoate (MBB, CAS#606-28-0) was found as one of the major chemicals from contaminated collection devices. This report aims to remind colleagues in the field of this potential contamination and call for tighter regulation and quality control of specimen collection devices.

      6. Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemalaexternal icon
        García JI, Meléndez J, Álvarez R, Mejía-Chew C, Kelley HV, Sidiki S, Castillo A, Mazariegos C, López-Téllez C, Forno D, Ayala N, Balada-Llasat JM, Mejía-Villatoro CR, Wang SH, Torrelles JB, Ikeda J.
        AIDS Res Ther. 2020 Oct 19;17(1):62.
        BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert(®) MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

      7. Borrelia miyamotoi strain LB-2001 retains plasmids and infectious phenotype throughout continuous culture passages as evaluated by multiplex PCRexternal icon
        Gilmore RD, Mikula S, Harris EK, Van Gundy TJ, Goodrich I, Brandt KS.
        Ticks Tick Borne Dis. 2020 Oct 6;12(1):101587.
        Borrelia miyamotoi is a tick-borne spirochete of the relapsing fever borrelia group and an emerging pathogen of public health significance. The genomes of relapsing fever borreliae and Lyme disease borreliae consist of multiple linear and circular plasmids in addition to the chromosome. Previous work with B. burgdorferi sensu lato found diminished infectivity upon continuous in vitro culture passage that was attributable to plasmid loss. The effect of long-term culture passage on B. miyamotoi is not known. We generated a series of plasmid-specific primer sets and developed a multiplex PCR assay to detect the 14 known plasmids of B. miyamotoi North American strains LB-2001 and CT13-2396. We assessed the plasmid content of B. miyamotoi LB-2001 over 64 culture passages spanning 15 months and determined that strain LB-2001 retained all plasmids upon prolonged in vitro cultivation and remained infectious in mice. We also found that strain LB-2001 lacks plasmid lp20-1 which is present in strain CT13-2396. These results suggest that B. miyamotoi remains genetically stable when cultured and passaged in vitro.

      8. A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cellsexternal icon
        Hua BL, Scholte FE, Ohlendorf V, Kopp A, Marklewitz M, Drosten C, Nichol ST, Spiropoulou C, Junglen S, Bergeron É.
        Elife. 2020 Oct 21;9.
        Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5 to 80% (1). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (2, 3). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a GPC variant, present in ticks, have severely impaired function in human cells.

      9. Subtype distribution of zoonotic pathogen Cryptosporidium felis in humans and animals in several countriesexternal icon
        Jiang W, Roellig DM, Lebbad M, Beser J, Troell K, Guo Y, Li N, Xiao L, Feng Y.
        Emerg Microbes Infect. 2020 Oct 21:1-22.
        Cryptosporidium felis is the major etiologic agent of cryptosporidiosis in felines and has been reported in numerous human cryptosporidiosis cases. Sequence analysis of the 60-kDa glycoprotein (gp60) gene has been developed for subtyping C. felis recently. In this study, 66 C. felis isolates from the United States, Jamaica, Peru, Portugal, Slovakia, Nigeria, Ethiopia, Kenya, China, India and Australia were subtyped using the newly established tool. Forty-four specimens yielded gp60 sequences, generating 23 subtypes clustered in 4 subtype families (XIXa, XIXc, XIXd and XIXe) with high bootstrap support in a phylogenetic analysis of sequence data. Among them, XIXa showed high genetic diversity at the nucleotide level, with the formation of 18 subtypes from both cats and humans with different geographic distribution. In contrast, all 11 XIXd isolates derived from humans from various countries had identical sequences. Results of this study improve our understanding of the genetic diversity, host specificity and transmission dynamics of C. felis.

      10. SOX2 mediates carbon nanotube-induced fibrogenesis and fibroblast stem cell acquisitionexternal icon
        Kiratipaiboon C, Voronkova M, Ghosh R, Rojanasakul LW, Dinu CZ, Chen YC, Rojanasakul Y.
        ACS Biomater Sci Eng. 2020 ;6(9):5290-5304.
        Certain nanosized particles like carbon nanotubes (CNTs) are known to induce pulmonary fibrosis, but the underlying mechanisms are unclear, and efforts to prevent this disease are lacking. Fibroblast-associated stem cells (FSCs) have been suggested as a critical driver of fibrosis induced by CNTs by serving as a renewable source of extracellular matrix-producing cells; however, a detailed understanding of this process remains obscure. Here, we demonstrated that single-walled CNTs induced FSC acquisition and fibrogenic responses in primary human lung fibroblasts. This was indicated by increased expression of stem cell markers (e.g., CD44 and ABCG2) and fibrogenic markers (e.g., collagen and α-SMA) in CNT-exposed cells. These cells also showed increased sphere formation, anoikis resistance, and aldehyde dehydrogenase (ALDH) activities, which are characteristics of stem cells. Mechanistic studies revealed sex-determining region Y-box 2 (SOX2), a self-renewal associated transcription factor, as a key driver of FSC acquisition and fibrogenesis. Upregulation and colocalization of SOX2 and COL1 were found in the fibrotic lung tissues of CNT-exposed mice via oropharyngeal aspiration after 56 days. The knockdown of SOX2 by gene silencing abrogated the fibrogenic and FSC-inducing effects of CNTs. Chromatin immunoprecipitation assays identified SOX2-binding sites on COL1A1 and COL1A2, indicating SOX2 as a transcription factor in collagen synthesis. SOX2 was also found to play a critical role in TGF-β-induced fibrogenesis through its collagen-and FSC-inducing effects. Since many nanomaterials are known to induce TGF-β, our findings that SOX2 regulate FSCs and fibrogenesis may have broad implications on the fibrogenic mechanisms and treatment strategies of various nanomaterial-induced fibrotic disorders.

      11. Biological effects of inhaled hydraulic fracturing sand dust. III. Cytotoxicity and pro-inflammatory responses in cultured murine macrophage cellsexternal icon
        Olgun NS, Morris AM, Stefaniak AB, Bowers LN, Knepp AK, Duling MG, Mercer RR, Kashon ML, Fedan JS, Leonard SS.
        Toxicol Appl Pharmacol. 2020 Oct 13;408:115281.
        Cultured murine macrophages (RAW 264.7) were used to investigate the effects of fracking sand dust (FSD) for its pro-inflammatory activity, in order to gain insight into the potential toxicity to workers associated with inhalation of FSD during hydraulic fracturing. While the role of respirable crystalline silica in the development of silicosis is well documented, nothing is known about the toxicity of inhaled FSD. The FSD (FSD 8) used in these studies was from an unconventional gas well drilling site. FSD 8was prepared as a 10 mg/ml stock solution in sterile PBS, vortexed for 15 s, and allowed to sit at room temperature for 30 min before applying the suspension to RAW 264.7cells. Compared to PBS controls, cellular viability was significantly decreased after a 24 h exposure to FSD. Intracellular reactive oxygen species (ROS) production and the production of IL-6, TNFα, and endothelin-1 (ET-1) were up-regulated as a result of the exposure, whereas the hydroxyl radical ((.)OH) was only detected in an acellular system. Immunofluorescent staining of cells against TNFα revealed that FSD 8 caused cellular blebbing, and engulfment of FSD 8 by macrophages was observed with enhanced dark-field microscopy. The observed changes in cellular viability, cellular morphology, free radical generation and cytokine production all confirm that FSD 8 is cytotoxic to RAW 264.7 cells and warrants future studies into the specific pathways and mechanisms by which these toxicities occur.

      12. Biological effects of inhaled hydraulic fracturing sand dust. IV. Pulmonary effectsexternal icon
        Russ KA, Thompson JA, Reynolds JS, Mercer RR, Porter DW, McKinney W, Dey RD, Barger M, Cumpston J, Batchelor TP, Kashon ML, Kodali V, Jackson MC, Sriram K, Fedan JS.
        Toxicol Appl Pharmacol. 2020 Oct 14:115284.
        Hydraulic fracturing creates fissures in subterranean rock to increase the flow and retrieval of natural gas. Sand ("proppant") in fracking fluid injected into the well bore maintains fissure patency. Fracking sand dust (FSD) is generated during manipulation of sand to prepare the fracking fluid. Containing respirable crystalline silica, FSD could pose hazards similar to those found in work sites where silica inhalation induces lung disease such as silicosis. This study was performed to evaluate the possible toxic effects following inhalation of a FSD (FSD 8) in the lung and airways. Rats were exposed (6 h/d × 4 d) to 10 or 30 mg/m(3) of a FSD, i.e., FSD 8, collected at a gas well, and measurements were performed 1, 7, 27 and, in one series of experiments, 90 d post-exposure. The following ventilatory and non-ventilatory parameters were measured in vivo and/or in vitro: 1) lung mechanics (respiratory system resistance and elastance, tissue damping, tissue elastance, Newtonian resistance and hysteresivity); 2) airway reactivity to inhaled methacholine (MCh); airway epithelium integrity (isolated, pefused trachea); airway efferent motor nerve activity (electric field stimulation in vitro); airway smooth muscle contractility; ion transport in intact and cultured epithelium; airway effector and sensory nerves; tracheal particle deposition; and neurogenic inflammation/vascular permeability. FSD 8 was without large effect on most parameters, and was not pro-inflammatory, as judged histologically and in cultured epithelial cells, but increased reactivity to inhaled MCh at some post-exposure time points and affected Na(+) transport in airway epithelial cells.

      13. Biological effects of inhaled hydraulic fracturing sand dust. V. Pulmonary inflammatory, cytotoxic and oxidant effectsexternal icon
        Sager TM, Roberts JR, Umbright CM, Barger M, Kashon ML, Fedan JS, Joseph P.
        Toxicol Appl Pharmacol. 2020 Oct 13;408:115280.
        The pulmonary inflammatory response to inhalation exposure to a fracking sand dust (FSD 8) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol of a FSD, i.e., FSD 8, at concentrations of 10 or 30 mg/m(3), 6 h/d for 4 d. The control and FSD 8-exposed rats were euthanized at post-exposure time intervals of 1, 7 or 27 d and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Deposition of FSD 8 particles was detected in the lungs of all the FSD 8-exposed rats. Analysis of bronchoalveolar lavage parameters of toxicity, oxidant generation, and inflammation did not reveal any significant persistent pulmonary toxicity in the FSD 8-exposed rats. Similarly, the lung histology of the FSD 8-exposed rats showed only minimal changes in influx of macrophages following the exposure. Determination of global gene expression profiles detected statistically significant differential expressions of only six and five genes in the 10 mg/m(3), 1-d post-exposure, and the 30 mg/m(3), 7-d post-exposure FSD 8 groups, respectively. Taken together, data obtained from the present study demonstrated that FSD 8 inhalation exposure resulted in no statistically significant toxicity or gene expression changes in the lungs of the rats. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) has been designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems.

      14. Influenza A virus nucleoprotein activates the JNK stress-signaling pathway for viral replication by sequestering host filamin A proteinexternal icon
        Sharma A, Batra J, Stuchlik O, Reed MS, Pohl J, Chow VT, Sambhara S, Lal SK.
        Front Microbiol. 2020 ;11.
        Influenza A virus (IAV) poses a major threat to global public health and is known to employ various strategies to usurp the host machinery for survival. Due to its fast-evolving nature, IAVs tend to escape the effect of available drugs and vaccines thus, prompting the development of novel antiviral strategies. High-throughput mass spectrometric screen of host-IAV interacting partners revealed host Filamin A (FLNA), an actin-binding protein involved in regulating multiple signaling pathways, as an interaction partner of IAV nucleoprotein (NP). In this study, we found that the IAV NP interrupts host FLNA-TRAF2 interaction by interacting with FLNA thus, resulting in increased levels of free, displaced TRAF2 molecules available for TRAF2-ASK1 mediated JNK pathway activation, a pathway critical to maintaining efficient viral replication. In addition, siRNA-mediated FLNA silencing was found to promote IAV replication (87% increase) while FLNA-overexpression impaired IAV replication (65% decrease). IAV NP was observed to be a crucial viral factor required to attain FLNA mRNA and protein attenuation post-IAV infection for efficient viral replication. Our results reveal FLNA to be a host factor with antiviral potential hitherto unknown to be involved in the IAV replication cycle thus, opening new possibilities of FLNA-NP interaction as a candidate anti-influenza drug development target.

      15. Laboratory-acquired dengue virus infection, United States, 2018external icon
        Sharp TM, Fisher TG, Long K, Coulson G, Medina FA, Herzig C, Koza MB, Muñoz-Jordán J, Paz-Bailey G, Moore Z, Williams C.
        Emerg Infect Dis. 2020 Jul;26(7):1534-1537.
        Investigation of a dengue case in a laboratory worker in North Carolina, USA, revealed that the case-patient prepared high-titer dengue virus stocks soon before illness onset. Improper doffing of gloves with an open finger wound likely resulted in cutaneous exposure. This case reinforces recommendations for enhanced precautions when working with high-titer dengue virus.

      16. Detection and discrimination of influenza B Victoria lineage deletion variant viruses by real-time RT-PCRexternal icon
        Shu B, Kirby MK, Warnes C, Sessions WM, Davis WG, Liu J, Wilson MM, Lindstrom S, Wentworth DE, Barnes JR.
        Euro Surveill. 2020 Oct;25(41).
        BackgroundDuring the 2016/17 influenza season, influenza B/VIC lineage variant viruses emerged with two (K(162)N(163)) or three (K(162)N(163)D(164)) amino acid (aa) deletions in the haemagglutinin (HA) protein. There are currently five antigenically distinct HA proteins expressed by co-circulating influenza B viruses: B/YAM, B/VIC V1A (no deletion), B/VIC V1A-2DEL (2 aa deletion) and two antigenically distinguishable groups of B/VIC V1A-3DEL (3 aa deletion). The prevalence of these viruses differs across geographical regions, making it critical to have a sensitive, rapid diagnostic assay that detects and distinguishes these influenza B variant viruses during surveillance.AimOur objective was to develop a real-time RT-PCR (rRT-PCR) assay for detection and discrimination of influenza B/VIC lineage variant viruses.MethodsWe designed a diagnostic assay with one pair of conserved primers and three probes specific to each genetic group. We used propagated influenza B/VIC variant viruses and clinical specimens to assess assay performance.ResultsThis rRT-PCR assay detects and distinguishes the influenza B/VIC V1A, B/VIC V1A-2DEL, and B/VIC V1A-3DEL variant viruses, with no cross-reactivity. This assay can be run as a multiplex reaction, allowing for increased testing efficiency and reduced cost.ConclusionCoupling this assay with the Centers for Disease Control and Prevention's Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Influenza B Lineage Genotyping Kit results in rapid detection and characterisation of circulating influenza B viruses. Detailed surveillance information on these distinct influenza B variant viruses will provide insight into their prevalence and geographical distribution and could aid in vaccine recommendations.

      17. Streptococcus pyogenes pbp2x mutation confers reduced susceptibility to β-lactam antibioticsexternal icon
        Vannice KS, Ricaldi J, Nanduri S, Fang FC, Lynch JB, Bryson-Cahn C, Wright T, Duchin J, Kay M, Chochua S, Van Beneden CA, Beall B.
        Clin Infect Dis. 2020 Jun 24;71(1):201-204.
        Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first step in developing β-lactam resistance.

      18. Sequential quadriplex real-time PCR for identifying 20 common emm types of Group A Streptococcusexternal icon
        Velusamy S, Jordak K, Kupor M, Chochua S, McGee L, Beall B.
        J Clin Microbiol. 2020 Oct 21.
        We developed a sequential quadriplex real-time PCR-based method for rapid identification of 20 emm types commonly found in invasive GAS (iGAS) strains recovered through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Each emm real-time PCR assay shows high specificity and accurately identified the respective target emm type, including emm subtypes in the United States. Furthermore, this method is useful for rapid typing of GAS isolates and culture-negative specimens during outbreak investigations.

      19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic of coronavirus disease 2019 (COVID-19). The spike protein expressed on the surface of this virus is highly glycosylated and plays an essential role during the process of infection. We conducted a comprehensive mass spectrometric analysis of the N-glycosylation profiles of the SARS-CoV-2 spike proteins using signature ions-triggered electron-transfer/higher-energy collision dissociation (EThcD) mass spectrometry. The patterns of N-glycosylation within the recombinant ectodomain and S1 subunit of the SARS-CoV-2 spike protein were characterized using this approach. Significant variations were observed in the distribution of glycan types as well as the specific individual glycans on the modification sites of the ectodomain and subunit proteins. The relative abundance of sialylated glycans in the S1 subunit compared to the full-length protein could indicate differences in the global structure and function of these two species. In addition, we compared N-glycan profiles of the recombinant spike proteins produced from different expression systems, including human embryonic kidney (HEK 293) cells and Spodoptera frugiperda (SF9) insect cells. These results provide useful information for the study of the interactions of SARS-CoV-2 viral proteins and for the development of effective vaccines and therapeutics.

    • Maternal and Child Health
      1. A multi-country study of prevalence and early childhood mortality among children with omphaloceleexternal icon
        Nembhard WN, Bergman JE, Politis MD, Arteaga-Vázquez J, Bermejo-Sánchez E, Canfield MA, Cragan JD, Dastgiri S, de Walle HE, Feldkamp ML, Nance A, Gatt M, Groisman B, Hurtado-Villa P, Kallén K, Landau D, Lelong N, Lopez-Camelo J, Martinez L, Morgan M, Pierini A, Rissmann A, Šípek A, Szabova E, Tagliabue G, Wertelecki W, Zarante I, Bakker MK, Kancherla V, Mastroiacovo P.
        Birth Defects Res. 2020 Oct 17.
        BACKGROUND: Omphalocele is the second most common abdominal birth defect and often occurs with other structural and genetic defects. The objective of this study was to determine omphalocele prevalence, time trends, and mortality during early childhood, by geographical region, and the presence of associated anomalies. METHODS: We conducted a retrospective study with 23 birth defect surveillance systems in 18 countries who are members of the International Clearinghouse for Birth Defects Surveillance and Research that submitted data on cases ascertained from 2000 through 2012, approximately 16 million pregnancies were surveyed that resulted in live births, stillbirths, or elective terminations of pregnancy for fetal anomalies (ETOPFA) and cases with omphalocele were included. Overall prevalence and mortality rates for specific ages were calculated (day of birth, neonatal, infant, and early childhood). We used Kaplan-Meier estimates with 95% confidence intervals (CI) to calculate cumulative mortality and joinpoint regression for time trend analyses. RESULTS: The prevalence of omphalocele was 2.6 per 10,000 births (95% CI: 2.5, 2.7) and showed no temporal change from 2000-2012 (average annual percent change = -0.19%, p = .52). The overall mortality rate was 32.1% (95% CI: 30.2, 34.0). Most deaths occurred during the neonatal period and among children with multiple anomalies or syndromic omphalocele. Prevalence and mortality varied by registry type (e.g., hospital- vs. population-based) and inclusion or exclusion of ETOPFA. CONCLUSIONS: The prevalence of omphalocele showed no temporal change from 2000-2012. Approximately one-third of children with omphalocele did not survive early childhood with most deaths occurring in the neonatal period.

    • Nutritional Sciences
      1. Correlates of sugar-sweetened beverage intake among low-income women during the first 1000 daysexternal icon
        Cheng ER, Batista E, Chen L, Nichols K, Park S, Charles N, Woo Baidal J.
        Public Health Nutr. 2020 Oct 22:1-6.
        OBJECTIVE: To describe prenatal and postpartum consumption of water, cows' milk, 100 % juice and sugar-sweetened beverages (SSB) among women enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) programme in New York City (NYC) and to identify correlates of SSB intake in this population. DESIGN: Cross-sectional data were collected from structured questionnaires that included validated beverage frequency questionnaires with the assistance of container samples. The association of maternal and household factors and non-SSB consumption with habitual daily energetic (kJ (kcal)) intake from SSB was assessed by using multivariable median regression. SETTING: WIC programme in NYC, NY. Data were collected in 2017. PARTICIPANTS: 388 pregnant or postpartum women (infant aged <2 years) from the NYC First 1000 Days Study. RESULTS: Median age was 28 years (interquartile range (IQR) 24-34); 94·1 % were Hispanic/Latina, and 31·4 % were pregnant. Overall, 87·7 % of pregnant and 89·1% of postpartum women consumed SSB ≥ once weekly, contributing to a median daily energetic intake of 410 kJ (98 kcal) (IQR (113-904 kJ) 27-216) and 464 kJ (111 kcal) (IQR (163-1013 kJ) 39-242), respectively. In adjusted analyses, only consumption of 100 % juice was associated with greater median energetic intake from SSB (adjusted β for each additional ounce = 13; 95% CI 8, 31 (3·2; 95 % CI 2·0, 7·3). CONCLUSIONS: Among pregnant and postpartum women in WIC-enrolled families, interventions to reduce SSB consumption should include reduction of 100 % juice consumption as a co-target of the intervention.

      2. Dietary supplement use in children and adolescents aged </= 19 years - United States, 2017-2018external icon
        Stierman B, Mishra S, Gahche JJ, Potischman N, Hales CM.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1557-1562.
        Dietary supplement use is common among children and adolescents. During 2013-2014, approximately one third of children and adolescents (persons aged ≤19 years) in the United States were reported to use a dietary supplement in the past 30 days, and use varied by demographic characteristics (1,2). Dietary supplements can contribute substantially to overall nutrient intake, having the potential to both mitigate nutrient shortfalls as well as to lead to nutrient intake above recommended upper limits (3). However, because nutritional needs should generally be met through food consumption according to the 2015-2020 Dietary Guidelines for Americans, only a few dietary supplements are specifically recommended for use among children and adolescents and only under particular conditions (4). The most recently released data from the National Health and Nutrition Examination Survey (NHANES) during 2017-2018 were used to estimate the prevalence of use among U.S. children and adolescents of any dietary supplement, two or more dietary supplements, and specific dietary supplement product types. Trends were calculated for dietary supplement use from 2009-2010 to 2017-2018. During 2017-2018, 34.0% of children and adolescents used any dietary supplement in the past 30 days, with no significant change since 2009-2010. Use of two or more dietary supplements increased from 4.3% during 2009-2010 to 7.1% during 2017-2018. Multivitamin-mineral products were used by 23.8% of children and adolescents, making these the products most commonly used. Because dietary supplement use is common, surveillance of dietary supplement use, combined with nutrient intake from diet, will remain an important component of monitoring nutritional intake in children and adolescents to inform clinical practice and dietary recommendations.

    • Occupational Safety and Health
      1. Welding fume inhalation exposure and high-fat diet change lipid homeostasis in rat liverexternal icon
        Boyce GR, Shoeb M, Kodali V, Meighan TG, Roach KA, McKinney W, Stone S, Powell MJ, Roberts JR, Zeidler-Erdely PC, Erdely A, Antonini JM.
        Toxicology Reports. 2020 ;7:1350-1355.
        It is estimated that greater than 1 million workers are exposed to welding fume (WF) by inhalation daily. The potentially toxic metals found in WF are known to cause multiple adverse pulmonary and systemic effects, including cardiovascular disease, and these metals have also been shown to translocate to the liver. This occupational exposure combined with a high fat (HF) Western diet, which has been shown to cause hyperlipidemia and non-alcoholic fatty liver disease (NAFLD), has the potential to cause significant mixed exposure metabolic changes in the liver. The goal of this study was to use matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to analyze the spatial distribution and abundance changes of lipid species in Sprague Dawley rat liver maintained on a HF diet combined with WF inhalation. The results of the MALDI-IMS analysis revealed unique hepatic lipid profiles for each treatment group. The HF diet group had significantly increased abundance of triglycerides and phosphatidylinositol lipids, as well as decreased lysophosphatidic lipids and cardiolipin. Ceramide-1-phosphate was found at higher abundance in the regular (REG) diet WF-exposed group which has been shown to regulate the eicosanoid pathway involved in pro-inflammatory response. The results of this study showed that the combined effects of WF inhalation and a HF diet significantly altered the hepatic lipidome. Additionally, pulmonary exposure to WF alone increased lipid markers of inflammation.

      2. Workers' compensation claims among private skilled nursing facilities, Ohio, 2001-2012external icon
        Bush AM, Reichard AA, Wurzelbacher SJ, Tseng CY, Lampl MP.
        Am J Ind Med. 2020 Oct 16.
        INTRODUCTION: Skilled nursing facilities have one of the highest rates of occupational injury and illness among all industries. This study quantifies the burden of occupational injury and illness in this industry using data from a single state-based workers' compensation (WC) system. METHODS: Ohio Bureau of Workers' Compensation claims from 2001 to 2012 were analyzed among privately owned, state-insured skilled nursing facilities and are presented as claim counts and rates per 100 full-time equivalents (FTE). Worker, employer, incident, and injury characteristics were examined among all claims and by medical-only (medical care expenses and/or less than eight days away from work) and lost-time (eight days or more away from work) claim types. RESULTS: There were 56,442 claims in this population of Ohio skilled nursing facilities from 2001 to 2012. Overexertion and bodily reaction, slips, trips, and falls, and contact with objects and equipment accounted for the majority of all WC claims (89%). Overexertion and bodily reaction, and slips, trips, and falls comprised 85% of the 10,793 lost-time claims. The highest injury event/exposure rates for all claims were for overexertion and bodily reaction (3.7 per 100 FTE for all claims), followed by slip, trips, and falls (2.1), and contact with objects and equipment (1.9). CONCLUSION: Understanding the details surrounding injury events and exposures resulting in WC claims can help better align prevention efforts, such as incorporation of safe patient handling policies and lifting aids, improvement in housekeeping practices, and employee training within skilled nursing facilities to prevent worker injury and mitigate related expenses.

      3. Objectives: The study objectives were to examine U.S. long-haul truck drivers (LHTDs)' opinions on their safety needs and to assess the associations of driver reported unrealistically tight delivery schedules with: (1) their opinions on their compensation, maximum speed limits, and Hours-of-Service (HOS) regulations, and (2) their behaviors of noncompliance with these safety laws and regulations. Method(s): National Institute for Occupational Safety and Health analyzed data from its 2010 national survey of LHTD health and injury. A total of 1,265 drivers completed the survey. Logistic regression was used to examine the associations between driver reported unrealistically tight delivery schedule and their opinion on safety and unsafe driving behaviors. Result(s): Drivers who reported often receiving an unrealistically tight delivery schedule (an estimated 15.5% of LHTDs) were significantly more likely than drivers who reported never receiving an unrealistically tight delivery schedule to report that: (1) increasing the current maximum speed limit on interstate highways by 10 miles per hour (mph) would improve safety (odds ratio (OR) = 2.1); (2) strictly enforcing HOS rules would not improve safety (OR = 1.8); (3) they often drove 10 mph or more over the speed limit (OR = 7.5); (4) HOS regulations were often violated (OR = 10.9); (5) they often continued to drive despite fatigue, bad weather, or heavy traffic because their must delivery or pick up a load at a given time (OR = 7.5); and (6) their work was never adequately rewarded (OR = 4.5). When presented with 11 potential safety strategies, the largest percentage of LHTDs (95.4%) selected that building more truck stops/parking areas would improve truck driver safety. Conclusion(s): Driver reported unrealistically tight delivery schedules are associated with drivers' beliefs in safety laws/regulations and risk-taking behaviors. LHTDs see building more truck stops/rest areas as the most wanted safety need among the 11 potential safety strategies that were asked about in the survey.

      4. Slips and falls on sloped roof surfaces remain an important safety issue among construction workers. The slip potential has been conventionally analyzed and assessed primarily based on ground reaction forces, which cannot differentiate the specific roles of each of the force factors (e.g., workers’ motions-induced dynamic forces and slope-induced static forces) contributing to the slip potential. Their differentiation may enhance the understanding of the slip mechanisms on the sloped roof surfaces and help develop effective walking and working strategies/tactics to minimize the dangerous slips on the elevated roofs. Hence, the objective of this study is to develop a biodynamic method as an additional tool for analyzing the slip potential of a worker walking or working on sloped roof surfaces. A whole-body biodynamic model is proposed and used to develop the alternative method, in which the slip potential is expressed as an analytical function of its major controlling factors including coefficient of friction, slope angle, and biodynamic forces. Some experimental data available in the literature are used to demonstrate the application of the proposed method. The results suggest that the slope may not change the basic trends of the biodynamic forces, but the slope may affect their magnitudes, which can be explained using the system's energy equation also derived from the whole-body biodynamic model. The analytical results suggest that reducing the body acceleration in uphill direction or the deceleration in downhill direction can reduce the slip potential. ‘Zigging’ and ‘zagging’ walking on a sloped surface may also reduce the slip potential, as it reduces the effective slope angle. The proposed biodynamic theory can be used to enhance the safety guidelines not only for roofers but also for people walking on ramps, inclined walkways, and mountain terrains.

      5. Risk factors for occupational heat-related illness among California workers, 2000-2017external icon
        Heinzerling A, Laws RL, Frederick M, Jackson R, Windham G, Materna B, Harrison R.
        Am J Ind Med. 2020 Oct 19.
        BACKGROUND: As climate change increases global temperatures, heat-related morbidity and mortality are projected to rise. Outdoor workers and those who perform exertional tasks are particularly susceptible to heat-related illness (HRI). Using workers' compensation data, we aimed to describe rates of occupational HRI in California and identify demographic and occupational risk factors to inform prevention efforts. METHODS: We identified HRI cases during 2000-2017 in the California Workers' Compensation Information System (WCIS) using International Classification of Diseases Ninth and Tenth Revision codes, WCIS nature and cause of injury codes, and HRI keywords. We assigned industry and occupation codes using the NIOSH Industry and Occupation Computerized Coding System (NIOCCS). We calculated HRI rates by sex, age group, year, county, industry, and occupation, and estimated confidence intervals using generalized linear models. RESULTS: We identified 15,996 HRI cases during 2000-2017 (6.0 cases/100,000 workers). Workers aged 16-24 years had the highest HRI rate (7.6) among age groups, and men (8.1) had a higher rate than women (3.5). Industry sectors with the highest HRI rates were Agriculture, Farming, Fishing, and Forestry (38.6), and Public Administration (35.3). Occupational groups with the highest HRI rates were Protective Services (56.6) and Farming, Fishing, and Forestry (36.6). Firefighters had the highest HRI rate (389.6) among individual occupations. CONCLUSIONS: Workers in certain demographic and occupational groups are particularly susceptible to HRI. Additional prevention efforts, including outreach and enforcement targeting high-risk groups, are needed to reduce occupational HRI. Workers' compensation data can provide timely information about temporal trends and risk factors for HRI.

      6. Barrier resistance of double layer isolation gownsexternal icon
        Kahveci Z, Kilinc-Balci FS, Yorio PL.
        Am J Infect Control. 2020 Oct 17.
        Isolation gowns are one of the crucial pieces of personal protective equipment (PPE) to prevent the migration of microorganisms and body fluids from patients to healthcare personnel and vice versa. Underperforming isolation gowns in terms of fluid resistance, could potentially put lives in danger. Wearing multiple layers of isolation gowns could theoretically increase the fluid penetration resistance. Extraordinary circumstances such as epidemics/pandemics and product recalls, bring extra burden on the health institutions in terms of PPE availability. Thus, shortages could occur, and PPE that provides an appropriate level of protection might not be available. Therefore, wearing multiple layers of lower barrier level gowns could be assumed as a solution. This study investigates if two-layer lower barrier level isolation gowns meet the barrier effectiveness requirements of a single higher barrier level isolation gown. Three ANSI/AAMI PB70 Level 2 isolation gowns were tested based on the ANSI/AAMI PB70 standard, in single and double-layer configuration. Test results demonstrated that the double layer isolation gown configuration does not always provide equal fluid resistance as the higher level of isolation gown according to results from the AATCC 42 and AATCC 127 standard test methods, which are described in ANSI/AAMI PB70.

    • Occupational Safety and Health - Mining
      1. Field testing of roof bolter canopy air curtain operating downwind of the continuous minerexternal icon
        Reed WR, Shahan M, Gangrade V, Ross G, Singh K, Grounds T.
        Min Metall Explor. 2020 .
        Roof bolter canopy air curtains (CACs) are gaining acceptance as a respirable dust control device that can provide roof bolter operators with protection from overexposure to respirable coal mine dust. Both lab and field studies on the effectiveness of roof bolter CACs have been published. Field studies have shown the effectiveness to be variable. However, in all previous field studies, none has been conducted when the roof bolting machine operates downwind of the continuous miner (CM)—a scenario for which the CAC was designed to provide respirable dust control. This study, performed by researchers from the National Institute for Occupational Safety and Health (NIOSH), was conducted to test a CAC on a roof bolter machine operating downwind of the CM. The results of testing demonstrated that the roof bolter CAC can effectively provide respirable dust protection for roof bolter operators with dust control efficiencies ranging from 11 to 40%.

    • Parasitic Diseases
      1. Evaluation of a facility-based inspection tool to assess lymphedema management services in Vietnamexternal icon
        Dung DT, Binh VT, Worrell CM, Brady M, Walsh V, Yajima A, Sifri Z, Fox LM.
        PLoS Negl Trop Dis. 2020 Oct 19;14(10):e0008773.
        Assuring availability of services for patients with lymphedema is required for countries to be validated as having achieved elimination of lymphatic filariasis (LF). A direct inspection protocol (DIP) tool, designed to measure the readiness to provide quality lymphedema management services, has recently been developed. The DIP tool includes 14 indicators across six quality themes: trained staff, case management and education materials, water infrastructure, medications and commodities, patient tracking system, and staff knowledge. We evaluated the use of the tool in Vietnam, where data were needed to inform validation efforts. To apply the tool in Vietnam, we compiled a list of 219 commune health stations (CHS) with known lymphedema patients and conducted a cross-sectional survey in 32 CHS; including 24 in Red River Delta region, 2 in the North Central region, and 6 in the South Central Coast region. The mean facility score, calculated by assigning 1 point per indicator, was 8.8 of 14 points (63%, range 4[29%]-13[93%]). Percentage of surveyed facilities with staff trained in last two years was 0%; availability of lymphedema management guidelines (56%); availability of information, education, and communication materials (16%); reliable improved water infrastructure (94%); availability of antiseptics (81%), antifungals (44%), analgesics or anti-inflammatories (97%), antibiotics (94%); supplies for lymphedema and acute attack management (100%); lymphedema patients recorded in last 12 months (9%); staff knowledge about lymphedema signs/symptoms (63%), lymphedema management strategies (72%), signs/symptoms of acute attacks (81%), and acute attack management strategies (75%). The tool allowed standardized assessment of readiness to provide quality services. Lack of trained health staff, limited patient tracking, and depletion of education materials were identified as challenges and addressed by the national program. Survey data were included in the validation dossier, providing evidence necessary for WHO to validate Vietnam as having eliminated lymphatic filariasis in 2018.

      2. Progress toward global eradication of dracunculiasis, January 2019-June 2020external icon
        Hopkins DR, Weiss AJ, Roy SL, Yerian S, Sapp SG.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1563-1568.
        Dracunculiasis (Guinea worm disease) is caused by the parasite Dracunculus medinensis and is acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae. The worm typically emerges through the skin on a lower limb approximately 1 year after infection, resulting in pain and disability (1). There is no vaccine or medicine to treat the disease; eradication efforts rely on case containment* to prevent water contamination. Other interventions to prevent infection include health education, water filtration, chemical treatment of unsafe water with temephos (an organophosphate larvicide to kill copepods), and provision of safe drinking water (1,2). The worldwide eradication campaign began in 1980 at CDC (1). In 1986, with an estimated 3.5 million cases(†) occurring each year in 20 African and Asian countries(§) (3), the World Health Assembly (WHA) called for dracunculiasis elimination (4). The global Guinea Worm Eradication Program (GWEP), led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund, CDC, and other partners, began assisting ministries of health in countries with dracunculiasis. This report, based on updated health ministry data (4), describes progress made during January 2019-June 2020 and updates previous reports (2,4,5). With only 54 human cases reported in 2019, 19 human cases reported during January 2019-June 2020, and only six countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, South Sudan, and importations into Cameroon), the achievement of eradication is within reach, but it is challenged by civil unrest, insecurity, and lingering epidemiologic and zoologic concerns, including 2,000 reported animal cases in 2019 and 1,063 animal cases in 2020, mostly in dogs. All national GWEPs remain fully operational, with precautions taken to ensure safety of program staff members and community members in response to the coronavirus disease 2019 (COVID-19) pandemic.

    • Public Health Leadership and Management
      1. Africa Centres for Disease Control and Prevention is closing gaps in disease detectionexternal icon
        Varma J, Maeda J, Magafu M, Onyebujoh PC.
        Health Secur. 2020 Oct 20.
        In 2017, the African Union established a new continent-wide public health agency, the Africa Centres for Disease Control and Prevention (Africa CDC). Many outbreaks are never detected in Africa, and among outbreaks that are detected, countries often respond slowly and ineffectively. To address these problems, Africa CDC is working to increase early detection and reporting, improve access to diagnostic tests, promote novel laboratory approaches, help establish national public health institutes, improve information exchange between health agencies, and enhance recording and reporting of acute public health events and vital statistics. The health security of Africa will be strengthened by this new public health agency's ability to build comprehensive, timely disease surveillance that rapidly detects and contains health threats.

    • Substance Use and Abuse
      1. Patterns of tobacco use and nicotine dependence among youth, United States, 2017-2018external icon
        Gomez Y, Creamer M, Trivers KF, Anic G, Morse AL, Reissig C, Agaku I.
        Prev Med. 2020 Oct 14:106284.
        This study examined patterns of tobacco product use and its influence on nicotine dependence among U.S. youth. Combined data from the 2017-2018 National Youth Tobacco Surveys were analyzed for students that reported current (past-30-day) use of e-cigarettes, cigarettes, cigars, smokeless tobacco, or hookah (n = 6106). Analyses assessed multiple product use (≥2 tobacco products) overall and by sex, school level, race/ethnicity, current use, and frequent use (use of a product for ≥20 of the preceding 30 days). Multivariable logistic regression was used to identify correlates of nicotine dependence. During 2017-2018, 40.8% of tobacco product users reported use of multiple products. Multiple product use ranged from 47.0% among e-cigarette users to 80.7% among cigarette users. Among frequent users of each respective product, 80.0% of cigarette smokers, 74.9% of cigar smokers, 73.6% of smokeless tobacco users, 70.7% of hookah smokers, and 40.3% of e-cigarette users reported use of multiple products. Most youth who reported nicotine dependence (64.0%) were multiple product users. E-cigarettes were the most common single product used (36.3%) and the product most commonly used in combination with other products; ecigarettes plus cigarettes (6.7%) was the most common product combination. Combustible product use, smokeless tobacco use, multiple product use and frequent use were associated with greater odds of nicotine dependence. Nicotine dependence among youth is especially influenced by cigarette use, smokeless tobacco use, frequent use of any tobacco product, and multiple product use. Proven tobacco control interventions in coordination with regulatory efforts can reduce youth tobacco product use.

      2. Country-level differences in nicotine vaping products used and biomarkers of exposure among long-term e-cigarette users and dual users remain understudied. This cross-sectional study was conducted in 2014 in the United States (n = 166), United Kingdom (n = 129), and Poland (n = 161). We compared patterns of tobacco product use and nicotine and toxicant exposure among cigarette-only smokers (n = 127); e-cigarette-only users (n = 124); dual users of tobacco cigarettes and e-cigarettes (n = 95); and non-users (control group, n = 110) across three countries using mixed-effects linear regression. Compared with cigarette smokers, e-cigarette-only users had lower levels of toxicant biomarkers, but higher levels of nicotine biomarkers. Dual users had higher levels of toxicant biomarkers than e-cigarette-only users but similar levels to cigarette-only smokers. E-cigarette users in Poland, who overwhelmingly used refillable tank devices, exhibited greater levels of nicotine, and toxicant biomarkers relative to e-cigarette users in US/UK. Despite smoking fewer cigarettes, dual users from Poland exhibited similar levels of nicotine biomarkers compared with UK dual users, but higher than US dual users. Country-level differences in e-cigarette devices used and smoking behaviors (e.g., intensity) may contribute to differences in biomarker levels among users of the same products residing in different countries.

      3. Availability and characteristics of hospital-affiliated tobacco-cessation programs in the U.S., 2000-2018external icon
        Wang X, VanFrank B, Zhang L, Shrestha S, Trivers KF.
        Am J Prev Med. 2020 Oct 9.
        INTRODUCTION: Smoking-cessation interventions can increase successful quitting, reduce healthcare costs, and enhance patients' health and well-being. This study assesses changes in the availability of hospital-affiliated smoking-cessation programs over time in the U.S. and examines the hospital characteristics associated with such programs. METHODS: Data were obtained from the American Hospital Association annual surveys. Joinpoint regressions were used to estimate the trends in having hospital-affiliated cessation programs between 2000 and 2018. A logit regression was used to estimate the association between hospital characteristics (bed size, location, teaching status, ownership) and having any hospital-affiliated cessation program. Analyses were conducted in 2019. RESULTS: The percentage of U.S. hospitals with any tobacco-cessation program increased from 23.8% (95% CI=22.7, 24.9) in 2000 to 45.5% (95% CI=44.2, 46.7) in 2018. There were sharp increases in the cessation programs between 2000 and 2002 but no change between 2015 and 2018. Hospitals with ≥200 beds (vs <200 beds; OR=2.6, 95% CI=2.5, 2.7), urban hospitals (vs rural; OR=1.3, 95% CI=1.2, 1.3), teaching hospitals (vs nonteaching; OR=1.7, 95% CI=1.7, 1.8), and private not-for-profit hospitals and public hospitals (vs private for-profit; OR=5.1, 95% CI=4.9, 5.3, and OR=3.2, 95% CI=3.0, 3.4, respectively) had higher odds of having a hospital-affiliated tobacco-cessation program. CONCLUSIONS: Less than half of U.S. hospitals reported having any hospital-affiliated cessation program in 2018. Although program prevalence nearly doubled between 2000 and 2015, this increase has not continued in recent years. Further efforts to promote and support hospital-affiliated cessation programs could be beneficial, especially among smaller, rural, nonteaching, and private for-profit hospitals.

    • Zoonotic and Vectorborne Diseases
      1. Age-dependent seroprevalence of dengue and chikungunya: inference from a cross-sectional analysis in Esmeraldas Province in coastal Ecuadorexternal icon
        Chis Ster I, Rodriguez A, Romero NC, Lopez A, Chico M, Montgomery J, Cooper P.
        BMJ Open. 2020 Oct 16;10(10):e040735.
        OBJECTIVES: There are few population-based estimates for prevalence of past exposure to dengue and chikungunya viruses despite common epidemiological features. Here, we have developed a novel statistical method to study patterns of age-dependent prevalence of immunity in a population following exposures to two viruses which share similar epidemiological features including mode of transmission and induction of long-lasting immunity. This statistical technique accounted for sociodemographic characteristics associated with individuals and households. SETTINGS: The data consist of a representative sample from an ongoing longitudinal birth cohort set-up in a tropical district in coastal Ecuador (Esmeraldas). PARTICIPANTS: We collected data and blood samples from 319 individuals belonging to 152 households following epidemics of the infections in 2015 in Latin America. PRIMARY OUTCOME: Plasma was tested for the presence of specific IgG antibodies to dengue and chikungunya viruses by commercial ELISA and defined a bivariate binary outcome indicating individuals' past exposure status to dengue and chikungunya (ie, presence/absence of IgG antibodies to dengue or chikungunya or both). RESULTS: Dengue seroprevalence increased rapidly with age reaching 97% (95% credible interval (CrI): 93%-99%) by 60 years. Chikungunya seroprevalence peaked at 42% (95% CrI: 18%-66%) around 9 years of age and averaged 27% (95% CrI: 8.7%-51.6%) for all ages. Rural areas were more likely to be associated with dengue-only exposure while urban areas and shorter distance to the nearest household were associated with exposures to both. Women living in urban settings were more likely to be chikungunya seropositive while rural men were more likely to be dengue seropositive. CONCLUSION: Dengue seroprevalence was strongly age dependent consistent with endemic exposure while that of chikungunya peaked in childhood consistent with the recent emergence of the virus in the study area. Our findings will inform control strategies for the two arboviruses in Ecuador including recommendations by the WHO on dengue vaccination.

      2. From people to panthera: Natural SARS-CoV-2 infection in tigers and lions at the Bronx Zooexternal icon
        McAloose D, Laverack M, Wang L, Killian ML, Caserta LC, Yuan F, Mitchell PK, Queen K, Mauldin MR, Cronk BD, Bartlett SL, Sykes JM, Zec S, Stokol T, Ingerman K, Delaney MA, Fredrickson R, Ivančić M, Jenkins-Moore M, Mozingo K, Franzen K, Bergeson NH, Goodman L, Wang H, Fang Y, Olmstead C, McCann C, Thomas P, Goodrich E, Elvinger F, Smith DC, Tong S, Slavinski S, Calle PP, Terio K, Torchetti MK, Diel DG.
        mBio. 2020 Oct 13;11(5).
        Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

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