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Issue 1, January 5, 2021

CDC Science Clips: Volume 13, Issue 1, January 5, 2021

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions.

  1. 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. Risk factors for amyotrophic lateral sclerosis: A regional United States case-control studyexternal icon
        Andrew AS, Bradley WG, Peipert D, Butt T, Amoako K, Pioro EP, Tandan R, Novak J, Quick A, Pugar KD, Sawlani K, Katirji B, Hayes TA, Cazzolli P, Gui J, Mehta P, Horton DK, Stommel EW.
        Muscle Nerve. 2021 Jan;63(1):52-59.
        Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted odds ratio [OR] 1.60 95% confidence interval [CI] 1.04-2.45), with significantly greater effects for injuries occurring 10 or more years prior to symptom onset (P = .037). ALS risk was increased for those reporting severe electrical burns (adjusted OR 2.86, 95% CI 1.37-6.03), with odds ratios highest for burns after age 30 (OR 3.14), and for burns 10 or more years prior to symptom onset (OR 3.09). Hobbies involving lead were the most strongly associated with ALS risk (adjusted OR 2.92, 95% CI 1.45-5.91). Exposures to lead 20 or more years prior to diagnosis had larger effect sizes compared to those occurring more recently. Holding a job in mechanics, painting, or construction was associated with ALS. The identification of these specific environmental factors associated with ALS highlight the need for future prospective and laboratory studies to assess causality, biological mechanisms, and find prevention or treatment opportunities.

      2. High disease severity among Asians in a US multiethnic cohort of individuals with systemic lupus erythematosusexternal icon
        DeQuattro K, Trupin L, Murphy LB, Rush S, Criswell LA, Lanata CM, Dall'Era M, Katz P, Yazdany J.
        Arthritis Care Res (Hoboken). 2020 Dec 18.
        OBJECTIVE: Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asians is lacking. We examined SLE disease activity, severity, and damage among Asians of primarily Chinese and Filipino descent in a multiethnic cohort. METHODS: California Lupus Epidemiology Study (CLUES, n=328) data were analyzed. Data were collected in English, Cantonese, Mandarin or Spanish, using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]) and disease damage (Systemic Lupus International Collaborating Clinics Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. RESULTS: Asians were the largest racial/ethnic group (38%; [Chinese=22%; Filipino=9%; Other=7%]). Average age at diagnosis (years) was younger among Asians (27.9), particularly Filipinos (22.2), compared with Whites (29.4) and Blacks (34.0). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asians was significantly higher than Whites (LSI 7.1 vs 6.5; p<0.05) but similar to Blacks and Hispanics. Early age at diagnosis was associated with greater organ damage among Asians, Blacks, and Hispanics, but not Whites. CONCLUSIONS: SLE was more severe among US Asians compared to Whites. Filipinos were affected at strikingly young ages. Asians and non-White groups with younger age at diagnosis had greater organ damage than Whites. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asians with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

      3. The relation of adiposity rebound to subsequent BMI in a large electronic health record databaseexternal icon
        Freedman DS, Goodman AB, King RJ, Kompaniyets L, Daymont C.
        Child Obes. 2020 Dec 22.
        Objective: The beginning of postinfancy increase in BMI has been termed the adiposity rebound, and an early rebound increases the risk for obesity in adolescence and adulthood. We examined whether the relation of the age at BMI rebound (age(rebound)) to subsequent BMI is independent of childhood BMI. Design: From the electronic health records of 2.8 million children, we selected 17,077 children examined at least once each year between ages 2 and <8 years, and who were reexamined between age 10 and <16 years. The mean age at the last visit was 12 years (SD = 1). We identified age(rebound) for each child using lowess, a smoothing technique. Results: Children who had an age(rebound) <3 years were, on average, 6.8 kg/m(2) heavier after age 10 years than were children with an age(rebound) >7 years. However, BMI after age 10 years was more strongly associated with BMI at the rebound (BMI(rebound)) than with age(rebound) (r = 0.63 vs. -0.49). Although the relation of age(rebound) to BMI at the last visit was mostly independent of the BMI(rebound), adjustment for age-5 BMI reduced the association's magnitude by about 55%. Conclusions: Both age(rebound) and the BMI(rebound) are independently related to BMI and obesity after age 10 years. However, a child's BMI(rebound) and at ages 5 and 7 years accounts for more of the variability in BMI levels after age 10 years than does age(rebound).

      4. Incidence and predictors of type 1 diabetes among younger adults aged 20-45 years: The Diabetes in Young Adults (DiYA) Studyexternal icon
        Lawrence JM, Slezak JM, Quesenberry C, Li X, Yu L, Rewers M, Alexander JG, Takhar HS, Sridhar S, Albright A, Rolka DB, Saydah S, Imperatore G, Ferrara A.
        Diabetes Res Clin Pract. 2020 Dec 15:108624.
        AIMS: To estimate incidence of type 1 diabetes (T1D) and to develop a T1D prediction model among young adults. METHODS: Adults 20-45 years newly-diagnosed with diabetes in 2017 were identified within Kaiser Permanente's healthcare systems in California and invited for diabetes autoantibody (DAA) testing. Multiple imputation was conducted to assign missing DAA status. The primary outcome for incidence rates (IR) and the prediction model was T1D defined by ≥1 positive DAA. RESULTS: Among 2,347,989 persons at risk, 7,862 developed diabetes, 2,063 had DAA measured, and 166 (8.0%) had ≥1 positive DAA. T1D IR (95% CI) per 100,000 person-years was 15.2 (10.2-20.1) for ages 20-29 and 38.2 (28.6-47.8) for ages 30-44 years. The age-standardized IRs were 32.5 (22.2-42.8) for men and 27.2 (21.0-34.5) for women. The age/sex-standardized IRs were 30.1 (23.5-36.8) overall; 41.4 (25.3-57.5) for Hispanics, 37.0 (11.6-62.4) for Blacks, 21.4 (14.3-28.6) for non-Hispanic Whites, and 19.4 (8.5-30.2) for Asians. Predictors of T1D among cases included female sex, younger age, lower BMI, insulin use and having T1D based on diagnostic codes. CONCLUSIONS: T1D may account for up to 8% of incident diabetes cases among young adults. Follow-up is needed to establish the clinical course of patients with one DAA at diagnosis.

      5. Background/Purpose: There is much interest in screening for and treating psychosocial distress in cancer patients; however, little is known about if and how psychosocial services are provided for patients demonstrating significant levels of distress. Oncology social workers (OSWs) are the primary providers of psychosocial care for cancer patients and their families, yet there is no widely-used and empirically-validated instrument that captures the range of interventions provided by OSWs. The purpose of this paper is to describe the development of the Oncology Social Work Intervention Index (OSWii), designed to measure interventions provided by OSWs, and the results of testing the instrument. Methods: We conducted a content analysis of data collected by the Association of Oncology Social Work’s Project to Assure Quality Cancer Care (APAQCC). We analyzed 3,194 responses from an open-ended question that described social work interventions following a distress screen. Five investigators coded the data in an iterative process to enhance instrument validity. The resulting instrument measuring OSWii was piloted with 38 oncology social workers across 156 individual cases. Results: OSWs who piloted the OSWii spent a majority of time (72%) engaging in clinical interventions. The user assessment revealed that data entry was rapid, the instrument was easy to use, and the content was relevant to the cancer treatment setting. Conclusions and Implications: Using a standardized instrument that reflects OSWs’ clinical interventions is critical for researchers to examine the impact of psychosocial interventions on patient outcomes. This index may also advance the translation of scientific findings into patient-centered psychosocial cancer care. This pilot test suggests that the OSWii is both scalable and useful.

      6. Defect-free care trends in the Paul Coverdell National Acute Stroke Program, Program, 2008-2018external icon
        Overwyk KJ, Yin X, Tong X, King SM, Wiltz JL.
        Am Heart J. 2020 Nov 27;232:177-184.
        BACKGROUND: In an effort to improve stroke quality of care and patient outcomes, quality of care metrics are monitored to assess utilization of evidence-based stroke care processes as part of the Paul Coverdell National Acute Stroke Program (PCNASP). We aimed to assess temporal trends in defect-free care (DFC) received by stroke patients in the PCNASP between 2008 and 2018. METHODS: Quality of care data for 10 performance measures were available for 849,793 patients aged ≥18 years who were admitted to a participating hospital with a clinical diagnosis of stroke between 2008 and 2018. A patient who receives care according to all performance measures for which they are eligible, receives "defect-free care" (DFC) (eg, appropriate medications, assessments, and education). Generalized estimating equations were used to examine the factors associated with receipt of DFC. RESULTS: DFC among ischemic stroke patients increased from 38.0% in 2008 to 80.8% in 2018 (P < .0001), with the largest improvement seen in receipt of stroke education (relative percent change, RPC = 64%). Similarly, DFC for hemorrhagic stroke and transient ischemic attack patients increased from 46.7% to 82.6% (RPC = 76.9%) and 39.9% to 85.0% (RPC = 113.0%) (P < .001), respectively. Among ischemic stroke patients, the adjusted odds for receiving DFC were lower for women, patients aged 18 to 54 years, Medicaid or Medicare participants, and patients with atrial fibrillation (P < .05). CONCLUSIONS: From 2008 to 2018, receipt of DFC by ischemic stroke patients significantly increased in the PCNASP; however certain subgroups were less likely to receive this level of care. Targeted quality improvement initiatives could result in even further improvements among all stroke patients and help reduce disparities in care.

      7. OBJECTIVE: To assess the prevalence of diagnosed diabetes among employed U.S. adults from 36 states by occupation group using data from 2014-2018 Behavioral Risk Factor Surveillance System. METHODS: Prevalence of diabetes was calculated by 22 broad and 93 detailed occupation groups among a sample of 366,633 employed respondents. Wald chi-square values were used to determine the significance of associations between diabetes and occupation groups after adjusting for sex, age, and race/ethnicity. RESULTS: The prevalence of diabetes was 6.4% among employed U.S. adults. The three broad occupation groups with the highest adjusted prevalence of diabetes were protective services (8.9%), farming, fishing, and forestry (8.8%), and community and social services (8.4%). CONCLUSIONS: Prevalence of diabetes differed by occupation. Work-related factors (e.g. shift work, job stress) should be further examined in relation to risk of developing diabetes.

    • Communicable Diseases
      1. Infant HIV diagnosis and turn-around time for testing in Malawi, 2015external icon
        Ali H, Minchella P, Chipungu G, Kim E, Kandulu J, Midiani D, Kim A, Swaminathan M, Gutreuter S, Nkengasong J, Singer D.
        Afr J Lab Med. 2020 ;9(1):904.
        BACKGROUND: For HIV-exposed infants in Malawi, there are missed opportunities at each step of the testing and treatment cascade. OBJECTIVE: This study assessed factors associated with HIV positivity among infants in Malawi and turn-around times for infant HIV testing. METHODS: HIV testing data for infants aged 0-18 months from 2012 to 2015 were extracted from the Malawi HIV laboratory information management system and analysed using logistic regression. Turn-around time was defined as time between collection of samples to results dispatch from the laboratory. RESULTS: A total of 106 997 tests were included in the analyses. A subset of 76 006 observations with complete dates were included in the turn-around time analysis. Overall positivity was 4.2%. Factors associated with positivity were increasing age (infants aged 3-6 months: adjusted odds ratio [aOR] = 2.24; infants aged 6-9 months: aOR = 3.42; infants aged > 9 months: aOR = 4.24), female sex (aOR = 1.08) and whether the mother was alive and not on antiretroviral therapy at time of the infant's test (aOR = 1.57). Provision of HIV prophylaxis to the infant after birth (aOR = 0.38) was found to be protective against HIV positivity. The median turn-around time was 24 days (increased from 19 to 34 days between 2012 and 2015). CONCLUSION: Infant HIV positivity has decreased in Malawi, whereas turn-around time has increased. Factors associated with positivity include increasing age, female sex, and whether the mother was alive and not on antiretroviral therapy at the time of the infant's test.

      2. The role of testing in reducing SARS-CoV-2 transmission on college campusesexternal icon
        Barrios LC, Green RF, Honein MA.
        J Adolesc Health. 2021 Jan;68(1):1-2.

      3. Time from HIV diagnosis to viral suppression: Survival analysis of statewide surveillance data in Alabama, 2012 to 2014external icon
        Batey DS, Dong X, Rogers RP, Merriweather A, Elopre L, Rana AI, Hall HI, Mugavero MJ.
        JMIR Public Health Surveill. 2020 May 22;6(2):e17217.
        BACKGROUND: Evaluation of the time from HIV diagnosis to viral suppression (VS) captures the collective effectiveness of HIV prevention and treatment activities in a given locale and provides a more global estimate of how effectively the larger HIV care system is working in a given geographic area or jurisdiction. OBJECTIVE: This study aimed to evaluate temporal and geographic variability in VS among persons with newly diagnosed HIV infection in Alabama between 2012 and 2014. METHODS: With data from the National HIV Surveillance System, we evaluated median time from HIV diagnosis to VS (<200 c/mL) overall and stratified by Alabama public health area (PHA) among persons with HIV diagnosed during 2012 to 2014 using the Kaplan-Meier approach. RESULTS: Among 1979 newly diagnosed persons, 1181 (59.67%) achieved VS within 12 months of diagnosis; 52.6% (353/671) in 2012, 59.5% (377/634) in 2013, and 66.9% (451/674) in 2014. Median time from HIV diagnosis to VS was 8 months: 10 months in 2012, 8 months in 2013, and 6 months in 2014. Across 11 PHAs in Alabama, 12-month VS ranged from 45.8% (130/284) to 84% (26/31), and median time from diagnosis to VS ranged from 5 to 13 months. CONCLUSIONS: Temporal improvement in persons achieving VS following HIV diagnosis statewide in Alabama is encouraging. However, considerable geographic variability warrants further evaluation to inform public health action. Time from HIV diagnosis to VS represents a meaningful indicator that can be incorporated into public health surveillance and programming.

      4. Early insights from statistical and mathematical modeling of key epidemiologic parameters of COVID-19external icon
        Biggerstaff M, Cowling BJ, Cucunubá ZM, Dinh L, Ferguson NM, Gao H, Hill V, Imai N, Johansson MA, Kada S, Morgan O, Pastore y Piontti A, Polonsky JA, Prasad PV, Quandelacy TM, Rambaut A, Tappero JW, Vandemaele KA, Vespignani A, Warmbrod KL, Wong JY.
        Emerg Infect Dis. 2020 Nov;26(11):e1-e14.
        We report key epidemiologic parameter estimates for coronavirus disease identified in peer-reviewed publications, preprint articles, and online reports. Range estimates for incubation period were 1.8-6.9 days, serial interval 4.0-7.5 days, and doubling time 2.3-7.4 days. The effective reproductive number varied widely, with reductions attributable to interventions. Case burden and infection fatality ratios increased with patient age. Implementation of combined interventions could reduce cases and delay epidemic peak up to 1 month. These parameters for transmission, disease severity, and intervention effectiveness are critical for guiding policy decisions. Estimates will likely change as new information becomes available.

      5. COVID-19-associated hospitalization rates and severe outcomes among veterans from 5 Veteran Affairs Medical Centers, February 27-July 17, 2020: Hospital-based surveillanceexternal icon
        Cardemil CV, Dahl R, Prill MM, Cates J, Brown S, Perea A, Marconi V, Bell L, Rodriguez-Barradas M, Rivera-Dominguez G, Beenhouwer D, Poteshkina A, Holodniy M, Lucero-Obusan C, Balachandran N, Hall AJ, Kim L, Langley G.
        JMIR Public Health Surveill. 2020 Dec 14.
        BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the US. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, is needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among Veterans in a multi-site surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers (VAMCs: Atlanta, Bronx, Houston, Palo Alto, and Los Angeles), collectively serving >396,000 patients annually. From February 27- July 17 2020, we actively identified SARS-CoV-2 positive inpatient cases through screening of admitted patients and review of laboratory test results. We manually abstracted medical charts for demographics, underlying medical conditions, and clinical outcomes of COVID-19 hospitalized patients. We calculated hospitalization incidence and incidence rate ratios, and relative risk (RR) for invasive mechanical ventilation, intensive care unit (ICU) admission, and death after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed hospitalized COVID-19 cases. Median age was 70 years, 66% were aged ≥65 years, and 94% were male. Most COVID-19 diagnoses were among non-Hispanic Blacks (52%), followed by non-Hispanic Whites (25%) and Hispanic or Latinos (18%). Hospitalization rates were highest among Veterans aged ≥85 years, Hispanic or Latino, and non-Hispanic Black (430, 317 and 298 per 100,000, respectively); Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with Veterans aged 18-29 years (95% CI: 5.7-34.6), while Hispanic or Latino and Black Veterans had a 4.6 and 4.2-fold increased rate of hospitalization compared with non-Hispanic White Veterans (95% CI: 3.6-5.9), respectively. Overall, 11.6% of patients required invasive mechanical ventilation, 26.6% were admitted to the intensive care unit (ICU), and 16.9% died in hospital. The adjusted RR for invasive mechanical ventilation and ICU admission did not differ by age group or race/ethnicity, but Veterans aged ≥65 had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged <65 years (95% CI: 2.4-8.6). CONCLUSIONS: COVID-19 surveillance at 5 VAMCs across the US demonstrated higher hospitalization rates and severe outcomes in older Veterans, and higher hospitalization rates in Hispanic or Latino and non-Hispanic Black Veterans compared to non-Hispanic White Veterans. These data highlight the need for targeted prevention and timely treatment for Veterans, with special attention to increasing age, Hispanic or Latino and non-Hispanic Black Veterans.

      6. On March 9, 2019, a one-day workshop titled "The current epidemiology of invasive Haemophilus influenzae disease in the Americas", jointly organized by the Public Health Agency of Canada (PHAC), the Canadian Institute of Health Research (CIHR), and the National Research Council Canada (NRC), brought together experts in the epidemiology and surveillance of invasive Haemophilus influenzae (Hi) disease from the Pan American Health Organization (PAHO) and its five regional reference laboratories in South America, USA, and Canada in Ottawa, Ontario, Canada. This workshop built upon recommendations of previous related workshops and incorporated updated data.

      7. Nigeria's public health response to the COVID-19 pandemic: January to May 2020external icon
        Dan-Nwafor C, Ochu CL, Elimian K, Oladejo J, Ilori E, Umeokonkwo C, Steinhardt L, Igumbor E, Wagai J, Okwor T, Aderinola O, Mba N, Hassan A, Dalhat M, Jinadu K, Badaru S, Arinze C, Jafiya A, Disu Y, Saleh F, Abubakar A, Obiekea C, Yinka-Ogunleye A, Naidoo D, Namara G, Muhammad S, Ipadeola O, Ofoegbunam C, Ogunbode O, Akatobi C, Alagi M, Yashe R, Crawford E, Okunromade O, Aniaku E, Mba S, Agogo E, Olugbile M, Eneh C, Ahumibe A, Nwachukwu W, Ibekwe P, Adejoro OO, Ukponu W, Olayinka A, Okudo I, Aruna O, Yusuf F, Alex-Okoh M, Fawole T, Alaka A, Muntari H, Yennan S, Atteh R, Balogun M, Waziri N, Ogunniyi A, Ebhodaghe B, Lokossou V, Abudulaziz M, Adebiyi B, Abayomi A, Abudus-Salam I, Omilabu S, Lawal L, Kawu M, Muhammad B, Tsanyawa A, Soyinka F, Coker T, Alabi O, Joannis T, Dalhatu I, Swaminathan M, Salako B, Abubakar I, Fiona B, Nguku P, Aliyu SH, Ihekweazu C.
        J Glob Health. 2020 Dec;10(2):020399.

      8. Current and past immunodeficiency are associated with higher hospitalization rates among persons on virologically suppressive antiretroviral therapy for up to eleven yearsexternal icon
        Davy-Mendez T, Napravnik S, Eron JJ, Cole SR, van Duin D, Wohl DA, Hogan BC, Althoff KN, Gebo KA, Moore RD, Silverberg MJ, Horberg MA, Gill MJ, Mathews WC, Klein MB, Colasanti JA, Sterling TR, Mayor AM, Rebeiro PF, Buchacz K, Li J, Nanditha NG, Thorne JE, Nijhawan A, Berry SA.
        J Infect Dis. 2020 Dec 26.
        BACKGROUND: Persons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. METHODS: In six US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (Years 2-5) and long-term (Years 6-11) suppression and lowest pre-suppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRR) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest pre-suppression CD4 count. RESULTS: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% White. Among patients with lowest pre-suppression CD4 <200 cells/μL (44%), patients with current CD4 200-350 versus >500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression. CONCLUSIONS: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies.

      9. The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID-19 Vaccine - United States, December 2020external icon
        Dooling K, Marin M, Wallace M, McClung N, Chamberland M, Lee GM, Talbot HK, Romero JR, Bell BP, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1657-1660.
        The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use.(†) On December 1, ACIP recommended that 1) health care personnel(§) and 2) residents of long-term care facilities(¶) be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.

      10. Cleaning and disinfection of frequently touched surfaces and frequent hand hygiene are recommended measures to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. Since the onset of the COVID-19 pandemic, poison center calls regarding exposures to cleaners, disinfectants, and hand sanitizers have increased as compared with prior years, indicating a need to evaluate household safety precautions. An opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020. Survey items evaluated knowledge regarding use and storage of cleaners, disinfectants, and hand sanitizers; attitudes about household cleaning and disinfection; and safety precautions practiced during the prior month. We assigned a knowledge score to each respondent to quantify knowledge of safety precautions and calculated median scores by demographic characteristics and attitudes. We identified gaps in knowledge regarding safe use and storage of cleaners, disinfectants, and hand sanitizers; the overall median knowledge score was 5.17 (95% CI: 4.85-5.50; maximum 9.00). Knowledge scores were lower among younger than older age-groups and among black non-Hispanic and Hispanic respondents compared with white non-Hispanic respondents. A greater proportion of respondents expressed knowledge of safety precautions than the proportion who engaged in these precautions. Tailored communication strategies should be used to reach populations with lower knowledge of cleaning and disinfection safety. In addition, as knowledge alone did not shape individual engagement in safety precautions, health promotion campaigns may specifically emphasize the health risks of unsafe use and storage of cleaners, disinfectants, and hand sanitizers to address risk perception.

      11. Laboratory evaluation of two point-of-care detection systems for early and accurate detectaion of influenza in the Lao People's Democratic Republicexternal icon
        Kittikraisak W, Khamphaphongphane B, Xayadeth S, Oulay VS, Khanthamaly V, Sengvilaipaseuth O, Davis CT, Yang G, Zanders N, Mott JA, Xangsayarath P.
        Int J Infect Dis. 2020 Dec 23.
        BACKGROUND: We evaluated molecular-based point-of-care influenza detection systems in a laboratory prior to the field evaluations of on-site specimen testing. METHODS: Performance of 1) insulated isothermal PCR on the POCKIT(TM) device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96(TM) Real-time Detection System was used as a gold standard for comparisons. RESULTS: Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT(TM) only correctly identified influenza A(M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT(TM) was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini had mixed results depending on the types and subtypes of influenza viruses. CONCLUSIONS: The performance of the two systems in a laboratory is promising and supports further evaluation in field settings.


      12. CD4 count at entry into HIV care and at antiretroviral therapy prescription in the US, 2005-2018external icon
        Lee JS, Humes EA, Hogan BC, Buchacz K, Eron JJ, Gill MJ, Sterling TR, Rebeiro PF, Lima VD, Mayor A, Silverberg MJ, Horberg MA, Moore RD, Althoff KN.
        Clin Infect Dis. 2020 Dec 31.
        From 2005 to 2018, among 32013 adults entering HIV care in the US, median time to ART prescription declined from 69 to 6 days, median CD4 count at entry into care increased from 300 to 362 cells/µL, and median CD4 count at ART prescription increased from 160 to 364 cells/µL.

      13. Rates and correlates of HIV incidence in Namibia's Zambezi region from 2014 to 2016: Sentinel, community-based cohort studyexternal icon
        Maher AD, Nakanyala T, Mutenda N, Banda KM, Prybylski D, Wolkon A, Jonas A, Sawadogo S, Ntema C, Chipadze MR, Sinvula G, Tizora A, Mwandemele A, Chaturvedi S, Agovi AM, Agolory S, Hamunime N, Lowrance DW, McFarland W, Patel SV.
        JMIR Public Health Surveill. 2020 Jun 24;6(2):e17107.
        BACKGROUND: Direct measures of HIV incidence are needed to assess the population-level impact of prevention programs but are scarcely available in the subnational epidemic hotspots of sub-Saharan Africa. We created a sentinel HIV incidence cohort within a community-based program that provided home-based HIV testing to all residents of Namibia's Zambezi region, where approximately 24% of the adult population was estimated to be living with HIV. OBJECTIVE: The aim of this study was to estimate HIV incidence, detect correlates of HIV acquisition, and assess the feasibility of the sentinel, community-based approach to HIV incidence surveillance in a subnational epidemic hotspot. METHODS: Following the program's initial home-based testing (December 2014-July 2015), we purposefully selected 10 clusters of 60 to 70 households each and invited residents who were HIV negative and aged ≥15 years to participate in the cohort. Consenting participants completed behavioral interviews and a second HIV test approximately 1 year later (March-September 2016). We used Poisson models to calculate HIV incidence rates between baseline and follow-up and multivariable Cox proportional hazard models to assess the correlates of seroconversion. RESULTS: Among 1742 HIV-negative participants, 1624 (93.23%) completed follow-up. We observed 26 seroconversions in 1954 person-years (PY) of follow-up, equating to an overall incidence rate of 1.33 per 100 PY (95% CI 0.91-1.95). Among women, the incidence was 1.55 per 100 PY (95% CI 1.12-2.17) and significantly higher among those aged 15 to 24 years and residing in rural areas (adjusted hazard ratio [aHR] 4.26, 95% CI 1.39-13.13; P=.01), residing in the Ngweze suburb of Katima Mulilo city (aHR 2.34, 95% CI 1.25-4.40; P=.01), who had no prior HIV testing in the year before cohort enrollment (aHR 3.38, 95% CI 1.04-10.95; P=.05), and who had engaged in transactional sex (aHR 17.64, 95% CI 2.88-108.14; P=.02). Among men, HIV incidence was 1.05 per 100 PY (95% CI 0.54-2.31) and significantly higher among those aged 40 to 44 years (aHR 13.04, 95% CI 5.98-28.41; P<.001) and had sought HIV testing outside the study between baseline and follow-up (aHR 8.28, 95% CI 1.39-49.38; P=.02). No seroconversions occurred among persons with HIV-positive partners on antiretroviral treatment. CONCLUSIONS: Nearly three decades into Namibia's generalized HIV epidemic, these are the first estimates of HIV incidence for its highest prevalence region. By creating a sentinel incidence cohort from the infrastructure of an existing community-based testing program, we were able to characterize current transmission patterns, corroborate known risk factors for HIV acquisition, and provide insight into the efficacy of prevention interventions in a subnational epidemic hotspot. This study demonstrates an efficient and scalable framework for longitudinal HIV incidence surveillance that can be implemented in diverse sentinel sites and populations.

      14. Linezolid use for the treatment of multidrug-resistant tuberculosis, TB centers of excellence, United States, 2013-2018external icon
        McDowell A, Haas M, Seaworth B, Wilson JW, Patrawalla A, Haley C, Lauzardo M, de Bruyn M, Goswami ND.
        J Clin Tuberc Other Mycobact Dis. 2021 Feb;22:100201.
        BACKGROUND: In 2019, the World Health Organization released guidelines reflecting major changes in multidrug-resistant tuberculosis (MDR-TB) management-prioritizing fluoroquinolones, bedaquiline, and linezolid (LZD) while de-emphasizing previously favored injectable agents. In some cases, linezolid use is associated with gastrointestinal intolerance, mitochondrial toxicity, and significant drug interactions. CDC's Division of Tuberculosis Elimination supports a network of regional TB Centers of Excellence, which provide medical consultation to healthcare providers. Consultations are documented in a medical consultation database (MCD) enabling evaluation of management questions and recommendations. We describe the scope of clinical inquiries and responses specific to linezolid use for MDR-TB in the US. RESEARCH QUESTION: What are the major themes of provider and patient challenges regarding the use of linezolid for the treatment of MDR-TB in the US? METHODS: We queried MCD consults categorized as "MDR/XDR-TB" from 1/1/2013 to 12/31/2018. Only linezolid-specific consultations were included; incomplete and duplicate entries were excluded as were those citing linezolid historically or theoretically. Subgroup characteristics were assessed (e.g., Center, year, provider type). A descriptive coding scheme was developed through inductive thematic analysis. RESULTS: In 2013-2018 of the 1889 consults regarding MDR/XDR-TB, 934 MDR-TB consults referenced linezolid; 137 met inclusion criteria, representing between 4 and 10% of MDR-TB consults annually. Four main themes emerged: adverse effects (71.5%); concerns about linezolid use due to co-morbidities or concurrent medication use (15.3%); dosing adjustments (8.8%); and monitoring and maintenance logistics (4.4%). INTERPRETATIONS: Linezolid consults consistently exceeded 4% of all consults annually over the 6-year period, suggesting a need for access to expert opinion for providers using linezolid to manage MDR-TB. While only a snapshot of MDR-TB in the US, this evaluation summarizes major provider concerns regarding particular adverse effects, and highlights a need for evidence-based guidance regarding linezolid dosing and toxicity management.

      15. Wildland firefighter exposure to smoke and COVID-19: A new risk on the fire lineexternal icon
        Navarro KM, Clark KA, Hardt DJ, Reid CE, Lahm PW, Domitrovich JW, Butler CR, Balmes JR.
        Sci Total Environ. 2020 Dec 11;760:144296.
        Throughout the United States, wildland firefighters respond to wildfires, performing arduous work in remote locations. Wildfire incidents can be an ideal environment for the transmission of infectious diseases, particularly for wildland firefighters who congregate in work and living settings. In this review, we examine how exposure to wildfire smoke can contribute to an increased likelihood of SARS-CoV-2 infection and severity of coronavirus disease (COVID-19). Human exposure to particulate matter (PM), a component of wildfire smoke, has been associated with oxidative stress and inflammatory responses; increasing the likelihood for adverse respiratory symptomology and pathology. In multiple epidemiological studies, wildfire smoke exposure has been associated with acute lower respiratory infections, such as bronchitis and pneumonia. Co-occurrence of SARS-CoV-2 infection and wildfire smoke inhalation may present an increased risk for COVID-19 illness in wildland firefighters due to PM based transport of SARS CoV-2 virus and up-regulation of angiotensin-converting enzyme II (ACE-2) (i.e. ACE-2 functions as a trans-membrane receptor, allowing the SARS-CoV-2 virus to gain entry into the epithelial cell). Wildfire smoke exposure may also increase risk for more severe COVID-19 illness such as cytokine release syndrome, hypotension, and acute respiratory distress syndrome (ARDS). Current infection control measures, including social distancing, wearing cloth masks, frequent cleaning and disinfecting of surfaces, frequent hand washing, and daily screening for COVID-19 symptoms are very important measures to reduce infections and severe health outcomes. Exposure to wildfire smoke may introduce additive or even multiplicative risk for SARS-CoV-2 infection and severity of disease in wildland firefighters. Thus, additional mitigative measures may be needed to prevent the co-occurrence of wildfire smoke exposure and SARS-CoV-2 infection.

      16. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020external icon
        Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1653-1656.
        On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts), a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). This vaccine is the second COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). Vaccination with the Moderna COVID-19 vaccine consists of 2 doses (100 μg, 0.5 mL each) administered intramuscularly, 1 month (4 weeks) apart. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Moderna COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,(†) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.(§) Use of all COVID-19 vaccines authorized under an EUA, including the Moderna COVID-19 vaccine, should be implemented in conjunction with ACIP's interim recommendations for allocating initial supplies of COVID-19 vaccines (3). The ACIP recommendation for the use of the Moderna COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

      17. Approaches to transitioning women into and out of prevention of mother-to-child transmission of HIV services for continued ART: a systematic reviewexternal icon
        Phillips TK, Teasdale CA, Geller A, Ng'eno B, Mogoba P, Modi S, Abrams EJ.
        J Int AIDS Soc. 2021 Jan;24(1):e25633.
        INTRODUCTION: Women living with HIV are required to transition into the prevention of mother-to-child transmission of HIV (PMTCT) services when they become pregnant and back to ART services after delivery. Transition can be a vulnerable time when many women are lost from HIV care yet there is little guidance on the optimal transition approaches to ensure continuity of care. We reviewed the available evidence on existing approaches to transitioning women into and out of PMTCT, outcomes following transition and factors influencing successful transition. METHODS: We searched PubMed and SCOPUS, as well as abstracts from international HIV-focused meetings, from January 2006 to July 2020. Studies were included that examined three points of transition: pregnant women already on ART into PMTCT (transition 1), pregnant women living with HIV not yet on ART into treatment services (transition 2) and postpartum women from PMTCT into general ART services after delivery (transition 3). Results were grouped and reported as descriptions of transition approach, comparison of outcomes following transition and factors influencing successful transition. RESULTS & DISCUSSION: Out of 1809 abstracts located, 36 studies (39 papers) were included in this review. Three studies included transition 1, 26 transition 2 and 17 transition 3. Approaches to transition were described in 26 studies and could be grouped into the provision of information at the point of transition (n = 8), strengthened communication or linkage of data between services (n = 4), use of transition navigators (n = 12), and combination approaches (n = 4). Few studies were designed to directly assess transition and only nine compared outcomes between transition approaches, with substantial heterogeneity in study design, setting and outcomes. Four themes were identified in 25 studies reporting on factors influencing successful transition: fear, knowledge and preparedness, clinic characteristics and the transition requirements and process. CONCLUSIONS: This review highlights that, despite the need for women to transition into and out of PMTCT services for continued ART in many settings, there is very limited evidence on optimal transition approaches. Ongoing operational research is required to identify sustainable and acceptable transition approaches and service delivery models that support continuity of HIV care during and after pregnancy.

      18. Performance of an antigen-based test for asymptomatic and symptomatic SARS-CoV-2 testing at two university campuses - Wisconsin, September-October 2020external icon
        Pray IW, Ford L, Cole D, Lee C, Bigouette JP, Abedi GR, Bushman D, Delahoy MJ, Currie D, Cherney B, Kirby M, Fajardo G, Caudill M, Langolf K, Kahrs J, Kelly P, Pitts C, Lim A, Aulik N, Tamin A, Harcourt JL, Queen K, Zhang J, Whitaker B, Browne H, Medrzycki M, Shewmaker P, Folster J, Bankamp B, Bowen MD, Thornburg NJ, Goffard K, Limbago B, Bateman A, Tate JE, Gieryn D, Kirking HL, Westergaard R, Killerby M.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1642-1647.
        Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).

      19. HIV patient navigation in the United States: A qualitative meta-synthesis of navigators' experiencesexternal icon
        Roland KB, Higa DH, Leighton CA, Mizuno Y, DeLuca JB, Koenig LJ.
        Health Promot Pract. 2020 Dec 27.
        Patient navigation is increasingly used to link and (re)engage persons with human immunodeficiency virus (HIV) to care. A more holistic understanding of patient navigation can be achieved by exploring the experiences of navigators, the persons who comprise half of the navigation process. We conducted a meta-synthesis of navigator experiences with HIV patient navigation using a phenomenological approach. We identified nine relevant studies. Data were analyzed using thematic synthesis. Analysis identified two overarching themes relating to (1) the breadth and depth of bidirectional relationships and functional activities that navigators undertake to connect their clients to care and (2) the inherently personal experience of delivering navigation services. From these thematic findings, we recommend that HIV patient navigators exhibit capacity and expertise in developing and maintaining interpersonal relationships with clients and health care systems/providers and develop self-care practices and emotional boundaries with clients. Our review seeks to advance public health research and practice by articulating key experiences and perspectives of HIV patient navigators, drawing findings and recommendations applicable to the development, implementation, and evaluation of HIV patient navigation.

      20. Implications of shortened quarantine among household contacts of index patients with confirmed SARS-CoV-2 infection - Tennessee and Wisconsin, April-September 2020external icon
        Rolfes MA, Grijalva CG, Zhu Y, McLean HQ, Hanson KE, Belongia EA, Halasa NB, Kim A, Meece J, Reed C, Talbot HK, Fry AM.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1633-1637.
        To prevent further transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), CDC currently recommends that persons who have been in close contact with someone with SARS-CoV-2 infection should quarantine (stay away from other persons) for 14 days after the last known contact.* However, quarantine might be difficult to maintain for a prolonged period. A shorter quarantine might improve compliance, and CDC recommends two options to reduce the duration of quarantine for close contacts without symptoms, based on local circumstances and availability of testing: 1) quarantine can end on day 10 without a test or 2) quarantine can end on day 7 after receiving a negative test result.(†) However, shorter quarantine might permit ongoing disease transmission from persons who develop symptoms or become infectious near the end of the recommended 14-day period. Interim data from an ongoing study of household transmission of SARS-CoV-2 were analyzed to understand the proportion of household contacts that had detectable virus after a shortened quarantine period. Persons who were household contacts of index patients completed a daily symptom diary and self-collected respiratory specimens for 14 days. Specimens were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). Among 185 household contacts enrolled, 109 (59%) had detectable SARS-CoV-2 at any time; 76% (83/109) of test results were positive within 7 days, and 86% (94 of 109) were positive within 10 days after the index patient's illness onset date. Among household contacts who received negative SARS-CoV-2 test results and were asymptomatic through day 7, there was an 81% chance (95% confidence interval [CI] = 67%-90%) of remaining asymptomatic and receiving negative RT-PCR test results through day 14; this increased to 93% (95% CI = 78%-98%) for household members who were asymptomatic with negative RT-PCR test results through day 10. Although SARS-CoV-2 quarantine periods shorter than 14 days might be easier to adhere to, there is a potential for onward transmission from household contacts released before day 14.

      21. HIV treatment cascade among people who inject drugs in Ukraineexternal icon
        Sazonova Y, Kulchynska R, Sereda Y, Azarskova M, Novak Y, Saliuk T, Kornilova M, Liulchuk M, Vitek C, Dumchev K.
        PLoS One. 2020 ;15(12):e0244572.
        The HIV treatment cascade is an effective tool to track progress and gaps in the HIV response among key populations. People who inject drugs (PWID) remain the most affected key population in Ukraine with HIV prevalence of 22% in 2015. We performed secondary analysis of the 2017 Integrated Bio-Behavioral Surveillance (IBBS) survey data to construct the HIV treatment cascade for PWID and identify correlates of each indicator achievement. The biggest gap in the cascade was found in the first "90", HIV status awareness: only 58% [95% CI: 56%-61%] of HIV-positive PWID reported being aware of their HIV-positive status. Almost 70% [67%-72%] of all HIV-infected PWID who were aware of their status reported that they currently received antiretroviral therapy (ART). Almost three quarters (74% [71%-77%]) of all HIV-infected PWID on ART were virally suppressed. Access to harm reduction services in the past 12 months and lifetime receipt of opioid agonist treatment (OAT) had the strongest association with HIV status awareness. Additionally, OAT patients who were aware of HIV-positive status had 1.7 [1.2-2.3] times the odds of receiving ART. Being on ART for the last 6 months or longer increased odds to be virally suppressed; in contrast, missed recent doses of ART significantly decreased the odds of suppression. The HIV treatment cascade analysis for PWID in Ukraine revealed substantial gaps at each step and identified factors contributing to achievement of the outcomes. More intensive harm reduction outreach along with targeted case finding could help to fill the HIV awareness gap among PWID in Ukraine. Scale up of OAT and community-level linkage to care and ART adherence interventions are viable strategies to improve ART coverage and viral suppression among PWID.

      22. Considerations for pooled testing of employees for SARS-CoV-2external icon
        Schulte PA, Weissman DN, Luckhaupt SE, de Perio MA, Beezhold D, Piacentino JD, Radonovich LJ, Hearl FJ, Howard J.
        J Occup Environ Med. 2021 Jan 1;63(1):1-9.
        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 medrixiv.org prior to August 2020. RESULTS/CONCLUSIONS: 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.

      23. Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to actionexternal icon
        Taylor MM, Kobeissi L, Kim C, Amin A, Thorson AE, Bellare NB, Brizuela V, Bonet M, Kara E, Thwin SS, Kuganantham H, Ali M, Oladapo OT, Broutet N.
        Lancet Glob Health. 2020 Dec 16.
        Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

      24. BACKGROUND: Health inequities among people with HIV may be compounded by disparities in the prevalence of comorbidities associated with increased risk of severe illness from COVID-19. SETTING: Complex sample survey designed to produce nationally representative estimates of behavioral and clinical characteristics of adults with diagnosed HIV in the United States. METHODS: We estimated prevalence of having ≥1 diagnosed comorbidity associated with severe illness from COVID-19 and prevalence differences (PD) by race/ethnicity, income level, and type of health insurance. We considered PDs ≥5 percentage points to be meaningful from a public health perspective. RESULTS: An estimated 37.9% (95% CI, 36.6 to 39.2) of adults receiving HIV care had ≥1 diagnosed comorbidity associated with severe illness from COVID-19. Compared with non-Hispanic Whites, non-Hispanic Blacks or African Americans were more likely (adjusted prevalence difference [APD], 7.8 percentage points [95% CI, 5.7 to 10.0]) and non-Hispanic Asians were less likely (APD, -13.7 percentage points [95% CI, -22.3 to -5.0]) to have ≥1 diagnosed comorbidity after adjusting for age differences. There were no meaningful differences between non-Hispanic Whites and adults in other racial/ethnic groups. Those with low income, were more likely to have ≥1 diagnosed comorbidity (PD, 7.3 percentage points [95% CI, 5.1 to 9.4]). CONCLUSIONS: Among adults receiving HIV care, non-Hispanic Blacks and those with low income were more likely to have ≥1 diagnosed comorbidity associated with severe COVID-19. Building health equity among people with HIV during the COVID-19 pandemic may require reducing the impact of comorbidities in heavily affected communities.

      25. Community-setting pneumonia-associated hospitalizations by level of urbanization-New York City versus other areas of New York State, 2010-2014external icon
        Wu M, Whittemore K, Huang CC, Corrado RE, Culp GM, Lim S, Schluger NW, Daskalakis DC, Lucero DE, Vora NM.
        PLoS One. 2020 ;15(12):e0244367.
        BACKGROUND: New York City (NYC) reported a higher pneumonia and influenza death rate than the rest of New York State during 2010-2014. Most NYC pneumonia and influenza deaths are attributed to pneumonia caused by infection acquired in the community, and these deaths typically occur in hospitals. METHODS: We identified hospitalizations of New York State residents aged ≥20 years discharged from New York State hospitals during 2010-2014 with a principal diagnosis of community-setting pneumonia or a secondary diagnosis of community-setting pneumonia if the principal diagnosis was respiratory failure or sepsis. We examined mean annual age-adjusted community-setting pneumonia-associated hospitalization (CSPAH) rates and proportion of CSPAH with in-hospital death, overall and by sociodemographic group, and produced a multivariable negative binomial model to assess hospitalization rate ratios. RESULTS: Compared with non-NYC urban, suburban, and rural areas of New York State, NYC had the highest mean annual age-adjusted CSPAH rate at 475.3 per 100,000 population and the highest percentage of CSPAH with in-hospital death at 13.7%. NYC also had the highest proportion of CSPAH patients residing in higher-poverty-level areas. Adjusting for age, sex, and area-based poverty, NYC residents experienced 1.3 (95% confidence interval [CI], 1.2-1.4), non-NYC urban residents 1.4 (95% CI, 1.3-1.6), and suburban residents 1.2 (95% CI, 1.1-1.3) times the rate of CSPAH than rural residents. CONCLUSIONS: In New York State, NYC as well as other urban areas and suburban areas had higher rates of CSPAH than rural areas. Further research is needed into drivers of CSPAH deaths, which may be associated with poverty.

      26. Impact of COVID-19 pandemic on global poliovirus surveillanceexternal icon
        Zomahoun DJ, Burman AL, Snider CJ, Chauvin C, Gardner T, Lickness JS, Ahmed JA, Diop O, Gerber S, Anand A.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1648-1652.
        On January 30, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern (1). On March 24, 2020, the Global Polio Eradication Initiative (GPEI) suspended all polio supplementary immunization activities and recommended the continuation of polio surveillance (2). In April 2020, GPEI shared revised polio surveillance guidelines in the context of the COVID-19 pandemic, which focused on reducing the risk for transmission of SARS-CoV-2, the virus that causes COVID-19, to health care workers and communities by modifying activities that required person-to-person contact, improving hand hygiene and personal protective equipment use practices, and overcoming challenges related to movement restrictions, while continuing essential polio surveillance functions (3). GPEI assessed the impact of the COVID-19 pandemic on polio surveillance by comparing data from January to September 2019 to the same period in 2020. Globally, the number of acute flaccid paralysis (AFP) cases reported declined 33% and the mean number of days between the second stool collected and receipt by the laboratory increased by 70%. Continued analysis of AFP case reporting and stool collection is critical to ensure timely detection and response to interruptions of polio surveillance.

    • Disaster Control and Emergency Services
      1. Patterns of posttraumatic stress symptoms among international humanitarian aid workersexternal icon
        Greene-Cramer BJ, Hulland EN, Russell SP, Eriksson CB, Lopes-Cardozo B.
        Traumatology. 2020 Dec.
        Most studies of mental health in humanitarian aid workers have found low levels of posttraumatic stress disorder, making it hard to disaggregate and look at differences between subgroups. This study sought to identify the risk and protective factors associated with resistant, resilient, and nonresilient trajectories of stress response over time that could be used to inform more targeted training and organizational support programs for aid workers. Aid workers from 19 qualifying humanitarian organizations who aged >=18 years and were to deploy for 3 to 12 months completed questionnaires at 3 time points (pre, post, and follow-up). We identified 3 unique groups (nonresilient, resistant, and resilient) using latent class growth analysis and identified predictors of subgroup classification using multivariate logistic regression. Single individuals were less likely to be in the resilient group than in the resistant group compared to coupled individuals. Individuals with one prior deployment were three times more likely to be nonresilient than resistant compared to individuals with no previous deployments. There was no significant difference in resistant, resilient, and nonresilient classification for individuals with >2 deployments. Findings suggest a need for supplemental training and psychosocial support post the first deployment as well as resources focused on potential this should be cumulative rather than accumulative effects of stress and trauma exposure for more seasoned deployers.

      2. Going viral: The 3 Rs of social media messaging during public health emergenciesexternal icon
        Murthy BP, LeBlanc TT, Vagi SJ, Avchen RN.
        Health Secur. 2020 Dec 28.

      3. Cortisol awakening response over the course of humanitarian aid deployment: a prospective cohort studyexternal icon
        Qing Y, van Zuiden M, Eriksson C, Lopes Cardozo B, Simon W, Ager A, Snider L, Sabin ML, Scholte W, Kaiser R, Rijnen B, Olff M.
        Eur J Psychotraumatol. 2020 ;11(1).
        Background: Internationally deployed humanitarian aid (HA) workers are routinely confronted with potentially traumatic stressors. However, it remains unknown whether HA deployment and related traumatic stress are associated with long-term changes in hypothalamic-pituitary-adrenal (HPA) axis function. Therefore, we investigated whether cortisol awakening response (CAR) decreased upon deployment and whether this was moderated by previous and recent trauma exposure and parallel changes in symptom severity and perceived social support. Methods: In this prospective study, n = 86 HA workers (68% females) completed questionnaires regarding trauma exposure, posttraumatic stress disorder (PTSD), anxiety and depressive symptoms and perceived social support, as well as salivary cortisol assessments at awakening and 30 minutes post-awakening at before, early and 3–6 months post-deployment. Results: Linear mixed models showed significantly decreased CAR (b(SE) = −.036(.011), p =.002) and awakening cortisol over time (b(SE) = −.007(.003), p =.014). The extent of awakening cortisol change was significantly moderated by interactions between previous and recent trauma exposure. Also, a steeper awakening cortisol decrease was significantly associated with higher mean anxiety and PTSD symptoms across assessments. No significant effects were found for social support. Conclusions: We observed attenuated CAR and awakening cortisol upon HA deployment, with a dose-response effect between trauma exposure before and during the recent deployment on awakening cortisol. Awakening cortisol change was associated with PTSD and anxiety symptom levels across assessments. Our findings support the need for organizational awareness that work-related exposures may have long-lasting biological effects. Further research assessing symptoms and biological measures in parallel is needed to translate current findings into guidelines on the individual level.

    • Disease Reservoirs and Vectors
      1. Relative contributions of various endogenous and exogenous factors to the mosquito microbiotaexternal icon
        Bogale HN, Cannon MV, Keita K, Camara D, Barry Y, Keita M, Coulibaly D, Kone AK, Doumbo OK, Thera MA, Plowe CV, Travassos M, Irish S, Serre D.
        Parasit Vectors. 2020 Dec 10;13(1):619.
        BACKGROUND: The commensal microbiota of mosquitoes impacts their development, immunity, and competency, and could provide a target for alternative entomological control approaches. However, despite the importance of the mosquito/microbiota interactions, little is known about the relative contribution of endogenous and exogenous factors in shaping the bacterial communities of mosquitoes. METHODS: We used a high-throughput sequencing-based assay to characterize the bacterial composition and diversity of 665 individual field-caught mosquitoes, as well as their species, genotype at an insecticide resistance locus, blood-meal composition, and the eukaryotic parasites and viruses they carry. We then used these data to rigorously estimate the individual effect of each parameter on the bacterial diversity as well as the relative contribution of each parameter to the microbial composition. RESULTS: Overall, multivariate analyses did not reveal any significant contribution of the mosquito species, insecticide resistance, or blood meal to the bacterial composition of the mosquitoes surveyed, and infection with parasites and viruses only contributed very marginally. The main driver of the bacterial diversity was the location at which each mosquito was collected, which explained roughly 20% of the variance observed. CONCLUSIONS: This analysis shows that when confounding factors are taken into account, the site at which the mosquitoes are collected is the main driver of the bacterial diversity of wild-caught mosquitoes, although further studies will be needed to determine which specific components of the local environment affect bacterial composition.

      2. Equine-like H3 avian influenza viruses in wild birds, Chileexternal icon
        Bravo-Vasquez N, Yao J, Jimenez-Bluhm P, Meliopoulos V, Freiden P, Sharp B, Estrada L, Davis A, Cherry S, Livingston B, Danner A, Schultz-Cherry S, Hamilton-West C.
        Emerg Infect Dis. 2020 Dec;26(12):2887-2898.
        Since their discovery in the United States in 1963, outbreaks of infection with equine influenza virus (H3N8) have been associated with serious respiratory disease in horses worldwide. Genomic analysis suggests that equine H3 viruses are of an avian lineage, likely originating in wild birds. Equine-like internal genes have been identified in avian influenza viruses isolated from wild birds in the Southern Cone of South America. However, an equine-like H3 hemagglutinin has not been identified. We isolated 6 distinct H3 viruses from wild birds in Chile that have hemagglutinin, nucleoprotein, nonstructural protein 1, and polymerase acidic genes with high nucleotide homology to the 1963 H3N8 equine influenza virus lineage. Despite the nucleotide similarity, viruses from Chile were antigenically more closely related to avian viruses and transmitted effectively in chickens, suggesting adaptation to the avian host. These studies provide the initial demonstration that equine-like H3 hemagglutinin continues to circulate in a wild bird reservoir.

      3. Protozoan parasites of the genus Trypanosoma infect a broad diversity of vertebrates and several species cause significant illness in humans. However, understanding of the phylogenetic diversity, host associations, and infection dynamics of Trypanosoma species in naturally infected animals is incomplete. This study investigated the presence of Trypanosoma spp. in wild rodents and lagomorphs in northern New Mexico, United States, as well as phylogenetic relationships among these parasites. A total of 458 samples from 13 rodent and one lagomorph species collected between November 2002 and July 2004 were tested by nested PCR targeting the 18S ribosomal RNA gene (18S rRNA). Trypanosoma DNA was detected in 25.1% of all samples, with the highest rates of 50% in Sylvilagus audubonii, 33.1% in Neotoma micropus, and 32% in Peromyscus leucopus. Phylogenetic analysis of Trypanosoma sequences revealed five haplotypes within the subgenus Herpetosoma (T. lewisi clade). Focused analysis on the large number of samples from N. micropus showed that Trypanosoma infection varied by age class and that the same Trypanosoma haplotype could be detected in recaptured individuals over multiple months. This is the first report of Trypanosoma infections in Dipodomys ordii and Otospermophilus variegatus, and the first detection of a haplotype phylogenetically related to T. nabiasi in North America in S. audubonii. This study lends important new insight into the diversity of Trypanosoma species, their geographic ranges and host associations, and the dynamics of infection in natural populations.

      4. Effects of anthropogenic habitat disturbance and Giardia duodenalis infection on a sentinel species' gut bacteriaexternal icon
        Kuthyar S, Kowalewski MM, Roellig DM, Mallott EK, Zeng Y, Gillespie TR, Amato KR.
        Ecol Evol. 2020 .
        Habitat disturbance, a common consequence of anthropogenic land use practices, creates human–animal interfaces where humans, wildlife, and domestic species can interact. These altered habitats can influence host–microbe dynamics, leading to potential downstream effects on host physiology and health. Here, we explored the effect of ecological overlap with humans and domestic species and infection with the protozoan parasite Giardia duodenalis on the bacteria of black and gold howler monkeys (Alouatta caraya), a key sentinel species, in northeastern Argentina. Fecal samples were screened for Giardia duodenalis infection using a nested PCR reaction, and the gut bacterial community was characterized using 16S rRNA gene amplicon sequencing. Habitat type was correlated with variation in A. caraya gut bacterial community composition but did not affect gut bacterial diversity. Giardia presence did not have a universal effect on A. caraya gut bacteria across habitats, perhaps due to the high infection prevalence across all habitats. However, some bacterial taxa were found to vary with Giardia infection. While A. caraya's behavioral plasticity and dietary flexibility allow them to exploit a range of habitat conditions, habitats are generally becoming more anthropogenically disturbed and, thus, less hospitable. Alterations in gut bacterial community dynamics are one possible indicator of negative health outcomes for A. caraya in these environments, since changes in host–microbe relationships due to stressors from habitat disturbance may lead to negative repercussions for host health. These dynamics are likely relevant for understanding organism responses to environmental change in other mammals.

      5. Prevalence of single and coinfections of human pathogens in Ixodes ticks from five geographical regions in the United States, 2013-2019external icon
        Lehane A, Maes SE, Graham CB, Jones E, Delorey M, Eisen RJ.
        Ticks Tick Borne Dis. 2020 Dec 17;12(2):101637.
        As the geographic distributions of medically important ticks and tick-borne pathogens continue to expand in the United States, the burden of tick-borne diseases continues to increase along with a growing risk of coinfections. Coinfection with multiple tick-borne pathogens may amplify severity of disease and complicate diagnosis and treatment. By testing 13,400 Ixodes ticks from 17 US states spanning five geographical regions for etiological agents of Lyme disease (Borrelia burgdorferi sensu stricto [s.s.] and Borrelia mayonii), Borrelia miyamotoi disease (Borrelia miyamotoi), anaplasmosis (Anaplasma phagocytophilum), and babesiosis (Babesia microti) we show that B. burgdorferi s.s. was the most prevalent and widespread pathogen. Borrelia miyamotoi, A. phagocytophilum, and B. microti were widespread but less prevalent than B. burgdorferi s.s. Coinfections with B. burgdorferi s.s. and A. phagocytophilum or B. microti were most common in the Northeast and occurred at rates higher than expected based on rates of single infections in that region.

      6. Human-pathogenic Kasokero virus in field-collected ticksexternal icon
        Schuh AJ, Amman BR, Patel K, Sealy TK, Swanepoel R, Towner JS.
        Emerg Infect Dis. 2020 Dec;26(12):2944-2950.
        Kasokero virus (KASV; genus Orthonairovirus) was first isolated in 1977 at Uganda Virus Research Institute from serum collected from Rousettus aegyptiacus bats captured at Kasokero Cave, Uganda. During virus characterization studies at the institute, 4 laboratory-associated infections resulted in mild to severe disease. Although orthonairoviruses are typically associated with vertebrate and tick hosts, a tick vector of KASV never has been reported. We tested 786 Ornithodoros (Reticulinasus) faini tick pools (3,930 ticks) for KASV. The ticks were collected from a large R. aegyptiacus bat roosting site in western Uganda. We detected KASV RNA in 43 tick pools and recovered 2 infectious isolates, 1 of which was derived from host blood-depleted ticks. Our findings suggest that KASV is maintained in an enzootic transmission cycle involving O. (R.) faini ticks and R. aegyptiacus bats and has the potential for incidental virus spillover to humans.

    • Environmental Health
      1. Mold cleanup practices vary by sociodemographic and allergy factorsexternal icon
        Damon SA, Chew GL.
        J Environ Health. 2020 ;83(5):18-21.
        We examined mold cleanup practices in the U.S. in a general population that was not selected on a history of natural disaster. We used a population-based survey (n = 3,624) to assess associations between (1) sociodemographic, housing, and respiratory health variables and (2) mold cleanup, personal protective equipment (PPE) use, and cleaning agent use. Bleach was the most commonly used cleaning agent, with approximately 90% of residents reporting using bleach alone or with other agents. More respondents used gloves (76%) than any other PPE. The use of PPE varied: 42% of bleach users wore a facemask/respirator compared with only 19% of soap and water users. Hispanic populations frequently reported mold cleanup. Bleach use was less likely in the Western region of the country and among Asians. Although green products were rarely used, Asians were more likely to use them. Bleach was the most commonly used cleaning agent for mold and PPE use was common when using bleach, which supports the need for current Centers for Disease Control and Prevention safe-use recommendations.

      2. Incidence of uterine leiomyoma in relation to urinary concentrations of phthalate and phthalate alternative biomarkers: A prospective ultrasound studyexternal icon
        Fruh V, Claus Henn B, Weuve J, Wesselink AK, Orta OR, Heeren T, Hauser R, Calafat AM, Williams PL, Baird DD, Wise LA.
        Environ Int. 2020 Dec 21;147:106218.
        BACKGROUND: Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. OBJECTIVES: We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. METHODS: We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23-35 years who were recruited during 2010-2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. RESULTS: Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m(2). HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). DISCUSSION: In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly.

      3. Human health and ocean pollutionexternal icon
        Landrigan PJ, Stegeman JJ, Fleming LE, Allemand D, Anderson DM, Backer LC, Brucker-Davis F, Chevalier N, Corra L, Czerucka D, Bottein MD, Demeneix B, Depledge M, Deheyn DD, Dorman CJ, Fénichel P, Fisher S, Gaill F, Galgani F, Gaze WH, Giuliano L, Grandjean P, Hahn ME, Hamdoun A, Hess P, Judson B, Laborde A, McGlade J, Mu J, Mustapha A, Neira M, Noble RT, Pedrotti ML, Reddy C, Rocklöv J, Scharler UM, Shanmugam H, Taghian G, van de Water J, Vezzulli L, Weihe P, Zeka A, Raps H, Rampal P.
        Ann Glob Health. 2020 Dec 3;86(1):151.
        BACKGROUND: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. GOALS: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. METHODS: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. ENVIRONMENTAL FINDINGS: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. ECOSYSTEM FINDINGS: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. HUMAN HEALTH FINDINGS: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children's risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals - phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste - can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale. CONCLUSIONS: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. RECOMMENDATIONS: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.

      4. Young children's exposure to phenols in the home: Associations between house dust, hand wipes, silicone wristbands, and urinary biomarkersexternal icon
        Levasseur JL, Hammel SC, Hoffman K, Phillips AL, Zhang S, Ye X, Calafat AM, Webster TF, Stapleton HM.
        Environ Int. 2020 Dec 17;147:106317.
        BACKGROUND: Environmental phenols, such as parabens, bisphenol A, and triclosan, are ubiquitous in indoor environments because of their use in packaging, plastics, personal care products, and as anti-microbials. The primary pathways of exposure, as well as habits and behaviors that may lead to greater exposure, are still unclear. OBJECTIVES: Herein, we investigate the relationships between phenols found in residential environments by comparing levels in paired samples of house dust and hand wipes with children's urine. In addition, phenols were analyzed in a novel exposure tool, the silicone wristbands, to investigate which external matrix best correlates with individual exposure based on urinary phenol biomarkers. METHODS: Children aged 3-6 years in central North Carolina, United States, provided paired hand wipe (n = 202), wristband (n = 76), and spot urine samples (n = 180), while legal guardians completed questionnaires on habits and behaviors. House dust samples (n = 186) were collected from the main living area during home visits completed between 2014 and 2016. RESULTS: Environmental phenols were detected frequently in all matrices investigated. Ethyl, methyl, and propylparaben levels observed in hand wipes, dust, and on wristbands were significantly correlated to their associated urinary biomarkers. In addition, intra-paraben correlations were noted, with biomarkers of ethyl, methyl, and propylparabens generally positively and significantly correlated, which suggests co-application of parabens in products. Triclosan levels in dust were positive and significantly correlated with levels in hand wipes and wristbands and with urinary concentrations, suggesting non-personal care product sources may be important in children's overall triclosan exposure. Generally, chemicals on wristbands were more highly correlated with urinary biomarkers than with chemicals in hand wipes or house dust. In addition, more frequent lotion use was positively associated with urinary concentrations of paraben biomarkers. CONCLUSIONS: Our results suggest that the home environment is an important source of exposure which has been under-investigated for some environmental phenols (e.g., triclosan in house dust). Associations between wristbands and biomarkers of exposure, which were stronger than for hand wipes and house dust, suggest that silicone wristbands may provide a suitable exposure assessment tool for some phenols.

      5. Prenatal exposure to per- and polyfluoroalkyl substances, umbilical cord blood DNA methylation, and cardio-metabolic indicators in newborns: The Healthy Start Studyexternal icon
        Starling AP, Liu C, Shen G, Yang IV, Kechris K, Borengasser SJ, Boyle KE, Zhang W, Smith HA, Calafat AM, Hamman RF, Adgate JL, Dabelea D.
        Environ Health Perspect. 2020 Dec;128(12):127014.
        BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother-infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR) < 0.05 and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted p < 0.05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (ρ = 0.28 - 0.76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR <  0.05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR <  0.1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888.

      6. Identifying windows of susceptibility to endocrine disrupting chemicals in relation to gestational weight gain among pregnant women attending a fertility clinicexternal icon
        Tyagi P, James-Todd T, Mínguez-Alarcón L, Ford JB, Keller M, Petrozza J, Calafat AM, Hauser R, Williams PL, Bellavia A.
        Environ Res. 2020 Dec 25;194:110638.
        BACKGROUND: Exposure to endocrine disrupting chemicals (EDC), such as phthalates and phenols, during pregnancy may be associated with excessive gestational weight gain (GWG), an important predictor of future health of the mother and the offspring. There is however a paucity of literature examining this association, and no study has accounted for the complex nature of EDCs exposure as a time-varying mixture of chemicals. OBJECTIVE: We examined the association between trimester-specific EDCs mixture and GWG in pregnant women attending a fertility clinic, to identify windows of susceptibility to such exposures, and assess the individual contribution of each chemical over pregnancy. METHODS: We included 243 pregnant women from the Environment and Reproductive Health (EARTH) Study, who provided up to 3 urine samples (one per trimester), and with available data on GWG. Urinary concentrations of 7 phthalate metabolites, bisphenol A, and 2 parabens, corrected for specific gravity, were included in the analysis. The association between trimester-specific EDCs mixture and GWG was evaluated using multiple regression models - categorizing exposures into concentration quartiles- and with Bayesian Kernel Machine Regression (BKMR), while adjusting for potential confounders. Hierarchical BKMR (hBKMR) was used to account for the time-varying nature of chemical concentrations over pregnancy, identifying the most important trimester and most important EDC within each trimester. RESULTS: During 1st trimester, higher GWG was observed at higher sum of metabolites of di (2-ethylhexyl) phthalate (ΣDEHP) from both multiple regression (e.g. comparing the 4th quartile with the 1st: β = 2.36 kg, 95% CI: 0.47, 5.19) and BKMR. During 2nd and 3rd trimesters, positive associations with mono-n-butyl phthalate and propylparaben, and negative with ΣDEHP and methylparaben were observed. When evaluating exposures as a time-varying mixture with hBKMR, 1st trimester was the most important exposure window when evaluating prenatal urinary EDCs in relation to GWG. Within the 1st trimester, urinary ΣDEHP, mono-isobutyl phthalate and propylparaben had the highest contribution in the positive association between the mixture and GWG. CONCLUSION: We observed positive associations between urinary EDCs during pregnancy, especially DEHP metabolites, and GWG. Our results suggest the 1st trimester of pregnancy as the time window of highest susceptibility to the effects of EDCs on GWG, with potential indication for the design of public health interventions, informing prevention strategies for reducing sources of exposure at specific time points.

      7. Maternal exposure to disinfection by-products and risk of hypospadias in the National Birth Defects Prevention Study (2000-2005)external icon
        Zaganjor I, Luben TJ, Desrosiers TA, Keil AP, Engel LS, Michalski AM, Carmichael SL, Nembhard WN, Shaw GM, Reefhuis J, Yazdy MM, Langlois PH, Feldkamp ML, Romitti PA, Olshan AF, The National Birth Defects Prevention S.
        Int J Environ Res Public Health. 2020 Dec 21;17(24).
        The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias.

    • Food Safety
      1. Carriage and gene content variability of the pESI-like plasmid associated with Salmonella infantis recently established in United States poultry productionexternal icon
        McMillan EA, Wasilenko JL, Tagg KA, Chen JC, Simmons M, Gupta SK, Tillman GE, Folster J, Jackson CR, Frye JG.
        Genes (Basel). 2020 Dec 18;11(12).
        Salmonella Infantis carrying extended spectrum β-lactamase bla(CTX-M-65) on a pESI-like megaplasmid has recently emerged in United States poultry. In order to determine the carriage rate and gene content variability of this plasmid in U.S. Salmonella Infantis, whole genome sequences of Salmonella isolates from humans and animals in the U.S. and internationally containing the pESI-like plasmid were analyzed. The U.S. Department of Agriculture Food Safety and Inspection Service (FSIS) identified 654 product sampling isolates containing pESI-like plasmids through hazard analysis and critical control point (HACCP) verification testing in 2017 and 2018. The Centers for Disease Control and Prevention identified 55 isolates with pESI-like plasmids in 2016-2018 through the National Antimicrobial Resistance Monitoring System. Approximately 49% of pESI-like plasmids from FSIS verification isolates and 71% from CDC NARMS contained bla(CTX-M-65). Pan-plasmid genome analysis was also performed. All plasmids contained traN and more than 95% contained 172 other conserved genes; 61% contained bla(CTX-M-65). In a hierarchical clustering analysis, some plasmids from U.S. animal sources clustered together and some plasmids from South America clustered together, possibly indicating multiple plasmid lineages. However, most plasmids contained similar genes regardless of origin. Carriage of the pESI-like plasmid in U.S. appears to be limited to Salmonella Infantis and carriage rates increased from 2017 to 2018.

    • Genetics and Genomics
      1. Metagenomic sequencing generates the whole genomes of porcine rotavirus A, C, and H from the United Statesexternal icon
        Hull JJ, Qi M, Montmayeur AM, Kumar D, Velasquez DE, Moon SS, Magaña LC, Betrapally N, Ng TF, Jiang B, Marthaler D.
        PLoS One. 2020 ;15(12):e0244498.
        The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains. Here, we used a metagenomic approach to sequence the 11 segments of RVA, RVC and RVH strains from piglets in the United States (US) and explore the evolutionary relations of these RV species. Metagenomics identified Astroviridae, Picornaviridae, Caliciviridae, Coronoviridae in samples MN9.65 and OK5.68 while Picobirnaviridae and Arteriviridae were only identified in sample OK5.68. Whole genome sequencing and phylogenetic analyses identified multiple genotypes with the RVA of strain MN9.65 and OK5.68, with the genome constellation of G5/G9-P[7]/P[13]-I5/I5- R1/R1-C1-M1-A8-N1-T7-E1/E1-H1 and G5/G9-P[6]/P[7]-I5-R1/R1-C1-M1-A8-N1-T1/T7-E1/E1-H1, respectively. The RVA strains had a complex evolutionary relationship with other mammalian strains. The RVC strain OK5.68 had a genome constellation of G9-P[6]-I1-R1-C5-M6-A5-N1-T1-E1-H1, and shared an evolutionary relationship with porcine strains from the US. The RVH strains MN9.65 and OK5.68 had the genome constellation of G5-P1-I1-R1-C1-M1-A5-N1-T1-E4-H1 and G5-P1-I1-R1-C1-M1-A5-N1-T1-E1-H1, indicating multiple RVH genome constellations are circulating in the US. These findings allow us to understand the complexity of the enteric virome, develop improved screening methods for RVC and RVH strains, facilitate expanded rotavirus surveillance in pigs, and increase our understanding of the origin and evolution of rotavirus species.

      2. Human Calicivirus Typing tool: A web-based tool for genotyping human norovirus and sapovirus sequencesexternal icon
        Tatusov RL, Chhabra P, Diez-Valcarce M, Barclay L, Cannon JL, Vinjé J.
        J Clin Virol. 2020 Dec 13;134:104718.
        BACKGROUND: The family Caliciviridae consists of a genetically diverse group of RNA viruses that infect a wide range of host species including noroviruses and sapoviruses which cause acute gastroenteritis in humans. Typing of these viruses relies on sequence-based approaches, and therefore there is a need for rapid and accurate web-based typing tools. OBJECTIVE: To develop and evaluate a web-based tool for rapid and accurate genotyping of noroviruses and sapoviruses. METHODS: The Human Calicivirus Typing (HuCaT) tool uses a set of curated reference sequences that are compared to query sequences using a k-mer (DNA substring) based algorithm. Outputs include alignments and phylogenetic trees of the 12 top matching reference sequences for each query. RESULTS: The HuCaT tool was validated with a set of 1310 norovirus and 239 sapovirus sequences covering all known human norovirus and sapovirus genotypes. HuCaT tool assigned genotypes to all queries with 100 % accuracy and was much faster (17 s) than BLAST (150 s) or phylogenetic analyses approaches. CONCLUSIONS: The web-based HuCaT tool supports rapid and accurate genotyping of human noroviruses and sapoviruses.

    • Global Health
      1. Precision global health for real-time actionexternal icon
        Flahault A, Utzinger J, Eckerle I, Sheath DJ, de Castañeda RR, Bolon I, Bempong NE, Andayi F.
        Lancet Digit Health. 2020 Feb;2(2):e58-e59.

    • Health Behavior and Risk
      1. Experienced homophobia and HIV infection risk among U.S. Gay, bisexual, and other men who have sex with men: A meta-analysisexternal icon
        Jeffries WL, Flores SA, Rooks-Peck CR, Gelaude DJ, Belcher L, Ricks PM, Millett GA.
        LGBT Health. 2020 Dec 28.
        Purpose: Experienced homophobia-negative treatment and perceptions that gay, bisexual, and other men who have sex with men (MSM) encounter because of their sexual orientations-may promote HIV infection among MSM. We conducted a rapid review and meta-analysis to examine experienced homophobia in relation to HIV infection risk. Methods: We searched Embase, MEDLINE, PsycINFO, and Sociological Abstracts to acquire data from U.S. studies published during 1992-2017. Studies examined experienced homophobia in relation to sexual risk behavior, poor HIV care continuum engagement, and diagnosed HIV infection. Random-effects models yielded summary odds ratios (ORs) and 95% confidence intervals (CIs). Results: Experienced homophobia was associated with having any sexual risk behavior (OR = 1.33, 95% CI = 1.25-1.42, I(2) = 89.2%), receptive condomless anal sex (CAS) (OR = 1.33, 95% CI = 1.14-1.56, I(2) = 63.6%), HIV-discordant CAS (OR = 1.66, 95% CI = 1.29-2.13, I(2) = 85.3%), an increased number of sex partners (OR = 1.16, 95% CI = 1.13-1.19, I(2) = 0.0%), diagnosed HIV infection (OR = 1.34, 95% CI = 1.10-1.64, I(2) = 86.3%), and poor HIV care continuum engagement among MSM living with HIV (OR = 1.45, 95% CI = 1.02-2.08, I(2) = 47.0%). Effect sizes for any sexual risk behavior were larger in samples with ≥50% Black or Latino (vs. White) MSM and for family-based mistreatment and perceived sexual minority stigma (vs. other homophobia types). Conclusion: Experienced homophobia is associated with HIV infection risk among MSM. Its association with sexual risk behavior may be stronger among Black and Latino (vs. White) MSM and for family-based mistreatment and perceived sexual minority stigma (vs. other homophobia types). Research is needed to better understand causality in these relationships and the role of interventions to reduce homophobia.

    • Health Economics
      1. Economics of interventions to increase active travel to school: A Community Guide Systematic Reviewexternal icon
        Jacob V, Chattopadhyay SK, Reynolds JA, Hopkins DP, Morgan JA, Brown DR, Kochtitzky CS, Cuellar AE, Kumanyika SK.
        Am J Prev Med. 2021 Jan;60(1):e27-e40.
        CONTEXT: The number of children who bicycle or walk to school has steadily declined in the U.S. and other high-income countries. In response, several countries responded in recent years by funding infrastructure and noninfrastructure programs that improve the safety, convenience, and attractiveness of active travel to school. The objective of this study is to synthesize the economic evidence for the cost and benefit of these programs. EVIDENCE ACQUISITION: Literature from the inception of databases to July 2018 were searched, yielding 9 economic evaluation studies. All analyses were done in September 2018-May 2019. EVIDENCE SYNTHESIS: All the studies reported cost, 6 studies reported cost benefit, and 2 studies reported cost effectiveness. The cost-effectiveness estimates were excluded on the basis of quality assessment. Cost of interventions ranged widely, with higher cost reported for the infrastructure-heavy projects from the U.S. ($91,000-$179,000 per school) and United Kingdom ($227,000-$665,000 per project). Estimates of benefits differed in the inclusion of improved safety for bicyclists and pedestrians, improved health from increased physical activity, and reduced environmental impacts due to less automobile use. The evaluations in the U.S. focused primarily on safety. The overall median benefit‒cost ratio was 4.4:1.0 (IQR=2.2:1-6.0:1, 6 studies). The 2-year benefit-cost ratios for U.S. projects in California and New York City were 1.46:1 and 1.79:1, respectively. CONCLUSIONS: The evidence indicates that interventions that improve infrastructure and enhance the safety and ease of active travel to schools generate societal economic benefits that exceed the societal cost.


      2. Cost effectiveness analysis of implementing tuberculosis screening among applicants for non-immigrant U.S. work visasexternal icon
        Sayed BA, Posey DL, Maskery B, Wingate LT, Cetron MS.
        Pneumonia (Nathan). 2020 Dec 25;12(1):15.
        BACKGROUND: While persons who receive immigrant and refugee visas are screened for active tuberculosis before admission into the United States, nonimmigrant visa applicants (NIVs) are not routinely screened and may enter the United States with infectious tuberculosis. OBJECTIVES: We evaluated the costs and benefits of expanding pre-departure tuberculosis screening requirements to a subset of NIVs who arrive from a moderate (Mexico) or high (India) incidence tuberculosis country with temporary work visas. METHODS: We developed a decision tree model to evaluate the program costs and estimate the numbers of active tuberculosis cases that may be diagnosed in the United States in two scenarios: 1) "Screening": screening and treatment for tuberculosis among NIVs in their home country with recommended U.S. follow-up for NIVs at elevated risk of active tuberculosis; and, 2) "No Screening" in their home country so that cases would be diagnosed passively and treatment occurs after entry into the United States. Costs were assessed from multiple perspectives, including multinational and U.S.-only perspectives. RESULTS: Under "Screening" versus "No Screening", an estimated 179 active tuberculosis cases and 119 hospitalizations would be averted in the United States annually via predeparture treatment. From the U.S.-only perspective, this program would result in annual net cost savings of about $3.75 million. However, rom the multinational perspective, the screening program would cost $151,388 per U.S. case averted for Indian NIVs and $221,088 per U.S. case averted for Mexican NIVs. CONCLUSION: From the U.S.-only perspective, the screening program would result in substantial cost savings in the form of reduced treatment and hospitalization costs. NIVs would incur increased pre-departure screening and treatment costs.

    • Healthcare Associated Infections
      1. Scientific evidence for the control of antimicrobial resistanceexternal icon
        Alpuche Aranda CM, Arias CA, Espinal Tejada C, Forde C, Park B, Rossi F, Thormann M.
        Rev Panam Salud Publica. 2020 ;44:e128.

      2. Trends in U.S. outpatient antibiotic prescriptions during the COVID-19 pandemicexternal icon
        King LM, Lovegrove MC, Shehab N, Tsay S, Budnitz DS, Geller AI, Lind JN, Roberts R, Hicks LA, Kabbani S.
        Clin Infect Dis. 2020 Dec 29.
        BACKGROUND: The objective of our study was to describe trends in U.S. outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies in January 2017-May 2020. We averaged estimates from 2017-2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017- 2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected due to seasonal trends alone, possibly related to the COVID-19 pandemic and associated mitigation measures.

      3. BACKGROUND: Inappropriate antibiotic use is common. Understanding how patients view antibiotic risks and/or benefits could inform development of patient education materials and clinician communication strategies. We explored current knowledge, attitudes, and behaviors related to antibiotics among populations with high antibiotic use. METHODS: We conducted 12 focus groups with adult patients and parents across the United States by telephone in March 2017. Purposive sampling was used to identify participants with high antibiotic use. We transcribed the discussions verbatim and performed thematic analysis. RESULTS: We identified 4 major themes. First, participants expressed uncertainty regarding which clinical syndromes required antibiotics, and emotion often influenced their desire for antibiotics. Second, they had a limited understanding of antibiotic risks. Antibiotic resistance was viewed as the primary risk but was seen as a "distant, future" issue, whereas immediate adverse events, such as side effects, were minimized; however, patients expressed concern when told about the risk of serious adverse events. Third, they prioritized antibiotic benefits over risks in their decision-making, both due to an inaccurate estimation of antibiotic risks and/or benefits and a tendency to prioritize instant gratification. Fourth, most participants were willing to defer to their clinicians' decisions about antibiotics, especially if their clinician provided symptomatic treatment and anticipatory guidance. CONCLUSIONS: Patients have a limited understanding of antibiotic risks, potentially explaining why they are willing to try antibiotics even if it is unclear antibiotics will help. Educating patients on the potential antibiotic risks versus benefits, rather than just antibiotic resistance, may have a bigger impact on their decision-making.

    • Immunity and Immunization

      1. Vaccine effectiveness against influenza-associated hospitalizations among adults, 2018-2019, US Hospitalized Adult Influenza Vaccine Effectiveness Networkexternal icon
        Ferdinands JM, Gaglani M, Ghamande S, Martin ET, Middleton D, Monto AS, Silveira F, Talbot HK, Zimmerman R, Smith ER, Patel M.
        J Infect Dis. 2020 Dec 18.
        We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was -2% (95%CI -65, 37) and differed significantly by age, with VE of -130% (95% CI -374, -27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.

      2. Strengthening vaccine confidence and acceptance in the pediatric provider officeexternal icon
        Mbaeyi S, Fisher A, Cohn A.
        Pediatr Ann. 2020 Dec 1;49(12):e523-e531.
        Although vaccine acceptance and uptake are overall high among children in the United States, vaccine delays or refusals are a growing concern. Vaccine hesitancy is a challenge for the pediatric provider, given the diverse factors associated with hesitancy and the limited evidence on effective strategies for addressing vaccine hesitancy in the provider office. In this article, we review available evidence and approaches for vaccine communication, including the importance of using a whole-team approach, building trust, starting the conversation early, using a presumptive approach for vaccine recommendations, motivational interviewing with parents who have concerns for vaccines, and additional techniques for responding to parent questions. We also review organizational strategies to help create a culture of immunization in the practice, including evidence-based approaches for increasing vaccine uptake and efficiency. Although these communication approaches and organizational strategies are intended to reassure parents who are vaccine hesitant that all routine, universally recommended vaccines are safe and effective, they likely will take on increased significance as the development, implementation, and evaluation of coronavirus disease 2019 vaccines continue to unfold. [Pediatr Ann. 2020;49(12):e523-e531.].

      3. Vaccine effectiveness against prevalent anal and oral human papillomavirus infection among men who have sex with men - United States, 2016-2018external icon
        Meites E, Winer RL, Newcomb ME, Gorbach PM, Querec TD, Rudd J, Collins T, Lin J, Moore J, Remble T, Swanson F, Franz J, Bolan RK, Golden MR, Mustanski B, Crosby RA, Unger ER, Markowitz LE.
        J Infect Dis. 2020 Nov 13;222(12):2052-2060.
        BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended for young adult men who have sex with men (MSM) since 2011. METHODS: The Vaccine Impact in Men study surveyed MSM and transgender women aged 18-26 years in 3 US cities during 2016-2018. Self-collected anal swab and oral rinse specimens were assessed for 37 types of HPV. We compared HPV prevalence among vaccinated and unvaccinated participants and determined adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). RESULTS: Among 1767 participants, 704 (39.8%) self-reported receiving HPV vaccine. Median age at vaccination (18.7 years) was older than age at first sex (15.7 years). Quadrivalent vaccine-type HPV was detected in anal or oral specimens from 475 (26.9%) participants. Vaccine-type HPV prevalence was lower among vaccinated (22.9%) compared with unvaccinated (31.6%) participants; aPR for those who initiated vaccination at age ≤18 years was 0.41 (CI, 0.24-0.57) and at age >18 years was 0.82 (CI, 0.67-0.98). Vaccine effectiveness of at least 1 HPV vaccine dose at age ≤18 years or >18 years was 59% and 18%, respectively. CONCLUSIONS: Findings suggest real-world effectiveness of HPV vaccination among young adult MSM. This effect was stronger with younger age at vaccination.

      4. The impact of physical frailty on the response to inactivated influenza vaccine in older adultsexternal icon
        Moehling KK, Zhai B, Schwarzmann WE, Chandran UR, Ortiz M, Nowalk MP, Nace D, Lin CJ, Susick M, Levine MZ, Alcorn JF, Zimmerman RK.
        Aging (Albany NY). 2020 Dec 9;12.
        Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log(2) HAI titers, and fold-rise in log(2) HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.

      5. BACKGROUND: In November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax(®), ccIIV3), was approved in the United States for adults aged ≥18 years. A quadrivalent version (ccIIV4) was later approved in 2016 and replaced ccIIV3. The safety of ccIIV3 or ccIIV4 (ccIIV) was not assessed for pregnant women or their infants during pre-licensure studies. OBJECTIVE: To assess the safety of ccIIV administered during pregnancy in pregnant women and their infants whose reports were submitted to VAERS during 2013-2020. MATERIAL AND METHODS: We searched VAERS for United States reports of adverse events (AEs) in pregnant women who received ccIIV from 1 July 2013 through 31 May 2020. Clinicians reviewed reports and available medical records and assigned a primary clinical category for each report. Reports were coded as serious based on the Code of Federal Regulations definition. RESULTS: VAERS received 391 reports following ccIIV administered to pregnant women. Twenty-four (6.1%) were serious. Two neonatal deaths were reported. No maternal deaths occurred. Among reports with trimester information (n = 340), ccIIV was administered during the second trimester in 170 (50%). The most frequent pregnancy-specific AE was premature delivery in 85 (21.7%) reports, followed by dysmature placenta in 13 (3.3%) and pre-eclampsia/eclampsia in ten (2.3%). The most common non-pregnancy specific conditions were infectious conditions in 32 (8.2%). Among infant conditions, low birth weight was reported in 62 (15.9%) reports. Fifteen birth defects were reported; in 12 with gestational age information, administration of the vaccine occurred late in the second trimester or later. CONCLUSIONS: Review of maternal ccIIV reports in VAERS was not unexpectedly different from other maternal influenza vaccine safety VAERS reviews.

      6. Diarrheal deaths after the introduction of rotavirus vaccination in 4 countriesexternal icon
        Paternina-Caicedo A, Parashar U, Garcia-Calavaro C, de Oliveira LH, Alvis-Guzman N, De la Hoz-Restrepo F.
        Pediatrics. 2021 Jan;147(1).
        BACKGROUND: We aim in our analysis to estimate the reduction of diarrhea-related mortality rates after introduction of a rotavirus vaccine in subregions of 4 Latin American countries. METHODS: We selected diarrhea-related deaths from individual-level data from death certificates in Brazil, Colombia, Ecuador, and Mexico. Counts were aggregated by region, year and month, and age group for each country. We ran an interrupted time-series analysis using Poisson regression to obtain seasonal and trend-adjusted estimates of impact. Results are reported as percentages (1 - mortality rate ratio). RESULTS: We found a reduction in diarrhea-related mortality in children <5 years old of 18% (95% confidence interval [CI], 15 to 20) for Mexico, 39% (95% CI, 35 to 44) for Colombia, 19 (95% CI, 17 to 22) for Brazil, and -26% (95% CI, -40 to -14) for Ecuador. Using wavelet analyses, we found a reduction of 6- and 12-month seasonality in Brazil, Colombia, and Mexico. We also found that the increased reduction of diarrhea-related deaths was larger with greater prevaccine burden of diarrhea in infants. CONCLUSIONS: Our findings and available evidence support the recommendation from the World Health Organization for the monovalent and/or pentavalent rotavirus vaccine in countries worldwide. We found an increased benefit in those settings with a higher burden of infant diarrhea-related deaths.

      7. Effect of antigenic drift on influenza vaccine effectiveness in the United States - 2019-2020external icon
        Tenforde MW, Kondor RJ, Chung JR, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Belongia EA, McLean HQ, Gaglani M, Rao A, Kim SS, Stark TJ, Barnes JR, Wentworth D, Patel MM, Flannery B.
        Clin Infect Dis. 2020 Dec 25.
        BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95%CI: 37-52) against B/Victoria and 30% (95%CI: 21-39) against A(H1N1)pdm09 associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95%CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.

      8. Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020external icon
        Tenforde MW, Talbot HK, Trabue CH, Gaglani M, McNeal TM, Monto AS, Martin ET, Zimmerman RK, Silveira F, Middleton DB, Olson SM, Garten Kondor RJ, Barnes JR, Ferdinands JM, Patel MM.
        J Infect Dis. 2020 Dec 30.
        BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

    • Informatics
      1. BACKGROUND: In molecular epidemiology, comparison of intra-host viral variants among infected persons is frequently used for tracing transmissions in human population and detecting viral infection outbreaks. Application of Ultra-Deep Sequencing (UDS) immensely increases the sensitivity of transmission detection but brings considerable computational challenges when comparing all pairs of sequences. We developed a new population comparison method based on convex hulls in hamming space. We applied this method to a large set of UDS samples obtained from unrelated cases infected with hepatitis C virus (HCV) and compared its performance with three previously published methods. RESULTS: The convex hull in hamming space is a data structure that provides information on: (1) average hamming distance within the set, (2) average hamming distance between two sets; (3) closeness centrality of each sequence; and (4) lower and upper bound of all the pairwise distances among the members of two sets. This filtering strategy rapidly and correctly removes 96.2% of all pairwise HCV sample comparisons, outperforming all previous methods. The convex hull distance (CHD) algorithm showed variable performance depending on sequence heterogeneity of the studied populations in real and simulated datasets, suggesting the possibility of using clustering methods to improve the performance. To address this issue, we developed a new clustering algorithm, k-hulls, that reduces heterogeneity of the convex hull. This efficient algorithm is an extension of the k-means algorithm and can be used with any type of categorical data. It is 6.8-times more accurate than k-mode, a previously developed clustering algorithm for categorical data. CONCLUSIONS: CHD is a fast and efficient filtering strategy for massively reducing the computational burden of pairwise comparison among large samples of sequences, and thus, aiding the calculation of transmission links among infected individuals using threshold-based methods. In addition, the convex hull efficiently obtains important summary metrics for intra-host viral populations.

    • Injury and Violence
      1. Development of a machine learning model using multiple, heterogeneous data sources to estimate weekly US suicide fatalitiesexternal icon
        Choi D, Sumner SA, Holland KM, Draper J, Murphy S, Bowen DA, Zwald M, Wang J, Law R, Taylor J, Konjeti C, De Choudhury M.
        JAMA Netw Open. 2020 Dec 1;3(12):e2030932.
        IMPORTANCE: Suicide is a leading cause of death in the US. However, official national statistics on suicide rates are delayed by 1 to 2 years, hampering evidence-based public health planning and decision-making. OBJECTIVE: To estimate weekly suicide fatalities in the US in near real time. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional national study used a machine learning pipeline to combine signals from several streams of real-time information to estimate weekly suicide fatalities in the US in near real time. This 2-phase approach first fits optimal machine learning models to each individual data stream and subsequently combines predictions made from each data stream via an artificial neural network. National-level US administrative data on suicide deaths, health services, and economic, meteorological, and online data were variously obtained from 2014 to 2017. Data were analyzed from January 1, 2014, to December 31, 2017. EXPOSURES: Longitudinal data on suicide-related exposures were obtained from multiple, heterogeneous streams: emergency department visits for suicide ideation and attempts collected via the National Syndromic Surveillance Program (2015-2017); calls to the National Suicide Prevention Lifeline (2014-2017); calls to US poison control centers for intentional self-harm (2014-2017); consumer price index and seasonality-adjusted unemployment rate, hourly earnings, home price index, and 3-month and 10-year yield curves from the Federal Reserve Economic Data (2014-2017); weekly daylight hours (2014-2017); Google and YouTube search trends related to suicide (2014-2017); and public posts on suicide on Reddit (2 314 533 posts), Twitter (9 327 472 tweets; 2015-2017), and Tumblr (1 670 378 posts; 2014-2017). MAIN OUTCOMES AND MEASURES: Weekly estimates of suicide fatalities in the US were obtained through a machine learning pipeline that integrated the above data sources. Estimates were compared statistically with actual fatalities recorded by the National Vital Statistics System. RESULTS: Combining information from multiple data streams, the machine learning method yielded estimates of weekly suicide deaths with high correlation to actual counts and trends (Pearson correlation, 0.811; P < .001), while estimating annual suicide rates with low error (0.55%). CONCLUSIONS AND RELEVANCE: The proposed ensemble machine learning framework reduces the error for annual suicide rate estimation to less than one-tenth of that of current forecasting approaches that use only historical information on suicide deaths. These findings establish a novel approach for tracking suicide fatalities in near real time and provide the potential for an effective public health response such as supporting budgetary decisions or deploying interventions.

      2. Experiences and correlates of violence among American Indian and Alaska Native Youth: A brief reportexternal icon
        Edwards KM, Banyard VL, Charge LL, Kollar LM, Fortson B.
        J Interpers Violence. 2020 Dec 28.
        The purpose of this paper is to document the scope and correlates of past 6-month victimization among American Indian (AI) and Alaska Native (AN) youth. Types of victimization under investigation included sexual assault, dating violence, bullying, sharing of nude photos, sexual harassment, homophobic teasing, and racism. Participants were 400 AI and AN youth in grades 7-10 who completed a survey in school. Results documented concerning rates of all forms of victimization among AI and AN youth during the past 6 months. Although most forms of victimization were related, bullying (at school and electronically), racism, and sexual harassment occurred more often than sexual assault and dating violence. Older youth, girls, and sexual minorities were more likely to report some forms of violence than younger youth, boys, and heterosexual youth respectively. Compared to nonvictims, victim status was consistently related to depressive symptoms, suicidal ideation, and alcohol use and was less consistently correlated with feelings of school mattering. Evidence-based, culturally grounded prevention and response efforts are needed for AI and AN youth, as well as broader initiatives that seek to reduce health disparities among AI and AN youth.

      3. Effect of a community-based gender norms program on sexual violence perpetration by adolescent boys and young men: A cluster randomized clinical trialexternal icon
        Miller E, Jones KA, Culyba AJ, Paglisotti T, Dwarakanath N, Massof M, Feinstein Z, Ports KA, Espelage D, Pulerwitz J, Garg A, Kato-Wallace J, Abebe KZ.
        JAMA Netw Open. 2020 Dec 1;3(12):e2028499.
        IMPORTANCE: Engaging adolescent boys and young men in preventing violence against women is a potentially impactful public health strategy. OBJECTIVE: To evaluate the effectiveness of a community-based, gender-transformative program (ie, Manhood 2.0) on perpetration of gender-based violence by adolescent boys and young men. DESIGN, SETTING, AND PARTICIPANTS: In this unblinded cluster randomized clinical trial, neighborhoods were designated as the unit of clustering (1:1 allocation). Three-month (ie, time point 2 [T2]) and 9-month (ie, time point 3 [T3]) follow-ups were conducted. The trial took place in 20 Pittsburgh, Pennsylvania, neighborhoods and 1 centrally located site with concentrated disadvantage. Pittsburgh-based adolescent boys and young men (ages 13 to 19 years) were recruited between July 27, 2015, and June 5, 2017, through youth-serving organizations and community-based alternatives to residential placement for juvenile justice-involved youth. Intention-to-treat analysis was conducted from June 2018 to November 2019. INTERVENTIONS: Manhood 2.0, an international program adapted for adolescent boys and young men in US urban communities, encourages these individuals to challenge gender norms that foster violence against women and unhealthy sexual relationships. Individuals in the control population received job-readiness training. Each program was 18 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was change in participant-level perpetration of sexual violence (SV) or adolescent relationship abuse (ARA) at T3. RESULTS: Among 866 participants, 465 individuals (54%) enrolled in 11 intervention clusters and 401 individuals (46%) enrolled in 10 control clusters. In the intervention group, 325 participants (70%) were analyzed at T2 and 334 participants (72%) were analyzed at T3; in the control group, 262 participants (65%) were analyzed at T2 and 301 participants (75%) were analyzed at T3. Mean (SD) age was 15.5 (1.6) years; 609 participants (70%) self-identified as non-Hispanic Black, and 178 (20%) self-identified as Hispanic, multiracial, or other race/ethnicity other than White. Among individuals in the intervention group, 296 participants (64%) reported any SV or ARA perpetration at baseline, and 173 participants (52%) reported any SV or ARA perpetration at T3. Among individuals in the control group, 213 participants (53%) reported any SV or ARA perpetration at baseline, and 124 participants (41%) reported any SV or ARA perpetration at T3). The difference in reduction between groups was not significant. There was no evidence of an intervention effect for the primary outcome (adjusted odds ratio [OR], 1.32; 95% CI, 0.86-2.01; P = .20). CONCLUSIONS AND RELEVANCE: The findings from this evaluation of a community-based gender-transformative program for adolescent boys and young men did not show a significant intervention effect in reducing SV or ARA perpetration between Manhood 2.0 and a job-readiness control program. Combining gender-transformative approaches with job-readiness programs may be relevant for violence prevention in low-resource urban settings. Attention to improving implementation and strategies to sustain such community-based efforts are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02427061.

      4. Community-level risk & protective correlates of violent crimesexternal icon
        Reidy DE, Huntington C, Smith HW, Bogen KW, Estefan LF, Orchowski LO.
        Prev Med. 2020 Dec 17:106380.
        Despite declining rates over the past several decades, violence continues to be a pervasive public health problem. To date, we have very little knowledge about the factors at the outer layers of the social ecology that may serve to protect or exacerbate violence. The purpose of the present research is to identify community-level risk and protective correlates of multiple forms of violent crime. Official crime data were collected from 36 of the municipalities (92%) across the state of Rhode Island. Additionally, the research team identified 23 types of community establishments and identified the number of each for each of the 36 municipalities. Semi-partial correlations were computed between the 23 community variables and each of nine types of violent crimes. While there were a number of significant results, only a few meaningful patterns were found. The number of transit stations was associated with all forms of sexual violence, sex trafficking, and general physical assault. Gun dealers were associated with domestic assault, child abuse, kidnapping, and assault with a weapon, but inversely related to sex trafficking. Boys and Girls Clubs were negatively associated with the number of assaults, assaults with a weapon, sexual assaults, sexual assaults on a child, sex trafficking, and kidnappings. Contrary to prior findings, the number of alcohol outlets was generally unrelated to violent crime. These findings must be interpreted with great caution given nature of the research design. However, this study provides an initial step to advance the research on community-level risk and protective factors for violence.

      5. Understanding traumatic brain injury in females: A state-of-the-art summary and future directionsexternal icon
        Valera EM, Joseph AC, Snedaker K, Breiding MJ, Robertson CL, Colantonio A, Levin H, Pugh MJ, Yurgelun-Todd D, Mannix R, Bazarian JJ, Turtzo LC, Turkstra LS, Begg L, Cummings DM, Bellgowan PS.
        J Head Trauma Rehabil. 2021 Jan 1;36(1):E1-e17.
        In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI. The workshop, and the current literature, clearly highlighted that females have been underrepresented in TBI studies and clinical trials and have often been excluded (or ovariectomized) in preclinical studies. Such an absence in research on females has led to an incomplete, and perhaps inaccurate, understanding of TBI in females. The presentations and discussions centered on the existing knowledge regarding sex differences in TBI research and how these differences could be incorporated in preclinical and clinical efforts going forward. Now, a little over 2 years later, we summarize the issues and state of the science that emerged from the "Understanding TBI in Women" workshop while incorporating updates where they exist. Overall, despite some progress, there remains an abundance of research focused on males and relatively little explicitly on females.

    • Laboratory Sciences
      1. Assessing the in vitro impact of ceftazidime on aztreonam/avibactam susceptibility testing for highly resistant MBL-producing Enterobacteralesexternal icon
        Bhatnagar A, Ransom EM, Machado MJ, Boyd S, Reese N, Anderson K, Lonsway D, Elkins CA, Rasheed JK, Patel JB, Karlsson M, Brown AC, Lutgring JD.
        J Antimicrob Chemother. 2020 Dec 27.
        BACKGROUND: Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC. OBJECTIVES: To determine whether increasing ceftazidime concentrations affect the MICs of aztreonam/avibactam alone. METHODS: A custom 8 × 8 chequerboard broth microdilution (BMD) panel was made using a digital dispenser (Hewlett-Packard, Corvallis, OR, USA). The panel included orthogonal 2-fold dilution series of aztreonam and ceftazidime ranging from 0.5 to 64 mg/L. Avibactam concentration was kept constant at 4 mg/L throughout the chequerboard. Thirty-seven Enterobacterales isolates from the CDC & FDA Antibiotic Resistance Isolate Bank or CDC's internal collection with intermediate or resistant interpretations to aztreonam and ceftazidime/avibactam were included for testing. All isolates harboured at least one of the following MBL genes: blaIMP, blaNDM or blaVIM. RESULTS: Regardless of the concentration of ceftazidime, aztreonam/avibactam with ceftazidime MICs for all 37 isolates were within one 2-fold doubling dilution of the aztreonam/avibactam MIC. CONCLUSIONS: Ceftazidime, in the combination ceftazidime/avibactam/aztreonam, did not affect the in vitro activity of aztreonam/avibactam in this sample of isolates. These findings can help assure clinical and public health laboratories that testing of aztreonam/avibactam by BMD can act as a reliable surrogate test when the combination of ceftazidime/avibactam and aztreonam is being considered for treatment of highly antibiotic-resistant MBL-producing Enterobacterales.

      2. Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and β-CTX in bloodexternal icon
        Bhattoa HP, Cavalier E, Eastell R, Heijboer AC, Jørgensen NR, Makris K, Ulmer CZ, Kanis JA, Cooper C, Silverman SL, Vasikaran SD.
        Clin Chim Acta. 2020 Dec 28.
        Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX.

      3. Evaluation of two real-time, TaqMan reverse transcription-PCR assays for detection of rabies virus in circulating variants from Argentina: Influence of sequence variationexternal icon
        Caraballo DA, Lombardo MA, Becker P, Sabio MS, Lema C, Martínez LM, Beltrán FJ, Li Y, Cisterna DM.
        Viruses. 2020 Dec 25;13(1).
        In rabies diagnosis, it is essential to count on a rapid test to give a quick response. The combined sensitivity and robustness of the TaqMan RT-PCR assays (qRT-PCR) have made these methods a valuable alternative for rabies virus (RABV) detection. We conducted a study to compare the applicability of two widely used qRT-PCR assays targeting the nucleoprotein gene (LysGT1 assay) and leader sequences (LN34 qRT-PCR assay) of RABV genomes, in all variants circulating in Argentina. A total of 44 samples obtained from bats, dogs, cattle, and horses, that were previously tested for rabies by FAT and conventional RT-PCR, were used in the study. All variants were successfully detected by the pan-lyssavirus LN34 qRT-PCR assay. The LysGT1 assay failed to detect three bat-related variants. We further sequenced the region targeted by LysGT1 and demonstrated that the presence of three or more mismatches with respect to the primers and probe sequences precludes viral detection. We conclude that the LysGT1 assay is prone to yield variant-dependent false-negative test results, and in consequence, the LN34 assay would ensure more effective detection of RABV in Argentina.

      4. Detection of active BoNT/C and D by EndoPep-MS using MALDI biotyper instrument and comparison with the mouse test bioassayexternal icon
        Drigo I, Tonon E, Pascoletti S, Anniballi F, Kalb SR, Bano L.
        Toxins (Basel). 2020 Dec 24;13(1).
        Botulinum neurotoxins (BoNTs) are among the most poisonous known biological substances, and therefore the availability of reliable, easy-to use tools for BoNT detection are important goals for food safety and human and animal health. The reference method for toxin detection and identification is the mouse bioassay (MBA). An EndoPep-MS method for BoNT differentiation has been developed based on mass spectrometry. We have validated and implemented the EndoPep-MS method on a Bruker MALDI Biotyper for the detection of BoNT/C and D serotypes. The method was extensively validated using experimentally and naturally contaminated samples comparing the results with those obtained with the MBA. Overall, the limit of detection (LoD) for both C and D toxins were less than or equal to two mouse lethal dose 50 (mLD(50)) per 500 µL for all tested matrices with the exception of feces spiked with BoNT/C which showed signals not-related to specific peptide fragments. Diagnostic sensitivity, specificity and positive predictive value were 100% (95% CI: 87.66-100%), 96.08% (95% CI: 86.54-99.52%), and 93.33% (95% CI: 78.25-98.20%), respectively, and accuracy was 97.47% (95% CI: 91.15-99.69%). In conclusion, the tests carried out showed that the EndoPep-MS method, initially developed using more powerful mass spectrometers, can be applied to the Bruker MALDI Biotyper instrument with excellent results including for detection of the proteolytic activity of BoNT/C, BoNT/D, BoNT/CD, and BoNT/DC toxins.

      5. TMEM41B Is a pan-flavivirus host factorexternal icon
        Hoffmann HH, Schneider WM, Rozen-Gagnon K, Miles LA, Schuster F, Razooky B, Jacobson E, Wu X, Yi S, Rudin CM, MacDonald MR, McMullan LK, Poirier JT, Rice CM.
        Cell. 2020 Dec 9.
        Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection, we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results, we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms present at nearly 20% in East Asian populations reduce flavivirus infection. Based on our mechanistic studies, we propose that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication.

      6. DNA molecules containing repetitive motifs are prone to expand in their lengths. Once there appear a head to tail tandem of two identical DNA sequences in the system, they can propagate indefinitely by the mechanism involving cycles of staggered annealing of complementary DNA strands of variable lengths and polymerase mediated filling-in of the generated overhangs. Microgene Polymerization Reaction (MPR) is an experimental model for expansion of short repetitive DNA to longer lengths. The testable kinetic model of (MPR) was formulated and solved numerically by Itsko et al. in Kinetics of Repeat propagation in the Microgene Polymerization Reaction (2009). Here, the simple cases of MPR were solved analytically. It was found that the repeats propagate according to Gumbel probability density function when the distribution of lengths of obtained polymers follows inverted Gumbel probability density function.

      7. Cryoprotectant toxicity and hypothermic sensitivity among Anopheles larvaeexternal icon
        Nesbitt JE, Swei A, Hunt C, Dotson E, Toner M, Sandlin RD.
        Cryobiology. 2020 Dec 28.
        Laboratory rearing of mosquitoes is commonly practiced by researchers studying mosquito-borne infectious diseases and vector control methods. In the absence of cryopreservation methods to stabilize unique or genetically modified strains, mosquito lines must be continuously maintained, a laborious process that risks selection effects, contamination, and genetic drift. Towards the development of a cryopreservation protocol, a range of commonly used cryoprotectants were systematically characterized here both individually and as cocktails. Among first instar, feeding-stage An. gambiae and An. stephensi larvae, cryoprotectant toxicity followed the order of dimethyl sulfoxide > ethylene glycol > methanol. The resulting LD(50) values were used as the basis for the development of cryoprotectant cocktail solutions, where formulation optimization was streamlined using Taguchi methods of experimental design. Sensitivity to hypothermia was further evaluated to determine the feasibility of CPA loading at reduced temperatures and slow-cooling approaches to cryopreservation. The information described here contributes to the knowledge base necessary to inform the development of a cryopreservation protocol for Anopheles larvae.

      8. Molecular characterizations of the microsporidian pathogen Enterocytozoon bieneusi at the ribosomal internal transcribed spacer (ITS) locus have identified nearly 500 genotypes in 11 phylogenetic groups with different host ranges. Among those, one unique group of genotypes, Group 11, is commonly found in dogs. Genetic characterizations of those and many divergent E. bieneusi genotypes at other genetic loci are thus far impossible. In this study, we sequenced 151 E. bieneusi isolates from several ITS genotype groups at the 16S rRNA locus and two new semi-conservative genetic markers (casein kinase 1 (ck1) and spore wall protein 1 (swp1)). Comparison of the near full (~1,200 bp) 16S rRNA sequences showed mostly two to three nucleotide substitutions between Group 1 and Group 2 genotypes, while Group 11 isolates differed from those by 26 (2.2%) nucleotides. Sequence analyses of the ck1 and swp1 loci confirmed the genetic uniqueness of Group 11 genotypes, which produced sequences very divergent from other groups. In contrast, genotypes in Groups 1 and 2 produced similar nucleotide sequences at these genetic loci, and there was discordant placement of ITS genotypes among loci in phylogenetic analyses of sequences. These results suggest that the canine-adapted Group 11 genotypes are genetically divergent from other genotype groups of E. bieneusi, possibly representing a different Enterocytozoon sp. They also indicate that there is no clear genetic differentiation of ITS Groups 1 and 2 at other genetic loci, supporting the conclusion on the lack of strict host specificity in both groups. Data and genetic markers from the study should facilitate population genetic characterizations of E. bieneusi isolates and improve our understanding of the zoonotic potential of E. bieneusi in domestic animals.

      9. Topical exposure to triclosan inhibits Th1 immune responses and reduces T cells responding to influenza infection in miceexternal icon
        Shane HL, Othumpangat S, Marshall NB, Blachere F, Lukomska E, Weatherly LM, Baur R, Noti JD, Anderson SE.
        PLoS One. 2020 ;15(12):e0244436.
        Healthcare workers concurrently may be at a higher risk of developing respiratory infections and allergic disease, such as asthma, than the general public. Increased incidence of allergic diseases is thought to be caused, in part, due to occupational exposure to chemicals that induce or augment Th2 immune responses. However, whether exposure to these chemical antimicrobials can influence immune responses to respiratory pathogens is unknown. Here, we use a BALB/c murine model to test if the Th2-promoting antimicrobial chemical triclosan influences immune responses to influenza A virus. Mice were dermally exposed to 2% triclosan for 7 days prior to infection with a sub-lethal dose of mouse adapted PR8 A(H1N1) virus (50 pfu); triclosan exposure continued until 10 days post infection (dpi). Infected mice exposed to triclosan did not show an increase in morbidity or mortality, and viral titers were unchanged. Assessment of T cell responses at 10 dpi showed a decrease in the number of total and activated (CD44hi) CD4+ and CD8+ T cells at the site of infection (BAL and lung) in triclosan exposed mice compared to controls. Influenza-specific CD4+ and CD8+ T cells were assessed using MHCI and MHCII tetramers, with reduced populations, although not reaching statistical significance at these sites following triclosan exposure. Reductions in the Th1 transcription factor T-bet were seen in both activated and tetramer+ CD4+ and CD8+ T cells in the lungs of triclosan exposed infected mice, indicating reduced Th1 polarization and providing a potential mechanism for numerical reduction in T cells. Overall, these results indicate that the immune environment induced by triclosan exposure has the potential to influence the developing immune response to a respiratory viral infection and may have implications for healthcare workers who may be at an increased risk for developing infectious diseases.

      10. Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosisexternal icon
        Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Johnson JL, Whitworth WC, Bliven-Sizemore E, Nsubuga P, Dorman SE, Savic R.
        J Antimicrob Chemother. 2020 Dec 29.
        BACKGROUND: Rifapentine exposure is associated with bactericidal activity against Mycobacterium tuberculosis, but high interindividual variation in plasma concentrations is encountered. OBJECTIVES: To investigate a genomic association with interindividual variation of rifapentine exposure, SNPs of six human genes involving rifamycin metabolism (AADAC, CES2), drug transport (SLCO1B1, SLCO1B3) and gene regulation (HNF4A, PXR) were evaluated. METHODS: We characterized these genes in 173 adult participants in treatment trials of the Tuberculosis Trials Consortium. Participants were stratified by self-identified race (black or non-black), and rifapentine AUC from 0 to 24 h (AUC0-24) was adjusted by analysis of covariance for SNPs, rifapentine dose, sex, food and HIV coinfection. This study was registered at ClinicalTrials.gov under identifier NCT01043575. RESULTS: The effect on rifapentine least squares mean AUC0-24 in black participants overall decreased by -10.2% for AADAC rs1803155 G versus A allele (Wald test: P = 0.03; false discovery rate, 0.10). Black participants with one G allele in AADAC rs1803155 were three times as likely to have below target bactericidal rifapentine exposure than black participants with the A allele (OR, 2.97; 95% CI: 1.16, 7.58). With two G alleles, the OR was greater. In non-black participants, AADAC rs1803155 SNP was not associated with rifapentine exposure. In both black and non-black participants, other evaluated genes were not associated with rifapentine exposure (P > 0.05; false discovery rate > 0.10). CONCLUSIONS: Rifapentine exposure in black participants varied with AADAC rs1803155 genotype and the G allele was more likely to be associated with below bactericidal target rifapentine exposure. Further pharmacogenomic study is needed to characterize the association of the AADAC rs1803155 with inadequate rifapentine exposure in different patient groups.

    • Maternal and Child Health
      1. Association between pica and gastrointestinal symptoms in preschoolers with and without autism spectrum disorder, Study to Explore Early Developmentexternal icon
        Fields VL, Soke GN, Reynolds A, Tian LH, Wiggins L, Maenner M, DiGuiseppi C, Kral TV, Hightshoe K, Ladd-Acosta C, Schieve LA.
        Disabil Health J. 2020 Dec 13:101052.
        BACKGROUND: Pica, the repeated ingestion of nonfood items, can result in gastrointestinal (GI) outcomes. Children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) are disproportionately affected by both pica and GI symptoms. Study of the inter-relationship between pica, GI symptoms, and ASD/DD is limited. OBJECTIVE/HYPOTHESIS: We assessed associations between pica and GI symptoms in preschool-aged children with and without ASD and other (non-ASD) DDs in the Study to Explore Early Development. METHODS: Our sample included children with ASD (n = 1244), other DDs (n = 1593), and population (POP) controls (n = 1487). Data to define final case-control status, pica, and GI symptoms were from standardized developmental assessments/questionnaires. Prevalence ratios, adjusted for sociodemographic factors (aPRs), and 95% confidence intervals were derived from modified Poisson regression. RESULTS: Within each group (ASD, DD, POP) and for the total sample, pica was associated with vomiting (aPR for total sample 2.6 [1.7, 4.0]), diarrhea (1.8 [1.4, 2.2]), and loose stools (1.8 [1.4, 2.2]). In the DD group, pica was associated with constipation (1.4 [1.03, 1.9]) and pain on stooling (1.8 [1.2, 2.6]). In analyses of the subgroup without pica, increases in GI symptoms were still evident in the ASD and DD groups compared to POP group. CONCLUSION: These findings highlight an important adverse effect of pica, GI symptoms, in children with and without ASD and DDs; nonetheless, pica does not fully explain the increased risk for GI symptoms among children with ASD and DDs. These findings inform the specialized healthcare needs of children with ASD and other DDs.

      2. Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based studyexternal icon
        Heinke D, Isenburg JL, Stallings EB, Short TD, Le M, Fisher S, Shan X, Kirby RS, Nguyen HH, Nestoridi E, Nembhard WN, Romitti PA, Salemi JL, Lupo PJ.
        Birth Defects Res. 2020 Dec 21.
        BACKGROUND: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited. METHODS: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013-2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (<35, ≥35) and infant sex. RESULTS: We identified 13,376 cases of Down syndrome. Prevalence among all programs was 12.7 per 10,000 live births. Among these children, 75% had at least one reported co-occurring birth defect diagnosis code. Among 6,210 cases identified by active programs, 66% had a cardiovascular defect with septal defects being the most common: atrial (32.5%), ventricular (20.6%), and atrioventricular (17.4%). Defect prevalence differed by infant sex more frequently than by maternal age. For example, atrioventricular septal defects were more common in female children (20.1% vs. 15.1%) while limb deficiencies were more prevalent in male children (0.4% vs. 0.1%). CONCLUSIONS: Our study provides updated prevalence estimates for structural defects, including rare defects, among children with Down syndrome using one of the largest and most recent cohorts to date. These data may aid clinical care and surveillance.

    • Occupational Safety and Health
      1. BACKGROUND: The objective was to update the 2011 Cochrane systematic review on the effectiveness of workplace interventions for the treatment of occupational asthma. METHODS: A systematic review was conducted with the selection of articles and reports through 2019. The quality of extracted data was evaluated, and meta-analyses were conducted using techniques recommended by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Data were extracted from 26 nonrandomized controlled before-and-after studies. The mean number of participants per study was 62 and the mean follow-up time was 4.5 years. Compared with continued exposure, removal from exposure had an increased likelihood of improved symptoms and change in spirometry. Reduction of exposure also had more favorable results for symptom improvement than continued exposure, but no difference for change in spirometry. Comparing exposure removal to reduction revealed an advantage for removal with both symptom improvement and change in spirometry for the larger group of patients exposed to low-molecular-weight agents. Also, the risk of unemployment was greater for exposure removal versus reduction. CONCLUSIONS: Exposure removal and reduction had better outcomes than continued exposure. Removal from exposure was more likely to improve symptoms and spirometry than reduction among patients exposed to low-molecular-weight agents. The potential benefits associated with exposure removal versus reduction need to be weighed against the potential for unemployment that is more likely with removal from exposure. The findings are based on data graded as very low quality, and additional studies are needed to generate higher quality data.

      2. The application of the theory coding scheme to interventions in occupational health psychologyexternal icon
        Horan KA, Streit JM, Beltramo JM, Post M.
        J Occup Environ Med. 2020 Dec 17.
        OBJECTIVE: There is a need to understand how and to what extent theory is used to inform OHP interventions. This study examines the utility of Michie and Prestwich's1 Theory Coding Scheme (TCS) to examine the theoretical base of OHP interventions. METHODS: We applied the TCS to a systematically derived sample of 27 papers that reported evaluation data for work-related interventions seeking to improve employee sleep quantity or quality. RESULTS: Results indicated that the original TCS was largely applicable to OHP sleep interventions. After several minor modifications to its evaluative criteria, the TCS successfully accommodates a range of OHP intervention designs. CONCLUSIONS: The revised TCS for OHP interventions allows for a more detailed understanding of the role and use of theory in OHP interventions and may prove to be a valuable tool for OHP researchers and practitioners.

      3. Prepregnancy handling of antineoplastic drugs and risk of miscarriage in female nursesexternal icon
        Nassan FL, Chavarro JE, Johnson CY, Boiano JM, Rocheleau CM, Rich-Edwards JW, Lawson CC.
        Ann Epidemiol. 2021 Jan;53:95-102.e2.
        PURPOSE: To examine the association betweenantineoplastic drug (AD) handling and risk of miscarriage. METHODS: Nurses' Health Study-3 participants self-reported AD administration and engineering controls (ECs) and personal protective equipment (PPE) use at baseline. We estimated the hazard ratio (HR) of miscarriage in relation to baseline AD handling using multivariable Cox proportional regression. RESULTS: Overall, 2440 nurses reported 3327 pregnancies, with 550 (17%) ended in miscarriages. Twelve percent of nurses self-reported currently handling AD and 28% previously handling AD. Compared with nurses who never handled AD, nurses who handled AD at baseline had an adjusted HR of miscarriage of 1.26 (95% confidence interval [CI], 0.97-1.64). This association was stronger after 12-weeks gestation (HR=2.39 [95% CI, 1.13-5.07]). Nurses who did not always use gloves had HR of 1.51 (95% CI, 0.91-2.51) compared with 1.19 (95% CI, 0.89-1.60) for those always using gloves; nurses who did not always use gowns had HR of 1.32 (95% CI, 0.95-1.83) compared with 1.19 (95% CI, 0.81-1.75) for nurses always using gowns. CONCLUSIONS: We observed a suggestive association between AD handling and miscarriage, particularly among nurses who did not consistently use PPE and EC with stronger associations for second trimester losses.

    • Occupational Safety and Health - Mining
      1. This paper was developed as part of an effort by the National Institute for Occupational Safety and Health (NIOSH) to identify risk factors associated with bumps in the prevention of fatalities and accidents in highly stressed, bump-prone ground conditions. Changes of failure mechanism with increasing confinement, from extensional-to shear-dominated failure, are widely observed in the rupture of intact specimens at the laboratory scale and in rock masses. In the previous analysis conducted in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of some specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength (AUCS) to unconfined compressive strength (UCS), the damage characteristics, and the post-yield dilatancy. These mechanical characteristics were found to be strongly anisotropic as a function of the orientation of the cleats relative to the loading direction. However, the transition from extensional to shear failure at the given confinements was not clearly identified. In this study, a total of 20 specimens were additionally prepared from the same coal sample used in the previous study and then tested under both unconfined and triaxial compressive conditions. The different confining stresses are used as analogs for different width-to-height (W/H) ratios of pillar strength. Although the W/H ratios of the specimens were not directly considered during testing, the equivalent W/H ratios of a pillar as a function of the confining stresses were estimated using an existing empirical solution. According to this relationship, the W/H at which in-situ pillar behavior would be expected to transition from brittle to ductile is identified.

    • Parasitic Diseases
      1. Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancyexternal icon
        Chotsiri P, Gutman J, Ahmed R, Poespoprodjo JR, Syafruddin D, Khairallah C, Asih PB, L'Lanziva A, Otieno K, Kariuki S, Ouma P, Were V, Katana A, Price RN, Desai M, Ter Kuile FO, Tarning J.
        Antimicrob Agents Chemother. 2020 Dec 23.
        Background: Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent-preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. Objective: This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Methods: Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4-8 weeks intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modelling with a prior approach. Results: In total data from 366 Kenyan and 101 Indonesian women were analysed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n=5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% CI: 1.8-26.5) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/mL). Translational simulations suggest that providing the full treatment dose of DP at monthly intervals provides sufficient protection to prevent malaria infection. Conclusions: Monthly administration of a DP has the potential to offer optimal prevention of malaria during pregnancy.

      2. Evolution of the monitoring and evaluation strategies to support the World Health Organization's Global Programme to Eliminate Lymphatic Filariasisexternal icon
        Lammie PJ, Gass KM, King J, Deming MS, Addiss DG, Biswas G, Ottesen EA, Henderson R.
        Int Health. 2020 Dec 22;13(Supplement_1):S65-s70.
        The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established with the ambitious goal of eliminating LF as a public health problem. The remarkable success of the GPELF over the past 2 decades in carrying out its principal strategy of scaling up and scaling down mass drug administration has relied first on the development of a rigorous monitoring and evaluation (M&E) framework and then the willingness of the World Health Organization and its community of partners to modify this framework in response to the practical experiences of national programmes. This flexibility was facilitated by the strong partnership that developed among researchers, LF programme managers and donors willing to support the necessary research agenda. This brief review summarizes the historical evolution of the GPELF M&E strategies and highlights current research needed to achieve the elimination goal.

      3. Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission.

    • Physical Activity
      1. Physical activity assessment and recommendation for adults with arthritis by primary care providers-DocStyles, 2018external icon
        Guglielmo D, Murphy LB, Theis KA, Helmick CG, Omura JD, Odom EL, Croft JB.
        Am J Health Promot. 2020 Dec 24:890117120981371.
        PURPOSE: To examine primary care providers' (PCPs) physical activity assessment and recommendation behaviors for adults with arthritis. DESIGN: Cross-sectional. SETTING: 2018 DocStyles online national market research survey of US physicians and nurse practitioners. SAMPLE: 1,389 PCPs seeing adults with arthritis. MEASURES: 2 independent behaviors (assessment and recommendation) as 3 non-mutually exclusive groups: "always assesses," "always recommends," and "both" ("always assesses and recommends"). ANALYSIS: Calculated percentages of each group (overall and by PCP characteristics), and multivariable-adjusted prevalence ratios (PRs) using binary logistic regression. RESULTS: Among PCPs, 49.2% always assessed and 57.7% always recommended physical activity; 39.7% did both. Across all 3 groups, percentages were highest for seeing ≥20 adults with arthritis weekly ("both": 56.4%; "always assesses": 66.7%; "always recommends": 71.3%) and lowest among obstetrician/gynecologists ("both": 26.9%; "always assesses": 36.8%; "always recommends": 40.7%). Multivariable-adjusted associations were strongest for seeing ≥20 adults with arthritis weekly (referent: 1-9 adults) and each of "always assesses" (PR = 1.5 [95% confidence interval (CI): 1.3-1.8] and "both" (PR = 1.6 [95% CI: 1.4-1.9]). CONCLUSIONS: Approximately 40% of PCPs sampled always engaged in both behaviors (assessing and recommending physical activity) with adults with arthritis; seeing a high volume of adults with arthritis was consistently related to engaging in each behavior. Evidence-based approaches to support PCP counseling include offering provider education and training, raising awareness of available resources, and using health system supports.

    • Public Health, General
      1. A science impact framework to measure impact beyond journal metricsexternal icon
        Ari MD, Iskander J, Araujo J, Casey C, Kools J, Chen B, Swain R, Kelly M, Popovic T.
        PLoS One. 2020 ;15(12):e0244407.
        Measuring the impact of public health science or research is important especially when it comes to health outcomes. Achieving the desired health outcomes take time and may be influenced by several contributors, making attribution of credit to any one entity or effort problematic. Here we offer a science impact framework (SIF) for tracing and linking public health science to events and/or actions with recognized impact beyond journal metrics. The SIF was modeled on the Institute of Medicine's (IOM) Degrees of Impact Thermometer, but differs in that SIF is not incremental, not chronological, and has expanded scope. The SIF recognizes five domains of influence: disseminating science, creating awareness, catalyzing action, effecting change and shaping the future (scope differs from IOM). For public health, the goal is to achieve one or more specific health outcomes. What is unique about this framework is that the focus is not just on the projected impact or outcome but rather the effects that are occurring in real time with the recognition that the measurement field is complex, and it takes time for the ultimate outcome to occur. The SIF is flexible and can be tailored to measure the impact of any scientific effort: from complex initiatives to individual publications. The SIF may be used to measure impact prospectively of an ongoing or new body of work (e.g., research, guidelines and recommendations, or technology) and retrospectively of completed and disseminated work, through linking of events using indicators that are known and have been used for measuring impact. Additionally, linking events offers an approach to both tell our story and also acknowledge other players in the chain of events. The value added by science can easily be relayed to the scientific community, policy makers and the public.

    • Reproductive Health
      1. Removing unnecessary medical barriers to contraception: Celebrating a decade of the U.S. medical eligibility criteria for contraceptive useexternal icon
        Curtis KM, Zapata LB, Pagano HP, Nguyen A, Reeves J, Whiteman MK.
        J Womens Health (Larchmt). 2020 Dec 23.
        In 2010, the Centers for Disease Control and Prevention (CDC) released the U.S. Medical Eligibility Criteria for Contraceptive Use, providing recommendations for health care providers on safe use of contraception for people with certain characteristics or medical conditions. Adapted from World Health Organization guidance, the goal of the recommendations is to remove unnecessary medical barriers to contraception. Over the past decade, CDC has updated recommendations based on new evidence, collaborated with national partners to disseminate and implement the guidelines, and conducted provider surveys to assess changes in attitudes and practices around contraception safety and provision. CDC remains committed to supporting evidence-based guidelines for safe use of contraception, as the basis for improving access to contraception and high-quality family planning services, reducing unintended pregnancy, and improving reproductive health in the United States.

      2. OBJECTIVES: This study examines receipt of formal sex education as a potential mechanism that may explain the observed associations between disability status and contraceptive use among young women with disabilities. STUDY DESIGN: Using the 2011-17 National Survey of Family Growth, we analyzed data from 2,861 women aged 18 to 24 years, who experienced voluntary first sexual intercourse with a male partner. Women whose first intercourse was involuntary (7% of all women reporting sexual intercourse) were excluded from the analytic sample. Mediation analysis was used to estimate the indirect effect of receipt of formal sex education before first sexual intercourse on the association between disability status and contraceptive use at first intercourse. RESULTS: Compared to nondisabled women, women with cognitive disabilities were less likely to report receipt of instruction in each of six discrete formal sex education topics and received instruction on a fewer number of topics overall (B = -0.286, 95% CI = -0.426 to -0.147), prior to first voluntary intercourse. In turn, the greater number of topics received predicted an increased likelihood of contraceptive use at first voluntary intercourse among these women (B = 0.188, 95% CI = 0.055 to 0.321). No significant association between non-cognitive disabilities and receipt of formal sex education or contraceptive use at first intercourse was observed. CONCLUSIONS: Given the positive association between formal sex education and contraceptive use among young adult women with and without disabilities, ongoing efforts to increase access to formal sex education are needed. Special attention is needed for those women with cognitive disabilities.

      3. Opportunities to address men's health during the perinatal period - Puerto Rico, 2017external icon
        Salvesen von Essen B, Kortsmit K, D'Angelo DV, Warner L, Smith RA, Simon C, Garfield CF, Virella WH, Vargas Bernal MI.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1638-1641.
        Decreased use of health care services (1), increased exposure to occupational hazards, and higher rates of substance use (2) might contribute to men's poorer health outcomes when compared with such outcomes for women (3). During the transition to fatherhood, paternal health and involvement during pregnancy might have an impact on maternal and infant outcomes (4-6). To assess men's health-related behaviors and participation in fatherhood-related activities surrounding pregnancy, the Puerto Rico Department of Health and CDC analyzed data from the paternal survey of the Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response (PRAMS-ZPER)* study. Fewer than one half (48.3%) of men attended a health care visit for themselves in the 12 months before their newborn's birth. However, most fathers attended one or more prenatal care visits (87.2%), were present at the birth (83.1%), and helped prepare for the newborn's arrival (e.g., by preparing the home [92.4%] or purchasing supplies [93.9%]). These findings suggest that opportunities are available for public health messaging directed toward fathers during the perinatal period to increase attention to their own health and health behaviors, and to emphasize the role they can play in supporting their families' overall health and well-being.

    • Social and Behavioral Sciences
      1. Cultural stress in the age of mass xenophobia: Perspectives from Latin/o adolescentsexternal icon
        Vos SR, Shrader CH, Alvarez VC, Meca A, Unger JB, Brown EC, Zeledon I, Soto D, Schwartz SJ.
        Int J Intercult Relat. 2021 ;80:217-230.
        During the last four years, xenophobic rhetoric directed toward Latino immigrants in U.S. media outlets and political forums has greatly increased. Using a general inductive approach, this qualitative study examined the forms of cultural stress, with a focus on discrimination and xenophobia, experienced by Latino adolescents in urban U.S. settings in 2018 and 2019. Six focus groups were conducted in Miami and Los Angeles (three groups per city) with first- and second-generation tenth-grade Latino students (n = 34). The following four themes emerged from the data: perceived discrimination from other Latino subgroups (in-group discrimination), perceived discrimination from non-Latino groups (out-group discrimination), internalization of stressors and discrimination experienced by participants' parents, and the current U.S. political rhetoric surrounding immigration. Understanding cultural stress among Latino adolescents provides valuable insight for future interventions to offset negative health outcomes associated with cultural stress.

    • Substance Use and Abuse
      1. Development and validation of a syndrome definition to identify suspected nonfatal heroin-involved overdoses treated in emergency departmentsexternal icon
        Scholl L, Liu S, Vivolo-Kantor A, Board A, Stein Z, Roehler DR, McGlone L, Hoots BE, Mustaquim D, Smith H.
        J Public Health Manag Pract. 2020 Dec 16;Publish Ahead of Print.
        CONTEXT: The Centers for Disease Control and Prevention (CDC) works closely with states and local jurisdictions that are leveraging data from syndromic surveillance systems to identify meaningful changes in overdose trends. CDC developed a suspected nonfatal heroin overdose syndrome definition for use with emergency department (ED) data to help monitor trends at the national, state, and local levels. OBJECTIVE: This study assesses the percentage of true-positive unintentional and undetermined intent heroin-involved overdose (UUHOD) captured by this definition. DESIGN/SETTING: CDC applied the UUHOD definition to ED data available in CDC's National Syndromic Surveillance Program (NSSP). Data were analyzed from 18 states that shared access to their syndromic data in NSSP with the CDC overdose morbidity team. Data were analyzed using queries and manual reviews to identify heroin overdose diagnosis codes and text describing chief complaint reasons for ED visits. MEASURES: The percentage of true-positive UUHOD was calculated as the number of true-positives divided by the number of total visits captured by the syndrome definition. RESULTS: In total, 99 617 heroin overdose visits were identified by the syndrome definition. Among 95 323 visits identified as acute heroin-involved overdoses, based on reviews of chief complaint text and diagnosis codes, 967 (1.0%) were classified as possible intentional drug overdoses. Among all 99 617 visits, 94 356 (94.7%) were classified as true-positive UUHOD; 2226 (2.2%) and 3035 (3.0%) were classified as "no" and "maybe" UUHOD, respectively. CONCLUSION: Analysis of the CDC heroin overdose syndrome definition determined that nearly all visits were captured accurately for patients presenting to the ED for a suspected acute UUHOD. This definition will continue to be valuable for ongoing heroin overdose surveillance and epidemiologic analysis of heroin overdose patterns. CDC will evaluate possible definition refinements as new products and terms for heroin overdose emerge.

    • Zoonotic and Vectorborne Diseases
      1. Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donorsexternal icon
        Brummitt SI, Kjemtrup AM, Harvey DJ, Petersen JM, Sexton C, Replogle A, Packham AE, Bloch EM, Barbour AG, Krause PJ, Green V, Smith WA.
        PLoS One. 2020 ;15(12):e0243950.
        The western blacklegged tick, Ixodes pacificus, an important vector in the western United States of two zoonotic spirochetes: Borrelia burgdorferi (also called Borreliella burgdorferi), causing Lyme disease, and Borrelia miyamotoi, causing a relapsing fever-type illness. Human cases of Lyme disease are well-documented in California, with increased risk in the north coastal areas and western slopes of the Sierra Nevada range. Despite the established presence of B. miyamotoi in the human-biting I. pacificus tick in California, clinical cases with this spirochete have not been well studied. To assess exposure to B. burgdorferi and B. miyamotoi in California, and to address the hypothesis that B. miyamotoi exposure in humans is similar in geographic range to B. burgdorferi, 1,700 blood donor sera from California were tested for antibodies to both pathogens. Sampling was from high endemic and low endemic counties for Lyme disease in California. All sera were screened using the C6 ELISA. All C6 positive and equivocal samples and nine randomly chosen C6 negative samples were further analyzed for B. burgdorferi antibody using IgG western blot and a modified two ELISA test system and for B. miyamotoi antibody using the GlpQ ELISA and B. miyamotoi whole cell sonicate western blot. Of the 1,700 samples tested in series, eight tested positive for antibodies to B. burgdorferi (0.47%, Exact 95% CI: 0.20, 0.93) and two tested positive for antibodies to B. miyamotoi (0.12%, Exact 95% CI: 0.01, 0.42). There was no statistically significant difference in seroprevalence for either pathogen between high and low Lyme disease endemic counties. Our results confirm a low frequency of Lyme disease and an even lower frequency of B. miyamotoi exposure among adult blood donors in California; however, our findings reinforce public health messaging that there is risk of infection by these emerging diseases in the state.

      2. Outbreak of anthrax associated with handling and eating meat from a cow, Uganda, 2018external icon
        Kisaakye E, Ario AR, Bainomugisha K, Cossaboom CM, Lowe D, Bulage L, Kadobera D, Sekamatte M, Lubwama B, Tumusiime D, Tusiime P, Downing R, Buule J, Lutwama J, Salzer JS, Matkovic E, Ritter J, Gary J, Zhu BP.
        Emerg Infect Dis. 2020 Dec;26(12):2799-2806.
        On April 20, 2018, the Kween District Health Office in Kween District, Uganda reported 7 suspected cases of human anthrax. A team from the Uganda Ministry of Health and partners investigated and identified 49 cases, 3 confirmed and 46 suspected; no deaths were reported. Multiple exposures from handling the carcass of a cow that had died suddenly were significantly associated with cutaneous anthrax, whereas eating meat from that cow was associated with gastrointestinal anthrax. Eating undercooked meat was significantly associated with gastrointestinal anthrax, but boiling the meat for >60 minutes was protective. We recommended providing postexposure antimicrobial prophylaxis for all exposed persons, vaccinating healthy livestock in the area, educating farmers to safely dispose of animal carcasses, and avoiding handling or eating meat from livestock that died of unknown causes.

      3. Discordant clinical outcomes in a monozygotic dichorionic-diamniotic twin pregnancy with probable Zika virus exposure. Case reportexternal icon
        Mercado M, Daza M, Moore CA, Valencia D, Rico A, Álvarez-Diaz DA, Brault AC, Fitzpatrick K, Mulkey SB.
        Trop Med Infect Dis. 2020 Dec 19;5(4).
        Prenatal exposure to Zika virus (ZIKV) is associated with congenital anomalies of the brain and the eye and neurodevelopmental sequelae. The spectrum of disease outcomes may relate to timing of infection as well as genetic and environmental factors. Congenital infections occurring in twin pregnancies can inform the clinical spectrum of these conditions and provide unique information regarding timing of infection and in utero environment with disease pathophysiology. Herein, we report a monozygotic dichorionic-diamniotic twin pregnancy with probable prenatal ZIKV exposure identified through the Colombian ZIKV disease surveillance system. Multidisciplinary clinical evaluations were provided to the twins during their first three years of life through a national program for children with in utero ZIKV exposure. Laboratory evidence of congenital infection as well as microcephaly, brain, eye, and neurodevelopmental compromise related to prenatal ZIKV infection were identified in only one infant of the twin pregnancy. This is the first report of monozygotic twins discordant for Zika-associated birth defects. The evaluation of the pathophysiology of discordance in disease outcome for congenital infections in twin pregnancies may lead to a better understanding of potential complex environmental and genetic interactions between the mother, her offspring, and an infectious exposure.

      4. Control and prevention of anthrax, Texas, USA, 2019external icon
        Sidwa T, Salzer JS, Traxler R, Swaney E, Sims ML, Bradshaw P, O'Sullivan BJ, Parker K, Waldrup KA, Bower WA, Hendricks K.
        Emerg Infect Dis. 2020 Dec;26(12):2815-2824.
        The zoonotic disease anthrax is endemic to most continents. It is a disease of herbivores that incidentally infects humans through contact with animals that are ill or have died from anthrax or through contact with Bacillus anthracis-contaminated byproducts. In the United States, human risk is primarily associated with handling carcasses of hoofstock that have died of anthrax; the primary risk for herbivores is ingestion of B. anthracis spores, which can persist in suitable alkaline soils in a corridor from Texas through Montana. The last known naturally occurring human case of cutaneous anthrax associated with livestock exposure in the United States was reported from South Dakota in 2002. Texas experienced an increase of animal cases in 2019 and consequently higher than usual human risk. We describe the animal outbreak that occurred in southwest Texas beginning in June 2019 and an associated human case. Primary prevention in humans is achieved through control of animal anthrax.

      5. An investigation into the epidemiology of chikungunya virus across neglected regions of Indonesiaexternal icon
        Stubbs SC, Johar E, Yudhaputri FA, Yohan B, Santoso MS, Hayati RF, Denis D, Blacklaws BA, Powers AM, Sasmono RT, Myint KS, Frost SD.
        PLoS Negl Trop Dis. 2020 Dec 21;14(12):e0008934.
        BACKGROUND: Chikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited. METHODOLOGY/PRINCIPAL FINDINGS: Four hundred and seventy nine acutely febrile patients presenting between September 2017-2019 were recruited from three city hospitals situated in Ambon, Maluku; Banjarmasin, Kalimantan; and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum sample while a separate sample was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4-3.2%. The single RT-PCR positive sample from this study and 24 archived samples collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic diversity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands. CONCLUSIONS/SIGNIFICANCE: Chikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia.


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

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