Volume 12, Issue 36, October 14, 2020

CDC Science Clips: Volume 12, Issue 36, October 14, 2020

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Risk factors for amyotrophic lateral sclerosis: a regional U.S. 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. 2020 Oct 1.
        INTRODUCTION: Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. METHODS: 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 (i.e., hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. RESULTS: Head trauma was associated with increased ALS risk (adjusted OR 1.60 95% CI 1.04-2.45), with significantly greater effects for injuries occurring 10 or more years prior to symptom onset (p=0.037). 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. DISCUSSION: 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. Examining the effectiveness of provider incentives to increase CRC screening uptake in neighborhood healthcare: A California Federally Qualified Health Centerexternal icon
        Barajas M, Tangka FK, Schultz J, Tantod K, Kempster YM, Omelu N, Hoover S, Thomas M, Richmond-Reese V, Subramanian S.
        Health Promot Pract. 2020 Sep 29.
        As an awardee of the Centers for Disease Control and Prevention's Colorectal Cancer Control Program, the California Department of Public Health partnered with Neighborhood Healthcare to implement evidence-based interventions and provider incentives (incentives offered to support staff, e.g., medical assistants, phlebotomists, front office staff, lab technicians) to improve colorectal cancer screening uptake. The objective of this study was to evaluate the effectiveness and cost of the provider incentive intervention implemented by Neighborhood Healthcare to increase colorectal cancer screening uptake. We collected and analyzed process and cost data to assess fecal immunochemical test (FIT) kit return rates to the health centers and the number of completed FIT kits. We estimated the costs of the preexisting interventions and the new interventions. Analyses were conducted for two time periods: preimplementation and implementation. Most Neighborhood Healthcare health centers experienced an increase in the percentage of FIT kit returns (average of 3.6 percentage points) and individuals screened (an average increase of 111 FIT kits per month) from the baseline period through the implementation period. The cost of the incentive intervention for each additional screen was $66.79. In conclusion, the results indicate that incentive programs can have an overall positive impact on both the percentage of FIT kits returned and the number of individuals screened.

      3. Cost and effectiveness of reminders to promote colorectal cancer screening uptake in rural Federally Qualified Health Centers in West Virginiaexternal icon
        Conn ME, Kennedy-Rea S, Subramanian S, Baus A, Hoover S, Cunningham C, Tangka FK.
        Health Promot Pract. 2020 Sep 29.
        The purpose of this study is to evaluate the effectiveness of the West Virginia Program to Increase Colorectal Cancer Screening in implementing patient reminders to increase fecal immunochemical test (FIT) kit return rates in nine federally qualified health centers (FQHCs). Using process measures and cost data collected, the authors examined the differences in the intensity of the phone calls across FQHCs and compared them with the return rates achieved. They also reported the cost per kit successfully returned as a result of the intervention. Across all FQHCs, 5,041 FIT kits were ordered, and the initial return rate (without a reminder) was 41.1%. A total of 2,201 patients received reminder phone calls; on average, patients received 1.61 reminder calls each. The reminder interventions increased the average FIT kit return rate to 60.7%. The average total cost per FIT kit returned across all FQHCs was $60.18, and the average cost of only the reminders was $11.20 per FIT kit returned. FQHCs achieved an average increase of 19.6 percentage points in FIT kit return rates, and costs across clinics varied. Clinics with high-quality health information systems that enabled tracking of patients with minimal effort were able to implement lower cost reminder interventions.

      4. The accuracy of provider diagnosed diabetes type in youth compared to an etiologic criteria in the SEARCH for Diabetes in Youth Studyexternal icon
        Crume TL, Hamman RF, Isom S, Divers J, Mayer-Davis EJ, Liese AD, Saydah S, Lawrence JM, Pihoker C, Dabelea D.
        Pediatr Diabetes. 2020 Sep 27.
        BACKGROUND: Although surveillance for diabetes in youth relies on provider-assigned diabetes type from medical records, its accuracy compared to an etiologic definition is unknown. METHODS: Using the SEARCH for Diabetes in Youth Registry, we evaluated the validity and accuracy of provider-assigned diabetes type abstracted from medical records against etiologic criteria that included the presence of diabetes autoantibodies (DAA) and insulin sensitivity. Youth who were incident for diabetes in 2002-06, 2008, or 2012 and had complete data on key analysis variables were included (n=4,001, 85% provider diagnosed type 1). The etiologic definition for type 1 diabetes was ≥1 positive DAA titer(s) or negative DAA titers in the presence of insulin sensitivity and for type 2 diabetes was negative DAA titers in the presence of insulin resistance. RESULTS: Provider diagnosed diabetes type correctly agreed with the etiologic definition of type for 89.9% of cases. Provider diagnosed type 1 diabetes was 96.9% sensitive, 82.8% specific, had a positive predictive value (PPV) of 97.0% and a negative predictive value (NPV) of 82.7%. Provider diagnosed type 2 diabetes was 82.8% sensitive, 96.9% specific, had a PPV and NPV of 82.7% and 97.0%, respectively. CONCLUSION: Provider diagnosis of diabetes type agreed with etiologic criteria for 90% of the cases. While the sensitivity and PPV were high for youth with type 1 diabetes, the lower sensitivity and PPV for type 2 diabetes highlights the value of DAA testing and assessment of insulin sensitivity status to ensure estimates are not biased by misclassification.

      5. The effectiveness and cost to improve colorectal cancer screening in a federally qualified homeless clinic in eastern Kentuckyexternal icon
        Hardin V, Tangka FK, Wood T, Boisseau B, Hoover S, DeGroff A, Boehm J, Subramanian S.
        Health Promot Pract. 2020 Sep 29.
        The objective of this study was to analyze the effectiveness and cost of patient incentives, together with patient navigation and patient reminders, to increase fecal immunochemical test (FIT) kit return rates and colorectal cancer screening uptake in one federally qualified health center (FQHC) in Appalachia. This FQHC is a designated homeless clinic, as 79.7% of its patient population are homeless. We collected process, outcome, and cost data from the FQHC for two time periods: usual care (September 2016-August 2017) and implementation (September 2017-September 2018). We reported the FIT kit return rate, the increase in return rate, and the additional number of individual screens. We also calculated the incremental cost per additional screen. The patient incentive program, with patient navigation and patient reminders, increased the number of FIT kits returned from the usual care period to the implementation period. The return rate increased by 25.9 percentage points (from 21.7% to 47.6%) with an additional 91 people screened at an incremental cost of $134.61 per screen. A patient incentive program, together with the assistance of patient navigators and supplemented with patient reminders, can help improve CRC screening uptake among vulnerable and homeless populations.

      6. Effectiveness and cost of implementing evidence-based interventions to increase colorectal cancer screening among an underserved population in Chicagoexternal icon
        Kim KE, Tangka FK, Jayaprakash M, Randal FT, Lam H, Freedman D, Carrier LA, Sargant C, Maene C, Hoover S, Joseph D, French C, Subramanian S.
        Health Promot Pract. 2020 Sep 29.
        With funding from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program, The University of Chicago Center for Asian Health Equity partnered with a federally qualified health center (FQHC) to implement multiple evidence-based interventions (EBIs) in order to improve colorectal cancer (CRC) screening uptake. The purpose of this study is to determine the effectiveness and cost of implementing a provider reminder system entered manually and supplemented with patient reminders and provider assessment and feedback. The FQHC collected demographic characteristics of the FQHC and outcome data from January 2015 through December 2015 (preimplementation period) and cost from January 2016 through September 2017 (implementation period). Cost data were collected for the implementation period. We report on the demographics of the eligible population, CRC screening order, completion rates by sociodemographic characteristics, and, overall, the effectiveness and cost of implementation. From the preimplementation phase to the implementation phase, there was a 21.2 percentage point increase in CRC screens completed. The total cost of implementing EBIs was $40908.97. We estimated that an additional 283 screens were completed because of the interventions, and the implementation cost of the interventions was $144.65 per additional screen. With the interventions, CRC screening uptake in Chicago increased for all race/ethnicity and demographic backgrounds at the FQHC, particularly for patients aged 50 to 64 years and for Asian, Hispanic, and uninsured patients.

      7. Economic evaluation of interventions to increase colorectal cancer screening at Federally Qualified Health Centersexternal icon
        Tangka FK, Subramanian S, Hoover S, DeGroff A, Joseph D, Wong FL, Richardson LC.
        Health Promot Pract. 2020 Sep 29.
        The Centers for Disease Control and Prevention (CDC) has a long-standing commitment to increase colorectal cancer (CRC) screening for vulnerable populations. In 2005, the CDC began a demonstration in five states and, with lessons learned, launched a national program, the Colorectal Cancer Control Program (CRCCP), in 2009. The CRCCP continues today and its current emphasis is the implementation of evidence-based interventions to promote CRC screening. The purpose of this article is to provide an overview of four CRCCP awardees and their federally qualified health center partners as an introduction to the accompanying series of research briefs where we present individual findings on impacts of evidence-based interventions on CRC screening uptake for each awardee. We also include in this article the conceptual framework used to guide our research. Our findings contribute to the evidence base and guide future program implementation to improve sustainability, increase CRC screening, and address disparities in screening uptake.

      8. State and regional variation in prescription- and payment-related promoters of adherence to blood pressure medicationexternal icon
        Yang PK, Ritchey MD, Tsipas S, Loustalot F, Wozniak GD.
        Prev Chronic Dis. 2020 Sep 24;17:E112.
        INTRODUCTION: Medication adherence can improve hypertension management. How blood pressure medications are prescribed and purchased can promote or impede adherence. METHODS: We used comprehensive dispensing data on prescription blood pressure medication from Symphony Health's 2017 Integrated Dataverse to assess how prescription- and payment-related factors that promote medication adherence (ie, fixed-dose combinations, generic formulations, mail order, low-cost or no-copay medications) vary across US states and census regions and across the market segments (grouped by patient age, prescriber type, and payer type) responsible for the greatest number of blood pressure medication fills. RESULTS: In 2017, 706.5 million prescriptions for blood pressure medication were filled, accounting for $29.0 billion in total spending (17.0% incurred by patients). As a proportion of all fills, factors that promoted adherence varied by state: fixed-dose combinations (from 5.8% in Maine to 17.9% in Mississippi); generic formulations (from 95.2% in New Jersey to 98.4% in Minnesota); mail order (from 4.7% in Rhode Island to 14.5% in Delaware); and lower or no copayment (from 56.6% in Utah to 72.8% in California). Furthermore, mean days' supply per fill (from 43.1 in Arkansas to 63.8 in Maine) and patient spending per therapy year (from $38 in Hawaii to $76 in Georgia) varied. Concentration of adherence factors differed by market segment. Patients aged 18 to 64 with a primary care physician prescriber and Medicaid coverage had the lowest concentration of fixed-dose combination fills, mean days' supply per fill, and patient spending per therapy year. Patients aged 65 years or older with a primary care physician prescriber and commercial insurance had the highest concentration of fixed-dose combinations fills and mail order fills. CONCLUSION: Addressing regional and market segment variation in factors promoting blood pressure medication adherence may increase adherence and improve hypertension management.

    • Communicable Diseases
      1. Does pulmonary aspergillosis complicate coronavirus disease 2019?external icon
        Beer KD, Jackson BR, Chiller T, Verweij PE, Van de Veerdonk FL, Wauters J.
        Crit Care Explor. 2020 Sep;2(9):e0211.
        OBJECTIVES: Aspergillus coinfection in coronavirus disease 2019 patients has rarely been described but may be occurring among coronavirus disease 2019 patients admitted to ICUs. Previous reports of viral coinfections with Aspergillus, including influenza-associated pulmonary aspergillosis, suggest that coronavirus disease 2019-associated aspergillosis is plausible. This report aims to summarize what is known about coronavirus disease 2019 complicated by Aspergillus, introduces coronavirus disease 2019-associated pulmonary aspergillosis as a possible clinical entity, and describes reasons clinical suspicion of Aspergillus is warranted in the critical care setting. DATA SOURCES: We summarize the available evidence suggesting the existence of Aspergillus coinfection among severe coronavirus disease 2019 patients. This includes published coronavirus disease 2019 patient case series, a case description, and a review of potential biologic mechanisms. STUDY SELECTION: Reports of coronavirus disease 2019 patient attributes were selected if they included clinical, microbiologic, or radiologic signs of invasive fungal infection. DATA EXTRACTION: Data included in summary tables were identified through a literature search for coronavirus disease 2019-associated pulmonary aspergillosis. DATA SYNTHESIS: We present descriptive data extracted from coronavirus disease 2019-associated pulmonary aspergillosis case series current at the time of article submission. DISCUSSION: Pulmonary aspergillosis is known to occur among influenza patients requiring intensive care and is associated with increased mortality. If Aspergillus coinfections are occurring among coronavirus disease 2019 patients, early clinical suspicion and testing are needed to understand the epidemiology of these infections and prevent associated mortality. As the coronavirus disease 2019 pandemic unfolds, reports on the existence of this coinfection are needed, and opportunities to contribute cases of Aspergillus coinfection among coronavirus disease 2019 patients to an ongoing registry are described.

      2. BACKGROUND: We assessed prevalence of testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection among persons who inject drugs (PWID). METHODS: Using a nationwide health insurance database for claims paid during 2010-2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and we used multivariate logistic regression models to assess demographic and clinical factors associated with testing. RESULTS: Of 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) were tested for HCV infections. Missed opportunities were independently associated with being male (odds ratios [ORs]: HIV, 0.50 [95% confidence interval {CI}, 0.49-0.50], P < .001; HCV, 0.66 [95% CI, 0.65-0.72], P < .001), rural residence (ORs: HIV, 0.67 [95% CI, 0.65-0.69], P < .001; HCV, 0.75 [95% CI, 0.73-0.77], P < .001), and receiving services for skin infections or endocarditis (adjusted ORs: HIV, 0.91 [95% CI, 0.87-0.95], P < .001; HCV, 0.90 [95% CI, 0.86-0.95], P < .001). CONCLUSIONS: Approximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use.

      3. Investigation and serologic follow-up of contacts of an early confirmed case-patient with COVID-19, Washington, USAexternal icon
        Chu V, Freeman-Ponder B, Lindquist S, Spitters C, Kawakami V, Dyal JW, Clark S, Bruce H, Duchin JS, DeBolt C, Podczervinski S, D'Angeli M, Pettrone K, Zacks R, Vahey G, Holshue ML, Lang M, Burke RM, Rolfes MA, Marlow M, Midgley CM, Lu X, Lindstrom S, Hall AJ, Fry AM, Thornburg NJ, Gerber SI, Pillai SK, Biggs HM.
        Emerg Infect Dis. 2020 Aug;26(8):1671-1678.
        We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

      4. Barriers to antiretroviral therapy adherence among HIV-positive Hispanic and Latino men who have sex with men -United States, 2015-2019external icon
        Crim SM, Tie Y, Beer L, Weiser J, Dasgupta S.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1437-1442.
        During 2018, estimated incidence of human immunodeficiency virus (HIV) infection among Hispanic and Latino (Hispanic/Latino) persons in the United States was four times that of non-Hispanic White persons (1). Hispanic/Latino men who have sex with men (MSM) accounted for 24% (138,023) of U.S. MSM living with diagnosed HIV infection at the end of 2018 (1). Antiretroviral therapy (ART) adherence is crucial for viral suppression, which improves health outcomes and prevents HIV transmission (2). Barriers to ART adherence among Hispanic/Latino MSM have been explored in limited contexts (3); however, nationally representative analyses are lacking. The Medical Monitoring Project reports nationally representative estimates of behavioral and clinical experiences of U.S. adults with diagnosed HIV infection. This analysis used Medical Monitoring Project data collected during 2015-2019 to examine ART adherence and reasons for missing ART doses among HIV-positive Hispanic/Latino MSM (1,673). On a three-item ART adherence scale with 100 being perfect adherence, 77.3% had a score of ≥85. Younger age, poverty, recent drug use, depression, and unmet needs for ancillary services were predictors of lower ART adherence. The most common reason for missing an ART dose was forgetting; 63.9% of persons who missed ≥1 dose reported more than one reason. Interventions that support ART adherence and access to ancillary services among Hispanic/Latino MSM might help improve clinical outcomes and reduce transmission.

      5. HIV-positive persons who inject drugs experience poor health outcomes and unmet needs for care servicesexternal icon
        Dasgupta S, Tie Y, Lemons-Lyn A, Broz D, Buchacz K, Shouse RL.
        AIDS Care. 2020 Sep 27:1-9.
        Comparison of social determinants of health and clinical outcomes between HIV-positive persons who inject drugs (PWID) and HIV-positive persons who do not inject drugs is essential to understanding disparities and informing HIV prevention and care efforts; however, nationally representative estimates are lacking. Interview and medical record data were collected for the Medical Monitoring Project during 2015-2018 among U.S. adults with diagnosed HIV. Among HIV-positive PWID (N=340) and HIV-positive persons who do not inject drugs (N=11,475), we reported weighted percentages and prevalence ratios with predicted marginal means to compare differences between groups (P<.05). Associations with clinical outcomes were adjusted for age, race/ethnicity, and gender. HIV-positive PWID were more likely to be homeless (29.1% vs. 8.1%) and incarcerated (18.3% vs. 4.9%). HIV-positive PWID were less likely to be retained in HIV care (aPR: 0.85 [95% CI: 0.77-0.94]), and were more likely to have poor HIV outcomes, have unmet needs for care services (aPR: 1.50 [1.39-1.61]), seek non-routine care, and experience healthcare discrimination (aPR: 1.42 [1.17-1.73]). Strengthening interventions supporting (1) continuity of care given high levels of incarceration and housing instability, (2) early ART initiation and adherence support, and (3) drug treatment and harm reduction programs to limit transmission risk may improve outcomes among HIV-positive PWID.

      6. Trends in COVID-19 incidence after implementation of mitigation measures - Arizona, January 22-August 7, 2020external icon
        Gallaway MS, Rigler J, Robinson S, Herrick K, Livar E, Komatsu KK, Brady S, Cunico J, Christ CM.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1460-1463.
        Mitigating the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), requires individual, community, and state public health actions to prevent person-to-person transmission. Community mitigation measures can help slow the spread of COVID-19; these measures include wearing masks, social distancing, reducing the number and size of large gatherings, pausing operation of businesses where maintaining social distancing is challenging, working from or staying at home, and implementing certain workplace and educational institution controls (1-4). The Arizona Department of Health Services' (ADHS) recommendations for mitigating exposure to SARS-CoV-2 were informed by continual monitoring of patient demographics, SARS-CoV-2 community spread, and the pandemic's impacts on hospitals. To assess the effect of mitigation strategies in Arizona, the numbers of daily COVID-19 cases and 7-day moving averages during January 22-August 7, 2020, relative to implementation of enhanced community mitigation measures, were examined. The average number of daily cases increased approximately 151%, from 808 on June 1, 2020 to 2,026 on June 15, 2020 (after stay-at-home order lifted), necessitating increased preventive measures. On June 17, local officials began implementing and enforcing mask wearing (via county and city mandates),* affecting approximately 85% of the state population. Statewide mitigation measures included limitation of public events; closures of bars, gyms, movie theaters, and water parks; reduced restaurant dine-in capacity; and voluntary resident action to stay at home and wear masks (when and where not mandated). The number of COVID-19 cases in Arizona peaked during June 29-July 2, stabilized during July 3-July 12, and further declined by approximately 75% during July 13-August 7. Widespread implementation and enforcement of sustained community mitigation measures informed by state and local officials' continual data monitoring and collaboration can help prevent transmission of SARS-CoV-2 and decrease the numbers of COVID-19 cases.

      7. Impact of breastfeeding, maternal antiretroviral treatment and health service factors on 18-month vertical transmission of HIV and HIV-free survival: results from a nationally representative HIV-exposed infant cohort, South Africaexternal icon
        Goga AE, Lombard C, Jackson D, Ramokolo V, Ngandu NK, Sherman G, Puren A, Chirinda W, Bhardwaj S, Makhari N, Ramraj T, Magasana V, Singh Y, Pillay Y, Dinh TH.
        J Epidemiol Community Health. 2020 Sep 26.
        BACKGROUND: We analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and 'MTCT-or-death', in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) <5% final MTCT and (2) case rate ≤50 (new paediatric HIV infections/100 000 live births). METHODS: 9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and 'MTCT or death' and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up. RESULTS: Cumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative 'MTCT-or-death' was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and 'MTCT-or-death', respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5-5.6)), undocumented maternal HIV status (aHR 2.21 (1.0-4.7)) and exclusive (aHR 2.3 (1.0-5.2)) or mixed (aHR 3.7 (1.2-11.4)) breastfeeding. Cumulative 'MTCT-or death' increased in households with 'no refrigerator' (aHR 1.7 (1.1-2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2-0.9)). CONCLUSIONS: While the <5% final MTCT target was met, the case rate was 25-times above target. Systems are needed in the first 6 months post-delivery to optimise HEU health and fast-track ART initiation in newly diagnosed mothers.

      8. High HIV and syphilis prevalence among female sex workers in Juba, South Sudanexternal icon
        Hakim AJ, Bolo A, Werner M, Achut V, Katoro J, Caesar G, Lako R, Taban AI, Wesson J, Okiria AG.
        PLoS One. 2020 ;15(9):e0239543.
        HIV prevalence is estimated to be 2.7% in South Sudan; however, little is known about the young country's epidemic. We conducted a respondent-driven sampling biobehavioral survey in Juba of female sex workers (FSW) aged ≥15 years who sold or exchanged sex in the last 6 months to learn more about this population. We enrolled 838 FSW from November 2015 to March 2016 and estimated HIV prevalence to be 37.8%. Prevalence of active syphilis was 7.3%. FSW were from South Sudan and most neighboring countries. Comprehensive knowledge of HIV was 11.1% and 64.2% of FSW had never spoken with an outreach worker. In multivariable analysis, HIV was associated with being from Uganda (aOR: 3.3, 95% CI: 1.7-6.1) or Kenya (aOR: 4.3, 95% CI: 1.5-13.0) versus from South Sudan. Our survey suggests that FSW may play a critical role in South Sudan's HIV epidemic and highlights the importance of tailoring services to the unique needs of FSW of all nationalities in Juba.

      9. High prevalence of chlamydia and gonorrhea and the need for STI testing among men who have sex with men and transgender women in Papua New Guineaexternal icon
        Hakim AJ, Iwamoto C, Badman SG, Willie B, Pekon S, Aeno H, Neo-Boli R, Ase S, Weikum D, Vallely AJ, Kelly-Hanku A.
        Sex Transm Dis. 2020 Sep 23.
        BACKGROUND: Papua New Guinea (PNG) has among the highest prevalence of sexually transmitted infections in the world but no estimates of Chlamydia trachomatis, Neisseria gonorrhoeae, or hepatitis B virus (HBV) are available among men who have sex with men (MSM) or transgender women (TGW). METHODS: We conducted respondent-driven sampling surveys among MSM and TGW in Port Moresby, Lae, and Mt. Hagen (2016-2017) to characterize prevalence of these infections. Eligibility criteria: aged>12 years, born male, could speak English or Tok Pisin and had oral or anal sex with another person born male in the past 6 months. Participants were surveyed face-to-face and offered testing for anorectal and genital chlamydia and gonorrhea, syphilis, HIV, and HBV. All results are RDS-weighted. RESULTS: We enrolled 400 participants in Port Moresby, 352 in Lae, and 111 in Mt. Hagen. Chlamydia prevalence in the three cities regardless of anatomical site was 19.9%, 19.2%, and 24.3%, respectively. Gonorrhea prevalence regardless of anatomical site was 10.3%, 9.4%, and 9.6%, respectively. HBV prevalence was 11.7%, 13.8%, and 13.6%, respectively. In multivariable analysis, syphilis was associated with having either chlamydia or gonorrhea in Port Moresby (adjusted odds ratio [aOR]: 4.0, 95% CI: 2.0-7.9) and Lae (aOR: 2.4, 95% CI: 1.2-5.0). CONCLUSIONS: There is a large unmet need among MSM and TGW in PNG for chlamydia and gonorrhea detection and treatment. The high prevalence of HBV reinforces the importance of ensuring introduction and scale up of HBV treatment and immunization. Urgent efforts are needed to introduce laboratory-based diagnosis for chlamydia and gonorrhea to ensure these populations have access to much needed treatment services.

      10. Characteristics associated with adults remembering to wash hands in multiple situations before and during the COVID-19 pandemic - United States, October 2019 and June 2020external icon
        Haston JC, Miller GF, Berendes D, Andújar A, Marshall B, Cope J, Hunter CM, Robinson BM, Hill VR, Garcia-Williams AG.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1443-1449.
        Washing hands often, especially during times when one is likely to acquire and spread pathogens,* is one important measure to help prevent the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), as well as other pathogens spread by respiratory or fecal-oral transmission (1,2). Studies have reported moderate to high levels of self-reported handwashing among adults worldwide during the COVID-19 pandemic (3-5)(†); however, little is known about how handwashing behavior among U.S. adults has changed since the start of the pandemic. For this study, survey data from October 2019 (prepandemic) and June 2020 (during pandemic) were compared to assess changes in adults' remembering to wash their hands in six situations.(§) Statistically significant increases in reported handwashing were seen in June 2020 compared with October 2019 in four of the six situations; the odds of remembering to wash hands was 2.3 times higher among respondents after coughing, sneezing, or blowing their nose, 2.0 times higher before eating at a restaurant, and 1.7 times higher before eating at home. Men, young adults aged 18-24 years, and non-Hispanic White (White) adults were less likely to remember to wash hands in multiple situations. Strategies to help persons remember to wash their hands frequently and at important times should be identified and implemented, especially among groups reporting low prevalence of remembering to wash their hands.

      11. Primary care providers play a vital role for HIV prevention and care in high burden areas of the Southeast United States. Studies reveal that only a third of these providers had previous HIV-related training. We evaluated the effects of targeted online continuing medical education training on HIV-related knowledge, attitudes and practices among providers in the Southeast. During April 2017-February 2018, we administered baseline and six-month follow-up surveys to assess changes attributed to online training among a representative sample of providers from six Southeast locations. Data were analyzed using logistic regression analysis (p < 0.05). Baseline and follow-up surveys were completed by 349 participants (61.2% female, 64.6% white, 69.6% physicians, and 27.5% aged 40 years or less); 18% (n = 63) of whom visited online training websites sent following the baseline survey. Comparing baseline versus follow-up responses, providers who completed online training were half as likely to identify "patients' age" (30% vs. 15%) and "patients' race" (3% vs. 1.4%) as barriers to discussing sex with clients; survey responses by participants who declined training remained unchanged. Based on baseline versus follow-up responses, providers who visited online training websites were more likely to become familiar with preexposure prophylaxis (PrEP) (38% vs. 58%); participants who declined training remained unchanged at 45%. No impact on clinical practices such as PrEP prescriptions was identified. Targeted online training can enhance HIV readiness and should be explored for providers in the Southeast, particularly for enhancing PrEP service delivery.

      12. HIV prevalence, risk factors for infection, and uptake of prevention, testing, and treatment among female sex workers in Namibiaexternal icon
        Jonas A, Patel SV, Katuta F, Maher AD, Banda KM, Gerndt K, Pietersen I, Menezes de Prata N, Mutenda N, Nakanyala T, Kisting E, Kawana B, Nietschke AM, Prybylski D, McFarland W, Lowrance DW.
        J Epidemiol Glob Health. 2020 Jun 19.
        BACKGROUND: In most settings, Female Sex Workers (FSW) bear a disproportionate burden of Human Immunodeficiency Virus (HIV) disease worldwide. Representative data to inform the development of behavioral and biomedical interventions for FSW in Namibia have not been published. OBJECTIVES: Our objectives were to measure HIV prevalence, identify risk factors for infection, and describe uptake of prevention, testing, and treatment among FSW in Namibia. METHODS: We conducted cross-sectional surveys using Respondent-driven Sampling (RDS) in the Namibian cities of Katima Mulilo, Oshikango, Swakopmund/Walvis Bay, and Windhoek. Participating FSW completed behavioral questionnaires and rapid HIV testing. RESULTS: City-specific ranges of key indicators were: HIV prevalence (31.0-52.3%), reached by prevention programs in the past 12 months (46.9-73.6%), condom use at last sex with commercial (82.1-91.1%) and non-commercial (87.0-94.2%) partners, and tested for HIV within past 12 months or already aware of HIV-positive serostatus (56.9-82.1%). Factors associated with HIV infection varied by site and included: older age, having multiple commercial or non-commercial sex partners, unemployment, being currently out of school, and lower education level. Among HIV-positive FSW, 57.1% were aware of their HIV-positive serostatus and 33.7% were on antiretroviral treatment. DISCUSSION: Our results indicate extremely high HIV prevalence and low levels of case identification and treatment among FSW in Namibia. Our results, which are the first representative community-based estimates among FSW in Namibia, can inform the scale-up of interventions to reduce the risk for HIV acquisition and onward transmission, including treatment as prevention and pre-exposure prophylaxis.

      13. Enrolment characteristics associated with retention among HIV negative Kenyan gay, bisexual and other men who have sex with men enrolled in the Anza Mapema cohort studyexternal icon
        Kunzweiler C, Bailey RC, Okall DO, Graham SM, Mehta SD, Otieno-Nyunya B, Djomand G, Otieno FO.
        J Int AIDS Soc. 2020 Oct;23 Suppl 6:e25598.
        INTRODUCTION: Most gay, bisexual and other men who have sex with men (GBMSM) live in rights-constrained environments making retaining them in research to be as hard as recruiting them. To evaluate Anza Mapema, an HIV risk-reduction programme in Kisumu, Kenya, we examined the enrolment sociodemographic, behavioural, psychosocial and clinical factors associated with missing two or more follow-up visits for GBMSM participating in Anza Mapema. METHODS: Between August 2015 and November 2017, GBMSM were enrolled and followed in a prospective cohort study with quarterly visits over 12 months. At enrolment, men were tested for HIV and sexually transmitted infections and completed questionnaires via audio computer-assisted self-interview. Because the Kenya Ministry of Health recommends HIV testing every three to six months for GBMSM, the retention outcome in this cross sectional analysis was defined as missing two consecutive follow-up visits (vs. not missing two or more consecutive visits). Multivariable logistic regression estimated the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations of the enrolment characteristics with the binary outcome of retention. RESULTS AND DISCUSSION: Among 609 enrolled HIV-negative GBMSM, the median age was 23 years (interquartile range, 21 to 28 years), 19.0% had completed ≤8 years of education and 4.1% had resided in the study area <1 year at enrolment. After enrolment, 19.7% missed two consecutive follow-up visits. In the final multivariable model, the odds of missing two consecutive follow-up visits were higher for men who: resided in the study area <1 year at enrolment (aOR, 4.14; 95% CI: 1.77 to 9.68), were not living with a male sexual partner (aOR, 1.59; 95% CI: 1.01 to 2.50), and engaged in transactional sex during the last three months (aOR, 1.70; 95% CI: 1.08 to 2.67). CONCLUSIONS: One in five men missed two consecutive follow-up visits during this HIV prevention study despite intensive retention efforts and compensation for travel and participation. Participants with recent community arrival may require special support to optimize their retention in HIV prevention activities. Live-in partners of participants may be enlisted to support greater engagement in prevention programmes, and men who engage in transactional sex will need enhanced counselling and support to stay in longitudinal studies.

      14. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection - United Kingdom and United States, March-August 2020external icon
        Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, Lee EH, Paneth-Pollak R, Geevarughese A, Lash MK, Dorsinville MS, Ballen V, Eiras DP, Newton-Cheh C, Smith E, Robinson S, Stogsdill P, Lim S, Fox SE, Richardson G, Hand J, Oliver NT, Kofman A, Bryant B, Ende Z, Datta D, Belay E, Godfred-Cato S.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1450-1456.
        During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.

      15. Gonorrhea testing, morbidity, and reporting using an integrated sexually transmitted disease registry in Indiana: 2004-2016external icon
        Ojo OC, Arno JN, Tao G, Patel CG, Zhang Z, Wang J, Holderman J, Dixon BE.
        Int J STD AIDS. 2020 Sep 30.
        Surveillance of gonorrhea (GC), the second most common notifiable disease in the United States, depends on case reports. Population-level data that contain the number of individuals tested in addition to morbidity are lacking. We performed a cross-sectional analysis of data obtained from individuals tested for GC recorded in a sexually transmitted disease (STD) registry in the state of Indiana. Descriptive statistics were performed, and a Poisson generalized linear model was used to evaluate the number of individuals tested for GC and the positivity rate. GC cases from a subset of the registry were compared to CDC counts to determine the completeness of the registry. A total of 1,870,811 GC tests were linked to 627,870 unique individuals. Individuals tested for GC increased from 54,334 in 2004 to 269,701 in 2016; likewise, GC cases increased from 2,039 to 5,997. However, positivity rate decreased from 3.75% in 2004 to 2.22% in 2016. The difference in the number of GC cases captured by the registry and those reported to the CDC was not statistically significant (P = 0.0665). Population-level data from an STD registry combining electronic medical records and public health case data may inform STD control efforts. In Indiana, increased testing rates appeared to correlate with increased GC morbidity.

      16. Adolescent with COVID-19 as the source of an outbreak at a 3-week family gathering - four states, June-July 2020external icon
        Schwartz NG, Moorman AC, Makaretz A, Chang KT, Chu VT, Szablewski CM, Yousaf AR, Brown MM, Clyne A, DellaGrotta A, Drobeniuc J, Korpics J, Muir A, Drenzek C, Bandy U, Kirking HL, Tate JE, Hall AJ, Lanzieri TM, Stewart RJ.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1457-1459.
        There is increasing evidence that children and adolescents can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-3). During July-August 2020, four state health departments and CDC investigated a COVID-19 outbreak that occurred during a 3-week family gathering of five households in which an adolescent aged 13 years was the index and suspected primary patient; 11 subsequent cases occurred.

      17. First mildly ill, nonhospitalized case of coronavirus disease 2019 (COVID-19) without viral transmission in the United States-Maricopa County, Arizona, 2020external icon
        Scott SE, Zabel K, Collins J, Hobbs KC, Kretschmer MJ, Lach M, Turnbow K, Speck L, White JR, Maldonado K, Howard B, Fowler J, Singh S, Robinson S, Pompa AP, Chatham-Stephens K, Xie A, Cates J, Lindstrom S, Lu X, Rolfes MA, Flanagan M, Sunenshine R.
        Clin Infect Dis. 2020 Jul 28;71(15):807-812.
        BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

      18. BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends specific regimens for chlamydia and dual therapy for gonorrhea to mitigate antimicrobial resistant gonorrhea in the CDC 2015 STD Treatment Guidelines. Only limited studies examining adherence to these recommendations have been conducted at private practices in the United States. METHODS: We used the OptumLabs® Data Warehouse (OLDW), a comprehensive, longitudinal data asset with de-identified persons with linked commercial insurance claims and clinical information, to identify persons aged 15-60 years who had valid nucleic acid amplification testing results demonstrating urogenital or extragenital gonorrhea or chlamydia in 2016-2018. We defined valid lab results as positive or negative. We then assessed the time of their first positive test and the type of treatment within 30 days to determine if there was evidence in the claims record that the CDC-recommended treatment was provided. We defined presumed treatment if the date of treatment was before the date of the positive test within 30 days. RESULTS: Among 6,476 patients with positive gonorrhea tests and 26,847 patients with positive chlamydia tests only, 34.8% and 64.2% had evidence of receiving the CDC-recommended therapy, respectively. About 11.6% of patients with positive gonorrhea tests with recommended dual treatment and 7.1% of patients with positive chlamydia tests only with recommended chlamydia treatment were presumptively treated. CONCLUSION: Analysis of treatment claims and medical records from private settings indicated low rates of recommended gonorrhea and chlamydia treatment. Validation of treatment claims is needed to support further quality of care interventions based on these data.

      19. Increasing HIV prevalence and injection drug use among men who have sex with men in Ho Chi Minh City, Vietnamexternal icon
        Tuan NA, Johnston LG, Thanh DC, Le LN, Hoang TV, Quang TD, Quoc NC, Nadol P, Hien NT, Abdul-Quader A.
        Int J STD AIDS. 2020 Sep 30.
        Vietnam has been conducting HIV/sexually transmitted infection (STI) integrated bio-behavioral surveillance surveys on men who have sex with men (MSM) as well as other key populations since 2005. Although HIV prevalence in the Vietnamese general population remains below 1%, it is expected to be much higher among MSM.Data on HIV prevalence and sexual and drug use behaviors were collected from MSM in Ho Chi Minh City (HCMC) in 2006 (n = 397), 2009 (n = 399) and 2013 (n = 350) using respondent-driven sampling. Eligible participants were males, aged ≥15 years who reported having manual, oral, or anal sexual activity with males in the past year and lived, worked or socialized in HCMC.HIV seroprevalence among MSM was 5.8% in 2006, 16.1% in 2009 and 12.1% in 2013 and prevalence of at least one STI (syphilis, gonorrhea and/or chlamydia infection) was 11.4% in 2006 and 15.6% in 2009 (no data for 2013). Significant, but small, increasing trends were found for MSM who reported ever testing and receiving results for HIV and for HIV prevalence. No significant changes for condom use, injecting and non-injecting drug use, or and receipt of free condoms were observed.Although a small percentage of MSM reported injecting drugs, HIV was positively associated with ever injecting drugs. Programs targeting MSM should include screening and treatment for injection drug use to most effectively control the HIV/AIDS epidemic among MSM in HCMC.

      20. Exploring how epidemic context influences syphilis screening impact: a mathematical modeling studyexternal icon
        Tuite AR, Testa C, Rönn M, Bellerose M, Gift T, Fridge J, Molotnikov L, Desmarais C, Berruti A, Menzies N, Malyuta Y, Hsu K, Salomon JA.
        Sex Transm Dis. 2020 Sep 23.
        BACKGROUND: The current syphilis epidemic in the United States is concentrated in gay, bisexual, and other men who have sex with men (MSM), but substantial heterosexual transmission is reported in some parts of the country. Using the U.S. states of Louisiana and Massachusetts as case studies, we investigated how epidemic context influences the impact of population screening approaches for syphilis control. METHODS: We constructed a compartmental metapopulation model parameterized to describe observed patterns of syphilis transmission. We estimated the impact of different approaches to screening, including perfect adherence to current U.S. screening guidelines in MSM. RESULTS: In Louisiana, where syphilis cases are more evenly distributed among MSM and heterosexual populations, we projected that screening according to guidelines would contribute to no change or an increase in syphilis burden, compared to burden with current estimated screening coverage. In Massachusetts, which has a more MSM-focused outbreak, we projected that screening according to guidelines would be as or more effective than current screening coverage in most population groups. CONCLUSIONS: MSM-focused approaches to screening may be insufficient for control when there is substantial transmission in heterosexual populations. Epidemic characteristics may be useful when identifying at-risk groups for syphilis screening.

      21. Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemicexternal icon
        Vrazo AC, Golin R, Fernando NB, Killam WP, Sharifi S, Phelps BR, Gleason MM, Wolf HT, Siberry GK, Srivastava M.
        J Int AIDS Soc. 2020 Sep;23(9):e25622.
        INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts.

      22. Preventing and responding to COVID-19 on college campusesexternal icon
        Walke HT, Honein MA, Redfield RR.
        Jama. 2020 Sep 29.

    • Disease Reservoirs and Vectors
      1. Heartland virus in lone star ticks, Alabama, USAexternal icon
        Newman BC, Sutton WB, Moncayo AC, Hughes HR, Taheri A, Moore TC, Schweitzer CJ, Wang Y.
        Emerg Infect Dis. 2020 Aug;26(8):1954-1956.
        We detected Heartland virus (HRTV) in lone star nymphs collected in 2018 in northern Alabama, USA. Real-time reverse transcription PCR selective for the small segment of the HRTV genome and confirmatory sequencing of positive samples showed high identity with HRTV strains sequenced from Tennessee and Missouri.

    • Environmental Health
      1. Empowered by tracking: Using data to solve public health problemspdf iconexternal icon
        Curtiss C, Ussery-Hall A.
        J Environ Health. 2020 ;83(3):28-30.
        The authors discuss the use of the Environmental Public Health Tracking Program of the U.S. Centers for Disease Control and Prevention to solve public health problems. Topics mentioned include the aim of the program to help address the public health data gaps that practitioners encounter, an example of data explorer side-by-side data maps, and how professionals are using the program.

      2. The Anniston Community Health Surveypdf iconexternal icon
        Cusack C, Pavuk M, Dutton N, Yang E, Serio T.
        J Environ Health. 2020 ;83(2):38-41.
        The article discusses the Anniston Community Health Survey (ACHS) I and ACHS Follow-Up and Dioxin Analyses (ACHSII) that were conducted by the Anniston Environmental Health Research Consortium in 2005-2007 and in 2014, respectively, to determine effects of polychlorinated biphenyl exposure (PCB) on the health of residents in Anniston, Alabama. Also mentioned is the use of age and race as essential determinants of PCB exposure and contamination among residents.

      3. Per- and polyfluoroalkyl substance exposure, gestational weight gain, and postpartum weight changes in Project Vivaexternal icon
        Mitro SD, Sagiv SK, Rifas-Shiman SL, Calafat AM, Fleisch AF, Jaacks LM, Williams PL, Oken E, James-Todd TM.
        Obesity (Silver Spring). 2020 Oct;28(10):1984-1992.
        OBJECTIVE: The purpose of this study was to test the extent to which pregnancy per- and polyfluoroalkyl substance (PFAS) concentrations were associated with gestational weight gain and postpartum weight changes. METHODS: This study was composed of 1,614 women recruited between 1999 and 2002 via the Project Viva cohort with pregnancy plasma concentrations of six PFAS, including perfluorooctanesulfonic acid, perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. Gestational weight gain was defined as the difference between last pregnancy weight and prepregnancy weight, 1-year postpartum weight retention as the difference between 1-year postpartum weight and prepregnancy weight, and 3-year postpartum weight change as the difference between 3-year postpartum weight and prepregnancy weight. RESULTS: During pregnancy, women gained 0.37 kg (95% CI: 0.11-0.62) more weight per doubling of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. At 1 year post partum, women retained 0.55 kg (95% CI: 0.07-1.04) more weight per doubling of PFOA. At 3 years post partum, women gained 0.91 kg (95% CI: 0.25-1.56) more weight per doubling in PFOA. Findings were similar after adjustment for all PFAS. Other PFAS were not associated with weight changes. Postpartum associations were stronger among women with higher prepregnancy BMI. Models were adjusted for demographics. CONCLUSIONS: Pregnancy PFAS were associated with greater gestational weight gain, weight retention, and weight gain years after pregnancy.

      4. Phthalates with potential adverse health effects are being replaced by other phthalates or phthalate alternatives. Little is known about temporal trends of phthalate exposure in pregnant women in the United States. We quantified 16 metabolites of eight phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) in 656 urine samples collected from 192 California pregnant women in 2007-2013 during their second and third trimesters of pregnancy who participated in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. We used multiple regression to estimate least squares geometric means of phthalate biomarker concentrations and annual percent changes over the study period. Biomarker concentrations of diethyl phthalate (DEP) and three phthalates with known toxicity and adverse health effects (i.e., butyl benzyl phthalate [BBzP], dibutyl phthalate [DBP], di(2-ethylhexyl) phthalate [DEHP]) decreased, while those of di-isobutyl phthalate [DiBP], di-isononyl phthalate [DiNP], and di-n-octyl phthalate [DOP] increased in California pregnant women during our study period. To understand broad social forces that may influence temporal trends and geographic variations in phthalate exposure across countries, we compared our phthalate biomarker concentrations with those of other populations. We observed over a factor of 2 differences in exposure across countries for some phthalate biomarkers and between pregnant and nonpregnant women for DEP.

      5. Correlates of urinary concentrations of phthalate and phthalate alternative metabolites among reproductive-aged Black women from Detroit, Michiganexternal icon
        Wesselink AK, Fruh V, Hauser R, Weuve J, Taylor KW, Orta OR, Claus Henn B, Bethea TN, McClean MD, Williams PL, Calafat AM, Baird DD, Wise LA.
        J Expo Sci Environ Epidemiol. 2020 Sep 26.
        BACKGROUND: Phthalates are endocrine-disrupting chemicals that are widely present in consumer products. In the United States, Black women are more highly exposed to phthalates than other racial/ethnic groups, yet information on predictors of phthalate exposure among Black women is limited. OBJECTIVE: We evaluated the association of demographics, lifestyle, reproductive history, and personal care product use with urinary concentrations of phthalate and phthalate alternative metabolites, using cross-sectional data from a study of 754 Black women from Detroit, Michigan (2010-2012). METHODS: Women completed questionnaires and provided urine specimens which were analyzed for 16 phthalate and phthalate alternative metabolites. We used linear regression models to estimate mean percentage differences and 95% confidence intervals (CIs) in concentrations across levels of correlates. RESULTS: Monoethyl phthalate (MEP) and MBP concentrations were positively associated with personal care product use, particularly nail products. Educational attainment was positively associated with high molecular weight phthalate concentrations but inversely associated with monobenzyl phthalate (MBzP) concentrations. Parity was positively associated with MBzP concentrations and inversely associated with concentrations of MEP and high molecular weight phthalates. SIGNIFICANCE: We found that sociodemographics, reproductive characteristics, and use of certain personal care products were associated with urinary phthalate concentrations among Black women. Our results emphasize the importance of examining exposure determinants among multiply marginalized populations.

    • Epidemiology and Surveillance
      1. Evaluation of the WHO global database on blood safetyexternal icon
        Kanagasabai U, Selenic D, Chevalier MS, Drammeh B, Qualls M, Shiraishi RW, Bock N, Benech I, Mili FD.
        Vox Sang. 2020 Sep 30.
        OBJECTIVE: While the Global Database on Blood Safety (GDBS) helps to monitor the status of adequate and safe blood availability, its presence alone does not serve as a solution to existing challenges. The objective of this evaluation was to determine the GDBS usefulness in improving the availability of adequate safe blood and its ability to function as a surveillance system. METHODS: The GDBS was evaluated using methods set out by the Centers for Disease Control and Prevention (CDC) Guidelines for assessing surveillance systems. Six recommended tasks were used to evaluate if the GDBS met the requirements of a surveillance system in a public health context. RESULTS: The majority of stakeholders engaged with GDBS found it was unique and useful. The GDBS answered all six questions essential for determining a blood safety surveillance system's usefulness. The GDBS fully met the needs to six of the eleven attributes used for evaluating the usefulness of a surveillance system. CONCLUSION: The GDBS is a unique global activity that provides vital data on safety of blood transfusion services across countries and regions. However, aspects of the GDBS such as timeliness of reporting and improvement of WHO Member States national blood information systems could enhance its effectiveness and potential to serve as a global surveillance system for blood safety.

    • Food Safety
      1. The article describes the revisions to the list of foodborne outbreak contributing factors (CF) that can be used to prevent future outbreaks and to improve food safety in the U.S. Topics mentioned include the categories of CF including poor personal hygiene and contaminated equipment, the proliferation factors that were added including the improper cooling of food, and the survival factors that were identified including the inadequate nontemperature dependent process like fermentation.

    • Genetics and Genomics
      1. Azithromycin susceptibility of Neisseria gonorrhoeae in the USA in 2017: a genomic analysis of surveillance dataexternal icon
        Gernert KM, Seby S, Schmerer MW, Thomas JC, Pham CD, Cyr SS, Schlanger K, Weinstock H, Shafer WM, Raphael BH, Kersh EN.
        Lancet Microbe. 2020 Aug;1(4):e154-e164.
        BACKGROUND: The number of cases of gonorrhoea in the USA and worldwide caused by Neisseria gonorrhoeae is increasing (555 608 reported US cases in 2017, and 87 million cases worldwide in 2016). Many countries report declining in vitro susceptibility of azithromycin, which is a concern because azithromycin and ceftriaxone are the recommended dual treatment in many countries. We aimed to identify strain types associated with decreased susceptibility to azithromycin. METHODS: We did a genomic analysis of N gonorrhoeae isolates obtained by the US Gonococcal Isolate Surveillance Project. Isolates were whole-genome sequenced based on decreased susceptibility to azithromycin (minimal inhibitory concentration [MIC] ≥2 μg/mL, using agar dilution antibiotic susceptibility testing) and geographical representation. Bioinformatic analyses established genomic diversity, strain population dynamics, and antimicrobial resistance profiles. FINDINGS: 410 isolates were sorted into more than 20 unique phylogenetic clades. One predominant persistent clade (consisting of 97 isolates) included the most isolates with azithromycin MICs of 2 μg/mL or higher (61 of 97 [63%] vs 59 of 311 [19%]; p<0·0001) and carried a mosaic mtr (multiple transferable resistance) locus (68 of 97 [70%] vs two of 313 [1%]; p<0·0001). Of the remaining 313 isolates, 57 (18%) had decreased susceptibility to azithromycin (MIC ≥4 μg/mL), which was attributed to 23S rRNA variants (56 of 57 [98%]) and formed phylogenetically diverse clades, showing various levels of clonal expansion. INTERPRETATION: Reduced azithromycin susceptibility was associated with expanding and persistent clades harbouring two well described resistance mechanisms, mosaic mtr locus and 23S rRNA variants. Understanding the role of recombination, particularly within the mtr locus, on the fitness and expansion of strains with decreased susceptibility has important implications for the public health response to minimise gonorrhoea transmission. FUNDING: US Centers for Disease Control and Prevention (CDC), CDC Combating Antibiotic Resistant Bacteria initiative, Oak Ridge Institute for Science Education, US Department of Energy/CDC/Emory University, National Institutes of Health, and Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs.

      2. Rapid, sensitive, full-genome sequencing of severe acute respiratory syndrome coronavirus 2external icon
        Paden CR, Tao Y, Queen K, Zhang J, Li Y, Uehara A, Tong S.
        Emerg Infect Dis. 2020 Oct;26(10):2401-2405.
        We describe validated protocols for generating high-quality, full-length severe acute respiratory syndrome coronavirus 2 genomes from primary samples. One protocol uses multiplex reverse transcription PCR, followed by MinION or MiSeq sequencing; the other uses singleplex, nested reverse transcription PCR and Sanger sequencing. These protocols enable sensitive virus sequencing in different laboratory environments.

      3. Signatures of somatic mutations and gene expression from p16INK4A positive head and neck squamous cell carcinomas (HNSCC)external icon
        Saba NF, Dinasarapu AR, Magliocca KR, Dwivedi B, Seby S, Qin ZS, Patel M, Griffith CC, Wang X, El-Deiry M, Steuer CE, Kowalski J, Shin DM, Zwick ME, Chen ZG.
        PLoS One. 2020 ;15(9):e0238497.
        Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC.

    • Health Communication and Education
      1. Based on the scholarship of abstract/concrete cognition, mental schema, and the integrated model of behavior change, this study found that using concrete over abstract language increased support for specific genetically modified (GM) applications and GM in general, and improved intentions to purchase products containing genetically modified organisms (GMOs). An online survey with an embedded 3 × 2 experiment was conducted using a national sample of U.S. adults (N = 1,470). Participants were randomly assigned to conditions that varied in abstract/concrete conceptualization of GMOs and were prompted to assess GM risk and benefit perceptions with respect to human health and the environment. Regardless of whether they assessed risks or benefits, participants who assessed GMOs through concrete terms compared to abstract terms showed an increase in positive emotions, which in turn increased their support for specific GM applications and GM in general, and their intentions to buy products with GMOs.

    • Health Disparities
      1. Sociodemographic determinants of Life's Simple 7: Implications for achieving cardiovascular health and health equity goalsexternal icon
        Egan BM, Li J, Sutherland SE, Jones DW, Ferdinand KC, Hong Y, Sanchez E.
        Ethn Dis. 2020 Fall;30(4):637-650.
        BACKGROUND: Life's Simple 7 (LS7; nutrition, physical activity, cigarette use, body mass index, blood pressure, cholesterol, glucose) predicts cardiovascular health. The principal objective of our study was to define demographic and socioeconomic factors associated with LS7 to better inform programs addressing cardiovascular health and health equity. METHODS: National Health and Nutrition Examination Surveys 1999-2016 data were analyzed on non-Hispanic White [NHW], NH Black [NHB], and Hispanic adults aged ≥20 years without cardiovascular disease. Each LS7 variable was assigned 0, 1, or 2 points for poor, intermediate, and ideal levels, respectively. Composite LS7 scores were grouped as poor (0-4 points), intermediate (5-9), and ideal (10-14). RESULTS: 32,803 adults were included. Mean composite LS7 scores were below ideal across race/ethnicity groups. After adjusting for confounders, NHBs were less likely to have optimal LS7 scores than NHW (multivariable odds ratios (OR .44; 95% CI .37-.53), whereas Hispanics tended to have better scores (1.18; .96-1.44). Hispanics had more ideal LS7 scores than NHBs, although Hispanics had lower incomes and less education, which were independently associated with fewer ideal LS7 scores. Adults aged ≥45 years were less likely to have ideal LS7 scores (.11; .09-.12) than adults aged <45 years. CONCLUSIONS: NHBs were the least likely to have optimal scores, despite higher incomes and more education than Hispanics, consistent with structural racism and Hispanic paradox. Programs to optimize lifestyle should begin in childhood to mitigate precipitous age-related declines in LS7 scores, especially in at-risk groups. Promoting higher education and reducing poverty are also important.

      2. Relationship between census tract-level poverty and domestically acquired Salmonella incidence: Analysis of Foodborne Diseases Active Surveillance Network Data, 2010-2016external icon
        Hadler JL, Clogher P, Libby T, Wilson E, Oosmanally N, Ryan P, Magnuson L, Lathrop S, McGuire S, Cieslak P, Fankhauser M, Ray L, Geissler A, Hurd S.
        J Infect Dis. 2020 Sep 14;222(8):1405-1412.
        BACKGROUND: The relationships between socioeconomic status and domestically acquired salmonellosis and leading Salmonella serotypes are poorly understood. METHODS: We analyzed surveillance data from laboratory-confirmed cases of salmonellosis from 2010-2016 for all 10 Foodborne Disease Active Surveillance Network (FoodNet) sites, having a catchment population of 47.9 million. Case residential data were geocoded, linked to census tract poverty level, and then categorized into 4 groups according to census tract poverty level. After excluding those reporting international travel before illness onset, age-specific and age-adjusted salmonellosis incidence rates were calculated for each census tract poverty level, overall and for each of the 10 leading serotypes. RESULTS: Of 52 821geocodable Salmonella infections (>96%), 48 111 (91.1%) were domestically acquired. Higher age-adjusted incidence occurred with higher census tract poverty level (P < .001; relative risk for highest [≥20%] vs lowest [<5%] census tract poverty level, 1.37). Children <5 years old had the highest relative risk (2.07). Although this relationship was consistent by race/ethnicity and by serotype, it was not present in 5 FoodNet sites or among those aged 18-49 years. CONCLUSION: Children and older adults living in higher-poverty census tracts have had a higher incidence of domestically acquired salmonellosis. There is a need to understand socioeconomic status differences for risk factors for domestically acquired salmonellosis by age group and FoodNet site to help focus prevention efforts.

      3. Prevalence of overweight and obesity among children enrolled in Head Start, 2012-2018external icon
        Imoisili O, Dooyema C, Kompaniyets L, Lundeen EA, Park S, Goodman AB, Blanck HM.
        Am J Health Promot. 2020 Sep 30.
        PURPOSE: Determine prevalence of overweight and obesity as reported in Head Start Program Information Reports. DESIGN: Serial cross-sectional census reports from 2012-2018. SETTING: Head Start programs countrywide, aggregated from program level to state and national level. SUBJECTS: Population of children enrolled in Head Start with reported weight status data. MEASURES: Prevalence of overweight (body mass index [BMI] ≥85th percentile to <95th percentile) and obesity (BMI ≥95th percentile). ANALYSIS: Used descriptive statistics to present the prevalence of overweight and obesity by state. Performed unadjusted regression analysis to examine annual trends or average annual changes in prevalence. RESULTS: In 2018, the prevalence of overweight was 13.7% (range: 8.9% in Alabama to 20.4% in Alaska). The prevalence of obesity was 16.6% (range: 12.5% in South Carolina to 27.1% in Alaska). In the unadjusted regression model, 34 states and the District of Columbia did not have a linear trend significantly different from zero. There was a statistically significant positive trend in obesity prevalence for 13 states and a negative trend for 3 states. CONCLUSION: The prevalence of obesity and overweight in Head Start children remained stable but continues to be high. Head Start reports may be an additional source of surveillance data to understand obesity prevalence in low-income young children.

    • Health Economics
      1. Inpatient admissions and costs for adolescents and young adults with congenital heart defects in New York, 2009-2013external icon
        Hsu WH, Sommerhalter KM, McGarry CE, Farr SL, Downing KF, Lui GK, Zaidi AN, Hsu DT, Van Zutphen AR.
        Birth Defects Res. 2020 Sep 29.
        OBJECTIVES: Most individuals born with congenital heart defects (CHDs) survive to adulthood, but healthcare utilization patterns for adolescents and adults with CHDs have not been well described. We sought to characterize the healthcare utilization patterns and associated costs for adolescents and young adults with CHDs. METHODS: We examined 2009-2013 New York State inpatient admissions of individuals ages 11-30 years with ≥1 CHD diagnosis codes recorded during any admission. We conducted multivariate linear regression using generalized estimating equations to examine associations between inpatient costs and sociodemographic and clinical variables. RESULTS: We identified 5,100 unique individuals with 9,593 corresponding hospitalizations over the study period. Median inpatient cost and length of stay (LOS) were $10,720 and 3.0 days per admission, respectively; 55.1% were emergency admissions. Admission volume increased 48.7% from 2009 (1,538 admissions) to 2013 (2,287 admissions), while total inpatient costs increased 91.8% from 2009 ($27.2 million) to 2013 ($52.2 million). Inpatient admissions and costs rose more sharply over the study period for those with nonsevere CHDs compared to severe CHDs. Characteristics associated with higher costs were longer LOS, severe CHD, cardiac/vascular hospitalization classification, surgical procedures, greater severity of illness, and admission in New York City. CONCLUSION: This study provides an informative baseline of health care utilization patterns and associated costs among adolescents and young adults with CHDs in New York State. Structured transition programs may aid in keeping this population in appropriate cardiac care as they move to adulthood.

      2. Despite the elimination of measles in the United States (US) in the year 2000, cases continue to occur, with measles outbreaks having occurred in various jurisdictions in the US in 2018 and 2019. Understanding the cost associated with measles outbreaks can inform cost-of-illness and cost-effectiveness studies of measles and measles prevention. We performed a literature review and identified 10 published studies from 2001 through 2018 that presented cost estimates from 11 measles outbreaks. The median total cost per measles outbreak was $152 308 (range, $9862-$1 063 936); the median cost per case was $32 805 (range, $7396-$76 154) and the median cost per contact was $223 (range, $81-$746). There were limited data on direct and indirect costs associated with measles. These findings highlight how costly measles outbreaks can be, the value of this information for public health department budgeting, and the importance of more broadly documenting the cost of measles outbreaks.

    • Healthcare Associated Infections
      1. Factors associated with Candida auris colonization and transmission in skilled nursing facilities with ventilator units, New York, 2016-2018external icon
        Rossow J, Ostrowsky B, Adams E, Greenko J, McDonald R, Vallabhaneni S, Forsberg K, Perez S, Lucas T, Alroy K, Slifka KJ, Walters M, Jackson BR, Quinn M, Chaturvedi S, Blog D.
        Clin Infect Dis. 2020 Sep 28.
        BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast that spreads in healthcare settings. People colonized with C. auris can transmit this pathogen and are at risk for invasive infections. New York State (NYS) has the largest U.S. burden (>500 colonized and infected people); many colonized individuals are mechanically ventilated or have tracheostomy and are residents of ventilator-capable skilled nursing facilities (vSNF). We evaluated factors associated with C. auris colonization among vSNF residents to inform prevention interventions. METHODS: During 2016-2018, the NYS Department of Health conducted point prevalence surveys (PPS) to detect C. auris colonization among residents of vSNFs. In a case-control investigation, we defined a case as C. auris colonization in a resident and identified up to four residents with negative swabs during the same PPS as controls. We abstracted data from medical records on facility transfers, antimicrobials, and medical history. RESULTS: We included 60 cases and 218 controls identified from 6 vSNFs. After controlling for potential confounders, the following characteristics were associated with C. auris colonization: being on a ventilator (aOR: 5.9; CI: 2.3-15.4), receiving carbapenem antibiotics in the prior 90 days (aOR: 3.5; CI: 1.6-7.6), having ≥1 acute care hospital visit in the prior six months (aOR: 4.2; CI: 1.9-9.6), and receiving systemic fluconazole in the prior 90 days (aOR: 6.0; CI: 1.6-22.6). CONCLUSIONS: Targeted screening of patients in vSNFs with the above risk factors for C. auris can help identify colonized patients and facilitate implementation of infection control measures. Antimicrobial stewardship may be an important factor in the prevention of C. auris colonization.

    • Immunity and Immunization
      1. Incorporating real-time influenza detection into the test-negative design for estimating influenza vaccine effectiveness: The real-time test-negative design (rtTND)external icon
        Feldstein LR, Self WH, Ferdinands JM, Randolph AG, Aboodi M, Baughman AH, Brown SM, Exline MC, Files DC, Gibbs K, Ginde AA, Gong MN, Grijalva CG, Halasa N, Khan A, Lindsell CJ, Newhams M, Peltan ID, Prekker ME, Rice TW, Shapiro NI, Steingrub J, Talbot HK, Halloran ME, Patel M.
        Clin Infect Dis. 2020 Sep 25.
        With rapid and accurate molecular influenza testing now widely available in clinical settings, influenza vaccine effectiveness (VE) studies can prospectively select participants for enrollment based on real-time results rather than enrolling all eligible patients regardless of influenza status, as in the traditional test-negative design (TND). Thus, we explore advantages and disadvantages of modifying the TND for estimating VE by using real-time, clinically available viral testing results paired with acute respiratory infection eligibility criteria for identifying influenza cases and test-negative controls prior to enrollment. This modification, which we have called the real-time test-negative design (rtTND), has the potential to improve influenza VE studies by optimizing the case-to-test-negative control ratio, more accurately classifying influenza status, improving study efficiency, reducing study cost, and increasing study power to adequately estimate VE. Important considerations for limiting biases in the rtTND include the need for comprehensive clinical influenza testing at study sites and accurate influenza tests.

      2. Progress toward poliomyelitis eradication - Afghanistan, January 2019-July 2020external icon
        Martinez M, Akbar IE, Wadood MZ, Shukla H, Jorba J, Ehrhardt D.
        MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1464-1468.
        Wild poliovirus type 1 (WPV1) transmission is ongoing only in Afghanistan and Pakistan (1). Following a decline in case numbers during 2013-2016, the number of cases in Afghanistan has increased each year during 2017-2020. This report describes polio eradication activities and progress toward polio eradication in Afghanistan during January 2019-July 2020 and updates previous reports (2,3). Since April 2018, insurgent groups have imposed bans on house-to-house vaccination. In September 2019, vaccination campaigns in areas under insurgency control were restarted only at health facilities. In addition, during March-June 2020, all campaigns were paused because of the coronavirus disease 2019 (COVID-19) pandemic. The number of WPV1 cases reported in Afghanistan increased from 21 in 2018 to 29 in 2019. During January-July 2020, 41 WPV1 cases were reported as of August 29, 2020 (compared with 15 during January-July 2019); in addition, 69 cases of circulating vaccine-derived poliovirus type 2 (cVDPV2), and one case of ambiguous vaccine-derived poliovirus type 2 (aVDPV2) (isolates with no evidence of person-to-person transmission or from persons with no known immunodeficiency) were detected. Dialogue with insurgency leaders through nongovernmental and international organizations is ongoing in an effort to recommence house-to-house campaigns, which are essential to stopping WPV1 transmission in Afghanistan. To increase community demand for polio vaccination, additional community health needs should be addressed, and polio vaccination should be integrated with humanitarian services.

      3. Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020
        Mbaeyi SA, Bozio CH, Duffy J, Rubin LG, Hariri S, Stephens DS, MacNeil JR.
        MMWR Recomm Rep. 2020 ;69(9):1-41.
        This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16-23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.

      4. Improving the quality and use of immunization and surveillance data: Summary report of the Working Group of the Strategic Advisory Group of Experts on Immunizationexternal icon
        Scobie HM, Edelstein M, Nicol E, Morice A, Rahimi N, MacDonald NE, Carolina Danovaro-Holliday M, Jawad J.
        Vaccine. 2020 Sep 16.
        Concerns about the quality and use of immunization and vaccine-preventable disease (VPD) surveillance data have been highlighted on the global agenda for over two decades. In August 2017, the Strategic Advisory Group of Experts (SAGE) established a Working Group (WG) onthe Quality and Use of Global Immunization and Surveillance Data to review the current status and evidence to make recommendations, which were presented to SAGE in October 2019. The WG synthesized evidence from landscape analyses, literature reviews, country case-studies, a data triangulation analysis, as well as surveys of experts. Data quality (DQ) was defined as data that are accurate, precise, relevant, complete, and timely enough for the intended purpose (fit-for-purpose), and data use as the degree to which data are actually used for defined purposes, e.g., immunization programme management, performance monitoring, decision-making. The WG outlined roles and responsibilities for immunization and surveillance DQ and use by programme level. The WG found that while DQ is dependent on quality data collection at health facilities, many interventions have targeted national and subnational levels, or have focused on new technologies, rather than the people and enabling environments required for functional information systems. The WG concluded that sustainable improvements in immunization and surveillance DQ and use will require efforts across the health system - governance, people, tools, and processes, including use of data for continuous quality improvement (CQI) - and that the approaches need to be context-specific, country-owned and driven from the frontline up. At the country level, major efforts are needed to: (1) embed monitoring DQ and use alongside monitoring of immunization and surveillance performance, (2) increase workforce capacity and capability for DQ and use, starting at the facility level, (3) improve the accuracy of immunization programme targets (denominators), (4) enhance use of existing data for tailored programme action (e.g., immunization programme planning, management and policy-change), (5) adopt a data-driven CQI approach as part of health system strengthening, (6) strengthen governance around piloting and implementation of new information and communication technology tools, and (7) improve data sharing and knowledge management across areas and organizations for improved transparency and efficiency. Global and regional partners are requested to support countries in adopting relevant recommendations for their setting and to continue strengthening the reporting and monitoring of immunization and VPD surveillance data through processes periodic needs assessment and revision processes. This summary of the WG's findings and recommendations can support "data-guided" implementation of the new Immunization Agenda 2030.

      5. Influenza economic burden among potential target risk groups for immunization in South Africa, 2013-2015external icon
        Tempia S, Moyes J, Cohen AL, Walaza S, McMorrow ML, Edoka I, Fraser H, Treurnicht FK, Hellferscee O, Wolter N, von Gottberg A, McAnerney JM, Dawood H, Variava E, Cohen C.
        Vaccine. 2020 Sep 23.
        BACKGROUND: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries. METHODS: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index. RESULTS: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death. CONCLUSION: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.

    • Laboratory Sciences
      1. Risk of transmissibility from neurodegenerative disease-associated proteins: Experimental knowns and unknownsexternal icon
        Asher DM, Belay E, Bigio E, Brandner S, Brubaker SA, Caughey B, Clark B, Damon I, Diamond M, Freund M, Hyman BT, Jucker M, Keene CD, Lieberman AP, Mackiewicz M, Montine TJ, Morgello S, Phelps C, Safar J, Schneider JA, Schonberger LB, Sigurdson C, Silverberg N, Trojanowski JQ, Frosch MP.
        J Neuropathol Exp Neurol. 2020 Oct 1.
        Recent studies in animal models demonstrate that certain misfolded proteins associated with neurodegenerative diseases can support templated misfolding of cognate native proteins, to propagate across neural systems, and to therefore have some of the properties of classical prion diseases like Creutzfeldt-Jakob disease. The National Institute of Aging convened a meeting to discuss the implications of these observations for research priorities. A summary of the discussion is presented here, with a focus on limitations of current knowledge, highlighting areas that appear to require further investigation in order to guide scientific practice while minimizing potential exposure or risk in the laboratory setting. The committee concluded that, based on all currently available data, although neurodegenerative disease-associated aggregates of several different non-prion proteins can be propagated from humans to experimental animals, there is currently insufficient evidence to suggest more than a negligible risk, if any, of a direct infectious etiology for the human neurodegenerative disorders defined in part by these proteins. Given the importance of this question, the potential for noninvasive human transmission of proteopathic disorders is deserving of further investigation.

      2. Indoor surface chemistry: Developing a molecular picture of reactions on indoor interfacesexternal icon
        Ault AP, Grassian VH, Carslaw N, Collins DB, Destaillats H, Donaldson DJ, Farmer DK, Jimenez JL, McNeill VF, Morrison GC, O'Brien RE, Shiraiwa M, Vance ME, Wells JR, Xiong W.
        Chem. 2020 Sep 19.
        Chemical reactions on indoor surfaces play an important role in air quality in indoor environments, where humans spend 90% of their time. We focus on the challenges of understanding the complex chemistry that takes place on indoor surfaces and identify crucial steps necessary to gain a molecular-level understanding of environmental indoor surface chemistry: (1) elucidate key surface reaction mechanisms and kinetics important to indoor air chemistry, (2) define a range of relevant and representative surfaces to probe, and (3) define the drivers of surface reactivity, particularly with respect to the surface composition, light, and temperature. Within the drivers of surface composition are the roles of adsorbed/absorbed water associated with indoor surfaces and the prevalence, inhomogeneity, and properties of secondary organic films that can impact surface reactivity. By combining laboratory studies, field measurements, and modeling we can gain insights into the molecular processes necessary to further our understanding of the indoor environment.

      3. Cross-protection by inactivated H5 pre-pandemic vaccine seed strains against diverse Goose/Guangdong lineage H5N1 highly pathogenic avian influenza virusesexternal icon
        Criado MF, Sá E. Silva M, Lee DH, de Lima Salge CA, Spackman E, Donis R, Wan XF, Swayne DE.
        J Virol. 2020 Sep 30.
        The highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world, and has caused lethal, sporadic infections in humans. Vaccines are important in HPAI control for both poultry and in pre-pandemic preparedness in humans. This study assessed inactivated pre-pandemic vaccine strains in a One Health framework, focusing on the genetic and antigenic diversity of field H5N1 Gs/GD viruses from the agricultural sector and assessing cross protection in a chicken challenge model. Nearly half (47.92%) of the forty-eight combinations of vaccine/challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death time (MDT) and the virus shedding titers were significantly lower compared to the sham group (p≤ 0.05). The antibody titers in the pre-challenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination inhibiting (HI) antibodies against homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters, homologous or closely related vaccine and challenge viruses, gave the best prediction protection. Through additional analysis, we identified a pattern of epitopes substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV in the agricultural sector and for human pre-pandemic preparedness. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.ImportanceThe sustained circulation of highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) in the agricultural sector and some wild birds has led to the evolution and selection of distinct viral lineages involved in the escape from vaccine protection. Our results using inactivated vaccine candidates from the human pandemic preparedness program in a chicken challenge model identified critical antigenic conformational epitopes on the H5 hemagglutinin (HA) from different clades that were associated with antibody recognition and escape. Even though other investigators have reported epitope mapping in the H5 HA, much of this information pertains to epitopes reactive towards mouse antibodies. Our findings validate changes in antigenic epitopes of HA associated with virus escape from antibody neutralization in chickens, which has direct relevance to field protection and virus evolution. Therefore, the knowledge of these immunodominant regions is essential to proactively develop diagnostic tests, improve surveillance platforms to monitor AIV outbreaks, and design more efficient and broad-spectrum agricultural and human prepandemic vaccines.

      4. Limited added value of oropharyngeal swabs for detecting pneumococcal carriage in adultsexternal icon
        Farrar JL, Odiembo H, Odoyo A, Bigogo G, Kim L, Lessa FC, Feikin DR, Breiman RF, Whitney CG, Carvalho MG, Pimenta FC.
        Open Forum Infect Dis. 2020 Sep;7(9):ofaa368.
        We compared pneumococcal isolation rates and evaluated the benefit of using oropharyngeal (OP) specimens in addition to nasopharyngeal (NP) specimens collected from adults in rural Kenya. Of 846 adults, 52.1% were colonized; pneumococci were detected from both NP and OP specimens in 23.5%, NP only in 22.9%, and OP only in 5.7%. Ten-valent pneumococcal conjugate vaccine strains were detected from both NP and OP in 3.4%, NP only in 4.1%, and OP only in 0.7%. Inclusion of OP swabs increased carriage detection by 5.7%; however, the added cost of collecting and processing OP specimens may justify exclusion from future carriage studies among adults.

      5. Four new species of the Hylomyscus anselli group (Mammalia: Rodentia: Muridae) from the Democratic Republic of Congo and Tanzaniaexternal icon
        Kerbis Peterhans JC, Hutterer R, Doty JB, Malekani JM, Moyer DC, Krásová J, Bryja J, Banasiak RA, Demos TC.
        Bonn Zoological Bulletin. 2020 ;69(1):55-83.
        As in many other small mammal groups from the Afrotropics, the number of species recognized within the genus Hylomyscus has increased considerably over the past dozen years. The last comprehensive review (2005) of the genus recognized eight species. Since that time, nine additional species have been elevated from synonymy (n = 4) or described as new (n = 5). Here we describe four additional new species supported by morphological and molecular evidence, all collected by the late William Stanley. Two of the new taxa are sympatric and come from the poorly known left bank (direction source to mouth) of the Congo River. One of these (Hylomyscus pygmaeus sp. nov.) is easily recognized, as it is tiny and significantly smaller than any known species of the genus; the second new species (Hylomyscus thornesmithae sp. nov.) is also small, and syntopic with the first. The third new species (Hylomyscus stanleyi sp. nov.), from the SW corner of Tanzania, is quite large and had been previously included within the hypodigm of Hylomyscus anselli following its recognition from within the synonymy of Hylomyscus denniae. The fourth species (Hylomyscus mpungamachagorum sp. nov.) is from Mahale Mountains National Park, western Tanzania. Our study reveals a much higher species diversity of the genus than previously known, providing insights into additional Afrotropical and Afromontane centers of endemism that require further exploration.

      6. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic coronavirus that was identified in 2012. MERS-CoV infection in humans can result in an acute, severe respiratory disease and in some cases multi-organ failure; the global mortality rate is approximately 35 %. The MERS-CoV spike (S) protein is a major target for neutralizing antibodies in infected patients. The MERS-CoV microneutralization test (MNt) is the gold standard method for demonstrating prior infection. However, this method requires the use of live MERS-CoV in biosafety level 3 (BSL-3) containment. The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. Using a panel of human sera from confirmed MERS-CoV patients, the VSV-MERS-CoV particle neutralization assay produced results that were highly comparable to those of the microneutralization test using live MERS-CoV. The results suggest that the VSV-MERS-CoV-S pseudotype neutralization assay offers a highly specific, sensitive and safer alternative method to detect MERS-CoV neutralizing antibodies in human sera.

      7. A culture collection of 50 Neisseria gonorrhoeae isolatesexternal icon
        Liu H, Vidyaprakash E, Schmerer MW, Pham DC, St Cyr S, Kersh EN.
        Microbiol Resour Announc. 2020 Oct 1;9(40).
        A culture collection of 50 Neisseria gonorrhoeae isolates is available from the CDC & FDA Antibiotic Resistance Isolate Bank. Associated data include antibiotic susceptibility information for azithromycin, cefixime, cefpodoxime, ceftriaxone, tetracycline, ciprofloxacin, penicillin, and spectinomycin and linked whole-genome sequences.

      8. Investigation of melioidosis using blood culture and indirect hemagglutination assay serology among patients with fever, Northern Tanzaniaexternal icon
        Maze MJ, Elrod MG, Biggs HM, Bonnewell J, Carugati M, Hoffmaster AR, Lwezaula BF, Madut DB, Maro VP, Mmbaga BT, Morrissey AB, Saganda W, Sakasaka P, Rubach MP, Crump JA.
        Am J Trop Med Hyg. 2020 Sep 28.
        Prediction models indicate that melioidosis may be common in parts of East Africa, but there are few empiric data. We evaluated the prevalence of melioidosis among patients presenting with fever to hospitals in Tanzania. Patients with fever were enrolled at two referral hospitals in Moshi, Tanzania, during 2007-2008, 2012-2014, and 2016-2019. Blood was collected from participants for aerobic culture. Bloodstream isolates were identified by conventional biochemical methods. Non-glucose-fermenting Gram-negative bacilli were further tested using a Burkholderia pseudomallei latex agglutination assay. Also, we performed B. pseudomallei indirect hemagglutination assay (IHA) serology on serum samples from participants enrolled from 2012 to 2014 and considered at high epidemiologic risk of melioidosis on the basis of admission within 30 days of rainfall. We defined confirmed melioidosis as isolation of B. pseudomallei from blood culture, probable melioidosis as a ≥ 4-fold rise in antibody titers between acute and convalescent sera, and seropositivity as a single antibody titer ≥ 40. We enrolled 3,716 participants and isolated non-enteric Gram-negative bacilli in five (2.5%) of 200 with bacteremia. As none of these five isolates was B. pseudomallei, there were no confirmed melioidosis cases. Of 323 participants tested by IHA, 142 (44.0%) were male, and the median (range) age was 27 (0-70) years. We identified two (0.6%) cases of probable melioidosis, and 57 (17.7%) were seropositive. The absence of confirmed melioidosis from 9 years of fever surveillance indicates melioidosis was not a major cause of illness.

      9. Tobacco smoke exposure exacerbated crystalline silica-induced lung toxicity in ratsexternal icon
        Sager TM, Umbright CM, Mustafa GM, Yanamala N, Leonard HD, McKinney WG, Kashon ML, Joseph P.
        Toxicol Sci. 2020 Sep 25.
        Smoking may modify the lung response to silica exposure including cancer and silicosis. Nevertheless, the precise role of exposure to tobacco smoke (TS) on the lung response to crystalline silica (CS) exposure and the underlying mechanisms need further clarification. The objectives of the present study were to determine the role of TS on lung response to CS exposure and the underlying mechanism(s). Male Fischer 344 rats were exposed by inhalation to air, CS (15 mg/m3, 6 hrs/day, 5 days), TS (80 mg/m3, 3 hrs/day, twice weekly, 6 months), or CS (15 mg/m3, 6 hrs/day, 5 days) followed by TS (80 mg/m3, 3 hrs/day, twice weekly, 6 months). The rats were euthanized 6 months and 3 weeks following initiation of the first exposure and the lung response was assessed. Silica exposure resulted in significant lung toxicity as evidenced by lung histological changes, enhanced neutrophil infiltration, increased LDH levels, enhanced oxidant production, and increased cytokine levels. The TS exposure alone had only a minimal effect on these toxicity parameters. However, the combined exposure to TS and CS exacerbated the lung response, compared to TS or CS exposure alone. Global gene expression changes in the lungs correlated with the lung toxicity severity. Bioinformatic analysis of the gene expression data demonstrated significant enrichment in functions, pathways, and networks relevant to the response to CS exposure which correlated with the lung toxicity detected. Collectively our data demonstrated an exacerbation of CS-induced lung toxicity by TS exposure and the molecular mechanisms underlying the exacerbated toxicity.

      10. Epidemiological correlates of PCR cycle threshold values in the detection of SARS-CoV-2external icon
        Salvatore PP, Dawson P, Wadhwa A, Rabold EM, Buono S, Dietrich EA, Reses HE, Vuong J, Pawloski L, Dasu T, Bhattacharyya S, Pevzner E, Hall AJ, Tate JE, Kirking HL.
        Clin Infect Dis. 2020 Sep 28.
        BACKGROUND: Detection of SARS-CoV-2 infection has principally been performed through the use of real-time reverse-transcription PCR (rRT-PCR) testing. Results of such tests can be reported as cycle threshold (Ct) values, which may provide semi-quantitative or indirect measurements of viral load. Previous reports have examined temporal trends in Ct values over the course of a SARS-CoV-2 infection. METHODS: Using testing data collected during a prospective household transmission investigation of outpatient and mild COVID-19 cases, we examined the relationship between Ct values of the viral RNA N1 target and demographic, clinical, and epidemiological characteristics collected through participant interviews and daily symptom diaries. RESULTS: We found Ct values are lowest (corresponding to higher viral RNA concentration) soon after symptom onset and are significantly correlated with time elapsed since onset (p<0.001); within 7 days after symptom onset, the median Ct value was 26.5 compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (p=0.01) and those reporting upper respiratory symptoms at the time of sample collection (p=0.001) and were higher among participants reporting no symptoms (p=0.05). CONCLUSIONS: These results emphasize the importance of early testing for SARS-CoV-2 among individuals with symptoms of respiratory illness and allows cases to be identified and isolated when their viral shedding may be highest.

      11. Complex genetic encoding of the hepatitis B virus on-drug persistenceexternal icon
        Thai H, Lara J, Xu X, Kitrinos K, Gaggar A, Chan HL, Xia GL, Ganova-Raeva L, Khudyakov Y.
        Sci Rep. 2020 Sep 23;10(1):15574.
        Tenofovir disoproxil fumarate (TDF) is one of the nucleotide analogs capable of inhibiting the reverse transcriptase (RT) activity of HIV and hepatitis B virus (HBV). There is no known HBV resistance to TDF. However, detectable variation in duration of HBV persistence in patients on TDF therapy suggests the existence of genetic mechanisms of on-drug persistence that reduce TDF efficacy for some HBV strains without affording actual resistance. Here, the whole genome of intra-host HBV variants (N = 1,288) was sequenced from patients with rapid (RR, N = 5) and slow response (SR, N = 5) to TDF. Association of HBV genomic and protein polymorphic sites to RR and SR was assessed using phylogenetic analysis and Bayesian network methods. We show that, in difference to resistance to nucleotide analogs, which is mainly associated with few specific mutations in RT, the HBV on-TDF persistence is defined by genetic variations across the entire HBV genome. Analysis of the inferred 3D-structures indicates no difference in affinity of TDF binding by RT encoded by intra-host HBV variants that rapidly decline or persist in presence of TDF. This finding suggests that effectiveness of TDF recognition and binding does not contribute significantly to on-drug persistence. Differences in patterns of genetic associations to TDF response between HBV genotypes B and C and lack of a single pattern of mutations among intra-host variants sensitive to TDF indicate a complex genetic encoding of the trait. We hypothesize that there are many genetic mechanisms of on-drug persistence, which are differentially available to HBV strains. These pervasive mechanisms are insufficient to prevent viral inhibition completely but may contribute significantly to robustness of actual resistance. On-drug persistence may reduce the overall effectiveness of therapy and should be considered for development of more potent drugs.

      12. Development of a sensitive high-resolution mass spectrometry approach for urea nitrogen quantitation in small volumes of bronchoalveolar lavage fluid (BALF)external icon
        Ulmer CZ, Smith B, Thonkulpitak J, Hardin J, Danilenko U, Frame T, Cheng PY, Vesper HW.
        J Am Soc Mass Spectrom. 2020 Sep 30.
        A sensitive, selective, and quantitative method incorporating high-resolution mass spectrometry was developed for the determination of blood urea nitrogen (BUN) in bronchoalveolar lavage fluid. The method requires no sample cleanup or derivatization prior to analysis. High-performance liquid chromatography (HPLC) on a Hypersil Gold PFP column (100 × 3 mm, 3 μm particle size) connected to a C18 guard column was employed for a 10 min chromatographic separation. The detection of urea was achieved using a Thermo Scientific Q-Exactive Plus instrument incorporating selected ion monitoring (SIM) modes for the protonated adduct of urea. The urea analytical measuring range for the method is 0.047-17.134 mg/dL, resulting in a BUN analytical measurement range of 0.022-8.007 mg/dL, which allows for quantitation over 3 orders of magnitude (R(2) = 0.999). In addition, the method is suitable for small sample volumes (15 μL) with a high level of accuracy, precision, and specificity.

      13. Two discrete choice experiments on laboratory safety decisions and practicesexternal icon
        Wirth O, Foreman AM, Friedel JE, Andrew ME.
        J Saf Res. 2020 .
        Introduction: The path toward enhancing laboratory safety requires a thorough understanding of the factors that influence the safety-related decision making of laboratory personnel. Method: We developed and administered a web-based survey to assess safety-related decision making of laboratory personnel of a government research organization. The survey included two brief discrete choice experiments (DCEs) that allowed for quantitative analysis of specific factors that potentially influence safety-related decisions and practices associated with two different hypothetical laboratory safety scenarios. One scenario related to reporting a laboratory spill, and the other scenario involved changing protective gloves between laboratory rooms. The survey also included several brief self-report measures of attitude, perception, and behavior related to safety practices. Results: Risk perception was the most influential factor in safety-related decision making in both scenarios. Potential negative consequences and effort associated with reporting an incident and the likelihood an incident was detected by others also affected reporting likelihood. Wearing gloves was also affected somewhat by perceived exposure risk, but not by other social or work-related factors included in the scenarios. Conclusions: The study demonstrated the promise of DCEs in quantifying the relative impact of several factors on safety-related choices of laboratory workers in two hypothetical but realistic scenarios. Participants were faced with hypothetical choice scenarios with realistic features instead of traditional scaling techniques that ask about attitudes and perceptions. The methods are suitable for addressing many occupational safety concerns in which workers face tradeoffs in their safety-related decisions and behavior. Practical Application: Safety-related decisions regarding laboratory practices such as incident reporting and use of PPE were influenced primarily by workers’ perceptions of risk of exposure and severity of risks to health and safety. This finding suggests the importance of providing laboratory workers with adequate and effective education and training on the hazards and risks associated with their work. DCEs are a promising research method for better understanding the relative influences of various personal, social, and organizational factors that shape laboratory safety decisions and practices. The information gained from DCEs may lead to more targeted training materials and interventions.

      14. 3,3'-dichlorobiphenyl is metabolized to a complex mixture of oxidative metabolites, including novel methoxylated metabolites, by HepG2 cellsexternal icon
        Zhang CY, Flor S, Ruiz P, Dhakal R, Hu X, Teesch LM, Ludewig G, Lehmler HJ.
        Environ Sci Technol. 2020 Sep 23.
        3,3'-Dichlorobiphenyl (PCB 11) is a byproduct of industrial processes and detected in environmental samples. PCB 11 and its metabolites are present in human serum, and emerging evidence demonstrates that PCB 11 is a developmental neurotoxicant. However, little is known about the metabolism of PCB 11 in humans. Here, we investigated the metabolism of PCB 11 and the associated metabolomics changes in HepG2 cells using untargeted high-resolution mass spectrometry. HepG2 cells were exposed for 24 h to PCB 11 in DMSO or DMSO alone. Cell culture media were analyzed with ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Thirty different metabolites were formed by HepG2 cells exposed to 10 μM PCB 11, including monohydroxylated, dihydroxylated, methoxylated-hydroxylated, and methoxylated-dihydroxylated metabolites and the corresponding sulfo and glucuronide conjugates. The methoxylated PCB metabolites were observed for the first time in a human-relevant model. 4-OH-PCB 11 (3,3'-dichlorobiphenyl-4-ol) and the corresponding catechol metabolite, 4,5-di-OH-PCB 11 (3',5-dichloro-3,4-dihydroxybiphenyl), were unambiguously identified based on liquid and gas chromatographic analyses. PCB 11 also altered several metabolic pathways, in particular vitamin B(6) metabolism. These results demonstrate that complex PCB 11 metabolite profiles are formed in HepG2 cells that warrant further toxicological investigation, particularly since catechol metabolites are likely reactive and toxic.

    • Maternal and Child Health
      1. CE: From the CDC: Understanding autism spectrum disorderexternal icon
        Christensen D, Zubler J.
        Am J Nurs. 2020 Oct;120(10):30-37.
        Autism spectrum disorder (ASD) is a condition characterized by impaired social communication as well as restricted and repetitive behaviors. It is considered a neurodevelopmental disorder because it is associated with neurologic changes that may begin in prenatal or early postnatal life, alters the typical pattern of child development, and produces chronic signs and symptoms that usually manifest in early childhood and have potential long-term consequences. In past decades, autism was conceptualized as a strictly defined set of behaviors, usually accompanied by intellectual impairment. Today, it is recognized as a spectrum, ranging from mild to severe, in which behaviors vary substantially and the majority of children who fall on the spectrum have average to above average intellectual ability. Here, the authors discuss the risk factors for ASD, its epidemiology, common concurrent conditions, evaluation, diagnosis, treatments, and outcomes.

      2. Receipt and timeliness of newborn hearing screening and diagnostic services among babies born in 2017 in 9 statesexternal icon
        Deng X, Ema S, Mason C, Nash A, Carbone E, Gaffney M.
        J Public Health Manag Pract. 2020 Sep 9.
        CONTEXT: By providing timely services at all steps along the continuum of the early hearing detection and intervention (EHDI) process, providers may be able to lessen potential adverse effects of late identification of hearing loss on children's language development. OBJECTIVE: To examine the timeliness of key events in the EHDI process from birth through diagnosis of hearing loss among different populations. DESIGN: Retrospective, cross-sectional. SETTING: Data pooled from 9 states' EHDI information systems were used to determine the extent to which timely screening and diagnosis were achieved by 754 613 infants born in calendar year 2017. Enrollment into early intervention for children diagnosed is not examined here due to incomplete data. PARTICIPANTS: Nine state EHDI programs were selected to participate in this study for their successful experience in using EHDI-IS to collect detailed child-level data. MAIN OUTCOME MEASURES: Age of service, rate of service receipt. RESULTS: Median age of newborn hearing screening was 1 day, and median age of hearing loss diagnosis was 68 days. Early completion of newborn hearing screening was associated with maternal education, maternal race/ethnicity, and admission into a neonatal intensive care unit (NICU). Receiving and completing follow-up diagnostic services were associated with maternal education, maternal race/ethnicity, age of screening, and enrollment into the Women, Infants, and Children program. CONCLUSIONS: Timely completion of the newborn hearing screening is achieved by most of the population among the participating states. Increased efforts may be considered by state EHDI programs to provide additional follow-up and education to underrepresented racial/ethnic groups, mothers with less education, and NICU infants and their families as these groups appear to be at an increased risk for delayed diagnostic testing for hearing loss.

      3. Assessing the relationship between neonatal abstinence syndrome and birth defects in Delawareexternal icon
        Hussaini KS, Drummond D, E. Bartoshesky L, Acheson A, Stomieroski K, A. Paul D, Kirby RS.
        Birth Defects Res. 2020 Sep 30.
        BACKGROUND: Neonatal abstinence syndrome (NAS) is a withdrawal syndrome in newborns and is frequently caused by maternal opioid use during pregnancy. Our study examines whether NAS is associated with birth defects in Delaware. METHODS: We conducted a retrospective analysis of linked Delaware birth certificate data (BCD), hospital discharge data (HDD), and birth defects registry (BDR) data to examine the association between NAS and birth defects for all hospital births to Delaware residents from 2010 to 2017. Birth defects data were abstracted from medical records from Delaware's BDR. We used International Classification of Diseases Ninth and Tenth Revision Clinical Modification (ICD-9-CM/ICD-10-CM) 779.5 and P96.1 codes to determine NAS using HDD and excluded iatrogenic cases of NAS. We estimated crude and adjusted odds ratio with 95% confidence intervals (CIs). RESULTS: During 2010-2017, there were 2,784 cases of birth defects and 1,651 cases of NAS in Delaware. Among infants with a diagnosis of NAS, 56 also had a birth defect (3.4%), similar to 2,728 birth defects among 79,636 infants without a diagnosis of NAS (3.4%). We found no statistically significant association between an NAS diagnosis and birth defects (adjusted odds ratios = 1.0; 95% CI: 0.8-1.3). CONCLUSIONS: Our multiyear state-wide study using linked BCD, HDD, and BDR data for Delaware did not show a statistically significant association between infants diagnosed with NAS and birth defects, overall.

      4. Kindergarten readiness in children who are deaf or hard of hearing who received early interventionexternal icon
        Meinzen-Derr J, Wiley S, Grove W, Altaye M, Gaffney M, Satterfield-Nash A, Folger AT, Peacock G, Boyle C.
        Pediatrics. 2020 Oct;146(4).
        BACKGROUND: Children who are deaf or hard of hearing (D/HH) have improved language outcomes when enrolled in early intervention (EI) before the age of 6 months. Little is understood about the long-term impact of EI on outcomes of kindergarten readiness (K-readiness). The study objective was to evaluate the impact of EI before the age of 6 months (early) versus after 6 months (later) on K-readiness in children who are D/HH. METHODS: In this study, we leveraged data from the Ohio Early Hearing Detection and Intervention Data Linkage Project, which linked records of 1746 infants identified with permanent hearing loss born from 2008 to 2014 across 3 Ohio state agencies; 417 had kindergarten records. The Kindergarten Readiness Assessment was used to identify children as ready for kindergarten; 385 had Kindergarten Readiness Assessment scores available. Multiple logistic regression was used to investigate the relationship between K-readiness and early EI entry while controlling for confounders (eg, hearing loss severity and disability status). RESULTS: Children who were D/HH and entered EI early (n = 222; 57.7% of the cohort) were more likely to demonstrate K-readiness compared with children who entered EI later (33.8% vs 20.9%; P = .005). Children who entered early had similar levels of K-readiness as all Ohio students (39.9%). After controlling for confounders, children who entered EI early were more likely to be ready for kindergarten compared with children who entered later (odds ratio: 2.02; 95% confidence interval 1.18-3.45). CONCLUSIONS: These findings support the sustained effects of early EI services on early educational outcomes among children who are D/HH. EI entry before the age of 6 months may establish healthy trajectories of early childhood development, reducing the risk for later academic struggles.

    • Mining
      1. Investigation of the anisotropic confinement-dependent brittleness of a Utah coalexternal icon
        Kim BH, Walton G, Larson MK, Berry S.
        Int J Coal Sci Technol. 2020 .
        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 an analysis published in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of 84 specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength 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, defined as the included angle. A total of four different included angles were used in the work performed in 2018. The authors found that the degree of anisotropic strength differed according to the included angle. 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. Because the authors already knew the most contrasting cases of the included angles from the previous work using the four included angles, they chose only two of the included angles (0° and 30°) for this study. For the triaxial compressive tests, a greater confining stress than the mean UCS was applied to the specimens in an attempt to identify the brittle-ductile transition of the coal. The new results have been compiled with the previous results in order to re-evaluate the confinement-dependency of the coal behavior. Additionally, the different confining stresses are used as analogs for different width-to-height (W/H) conditions 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.

    • Nutritional Sciences
      1. Distance and percentage distance from median BMI as alternatives to BMI z scoreexternal icon
        Freedman DS, Woo JG, Ogden CL, Xu JH, Cole TJ.
        Br J Nutr. 2020 Sep 14;124(5):493-500.
        BMI z (BMIz) score based on the Centers for Disease Control and Prevention growth charts is widely used, but it is inaccurate above the 97th percentile. We explored the performance of alternative metrics based on the absolute distance or % distance of a child's BMI from the median BMI for sex and age. We used longitudinal data from 5628 children who were first examined <12 years to compare the tracking of three BMI metrics: distance from median, % distance from median and % distance from median on a log scale. We also explored the effects of adjusting these metrics for age differences in the distribution of BMI. The intraclass correlation coefficient (ICC) was used to compare tracking of the metrics. Metrics based on % distance (whether on the original or log scale) yielded higher ICCs compared with distance from median. The ICCs of the age-adjusted metrics were higher than that of the unadjusted metrics, particularly among children who were (1) overweight or had obesity, (2) younger and (3) followed for >3 years. The ICCs of the age-adjusted metrics were also higher compared with that of BMIz among children who were overweight or obese. Unlike BMIz, these alternative metrics do not have an upper limit and can be used for assessing BMI in all children, even those with very high BMIs. The age-adjusted % from median (on a log or linear scale) works well for all ages, while unadjusted % from median is better limited to older children or short follow-up periods.

      2. Predictors of anaemia among adolescent schoolchildren of Ghanaexternal icon
        Gosdin L, Tripp K, Mahama AB, Quarshie K, Amoaful EF, Selenje L, Sharma D, Jefferds ME, Sharma AJ, Whitehead RD, Suchdev PS, Ramakrishnan U, Martorell R, Addo OY.
        J Nutr Sci. 2020 ;9:e43.
        Anaemia is a public health problem in Ghana. We sought to identify factors associated with haemoglobin concentration (Hb) and anaemia among school-attending adolescents. We analysed data from 2948 adolescent girls and 609 boys (10-19 years) selected from 115 schools from regions of Ghana as a secondary analysis of baseline surveys conducted at two time-points. We measured Hb, malaria from capillary blood, anthropometry and used a modified food frequency questionnaire to assess diet. Multivariable linear and Poisson regression models were used to identify predictors of Hb and anaemia. The prevalence of anaemia, malaria and geophagy were 24, 25, and 24 %, respectively, among girls and 13, 27 and 6 %, respectively, among boys. Girls engaging in geophagy had a 53 % higher adjusted prevalence of anaemia and 0⋅39 g/dl lower Hb. There were similar results among those who tested positive for malaria (+52 % anaemia; -0⋅42 g/dl Hb). Among girls, lower anaemia prevalence and higher Hb were associated with consumption of foods rich in haeme iron (-22 %; +0⋅18 g/dl), consumption of iron-fortified cereal/beverages consumed with citrus (-50 %; +0⋅37 g/dl) and being overweight (-22 %; +0⋅22 g/dl). Age was positively associated with anaemia among girls, but negatively associated among boys. Boys who tested positive for malaria had 0⋅31 g/dl lower Hb. Boys who were overweight or had obesity and consumed flour products were also more likely to be anaemic (119 and 56 %, respectively). Factors associated with Hb and anaemia may inform anaemia reduction interventions among school-going adolescents and suggest the need to tailor them uniquely for boys and girls.

      3. Meeting breastfeeding intentions differ by race/ethnicity, Infant and Toddler Feeding Practices Study-2external icon
        Hamner HC, Beauregard JL, Li R, Nelson JM, Perrine CG.
        Matern Child Nutr. 2020 Oct 1:e13093.
        Prenatal breastfeeding intentions impact breastfeeding practices. Racial/ethnic disparities exist in breastfeeding rates; it is unknown if prenatal intentions and meeting intentions differ by race/ethnicity. A longitudinal cohort of USDA's Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) which enrolled participants beginning in 2013 were used to estimate prenatal intentions for breastfeeding initiation, exclusive breast milk feeds at 1 and 3 months by race/ethnicity (n = 2070). Meeting intentions were determined by reported breast milk consumption at birth, 1 month and 3 months. Multivariable logistic regression was used to determine the association of race/ethnicity with meeting intentions. There were no differences in prenatal breastfeeding intentions between non-Hispanic White and non-Hispanic Black women (initiation: 86.9% and 87.2%; Month 1: 52.3% and 48.3%; Month 3: 43.8% and 40.9%; respectively), but a higher percentage of Hispanic women intended to breastfeed at all time points (95.5%, 68.3% and 56.4%; respectively, P < 0.05). Among women who intended to breastfeed at Month 1, non-Hispanic Black and Hispanic women had significantly lower odds of meeting intentions compared with non-Hispanic White women after adjusting for covariates (aORs: 0.63 [95% CI: 0.41, 0.98]; 0.64 [95% CI: 0.44, 0.92], respectively). Similar findings were seen for Month 3. Despite no differences in breastfeeding intentions, non-Hispanic Black women were less likely to meet their breastfeeding intentions than non-Hispanic White women. Hispanic women were more likely to intend to breastfeed yet were less likely to meet their intentions. This suggests that non-Hispanic Black and Hispanic women face challenges to meeting their longer breastfeeding intentions. Understanding how racism, bias and discrimination contribute to women not meeting their breastfeeding intentions may help efforts to reduce breastfeeding disparities.

    • Occupational Safety and Health
      1. Clinical decision support for worker health: A five-site qualitative needs assessment in primary care settingsexternal icon
        Ash JS, Chase D, Baron S, Filios MS, Shiffman RN, Marovich S, Wiesen J, Luensman GB.
        Appl Clin Inform. 2020 Aug;11(4):635-643.
        BACKGROUND:  Although patients who work and have related health issues are usually first seen in primary care, providers in these settings do not routinely ask questions about work. Guidelines to help manage such patients are rarely used in primary care. Electronic health record (EHR) systems with worker health clinical decision support (CDS) tools have potential for assisting these practices. OBJECTIVE:  This study aimed to identify the need for, and barriers and facilitators related to, implementation of CDS tools for the clinical management of working patients in a variety of primary care settings. METHODS:  We used a qualitative design that included analysis of interview transcripts and observational field notes from 10 clinics in five organizations. RESULTS:  We interviewed 83 providers, staff members, managers, informatics and information technology experts, and leaders and spent 35 hours observing. We identified eight themes in four categories related to CDS for worker health (operational issues, usefulness of proposed CDS, effort and time-related issues, and topic-specific issues). These categories were classified as facilitators or barriers to the use of the CDS tools. Facilitators related to operational issues include current technical feasibility and new work patterns associated with the coordinated care model. Facilitators concerning usefulness include users' need for awareness and evidence-based tools, appropriateness of the proposed CDS for their patients, and the benefits of population health data. Barriers that are effort-related include additional time this proposed CDS might take, and other pressing organizational priorities. Barriers that are topic-specific include sensitive issues related to health and work and the complexities of information about work. CONCLUSION:  We discovered several themes not previously described that can guide future CDS development: technical feasibility of the proposed CDS within commercial EHRs, the sensitive nature of some CDS content, and the need to assist the entire health care team in managing worker health.

      2. Health risk behavior profile of construction workers, 32 states, 2013 to 2016external icon
        Boal WL, Li J, Dong XS, Sussell A.
        J Occup Environ Med. 2020 Jul;62(7):493-502.
        BACKGROUND: Research has suggested that several health risk behaviors were more prevalent among construction workers than among the general workforce. METHODS: The prevalences of six health risk behaviors among construction workers were compared with workers in other industries using data from 32 states in the 2013 to 2016 Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: Smoking, smokeless tobacco use, binge drinking, no leisure-time physical activity, and not always using a seatbelt were significantly more prevalent (P < 0.001), and short sleep significantly less prevalent (P < 0.05), for all construction workers combined compared with workers in other industries. Prevalences varied substantially for all six health risk behaviors by construction occupation. CONCLUSIONS: Due to the high prevalence of some health risk behaviors, construction workers may benefit from interventions to reduce these behaviors, particularly since they are also potentially exposed to workplace hazards.

      3. Estimating trunk angle kinematics during lifting using a computationally efficient computer vision methodexternal icon
        Greene RL, Lu ML, Barim MS, Wang X, Hayden M, Hu YH, Radwin RG.
        Hum Factors. 2020 Sep 24.
        OBJECTIVE: A computer vision method was developed for estimating the trunk flexion angle, angular speed, and angular acceleration by extracting simple features from the moving image during lifting. BACKGROUND: Trunk kinematics is an important risk factor for lower back pain, but is often difficult to measure by practitioners for lifting risk assessments. METHODS: Mannequins representing a wide range of hand locations for different lifting postures were systematically generated using the University of Michigan 3DSSPP software. A bounding box was drawn tightly around each mannequin and regression models estimated trunk angles. The estimates were validated against human posture data for 216 lifts collected using a laboratory-grade motion capture system and synchronized video recordings. Trunk kinematics, based on bounding box dimensions drawn around the subjects in the video recordings of the lifts, were modeled for consecutive video frames. RESULTS: The mean absolute difference between predicted and motion capture measured trunk angles was 14.7°, and there was a significant linear relationship between predicted and measured trunk angles (R(2) = .80, p < .001). The training error for the kinematics model was 2.3°. CONCLUSION: Using simple computer vision-extracted features, the bounding box method indirectly estimated trunk angle and associated kinematics, albeit with limited precision. APPLICATION: This computer vision method may be implemented on handheld devices such as smartphones to facilitate automatic lifting risk assessments in the workplace.

      4. Biomechanical assessment while using production tables on mast climbing work platformsexternal icon
        Pan CS, Ning X, Wimer B, Zwiener J, Kau TY.
        Appl Ergon. 2020 Sep 25;90:103276.
        The objective of this study was to assess the impact of using alternative mast climbing work platform (MCWP) designs on trunk motion and postural stability with masonry workers while performing bricklaying and stepping down tasks using a conventional MCWP setting (i.e. with a step deck) as well as two types of production tables (straight- and L-shaped). The trunk angles and postural sway parameters of twenty-five masonry workers were recorded for the following tasks: (1) standing on a simulated MCWP and laying bricks on an adjacent wall, and (2) stepping down onto the step deck to get into position for doing the bricklaying task. Results indicated that the use of the L-shaped production table resulted in the lowest trunk ranges of motion and significantly reduced the workers' trunk angles in all three planes when compared to both the straight-shaped production table and the conventional approach of not using a production table. Data showed that both body sway velocity and area were significantly reduced when using either one of the production tables. The use of production tables significantly reduced impact sway forces when workers stepped from the main platform to the step deck. The use of production tables on MCWPs improved workers' postures and overall stability, which could reduce the risk of injury.

      5. BACKGROUND: Suicide is now the 10th leading cause of death in the United States. Suicide rates for health care providers are thought to be higher than for people in other occupations because of job strain and burnout. Despite the National Academy of Medicine's Action Collaborative on Clinician Well-Being and Resilience, which focuses on reducing stress and preventing suicide, a shortage of data limits our understanding of nurse suicide. Neither employers nor professional nursing associations track suicide data. PURPOSE: To determine the number of suicides and estimated rate of suicide among RNs, using data from the National Violent Death Reporting System (NVDRS). METHODS: We extracted data from the NVDRS, which is based on death certificates, coroner reports, and law enforcement reports, for the year 2015. The National Institute for Occupational Safety and Health's Industry and Occupation Computerized Coding System was used to code the data. Industry and occupation coding experts reviewed the coding for accuracy. RESULTS: Analysis of 2015 NVDRS data from 17 states showed that among civilian employed nurses ages 16 to 64 years, the estimated suicide rates for female and male nurses (11.4 and 29.3 per 100,000 nurses, respectively) were each higher than the rates for the comparable total population (8.2 and 26.1 per 100,000 people, respectively). CONCLUSIONS: Our findings indicate that RNs may die by suicide at higher rates than the total employed population in the 16-to-64-year age range. Implementation of evidence-based approaches to prevent suicide are warranted.

    • Occupational Safety and Health - Mining
      1. Accurately estimating load distributions and ground responses around underground openings plays a significant role in the safety of the operations in underground mines. Adequately designing pillars and other support measures relies highly on the accurate assessment of the mining-induced loads, as well as the load-bearing capacities of the supports. There are various methods that can be used to approximate mining-induced loads in stratified rock masses, both empirical and numerical. In this study, the numerical modeling approach recently developed at West Virginia University, which is based on the modeling approach developed by the National Institute for Occupational Safety and Health (NIOSH), is investigated using the finite difference software FLAC3D. The model includes the longwall panels, the adjacent chain pillar systems, and the different stratigraphic layers of the overburden. Using the 3D model, changes in loading conditions and deformations on the areas of interest, induced by an approaching longwall face, can be examined. This paper details the 3D modeling of a longwall panel utilizing this approach, and the verification of the results against field observations. The studied panel was 360 m wide with a 3-entry chain pillar system and about a 160-m average overburden depth around the studied area. The overburden strata consist of alternating layers of shale, sandstone, and limestone. The FLAC3D results were compared against field measurements from the mine site. The stress change values measured in the chain pillars were comparable with the modeling results. The model also replicated the surface subsidence profile obtained from field measurements fairly well. Overall, the 3D modeling approach was found to be successful for the case study longwall panel.

    • Parasitic Diseases
      1. Malaria case management and elimination readiness in health facilities of five districts of Madagascar in 2018external icon
        Anand A, Favero R, Dentinger C, Ralaivaomisa A, Ramamonjisoa S, Rabozakandraina O, Razafimandimby E, Razafindrakoto J, Wolf K, Steinhardt L, Gomez P, Rabary M, Andriamananjara MN, Mioramalala SA, Rakotovao JP.
        Malar J. 2020 Oct 1;19(1):351.
        BACKGROUND: Madagascar's Malaria National Strategic Plan 2018-2022 calls for progressive malaria elimination beginning in low-incidence districts (< 1 case/1000 population). Optimizing access to prompt diagnosis and quality treatment and improving outbreak detection and response will be critical to success. A malaria elimination readiness assessment (MERA) was performed in health facilities (HFs) of selected districts targeted for malaria elimination. METHODS: A mixed methods survey was performed in September 2018 in five districts of Madagascar. Randomly selected HFs were assessed for availability of malaria commodities and frequency of training and supervision conducted. Health providers (HPs) and community health volunteers (CHVs) were interviewed, and outpatient consultations at HFs were observed. To evaluate elimination readiness, a composite score ranging from 0 to 100 was designed from all study tools and addressed four domains: (1) resource availability, (2) case management (CM), (3) data management and use, and (4) training, supervision, and technical assistance; scores were calculated for each HF catchment area and district based on survey responses. Stakeholder interviews on malaria elimination planning were conducted at national, regional and district levels. RESULTS: A quarter of the 35 HFs surveyed had no rapid diagnostic tests (RDTs). Of 129 patients with reported or recorded fever among 300 consultations observed, HPs tested 56 (43%) for malaria. Three-quarters of the 35 HF managers reviewed data for trends. Only 68% of 41 HPs reported receiving malaria-specific training. Of 34 CHVs surveyed, 24% reported that treating fever was no longer among their responsibilities. Among treating CHVs, 13 (50%) reported having RDTs, and 11 (42%) had anti-malarials available. The average district elimination readiness score was 52 out of 100, ranging from 48 to 57 across districts. Stakeholders identified several challenges to commodity management, malaria CM, and epidemic response related to lack of training and funding disruptions. CONCLUSION: This evaluation highlighted gaps in malaria CM and elimination readiness in Madagascar to address during elimination planning. Strategies are needed that include training, commodity provision, supervision, and support for CHVs. The MERA can be repeated to assess progress in filling identified gaps and is a feasible tool that could be used to assess elimination targets in other countries.

      2. Establishing a national molecular surveillance program for the detection of Plasmodium falciparum markers of resistance to antimalarial drugs in Haitiexternal icon
        Hamre KE, Pierre B, Namuyinga R, Mace K, Rogier EW, Udhayakumar V, Boncy J, Lemoine JF, Chang MA.
        Am J Trop Med Hyg. 2020 Sep 28.
        Chloroquine remains the first-line treatment for uncomplicated malaria in Haiti, and until recently, sulfadoxine-pyrimethamine was the second-line treatment. A few studies have reported the presence of molecular markers for resistance in Plasmodium falciparum parasites, and in vivo therapeutic efficacy studies (TESs) have been limited. Recognizing the history of antimalarial resistance around the globe and the challenges of implementing TESs in low-endemic areas, the Ministry of Health established a surveillance program to detect molecular markers of antimalarial resistance in Haiti. Sentinel sites were purposefully selected in each of Haiti's 10 administrative departments; an 11th site was selected in Grand'Anse, the department with the highest number of reported cases. Factors considered for site selection included the number of malaria cases identified, observed skills of laboratory technicians conducting rapid diagnostic tests (RDTs), stock and storage conditions of RDTs, accuracy of data reporting to the national surveillance system, and motivation to participate. Epidemiologic data from 2,437 patients who tested positive for malaria from March 2016 to December 2018 and consented to provide samples for molecular sequencing are presented here. Of these, 936 (38.4%) patients reported self-treatment with any medication since the onset of their illness before diagnosis; overall, 69 (2.8%) patients reported taking an antimalarial. Ten patients (0.4%) reported travel away from their home for at least one night in the month before diagnosis. Establishing a molecular surveillance program for antimalarial drug resistance proved practical and feasible in a resource-limited setting and will provide the evidence needed to make informed treatment policy decisions at the national level.

      3. The use of serology for trachoma surveillance: Current status and priorities for future investigationexternal icon
        Martin DL, Saboyà-Díaz MI, Abashawl A, Alemayeh W, Gwyn S, Hooper PJ, Keenan J, Kalua K, Szwarcwald CL, Nash S, Oldenburg C, West SK, White M, Solomon AW.
        PLoS Negl Trop Dis. 2020 Sep;14(9):e0008316.

    • Reproductive Health

    • Statistics as Topic
      1. When observations are correlated, modeling the within-subject correlation structure using quantile regression for longitudinal data can be difficult unless a working independence structure is utilized. Although this approach ensures consistent estimators of the regression coefficients, it may result in less efficient regression parameter estimation when data are highly correlated. Therefore, several marginal quantile regression methods have been proposed to improve parameter estimation. In a longitudinal study some of the covariates may change their values over time, and the topic of time-dependent covariate has not been explored in the marginal quantile literature. As a result, we propose an approach for marginal quantile regression in the presence of time-dependent covariates, which includes a strategy to select a working type of time-dependency. In this manuscript, we demonstrate that our proposed method has the potential to improve power relative to the independence estimating equations approach due to the reduction of mean squared error.

    • Substance Use and Abuse
      1. Adolescent marijuana use and related risk behaviors, national findings from 2015 to 2017external icon
        Schauer GL, Clayton HB, Njai R, Grant AM.
        Am J Prev Med. 2020 Sep 22.
        INTRODUCTION: As policies legalizing nonmedical marijuana have increased in states, understanding the implications of marijuana use among adolescents is increasingly important. This study uses nationally representative data to assess behavioral risk factors among students with different patterns of marijuana use. METHODS: Data from the 2015 and 2017 Youth Risk Behavior Surveys, cross-sectional surveys conducted among a nationally representative sample of students in Grades 9-12 (n=30,389), were used to examine the association between self-reported current marijuana use status and self-report of 30 risk behaviors across 3 domains: substance use, injury/violence, and sexual health. Among current marijuana users, authors assessed differences between established (≥100 lifetime uses) and nonestablished (<100 uses) users. Multivariable models were used to calculate adjusted prevalence ratios. Data were analyzed in 2019. RESULTS: Current marijuana users (regardless of use pattern) had a significantly greater likelihood of engaging in 27 of the 30 behaviors assessed across the 3 domains than the noncurrent users. Those with established use patterns (versus nonestablished) had a greater risk of lifetime use of most other substances (licit and illicit, including tobacco, alcohol, heroin, misuse of opioids), some injury/violence behaviors (including driving while using marijuana and suicide ideation and attempt), and sexual risk behaviors. CONCLUSIONS: Both established and nonestablished patterns of adolescent marijuana use are associated with a number of other risky behaviors. In addition to interventions focused on preventing youth initiation of marijuana, clinicians and public health professionals should consider interventions to help adolescents who have nonestablished use patterns to avoid continued, established use.

    • Zoonotic and Vectorborne Diseases
      1. Metabolic response in patients with post-treatment Lyme disease symptoms/syndromeexternal icon
        Fitzgerald BL, Graham B, Delorey MJ, Pegalajar-Jurado A, Islam MN, Wormser GP, Aucott JN, Rebman AW, Soloski MJ, Belisle JT, Molins CR.
        Clin Infect Dis. 2020 Sep 25.
        BACKGROUND: Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of Lyme disease patients following antibiotic treatment. Biomarkers or specific clinical symptoms to identify PTLDS patients do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥ 6 months following antibiotic treatment for Lyme disease. METHODS: Untargeted liquid chromatography-mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included: 1) defining altered classes of metabolites; 2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different timepoints; 3) changes in the longitudinal abundance of metabolites; 4) linear discriminant analysis to evaluate robustness in a second patient cohort. RESULTS: This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple timepoints. The metabolites with differential abundance included those from glycerophospholipid, bile acid and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS vs non-PTLDS patients. Small numbers of metabolites (6-40) could be used to define PTLDS vs. non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients. CONCLUSIONS: These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.

      2. A heterogenous swine show circuit drives zoonotic transmission of influenza A viruses in the United Statesexternal icon
        Nelson MI, Perofsky A, McBride DS, Rambo-Martin BL, Wilson MM, Barnes JR, van Bakel H, Khan Z, Dutta J, Nolting JM, Bowman AS.
        J Virol. 2020 Sep 30.
        Influenza pandemics are associated with severe morbidity, mortality, and social and economic disruption. Every summer in the United States, youths attending agricultural fairs are exposed to genetically diverse influenza A viruses (IAVs) circulating in exhibition swine, resulting in over 450 lab-confirmed zoonotic infections since 2010. Exhibition swine represent a small, defined population (∼1.5% of the US herd), presenting a realistic opportunity to mitigate a pandemic threat by reducing IAV transmission in the animals themselves. Through intensive surveillance and genetic sequencing of IAVs in exhibition swine in six US states in 2018 (n = 212), we characterize how a heterogenous circuit of swine shows, comprised of fairs with different sizes and geographic coverage, facilitates IAV transmission among exhibition swine and into humans. Specifically, we identify the role of an early-season national show in the propagation and spatial dissemination of a specific virus (H1δ-2) that becomes dominant among exhibition swine and is associated with the majority of zoonotic infections in 2018. These findings suggest that a highly targeted mitigation strategy, such as postponing swine shows for 1-2 weeks following the early-season national show, could potentially reduce IAV transmission in exhibition swine and spillover into humans, and merits further study.IMPORTANCE The varying influenza A virus (IAV) exposure and infection status of individual swine facilitates introduction, transmission, and dissemination of diverse IAVs. Since agricultural fairs bring people into intimate contact with swine is provides a unique interface for zoonotic transmission of IAV. Understanding the transmission dynamics of IAV through exhibition swine is critical to mitigating the high incidence of variant IAV cases reported in association with agricultural fairs. We used genomic sequences from our exhibition swine surveillance to characterize the hemagglutinin and full genotypic diversity of IAV at early season shows and the subsequent dissemination through later season agricultural fairs. We were able to identify a critical time point with large implications for downstream IAV and zoonotic transmission. With improved understanding of evolutionary origins of zoonotic IAV, we can inform public health mitigation strategies to ultimately reduce zoonotic IAV transmission and risk of pandemic IAV emergence.

      3. Zika virus disease in Colombia - preliminary reportexternal icon
        Pacheco O, Beltrán M, Nelson CA, Valencia D, Tolosa N, Farr SL, Padilla AV, Tong VT, Cuevas EL, Espinosa-Bode A, Pardo L, Rico A, Reefhuis J, González M, Mercado M, Chaparro P, Martínez Duran M, Rao CY, Muñoz MM, Powers AM, Cuéllar C, Helfand R, Huguett C, Jamieson DJ, Honein MA, Ospina Martínez ML.
        N Engl J Med. 2020 Aug 6;383(6):e44.
        BACKGROUND: Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. In October 2015, an outbreak of ZVD was declared after laboratory-confirmed disease was identified in nine patients. METHODS: Using the national population-based surveillance system, we assessed patients with clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results and pregnancy outcomes were evaluated for a subgroup of pregnant women. Concurrently, we investigated reports of microcephaly for evidence of congenital ZVD. RESULTS: By April 2, 2016, there were 65,726 cases of ZVD reported in Colombia, of which 2485 (4%) were confirmed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay. The overall reported incidence of ZVD among female patients was twice that in male patients. A total of 11,944 pregnant women with ZVD were reported in Colombia, with 1484 (12%) of these cases confirmed on RT-PCR assay. In a subgroup of 1850 pregnant women, more than 90% of women who were reportedly infected during the third trimester had given birth, and no infants with apparent abnormalities, including microcephaly, have been identified. A majority of the women who contracted ZVD in the first or second trimester were still pregnant at the time of this report. Among the cases of microcephaly investigated from January 2016 through April 2016, four patients had laboratory evidence of congenital ZVD; all were born to asymptomatic mothers who were not included in the ZVD surveillance system. CONCLUSIONS: Preliminary surveillance data in Colombia suggest that maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus. However, the monitoring of the effect of ZVD on pregnant women in Colombia is ongoing. (Funded by Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

      4. Japanese encephalitis virus as cause of acute encephalitis, Bhutanexternal icon
        Wangchuk S, Tamang TD, Darnal JB, Pelden S, Lhazeen K, Mynak ML, Letson GW, Khare S, Leader BT, Marfin AA, Hills SL.
        Emerg Infect Dis. 2020 Sep;26(9):2239-2242.
        In 2011, Bhutan's Royal Centre for Disease Control began Japanese encephalitis (JE) surveillance at 5 sentinel hospitals throughout Bhutan. During 2011-2018, a total of 20 JE cases were detected, indicating JE virus causes encephalitis in Bhutan. Maintaining JE surveillance will help improve understanding of JE epidemiology in this country.

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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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