Volume 13, Issue 27, August 3, 2021

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CDC Science Clips: Volume 13, Issue 27, August 3, 2021

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

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  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Communicable Diseases
      • Black men who have sex with men living in states with HIV criminalization laws report high stigma, 23 U.S. cities, 2017external icon
        Baugher AR, Whiteman A, Jeffries WL, Finlayson T, Lewis R, Wejnert C.
        Aids. 2021 Aug 1;35(10):1637-1645.
        OBJECTIVES: To examine the association between HIV laws, perceived community stigma, and behaviors and to compare differences between and within Black and White men who have sex with men (MSM). DESIGN/METHODS: National HIV Behavioral Surveillance conducted interviews and HIV testing with MSM in 23 U.S. cities in 2017 using venue-based sampling methods. We used weighted cross-sectional data to compare MSM living in states with versus without HIV laws using Rao-Scott chi-square tests. We modeled the association between stigma and state HIV laws within racial groups to obtain adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs). RESULTS: Among 7392 MSM, 56% lived in a state with HIV laws. In law states, Black MSM were more likely than White MSM to report their community would discriminate against persons with HIV (PWH) (59 versus 34%), not support the rights of PWH (20 versus 9%), not be friends with PWH (19 versus 10%), believe PWH 'got what they deserved' (27 versus 16%), and be intolerant of MSM (14 versus 5%). Adjusted for confounders, Black MSM in HIV law states were more likely to think their community would discriminate against PWH (aPR, 1.14; 95% CI, 1.02-1.29; P = 0.02) and be intolerant toward MSM (aPR, 2.02; 95% CI, 1.43-2.86; P < 0.001) than Black MSM in states without such laws. CONCLUSIONS: HIV laws were related to higher stigma, but only for Black MSM. Future research regarding HIV-related laws should account for racial/ethnic disparities. Modernizing laws can delegitimize stigma and promote focusing on effective HIV prevention strategies.

      • Household Transmission of SARS-CoV-2 from Children and Adolescentsexternal icon
        Chu VT, Yousaf AR, Chang K, Schwartz NG, McDaniel CJ, Lee SH, Szablewski CM, Brown M, Drenzek CL, Dirlikov E, Rose DA, Villanueva J, Fry AM, Hall AJ, Kirking HL, Tate JE, Lanzieri TM, Stewart RJ.
        N Engl J Med. 2021 Jul 21.

    • Food Safety
    • Health Behavior and Risk
      • BACKGROUND: Approximately 8.8% of US high school students attended private schools in 2015. Few studies have characterized health risk behaviors among these students or compared prevalence of behaviors between students in private and public schools using a contemporary, nationally representative sample. METHODS: Pooled 2007-2017 national Youth Risk Behavior Survey data were used to estimate the prevalence of 35 health risk behaviors for 89,848 public and private high school students. Unadjusted prevalence ratios were used to compare prevalence by school type. Differences in behaviors by school type were explored by sex and grade. RESULTS: Among private school students, the prevalence ranged from 5.0% to 31.9% for sexual risk behaviors; from 0.8% to 30.1% for substance use behaviors; from 0.7% to 21.8% for behaviors related mental health and suicide; from 3.2% to 6.8% for violence victimization experiences; and from 3.1% to 52.9% for behaviors related to unhealthy diet and physical inactivity. Private school students were less likely than public school students to report most behaviors; differences by school type were generally consistent across sex and grade. CONCLUSIONS: Students in both public and private schools reported health risk behaviors. Findings might inform prevention activities by identifying behaviors to prioritize in each school setting.

    • Health Disparities
    • Immune System Disorders
      • BACKGROUND: While year-round exposure to pollen is linked to a large burden of allergic diseases, location-specific risk information on pollen types and allergy outcomes are limited. We characterize the relationship between acute exposure to tree, grass and weed pollen taxa and two allergy outcomes (allergic rhinitis physician visit and prescription allergy medication fill) across 28 metropolitan statistical areas (MSA) in the United States. METHODS: We obtained daily pollen data from National Allergy Bureau (NAB) monitors at these 28 MSAs for 2008-2015. We revised the NAB guidelines to classify taxa-specific pollen severity each day. Daily information on allergic rhinitis and prescribed allergy medications for individuals with employer-based health insurance from the IBM MarketScan Research database for these MSAs. We combined the daily pollen and health data for each MSA into a longitudinal dataset. We conducted a MSA-specific conditional quasi-Poisson regression analysis to assess how different levels of pollen concentration impact the health outcomes, controlling for local air pollution, meteorology and Influenza-like illness (ILI). We used a random effects meta-analysis to produce an overall risk estimate for each pollen type and health outcome. RESULTS: The seasonal distribution of pollen taxa and associated health impacts varied across the MSAs. Relative risk of allergic rhinitis visits increased as concentrations increased for all pollen types; relative risk of medication fills increased for tree and weed pollen only. We observed an increase in health risk even on days with moderate levels of pollen concentration. 7-day average concentration of pollen had stronger association with the health outcomes compared to the same-day measure. Controlling for air pollution and ILI had little impact on effect estimates. CONCLUSION: This analysis expands the catalogue of associations between different pollen taxa and allergy-related outcomes across multiple MSAs. The effect estimates we present can be used to project the burden of allergic disease in specific locations in the future as well inform patients with allergies on impending pollen exposure.

    • Injury and Violence
      • INTRODUCTION: Traumatic brain injury is a major cause of death and disability in the U.S., and research shows that individuals who suffer traumatic brain injury have an increased risk for suicide. This study examines the characteristics of suicide decedents with a documented traumatic brain injury history using a database containing circumstantial data on suicides and examines the differences in traumatic brain injury‒ and nontraumatic brain injury‒related suicides within the general population and within individuals with a history of military service. METHODS: Logistic regression models estimated AORs and 95% CIs of suicide among those with and without a previous traumatic brain injury using data from the 2003-2017 National Violent Death Reporting System (analyzed in 2020). RESULTS: From 2003 to 2017, a total of 203,157 suicide decedents were identified, and 993 had a documented traumatic brain injury before suicide. Among those with a documented traumatic brain injury, a higher percentage were White non-Hispanic. Firearm injuries were the most common method of suicide for both groups. Poisoning was more common among decedents with a previous traumatic brain injury than among those without. Male individuals, those who were single, and those who served in the military were 1.4 times more likely to have a documented traumatic brain injury history before the suicide. Almost 1 in 5 suicides (18.9%) documenting traumatic brain injury occurred among individuals with a history of military service. CONCLUSIONS: Comprehensive suicide prevention approaches are imperative. Healthcare providers can play a role in assessing and identifying patients at increased risk of suicide, including those who have experienced falls or injuries that often result in traumatic brain injury, and provide tailored interventions or referrals.

    • Laboratory Sciences
      • Lithium-ion battery explosion aerosols: Morphology and elemental compositionexternal icon
        Barone TL, Dubaniewicz TH, Friend SA, Zlochower IA, Bugarski AD, Rayyan NS.
        Aerosol Sci Technol. 2021 .
        Aerosols emitted by the explosion of lithium-ion batteries were characterized to assess potential exposures. The explosions were initiated by activating thermal runaway in three commercial batteries: (1) lithium nickel manganese cobalt oxide (NMC), (2) lithium iron phosphate (LFP), and (3) lithium titanate oxide (LTO). Post-explosion aerosols were collected on anodisc filters and analyzed by scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). The SEM and EDS analyses showed that aerosol morphologies and compositions were comparable to individual grains within the original battery materials for the NMC cell, which points to the fracture and ejection of the original battery components during the explosion. In contrast, the LFP cell emitted carbonaceous cenospheres, which suggests aerosol formation by the decomposition of organics within molten microspheres. LTO explosion aerosols showed characteristics of both types of emissions. The abundance of elements from the anode, cathode, and separator in respirable aerosols underscored the need for the selection of low-toxicity battery materials due to potential exposures in the event of battery thermal runaway. Copyright © This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.

      • Collective insights of public-private partnership impacts and sustainability: A qualitative analysisexternal icon
        Strasser S, Stauber C, Shrivastava R, Riley P, O'Quin K.
        PLoS One. 2021 ;16(7):e0254495.
        The global Coronavirus or COVID-19 pandemic exposed the weakness of healthcare systems including laboratory systems and is a call to action for unprecedented collaboration and partnerships to deal with the global crisis. The United States (U.S.) President's Emergency Plan for AIDS Relief (PEPFAR) establishes the global HIV/AIDS treatment agenda in alignment with the UNAIDS 90-90-90 treatment targets to achieve epidemic control related to enhanced testing, treatment, and viral suppression. A strategic PEPFAR priority area recognizes that large-scale collective efforts and sharing of resources bear greater potential impact for lasting change than any single organization or entity can achieve alone. An important vehicle utilized within the global public health context is the public-private partnership (PPP) model whereby multiple international organizations forge unified project charters to collectively reach mutually agreed goals. While touted as an ideal mechanism to synthesize resources and maximize gain in numerous applications, little is known from a seasoned stakeholder perspective regarding PPP implementation and sustainability issues. The purpose of this research is to holistically examine perceptions of PPP model sustainability related to inputs and impacts among a collective network of stakeholders experienced with PEPFAR workforce development, laboratory-system strengthening project implementation. Interviews were conducted with frontline stakeholders from public and private sector organizations based in the US and select PEPFAR-supported priority countries. Analysis revealed three dominant themes: PPP impacts, keys of successful collaboration, and logistical challenges and opportunities to enhance sustainability of PPP outcomes in the future.

    • Chronic Diseases and Conditions
      • Measuring Multimorbidity: Selecting the Right Instrument for the Purpose and the Data Sourceexternal icon
        Suls J, Bayliss EA, Berry J, Bierman AS, Chrischilles EA, Farhat T, Fortin M, Koroukian SM, Quinones A, Silber JH, Ward BW, Wei M, Young-Hyman D, Klabunde CN.
        Med Care. 2021 Aug 1;59(8):743-756.
        BACKGROUND: Adults have a higher prevalence of multimorbidity-or having multiple chronic health conditions-than having a single condition in isolation. Researchers, health care providers, and health policymakers find it challenging to decide upon the most appropriate assessment tool from the many available multimorbidity measures. OBJECTIVE: The objective of this study was to describe a broad range of instruments and data sources available to assess multimorbidity and offer guidance about selecting appropriate measures. DESIGN: Instruments were reviewed and guidance developed during a special expert workshop sponsored by the National Institutes of Health on September 25-26, 2018. RESULTS: Workshop participants identified 4 common purposes for multimorbidity measurement as well as the advantages and disadvantages of 5 major data sources: medical records/clinical assessments, administrative claims, public health surveys, patient reports, and electronic health records. Participants surveyed 15 instruments and 2 public health data systems and described characteristics of the measures, validity, and other features that inform tool selection. Guidance on instrument selection includes recommendations to match the purpose of multimorbidity measurement to the measurement approach and instrument, review available data sources, and consider contextual and other related constructs to enhance the overall measurement of multimorbidity. CONCLUSIONS: The accuracy of multimorbidity measurement can be enhanced with appropriate measurement selection, combining data sources and special considerations for fully capturing multimorbidity burden in underrepresented racial/ethnic populations, children, individuals with multiple Adverse Childhood Events and older adults experiencing functional limitations, and other geriatric syndromes. The increased availability of comprehensive electronic health record systems offers new opportunities not available through other data sources.

    • Occupational Safety and Health
      • Carbon monoxide exposures in wildland firefighters in the United States and targets for exposure reductionexternal icon
        Semmens EO, Leary CS, West MR, Noonan CW, Navarro KM, Domitrovich JW.
        J Expo Sci Environ Epidemiol. 2021 Jul 20.
        BACKGROUND: Every year thousands of wildland firefighters (WFFs) work to suppress wildfires to protect public safety, health, and property. Although much effort has been put toward mitigating air pollutant exposures for the public and WFFs, the current burden in this worker population is unclear as are the most effective exposure reduction strategies. OBJECTIVE: Quantify fireline carbon monoxide (CO) exposures in WFFs and identify predictors of exposures. METHODS: We collected 1-min breathing zone CO measurements on 246 WFFs assigned to fires between 2015 and 2017. We used generalized estimating equations to evaluate predictors of CO exposure. RESULTS: Approximately 5% of WFFs had fireline CO exposure means exceeding the National Wildfire Coordinating Group's occupational exposure limit of 16 ppm. Relative to operational breaks, direct suppression-related job tasks were associated with 56% (95% CI: 47%, 65%) higher geometric mean CO concentrations, adjusted for incident type, crew type, and fire location. WFF perception of smoke exposure was a strong predictor of measured CO exposure. SIGNIFICANCE: Specific job tasks related to direct suppression and WFF perceptions of smoke exposure are potential opportunities for targeted interventions aimed at minimizing exposure to smoke.

    • Substance Use and Abuse
      • Biomarkers of Inflammation and Oxidative Stress Among Adult Former Smoker, Current E-Cigarette Users Results from Wave 1 PATH Studyexternal icon
        Christensen CH, Chang JT, Rostron BL, Hammad HT, van Bemmel DM, Del Valle-Pinero AY, Wang B, Mishina EV, Faulcon LM, DePina A, Brown-Baker L, Kimmel HL, Lambert E, Blount BC, Vesper HW, Wang L, Goniewicz ML, Hyland A, Travers MJ, Hatsukami DK, Niaura R, Cummings KM, Taylor KA, Edwards KC, Borek N, Ambrose BK, Chang CM.
        Cancer Epidemiol Biomarkers Prev. 2021 Jul 21.
        BACKGROUND: Former smokers who currently use e-cigarettes have lower concentrations of biomarkers of tobacco toxicant exposure than current smokers. It is unclear whether tobacco toxicant exposure reductions may lead to health risk reductions. METHODS: We compared inflammatory biomarkers (high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1)) and an oxidative stress marker (F2-isoprostane) among 3,712 adult participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study by tobacco user groups: dual users of cigarettes and e-cigarettes; former smokers who currently use e-cigarettes-only; current cigarette-only smokers; former smokers who do not currently use any tobacco; and never tobacco users. We calculated geometric means (GMs) and estimated adjusted geometric mean ratios (GMRs). RESULTS: Dual users experienced greater concentration of F2-isoprostane than current cigarette-only smokers (GMR 1.09 [95%CI 1.03, 1.15]). Biomarkers were similar between former smokers who currently use e-cigarettes and both former smokers who do not use any tobacco and never tobacco users, but among these groups most biomarkers were lower than those of current cigarette-only smokers. The concentration of F2-isoprostane decreased by time since smoking cessation among both exclusive e-cigarette users (p-trend=0.03) and former smokers who do not currently use any tobacco (p-trend=0.0001). CONCLUSIONS: Dual users have greater concentration of F2-isoprostane than smokers. Exclusive e-cigarette users have biomarker concentrations that are similar to those of former smokers who do not currently use tobacco, and lower than those of exclusive cigarette smokers. IMPACT: This study contributes to an understanding of the health effects of e-cigarettes.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Cytokine profiles in children with acute intussusception in South Africaexternal icon
        Bessey TK, Parashar UD, Tate JE, Madhi SA, Jiang B, Groome MJ.
        Cytokine. 2021 Jul 17;146:155639.
        Serum specimens of children hospitalized with acute intussusception (IS; n = 407) were analyzed for various pro- and anti-inflammatory cytokines to identify host markers specifically for IS compared to other surgical conditions (n = 235) or acute gastroenteritis (AGE; n = 68) in a cross-sectional study design. We showed that children with IS had elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, MIP-1β, IL-1β, IL-2, IL-6, IL-7, IL-8, and IL-17 as well as anti-inflammatory cytokines IL-1RA, IL-4, IL-5, and IL-13 compared to those admitted with surgical conditions or AGE symptoms, indicating these cytokines as markers for IS. In addition, we showed an increase in C-reactive protein (CRP) levels in children with IS. This study is the first to show a broad cytokine profile and identify cytokine markers in children with IS.

      2. Prevalence of human papillomavirus genotypes in high-grade cervical precancer and invasive cervical cancer from cancer registries before and after vaccine introduction in the United Statesexternal icon
        Mix JM, Saraiya M, Thompson TD, Querec TD, Greek A, Tucker TC, Peters ES, Lynch CF, Hernandez BY, Copeland G, Goodman MT, Unger ER.
        Cancer. 2021 Jul 21.
        BACKGROUND: US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability. METHODS: Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type-specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors. RESULTS: A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers. CONCLUSIONS: The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

    • Communicable Diseases
      1. The 2020 Sturgis motorcycle rally resulted in widespread transmission of severe acute respiratory syndrome coronavirus 2 across the United States. At least 649 coronavirus disease 2019 cases were identified, including secondary and tertiary spread to close contacts. To limit transmission, persons attending events should be vaccinated or wear masks and practice physical distancing if unvaccinated. Persons with a known exposure should be managed according to their coronavirus disease 2019 vaccination or prior infection status and may include quarantine and coronavirus disease 2019 testing.

      2. Late Conditions Diagnosed 1-4 Months Following an Initial Coronavirus Disease 2019 (COVID-19) Encounter: A Matched-Cohort Study Using Inpatient and Outpatient Administrative Data-United States, 1 March-30 June 2020external icon
        Chevinsky JR, Tao G, Lavery AM, Kukielka EA, Click ES, Malec D, Kompaniyets L, Bruce BB, Yusuf H, Goodman AB, Dixon MG, Nakao JH, Datta SD, MacKenzie WR, Kadri SS, Saydah S, Giovanni JE, Gundlapalli AV.
        Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S5-s16.
        BACKGROUND: Late sequelae of COVID-19 have been reported; however, few studies have investigated the time course or incidence of late new COVID-19-related health conditions (post-COVID conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed type, association, and timing of post-COVID conditions following COVID-19 diagnosis. METHODS: Using the Premier Healthcare Database Special COVID-19 Release (release date, 20 October 2020) data, during March-June 2020, 27 589 inpatients and 46 857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted ORs were calculated to assess for late conditions that were more common in case-patients than control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31-120 days following a COVID-19 encounter. RESULTS: During 31-120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced ≥1 of 5 post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced ≥1 of 10 post-COVID conditions. During 31-60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and also more likely to experience a range of conditions affecting multiple body systems (eg, nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal symptoms) than outpatient control-patients. CONCLUSIONS: These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform healthcare practice and resource planning for follow-up COVID-19 care.

      3. Monitoring emerging HIV drug resistance in sub-Saharan Africa in the era of dolutegravirexternal icon
        da Silva J, Pals S, Chang J, Hackett S, Godfrey C, Raizes E.
        J Infect Dis. 2021 Jul 20.
        Dolutegravir-based regimens are now standard of care for HIV treatment for millions of people around Sub-Saharan Africa. To ensure its continued efficacy, monitoring of emerging drug resistance that inform a treatment strategy amongst those failing is crucial. Here we outline the plan by the President Emergence Plan for AIDS Relief to leverage viral load infra structure to implement effective drug resistance surveillance in the countries it supports.

      4. Role of Age in Spread of Influenza, 2011-2019, U.S. Influenza Vaccine Effectiveness Networkexternal icon
        Griggs EP, Flannery B, Foppa IM, Gaglani M, Murthy K, Jackson ML, Jackson LA, Belongia EA, McLean HQ, Martin ET, Monto AS, Zimmerman RK, Balasubramani GK, Chung JR, Patel M.
        Am J Epidemiol. 2021 Jul 16.
        Intra-season timing of influenza infection among persons of different ages could reflect relative contributions to propagation of seasonal epidemics and has not been examined among ambulatory patients. We calculated risk ratios derived from comparing weekly influenza cases pre-peak versus post-peak during the 2010-2011 through 2018-2019 influenza seasons using data from the US Influenza Vaccine Effectiveness network. We sought to determine age specific differences during the ascent versus the descent of a season by influenza virus types and subtypes. We estimated credible intervals around the risk ratios using Bayesian joint posterior sampling of weekly cases. Our population consisted of ambulatory patients with laboratory-confirmed influenza enrolled at five study sites during nine influenza seasons after the 2009 influenza A virus subtype H1N1 (H1N1) pandemic. We observed that young children aged <5 years tended to be more often infected with H1N1 during the pre-peak period while adults aged ≥65 years tended to be more often infected with H1N1 during the post-peak period. However, for influenza A virus subtype H3N2 children aged <5 years were more often infected during the post-peak period. These results may reflect a contribution of different age groups to seasonal spread, which may differ by influenza virus type and subtype.

      5. Changes in Emergency Medical Services Before and During the COVID-19 Pandemic in the United States, January 2018-December 2020external icon
        Handberry M, Bull-Otterson L, Dai M, Mann NC, Chaney E, Ratto J, Horiuchi K, Siza C, Kulkarni A, Gundlapalli AV, Boehmer TK.
        Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S84-s91.
        BACKGROUND: As a result of the continuing surge of coronavirus disease 2019 (COVID-19), many patients have delayed or missed routine screening and preventive services. Medical conditions, such as coronary heart disease, mental health issues, and substance use disorder, may be identified later, leading to increases in patient morbidity and mortality. METHODS: National Emergency Medical Services Information System data were used to assess 911 emergency medical services (EMS) activations during 2018-2020. For specific activation types, the percentage of total activations was calculated per week, and Joinpoint analysis was used to identify changes over time. RESULTS: Since March 2020, the number of 911 EMS activations has decreased, while the percentages of on-scene death, cardiac arrest, and opioid use/overdose EMS activations were higher than prepandemic levels. During the early pandemic period, percentages of total EMS activations increased for on-scene death (from 1.3% to 2.4% during weeks 11-15), cardiac arrest (from 1.3% to 2.2% during weeks 11-15), and opioid use/overdose (from 0.6% to 1.1% during weeks 8-18). The percentages then declined but remained above prepandemic levels through calendar week 52. CONCLUSIONS: The COVID-19 pandemic has indirect consequences, such as relative increases in EMS activations for cardiac events and opioid use/overdose, possibly linked to disruptions is healthcare access and health-seeking behaviors. Increasing telehealth visits and other opportunities for patient-provider touch points for chronic disease and substance use disorders that emphasize counseling, preventive care, and expanded access to medications can disrupt delayed care-seeking during the pandemic and potentially prevent premature death.

      6. Increasing sexually transmitted infections among adolescents in the USAexternal icon
        Leichliter JS, Haderxhanaj LT, Obafemi OA.
        Lancet Child Adolesc Health. 2021 Jul 15.

      7. Growth and Metabolic Changes After Antiretroviral Initiation in South African Childrenexternal icon
        Masi-Leone M, Arpadi S, Teasdale C, Yuengling KA, Mutiti A, Mogashoa M, Rivadeneira ED, Abrams EJ, Jao J.
        Pediatr Infect Dis J. 2021 Jul 20.
        BACKGROUND: Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV <12 years initiating World Health Organization recommended first-line antiretroviral therapy (ART) from 2012 to 2015. METHODS: Z scores for length-for-age (LAZ), weight-for-age (WAZ) and body mass index-for-age were calculated. Lipids (total cholesterol, low-density lipoprotein and high-density lipoprotein) were measured. Hemoglobin A1C ≥5.8 was defined as at risk for type 2 diabetes. Mixed effects models were used to assess the association of VL at ART initiation with Z scores and lipids over time. RESULTS: Of 241 CLHIV, 151 (63%) were <3 years initiating LPV/r-based ART and 90 (37%) were ≥3 years initiating EFV-based ART. Among CLHIV <3 years, higher VL at ART initiation was associated with lower mean LAZ (ß: -0.30, P=0.03), WAZ (ß: -0.32, P=0.01) and low-density lipoprotein (ß: -6.45, P=0.03) over time. Among CLHIV ≥3, a log 10 increase in pretreatment VL was associated with lower mean LAZ (ß: -0.29, P=0.07) trending towards significance and lower WAZ (ß: -0.32, P=0.05) as well as with more rapid increases in LAZ (ß: 0.14 per year, P=0.01) and WAZ (ß: 0.19 per year, P=0.04). Thirty percent of CLHIV were at risk for type 2 diabetes at ART initiation. CONCLUSIONS: CLHIV initiating ART <3 years exhibited positive gains in growth and lipids, though high viremia at ART initiation was associated with persistently low growth and lipids, underscoring the need for early diagnosis and rapid treatment initiation. Future studies assessing the long-term cardiometabolic impact of these findings are warranted.

      8. Delayed Tuberculosis Diagnoses During the Coronavirus Disease 2019 (COVID-19) Pandemic in 2020-King County, Washingtonexternal icon
        Narita M, Hatt G, Gardner Toren K, Vuong K, Pecha M, Jereb JA, Goswami ND.
        Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S74-s76.

      9. Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021external icon
        Olsen SJ, Winn AK, Budd AP, Prill MM, Steel J, Midgley CM, Kniss K, Burns E, Rowe T, Foust A, Jasso G, Merced-Morales A, Davis CT, Jang Y, Jones J, Daly P, Gubareva L, Barnes J, Kondor R, Sessions W, Smith C, Wentworth DE, Garg S, Havers FP, Fry AM, Hall AJ, Brammer L, Silk BJ.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 23;70(29):1013-1019.
        The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.

      10. Prevalence of SARS-CoV-2 Antibodies in New York City Adults, June-October 2020: A Population-Based Surveyexternal icon
        Parrott JC, Maleki AN, Vassor VE, Osahan S, Hsin Y, Sanderson M, Fernandez S, Levanon Seligson A, Hughes S, Wu J, DeVito AK, LaVoie SP, Rakeman JL, Gould LH, Alroy KA.
        J Infect Dis. 2021 Jul 15;224(2):188-195.
        BACKGROUND: Serosurveys help to ascertain burden of infection. Prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys in New York City (NYC) used nonrandom samples. During June-October 2020, the NYC Health Department conducted a population-based survey estimating SARS-CoV-2 antibody prevalence in NYC adults. METHODS: Participants were recruited from the NYC 2020 Community Health Survey. We estimated citywide and stratified antibody prevalence using a hybrid design: serum tested with the DiaSorin LIAISON SARS-CoV-2 S1/S2 IgG assay and self-reported antibody test results were used together. We estimated univariate frequencies and 95% confidence intervals (CI), accounting for complex survey design. Two-sided P values ≤ .05 were statistically significant. RESULTS: There were 1074 respondents; 497 provided blood and 577 provided only a self-reported antibody test result. Weighted prevalence was 24.3% overall (95% CI, 20.7%-28.3%). Latino (30.7%; 95% CI, 24.1%-38.2%; P < .01) and black (30.7%; 95% CI, 21.9%-41.2%; P = .02) respondents had a higher weighted prevalence compared with white respondents (17.4%; 95% CI, 12.5%-23.7%). CONCLUSIONS: By October 2020, nearly 1 in 3 black and 1 in 3 Latino NYC adults had SARS-CoV-2 antibodies, highlighting unequal impacts of the coronavirus disease 2019 (COVID-19) pandemic on black and Latino NYC adults.

      11. Optimizing Provider Preexposure Prophylaxis (PrEP) Training: A Cross-Sectional Analysis of Recommendations from Providers Across the PrEP Implementation Cascadeexternal icon
        Rao S, Reed AE, Parchem B, Edelman EJ, Magnus M, Hansen NB, Kershaw TS, Earnshaw VA, Krakower DS, Dovidio JF, Mayer KH, Underhill K, Rosenberger JG, Ogburn DF, Betancourt JR, Calabrese SK.
        AIDS Behav. 2021 Jul 21:1-14.
        Expanding PrEP access necessitates training that supports healthcare providers' progression along the PrEP implementation cascade, moving from PrEP awareness to prescription. We surveyed 359 USA providers about PrEP training content and format recommendations. We examined the association between cascade location and training recommendations. Most providers were aware of PrEP (100%), willing to prescribe PrEP (97.2%), had discussed PrEP with patients (92.2%), and had prescribed PrEP (79.9%). Latent class regression analysis revealed that cascade location was associated with training recommendations. Although all providers recommended PrEP-specific content (e.g., patient eligibility), providers who were located further along the cascade also recommended more comprehensive content, including sexual history-taking and sexual and gender minority competence training. Providers further along the cascade were also more likely to recommend interactive training formats (e.g., role-playing). These insights from providers furthest along the cascade indicate the importance of including comprehensive content and interactive formats in future PrEP training initiatives.

      12. Changes in Seasonal Respiratory Illnesses in the United States During the Coronavirus Disease 2019 (COVID-19) Pandemicexternal icon
        Rodgers L, Sheppard M, Smith A, Dietz S, Jayanthi P, Yuan Y, Bull L, Wotiz S, Schwarze T, Azondekon R, Hartnett K, Adjemian J, Kirking HL, Kite-Powell A.
        Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S110-s117.
        BACKGROUND: Respiratory tract infections are common, often seasonal, and caused by multiple pathogens. We assessed whether seasonal respiratory illness patterns changed during the COVID-19 pandemic. METHODS: We categorized emergency department (ED) visits reported to the National Syndromic Surveillance Program according to chief complaints and diagnosis codes, excluding visits with diagnosed SARS-CoV-2 infections. For each week during 1 March 2020 through 26 December 2020 ("pandemic period"), we compared the proportion of ED visits in each respiratory category with the proportion of visits in that category during the corresponding weeks of 2017-2019 ("pre-pandemic period"). We analyzed positivity of respiratory viral tests from 2 independent clinical laboratories. RESULTS: During March 2020, cough, shortness of breath, and influenza-like illness accounted for twice as many ED visits compared with the pre-pandemic period. During the last 4 months of 2020, all respiratory conditions, except shortness of breath, accounted for a smaller proportion of ED visits than during the pre-pandemic period. Percent positivity for influenza virus, respiratory syncytial virus, human parainfluenza virus, adenoviruses, and human metapneumovirus was lower in 2020 than 2019. Although test volume decreased, percent positivity was higher for rhinovirus/enterovirus during the final weeks of 2020 compared with 2019, with ED visits similar to the pre-pandemic period. CONCLUSIONS: Broad reductions in respiratory test positivity and respiratory ED visits (excluding COVID-19) occurred during 2020. Interventions for mitigating spread of SARS-CoV-2 likely also reduced transmission of other pathogens. Timely surveillance is needed to understand community health threats, particularly when current trends deviate from seasonal norms.

      13. Performance of Repeat BinaxNOW Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Testing in a Community Setting, Wisconsin, November 2020-December 2020external icon
        Shah MM, Salvatore PP, Ford L, Kamitani E, Whaley MJ, Mitchell K, Currie DW, Morgan CN, Segaloff HE, Lecher S, Somers T, Van Dyke ME, Bigouette JP, Delaney A, DaSilva J, O'Hegarty M, Boyle-Estheimer L, Abdirizak F, Karpathy SE, Meece J, Ivanic L, Goffard K, Gieryn D, Sterkel A, Bateman A, Kahrs J, Langolf K, Zochert T, Knight NW, Hsu CH, Kirking HL, Tate JE.
        Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S54-s57.
        Repeating the BinaxNOW antigen test for severe acute respiratory syndrome coronavirus 2 using 2 groups of readers within 30 minutes resulted in high concordance (98.9%) in 2110 encounters. Same-day repeat antigen testing did not significantly improve test sensitivity (77.2% to 81.4%) while specificity remained high (99.6%).

      14. Sexually Transmitted Infections Treatment Guidelines, 2021external icon
        Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA.
        MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.
        These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

    • Disease Reservoirs and Vectors
      1. Cross-sectional study and genotyping of rotavirus-A infections in ruminants in Kuwaitexternal icon
        Abdou NM, Majeed QA, Saad AA, Mijatovic-Rustempasic S, Bowen MD, Samy A.
        BMC Vet Res. 2021 Jul 17;17(1):245.
        BACKGROUND: Group A rotaviruses (RVA) are zoonotic pathogens responsible for acute enteritis in human and neonatal ruminants. This research aimed to determine the prevalence of RVA in ruminants (cattle, sheep, and goats) and investigate the circulating RVA genotypes in these animals in Kuwait. We conducted a cross-sectional study to detect RVA in ruminants, using an immunochromatography test (IC), direct sandwich ELISA test, and real-time RT-PCR (RT-qPCR) assay using fecal samples. RESULTS: A total of 400 cattle, 334 sheep, and 222 goats were examined. The prevalence of RVA was 5.3, 1.2, and 2.3%, respectively, using IC. The ELISA test detected RVA from 4.3% of cattle, 0.9% of sheep, and 1.8% of goats. There was a significant association between the occurrence of diarrhea and the presence of RVA in bovine fecal samples (p-value = 0.0022), while no statistical association between diarrhea and the presence of RVA in fecal samples of sheep and goats was observed (p-value = 0.7250; p-value = 0.4499, respectively). Twenty-three of the IC-positive samples (17 from cattle, two from sheep, and four from goats) were tested using a RT-qPCR RVA detection assay targeting the NSP3 gene. The results showed that 21 of 23 IC-positive samples tested positive by RT-qPCR. Detection of RVA genotypes revealed that G10P[11] was the predominant strain in cattle (58.8%), followed by G8P[1] (11.7%). One sheep sample was genotyped as G8P[1]. In addition, G6P[1] and G6P[14] were detected in goat samples. CONCLUSION: The present study revealed that the IC was more sensitive in detecting RVA antigen in fecal samples than the ELISA test. A higher occurrence of RVA infection was observed in cattle than in sheep and goats. This study suggests that RVA might be a risk factor of diarrhea in bovine calves less than 2 weeks old. This research also demonstrates the circulation of RVA in sheep and goat populations in Kuwait. Finally, the G10P[11] RVA genotype was the most prevalent genotype identified from cattle samples.

      2. Aedes aegypti Identified in York, Nebraska, Through Routine Arboviral Surveillance-August-October 2019external icon
        Donahue MA, Hamik J, Phinney S, Schneider R, McDougall L, Koirala S, Buss B.
        J Am Mosq Control Assoc. 2021 Jun 1;37(2):106-108.
        On August 27, 2019, Aedes aegypti mosquitoes were identified in a neighborhood located in York, NE, through routine arboviral surveillance. Expanded surveillance using traps and morphologic identification revealed 118 adult Ae. aegypti throughout the adjacent neighborhood, including identification from larval sampling. Our findings describe the first recorded Ae. aegypti introduction in Nebraska and provide evidence of a breeding mosquito population, which suggests suitable habitat and the risk of potential establishment, raising concerns about prevention of arboviral diseases in Nebraska.

      3. Modeling future climate suitability for the western blacklegged tick, Ixodes pacificus, in California with an emphasis on land access and ownershipexternal icon
        Hahn MB, Feirer S, Monaghan AJ, Lane RS, Eisen RJ, Padgett KA, Kelly M.
        Ticks Tick Borne Dis. 2021 Jul 13;12(5):101789.
        In the western United States, Ixodes pacificus Cooley & Kohls (Acari: Ixodidae) is the primary vector of the agents causing Lyme disease and granulocytic anaplasmosis in humans. The geographic distribution of the tick is associated with climatic variables that include temperature, precipitation, and humidity, and biotic factors such as the spatial distribution of its primary vertebrate hosts. Here, we explore (1) how climate change may alter the geographic distribution of I. pacificus in California, USA, during the 21(st) century, and (2) the spatial overlap among predicted changes in tick habitat suitability, land access, and ownership. Maps of potential future suitability for I. pacificus were generated by applying climate-based species distribution models to a multi-model ensemble of climate change projections for the Representative Concentration Pathway (RCP) 4.5 (moderate emission) and 8.5 (high emission) scenarios for two future periods: mid-century (2026-2045) and end-of-century (2086-2099). Areas climatically-suitable for I. pacificus are projected to expand by 23% (mid-century RCP 4.5) to 86% (end-of-century RCP 8.5) across California, compared to the historical period (1980-2014), with future estimates of total suitable land area ranging from about 88 to 133 thousand km(2), or up to about a third of California. Regions projected to have the largest area increases in suitability by end-of-century are in northwestern California and the south central and southern coastal ranges. Over a third of the future suitable habitat is on lands currently designated as open access (i.e. publicly available), and by 2100, the amount of these lands that are suitable habitat for I. pacificus is projected to more than double under the most extreme emissions scenario (from ~23,000 to >51,000 km(2)). Of this area, most is federally-owned (>45,000 km(2)). By the end of the century, 26% of all federal land in the state is predicted to be suitable habitat for I. pacificus. The resulting maps may facilitate regional planning and preparedness by informing public health and vector control decision-makers.

      4. Crossroads of highly pathogenic H5N1: Overlap between wild and domestic birds in the Black Sea-Mediterranean impacts global transmissionexternal icon
        Hill NJ, Smith LM, Muzaffar SB, Nagel JL, Prosser DJ, Sullivan JD, Spragens KA, Demattos CA, Demattos CC, El Sayed L, Erciyas-Yavuz K, Davis CT, Jones J, Kis Z, Donis RO, Newman SA, Takekawa JY.
        Virus Evolution. 2021 ;7(1).
        Understanding transmission dynamics that link wild and domestic animals is a key element of predicting the emergence of infectious disease, an event that has highest likelihood of occurring wherever human livelihoods depend on agriculture and animal trade. Contact between poultry and wild birds is a key driver of the emergence of highly pathogenic avian influenza (HPAI), a process that allows for host switching and accelerated reassortment, diversification, and spread of virus between otherwise unconnected regions. This study addresses questions relevant to the spillover of HPAI at a transmission hotspot: what is the nature of the wild bird-poultry interface in Egypt and adjacent Black Sea-Mediterranean countries and how has this contributed to outbreaks occurring worldwide? Using a spatiotemporal model of infection risk informed by satellite tracking of waterfowl and viral phylogenetics, this study identified ecological conditions that contribute to spillover in this understudied region. Results indicated that multiple ducks (Northern Shoveler and Northern Pintail) hosted segments that shared ancestry with HPAI H5 from both clade 2.2.1 and clade 2.3.4 supporting the role of Anseriformes in linking viral populations in East Asia and Africa over large distances. Quantifying the overlap between wild ducks and H5N1-infected poultry revealed an increasing interface in late winter peaking in early spring when ducks expanded their range before migration, with key differences in the timing of poultry contact risk between local and long-distance migrants. Copyright © 2020 Published by Oxford University Press 2020. This work is written by a US Government employee and is in the public domain in the US.

      5. A Survey of Tick Surveillance and Control Practices in the United Statesexternal icon
        Mader EM, Ganser C, Geiger A, Harrington LC, Foley J, Smith RL, Mateus-Pinilla N, Teel PD, Eisen RJ.
        J Med Entomol. 2021 Jul 16;58(4):1503-1512.
        Tickborne diseases are an increasing public health threat in the United States. Prevention and diagnosis of tickborne diseases are improved by access to current and accurate information on where medically important ticks and their associated human and veterinary pathogens are present, their local abundance or prevalence, and when ticks are actively seeking hosts. The true extent of tick and tickborne pathogen expansion is poorly defined, in part because of a lack of nationally standardized tick surveillance. We surveyed 140 vector-borne disease professionals working in state, county, and local public health and vector control agencies to assess their 1) tick surveillance program objectives, 2) pathogen testing methods, 3) tick control practices, 4) data communication strategies, and 5) barriers to program development and operation. Fewer than half of respondents reported that their jurisdiction was engaged in routine, active tick surveillance, but nearly two-thirds reported engaging in passive tick surveillance. Detection of tick presence was the most commonly stated current surveillance objective (76.2%). Most of the programs currently supporting tick pathogen testing were in the Northeast (70.8%), Upper and Central Midwest (64.3%), and the West (71.4%) regions. The most common pathogens screened for were Rickettsia spp. (Rickettsiales: Rickettsiaceae) and bacterial and viral agents transmitted by Ixodes (Acari: Ixodidae) ticks. Only 12% of respondents indicated their jurisdiction directly conducts or otherwise financially supports tick control. Responses indicated that their ability to expand the capacity of tick surveillance and control programs was impeded by inconsistent funding, limited infrastructure, guidance on best practices, and institutional capacity to perform these functions.

      6. The community-wide effectiveness of municipal larval control programs for West Nile virus risk reduction in Connecticut, United Statesexternal icon
        McMillan JR, Harden CA, Burtis JC, Breban MI, Shepard JJ, Petruff TA, Misencik MJ, Bransfield AB, Poggi JD, Harrington LC, Andreadis TG, Armstrong PM.
        Pest Manag Sci. 2021 Jul 16.
        BACKGROUND: Mosquito larval control through the use of insecticides is the most common strategy for suppressing West Nile virus (WNV) vector populations in Connecticut (CT), United States. To evaluate the ability of larval control to reduce entomological risk metrics associated with WNV, we performed WNV surveillance and assessments of municipal larvicide application programs in Milford and Stratford, CT in 2019 and 2020. Each town treated catch basins and non-basin habitats (Milford only) with biopesticide products during both WNV transmission seasons. Adult mosquitoes were collected weekly with gravid and CO(2) -baited light traps and tested for WNV; larvae and pupae were sampled weekly from basins within 500 m of trapping sites, and Culex pipiens larval mortality was determined with lab bioassays of catch basin water samples. RESULTS: Declines in 4th instar larvae and pupae were observed in catch basins up to 2-weeks post-treatment, and we detected a positive relationship between adult female Cx. pipiens collections in gravid traps and pupal abundance in basins. We also detected a significant difference in total light trap collections between the two towns. Despite these findings, Cx. pipiens adult collections and WNV mosquito infection prevalence in gravid traps were similar between towns. CONCLUSION: Larvicide applications reduced pupal abundance and the prevalence of host-seeking adults with no detectable impact on entomological risk metrics for WNV. Further research is needed to better determine the level of mosquito larval control required to reduce WNV transmission risk. This article is protected by copyright. All rights reserved.

    • Environmental Health
      1. Heat-Related Emergency Department Visits During the Northwestern Heat Wave - United States, June 2021external icon
        Schramm PJ, Vaidyanathan A, Radhakrishnan L, Gates A, Hartnett K, Breysse P.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 23;70(29):1020-1021.
        Record high temperatures are occurring more frequently in the United States, and climate change is causing heat waves to become more intense (1), directly impacting human health, including heat-related illnesses and deaths. On average, approximately 700 heat-related deaths occur in the United States each year (2). In the northwestern United States, increasing temperatures are projected to cause significant adverse health effects in the coming years (3). During June 25-30, 2021, most of Oregon and Washington were under a National Weather Service excessive heat warning.* Hot conditions persisted in parts of Oregon, Washington, or Idaho through at least July 14, 2021. The record-breaking heat had the largest impact in Oregon and Washington, especially the Portland metropolitan area, with temperatures reaching 116°F (46.7°C), which is 42°F (5.6°C) hotter than the average daily maximum June temperature.

    • Genetics and Genomics
      1. BACKGROUND AND AIMS: Information is limited regarding hepatitis B virus (HBV) genotype and the outcome of chronic HBV (CHB) infection. We examined HBV genotype on hepatocellular carcinoma (HCC) occurrence in Alaska Native (AN) persons with CHB where five HBV genotypes are found, A2, B6, C2, D and F1. APPROACH AND RESULTS: We calculated HCC incidence per 1000 person-years of follow-up to determine which groups by age, sex, and genotype met current American Association for the Study of Liver Diseases HCC surveillance criteria. We used Poisson regression to compare HCC risk by genotype, age, sex, and Alaska region. Incidence of HCC was calculated using the sex specific AASLD cutoff recommended for the Asian population of 50 years for women and 40 years for men. HCC screening was conducted semiannually using alpha-fetoprotein levels and abdominal ultrasound. Among 1185 AN persons, median follow up was 35.1 years; 667 (63%) were male. The HBV genotype distribution was: 49% D, 18% F, 13% A, 6% C, 3% B, 0.1% H, and 12% undetermined. Sixty-three cases of HCC occurred. HCC incidence for genotype F was 5.73 per 1000 person-years of follow-up, followed by 4.77 for C, 1.28 for A, 0.47 for D and 0.00 for B. The HCC risk was higher for genotypes F (Relative rate [RR] : 12.7, 95% confidence interval [CI]: 6.1-26.4) , C (RR: 10.6, 95% CI: 4.3-26.0) and A (RR: 2.9, 95% CI: 1.0-8.0) compared to genotypes B or D. Among males < 40 years of age and females < 50 years of age, genotype F had the highest incidence (4.79/1000 person-years). CONCLUSIONS: HBV genotype was strongly associated with HCC HBV genotype should be considered in risk factor stratification.

      2. Detection and identification of Giardia species using real-time PCR and sequencingexternal icon
        Narayanan J, Murphy JL, Hill VR.
        J Microbiol Methods. 2021 Jul 13:106279.
        We report a specific region of Giardia spp. 18S ribosomal RNA (18S rDNA) that serves as an ideal target for quantitative PCR (qPCR) detection and sequencing to identify Giardia species, including the clinically-relevant G. duodenalis, in clinical and environmental samples. The presence of multiple copies of the 18S rDNA gene and variations in the selected 18S genomic region enabled the development of a rapid, sensitive qPCR screening method for the detection of Giardia spp. The analytical sensitivity of the Giardia qPCR assay was determined to be a cyst equivalent of 0.4 G. duodenalis cysts per PCR reaction. Amplicon sequencing of the PCR product confirmed Giardia spp. detection and among the 35 sequences obtained, 31, 3 and 1 isolates were classified as belonging to G. duodenalis, G. microti and G. muris, respectively. The TaqMan assay reported here may be useful for the detection of low levels of Giardia in clinical and environmental samples, and further enables the effective use of direct sequencing of the PCR product for Giardia confirmation and to identify major species of Giardia, including G. duodenalis.

      3. Genomic Diversity of Haemophilus influenzae Serotype a in an Outbreak Community, Alaska 2018external icon
        Nolen LD, DeByle C, Topaz N, Simons BC, Tiffany A, Reasonover A, Castrodale L, McLaughlin J, Klejka J, Wang X, Bruce M.
        J Infect Dis. 2021 Jul 16.
        BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, four invasive Hia cases occurred in an Alaska community. We used whole-genome sequencing (WGS) to evaluate the relationship of the bacteria from this community and other Alaska patients with invasive Hia. METHODS: All carriage (15) and invasive (4) Hia isolates from the outbreak community, together with 15 non-outbreak Alaska invasive Hia surveillance isolates from 2018, were tested for antimicrobial susceptibility and characterized using WGS. RESULTS: Phylogenetic analysis of both invasive and carriage Hia isolates revealed two major clades that differed by an average of 300 core single nucleotide polymorphisms (SNPs). All isolates from the outbreak community were clustered in one subclade, within a larger clade containing 3 non-outbreak invasive Hia isolates. Comparative genomics did not reveal any genetic mutations that distinguished carriage from invasive isolates. Three (20%) community isolates were rifampin-resistant and had a previously unreported mutation in the rpoB gene. CONCLUSIONS: In the outbreak community, Hia isolates from carriers were indistinguishable from the invasive Hia isolates. Overall, invasive Hia isolates from Alaska in 2018 were genetically similar. The rifampin resistance mutation is concerning as rifampin is the first-line medication for Hia prophylaxis.

      4. Identification of Prognostic and Chemopredictive microRNAs for Non-Small-Cell Lung Cancer by Integrating SEER-Medicare Dataexternal icon
        Ye Q, Putila J, Raese R, Dong C, Qian Y, Dowlati A, Guo NL.
        Int J Mol Sci. 2021 Jul 17;22(14).
        This study developed a novel methodology to correlate genome-scale microRNA (miRNA) expression profiles in a lung squamous cell carcinoma (LUSC) cohort (n = 57) with Surveillance, Epidemiology, and End Results (SEER)-Medicare LUSC patients (n = 33,897) as a function of composite tumor progression indicators of T, N, and M cancer stage and tumor grade. The selected prognostic and chemopredictive miRNAs were extensively validated with miRNA expression profiles of non-small-cell lung cancer (NSCLC) patient samples collected from US hospitals (n = 156) and public consortia including NCI-60, The Cancer Genome Atlas (TCGA; n = 1016), and Cancer Cell Line Encyclopedia (CCLE; n = 117). Hsa-miR-142-3p was associated with good prognosis and chemosensitivity in all the studied datasets. Hsa-miRNA-142-3p target genes (NUP205, RAN, CSE1L, SNRPD1, RPS11, SF3B1, COPA, ARCN1, and SNRNP200) had a significant impact on proliferation in 100% of the tested NSCLC cell lines in CRISPR-Cas9 (n = 78) and RNA interference (RNAi) screening (n = 92). Hsa-miR-142-3p-mediated pathways and functional networks in NSCLC short-term survivors were elucidated. Overall, the approach integrating SEER-Medicare data with comprehensive external validation can identify miRNAs with consistent expression patterns in tumor progression, with potential implications for prognosis and prediction of chemoresponse in large NSCLC patient populations.

    • Health Economics
      1. PURPOSE: The Michigan Department of Health and Human Services, in collaboration with St. John Providence Health System, initiated voluntary school-wide sexually transmitted disease (STD) screenings in four Detroit public high schools. We sought to assess the cost-effectiveness of the STD screening program from 2010 to 2015, with a focus on chlamydia. METHODS: The costs and effectiveness of the school-based screening were compared with those of a "no school screening" scenario using a healthcare system perspective. A decision tree model was constructed to project cases of chlamydia, epididymitis, and pelvic inflammatory disease (PID) in each of the two scenarios among students tested positive and their partners. Health effects were measured as cases of PID prevented, and quality-adjusted life-years (QALYs) gained. Cost estimates included program costs, chlamydia testing/treatment costs in the absence of school screening, and treatment costs for epididymitis, PID, and PID sequelae. The incremental cost-effectiveness ratio (ICER) was measured as cost/QALY gained. Multivariate sensitivity analyses were conducted on key parameter estimates and assumptions used. RESULTS: Under base-case assumptions, at a total program cost of $333,848 over 5 years, the program prevented an estimated 1.9 cases of epididymitis and 17.3 cases of PID, resulting in an ICER of $38,235/QALY gained (yearly ICER ranging from $27,417 to $50,945/QALY). Of 10,000 Monte Carlo simulation runs, the yearly ICER remained ≤$50,000/QALY in 64%-98% of the simulation runs. CONCLUSIONS: We found favorable cost-effectiveness ratios for Michigan's school-wide STD screening program in Detroit. School-based STD screening programs of this type warrant careful considerations by policy makers and program planners.

    • Healthcare Associated Infections
      1. With this survey, we investigated healthcare-associated invasive mold infection (HA-IMI) surveillance and air sampling practices in US acute-care hospitals. More than half of surveyed facilities performed HA-IMI surveillance and air sampling. HA-IMI surveillance was more commonly performed in academic versus nonacademic facilities. HA-IMI case definitions and sampling strategies varied widely among respondents.

      2. Notes from the Field: Transmission of Pan-Resistant and Echinocandin-Resistant Candida auris in Health Care Facilities - Texas and the District of Columbia, January-April 2021external icon
        Lyman M, Forsberg K, Reuben J, Dang T, Free R, Seagle EE, Sexton DJ, Soda E, Jones H, Hawkins D, Anderson A, Bassett J, Lockhart SR, Merengwa E, Iyengar P, Jackson BR, Chiller T.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 23;70(29):1022-1023.

      3. Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studiesexternal icon
        Sharma A, Luvsansharav UO, Paul P, Lutgring JD, Call DR, Omulo S, Laserson K, Araos R, Munita JM, Verani J, Chowdhury F, Muneer SM, Espinosa-Bode A, Ramay B, Cordon-Rosales C, Kumar CP, Bhatnagar T, Gupta N, Park B, Smith RM.
        BMC Public Health. 2021 Jul 16;21(1):1412.
        BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

    • Immunity and Immunization
      1. Persistence of Maternal Anti-Rotavirus Immunoglobulin G in the Post-Rotavirus Vaccine Eraexternal icon
        Payne DC, McNeal M, Staat MA, Piasecki AM, Cline A, DeFranco E, Goveia MG, Parashar UD, Burke RM, Morrow AL.
        J Infect Dis. 2021 Jul 2;224(1):133-136.
        To assess whether titers of anti-rotavirus immunoglobulin G persist during the post-rotavirus vaccine era, the Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) Cohort analyzed serum samples collected from Cincinnati-area mothers and young infants in 2017-2018. Rotavirus-specific antibodies continue to be transferred from US mothers to their offspring in the post-rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

      2. Important Considerations for COVID-19 Vaccination of Children With Developmental Disabilitiesexternal icon
        Tinker SC, Cogswell ME, Peacock G, Ryerson AB.
        Pediatrics. 2021 Jul 16.

    • Laboratory Sciences
      1. Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survivalexternal icon
        De La Cruz JA, Ganesh T, Diebold BA, Cao W, Hofstetter A, Singh N, Kumar A, McCoy J, Ranjan P, Smith SM, Sambhara S, Lambeth JD, Gangappa S.
        PLoS One. 2021 ;16(7):e0254632.
        Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.

      2. Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to contemporary EV-D68 isolatesexternal icon
        Freeman MC, Wells AI, Ciomperlik-Patton J, Myerburg MM, Yang L, Konopka-Anstadt J, Coyne CB.
        Elife. 2021 Jul 1;10.
        Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and is associated with acute flaccid myelitis (AFM). EV-D68 is often detected in patient respiratory samples but has also been detected in stool and wastewater, suggesting the potential for both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical pre-2014 isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with earlier isolates and that the respiratory, but not intestinal, epithelium induces a robust type III interferon response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that a subset of isolates have the potential to target both the human airway and gastrointestinal tracts.

      3. A transwell assay method to evaluate Borrelia burgdorferi sensu stricto migratory chemoattraction toward tick saliva proteinsexternal icon
        Van Gundy TJ, Ullmann AJ, Brandt KS, Gilmore RD.
        Ticks Tick Borne Dis. 2021 Jul 12;12(5):101782.
        We developed a transwell assay to quantify migration of the Lyme disease agent, Borrelia burgdorferi sensu stricto (s.s.), toward Ixodes scapularis salivary gland proteins. The assay was designed to assess B. burgdorferi s.s. migration upward against gravity through a transwell polycarbonate membrane overlaid with 6% gelatin. Borreliae that channeled into the upper transwell chamber in response to test proteins were enumerated by flow cytometry. The transwell assay measured chemoattractant activity for B. burgdorferi s.s. from salivary gland extract (SGE) harvested from nymphal ticks during bloodmeal engorgement on mice 42 h post-attachment and saliva collected from adult ticks. Additionally, SGE protein fractions separated by size exclusion chromatography demonstrated various levels of chemoattractant activity in the transwell assay. Sialostatin L, and Salp-like proteins 9 and 11 were identified by mass spectrometry in SGE fractions that exhibited elevated activity. Recombinant forms of these proteins were tested in the transwell assay and showed positive chemoattractant properties compared to controls and another tick protein, S15A. These results were reproducible providing evidence that the transwell assay is a useful method for continuing investigations to find tick saliva components instrumental in driving B. burgdorferi s.s. chemotaxis.

    • Maternal and Child Health

    • Nutritional Sciences
      1. Changes in adiposity among children and adolescents in the United States, 1999-2006 to 2011-2018external icon
        Stierman B, Ogden CL, Yanovski JA, Martin CB, Sarafrazi N, Hales CM.
        Am J Clin Nutr. 2021 Jul 22.
        BACKGROUND: Data from the NHANES indicate that BMI has increased in some subgroups of children and adolescents in the United States over the past 20 y; however, BMI is an indirect measure of body fatness. OBJECTIVES: We assessed changes in DXA-derived measures of adiposity in a nationally representative population of US children and adolescents aged 8-19 y from 1999-2006 to 2011-2018. METHODS: Using data from the NHANES, we compared the means and distributions of DXA-derived percentage body fat (%BF) and fat mass index (FMI; fat mass/height2 in kg/m2) between 1999-2006 (n = 10,231) and 2011-2018 (n = 6923) among males and females by age group, race and Hispanic origin, and BMI categories. Estimates were standardized by age and race and Hispanic origin. RESULTS: From 1999-2006 to 2011-2018, mean %BF increased from 25.6% to 26.3% (change in %BF: 0.7%; 95% CI: 0.2%, 1.2%; P < 0.01) among all males, whereas mean %BF increased from 33.0% to 33.7% (change in %BF: 0.7%; 95% CI: 0.2%, 1.2%; P = 0.01) and mean FMI increased from 7.7 to 8.0 fat mass kg/m2 (change in FMI: 0.3 fat mass kg/m2; 95% CI: 0.0, 0.6 fat mass kg/m2; P = 0.02) among all females. Changes were not consistent across all age, race and Hispanic origin, and BMI categories. Both %BF and FMI increased among Mexican-American children and adolescents, but not other race and Hispanic origin groups. CONCLUSIONS: Among US children and adolescents, DXA-derived measures of adiposity increased from 1999-2006 to 2011-2018, albeit not consistently in every age, race and Hispanic origin, and BMI subgroup. These data reinforce the need to consider other measures, besides BMI categories, when studying adiposity in children and adolescents.

    • Occupational Safety and Health
      1. Evaluation of advanced curve speed warning system for fire trucksexternal icon
        Simeonov P, Hsiao H, Nimbarte A, Current R, Ammons D, Choi HS, Rahman MM, Weaver D.
        Appl Ergon. 2021 Jul 15;97:103527.
        A curve speed warning system (CSWS) for firetrucks was developed and tested in this study. The CSWS algorithm was developed based on guidelines in the public domain for general vehicles and modified for firetrucks for their configuration and emergency driving. Twenty-four firefighters participated in the test in a driving simulator. The results show that the CSWS was effective in issuing preemptive warnings when the drivers were approaching curves with unsafe speed during emergency responses. Drivers reduced their driving speed at curve approaching and entering phases for most challenging curves, without affecting the overall time in completing the test route. Drivers had reduced number of severe braking and decreased average in-curve distance traveled over the safety speed limits, when the CSWS was in use. Drivers also rated the CSWS as assisting, effective and useful. In summary, the CSWS can enhance firetruck safety during emergency driving without sacrificing drivers' precious response time.

    • Reproductive Health
      1. Assisted Reproductive Technology and Perinatal Mortality: Selected States (2006-2011)external icon
        Chang J, Zhang Y, Boulet SL, Crawford SB, Copeland GE, Bernson D, Kirby RS, Kissin DM, Barfield WD.
        Am J Perinatol. 2021 Jul 19.
        OBJECTIVE:  This study aimed to compare trends and characteristics of assisted reproductive technology (ART) and non-ART perinatal deaths and to evaluate the association of perinatal mortality and method of conception (ART vs. non-ART) among ART and non-ART deliveries in Florida, Massachusetts, and Michigan from 2006 to 2011. STUDY DESIGN:  Retrospective cohort study using linked ART surveillance and vital records data from Florida, Massachusetts, and Michigan. RESULTS:  During 2006 to 2011, a total of 570 ART-conceived perinatal deaths and 25,158 non-ART conceived perinatal deaths were identified from the participating states. Overall, ART perinatal mortality rates were lower than non-ART perinatal mortality rates for both singletons (7.0/1,000 births vs. 10.2/1,000 births) and multiples (22.8/1,000 births vs. 41.2/1,000 births). At <28 weeks of gestation, the risk of perinatal death among ART singletons was significantly lower than non-ART singletons (adjusted risk ratio [aRR] = 0.46, 95% confidence interval [CI]: 0.26-0.85). Similar results were observed among multiples at <28 weeks of gestation (aRR = 0.64, 95% CI: 0.45-0.89). CONCLUSION:  Our findings suggest that ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation, which may be explained by earlier detection and management of fetal and maternal conditions among ART-conceived pregnancies. These findings provide valuable information for health care providers, including infertility specialists, obstetricians, and pediatricians when counseling ART users on risk of treatment. KEY POINTS: · ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation.. · ART perinatal mortality rates were lower than that for non-ART perinatal mortality.. · This study used linked data to examine associations between use of ART and perinatal deaths..

    • Substance Use and Abuse
      1. Substance Use among Men Who Have Sex with Menexternal icon
        Compton WM, Jones CM.
        N Engl J Med. 2021 Jul 22;385(4):352-356.

    • Zoonotic and Vectorborne Diseases
      1. PURPOSE OF REVIEW: Lack of recognition of congenital Chagas disease in infants of mothers from endemic regions who are living in countries nonendemic for Trypanosoma cruzi infection suggests a high rate of underdiagnosis. Pregnancy is the optimal access point for identifying Chagas disease in at-risk mothers and their infants. In this review, we update progress toward implementation of pregnancy-based screening for congenital Chagas disease in nonendemic settings. RECENT FINDINGS: International organizations have updated recommendations for diagnosis, treatment and prevention of congenital Chagas disease. Reports of successful implementation of pregnancy-based screening at some centers provide a model for optimizing diagnosis of congenital Chagas disease. Screening family members of index patients may identify additional T. cruzi-infected persons. Promising tests to augment current diagnostic modalities for maternal and congenital Chagas disease are in development. Universal or risk-based screening would be cost-effective. More healthcare providers are now aware that treatment of congenital Chagas disease is curative and are promoting efforts to make pregnancy-based screening for congenital Chagas disease a standard of care. SUMMARY: Ongoing efforts to implement routine pregnancy-based screening for congenital Chagas disease in nonendemic regions will mutually benefit infants, their mothers and family members and can prevent potentially fatal Chagas cardiomyopathy.

      2. Frequency of Zika Virus Immunoglobulin M Antibody in Persons with West Nile Virus Infectionexternal icon
        Hills SL, Laven J, Biggerstaff BJ, Kosoy O, Staples JE, Panella A.
        Vector Borne Zoonotic Dis. 2021 Jul 22.
        West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viruses in the family Flaviviridae. Residents in, and travelers to, areas where the viruses are circulating are at risk for infection, and both viruses can cause an acute febrile illness. Given known cross-reactivity in flavivirus serologic assays, it is possible a patient with acute WNV infection could be misdiagnosed as having ZIKV infection if appropriate testing is not conducted. To understand how frequently persons with WNV infection have detectable cross-reactive ZIKV immunoglobulin M (IgM) antibody, we used archived serum samples from patients in the United States with recent WNV infection confirmed by a microsphere-based immunoassay test for IgM antibody and neutralizing antibody testing. Samples were tested for ZIKV IgM antibody with the Centers for Disease Control and Prevention (CDC) ZIKV IgM antibody capture enzyme-linked immunosorbent assay. Among 153 sera from patients with acute WNV infection, the ZIKV IgM antibody result was positive in 56 (37%; 95% confidence interval [CI] 29-44%) and equivocal in 28 (18%; 95% CI 13-25%). With 55% of samples having cross-reactive antibodies, it is important for health care providers to request appropriate testing based on the most likely cause of a patient's possible arboviral infection considering their clinical symptoms and signs, travel history, and place of residence. For cases where the epidemiology does not support the preliminary IgM findings, confirmatory neutralizing antibody testing should be performed. These measures will avoid an incorrect diagnosis of ZIKV infection, based on cross-reactive antibodies, in a person truly infected with WNV.

      3. La Crosse Virus Disease in the United States, 2003-2019external icon
        Vahey GM, Lindsey NP, Staples JE, Hills SL.
        Am J Trop Med Hyg. 2021 Jul 19.
        La Crosse virus (LACV) is an arthropod-borne virus that can cause a nonspecific febrile illness, meningitis, or encephalitis. We reviewed U.S. LACV surveillance data for 2003-2019, including human disease cases and nonhuman infections. Overall, 318 counties in 27 states, principally in the Great Lakes, mid-Atlantic, and southeastern regions, reported LACV activity. A total of 1,281 human LACV disease cases were reported, including 1,183 (92%) neuroinvasive disease cases. The median age of cases was 8 years (range: 1 month-95 years); 1,130 (88%) were aged < 18 years, and 754 (59%) were male. The most common clinical syndromes were encephalitis (N = 960; 75%) and meningitis (N = 219, 17%). The case fatality rate was 1% (N = 15). A median of 74 cases (range: 35-130) was reported per year. The average annual national incidence of neuroinvasive disease cases was 0.02 per 100,000 persons. West Virginia, North Carolina, Tennessee, and Ohio had the highest average annual state incidences (0.16-0.61 per 100,000), accounting for 80% (N = 1,030) of cases. No animal LACV infections were reported. Nine states reported LACV-positive mosquito pools, including three states with no reported human disease cases. La Crosse virus is the most common cause of pediatric neuroinvasive arboviral disease in the United States. However, surveillance data likely underestimate LACV disease incidence. Healthcare providers should consider LACV disease in patients, especially children, with febrile illness, meningitis, or encephalitis in areas where the virus circulates and advise their patients on ways to prevent mosquito bites.

      4. Inference of Nipah virus evolution, 1999-2015external icon
        Whitmer SL, Lo MK, Sazzad HM, Zufan S, Gurley ES, Sultana S, Amman B, Ladner JT, Rahman MZ, Doan S, Satter SM, Flora MS, Montgomery JM, Nichol ST, Spiropoulou CF, Klena JD.
        Virus Evolution. 2021 ;7(1).
        Despite near-annual human outbreaks of Nipah virus (NiV) disease in Bangladesh, typically due to individual spillover events from the local bat population, only twenty whole-genome NiV sequences exist from humans and ten from bats. NiV whole-genome sequences from annual outbreaks have been challenging to generate, primarily due to the low viral load in human throat swab and serum specimens. Here, we used targeted enrichment with custom NiV-specific probes and generated thirty-five additional unique full-length genomic sequences directly from human specimens and viral isolates. We inferred the temporal and geographic evolutionary history of NiV in Bangladesh and expanded a tool to visualize NiV spatio-temporal spread from a Bayesian continuous diffusion analysis. We observed that strains from Bangladesh segregated into two distinct clades that have intermingled geographically in Bangladesh over time and space. As these clades expanded geographically and temporally, we did not observe evidence for significant branch and site-specific selection, except for a single site in the Henipavirus L polymerase. However, the Bangladesh 1 and 2 clades are differentiated by mutations initially occurring in the polymerase, with additional mutations accumulating in the N, G, F, P, and L genes on external branches. Modeling the historic geographical and temporal spread demonstrates that while widespread, NiV does not exhibit significant genetic variation in Bangladesh. Thus, future public health measures should address whether NiV within in the bat population also exhibits comparable genetic variation, if zoonotic transmission results in a genetic bottleneck and if surveillance techniques are detecting only a subset of NiV. Copyright © 2020 Published by Oxford University Press 2020. This work is written by a US Government employee and is in the public domain in the US.

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