Issue 9, March 9, 2021

CDC Science Clips: Volume 13, Issue 9, March 9, 2021

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Prevalence of Cigarette Smoking among Patients with Different Histologic Types of Kidney Cancerexternal icon
        Gansler T, Fedewa SA, Flanders WD, Pollack LA, Siegel DA, Jemal A.
        Cancer Epidemiol Biomarkers Prev. 2020 Jul;29(7):1406-1412.
        BACKGROUND: Cigarette smoking is causally linked to renal cell carcinoma (RCC). However, associations for individual RCC histologies are not well described. Newly available data on tobacco use from population-based cancer registries allow characterization of associations with individual RCC types. METHODS: We analyzed data for 30,282 RCC cases from 8 states that collected tobacco use information for a National Program of Cancer Registry project. We compared the prevalence and adjusted prevalence ratios (aPR) of cigarette smoking (current vs. never, former vs. never) among individuals diagnosed between 2011 and 2016 with clear cell RCC, papillary RCC, chromophobe RCC, renal collecting duct/medullary carcinoma, cyst-associated RCC, and unclassified RCC. RESULTS: Of 30,282 patients with RCC, 50.2% were current or former cigarette smokers. By histology, proportions of current or formers smokers ranged from 38% in patients with chromophobe carcinoma to 61.9% in those with collecting duct/medullary carcinoma. The aPRs (with the most common histology, clear cell RCC, as referent group) for current and former cigarette smoking among chromophobe RCC cases (4.9% of our analytic sample) were 0.58 [95% confidence interval (CI), 0.50-0.67] and 0.88 (95% CI, 0.81-0.95), respectively. Other aPRs were slightly increased (papillary RCC and unclassified RCC, current smoking only), slightly decreased (unclassified RCC, former smoking only), or not significantly different from 1.0 (collecting duct/medullary carcinoma and cyst-associated RCC). CONCLUSIONS: Compared with other RCC histologic types, chromophobe RCC has a weaker (if any) association with smoking. IMPACT: This study shows the value of population-based cancer registries' collection of smoking data, especially for epidemiologic investigation of rare cancers.

      2. Body Mass Index and Blood Pressure Improvements With a Pediatric Weight Management Intervention at Federally Qualified Health Centersexternal icon
        Imoisili OE, Lundeen EA, Freedman DS, Womack LS, Wallace J, Hambidge SJ, Federico S, Everhart R, Harr D, Vance J, Kompaniyets L, Dooyema C, Park S, Blanck HM, Goodman AB.
        Acad Pediatr. 2020 Dec 3.
        OBJECTIVE: The Mind, Exercise, Nutrition, Do It! 7-13 (MEND 7-13) program was adapted in 2016 by 5 Denver Health federally qualified health centers (DH FQHC) into MEND+, integrating clinician medical visits into the curriculum and tracking health measures within an electronic health record (EHR). We examined trajectories of body mass index (BMI, kg/m(2)) percentile, and systolic and diastolic blood pressures (SBP and DBP) among MEND+ attendees in an expanded age range of 4 to 17 years, and comparable nonattendees. METHODS: Data from April 2015 to May 2018 were extracted from DH FQHC EHR for children eligible for MEND+ referral (BMI ≥85th percentile). The sample included 347 MEND+ attendees and 21,061 nonattendees. Mixed-effects models examined average rate of change for BMI percent of the 95th percentile (%BMIp95), SBP and DBP (mm Hg), after completion of the study period. RESULTS: Most children were ages 7 to 13 years, half were male, and most were Hispanic. An average of 4.2 MEND+ clinical sessions were attended. Before MEND+, %BMIp95 increased by 0.247 units/month among MEND+ attendees. After attending, %BMIp95 decreased by 0.087 units/month (P < .001). Eligible nonattendees had an increase of 0.084/month in %BMIp95. Before MEND+ attendance, SBP and DBP increased by 0.041 and 0.022/month, respectively. After MEND+ attendance, SBP and DBP decreased by 0.254/month (P < .001) and 0.114/month (P < .01), respectively. SBP and DBP increased by 0.033 and 0.032/month in eligible nonattendees, respectively. CONCLUSIONS: %BMIp95, SBP, and DBP significantly decreased among MEND+ attendees when implemented in community-based clinical practice settings at DH FQHC.

      3. BACKGROUND: Individuals with congenital heart defects (CHDs) are recommended to receive all inpatient cardiac and non-cardiac care at facilities that can offer specialized care. We describe geographic accessibility to such centers in New York State and determine several factors associated with receiving care there. METHODS: We used inpatient hospitalization data from the Statewide Planning and Research Cooperative System (SPARCS) in New York State 2008-2013. In the absence of specific adult CHD care center designations during our study period, we identified pediatric/adult and adult-only cardiac surgery centers through the Cardiac Surgery Reporting System to estimate age-based specialized care. We calculated one-way drive and public transit time (in minutes) from residential address to centers using R gmapsdistance package and the Google Maps Distance Application Programming Interface (API). We calculated prevalence ratios using modified Poisson regression with model-based standard errors, fit with generalized estimating equations clustered at the hospital level and sub-clustered at the individual level. RESULTS: Individuals with CHDs were more likely to seek care at pediatric/adult or adult-only cardiac surgery centers if they had severe CHDs, private health insurance, higher severity of illness at encounter, a surgical procedure, cardiac encounter, and shorter drive time. These findings can be used to increase care receipt (especially for non-cardiac care) at pediatric/adult or adult-only cardiac surgery centers, identify areas with limited access, and reduce disparities in access to specialized care among this high-risk population.

      4. Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settingsexternal icon
        Magliano DJ, Chen L, Islam RM, Carstensen B, Gregg EW, Pavkov ME, Andes LJ, Balicer R, Baviera M, Boersma-van Dam E, Booth GL, Chan JC, Chua YX, Fosse-Edorh S, Fuentes S, Gulseth HL, Gurevicius R, Ha KH, Hird TR, Jermendy G, Khalangot MD, Kim DJ, Kiss Z, Kravchenko VI, Leventer-Roberts M, Lin CY, Luk AO, Mata-Cases M, Mauricio D, Nichols GA, Nielen MM, Pang D, Paul SK, Pelletier C, Pildava S, Porath A, Read SH, Roncaglioni MC, Lopez-Doriga Ruiz P, Shestakova M, Vikulova O, Wang KL, Wild SH, Yekutiel N, Shaw JE.
        Lancet Diabetes Endocrinol. 2021 Feb 23.
        BACKGROUND: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. METHODS: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. FINDINGS: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. INTERPRETATION: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

      5. Proximity to freshwater blue space and type 2 diabetes onset: The importance of historical and economic contextexternal icon
        Poulsen MN, Schwartz BS, DeWalle J, Nordberg C, Pollak JS, Silva J, Mercado CI, Rolka DB, Siegel KR, Hirsch AG.
        Landsc Urban Plann. 2021 ;209.
        Salutogenic effects of living near aquatic areas (blue space) remain underexplored, particularly in non-coastal and non-urban areas. We evaluated associations of residential proximity to inland freshwater blue space with new onset type 2 diabetes (T2D) in central and northeast Pennsylvania, USA, using medical records to conduct a nested case-control study. T2D cases (n = 15,888) were identified from diabetes diagnoses, medication orders, and laboratory test results and frequency-matched on age, sex, and encounter year to diabetes-free controls (n = 79,435). We calculated distance from individual residences to the nearest lake, river, tributary, or large stream, and residence within the 100-year floodplain. Logistic regression models adjusted for community socioeconomic deprivation and other confounding variables and stratified by community type (townships [rural/suburban], boroughs [small towns], city census tracts). Compared to individuals living ≥ 1.25 miles from blue space, those within 0.25 miles had 8% and 17% higher odds of T2D onset in townships and boroughs, respectively. Among city residents, T2D odds were 38–39% higher for those living 0.25 to < 0.75 miles from blue space. Residing within the floodplain was associated with 16% and 14% higher T2D odds in townships and boroughs. A post-hoc analysis demonstrated patterns of lower residential property values with nearer distance to the region's predominant waterbody, suggesting unmeasured confounding by socioeconomic disadvantage. This may explain our unexpected findings of higher T2D odds with closer proximity to blue space. Our findings highlight the importance of historic and economic context and interrelated factors such as flood risk and lack of waterfront development in blue space research.

      6. Nonmedical Marijuana Use and Cardiovascular Events : A Systematic Reviewexternal icon
        Yang PK, Odom EC, Patel R, Loustalot F, Coleman King S.
        Public Health Rep. 2021 Feb 26:33354920988285.
        INTRODUCTION: Although marijuana use has increased since 2012, the perceived risk of adverse outcomes has decreased. This systematic review summarizes articles that examined the association between nonmedical marijuana use (ie, observed smoking, self-report, or urinalysis) and cardiovascular events in observational or experimental studies of adults aged ≥18. METHODS: We searched Medline, EMBASE, PsycInfo, CINAHL, Cochrane Library Database, and Global Health from January 1, 1970, through August 31, 2018. Of 3916 citations, 16 articles fit the following criteria: (1) included adults aged ≥18; (2) included marijuana/cannabis use that is self-reported smoked, present in diagnostic coding, or indicated through a positive diagnostic test; (3) compared nonuse of cannabis; (4) examined events related to myocardial infarction, angina, acute coronary syndrome, and/or stroke; (5) published in English; and (6) had observational or experimental designs. RESULTS: Of the 16 studies, 4 were cohort studies, 8 were case-control studies, 1 was a case-crossover study, 2 were randomized controlled trials, and 1 was a descriptive study. Studies ranged from 10 participants to 118 659 619 hospitalizations. Marijuana use was associated with an increased likelihood of myocardial infarction within 24 hours in 2 studies and stroke in 6 studies. Results of studies suggested an increased risk for angina and acute coronary syndrome, especially among people with a history of a cardiovascular event. CONCLUSION: This review suggests that people who use marijuana may be at increased risk for cardiovascular events. As states expand new laws permitting marijuana use, it will be important to monitor the effect of marijuana use on cardiovascular disease outcomes, perhaps through the inclusion of data on nonmedical marijuana use in diverse national and local surveillance systems.

    • Communicable Diseases
      1. Formative assessment to identify perceived benefits and barriers of HIV oral self-testing among female sex workers, service providers, outreach workers, and peer educators to inform scale-up in Kenyaexternal icon
        Agot K, Cain M, Medley A, Kimani J, Gichangi P, Kiio C, Mukiri E, Odonde P, Toroitich-Ruto C, Bingham T, Downer M, Chesang K.
        AIDS Care. 2021 Mar 3:1-8.
        In Kenya, HIV prevalence estimates among female sex workers (FSWs) are almost five times higher than among women in the general population. However, only 68% of infected FSWs are aware of their HIV-positive status. We aimed to identify perceived benefits, opportunities, and barriers of HIV self-testing (HIVST) in improving testing coverage among FSWs. Twenty focus group discussions were conducted with 77 service providers, 42 peer educators (PEs) and outreach workers, and 37 FSWs attending drop-in centers (DiCEs) in four regions of Kenya. An additional 8 FSWs with HIV-negative or unknown status-completed in-depth interviews. Data were analyzed thematically. Acceptability of HIVST was high, with cited benefits including confidentiality, convenience, and ease of use. Barriers included absence of counseling, potential for inaccurate results, fear of partner reaction, possible misuse, and fear that HIVST could lead to further stigmatization. PEs and DiCEs were the preferred models for distributing HIVST kits. FSWs wanted kits made available free or at a nominal cost (100 Kenya Shillings or ∼USD 1). Linkage to confirmatory testing, the efficiency of distributing HIVST kits using peers and DiCEs, and the types and content of effective HIVST messaging require further research.

      2. Rural-Urban Residence and Maternal Hepatitis C Infection, U.S.: 2010-2018external icon
        Ahrens KA, Rossen LM, Burgess AR, Palmsten KK, Ziller EC.
        Am J Prev Med. 2021 Feb 24.
        INTRODUCTION: The prevalence of hepatitis C virus infection among women delivering live births in the U.S. may be higher in rural areas where county-level estimates may be unreliable. The aim of this study is to model county-level maternal hepatitis C virus infection among deliveries in the U.S. METHODS: In 2020, U.S. natality files (2010-2018) with county-level maternal residence information were used from states that had adopted the 2003 revised U.S. birth certificate, which included a field for hepatitis C virus infection present during pregnancy. Hierarchical Bayesian spatial models with spatiotemporal random effects were applied to produce stable annual county-level estimates of maternal hepatitis C virus infection for years when all states had adopted the revised birth certificate (2016-2018). Models included a 6-Level Urban-Rural County Classification Scheme along with the birth year and county-specific covariates to improve posterior predictions. RESULTS: Among approximately 32 million live births, the overall prevalence of maternal hepatitis C virus infection was 3.5 per 1,000 births (increased from 2.0 in 2010 to 5.0 in 2018). During 2016-2018, posterior predicted median county-level maternal hepatitis C virus infection rates showed that nonurban counties had 3.5-3.8 times higher rates of hepatitis C virus than large central metropolitan counties. The counties in the top 10th percentile for maternal hepatitis C virus rates in 2018 were generally located in Appalachia, in Northern New England, along the northern border in the Upper Midwest, and in New Mexico. CONCLUSIONS: Further implementation of community-level interventions that are effective in reducing maternal hepatitis C virus infection and its subsequent morbidity may help to reduce geographic and rural disparities.

      3. Testing early warning and response systems through a full-scale exercise in Vietnamexternal icon
        Clara A, Dao AT, Tran Q, Tran PD, Dang TQ, Nguyen HT, Tran QD, Rzeszotarski P, Talbert K, Stehling-Ariza T, Veasey F, Clemens L, Mounts AW, Lofgren H, Balajee SA, Do TT.
        BMC Public Health. 2021 Feb 26;21(1):409.
        BACKGROUND: Simulation exercises can functionally validate World Health Organization (WHO) International Health Regulations (IHR 2005) core capacities. In 2018, the Vietnam Ministry of Health (MOH) conducted a full-scale exercise (FSX) in response to cases of severe viral pneumonia with subsequent laboratory confirmation for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) to evaluate the country's early warning and response capabilities for high-risk events. METHODS: An exercise planning team designed a complex fictitious scenario beginning with one case of severe viral pneumonia presenting at the hospital level and developed all the materials required for the exercise. Actors, controllers and evaluators were trained. In August 2018, a 3-day exercise was conducted in Quang Ninh province and Hanoi city, with participation of public health partners at the community, district, province, regional and national levels. Immediate debriefings and an after-action review were conducted after all exercise activities. Participants assessed overall exercise design, conduction and usefulness. RESULTS: FSX findings demonstrated that the event-based surveillance component of the MOH surveillance system worked optimally at different administrative levels. Detection and reporting of signals at the community and health facility levels were appropriate. Triage, verification and risk assessment were successfully implemented to identify a high-risk event and trigger timely response. The FSX identified infection control, coordination with internal and external response partners and process documentation as response challenges. Participants positively evaluated the exercise training and design. CONCLUSIONS: This exercise documents the value of exercising surveillance capabilities as part of a real-time operational scenario before facing a true emergency. The timing of this exercise and choice of disease scenario was particularly fortuitous given the subsequent appearance of COVID-19. As a result of this exercise and subsequent improvements made by the MOH, the country may have been better able to deal with the emergence of SARS-CoV-2 and contain it.

      4. SARS-CoV-2 Infection Risk Among Active Duty Military Members Deployed to a Field Hospital - New York City, April 2020external icon
        Clifton GT, Pati R, Krammer F, Laing ED, Broder CC, Mendu DR, Simons MP, Chen HW, Sugiharto VA, Kang AD, Stadlbauer D, Pratt KP, Bandera BC, Fritz DK, Millar EV, Burgess TH, Chung KK.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):308-311.

      5. Brief Report: Modeling the Impact of Voluntary Medical Male Circumcision on Cervical Cancer in Ugandaexternal icon
        Davis SM, Habel MA, Pretorius C, Yu T, Toledo C, Farley T, Kabuye G, Samuelson J.
        J Acquir Immune Defic Syndr. 2021 Mar 1;86(3):323-328.
        BACKGROUND: In addition to providing millions of men with lifelong lower risk for HIV infection, voluntary medical male circumcision (VMMC) also provides female partners with health benefits including decreased risk for human papillomavirus (HPV) and resultant cervical cancer (CC). SETTING: We modeled potential impacts of VMMC on CC incidence and mortality in Uganda as an additional benefit beyond HIV prevention. METHODS: HPV and CC outcomes were modeled using the CC model from the Spectrum policy tool suite, calibrated for Uganda, to estimate HPV infection incidence and progression to CC, using a 50-year (2018-2067) time horizon. 2016 Demographic Health Survey data provided baseline VMMC coverage. The baseline (no VMMC scale-up beyond current coverage, minimal HPV vaccination coverage) was compared with multiple scenarios to assess the varying impact of VMMC according to different implementations of HPV vaccination and HPV screening programs. RESULTS: Without further intervention, annual CC incidence was projected to rise from 16.9 to 31.2 per 100,000 women in 2067. VMMC scale-up alone decreased 2067 annual CC incidence to 25.3, averting 13,000 deaths between 2018 and 2067. With rapidly-achieved 90% HPV9 vaccination coverage for adolescent girls and young women, 2067 incidence dropped below 10 per 100,000 with or without a VMMC program. With 45% vaccine coverage, the addition of VMMC scaleup decreased incidence by 2.9 per 100,000 and averted 8000 additional deaths. Similarly, with HPV screen-and-treat without vaccination, the addition of VMMC scaleup decreased incidence by 5.1 per 100,000 and averted 10,000 additional deaths. CONCLUSIONS: Planned VMMC scale-up to 90% coverage from current levels could prevent a substantial number of CC cases and deaths in the absence of rapid scale-up of HPV vaccination to 90% coverage.

      6. Expansion of Preexposure Prophylaxis Capacity in Response to an HIV Outbreak Among People Who Inject Drugs-Cabell County, West Virginia, 2019external icon
        Furukawa NW, Weimer M, Willenburg KS, Kilkenny ME, Atkins AD, McClung RP, Hansen Z, Napier K, Handanagic S, Carnes NA, Kemp Rinderle J, Neblett-Fanfair R, Oster AM, Smith DK.
        Public Health Rep. 2021 Mar 1:33354921994202.
        From January 1, 2018, through October 9, 2019, 82 HIV diagnoses occurred among people who inject drugs (PWID) in Cabell County, West Virginia. Increasing the use of HIV preexposure prophylaxis (PrEP) among PWID was one of the goals of a joint federal, state, and local response to this HIV outbreak. Through partnerships with the local health department, a federally qualified health center, and an academic medical system, we integrated PrEP into medication-assisted treatment, syringe services program, and primary health care settings. During the initial PrEP implementation period (April 18-May 17, 2019), 110 health care providers and administrators received PrEP training, the number of clinics offering PrEP increased from 2 to 15, and PrEP referrals were integrated with partner services, outreach, and testing activities. The number of people on PrEP increased from 15 in the 6 months before PrEP expansion to 127 in the 6 months after PrEP implementation. Lessons learned included the importance of implementing PrEP within existing health care services, integrating PrEP with other HIV prevention response activities, adapting training and material to fit the local context, and customizing care to meet the needs of PWID. The delivery of PrEP to PWID is challenging but complements other HIV prevention interventions. The expansion of PrEP in response to this HIV outbreak in Cabell County provides a framework for expanding PrEP in other outbreak and non-outbreak settings.

      7. Community Transmission of SARS-CoV-2 at Three Fitness Facilities - Hawaii, June-July 2020external icon
        Groves LM, Usagawa L, Elm J, Low E, Manuzak A, Quint J, Center KE, Buff AM, Kemble SK.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):316-320.

      8. Immunologic and Epidemiologic Drivers of Norovirus Transmission in Daycare and School Outbreaksexternal icon
        Havumaki J, Eisenberg JN, Mattison CP, Lopman BA, Ortega-Sanchez IR, Hall AJ, Hutton DW, Eisenberg MC.
        Epidemiology. 2021 Feb 26.
        BACKGROUND: Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms. METHODS: We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted 'immunity'), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data. RESULTS: Including immunity in the model led to attack rates that were consistent with the data. However, immunity alone resulted in the majority of outbreak durations being relatively short. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data. CONCLUSIONS: The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. More studies on how best to design interventions which leverage population immunity and encourage more rigorous individual exclusion may improve venue-level control measures.

      9. Estimated SARS-CoV-2 Seroprevalence Among Persons Aged <18 Years - Mississippi, May-September 2020external icon
        Hobbs CV, Drobeniuc J, Kittle T, Williams J, Byers P, Satheshkumar PS, Inagaki K, Stephenson M, Kim SS, Patel MM, Flannery B.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):312-315.

      10. Research Synthesis, HIV Prevention Response, and Public Health: CDC's HIV/AIDS Prevention Research Synthesis Projectexternal icon
        Koenig LJ, Lyles CM, Higa D, Mullins MM, Sipe TA.
        Public Health Rep. 2021 Feb 26:33354920988871.
        OBJECTIVE: Research synthesis, through qualitative or quantitative systematic reviews, allows for integrating results of primary research to improve public health. We examined more than 2 decades of work in HIV prevention by the Centers for Disease Control and Prevention's (CDC's) HIV/AIDS Prevention Research Synthesis (PRS) Project. We describe the context and contributions of research synthesis, including systematic reviews and meta-analyses, through the experience of the PRS Project. METHODS: We reviewed PRS Project publications and products and summarized PRS contributions from 1996 to July 2020 in 4 areas: synthesis of interventions and epidemiologic studies, synthesis methods, prevention programs, and prevention policy. RESULTS: PRS Project publications summarized risk behaviors and effects of prevention interventions (eg, changing one's perception of risk, teaching condom negotiation skills) across populations at risk for HIV infection and intervention approaches (eg, one-on-one or group meetings) as the HIV/AIDS epidemic and science evolved. We used the PRS Project cumulative database and intervention efficacy reviews to contribute to prevention programs and policies through identification of evidence-based interventions and development of program guidance. Subject matter experts and scientific evidence informed PRS Project products and contributions, which were implemented through strategic programmatic partnerships. CONCLUSIONS: The contributions of the PRS Project to HIV prevention and public health efforts in the United States can be credited to CDC's long-standing support of the project and its context within a federal prevention agency, where HIV programs and policies were developed and implemented. The effect of the PRS Project was likely facilitated by opportunities to directly influence program and policy because of connections with other research translation activities and program and policy decision making within CDC.

      11. Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysisexternal icon
        Lafond KE, Porter RM, Whaley MJ, Suizan Z, Ran Z, Aleem MA, Thapa B, Sar B, Proschle VS, Peng Z, Feng L, Coulibaly D, Nkwembe E, Olmedo A, Ampofo W, Saha S, Chadha M, Mangiri A, Setiawaty V, Ali SS, Chaves SS, Otorbaeva D, Keosavanh O, Saleh M, Ho A, Alexander B, Oumzil H, Baral KP, Huang QS, Adebayo AA, Al-Abaidani I, von Horoch M, Cohen C, Tempia S, Mmbaga V, Chittaganpitch M, Casal M, Dang DA, Couto P, Nair H, Bresee JS, Olsen SJ, Azziz-Baumgartner E, Nuorti JP, Widdowson MA.
        PLoS Med. 2021 Mar 1;18(3):e1003550.
        BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

      12. COVID-19 Outbreak Among Attendees of an Exercise Facility - Chicago, Illinois, August-September 2020external icon
        Lendacki FR, Teran RA, Gretsch S, Fricchione MJ, Kerins JL.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):321-325.

      13. Assessing the quality of reporting to China’s national TB surveillance systemsexternal icon
        Li T, Yang L, Smith-Jeffcoat SE, Wang A, Guo H, Chen W, Du X, Zhang H.
        Int J Environ Res Public Health. 2021 ;18(5):1-13.
        (1) Background: The reliability of disease surveillance may be restricted by sensitivity or ability to capture all disease. Objective: To quantify under-reporting and concordance of recording persons with tuberculosis (TB) in national TB surveillance systems: the Infectious Disease Reporting System (IDRS) and Tuberculosis Information Management System (TBIMS). (2) Methods: This retrospective review includes 4698 patients identified in 2016 in China. County staff linked TB patients identified from facility-specific health and laboratory information systems with records in IDRS and TBIMS. Under-reporting was calculated, and timeliness, concordance, accuracy, and completeness were analyzed. Multivariable logistic regression was used to examine factors associated with under-reporting. (3) Results: We found that 505 (10.7%) patients were missing within IDRS and 1451 (30.9%) patients were missing within TBIMS. Of 171 patient records reviewed in IDRS and 170 patient records in TBIMS, 12.3% and 6.5% were found to be untimely, and 10.7% and 7.1% were found to have an inconsistent home address. The risk of under-reporting to both IDRS and TBIMS was greatest at tertiary health facilities and among non-residents; the risk of under-reporting to TBIMS was greatest with patients aged 65 or older and with extrapulmonary TB (EPTB). (4) Conclusions: It is important to improve the reporting and recording of TB patients. Local TB programs that focus on training, and mentoring high-burden hospitals, facilities that cater to EPTB, and migrant patients may improve reporting and recording.

      14. Changes in SARS CoV-2 Seroprevalence Over Time in Ten Sites in the United States, March - August, 2020external icon
        Lim T, Delorey M, Bestul N, Johannsen M, Reed C, Hall AJ, Fry AM, Edens C, Semenova V, Li H, Browning P, Desai R, Epperson M, Jia T, Thornburg NJ, Schiffer J, Havers FP.
        Clin Infect Dis. 2021 Feb 26.
        BACKGROUND: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale. METHODS: We performed serologic testing on a convenience sample of residual sera obtained from persons of all ages, at ten sites in the United States from March 23 through August 14, 2020, from routine clinical testing at commercial laboratories. We age-sex-standardized our seroprevalence rates using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a two-stage bootstrap. We used Bayesian modeling to test whether seroprevalence changes over time were statistically significant. RESULTS: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites. CONCLUSIONS: Estimated seroprevalence was low in most sites, indicating that most people in the U.S. have not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection.

      15. Housing quality in a rural and an urban settlement in South Africaexternal icon
        Mathee A, Moyes J, Mkhencele T, Kleynhans J, Language B, Piketh S, Moroe E, Wafawanaka F, Martinson N, McMorrow M, Tempia S, Kahn K, Cohen C.
        Int J Environ Res Public Health. 2021 ;18(5):1-17.
        During 2016 to 2018, a prospective household cohort study of influenza and respiratory syncytial virus community burden and transmission dynamics (the PHIRST study) was undertaken to examine the factors associated with influenza and other respiratory pathogen transmissions in South Africa. We collected information on housing conditions in the PHIRST study sites: Rural villages near Agincourt, Bushbuckridge Municipality, Mpumalanga Province, and urban Jouberton Township in North West Province. Survey data were collected from 159 and 167 study households in Agincourt and Jouberton, respectively. Multiple housing-related health hazards were identified in both sites, but particularly in Agincourt. In Agincourt, 75% (119/159) of households reported daily or weekly interruptions in water supply and 98% (154/159) stored drinking water in miscella-neous containers, compared to 1% (1/167) and 69% (115/167) of households in Jouberton. Fuels other than electricity (such as wood) were mainly used for cooking by 44% (70/159) and 7% (11/167) of Agincourt and Jouberton households, respectively; and 67% (106/159) of homes in Agincourt versus 47% (79/167) in Jouberton were located on unpaved roads, which is associated with the generation of dust and particulate matter. This study has highlighted housing conditions in Agincourt and Jouberton that are detrimental to health, and which may impact disease severity or transmission in South African communities.

      16. Presence of Antibodies Against Haemophilus influenzae Serotype a in Alaska Before and After the Emergence of Invasive Infectionsexternal icon
        McClure M, Miernyk K, Bruden D, Rudolph K, Hennessy TW, Bruce MG, Nolen LD.
        J Infect Dis. 2021 Feb 3;223(2):326-332.
        BACKGROUND: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. Haemophilus influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska. METHODS: We quantified immunoglobulin G antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades before (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race. RESULTS: The anti-Hia was >0.1 µg/mL in 88.1% (348 of 395) and 91.0% (404 of 444) of samples from the decades prior and after the emergence of Hia, respectively (P = .17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 vs 2.08 µg/mL, P = .91 for age ≥5) or between AN and non-AN people (2.50 vs 2.60 µg/mL, P = .26). CONCLUSIONS: Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease.

      17. Persistent SARS-CoV-2 RNA Shedding without Evidence of Infectiousness: A Cohort Study of Individuals with COVID-19external icon
        Owusu D, Pomeroy MA, Lewis NM, Wadhwa A, Yousaf AR, Whitaker B, Dietrich E, Hall AJ, Chu V, Thornburg N, Christensen K, Kiphibane T, Willardson S, Westergaard R, Dasu T, Pray IW, Bhattacharyya S, Dunn A, Tate JE, Kirking HL, Matanock A.
        J Infect Dis. 2021 Feb 27.
        BACKGROUND: To better understand SARS-CoV-2 shedding duration and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described characteristics associated with viral RNA shedding resolution1, and determined if replication-competent viruses could be recovered ≥10 days after symptom onset among individuals with mild to moderate COVID-19. METHODS: We collected serial nasopharyngeal specimens at various time points from 109 individuals with rRT-PCR-confirmed COVID-19 in Utah and Wisconsin. We calculated probability of viral RNA shedding resolution using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR-positive nasopharyngeal specimens collected ≥10 days after symptom onset. RESULTS: The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio [aHR]: 3.01; 95% CI: 1.6-5.6) and longer among those aged ≥50 years (aHR: 0.50; 95% CI: 0.3-0.9) compared to participants aged 18-49 years. No replication-competent viruses were recovered. CONCLUSIONS: Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.

      18. Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children: Multicenter Surveillance, United States, January-March 2020external icon
        Rha B, Lively JY, Englund JA, Staat MA, Weinberg GA, Selvarangan R, Halasa NB, Williams JV, Boom JA, Sahni LC, Michaels MG, Stewart LS, Harrison CJ, Szilagyi PG, McNeal MM, Klein EJ, Strelitz B, Lacombe K, Schlaudecker E, Moffatt ME, Schuster JE, Pahud BA, Weddle G, Hickey RW, Avadhanula V, Wikswo ME, Hall AJ, Curns AT, Gerber SI, Langley G.
        J Pediatric Infect Dis Soc. 2020 Nov 10;9(5):609-612.
        Previous reports of coronavirus disease 2019 among children in the United States have been based on health jurisdiction reporting. We performed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing on children enrolled in active, prospective, multicenter surveillance during January-March 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.

      19. OBJECTIVE: The Centers for Disease Control and Prevention (CDC) recommends initial and follow-up sexually transmitted infection (STI) and HIV testing when taking HIV pre-exposure prophylaxis (PrEP). We assessed frequencies of STIs and HIV testing and rates of STIs before and after PrEP initiation among males aged ≥18 years. METHODS: We used the OptumLabs ® database for this cohort study. We measured STI/HIV testing rates and prevalence in two-time intervals: 1) within 90 days before and on the date of PrEP initiation and 2) within 45 days of the 180th day after the date of PrEP initiation. RESULTS: Of 4210 males who initiated PrEP in 2016-2017 and continuously used PrEP for ≥180 days, 45.7%, 45.7%, and 56.0% were tested for chlamydia, gonorrhea, and HIV, respectively, at the 2nd time interval. These percentages were significantly lower than those at the 1st time interval (58.3%, 57.9%, and 73.5%, respectively, p < 0.01). Chlamydia and gonorrhea prevalence at the 2nd time interval was 6.5% and 6.2%, respectively, versus 5.0% and 4.7%, respectively, at the 1st time interval. Most gonorrhea or chlamydia infections at the 2nd time intervals appear to be new infections new infections. CONCLUSION: STI/HIV testing for PrEP users in the real-world private settings is much lower than in clinical trials. High STI prevalence before and after PrEP initiation in this study suggests that patients taking PrEP have increased risk of acquiring STI. Interventions to improve provider adherence for PrEP users are urgently needed.

      20. Assessing self-reported discrimination among men who have sex with men (MSM)external icon
        Whiteman A, Baugher A, Sionean C.
        Aids. 2021 Jan 1;35(1):141-146.
        OBJECTIVES: To determine the prevalence of four forms of sexual identity discrimination among MSM in 23 US metropolitan statistical areas, examine racial/ethnic and socioeconomic disparities in each form of discrimination. METHODS: We examined interview data collected during 2017 for National HIV Behavioral Surveillance (n = 10 029 respondents) and used generalized linear models to assess the association between the prevalence of reported discrimination during the previous 12 months and selected sociodemographic groups. RESULTS: Overall, 34% of participants reported experiencing verbal discrimination; 16%, discrimination in a workplace, school, or a healthcare setting; and 8%, physical assault. MSM who had reported experiencing discrimination were most likely to be young, had achieved lower education, and had lower incomes. High prevalence of reported discrimination was associated with young age, lower education, lower household income, sexual identity disclosure, and lower perceived community tolerance of gay or bisexual persons. CONCLUSION: MSM discrimination affects different groups and occurs in multiple settings. Addressing discrimination should be an integral aspect of multifaceted efforts to improve MSM health.

      21. SARS-CoV-2 spike D614G change enhances replication and transmissionexternal icon
        Zhou B, Thi Nhu Thao T, Hoffmann D, Taddeo A, Ebert N, Labroussaa F, Pohlmann A, King J, Steiner S, Kelly JN, Portmann J, Halwe NJ, Ulrich L, Trüeb BS, Fan X, Hoffmann B, Wang L, Thomann L, Lin X, Stalder H, Pozzi B, de Brot S, Jiang N, Cui D, Hossain J, Wilson M, Keller M, Stark TJ, Barnes JR, Dijkman R, Jores J, Benarafa C, Wentworth DE, Thiel V, Beer M.
        Nature. 2021 Feb 26.
        During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic(1). However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2), (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

    • Disaster Control and Emergency Services
      1. Hurricanes and other natural disasters leave behind multifaceted and complex environmental challenges that may contribute to adverse health outcomes, such as increased potential for exposure to vector-borne disease. Through an incident management system tailored for the Centers for Disease Control and Prevention (CDC), the National Center for Environmental Health/Agency for Toxic Substances and Disease Registry (NCEH/ATSDR) fulfills a leadership role in facilitating the agency's natural disaster emergency response activities through coordination with other CDC programs, liaising with other government agencies and impacted jurisdictions, and responding to requests for technical assistance. On the ground, NCEH/ATSDR deploys environmental health (EH) practitioners who provide consultation and inform mosquito control efforts from a systematic perspective. In the wake of recent hurricanes, NCEH staff mobilized to manage critical elements of the responses and to provide assets for addressing environmental hazards and conditions that contributed to the presence of mosquitoes. In this article, we describe NCEH/ATSDR's emergency response roles and responsibilities, interactions within the national emergency response framework, and provision of EH technical assistance and resources, particularly in the context of postdisaster mosquito control.

    • Environmental Health
      1. Prenatal exposure to per- and polyfluoroalkyl substances and cognitive development in infancy and toddlerhoodexternal icon
        Oh J, Schmidt RJ, Tancredi D, Calafat AM, Roa DL, Hertz-Picciotto I, Shin HM.
        Environ Res. 2021 Feb 26:110939.
        BACKGROUND: /Objective: Per- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal PFAS serum concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood. METHODS: We included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson models to estimate associations expressed as relative risks (RR). RESULTS: Among six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (β = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03). CONCLUSIONS: Prenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.

      2. Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birthexternal icon
        Zhang Y, Mustieles V, Williams PL, Wylie BJ, Souter I, Calafat AM, Demokritou M, Lee A, Vagios S, Hauser R, Messerlian C.
        Environ Int. 2021 Feb 25;151:106440.
        BACKGROUND: Parental preconception exposure to select phenols and phthalates was previously associated with increased risk of preterm birth in single chemical analyses. However, the joint effect of phenol and phthalate mixtures on preterm birth is unknown. METHODS: We included 384 female and 211 male (203 couples) participants seeking infertility treatment in the Environment and Reproductive Health (EARTH) Study who gave birth to 384 singleton infants between 2005 and 2018. Mean preconception urinary concentrations of bisphenol A (BPA), parabens, and eleven phthalate biomarkers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal component analysis (PCA) with log-Poisson regression and Probit Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection to examine maternal and paternal phenol and phthalate mixtures in relation to preterm birth. Couple-based BKMR model was fit to assess couples' joint mixtures in relation to preterm birth. RESULTS: PCA identified the same four factors for maternal and paternal preconception mixtures. Each unit increase in PCA scores of maternal (adjusted Risk Ratio (aRR): 1.36, 95%CI: 1.00, 1.84) and paternal (aRR: 1.47, 95%CI: 0.90, 2.42) preconception DEHP-BPA factor was positively associated with preterm birth. Maternal and paternal BKMR models consistently presented the DEHP-BPA factor with the highest group Posterior Inclusion Probability (PIP). BKMR models further showed that maternal preconception BPA and mono(2-ethyl-5-hydroxyhexyl) phthalate, and paternal preconception mono(2-ethylhexyl) phthalate were positively associated with preterm birth when the remaining mixture components were held at their median concentrations. Couple-based BKMR models showed a similar relative contribution of paternal (PIP: 61%) and maternal (PIP: 77%) preconception mixtures on preterm birth. We found a positive joint effect on preterm birth across increasing quantiles of couples' total mixture concentrations. CONCLUSION: In this prospective cohort of subfertile couples, maternal BPA and DEHP, and paternal DEHP exposure before conception were positively associated with preterm birth. Both parental windows jointly contributed to the outcome. These results suggest that preterm birth may be a couple-based pregnancy outcome.

    • Genetics and Genomics
      1. Genomic characterization of 99 viruses from the bunyavirus families Nairoviridae, Peribunyaviridae, and Phenuiviridae, including 35 previously unsequenced virusesexternal icon
        Kapuscinski ML, Bergren NA, Russell BJ, Lee JS, Borland EM, Hartman DA, King DC, Hughes HR, Burkhalter KL, Kading RC, Stenglein MD.
        PLoS Pathog. 2021 Mar 1;17(3):e1009315.
        Bunyaviruses (Negarnaviricota: Bunyavirales) are a large and diverse group of viruses that include important human, veterinary, and plant pathogens. The rapid characterization of known and new emerging pathogens depends on the availability of comprehensive reference sequence databases that can be used to match unknowns, infer evolutionary and pathogenic potential, and make response decisions in an evidence-based manner. In this study, we determined the coding-complete genome sequences of 99 bunyaviruses in the Centers for Disease Control and Prevention's Arbovirus Reference Collection, focusing on orthonairoviruses (family Nairoviridae), orthobunyaviruses (Peribunyaviridae), and phleboviruses (Phenuiviridae) that either completely or partially lacked genome sequences. These viruses had been collected over 66 years from 27 countries from vertebrates and arthropods representing 37 genera. Many of the viruses had been characterized serologically and through experimental infection of animals but were isolated in the pre-sequencing era. We took advantage of our unusually large sample size to systematically evaluate genomic characteristics of these viruses, including reassortment, and co-infection. We corroborated our findings using several independent molecular and virologic approaches, including Sanger sequencing of 197 genome segments, and plaque isolation of viruses from putative co-infected virus stocks. This study contributes to the described genetic diversity of bunyaviruses and will enhance the capacity to characterize emerging human pathogenic bunyaviruses.

    • Global Health
      1. Health Problems in Travellers to Nepal Visiting CIWEC Clinic in Kathmandu - A GeoSentinel Analysisexternal icon
        Pandey P, Lee K, Amatya B, Angelo KM, Shlim DR, Murphy H.
        Travel Med Infect Dis. 2021 Feb 24:101999.
        BackgroundNepal has always been a popular international travel destination. There is limited published data, however, on the spectrum of illnesses acquired by travellers to Nepal. MethodsGeoSentinel is a global data collection network of travel and tropical medicine providers that monitors travel-related morbidity. Records for ill travellers with at least one confirmed or probable diagnosis, were extracted from the GeoSentinel database for the CIWEC Clinic Kathmandu site from January 1, 2009 to December 31, 2017. ResultsA total of 24,271 records were included. The median age was 30 years (range: 0-91); 54% were female. The top 3 system-based diagnoses in travellers were: gastrointestinal (32%), pulmonary (16%), and dermatologic (9%). Altitude illness comprised 9% of all diagnoses. There were 278 vaccine-preventable diseases, most frequently influenza A (41%) and typhoid fever (19%; S. typhi 52 and S. paratyphi 62). Of 64 vector-borne illnesses, dengue was the most frequent (64%), followed by imported malaria (14%). There was a single traveller with Japanese encephalitis. Six deaths were reported. ConclusionsTravel lers to Nepal face a wide spectrum of illnesses, particularly diarrhoea, respiratory disease, and altitude illness. Pre-travel consultations for travellers to Nepal should focus on prevention and treatment of diarrhoea and altitude illness, along with appropriate immunizations and travel advice.

    • Health Disparities
      1. Urban-Rural Differences in Pregnancy-Related Deaths, United States, 2011-2016external icon
        Merkt PT, Kramer MR, Goodman DA, Brantley MD, Barrera CM, Eckhaus L, Petersen EE.
        Am J Obstet Gynecol. 2021 Feb 25.
        BACKGROUND: The U.S. pregnancy-related mortality ratio has not improved over the past decade and includes striking disparities by race/ethnicity and by state. Understanding differences in pregnancy-related mortality across and within urban and rural areas can guide the development of interventions for preventing future pregnancy-related deaths. OBJECTIVE: We sought to compare pregnancy-related mortality across and within urban and rural counties by race/ethnicity and age. STUDY DESIGN: We conducted a descriptive analysis of 3,747 pregnancy-related deaths during 2011-2016 (the most recent available) with available ZIP code or county data in the Pregnancy Mortality Surveillance System, among Hispanic and non-Hispanic White, Black, American Indian/Alaska Native, and Asian/Pacific Islander women ages 15-44 years. We aggregated data by U.S. county and grouped counties per the National Center for Health Statistics Urban-Rural Classification Scheme for Counties. We used R statistical software, epitools, to calculate the pregnancy-related mortality ratio (number of pregnancy-related deaths per 100,000 live births) for each urban-rural grouping, obtain 95% confidence intervals, and perform exact tests of ratio comparisons using the Poisson distribution. RESULTS: Of the total 3,747 pregnancy-related deaths analyzed, 52% occurred in large metro counties and 7% occurred in noncore (rural) counties. Large metro counties had the lowest pregnancy-related mortality ratio (14.8, 95% CI: 14.2-15.5) while noncore counties had the highest (24.1, 95% CI: 21.4-27.1), including for most race/ethnicity and age groups. Pregnancy-related mortality ratio age disparities increased with rurality. Women ages 25-34 years and ages 35-44 years living in noncore counties had pregnancy-related mortality ratios 1.5 and 3 times higher, respectively, than women of the same age groups in large metro counties. Within each urban-rural category, pregnancy-related mortality ratios were higher among non-Hispanic Black women compared to non-Hispanic White women. Non-Hispanic American Indian/Alaska Native pregnancy-related mortality ratios in small metro, micropolitan, and noncore counties were 2-3 times that of non-Hispanic White women in the same areas. CONCLUSION: Although more than half of pregnancy-related deaths occurred in large metro counties, the pregnancy-related mortality ratio rose with increasing rurality. Disparities existed among urban-rural categories, including by age group and by race/ethnicity. Geographic location is an important context for initiatives to prevent future deaths and eliminate disparities. Further research is needed to better understand reasons for the observed urban-rural differences and to guide a multifactorial response to reduce pregnancy-related deaths.

    • Health Economics
      1. Effects of Access to Legal Same-Sex Marriage on Marriage and Healthexternal icon
        Carpenter CS, Eppink ST, Gonzales G, McKay T.
        J Policy Anal Manage. 2021 .
        We provide the first comprehensive evidence on the effects of access to legal same-sex marriage (SSM) on marriage and adult health using the full rollout of marriage equality across the United States. Using data from the CDC BRFSS from 2000 to 2017, we relate changes in outcomes for individuals in same-sex households (SSH) coincident with adoption of legal SSM in two-way fixed effects models. A substantial share of these households includes gay and lesbian couples. For men in SSH, we find robust evidence that access to legal SSM significantly increased marriage take-up, health insurance coverage, access to care, and healthcare utilization. Results for women in SSH are inconclusive apart from a clear increase in marriage take-up. Our results provide the first evidence that legal access to SSM significantly improved health for adult gay men.

      2. Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990-2015external icon
        González-Roldán JF, Undurraga EA, Meltzer MI, Atkins C, Vargas-Pino F, Gutiérrez-Cedillo V, Hernández-Pérez JR.
        PLoS Negl Trop Dis. 2021 Mar 4;15(3):e0009130.
        BACKGROUND: Rabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990-2015. METHODOLOGY: Combining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results. PRINCIPAL FINDINGS: Results suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns. CONCLUSIONS: Annual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.

    • Healthcare Associated Infections
      1. Donor-derived human herpesvirus 8 and development of Kaposi sarcoma among 6 recipients of organs from donors with high-risk sexual and substance use behaviorexternal icon
        Dollard SC, Annambhotla P, Wong P, Meneses K, Amin MM, La Hoz RM, Lease ED, Budev M, Arrossi AV, Basavaraju SV, Thomas CP.
        Am J Transplant. 2021 Feb;21(2):681-688.
        Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV-8) infection or through donor-derived HHV-8 transmission. We describe 6 cases of donor-derived HHV-8 infection and KS investigated from July 2018 to January 2020. Organs from 6 donors, retrospectively identified as HHV-8-positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of 6 donors had risk factors for HHV-8 infection reported in donor history questionnaires. Fourteen of 22 organ recipients (64%) had evidence of posttransplant HHV-8 infection. Lung recipients were particularly susceptible to KS. Four of the 6 recipients who developed KS died from KS or associated complications. The US opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase the risk of HHV-8 transmission to recipients. Better awareness of the risk of posttransplant KS for recipients of organs from donors with HHV-8 infection risk could be useful for recipient management. Testing donors and recipients for HHV-8 is currently challenging with no validated commercial serology kits available. Limited HHV-8 antibody testing is available through some US reference laboratories and the Centers for Disease Control and Prevention.

      2. Recovery efficiency of two glove-sampling methodsexternal icon
        Lyons AK, Rose LJ, Noble-Wang J.
        Infect Control Hosp Epidemiol. 2021 Mar 2:1-3.
        Two methods to sample pathogens from gloved hands were compared: direct imprint onto agar and a sponge-wipe method. The sponge method was significantly better at recovering Clostridiodes difficile spores, and no difference was observed between the methods at 101 inoculum for carbapenemase-producing KPC+ Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii.

      3. Outbreak of hepatitis B and hepatitis C virus infections associated with a cardiology clinic, West Virginia, 2012-2014external icon
        Tressler SR, Del Rosario MC, Kirby MD, Simmons AN, Scott MA, Ibrahim S, Forbi JC, Thai H, Xia GL, Lyman M, Collier MG, Patel PR, Bixler D.
        Infect Control Hosp Epidemiol. 2021 Mar 1:1-6.
        OBJECTIVE: To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic. DESIGN: Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome. SETTING: Outpatient cardiology clinic. PATIENTS: Patients undergoing MPI. METHODS: Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed. RESULTS: During 2012-2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%-99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified. CONCLUSIONS: This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings.

    • Immunity and Immunization
      1. Availability of Adult Vaccination Services by Provider Type and Settingexternal icon
        Granade CJ, McCord RF, Bhatti AA, Lindley MC.
        Am J Prev Med. 2021 Feb 22.
        INTRODUCTION: Knowledge regarding the benefits for adult vaccination services under Medicaid's fee-for-service arrangement is dated; little is known regarding the availability of vaccination services for adult Medicaid beneficiaries in MCO arrangements. This study evaluates the availability of provider reimbursement benefits for adult vaccination services under fee-for-service and MCO arrangements for different types of healthcare providers and settings. METHODS: A total of 43 Medicaid directors across the 50 U.S. states and the District of Columbia participated in a semistructured survey conducted from June 2018 to June 2019 (43/51). The frequency of Medicaid fee-for-service and MCO arrangements reporting reimbursement for adult vaccination services by various provider types and settings were assessed in 2019. Elements of vaccination services examined in this study were vaccine purchase, vaccine administration, and vaccination-related counseling. RESULTS: Under fee-for-service, 41 Medicaid programs reimburse primary care providers for adult vaccine purchase (41/43); fewer programs reimburse vaccine administration and vaccination-related counseling (33/43 and 30/43, respectively). Similar results were observed for obstetricians-gynecologists, nurse practitioners, and pharmacies. Although 24 fee-for-service (24/43) and 23 MCO (23/34) arrangements cover adult vaccination services in most settings, long-term care facilities have the lowest reported reimbursement eligibility. CONCLUSIONS: In most jurisdictions, vaccination services for adult Medicaid beneficiaries are available for a variety of healthcare provider types and settings under both fee-for-service and MCO arrangements. However, because provider reimbursement benefits remain inconsistent for adult vaccination counseling services and within long-term care facilities, access to adult vaccination services may be reduced for Medicaid beneficiaries who depend on these resources.

      2. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Janssen COVID-19 Vaccine - United States, February 2021external icon
        Oliver SE, Gargano JW, Scobie H, Wallace M, Hadler SC, Leung J, Blain AE, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, MacNeil J, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):329-332.

    • Injury and Violence
      1. Drowning in Uganda: examining data from administrative sourcesexternal icon
        Clemens T, Oporia F, Parker EM, Yellman MA, Ballesteros MF, Kobusingye O.
        Inj Prev. 2021 Feb 26.
        BACKGROUND: Drowning death rates in the African region are estimated to be the highest in the world. Data collection and surveillance for drowning in African countries are limited. We aimed to establish the availability of drowning data in multiple existing administrative data sources in Uganda and to describe the characteristics of drowning based on available data. METHODS: We conducted a retrospective descriptive study in 60 districts in Uganda using existing administrative records on drowning cases from January 2016 to June 2018 in district police offices, marine police detachments, fire/rescue brigade detachments, and the largest mortuary in those districts. Data were systematically deduplicated to determine and quantify unique drowning cases. RESULTS: A total of 1435 fatal and non-fatal drowning cases were recorded; 1009 (70%) in lakeside districts and 426 (30%) in non-lakeside districts. Of 1292 fatal cases, 1041 (81%) were identified in only one source. After deduplication, 1283 (89% of recorded cases; 1160 fatal, 123 non-fatal) unique drowning cases remained. Data completeness varied by source and variable. When demographic characteristics were known, fatal victims were predominantly male (n=876, 85%), and the average age was 24 years. In lakeside districts, 81% of fatal cases with a known activity at the time of drowning involved boating. CONCLUSION: Drowning cases are recorded in administrative sources in Uganda; however, opportunities to improve data coverage and completeness exist. An improved understanding of circumstances of drowning in both lakeside and non-lakeside districts in Uganda is required to plan drowning prevention strategies.

      2. OBJECTIVE: To assess adherence to 5 key recommendations in the Centers for Disease Control and Prevention evidence-based guideline on pediatric mild traumatic brain injury, this article presents results from the 2019 DocStyles survey. STUDY DESIGN: Cross-sectional, web-based survey of 653 healthcare providers. RESULTS: Most healthcare providers reported adhering to the recommendations regarding the use of computed tomography and providing education and reassurance to patients and their families. However, less than half reported routinely examining their patients with mild traumatic brain injury (mTBI) using age-appropriate, validated symptom scales, assessing for risk factors for prolonged recovery, and advising patients to return to noncontact, light aerobic activities within 2 to 3 days. Self-reported mTBI diagnosis, prognosis, and management practices varied by specialty. Only 3.8% of healthcare providers answered all 7 questions in a way that is most consistent with the 5 recommendations examined from the Centers for Disease Control and Prevention Pediatric mTBI Guideline. CONCLUSION: This study highlights several important information gaps regarding pediatric mTBI diagnosis and management. Further efforts to improve adoption of guideline recommendations may be beneficial to ensure optimal outcomes for children following an mTBI.

    • Laboratory Sciences
      1. Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infectionexternal icon
        Bessières M, Plebanek E, Chatterjee P, Shrivastava-Ranjan P, Flint M, Spiropoulou CF, Warszycki D, Bojarski AJ, Roy V, Agrofoglio LA.
        Eur J Med Chem. 2021 Jan 27;214:113211.
        Novel 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles were designed and synthesized as Ebola virus inhibitors. The proposed structures of the new prepared benzimidazole-piperidine hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-Ebola activity. Among tested molecules, compounds 26a (EC(50=)0.93 μM, SI = 10) and 25a (EC(50=)0.64 μM, SI = 20) were as potent as and more selective than Toremifene reference drug (EC(50) = 0.38 μM, SI = 7) against cell line. Data suggests that the mechanism by which 25a and 26a block EBOV infection is through the inhibition of viral entry at the level of NPC1. Furthermore, a docking study revealed that several of the NPC1 amino acids that participate in binding to GP are involved in the binding of the most active compounds 25a and 26a. Finally, in silico ADME prediction indicates that 26a is an idealy drug-like candidate. Our results could enable the development of small molecule drug capable of inhibiting Ebola virus, especially at the viral entry step.

      2. Subtype Diagnosis of Sporadic Creutzfeldt-Jakob Disease with Diffusion Magnetic Resonance Imagingexternal icon
        Bizzi A, Pascuzzo R, Blevins J, Moscatelli ME, Grisoli M, Lodi R, Doniselli FM, Castelli G, Cohen ML, Stamm A, Schonberger LB, Appleby BS, Gambetti P.
        Ann Neurol. 2021 Mar;89(3):560-572.
        OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI). METHODS: MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy-confirmed diagnosis of "pure" sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure-prion subtype classification algorithm with MRI (PriSCA_MRI)-uses only MRI examinations; the second-PriSCA_MRI + Gen-includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow-up. RESULTS: PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy. PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes. Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. INTERPRETATION: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560-572.

      3. Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabsexternal icon
        Bowden KE, Joseph SJ, Cartee JC, Ziklo N, Danavall D, Raphael BH, Read TD, Dean D.
        mSphere. 2021 Mar 3;6(2).
        Chlamydia trachomatis, an obligately intracellular bacterium, is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. Numbers of U.S. infections of the urogenital tract and rectum have increased annually. Because C. trachomatis is not easily cultured, comparative genomic studies are limited, restricting our understanding of strain diversity and emergence among populations globally. While Agilent SureSelect(XT) target enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal samples, public access to these libraries is not available. We therefore designed an RNA bait library (34,795 120-mer probes based on 85 genomes, versus 33,619 probes using 74 genomes in a previous one) to augment organism sequencing from clinical samples that can be shared with the scientific community, enabling comparison studies. We describe the library and limit of detection for genome copy input, and we present results of 100% efficiency and high-resolution determination of recombination and identical genomes within vaginal-rectal specimen pairs in women. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, which limits our understanding of urogenital and rectal C. trachomatis transmission and impact on morbidity. To provide a publicly available workflow for whole-genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we developed and report on an RNA bait library to enrich the organism from clinical samples for sequencing. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis and identified recombinant and identical C. trachomatis genomes in paired vaginal-rectal samples from women. Our workflow provides a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital, and rectal infections and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity.

      4. Illicit use of the potent opioid fentanyl and its analogs (fentanyls) are on the rise in the United States. As use increases, drug production tends to also increase, leading to more locations being contaminated with the potentially lethal substance. Because fentanyl-contaminated locations may present a risk to the general public, a method for sampling, identifying, and quantitating these fentanyls from surfaces is in need. This research developed and optimized a surface-wipe collection and extraction method for 17 fentanyls and 10 common fentanyl adulterants from a non-porous surface and quantitated the amount of each compound collected with liquid chromatography tandem mass spectrometry. The final, optimized surface-wipe method resulted in an average collection and extraction efficiency (±SD) of 62.0 (±14.0)%, with a range of 34.1 (±2.6) – 82.5 (±9.6)%. While legislation has yet to be implemented regarding remediation levels for fentanyl-contaminated locations, when such legislation is drafted, this method can be implemented to determine the safety of these locations prior to and after decontamination has occurred.

      5. Comparison of performance between Fast Track Diagnostics Respiratory Kit and the CDC global reference laboratory for influenza rRT-PCR panel for detection of influenza A and influenza Bexternal icon
        Cissé A, Milucky J, Ilboudo AK, Waller JL, Bicaba B, Medah I, Mirza S, Whitney CG, Tarnagda Z.
        Influenza Other Respir Viruses. 2021 Feb 26.
        BACKGROUND: Reliable diagnostics are a key to identifying influenza infections. OBJECTIVES: Our objectives were to describe the detection of influenza among severe acute respiratory infection (SARI) cases, to compare test results from the Fast Track Diagnostics (FTD) Kit for influenza detection to the Centers for Disease Control (CDC) human influenza virus detection and characterization panel, and to assess seasonality of influenza in Burkina Faso. METHODS: Nasopharyngeal and oropharyngeal specimens from SARI cases (hospitalized patients with fever, cough, and onset in the previous 10 days) were tested using the FTD-33 Kit and the CDC rRT-PCR influenza assays. We assessed sensitivity and specificity of the FTD-33 Kit for detecting influenza A, influenza B, and the influenza A(H1N1)pdm09 strain using the CDC human influenza rRT-PCR panel as the gold standard. RESULTS: From December 2016 to February 2019, 1706 SARI cases were identified, 1511 specimens were tested, and 211 were positive for influenza A (14.0%) and 100 for influenza B (6.6%) by either assay. Higher influenza circulation occurred between November and April with varying peaks of influenza A and influenza B. Sensitivity of the FTD-33 assay was 91.9% for influenza A, 95.7% for influenza B, and 93.8% for A(H1N1)pdm09 subtype. Specificity was over 99% for all three tests. CONCLUSIONS: Our study indicates that Burkina Faso has one peak of influenza each year which is similar to the Northern Hemisphere and differs from other countries in West Africa. We found high concordance of influenza results between the two assays indicating FTD-33 can be used to reliably detect influenza among SARI cases.

      6. Impact of T-Cell Xtend on T-SPOT.TB Assay in High-Risk Individuals after Delayed Blood Sample Processingexternal icon
        Feng PJ, Wu Y, Ho CS, Chinna L, Whelen AC, Largen A, Brostrom R, Reves R, Belknap R, Cattamanchi A, Banaei N.
        J Clin Microbiol. 2021 Mar 3.
        T-SPOT®.TB (T-SPOT) is an interferon-gamma release assay (IGRA) used to detect infection with Mycobacterium tuberculosis based on the number of spot-forming T-cells; however, delays in sample processing have been shown to reduce the number of these spots that are detected following laboratory processing. Adding T-Cell Xtend (XT) into blood samples before processing reportedly extends the amount of time allowed between blood collection and processing up to 32 hours. In this study, paired blood samples from 306 adolescents and adults at high risk for latent tuberculosis (TB) infection (LTBI) or progression to TB disease were divided into three groups: 1) early processing (∼4.5 hours after collection) with and without XT, 2) delayed processing (∼24 hours after collection) with and without XT, and 3) early processing without XT and delayed processing with XT. The participants' paired samples were processed at a local laboratory and agreement of qualitative and quantitative results were assessed. The addition of XT did not consistently increase or decrease the number of spots. In groups 1, 2, and 3, samples processed with XT had 13% (10/77), 28.0% (30/107) and 24.6% (30/122), respectively, more spots while 33.8% (26/77), 26.2% (28/107), and 38.5% (47/122) had less spots compared with samples processed without XT. The findings suggest that XT does not reliably mitigate the loss of spot-forming T-cells in samples with processing delay.

      7. New pneumococcal serotype 15Dexternal icon
        Pimenta F, Moiane B, Gertz RE, Chochua S, Snippes Vagnone PM, Lynfield R, Sigaúque B, Carvalho MD, Beall B.
        J Clin Microbiol. 2021 Mar 3.
        The pneumococcal serogroup 15 comprises 4 capsular polysaccharide serotypes (15A, 15B, 15C, 15F) that collectively account for an impactful disease burden (1,2).….

    • Nutritional Sciences
      1. An Integrated Enhanced Infant and Young Child Feeding (IYCF) and Micronutrient Powder Intervention Improved Select IYCF Practices Among Caregivers of Children Aged 12-23 Months in Eastern Ugandaexternal icon
        Ford ND, Ruth LJ, Ngalombi S, Lubowa A, Halati S, Ahimbisibwe M, Whitehead RD, Mapango C, Jefferds ME.
        Curr Dev Nutr. 2021 Feb;5(2):nzab003.
        BACKGROUND: There is little evidence of the impact of integrated programs distributing nutrition supplements with behavior change on infant and young child feeding (IYCF) practices. OBJECTIVE: We evaluated the impact of an integrated IYCF/micronutrient powder intervention on IYCF practices among caregivers of children aged 12-23 mo in eastern Uganda. METHODS: We used pre-post data from 2 population-based, cross-sectional surveys representative of children aged 12-23 mo in Amuria (intervention) and Soroti (nonintervention) districts (n = 2816). Caregivers were interviewed in June/July at baseline in 2015 and 12 mo after implementation in 2016. We used generalized linear mixed models with cluster as a random effect to calculate the average intervention effect on receiving IYCF counseling, ever breastfed, current breastfeeding, bottle feeding, introducing complementary feeding at age 6 mo, continued breastfeeding at ages 1 and 2 y, minimum meal frequency (MMF), minimum dietary diversity, minimum acceptable diet (MAD), and consumption of food groups the day preceding the survey. RESULTS: Controlling for child age and sex, household wealth and food security, and caregiver schooling, the intervention was positively associated with having received IYCF counseling by village health team [adjusted prevalence difference-in-difference (APDiD): +51.6%; 95% CI: 44.0%, 59.2%]; timely introduction of complementary feeding (APDiD: +21.7%; 95% CI: 13.4%, 30.1%); having consumed organs or meats (APDiD: +9.0%; 95% CI: 1.4%, 16.6%) or vitamin A-rich fruits or vegetables (APDiD: +17.5%; 95% CI: 4.5%, 30.5%); and MMF (APDiD: +18.6%; 95% CI: 11.2%, 25.9%). The intervention was negatively associated with having consumed grains, roots, or tubers (APDiD: -4.4%; 95% CI: -7.0%, -1.7%) and legumes, nuts, or seeds (APDiD: -15.6%; 95% CI: -26.2%, -5.0%). Prevalences of some IYCF practices were low in Amuria at endline including MAD (19.1%; 95% CI :16.3%, 21.9%). CONCLUSIONS: The intervention had a positive impact on several IYCF practices; however, endline prevalence of some indicators suggests a continued need to improve complementary feeding practices.

      2. Food policy councils (FPCs) are one form of community coalition that aims to address challenges to local food systems and enhance availability, accessibility, and affordability of healthy foods for local residents. We used data from the 2014 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living, a nationally representative survey of US municipalities (n = 2029), to examine the prevalence of FPCs and cross-sectional associations between FPCs and four types of supports for healthy food access (approaches to help food stores, practices to support farmers markets, transportation-related supports, and community planning documents). Overall, 7.7% of municipalities reported having a local or regional FPC. FPCs were more commonly reported among larger municipalities with ≥50,000 people (29.2%, 95% Confidence Interval (CI): 21.6, 36.8) and western region municipalities (13.2%, 95% CI: 9.6, 16.8). After multivariable adjustment, municipalities with FPCs had significantly higher odds of having all four types of supports, compared to those without FPCs (adjusted odds ratio (aOR) range: 2.4–3.4). Among municipalities with FPCs (n = 156), 41% reported having a local government employee or elected official as a member, and 46% had a designated health or public health representative. Although FPCs were uncommon, municipalities that reported having a local or regional FPC were more likely to report having supports for healthy food access for their residents.

    • Occupational Safety and Health
      1. Survey: workplace violence prevention programs in nursing homesexternal icon
        Blando JD, Ridenour ML, Hartley D.
        J Healthc Prot Manage. 2021 Jan;37(1):100-113.
        A survey of facilities in two states--one with workplace violence prevention regulations and one without--indicates that nursing home administrators know that workplace violence is a risk in their facilities and have instituted policies and programs to prevent it. The programs, though, tend to be piecemeal and informal. Surprisingly, the programs in the regulated state were not more rigorous than those in the other state, probably because of lack of enforcement and limited awareness of the regulations.

      2. Firefighter hemodynamic responses to different fire training environmentsexternal icon
        Lefferts EC, Rosenberg AJ, Grigoriadis G, Wee SO, Kerber S, Fent KW, Horn GP, Smith DL, Fernhall B.
        Vasc Med. 2021 Feb 19:1358863x20987608.
        Firefighting is associated with an increased risk for a cardiovascular (CV) event, likely due to increased CV strain. The increase in CV strain during firefighting can be attributed to the interaction of several factors such as the strenuous physical demand, sympathetic nervous system activation, increased thermal burden, and the environmental exposure to smoke pollutants. Characterizing the impact of varying thermal burden and pollutant exposure on hemodynamics may help understand the CV burden experienced during firefighting. The purpose of this study was to examine the hemodynamic response of firefighters to training environments created by pallets and straw; oriented strand board (OSB); or simulated fire/smoke (fog). Twenty-three firefighters had brachial blood pressure measured and central blood pressure and hemodynamics estimated from the pressure waveform at baseline, and immediately and 30 minutes after each scenario. The training environment did not influence the hemodynamic response over time (interaction, p > 0.05); however, OSB scenarios resulted in higher pulse wave velocity and blood pressure (environment, p < 0.05). In conclusion, conducting OSB training scenarios appears to create the largest arterial burden in firefighters compared to other scenarios in this study. Environmental thermal burden in combination with the strenuous exercise, and psychological and environmental stress placed on firefighters should be considered when designing fire training scenarios and evaluating CV risk.

    • Occupational Safety and Health - Mining
      1. Why Do Haul Truck Fatal Accidents Keep Occurring?external icon
        Bellanca JL, Ryan ME, Orr TJ, Burgess-Limerick RJ.
        Min Metall Explor. 2021 .
        Powered haulage continues to be a large safety concern for the mining industry, accounting for approximately 50% of the mining fatal accidents every year. Among these fatal accidents, haul-truck-related accidents are the most common, with 6 of 28 and 6 of 27 fatal accidents occurring in 2017 and 2018, respectively. To better understand why these accidents continue to occur and what can be done to prevent them, researchers reviewed the 91 haul-truck-related fatal accidents that occurred in the USA from 2005 to 2018 and performed bow-tie analyses using the final reports published by the Mine Safety and Health Administration. The analyses explore the context of the accidents with a focus on the initiating event, event outcome, hazards present, and possible preventative and mitigative controls. Overall, the vast majority of the accidents resulted in a haul truck colliding with the environment, and the majority of these events were initiated by loss of situational awareness or loss of control. The majority of the hazards were related to design and organizational controls. The results of this study suggest a need to investigate operator decision-making and organizational controls and to focus on improving design and operation controls such as mine design and operational procedures.

      2. Purpose. Although a focus on safety communication between managers and employees has been prevalent, research around coworker influence in this communication has been fragmented in the literature. Methods. To examine these issues, researchers gathered survey data from 1,955 mine employees from surface stone, sand, and gravel (SSG) and industrial mineral operations across the United States between 2016 and 2018 and studied the relationships between justice perceptions, supervisor communication, and coworker communication on behavioral safety compliance. Results. Using structural equation modeling, coworker communication partially mediated the direct effects of supervisor communication and justice perceptions on behavioral safety compliance-where the indirect effects were greater for justice perceptions. Conclusion. The results demonstrate the value in formal and informal communication paths to facilitate employee safety compliance; and that enhanced perceptions of job fairness and adaptability enhances coworker communication, further improving compliance in an interdependent environment.Author Note:Emily J. Haas ORCID ID:, Emily J. Haas is a Senior Research Behavioral Scientist at the National Institute for Occupational Safety and Health, Pittsburgh Mining Research Division. Patrick L. Yorio is a Statistician at the National Institute for Occupational Safety and Health, National Personal Protective Technology Laboratory. We have no known conflict of interest to discloseDisclaimerThe findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. Mention of any company or product does not constitute endorsement by NIOSH.

      3. Illustrating the Luminaire Comparison Methodexternal icon
        Sammarco J, Helfrich W.
        IEEE Trans Ind Appl. 2021 .
        The Mine Safety and Health Administration (MSHA) enforces underground coal mining lighting regulations in the United States and for issues approvals for electrical devices and machines. Companies submit standard test and evaluation (ST&amp;E) documentation to MSHA when seeking approval on a machine with mounted lighting. Subsequent machine modifications, such as changing the type of light lamp from incandescent to light-emitting diode (LED), will require an update via the Revised Approval Modification Program (RAMP). Older incandescent and fluorescent lamps are being replaced by light-emitting diode (LED) technology having many advantages. Today, thousands of obsolete compact fluorescent lamps (CFLs) are used in underground coal mines. Replacing these with LED lamps requires RAMP documentation for each ST&amp;E and requires MSHA to review virtually thousands of RAMPS that would require an exorbitant amount of resources and would create backlogs that would take MSHA potentially years to process. This problem is addressed by the Luminaire Comparison Method (LCM) that determines if the luminous intensity from a luminaire with a replacement lamp meets or exceeds the luminous intensity of the luminaire with a legacy lamp. If it does, then the replacement lamp is determined as equivalent and can be used as a replacement. One RAMP can then replace multiple RAMPs that would be required without the method. One company estimates over <formula><tex>$700,000 USD in savings; another company has saved about $</tex></formula>200,000 USD using the LCM. It is projected that the LCM will save millions of dollars. This paper provides several examples to illustrate the LCM. USGov

    • Parasitic Diseases
      1. Giardiasis Outbreaks - United States, 2012-2017external icon
        Conners EE, Miller AD, Balachandran N, Robinson BM, Benedict KM.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):304-307.

      2. Certifying Guinea worm eradication in humans and animalsexternal icon
        Hopkins DR, Ijaz K, Weiss AJ, Roy SL.
        Lancet. 2021 Feb 27;397(10276):793-794.

      3. Performance of a fully-automated system on a WHO malaria microscopy evaluation slide setexternal icon
        Horning MP, Delahunt CB, Bachman CM, Luchavez J, Luna C, Hu L, Jaiswal MS, Thompson CM, Kulhare S, Janko S, Wilson BK, Ostbye T, Mehanian M, Gebrehiwot R, Yun G, Bell D, Proux S, Carter JY, Oyibo W, Gamboa D, Dhorda M, Vongpromek R, Chiodini PL, Ogutu B, Long EG, Tun K, Burkot TR, Lilley K, Mehanian C.
        Malar J. 2021 Feb 25;20(1):110.
        BACKGROUND: Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. METHODS: The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. RESULTS: The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. CONCLUSIONS: EasyScan GO's expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

      4. A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasisexternal icon
        Krentel A, Basker N, Beau de Rochars M, Bogus J, Dilliott D, Direny AN, Dubray C, Fischer PU, Ga AL, Goss CW, Hardy M, Howard C, Jambulingam P, King CL, Laman M, Lemoine JF, Mallya S, Robinson LJ, Samuela J, Schechtman KB, Steer AC, Supali T, Tavul L, Weil GJ.
        PLoS Negl Trop Dis. 2021 Mar;15(3):e0009002.
        BACKGROUND: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). METHODOLOGY/PRINCIPAL FINDINGS: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. CONCLUSIONS/SIGNIFICANCE: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

    • Substance Use and Abuse
      1. Street-drug lethality index: A novel methodology for predicting unintentional drug overdose fatalities in population researchexternal icon
        Hall OE, Trent Hall O, Eadie JL, Teater J, Gay J, Kim M, Cauchon D, Noonan RK.
        Drug Alcohol Depend. 2021 Feb 16;221:108637.
        BACKGROUND: Emerging evidence suggests the composition of local illicit drug markets varies over time and the availability and relative lethality of illicit drugs may contribute to temporal trends in overdose mortality. Law enforcement drug seizures represent a unique opportunity to sample the makeup of local drug markets. Prior research has associated shifts in the types of drugs seized and trends in unintentional drug overdose mortality. The present report builds on this work by demonstrating a novel methodology, the Street-Drug Lethality Index, which may serve as a low-lag predictor of unintentional overdose deaths. METHODS: Data included administrative records of law enforcement drug seizures and unintentional drug overdose deaths in Ohio from 2009 -to- 2018. Death records and lab results from drug seizures occurring during the calendar year 2017 were transformed via the described procedure to create lethality indices for individual drugs. These indices were then summed annually to create the independent variable for a linear regression model predicting unintentional overdose deaths for all years during the study period. RESULTS: The regression model explained 93 % of the year-to-year variance in unintentional overdose fatalities (slope = 0.009480; CI = 0.007369 to 0.011590; t(10) = 10.355942; P = 0.000007; Y = 11.808982 + 0.009480X, r(2) = 0.931). CONCLUSION: These findings contribute to a growing body of evidence that changes in the composition of the drug supply may predict trends in unintentional overdose mortality. The proposed methodology might inform future overdose prevention and response efforts as well as research.

      2. Prevalence of Electronic Cigarette Use Among Adult Workers - United States, 2017-2018external icon
        Syamlal G, Clark KA, Blackley DJ, King BA.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 5;70(9):297-303.

      3. Smoking and cessation behaviors in patients at federally funded health centers - United States, 2014external icon
        Trapl ES, VanFrank B, Kava CM, Trinh V, Land SR, Williams RS, Frost E, Babb S.
        Drug Alcohol Depend. 2021 Feb 15;221:108615.
        BACKGROUND: Federally funded health centers (HCs) provide care to the most vulnerable populations in the U.S., including populations with disproportionately higher smoking prevalence such as those with lower incomes. METHODS: This study compared characteristics of adult HC patients, by cigarette smoking status, and assessed smoking cessation-related behaviors using 2014 Health Center Patient Survey data; analysis was restricted to adults with data on cigarette smoking status (n = 5583). Chi-square and logistic regression analyses were conducted. RESULTS: Overall, 28.1 % were current smokers and 19.2 % were former smokers. Current smokers were more likely to report fair/poor health (48.2 %) and a high burden of behavioral health conditions (e.g., severe psychological distress 23.9 %) versus former and never smokers. Most current smokers reported wanting to quit in the past 12 months (79.0 %) and receiving advice to quit from a healthcare professional (78.7 %). In a multivariable model, age <45, non-white race, COPD diagnosis, and past 3-month marijuana use were significantly associated with desire to quit. Few former smokers (15.2 %) reported using cessation treatment, though use was higher among those who quit within the previous year (30.6 %). CONCLUSIONS: Although most current smokers reported a desire to quit, low uptake of evidence-based treatment may reduce the number who attempt to quit and succeed. Given the burden of tobacco use, future efforts could focus on identifying and overcoming unique personal, healthcare professional, or health system barriers to connecting them with cessation treatments. Increasing access to cessation treatments within HCs could reduce smoking-related disparities and improve population health.

      4. BACKGROUND AND OBJECTIVES: In previous studies, researchers have reported that youth with a lifetime history of prescription opioid misuse (POM) are at an increased risk for suicidal ideation, planning, and attempts. In this study, we investigate whether the association between youth POM and suicide outcomes differs by recency of POM (ie, none, past, or current misuse). METHODS: In this report, we use data from the 2019 Youth Risk Behavior Survey to examine associations between recency of POM (current POM, past POM, and no POM) and suicide risk behaviors among US high school students. RESULTS: After controlling for demographics, alcohol, and other drug use, both current POM and past POM were significantly associated with all suicide risk behaviors compared with no POM. Students who reported current POM had the highest adjusted prevalence ratios (aPRs) for suicidal ideation (aPR: 2.30; 95% confidence interval [CI] 1.97-2.69), planning (aPR: 2.33; 95% CI 1.99-2.79), attempts (aPR: 3.21; 95% CI 2.56-4.02), and feeling sad or hopeless (aPR: 1.59; 95% CI 1.37-1.84). Students who reported current POM also were significantly more likely than youth who reported past POM to report that they had seriously considered attempting suicide, made a suicide plan, and attempted suicide. CONCLUSIONS: Although POM, particularly current POM, is associated with increases in the risk for suicide-related behaviors and experiences of youth, comprehensive prevention approaches that address the intersections between suicide and POM provide a promising path forward for addressing these public health challenges among youth.

    • Zoonotic and Vectorborne Diseases
      1. Surveillance for West Nile Virus Disease - United States, 2009-2018external icon
        McDonald E, Mathis S, Martin SW, Staples JE, Fischer M, Lindsey NP.
        MMWR Surveill Summ. 2021 Mar 5;70(1):1-15.
        PROBLEM/CONDITION: West Nile virus (WNV) is an arthropodborne virus (arbovirus) in the family Flaviviridae and is the leading cause of domestically acquired arboviral disease in the contiguous United States. An estimated 70%-80% of WNV infections are asymptomatic. Symptomatic persons usually develop an acute systemic febrile illness. Less than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. REPORTING PERIOD: 2009-2018. DESCRIPTION OF SYSTEM: WNV disease is a nationally notifiable condition with standard surveillance case definitions. State health departments report WNV cases to CDC through ArboNET, an electronic passive surveillance system. Variables collected include patient age, sex, race, ethnicity, county and state of residence, date of illness onset, clinical syndrome, hospitalization, and death. RESULTS: During 2009-2018, a total of 21,869 confirmed or probable cases of WNV disease, including 12,835 (59%) WNV neuroinvasive disease cases, were reported to CDC from all 50 states, the District of Columbia, and Puerto Rico. A total of 89% of all WNV patients had illness onset during July-September. Neuroinvasive disease incidence and case-fatalities increased with increasing age, with the highest incidence (1.22 cases per 100,000 population) occurring among persons aged ≥70 years. Among neuroinvasive cases, hospitalization rates were >85% in all age groups but were highest among patients aged ≥70 years (98%). The national incidence of WNV neuroinvasive disease peaked in 2012 (0.92 cases per 100,000 population). Although national incidence was relatively stable during 2013-2018 (average annual incidence: 0.44; range: 0.40-0.51), state level incidence varied from year to year. During 2009-2018, the highest average annual incidence of neuroinvasive disease occurred in North Dakota (3.16 cases per 100,000 population), South Dakota (3.06), Nebraska (1.95), and Mississippi (1.17), and the largest number of total cases occurred in California (2,819), Texas (2,043), Illinois (728), and Arizona (632). Six counties located within the four states with the highest case counts accounted for 23% of all neuroinvasive disease cases nationally. INTERPRETATION: Despite the recent stability in annual national incidence of neuroinvasive disease, peaks in activity were reported in different years for different regions of the country. Variations in vectors, avian amplifying hosts, human activity, and environmental factors make it difficult to predict future WNV disease incidence and outbreak locations. PUBLIC HEALTH ACTION: WNV disease surveillance is important for detecting and monitoring seasonal epidemics and for identifying persons at increased risk for severe disease. Surveillance data can be used to inform prevention and control activities. Health care providers should consider WNV infection in the differential diagnosis of aseptic meningitis and encephalitis, obtain appropriate specimens for testing, and promptly report cases to public health authorities. Public health education programs should focus prevention messaging on older persons, because they are at increased risk for severe neurologic disease and death. In the absence of a human vaccine, WNV disease prevention depends on community-level mosquito control and household and personal protective measures. Understanding the geographic distribution of cases, particularly at the county level, appears to provide the best opportunity for directing finite resources toward effective prevention and control activities. Additional work to further develop and improve predictive models that can foreshadow areas most likely to be impacted in a given year by WNV outbreaks could allow for proactive targeting of interventions and ultimately lowering of WNV disease morbidity and mortality.

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