Issue 33, September 14, 2021

CDC Science Clips: Volume 13, Issue 33, Septemer 14, 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. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Randomized clinical trial of air cleaners to improve indoor air quality and COPD health: results of the Clean Air Studyexternal icon
        Hansel NN, Putcha N, Woo H, Peng R, Diette GB, Fawzy A, Wise RA, Romero K, Davis MF, Rule AM, Eakin MN, Breysse PN, McCormack MC, Koehler K.
        Am J Respir Crit Care Med. 2021 Aug 27.
        RATIONALE: Indoor particulate matter is associated with worse COPD outcomes. It remains unknown whether reductions of indoor pollutants improve respiratory morbidity. METHODS: Eligible former smokers with moderate-severe COPD received active or sham portable HEPA air cleaners and followed for six months in this blinded randomized controlled trial. The primary outcome was six-month change in Saint George's Respiratory Questionnaire (SGRQ). Secondary outcomes were exacerbation risk, respiratory symptoms, rescue medication use and 6MWD. Intention to treat analysis included all subjects and per protocol analysis included adherent participants (greater than 80% use of air cleaner). MAIN RESULTS: 116 participants were randomized of which 84.5% completed study. There was no statistically significant difference in total SGRQ score, but the active filter group had greater reduction in SGRQ symptom subscale (ß -7.7 [95% CI, -15.0 to -0.37]) and respiratory symptoms (BCSS, ß -0.8 [95% CI, -1.5 to -0.1); and lower rate of moderate exacerbations (IRR 0.32 [95% CI, 0.12-0.91]) and rescue medication use (IRR 0.54 [95% CI, 0.33-0.86]) compared to sham group (all p<0.05). In per protocol analysis, there was statistically significant difference in primary outcome between the active filter vs. sham group (SGRQ β-4.76 [95% CI, -9.2 to -0.34]) and in moderate exacerbation risk, BCSS and 6MWD. Participants spending more time indoors were more likely to have treatment benefit. CONCLUSIONS: This is the first environmental intervention study conducted among former smokers with COPD showing potential health benefits of portable HEPA air cleaners, particularly among those with greater adherence and spending a greater time indoors. Clinical trial registration available at, ID: NCT02236858.

    • Communicable Diseases
      • Deaths attributed to respiratory syncytial virus in young children in high-mortality rate settings: Report from Child Health and Mortality Prevention Surveillance (CHAMPS)external icon
        Blau DM, Baillie VL, Els T, Mahtab S, Mutevedzi P, Keita AM, Kotloff KL, Mehta A, Sow SO, Tapia MD, Tippett Barr BA, Oluoch BO, Onyango C, Revathi G, Verani JR, Abayneh M, Assefa N, Madrid L, Oundo JO, Scott JA, Bassat Q, Mandomando I, Sitoe A, Valente M, Varo R, Bassey IA, Cain CJ, Jambai A, Ogbuanu I, Ojulong J, Alam M, El Arifeen S, Gurley ES, Rahman A, Rahman M, Waller JL, Dewey B, Breiman RF, Whitney CG, Madhi SA.
        Clin Infect Dis. 2021 Sep 2;73(Supplement_3):S218-s228.
        BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings.

      • Estimated US infection- and vaccine-induced SARS-CoV-2 seroprevalence based on blood donations, July 2020-May 2021external icon
        Jones JM, Stone M, Sulaeman H, Fink RV, Dave H, Levy ME, Di Germanio C, Green V, Notari E, Saa P, Biggerstaff BJ, Strauss D, Kessler D, Vassallo R, Reik R, Rossmann S, Destree M, Nguyen KA, Sayers M, Lough C, Bougie DW, Ritter M, Latoni G, Weales B, Sime S, Gorlin J, Brown NE, Gould CV, Berney K, Benoit TJ, Miller MJ, Freeman D, Kartik D, Fry AM, Azziz-Baumgartner E, Hall AJ, MacNeil A, Gundlapalli AV, Basavaraju SV, Gerber SI, Patton ME, Custer B, Williamson P, Simmons G, Thornburg NJ, Kleinman S, Stramer SL, Opsomer J, Busch MP.
        Jama. 2021 Sep 2.
        IMPORTANCE: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. OBJECTIVE: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. DESIGN, SETTING, AND PARTICIPANTS: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. EXPOSURE: Calendar time. MAIN OUTCOMES AND MEASURES: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. RESULTS: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. CONCLUSIONS AND RELEVANCE: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

    • Environmental Health
      • The U.S. National Biomonitoring Network - enhancing capability and capacity to assess human chemical exposuresexternal icon
        Nassif J, Calafat AM, Aldous KM.
        Int J Hyg Environ Health. 2021 Aug 25;237:113828.
        BACKGROUND: With the increased use of biomonitoring in public health, biomonitoring networks are forming worldwide. The National Biomonitoring Network (NBN), created in 2018, is an interconnected system of U.S. government laboratories in collaboration with public health partners, to advance human biomonitoring science and practice. The NBN aims to harmonize biomonitoring data for use in routine public health practice. METHODS: The NBN has taken a systems approach to provide high-quality biomonitoring data by establishing quality standards, mentoring nascent programs, and enhancing analytical capability and capacity through technical assistance. Guided by a multi-disciplinary Network Steering Committee (NSC), the NBN has developed an organizational framework, membership criteria, and guidance practices related to study design, quality management and analytical measurements. To facilitate the production of these resources, the NSC established interdisciplinary workgroups of subject matter experts. RESULTS: To date, 20 state public health laboratories have joined the NBN. Differences in land-use practices, state and local laws and availability of resources resulted in considerable variability in the design and approach of NBN member biomonitoring programs. By contributing technical guidance, technical training, examples and templates for analytical and epidemiological practices and opportunities for collaboration and interaction, the NBN addressed some of these challenges. Important challenges remaining are to define minimum data variables for laboratory measurements, demographic and exposure information, and to identify an appropriate national repository for biomonitoring data. CONCLUSION: The current NBN membership has greatly benefited from the resources, collaboration and engagement with other state and federal scientists. The NBN hopes to expand membership and increase interaction with biomonitoring networks internationally. While the objectives of biomonitoring networks around the world may differ, understanding their structures, advantages and limitations inform the NBN and provide opportunity for cross-network collaboration.

    • Health Disparities
      • Tuberculosis in indigenous persons - United States, 2009-2019external icon
        Springer YP, Kammerer JS, Silk BJ, Langer AJ.
        J Racial Ethn Health Disparities. 2021 Aug 26.
        BACKGROUND: Populations of indigenous persons are frequently associated with pronounced disparities in rates of tuberculosis (TB) disease compared to co-occurring nonindigenous populations. METHODS: Using data from the National Tuberculosis Surveillance System on TB cases in U.S.-born patients reported in the United States during 2009-2019, we calculated incidence rate ratios and risk ratios for TB risk factors to compare cases in American Indian or Alaska Native (AIAN) and Native Hawaiian or other Pacific Islander (NHPI) TB patients to cases in White TB patients. RESULTS: Annual TB incidence rates among AIAN and NHPI TB patients were on average ≥10 times higher than among White TB patients. Compared to White TB patients, AIAN and NHPI TB patients were 1.91 (95% confidence interval (CI): 1.35-2.71) and 3.39 (CI: 1.44-5.74) times more likely to have renal disease or failure, 1.33 (CI: 1.16-1.53) and 1.63 (CI: 1.20-2.20) times more likely to have diabetes mellitus, and 0.66 (CI: 0.44-0.99) and 0.19 (CI: 0-0.59) times less likely to be HIV positive, respectively. AIAN TB patients were 1.84 (CI: 1.69-2.00) and 1.48 (CI: 1.27-1.71) times more likely to report using excess alcohol and experiencing homelessness, respectively. CONCLUSION: TB among U.S. indigenous persons is associated with persistent and concerning health disparities.

    • Healthcare Associated Infections
      • The impact of coronavirus disease 2019 (COVID-19) on healthcare-associated infections in 2020: A summary of data reported to the National Healthcare Safety Networkexternal icon
        Weiner-Lastinger LM, Pattabiraman V, Konnor RY, Patel PR, Wong E, Xu SY, Smith B, Edwards JR, Dudeck MA.
        Infect Control Hosp Epidemiol. 2021 Sep 3:1-14.
        OBJECTIVES: To determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infection (HAI) incidence in US hospitals, national- and state-level standardized infection ratios (SIRs) were calculated for each quarter in 2020 and compared to those from 2019. METHODS: Central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), select surgical site infections, and Clostridioides difficile and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia laboratory-identified events reported to the National Healthcare Safety Network for 2019 and 2020 by acute-care hospitals were analyzed. SIRs were calculated for each HAI and quarter by dividing the number of reported infections by the number of predicted infections, calculated using 2015 national baseline data. Percentage changes between 2019 and 2020 SIRs were calculated. Supporting analyses, such as an assessment of device utilization in 2020 compared to 2019, were also performed. RESULTS: Significant increases in the national SIRs for CLABSI, CAUTI, VAE, and MRSA bacteremia were observed in 2020. Changes in the SIR varied by quarter and state. The largest increase was observed for CLABSI, and significant increases in VAE incidence and ventilator utilization were seen across all 4 quarters of 2020. CONCLUSIONS: This report provides a national view of the increases in HAI incidence in 2020. These data highlight the need to return to conventional infection prevention and control practices and build resiliency in these programs to withstand future pandemics.

    • Immunity and Immunization
    • Laboratory Sciences
      • Systemic toxicity induced by topical application of heptafluorobutyric acid (PFBA) in a murine modelexternal icon
        Weatherly LM, Shane HL, Lukomska E, Baur R, Anderson SE.
        Food Chem Toxicol. 2021 Aug 30:112528.
        Heptafluorobutyric acid (PFBA) is a synthetic chemical belonging to the per- and polyfluoroalkyl substances (PFAS) group that includes over 5000 chemicals incorporated into numerous products. PFBA is a short-chain PFAS (C4) labeled as a safer alternative to legacy PFAS which have been linked to numerous health effects. Despite the high potential for dermal exposure, occupationally and environmentally, dermal exposure studies are lacking. Using a murine model, this study analyzed serum chemistries, histology, immune phenotyping, and gene expression to evaluate the systemic toxicity of sub-chronic dermal PFBA 15-day (15% v/v or 375 mg/kg/dose) or 28-day (3.75-7.5% v/v or 93.8-187.5 mg/kg/dose) exposures. PFBA exposure produced significant increases in liver and kidney weights and altered serum chemistries (all exposure levels). Immune-cell phenotyping identified significant increases in draining lymph node B-cells (15%) and CD11b + cells (3.75-15%) and skin T-cells (3.75-15%) and neutrophils (7.5-15%). Histopathological and gene expression changes were observed in both the liver and skin after dermal PFBA exposure. The findings indicate PFBA induces liver toxicity and alterations of PPAR target genes, suggesting a role of a PPAR pathway. These results demonstrate that sustained dermal exposure to PFBA induces systemic effects and raise concerns of short-chain PFAS being promoted as safer alternatives.

    • Military Medicine and Health
      • Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific communityexternal icon
        Keating D, Zundel CG, Abreu M, Krengel M, Aenlle K, Nichols D, Toomey R, Chao LL, Golier J, Abdullah L, Quinn E, Heeren T, Groh JR, Koo BB, Killiany R, Loggia ML, Younger J, Baraniuk J, Janulewicz P, Ajama J, Quay M, Baas PW, Qiang L, Conboy L, Kokkotou E, O'Callaghan JP, Steele L, Klimas N, Sullivan K.
        Life Sci. 2021 Aug 25:119903.
        AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

    • Occupational Safety and Health
      • Cardiovascular health research in the workplace: A workshop reportexternal icon
        Calitz C, Pratt C, Pronk NP, Fulton JE, Jinnett K, Thorndike AN, Addou E, Arena R, Brown AG, Chang CC, Latts L, Lerner D, Majors M, Mancuso M, Mills D, Sanchez E, Goff D.
        J Am Heart Assoc. 2021 Aug 28:e019016.
        Heart disease and stroke are the first and fifth leading causes of death in the United States, respectively. Employers have a unique opportunity to promote cardiovascular health, because >60% of US adults are employed, and most spend half of their waking hours at work. Despite the scope of the opportunity, <1 in 5 businesses implement evidence-based, comprehensive workplace health programs, policies, and practices. Integrated, systems-based workplace health approaches that harness data science and technology may have the potential to reach more employees and be cost-effective for employers. To evaluate the role of the workplace in promoting cardiovascular health across the lifespan, the National Heart, Lung, and Blood Institute, the National Institute for Occupational Safety and Health, and the American Heart Association convened a workshop on March 7, 2019, to share best practices, and to discuss current evidence and knowledge gaps, practical application, and dissemination of the evidence, and the need for innovation in workplace health research and practice. This report presents the broad themes discussed at the workshop and considerations for promoting worker cardiovascular health, including opportunities for future research.

    • Reproductive Health
      • Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessmentexternal icon
        Hug L, You D, Blencowe H, Mishra A, Wang Z, Fix MJ, Wakefield J, Moran AC, Gaigbe-Togbe V, Suzuki E, Blau DM, Cousens S, Creanga A, Croft T, Hill K, Joseph KS, Maswime S, McClure EM, Pattinson R, Pedersen J, Smith LK, Zeitlin J, Alkema L.
        Lancet. 2021 Aug 28;398(10302):772-785.
        BACKGROUND: Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents' Health (2016-30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. METHODS: For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks' gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. FINDINGS: Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9-2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5-15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8-27·7) per 1000 total births in west and central Africa to 2·9 (2·7-3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7-2·7) from 2000 to 2019, which was lower than the 2·9% (2·5-3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8-4·7) annual rate of reduction in mortality rate among children aged 1-59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0-49·9%, 50 having a decrease of 10·0-24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries, 34 were in sub-Saharan Africa, 16 were in east Asia and the Pacific, and 15 were in Latin America and the Caribbean. INTERPRETATION: Progress in reducing the rate of stillbirths has been slow compared with decreases in the mortality rate of children younger than 5 years. Accelerated improvements are most needed in the regions and countries with high stillbirth rates, particularly in sub-Saharan Africa. Future prevention of stillbirths needs increased efforts to raise public awareness, improve data collection, assess progress, and understand public health priorities locally, all of which require investment. FUNDING: Bill & Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office.

    • Substance Use and Abuse

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Communicable Diseases
      1. Association between COVID-19 and myocarditis using hospital-based administrative data - United States, March 2020-January 2021external icon
        Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, Romano SD, Gundlapalli AV, Oster ME, Harris AM.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1228-1232.
        Viral infections are a common cause of myocarditis, an inflammation of the heart muscle (myocardium) that can result in hospitalization, heart failure, and sudden death (1). Emerging data suggest an association between COVID-19 and myocarditis (2-5). CDC assessed this association using a large, U.S. hospital-based administrative database of health care encounters from >900 hospitals. Myocarditis inpatient encounters were 42.3% higher in 2020 than in 2019. During March 2020-January 2021, the period that coincided with the COVID-19 pandemic, the risk for myocarditis was 0.146% among patients diagnosed with COVID-19 during an inpatient or hospital-based outpatient encounter and 0.009% among patients who were not diagnosed with COVID-19. After adjusting for patient and hospital characteristics, patients with COVID-19 during March 2020-January 2021 had, on average, 15.7 times the risk for myocarditis compared with those without COVID-19 (95% confidence interval [CI] = 14.1-17.2); by age, risk ratios ranged from approximately 7.0 for patients aged 16-39 years to >30.0 for patients aged <16 years or ≥75 years. Overall, myocarditis was uncommon among persons with and without COVID-19; however, COVID-19 was significantly associated with an increased risk for myocarditis, with risk varying by age group. These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.

      2. Improving retention in antenatal and postnatal care: a systematic review of evidence to inform strategies for adolescents and young women living with HIVexternal icon
        Brittain K, Teasdale CA, Ngeno B, Odondi J, Ochanda B, Brown K, Langat A, Modi S, Abrams EJ.
        J Int AIDS Soc. 2021 Aug;24(8):e25770.
        INTRODUCTION: Young pregnant and postpartum women living with HIV (WLHIV) are at high risk of poor outcomes in prevention of mother-to-child transmission services. The aim of this systematic review was to collate evidence on strategies to improve retention in antenatal and/or postpartum care in this population. We also conducted a secondary review of strategies to increase attendance at antenatal care (ANC) and/or facility delivery among pregnant adolescents, regardless of HIV status, to identify approaches that could be adapted for adolescents and young WLHIV. METHODS: Selected databases were searched on 1 December 2020, for studies published between January 2006 and November 2020, with screening and data abstraction by two independent reviewers. We identified papers that reported age-disaggregated results for adolescents and young WLHIV aged <25 years at the full-text review stage. For the secondary search, we included studies among female adolescents aged 10 to 19 years. RESULTS AND DISCUSSION: Of 37 papers examining approaches to increase retention among pregnant and postpartum WLHIV, only two reported age-disaggregated results: one showed that integrated care during the postpartum period increased retention in HIV care among women aged 18 to 24 years; and another showed that a lay counsellor-led combination intervention did not reduce attrition among women aged 16 to 24 years; one further study noted that age did not modify the effectiveness of a combination intervention. Mobile health technologies, enhanced support, active follow-up and tracing and integrated services were commonly examined as standalone interventions or as part of combination approaches, with mixed evidence for each strategy. Of 10 papers identified in the secondary search, adolescent-focused services and continuity of care with the same provider appeared to be effective in improving attendance at ANC and/or facility delivery, while home visits and group ANC had mixed results. CONCLUSIONS: This review highlights the lack of evidence regarding effective strategies to improve retention in antenatal and/or postpartum care among adolescents and young WLHIV specifically, as well as a distinct lack of age-disaggregated results in studies examining retention interventions for pregnant WLHIV of all ages. Identifying and prioritizing approaches to improve retention of adolescents and young WLHIV are critical for improving maternal and child health.

      3. Etiology and clinical characteristics of severe pneumonia among young children in Thailand: Pneumonia Etiology Research for Child Health (PERCH) case-control study findings, 2012-2013external icon
        Bunthi C, Rhodes J, Thamthitiwat S, Higdon MM, Chuananon S, Amorninthapichet T, Paveenkittiporn W, Chittaganpitch M, Sawatwong P, Hammitt LL, Feikin DR, Murdoch DR, Deloria-Knoll M, O'Brien KL, Prosperi C, Maloney SA, Baggett HC, Akarasewi P.
        Pediatr Infect Dis J. 2021 Sep 1;40(9s):S91-s100.
        BACKGROUND: Pneumonia remains the leading cause of death among children <5 years of age beyond the neonatal period in Thailand. Using data from the Pneumonia Etiology Research for Child Health (PERCH) Study, we provide a detailed description of pneumonia cases and etiology in Thailand to inform local treatment and prevention strategies in this age group. METHODS: PERCH, a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children 1-59 months of age. The Thailand site enrolled children for 24 consecutive months during January 2012-February 2014 with staggered start dates in 2 provinces. Cases were children hospitalized with pre-2013 WHO-defined severe or very severe pneumonia. Community controls were randomly selected from health services registries in each province. Analyses were restricted to HIV-negative cases and controls. We calculated adjusted odds ratios (ORs) and 95% CIs comparing organism prevalence detected by nasopharyngeal/oropharyngeal (NP/OP) polymerase chain reaction between cases and controls. The PERCH Integrated Analysis (PIA) used Bayesian latent variable analysis to estimate pathogen-specific etiologic fractions and 95% credible intervals. RESULTS: Over 96% of both cases (n = 223) and controls (n = 659) had at least 1 organism detected; multiple organisms were detected in 86% of cases and 88% of controls. Among 98 chest Radiograph positive (CXR+) cases, respiratory syncytial virus (RSV) had the highest NP/OP prevalence (22.9%) and the strongest association with case status (OR 20.5; 95% CI: 10.2, 41.3) and accounted for 34.6% of the total etiologic fraction. Tuberculosis (TB) accounted for 10% (95% CrI: 1.6-26%) of the etiologic fraction among CXR+ cases. DISCUSSION: More than one-third of hospitalized cases of severe and very severe CXR+ pneumonia among children 1-59 months of age in Thailand were attributable to RSV. TB accounted for 10% of cases, supporting evaluation for TB among children hospitalized with pneumonia in high-burden settings. Similarities in pneumonia etiology in Thailand and other PERCH sites suggest that global control strategies based on PERCH study findings are relevant to Thailand and similar settings.

      4. Influenza antiviral treatment and length of stayexternal icon
        Campbell AP, Tokars JI, Reynolds S, Garg S, Kirley PD, Miller L, Yousey-Hindes K, Anderson EJ, Oni O, Monroe M, Kim S, Lynfield R, Smelser C, Muse AT, Felsen C, Billing LM, Thomas A, Mermel E, Lindegren ML, Schaffner W, Price A, Fry AM.
        Pediatrics. 2021 Sep 1.
        BACKGROUND: Antiviral treatment is recommended for hospitalized patients with suspected and confirmed influenza, but evidence is limited among children. We evaluated the effect of antiviral treatment on hospital length of stay (LOS) among children hospitalized with influenza. METHODS: We included children <18 years hospitalized with laboratory-confirmed influenza in the US Influenza Hospitalization Surveillance Network. We collected data for 2 cohorts: 1 with underlying medical conditions not admitted to the ICU (n = 309, 2012-2013) and an ICU cohort (including children with and without underlying conditions; n = 299, 2010-2011 to 2012-2013). We used a Cox model with antiviral receipt as a time-dependent variable to estimate hazard of discharge and a Kaplan-Meier survival analysis to determine LOS. RESULTS: Compared with those not receiving antiviral agents, LOS was shorter for those treated ≤2 days after illness onset in both the medical conditions (adjusted hazard ratio: 1.37, P = .02) and ICU (adjusted hazard ratio: 1.46, P = .007) cohorts, corresponding to 37% and 46% increases in daily discharge probability, respectively. Treatment ≥3 days after illness onset had no significant effect in either cohort. In the medical conditions cohort, median LOS was 3 days for those not treated versus 2 days for those treated ≤2 days after symptom onset (P = .005). CONCLUSIONS: Early antiviral treatment was associated with significantly shorter hospitalizations in children with laboratory-confirmed influenza and high-risk medical conditions or children treated in the ICU. These results support Centers for Disease Control and Prevention recommendations for prompt empiric antiviral treatment in hospitalized patients with suspected or confirmed influenza.

      5. Epidemiology, clinical features, and outcomes of coccidioidomycosis, Utah, 2006-2015external icon
        Carey A, Gorris ME, Chiller T, Jackson B, Beadles W, Webb BJ.
        Emerg Infect Dis. 2021 Sep;27(9):2269-2277.
        On the basis of a 1957 geographic Coccidioides seropositivity survey, 3 counties in southwestern Utah, USA, were considered coccidioidomycosis-endemic, but there has been a paucity of information on the disease burden in Utah since. We report findings from a recent clinical and epidemiologic study of coccidioidomycosis in Utah. To describe clinical characteristics, we identified all coccidioidomycosis cases in an integrated health system in the state during 2006-2015. For epidemiologic analysis, we used cases reported to the Utah Department of Health during 2009-2015. Mean state incidence was 1.83 cases/100,000 population/year. Washington County, in southwestern Utah, had the highest incidence, 17.2 cases/100,000 population/year. In a generalized linear model with time as a fixed effect, mean annual temperature, population, and new construction were associated with regional variations in incidence. Using these variables in a spatiotemporal model, we estimated the adjusted regional variation by county to predict areas where Coccidioides infections might increase.

      6. Pediatricians' knowledge and practices related to mumps diagnosis and preventionexternal icon
        Cataldi JR, O'Leary ST, Marlow MA, Beaty BL, Hurley LP, Crane LA, Brtnikova M, Gorman C, Pham HT, Lindley MC, Kempe A.
        J Pediatr. 2021 Aug 25.
        OBJECTIVES: To assess pediatricians' mumps knowledge and testing practices, to identify physician and practice characteristics associated with mumps testing practices, and to assess reporting and outbreak response knowledge and practices. STUDY DESIGN: From January-April 2020, we surveyed a nationally representative network of pediatricians. Descriptive statistics were generated for all items. Chi-square, t-tests, and Poisson regression were used to compare physician and practice characteristics between respondents who would rarely or never vs. sometimes or often/always test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting. RESULTS: The response rate was 67% (297/444). For knowledge, over half of pediatricians responded incorrectly or 'Don't know' for six of nine true/false statements about mumps epidemiology, diagnosis, and prevention; and over half reported they would need additional guidance on mumps buccal swab testing. For testing practices, 59% of respondents reported they would sometimes (35%) or often/always (24%) test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting; older physicians, rural physicians, and physicians from the Northeast or Midwest were more likely to test for mumps. Thirty-six percent of pediatricians reported they would often/always report a patient with suspected mumps to public health authorities. CONCLUSIONS: Pediatricians report mumps knowledge gaps and practices that do not align with public health recommendations. These gaps may lead to under-diagnosis and under-reporting of mumps cases, delaying public health response measures and contributing to ongoing disease transmission.

      7. Acanthamoeba castellanii encephalitis in a patient with AIDS: a case report and literature reviewexternal icon
        Damhorst GL, Watts A, Hernandez-Romieu A, Mel N, Palmore M, Ali IK, Neill SG, Kalapila A, Cope JR.
        Lancet Infect Dis. 2021 Aug 27.
        Amoebic encephalitis is a rare cause of CNS infection for which mortality exceeds 90%. We present the case of a 27-year-old man with AIDS who presented to a hospital in Atlanta (Georgia, USA) with tonic-clonic seizures and headache. His clinical condition deteriorated over several days. Brain biopsy revealed lymphohistiocytic inflammation and necrosis with trophozoites and encysted forms of amoebae. Immunohistochemical and PCR testing confirmed Acanthamoeba castellanii encephalitis, typically described as granulomatous amoebic encephalitis (GAE). No proven therapy for GAE is available, although both surgical and multiagent antimicrobial treatment strategies are often used. Most recently, these include the antileishmanial agent miltefosine. Here we review all cases of GAE due to Acanthamoeba spp in people with HIV/AIDS identified in the literature and reported to the Centers for Disease Control and Prevention. We describe this case as a reminder to the clinician to consider protozoal infections, especially free-living amoeba, in the immunocompromised host with a CNS infection refractory to traditional antimicrobial therapy.

      8. Prevalence of advanced HIV disease, cryptococcal antigenemia and suboptimal clinical outcomes among those enrolled in care in Vietnamexternal icon
        Dat VQ, Lyss S, Hoai Dung NT, Hung LM, Pals SL, Van Anh HT, Van Kinh N, Bateganya M.
        J Acquir Immune Defic Syndr. 2021 Aug 20.
        BACKGROUND: People living with advanced HIV disease (AHD) are at high risk of morbidity and mortality. We assessed the prevalence of cryptococcal antigenemia (CrAg) and clinical outcomes among patients newly presenting with CD4 ≤100 cells/μL in Vietnam. SETTING: Twenty-two public HIV clinics in Vietnam. METHODS: During August 2015-March 2017, ART-naïve adults presenting for care with CD4 ≤100 cells/μL were screened for CrAg. Those who consented to study enrollment were followed for up to 12 months and assessed for clinical outcomes. RESULTS: Of 3,504 patients with CD4 results, 1,354 (38.6%) had CD4 ≤100 cells/μL, of whom 1,177 (86.9%) enrolled in the study. Median age was 35 years (interquartile range 30-40); 872 (74.1%) were male, and 892 (75.8%) had CD4 <50 cells/μL. Thirty-six (3.1%) were CrAg positive. Overall 1,151 (97.8%) including all who were CrAg positive initiated ART. Of 881 (76.5%) followed for ≥12 months, 623 (70.7%) were still alive and on ART at 12 months, 54 (6.1%) had transferred to non-study clinics, 86 (9.8%) were lost to follow up (LTFU), and 104 (11.8%) had died. Among all 1,177 study participants, 143 (12.1%) died, most (123, 86.0%) before or within 6 months of enrollment. Twenty-seven (18.9%) died from pulmonary tuberculosis, 23 (16.1%) from extrapulmonary tuberculosis, 8 (5.6%) from Talaromyces marneffei infection, and 6 (4.2%) from opioid overdose. Eight deaths (5.8%) occurred among the 36 CrAg positive individuals. CONCLUSIONS: Late presentation for HIV care was common. The high mortality after entry in care calls for strengthening of the management of AHD.

      9. Introduction to the site-specific etiologic results from the Pneumonia Etiology Research for Child Health (PERCH) Studyexternal icon
        Deloria Knoll M, Prosperi C, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Madhi SA, Murdoch DR, Scott JA, Thea DM, O'Brien KL.
        Pediatr Infect Dis J. 2021 Sep 1;40(9s):S1-s6.
        The Pneumonia Etiology Research for Child Health (PERCH) study evaluated the etiology of severe and very severe pneumonia in children hospitalized in 7 African and Asian countries. Here, we summarize the highlights of in-depth site-specific etiology analyses published separately in this issue, including how etiology varies by age, mortality status, malnutrition, severity, HIV status, and more. These site-specific results impart important lessons that can inform disease control policy implications.

      10. Multiple variants of SARS-CoV-2 in a university outbreak after spring break - Chicago, Illinois, March-May 2021external icon
        Doyle K, Teran RA, Reefhuis J, Kerins JL, Qiu X, Green SJ, Choi H, Madni SA, Kamal N, Landon E, Albert RC, Pacilli M, Furtado LE, Hayden MK, Kunstman KJ, Bethel C, Megger L, Fricchione MJ, Ghinai I.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1195-1200.
        To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination. In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break. A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.2%) lived in on-campus dormitories. CDPH evaluated the role of travel and social connections, as well as the potential impact of SARS-CoV-2 variants, on transmission. Among 140 infected students who were interviewed, 89 (63.6%) reported recent travel outside Chicago during spring break, and 57 (40.7%) reported indoor social exposures. At the time of the outbreak, undergraduate-aged persons were largely ineligible for vaccination in Chicago; only three of the students with COVID-19 (1.9%) were fully vaccinated. Whole genome sequencing (WGS) of 104 specimens revealed multiple distinct SARS-CoV-2 lineages, suggesting several nearly simultaneous introductions. Most specimens (66; 63.5%) were B.1.1.222, a lineage not widely detected in Chicago before or after this outbreak. These results demonstrate the potential for COVID-19 outbreaks on university campuses after widespread student travel during breaks, at the beginning of new school terms, and when students participate in indoor social gatherings. To prevent SARS-CoV-2 transmission, colleges and universities should encourage COVID-19 vaccination; discourage unvaccinated students from travel, including during university breaks; implement serial COVID-19 screening among unvaccinated persons after university breaks; encourage masking; and implement universal serial testing for students based on community transmission levels.

      11. Pneumococcal meningitis outbreaks in Africa, 2000-2018: Systematic literature review and meningitis surveillance database analysesexternal icon
        Franklin K, Kwambana-Adams B, Lessa FC, Soeters HM, Cooper L, Coldiron ME, Mwenda J, Antonio M, Nakamura T, Novak R, Cohen AL.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S174-s183.
        BACKGROUND: The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. METHODS: Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. RESULTS: A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. CONCLUSIONS: Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.

      12. Ensuring optimal community HIV testing services in Nigeria using an enhanced community case-finding package (ECCP), October 2019-March 2020: Acceleration to HIV epidemic controlexternal icon
        Jahun I, Dirlikov E, Odafe S, Yakubu A, Boyd AT, Bachanas P, Nzelu C, Aliyu G, Ellerbrock T, Swaminathan M.
        HIV AIDS (Auckl). 2021 ;13:839-850.
        PURPOSE: The 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) showed Nigeria's progress toward the UNAIDS 90-90-90 targets: 47% of HIV-positive individuals knew their status; of these, 96% were receiving antiretroviral therapy (ART); and of these, 81% were virally suppressed. To improve identification of HIV-positive individuals, Nigeria developed an Enhanced Community Case-Finding Package (ECCP). We describe ECCP implementation in nine states and assess its effect. METHODS: ECCP included four core strategies (small area estimation [SAE] of people living with HIV [PLHIV], map of HIV-positive patients by residence, HIV risk-screening tool [HRST], and index testing [IT]) and four supportive strategies (alternative healthcare outlets, performance-based incentives for field testers, Project Extension for Community Healthcare Outcomes, and interactive dashboards). ECCP was deployed in nine of 10 states prioritized for ART scale-up. Weekly program data (October 2019-March 2020) were tracked and analyzed. RESULTS: Of the total 774 LGAs in Nigeria, using SAE, 103 (13.3%) high-burden LGAs were identified, in which 2605 (28.0%) out of 9,294 hotspots were prioritized by mapping newly identified PLHIV by residential addresses. Over 22 weeks, among 882,449 individuals screened using HRST, 723,993 (82.0%) were eligible and tested for HIV (state range, 43.7-90.4%), out of which 20,616 were positive. Through IT, an additional 3,724 PLHIV were identified. In total, 24,340 PLHIV were identified and 97.4% were linked to life-saving antiretroviral therapy. The number of newly identified PLHIV increased 17-fold over 22 weeks (week 1: 89; week 22: 1,632). Overall mean HIV positivity rate by state was 3.3% (range, 1.8-6.4%). CONCLUSION: Using ECCP in nine states in Nigeria increased the number of PLHIV in the community who knew their status, allowing them to access life-saving care and decreasing the risk of HIV transmission.

      13. Congenital syphilis diagnosed beyond the neonatal period in the United States: 2014-2018external icon
        Kimball A, Bowen VB, Miele K, Weinstock H, Thorpe P, Bachmann L, McDonald R, Machefsky A, Torrone E.
        Pediatrics. 2021 Sep;148(3).
        BACKGROUND AND OBJECTIVES: During 2014-2018, reported congenital syphilis (CS) cases in the United States increased 183%, from 462 to 1306 cases. We reviewed infants diagnosed with CS beyond the neonatal period (>28 days) during this time. METHODS: We reviewed surveillance case report data for infants with CS delivered during 2014-2018 and identified those diagnosed beyond the neonatal period with reported signs or symptoms. We describe these infants and identify possible missed opportunities for earlier diagnoses. RESULTS: Of the 3834 reported cases of CS delivered during 2014-2018, we identified 67 symptomatic infants diagnosed beyond the neonatal period. Among those with reported findings, 67% had physical examination findings of CS, 69% had abnormal long-bone radiographs consistent with CS, and 36% had reactive syphilis testing in the cerebrospinal fluid. The median serum nontreponemal titer was 1:256 (range: 1:1-1:2048). The median age at diagnosis was 67 days (range: 29-249 days). Among the 66 mothers included, 83% had prenatal care, 26% had a syphilis diagnosis during pregnancy or at delivery, and 42% were not diagnosed with syphilis until after delivery. Additionally, 24% had an initial negative test result and seroconverted during pregnancy. CONCLUSIONS: Infants with CS continue to be undiagnosed at birth and present with symptoms after age 1 month. Pediatric providers can diagnose and treat infants with CS early by following guidelines, reviewing maternal records and confirming maternal syphilis status, advocating for maternal testing at delivery, and considering the diagnosis of CS, regardless of maternal history.

      14. Symptoms reported with new onset of loss of taste or smell in individuals with and without SARS-CoV-2 infectionexternal icon
        Koyama AK, Siegel DA, Oyegun E, Hampton W, Maddox N, Koumans EH.
        JAMA Otolaryngol Head Neck Surg. 2021 Sep 2.

      15. Migration in Namibia and its association with HIV acquisition and treatment outcomesexternal icon
        Low A, Sachathep K, Rutherford G, Nitschke AM, Wolkon A, Banda K, Miller LA, Solmo C, Jackson K, Patel H, McCracken S, Findley S, Mutenda N.
        PLoS One. 2021 ;16(9):e0256865.
        BACKGROUND: In the 21st century, understanding how population migration impacts human health is critical. Namibia has high migration rates and HIV prevalence, but little is known about how these intersect. We examined the association between migration and HIV-related outcomes using data from the 2017 Namibia Population-based HIV Impact Assessment (NAMPHIA). METHODS AND FINDINGS: The NAMPHIA survey selected a nationally representative sample of adults in 2017. All adults aged 15-64 years were invited to complete an interview and home-based HIV test. Recent infection (<130 days) was measured using HIV-1 LAg avidity combined with viral load (>1000 copies/mL) and antiretroviral analyte data. Awareness of HIV status and antiretroviral use were based on self-report and/or detectable antiretrovirals in blood. Viremia was defined as having a viral load ≥1000 copies/mL, including all participants in the denominator regardless of serostatus. We generated community viremia values as a weighted proportion at the EA level, excluding those classified as recently infected. Significant migrants were those who had lived outside their current region or away from home >one month in the past three years. Recent cross-community in-migrants were those who had moved to the community <two years ago. Separate analyses were done to compare significant migrants to non-migrants and recent cross-community in-migrants to those who in-migrated >two years ago to determine the association of migration and timing with recent infection or viral load suppression (VLS). All proportions are weighted. Of eligible adults, we had HIV results and migration data on 9,625 (83.9%) of 11,474 women and 7,291 (73.0%) of 9,990 men. Most respondents (62.5%) reported significant migration. Of cross-community in-migrants, 15.3% were recent. HIV prevalence was 12.6% and did not differ by migration status. Population VLS was 77.4%. Recent cross-community in-migration was associated with recent HIV infection (aOR: 4.01, 95% CI 0.99-16.22) after adjusting for community viremia. Significant migration (aOR 0.73, 95% CI: 0.55-0.97) and recent cross-community in-migration (aOR 0.57, 95% CI: 0.35-0.92) were associated with lower VLS, primarily due to lack of awareness of HIV infection. The study was limited by lack of precise data on trajectory of migration. CONCLUSIONS: Despite a high population-level VLS, Namibia still has migrant populations that are not accessing effective treatment for HIV. Targeting migrants with effective prevention and testing programs in communities with viremia could enable further epidemic control.

      16. Epidemiologically linked COVID-19 outbreaks at a youth camp and men's conference - Illinois, June-July 2021external icon
        Matthias J, Patrick S, Wiringa A, Pullman A, Hinton S, Campos J, Belville T, Sinner Mph M, Buchanan TT, Sim B, Goldesberry KE.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1223-1227.
        On June 30, 2021, the Illinois Department of Public Health (IDPH) contacted CDC concerning COVID-19 outbreaks at two events sponsored by the same organization: a 5-day overnight church camp for persons aged 14-18 years and a 2-day men's conference. Neither COVID-19 vaccination nor COVID-19 testing was required before either event. As of August 13, a total of 180 confirmed and probable cases had been identified among attendees at the two events and their close contacts. Among the 122 cases associated with the camp or the conference (primary cases), 18 were in persons who were fully vaccinated, with 38 close contacts. Eight of these 38 close contacts subsequently became infected with SARS-CoV-2, the virus that causes COVID-19 (secondary cases); among the eight close contacts with secondary cases, one half (four) were fully vaccinated. Among the 180 total persons with outbreak-associated cases, five (2.8%) were hospitalized; no deaths occurred. None of the vaccinated persons with cases were hospitalized. Approximately 1,000 persons across at least four states were exposed to SARS-CoV-2 through attendance at these events or through close contact with a person who had a primary case. This investigation underscores the impact of secondary SARS-CoV-2 transmission during large events, such as camps and conferences, when COVID-19 prevention strategies are not implemented. In Los Angeles County, California, during July 2021, when the SARS-CoV-2 B.1.617.2 (Delta) variant was predominant, unvaccinated residents were five times more likely to be infected and 29 times more likely to be hospitalized from infection than were vaccinated residents (1). Implementation of multiple prevention strategies, including vaccination and nonpharmaceutical interventions such as masking, physical distancing, and screening testing, are critical to preventing SARS-CoV-2 transmission and serious complications from COVID-19.

      17. Global respiratory syncytial virus-related infant community deathsexternal icon
        Mazur NI, Löwensteyn YN, Willemsen JE, Gill CJ, Forman L, Mwananyanda LM, Blau DM, Breiman RF, Madhi SA, Mahtab S, Gurley ES, El Arifeen S, Assefa N, Scott JA, Onyango D, Tippet Barr BA, Kotloff KL, Sow SO, Mandomando I, Ogbuanu I, Jambai A, Bassat Q, Caballero MT, Polack FP, Omer S, Kazi AM, Simões EA, Satav A, Bont LJ.
        Clin Infect Dis. 2021 Sep 2;73(Supplement_3):S229-s237.
        BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

      18. SARS-CoV-2 wastewater surveillance for public health actionexternal icon
        McClary-Gutierrez JS, Mattioli MC, Marcenac P, Silverman AI, Boehm AB, Bibby K, Balliet M, de Los Reyes FL, Gerrity D, Griffith JF, Holden PA, Katehis D, Kester G, LaCross N, Lipp EK, Meiman J, Noble RT, Brossard D, McLellan SL.
        Emerg Infect Dis. 2021 Sep;27(9):1-8.
        Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has garnered extensive public attention during the coronavirus disease pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantification of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, bridging the communication and knowledge gaps between researchers and public health responders is needed. We describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethics consideration for monitoring. Although wastewater surveillance to assess community infections is not a new idea, the coronavirus disease pandemic might be the initiating event to make this emerging public health tool a sustainable nationwide surveillance system, provided that these barriers are addressed.

      19. BACKGROUND: HIV-related discrimination in health care settings is associated with negative health outcomes among persons with HIV (PWH). This paper describes and compares differences in the prevalence of self-reported experiences with discrimination in health care settings by sociodemographic and clinical care factors among persons with diagnosed HIV in the United States. METHODS: We analyzed interview and medical record data collected 6/2018-5/2019 from 3850 PWH who had received HIV care in the past 12 months. We calculated weighted percentages and associated 95% confidence intervals and assessed the association between any experience of discrimination and selected sociodemographic and clinical characteristics using prevalence ratios with predicted marginal means. RESULTS: About 25% of PWH who had an HIV care visit in the past 12 months reported experiencing any discrimination. Experiences with discrimination were significantly more prevalent among persons 18-29 years (34%); transgender persons (41%); persons of gay (25%), bisexual (31%), or other (40%) sexual orientations; and persons who did not have a regular provider (39%), lived at/below poverty level (28%), were homeless (39%) or incarcerated (37%) in the past 12 months. PWH who experienced discrimination were more likely to have missed at least one HIV care visit, not be taking ART, and have missed ART doses. Recent and sustained viral suppression were not significantly associated with experiencing any discrimination. CONCLUSIONS: Interventions that address the sociocultural and structural factors associated with discrimination in all health care settings are needed to improve health outcomes among PWH and end the HIV epidemic in the United States.

      20. The global landscape of pediatric bacterial meningitis data reported to the World Health Organization-Coordinated Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2014-2019external icon
        Nakamura T, Cohen AL, Schwartz S, Mwenda JM, Weldegebriel G, Biey JN, Katsande R, Ghoniem A, Fahmy K, Rahman HA, Videbaek D, Daniels D, Singh S, Wasley A, Rey-Benito G, de Oliveira L, Ortiz C, Tondo E, Liyanage JB, Sharifuzzaman M, Grabovac V, Batmunkh N, Logronio J, Heffelfinger J, Fox K, De Gouveia L, von Gottberg A, Du Plessis M, Kwambana-Adams B, Antonio M, El Gohary S, Azmy A, Gamal A, Voropaeva E, Egorova E, Urban Y, Duarte C, Veeraraghavan B, Saha S, Howden B, Sait M, Jung S, Bae S, Litt D, Seaton S, Slack M, Antoni S, Ouattara M, Van Beneden C, Serhan F.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S161-s173.
        BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

      21. Severity of illness by pregnancy status among laboratory-confirmed SARS-CoV-2 infections occurring in reproductive-aged women in Colombiaexternal icon
        Rozo N, Valencia D, Newton SM, Avila G, Gonzalez MA, Sancken CL, Burkel VK, Ellington SR, Gilboa SM, Rao CY, Azziz-Baumgartner E, Ospina ML, Prieto FE, Tong VT.
        Paediatr Perinat Epidemiol. 2021 Sep 1.
        BACKGROUND: Multiple studies have described increased risk of severe coronavirus disease (COVID-19) among pregnant women compared to nonpregnant women. The risk in middle-income countries where the distributions of age groups and preexisting conditions may differ is less known. OBJECTIVES: To determine whether pregnant women with SARS-CoV-2 infection are at increased risk for severe COVID-19 compared to nonpregnant women in Colombia. METHODS: We analysed national surveillance data from Colombia, of women aged 15-44 years with laboratory-confirmed infection with SARS-CoV-2 by molecular or antigen testing, from 6 March 2020 to 12 December 2020. An enhanced follow-up of pregnant women with COVID-19 was established to monitor pregnancy and birth outcomes. RESULTS: Of 371,363 women aged 15-44 years with laboratory-confirmed SARS-CoV-2 infection, 1.5% (n = 5614) were reported as pregnant; among those, 2610 (46.5%) were considered a complete pregnancy for reporting purposes at the time of analysis. Hospitalisation (23.9%) and death (1.3%) occurred more frequently among pregnant symptomatic women compared to nonpregnant symptomatic women (2.9% and 0.3%, respectively). Compared to nonpregnant symptomatic women, pregnant symptomatic women were at increased risk of hospitalisation (adjusted risk ratio (RR) 2.19, 95% confidence interval (CI) 2.07, 2.32) and death (RR 1.82, 95% CI 1.60, 2.07), after adjusting for age, type of health insurance and presence of certain underlying medical conditions. Among complete pregnancies, 55 (2.1%) were pregnancy losses, 72 (2.8%) resulted in term low birthweight infants and 375 (14.4%) were preterm deliveries. CONCLUSIONS: Although pregnant women were infrequently reported with laboratory-confirmed SARS-CoV-2 infection, pregnant symptomatic women with COVID-19 were at increased risk for hospitalisation and death compared to nonpregnant symptomatic women. Almost all infections we reported on were third-trimester infections; ongoing follow-up is needed to determine pregnancy outcomes among women infected earlier in pregnancy. Healthcare providers should counsel pregnant women about preventive measures to protect from SARS-CoV-2 infection and when to seek care.

      22. Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcomeexternal icon
        Sulaiman I, Chung M, Angel L, Tsay JJ, Wu BG, Yeung ST, Krolikowski K, Li Y, Duerr R, Schluger R, Thannickal SA, Koide A, Rafeq S, Barnett C, Postelnicu R, Wang C, Banakis S, Pérez-Pérez L, Shen G, Jour G, Meyn P, Carpenito J, Liu X, Ji K, Collazo D, Labarbiera A, Amoroso N, Brosnahan S, Mukherjee V, Kaufman D, Bakker J, Lubinsky A, Pradhan D, Sterman DH, Weiden M, Heguy A, Evans L, Uyeki TM, Clemente JC, de Wit E, Schmidt AM, Shopsin B, Desvignes L, Wang C, Li H, Zhang B, Forst CV, Koide S, Stapleford KA, Khanna KM, Ghedin E, Segal LN.
        Nat Microbiol. 2021 Aug 31.
        Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

      23. Risk factors for hospitalization among persons with COVID-19-Coloradoexternal icon
        Vahey GM, McDonald E, Marshall K, Martin SW, Chun H, Herlihy R, Tate JE, Kawasaki B, Midgley CM, Alden N, Killerby ME, Staples JE.
        PLoS One. 2021 ;16(9):e0256917.
        BACKGROUND: Most current evidence on risk factors for hospitalization because of coronavirus disease 2019 (COVID-19) comes from studies using data abstracted primarily from electronic health records, limited to specific populations, or that fail to capture over-the-counter medications and adjust for potential confounding factors. Properly understanding risk factors for hospitalization will help improve clinical management and facilitate targeted prevention messaging and forecasting and prioritization of clinical and public health resource needs. OBJECTIVES: To identify risk factors for hospitalization using patient questionnaires and chart abstraction. METHODS: We randomly selected 600 of 1,738 laboratory-confirmed Colorado COVID-19 cases with known hospitalization status and illness onset during March 9-31, 2020. In April 2020, we collected demographics, social history, and medications taken in the 30 days before illness onset via telephone questionnaire and collected underlying medical conditions in patient questionnaires and medical record abstraction. RESULTS: Overall, 364 patients participated; 128 were hospitalized and 236 were non-hospitalized. In multivariable analysis, chronic hypoxemic respiratory failure with oxygen requirement (adjusted odds ratio [aOR] 14.64; 95% confidence interval [CI] 1.45-147.93), taking opioids (aOR 8.05; CI 1.16-55.77), metabolic syndrome (aOR 5.71; CI 1.18-27.54), obesity (aOR 3.35; CI 1.58-7.09), age ≥65 years (aOR 3.22; CI 1.20-7.97), hypertension (aOR 3.14; CI 1.47-6.71), arrhythmia (aOR 2.95; CI 1.00-8.68), and male sex (aOR 2.65; CI 1.44-4.88), were significantly associated with hospitalization. CONCLUSION: We identified patient characteristics, medications, and medical conditions, including some novel ones, associated with hospitalization. These data can be used to inform clinical and public health resource needs.

    • Disaster Control and Emergency Services
      1. Developing public health emergency response leaders in incident management: A scoping review of educational interventionsexternal icon
        Li Y, Hsu EB, Pham N, Davis XM, Podgornik MN, Trigoso SM.
        Disaster Med Public Health Prep. 2021 Aug 31:1-30.
        During emergency responses, public health leaders frequently serve in incident management roles that differ from their routine job functions. Leaders' familiarity with incident management principles and functions can influence response outcomes. Therefore, training and exercises in incident management are often required for public health leaders. To describe existing methods of incident management training and exercises in the literature, we queried 6 English language databases and found 786 relevant articles. Five themes emerged: (1) experiential learning as an established approach to foster engaging and interactive learning environments and optimize training design; (2) technology-aided decision support tools are increasingly common for crisis decision-making; (3) integration of leadership training in the education continuum is needed for developing public health response leaders; (4) equal emphasis on competency and character is needed for developing capable and adaptable leaders; and (5) consistent evaluation methodologies and metrics are needed to assess the effectiveness of educational interventions.These findings offer important strategic and practical considerations for improving the design and delivery of educational interventions to develop public health emergency response leaders. This review and ongoing real-world events could facilitate further exploration of current practices, emerging trends, and challenges for continuous improvements in developing public health emergency response leaders.

    • Disease Reservoirs and Vectors
      1. Spatial heterogeneity of sympatric tick species and tick-borne pathogens emphasizes the need for surveillance for effective tick controlexternal icon
        Machtinger ET, Nadolny RM, Vinyard BT, Eisen L, Hojgaard A, Haynes SA, Bowman L, Casal C, Li AY.
        Vector Borne Zoonotic Dis. 2021 Aug 31.
        Three tick species that can transmit pathogen causing disease are commonly found parasitizing people and animals in the mid-Atlantic United States: the blacklegged tick (Ixodes scapularis Say), the American dog tick (Dermacentor variabilis [Say]), and the lone star tick (Amblyomma americanum [L.]) (Acari: Ixodidae). The potential risk of pathogen transmission from tick bites acquired at schools in tick-endemic areas is a concern, as school-aged children are a high-risk group for tick-borne disease. Integrated pest management (IPM) is often required in school districts, and continued tick range expansion and population growth will likely necessitate IPM strategies to manage ticks on school grounds. However, an often-overlooked step of tick management is monitoring and assessment of local tick species assemblages to inform the selection of control methodologies. The purpose of this study was to evaluate tick species presence, abundance, and distribution and the prevalence of tick-borne pathogens in both questing ticks and those removed from rodent hosts on six school properties in Maryland. Overall, there was extensive heterogeneity in tick species dominance, abundance, and evenness across the field sites. A. americanum and I. scapularis were found on all sites in all years. Overall, A. americanum was the dominant tick species. D. variabilis was collected in limited numbers. Several pathogens were found in both questing ticks and those removed from rodent hosts, although prevalence of infection was not consistent between years. Borrelia burgdorferi, Ehrlichia chaffeensis, Ehrlichia ewingii, and Ehrlichia "Panola Mountain" were identified in questing ticks, and B. burgdorferi and Borrelia miyamotoi were detected in trapped Peromyscus spp. mice. B. burgdorferi was the dominant pathogen detected. The impact of tick diversity on IPM of ticks is discussed.

    • Environmental Health
      1. Evaluation of syndromic surveillance data for studying harmful algal bloom-associated illnesses - United States, 2017-2019external icon
        Lavery AM, Backer LC, Roberts VA, DeVies J, Daniel J.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1191-1194.
        Harmful algal and cyanobacterial blooms (harmful algal blooms) are large colonies of algae or cyanobacteria that can harm humans, animals, and the environment (1-3). The number of algal blooms has been increasing in the United States, augmented by increasing water temperatures and nutrients in water from industry and agricultural run-off (4,5). The extent to which harmful algal bloom exposures cause human illness or long-term health effects is unknown. As the number of blooms increases annually, the likelihood of negative health outcomes (e.g., respiratory or gastrointestinal illness) from exposure also increases (4,5). To explore the utility of syndromic surveillance data for studying health effects from harmful algal bloom exposures, CDC queried emergency department (ED) visit data from the National Syndromic Surveillance Program (NSSP) for harmful algal bloom exposure-associated administrative discharge diagnosis codes and chief complaint text terms related to harmful algal bloom exposure (6). A total of 321 harmful algal bloom-associated ED visits were identified during January 1, 2017-December 31, 2019. An increase in harmful algal bloom-associated ED visits occurred during warmer months (June-October), consistent with seasonal fluctuations of blooms and recent publications (6,7). Although syndromic surveillance data are helpful for understanding harmful algal bloom-associated ED visits in the United States, exposures were documented infrequently with discharge diagnosis codes; 67% of harmful algal bloom-associated ED visits were identified through querying chief complaint text. Improving the documentation of harmful algal bloom exposures in medical records would further benefit future health studies.

      2. Integrated disease management: arboviral infections and waterborne diarrhoeaexternal icon
        Overgaard HJ, Dada N, Lenhart A, Stenström TA, Alexander N.
        Bull World Health Organ. 2021 Aug 1;99(8):583-592.
        Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems. We believe that these two disease groups share common risk factors, namely inadequate household water management, poor sanitation and solid waste management. Where water provision is inadequate, water storage is essential. Aedes mosquitoes commonly breed in household water storage containers, which can hold water contaminated with enteric disease-causing organisms. Microbiological contamination of water between source and point-of-use is a major cause of reduced drinking-water quality. Inadequate sanitation and solid waste management increase not only risk of water contamination, but also the availability of mosquito larval habitats. In this article we discuss integrated interventions that interrupt mosquito breeding while also providing sanitary environments and clean water. Specific interventions include improving storage container design, placement and maintenance and scaling up access to piped water. Vector control can be integrated into sanitation projects that target sewers and drains to avoid accumulation of stagnant water. Better management of garbage and solid waste can reduce the availability of mosquito habitats while improving human living conditions. Our proposed integration of disease interventions is consistent with strategies promoted in several global health frameworks, such as the sustainable development goals, the global vector control response, behavioural change, and water, sanitation and hygiene initiatives. Future research should address how interventions targeting water, sanitation, hygiene and community waste disposal also benefit Aedes-borne disease control. The projected effects of climate change mean that integrated management and control strategies will become increasingly important.

    • Genetics and Genomics
      1. Coding-complete sequence of a SARS-CoV-2 B.1.1.25 lineage obtained from an 8-day-old deceased neonateexternal icon
        Alam M, Jahan MI, Jahan S, Blau DM, Rahman A, Rahman MZ, Hossain MZ, Gurley ES, Arifeen SE, Rahman M.
        Microbiol Resour Announc. 2021 Sep 2;10(35):e0075621.
        We report the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, hCoV-19/Bangladesh/icddrb-CHAMPS-BDAA02205/2021, obtained from a nasopharyngeal swab from a deceased neonate from Faridpur, Bangladesh. The strain belongs to lineage B.1.1.25 but contains some notable mutations similar to the B.1.1.7 lineage.

      2. Complete genome sequence of Rhodococcus sp. strain W8901, a human clinical specimen, assembled using MiSeq and MinION sequence dataexternal icon
        Gulvik CA, Batra D, Howard DT, Sheth M, Humrighouse BW, Lee J, McQuiston JR, Lasker BA.
        Microbiol Resour Announc. 2021 Sep 2;10(35):e0061321.
        Rhodococcus sp. strain W8901 is a Gram-positive, aerobic, mycolic acid-containing coccobacillus obtained from a patient with acute lymphocytic leukemia. Here, we report on the complete, circular genome sequence obtained using Illumina MiSeq and Oxford Nanopore Technologies MinION reads in order to better resolve the phylogeny of a rare pathogen.

    • Health Disparities
      1. OBJECTIVE: During 2000-2014, age-standardized five-year net survival for cervical cancer was 63-64% in the United States. Using data from CONCORD-3, we analyzed cervical cancer survival trends by race, stage and period of diagnosis. METHODS: Data from 41 state-wide population-based cancer registries on 138,883 women diagnosed with cervical cancer during 2001-2014 were available. Vital status was followed up until December 31, 2014. We estimated age-standardized five-year net survival, by race (Black or White), stage and calendar period of diagnosis (2001-2003, 2004-2008, 2009-2014) in each state, and for all participating states combined. RESULTS: White women were most commonly diagnosed with localized tumors (45-50%). However, for Black women, localized tumors were the most common stage (43.0%) only during 2001-2003. A smaller proportion of Black women received cancer-directed surgery than White women. For all stages combined, five-year survival decreased between 2001-2003 and 2009-2014 for both White (64.7% to 63.0%) and Black (56.7% to 55.8%) women. For localized and regional tumors, survival increased over the same period for both White (by 2-3%) and Black women (by 5%). Survival did not change for Black women diagnosed with distant tumors but increased by around 2% for White women. CONCLUSIONS: Despite similar screening coverage for both Black and White women and improvements in stage-specific survival, Black women still have poorer survival than White women. This may be partially explained by inequities in access to optimal treatment. The results from this study highlight the continuing need to address the disparity in cervical cancer survival between White and Black women in the United States.

    • Healthcare Associated Infections
      1. Gram-negative bacteria harboring multiple carbapenemase genes, United States, 2012-2019external icon
        Ham DC, Mahon G, Bhaurla SK, Horwich-Scholefield S, Klein L, Dotson N, Rasheed JK, McAllister G, Stanton RA, Karlsson M, Lonsway D, Huang JY, Brown AC, Walters MS.
        Emerg Infect Dis. 2021 ;27(9):2475-2479.
        Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation.

      2. Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global surveyexternal icon
        Tomczyk S, Taylor A, Brown A, de Kraker ME, El-Saed A, Alshamrani M, Hendriksen RS, Jacob M, Löfmark S, Perovic O, Shetty N, Sievert D, Smith R, Stelling J, Thakur S, Vietor AC, Eckmanns T.
        J Antimicrob Chemother. 2021 Sep 2.
        OBJECTIVES: The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Surveillance and Quality Assessment Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control. METHODS: From October to December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire, including Likert scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed and free-text questions were thematically analysed. RESULTS: Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; P < 0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (P < 0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased ICU admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antimicrobial prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19. CONCLUSIONS: This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses highlight important actions to help ensure that AMR remains a global health priority, including engaging with GLASS to facilitate reliable AMR surveillance data, seizing the opportunity to develop more sustainable IPC programmes, promoting integrated antibiotic stewardship guidance, leveraging increased laboratory capabilities and other system-strengthening efforts.

    • Immunity and Immunization
      1. High prevalence of vaccine-type infections among children with pneumococcal pneumonia and effusion after 13-valent pneumococcal conjugate vaccine introduction in the Dominican Republicexternal icon
        Ahmed SS, Lessa FC, Coradin H, Sánchez J, Carvalho MD, Soda E, Peña C, Fernández J, Cedano D, Whitney CG, Feris-Iglesias J.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S228-s236.
        BACKGROUND: In 2013, the Dominican Republic introduced 13-valent pneumococcal conjugate vaccine (PCV13) using a 3-dose schedule (at 2, 4 and 12 months of age). We evaluated the impact of PCV13 on serotypes causing pneumococcal pneumonia with pleural effusion. METHODS: Surveillance data after PCV13 introduction (July 2014 to June 2016) were compared with data before PCV13 introduction (July 2009 to June 2011). Cases were defined as radiologic evidence of pneumonia with pleural effusion in a child aged <15 years. Pneumococcus was detected in pleural fluid by either culture or polymerase chain reaction, and serotyping was performed. The Ministry of Health's PCV13 uptake data for 2014-2016 were obtained. RESULTS: The prevalence of pneumococcus among cases was similar before and after PCV13 introduction (56.4% and 52.8%, respectively). The proportion of pneumococcal cases caused by vaccine serotypes was 86% for children <2 years old both before and PCV13 introduction. Compared with before PCV13, serotype 14 accounted for a smaller (28% vs 13%, respectively; P = .02) and serotype 1 for a larger (23% vs 37%; P = .09) proportion of pneumococcal cases after PCV13 introduction. National uptake for the first, second, and third PCV13 doses was 94%, 81%, and 28%, respectively, in 2014 and 75%, 61%, and 26% in 2015. DISCUSSION: While the decrease in pneumococcal pneumonia with pleural effusion caused by serotype 14 may reflect an early effect of PCV13 implementation, other vaccine serotypes, including serotype 1, are not well controlled. Better PCV13 coverage for all 3 doses is needed.

      2. Impact of 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage rates of Streptococcus pneumoniae in a rural community in the Dominican Republicexternal icon
        Dunn MG, Lessa FC, Sánchez J, Cordero R, Feris-Iglesias J, Cedano D, Carvalho MD, Fernández J, Feemster KA.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S237-s247.
        BACKGROUND: Invasive pneumococcal disease (IPD) leads to thousands of pediatric deaths annually. Pneumococcal colonization precedes IPD. In 2013, the Dominican Republic introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into its routine infant immunization program, with doses at ages 2, 4, and 12 months. Prevalence of pneumococcal nasopharyngeal colonization was evaluated post-PCV13 introduction. METHODS: A prospective cohort study of 125 children aged 2-35 months was conducted in a rural Dominican Republic community November 2016 through July 2017. Nasopharyngeal swabs and clinical and vaccination data were collected at enrollment and 4-6 months later. Serotypes included in PCV13 were defined as vaccine-type. Colonization rates and serotype distribution were compared at baseline and follow-up, and the association between colonization and vaccination status among the entire cohort was evaluated at each time point. RESULTS: Of 125 children enrolled, 118 (94%) completed follow-up. Overall and vaccine-type pneumococcal colonization rates were 62% and 25%, respectively, at baseline and 60% and 28% at follow-up. Among children age-eligible for 3 doses, 50% and 51% were fully vaccinated at baseline and follow-up, respectively. At baseline assessment, children up-to-date for age for PCV13 were less likely to be colonized with vaccine-type pneumococci than children not up-to-date, and the same was found for fully vaccinated children (3 doses) compared to those not fully vaccinated (odds ratios [ORs], 0.38 [95% confidence interval {CI}, .18-.79], and 0.14 [95% CI, .04-.45], respectively). The same associations were not found at follow-up assessment. CONCLUSIONS: Three years post -PCV13 introduction, vaccine-type colonization rates remained high. Low vaccination coverage for 3 PCV13 doses may have contributed. The protective effect of PCV13 on vaccine-type carriage suggests an increase in PCV13 coverage could lead to substantial declines in pneumococcal vaccine-type carriage.

      3. Nasopharyngeal carriage of Streptococcus pneumoniae among young children in Haiti before pneumococcal conjugate vaccine introductionexternal icon
        Francois Watkins LK, Milucky JL, McGee L, Siné St-Surin F, Liu P, Tran T, Chochua S, Joseph G, Shang N, Juin S, Dely P, Patel R, Van Beneden CA.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S248-s257.
        BACKGROUND: Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). METHODS: We conducted a cross-sectional study of children aged 6-24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. RESULTS: Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. CONCLUSIONS: Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.

      4. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Seasonexternal icon
        Grohskopf LA, Alyanak E, Ferdinands JM, Broder KR, Blanton LH, Talbot HK, Fry AM.
        MMWR Recomm Rep. 2021 Aug 27;70(5):1-28.
        This report updates the 2020-21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021-22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4).The 2021-22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at Recommendations for the use of COVID-19 vaccines are available at, and additional clinical guidance is available at described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021-22 season are expected to be quadrivalent. Second, the composition of 2021-22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture-based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021-22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (; vaccination and health care providers should check this site periodically for additional information.

      5. COVID-19 vaccination in the Federal Bureau of Prisons, December 2020-April 2021external icon
        Hagan LM, Dusseau C, Crockett M, Rodriguez T, Long MJ.
        Vaccine. 2021 Aug 14.
        OBJECTIVES: To describe COVID-19 vaccine distribution operations in United States Federal Bureau of Prisons (BOP) institutions and offices from December 16, 2020-April 14, 2021, report vaccination coverage among staff and incarcerated people, and identify factors associated with vaccination acceptance among incarcerated people. METHODS: The BOP COVID-19 vaccination plan and implementation timeline are described. Descriptive statistics and vaccination coverage were calculated for the BOP incarcerated population using data from the BOP electronic medical record. Coverage among staff was calculated using data from the Centers for Disease Control and Prevention Vaccination Administration Management System. Vaccination coverage in the BOP versus the overall United States adult population was compared by state/territory. Univariate and multivariable logistic regression models were developed to identify demographic, health-related, and institution-level factors associated with vaccination acceptance among incarcerated people, using hierarchical linear modeling to account for institution-level clustering. RESULTS: By April 14, 2021, BOP had offered COVID-19 vaccination to 37,870 (100%) staff and 88,173/126,413 (69.8%) incarcerated people, with acceptance rates of 50.2% and 64.2%, respectively. At the time of analysis, vaccination coverage in BOP was comparable to coverage in the overall adult population in the states and territories where BOP institutions and offices are located. Among incarcerated people, factors associated with lower vaccination acceptance included younger age, female sex, non-Hispanic Black and Asian race/ethnicity, and having few underlying medical conditions; factors associated with higher acceptance included having a prior SARS-CoV-2 infection, being born outside the United States, and being assigned to a Federal Detention Center. CONCLUSIONS: Early COVID-19 vaccination efforts in BOP have achieved levels of coverage similar to the general population. To build on this initial success, BOP can consider strategies including re-offering vaccination to people who initially refused and tailoring communication strategies to groups with lower acceptance rates.

      6. Pneumococcal carriage in Burkina Faso after 13-valent pneumococcal conjugate vaccine introduction: Results from 2 cross-sectional population-based surveysexternal icon
        Kaboré L, Adebanjo T, Njanpop-Lafourcade BM, Ouangraoua S, Tarbangdo FT, Meda B, Velusamy S, Bicaba B, Aké F, McGee L, Yaro S, Betsem E, Gervaix A, Gessner BD, Whitney CG, Moïsi JC, Van Beneden CA.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S258-s266.
        BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

      7. Toward establishing integrated, comprehensive, and sustainable meningitis surveillance in Africa to better inform vaccination strategiesexternal icon
        Kwambana-Adams BA, Cohen AL, Hampton L, Nhantumbo AA, Heyderman RS, Antonio M, Bita A, Mwenda JM.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S299-s306.
        Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.

      8. COVID-19 vaccination coverage among adolescents aged 12-17 years - United States, December 14, 2020-July 31, 2021external icon
        Murthy BP, Zell E, Saelee R, Murthy N, Meng L, Meador S, Reed K, Shaw L, Gibbs-Scharf L, McNaghten AD, Patel A, Stokley S, Flores S, Yoder JS, Black CL, Harris LQ.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1206-1213.
        Although severe COVID-19 illness and hospitalization are more common among adults, these outcomes can occur in adolescents (1). Nearly one third of adolescents aged 12-17 years hospitalized with COVID-19 during March 2020-April 2021 required intensive care, and 5% of those hospitalized required endotracheal intubation and mechanical ventilation (2). On December 11, 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 vaccine for adolescents aged 16-17 years; on May 10, 2021, the EUA was expanded to include adolescents aged 12-15 years; and on August 23, 2021, FDA granted approval of the vaccine for persons aged ≥16 years. To assess progress in adolescent COVID-19 vaccination in the United States, CDC assessed coverage with ≥1 dose* and completion of the 2-dose vaccination series(†) among adolescents aged 12-17 years using vaccine administration data for 49 U.S. states (all except Idaho) and the District of Columbia (DC) during December 14, 2020-July 31, 2021. As of July 31, 2021, COVID-19 vaccination coverage among U.S. adolescents aged 12-17 years was 42.4% for ≥1 dose and 31.9% for series completion. Vaccination coverage with ≥1 dose varied by state (range = 20.2% [Mississippi] to 70.1% [Vermont]) and for series completion (range = 10.7% [Mississippi] to 60.3% [Vermont]). By age group, 36.0%, 40.9%, and 50.6% of adolescents aged 12-13, 14-15, and 16-17 years, respectively, received ≥1 dose; 25.4%, 30.5%, and 40.3%, respectively, completed the vaccine series. Improving vaccination coverage and implementing COVID-19 prevention strategies are crucial to reduce COVID-19-associated morbidity and mortality among adolescents and to facilitate safer reopening of schools for in-person learning.

      9. Global rotavirus and pneumococcal conjugate vaccine introductions and the association with country disease surveillance, 2006-2018external icon
        Peck ME, Hampton LM, Antoni S, Ogbuanu I, Serhan F, Nakamura T, Walldorf JA, Cohen AL.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S184-s193.
        BACKGROUND: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. METHODS: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. RESULTS: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. CONCLUSIONS: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.

      10. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years - United States, 2020external icon
        Pingali C, Yankey D, Elam-Evans LD, Markowitz LE, Williams CL, Fredua B, McNamara LA, Stokley S, Singleton JA.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 3;70(35):1183-1190.
        The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) vaccines. Catch-up vaccination is recommended for hepatitis B (HepB); hepatitis A (HepA); measles, mumps, and rubella (MMR); and varicella (VAR) vaccines for adolescents whose childhood vaccinations are not current. Adolescents are also recommended to receive a booster dose of MenACWY vaccine at age 16 years, and shared clinical decision-making is recommended for the serogroup B meningococcal vaccine (MenB) for persons aged 16-23 years (1). To estimate coverage with recommended vaccines, CDC analyzed data from the 2020 National Immunization Survey-Teen (NIS-Teen) for 20,163 adolescents aged 13-17 years.* Coverage with ≥1 dose of HPV vaccine increased from 71.5% in 2019 to 75.1% in 2020. The percentage of adolescents who were up to date(†) with HPV vaccination (HPV UTD) increased from 54.2% in 2019 to 58.6% in 2020. Coverage with ≥1 dose of Tdap, ≥1 dose (and among adolescents aged 17 years, ≥2 doses) of MenACWY remained similar to coverage in 2019 (90.1%, 89.3%, and 54.4% respectively). Coverage increased for ≥2 doses of HepA among adolescents aged 13-17 years and ≥1 dose of MenB among adolescents aged 17 years. Adolescents living below the federal poverty level(§) had higher HPV vaccination coverage than adolescents living at or above the poverty level. Adolescents living outside a metropolitan statistical area (MSA)(¶) had lower coverage with ≥1 MenACWY and ≥1 HPV dose, and a lower proportion being HPV UTD than adolescents in MSA principal cities. In 2020, the COVID-19 pandemic disrupted routine immunization services. Results from the 2020 NIS-Teen reflect adolescent vaccination coverage before the COVID-19 pandemic. The 2020 NIS-Teen data could be used to assess the impact of the COVID-19 pandemic on catch-up vaccination but not on routine adolescent vaccination because adolescents included in the survey were aged ≥13 years, past the age when most routine adolescent vaccines are recommended, and most vaccinations occurred before March 2020. Continued efforts to reach adolescents whose routine medical care has been affected by the COVID-19 pandemic are necessary to protect persons and communities from vaccine-preventable diseases and outbreaks.

    • Informatics
      1. Factors affecting the adoption of electronic data reporting and outcomes among selected central cancer registries of the National Program of Cancer Registriesexternal icon
        Tangka FK, Edwards P, Pordell P, Wilson R, Blumenthal W, Jones SF, Jones M, Beizer J, Bernacet A, Cole-Beebe M, Subramanian S.
        JCO Clin Cancer Inform. 2021 Aug;5:921-932.
        PURPOSE: The CDC's National Program of Cancer Registries has expanded the use of electronic reporting to collect more timely information on newly diagnosed cancers. The adoption, implementation, and use of electronic reporting vary significantly among central cancer registries. We identify factors affecting the adoption of electronic reporting among these registries. METHODS: Directors and data managers of nine National Program of Cancer Registries took part in separate 1-hour telephone interviews in early 2019. Directors were asked about their registry's key data quality goals; staffing, resources, and tools used to aid processes; their definition and self-perception of electronic reporting adoption; key helpers and challenges; and cost and sustainability implications for adoption of electronic reporting. Data managers were asked about specific data collection processes, software applications, electronic reporting adoption and self-perception, information technology infrastructure, and helpers and challenges to data collection and processing, data quality, and sustainability of approach. RESULTS: Larger registries identified organizational capacity and technical expertise as key aides. Other help for implementing electronic reporting processes came from partnerships, funding availability, management support, legislation, and access to an interstate data exchange. Common challenges among lower adopters included lack of capacity at both registry and data source levels, insufficient staffing, and a lack of information technology or technical support. Other challenges consisted of automation and interoperability of software, volume of cases received, state political environment, and quality of data received. CONCLUSION: Feedback from the formative evaluation yielded several useful solutions that can guide implementation of electronic reporting and help refine the technical assistance provided to registries. Our findings may help guide future process and economic evaluations of electronic reporting and identify best practices to strengthen registry operations.

    • Injury and Violence
      1. OBJECTIVES: This study assessed associations between recent transactional sex (TS) and potential determinants and variations in patterns across two geographic regions with high HIV burden compared to the rest of Uganda, among adolescent girls and young women (AGYW). METHODS: In 2015, a nationally representative cross-sectional household survey was conducted in Uganda. A stratified multi-stage cluster sample design produced nationally representative estimates and sub-national estimates for AGYW in two high HIV burden regions, DREAMS Central 1 (Bukomansimbi, Ssembabule, and Rakai districts) and DREAMS Central 2 (Mubende, Mityana, Gomba, and Mukono districts), and the rest of Uganda. To identify associations between recent TS (defined as sex in the past 12 months in exchange for material support or help) and risk factors, multivariable logistic regressions were conducted. Interaction terms assessed the associations between violence and recent TS across geographic regions. RESULTS: Nationally, 14.2% of sexually active AGYW engaged in recent TS. Region-specific significant associations emerged between recent TS and marriage, family wealth, friendship, orphanhood, and sexual debut. In DREAMS Central 1 and 2, AGYW who witnessed violence in the home or community, or experienced sexual, physical, or emotional violence had higher odds of recent TS than AGYW who did not experience that form of violence (adjusted odds ratio ranged between 2.10 (95% CI, 1.07, 4.13) and 8.25 (95% CI, 3.40, 20.06)). The magnitude of association between recent TS and types of violence varied by region. CONCLUSIONS: Violence is strongly and consistently associated with recent TS, and patterns in prevalence and risk factors vary across regions in Uganda. Given the high risk of HIV association with recent TS, HIV epidemic control efforts may benefit from focus on comprehensive violence prevention and target persons who engage in TS. Comprehensive HIV prevention programming aimed at keeping AGYW HIV-negative should incorporate prevention of violence and TS as key components to facilitate HIV epidemic control in this vulnerable population.

    • Laboratory Sciences
      1. The role of molecular testing in pediatric meningitis surveillance in southern and east African countries, 2008-2017external icon
        du Plessis M, de Gouveia L, Freitas C, Abera NA, Lula BS, Raboba JL, Nhantumbo AA, Jantjies E, Uwimana J, Phungwayo N, Maphalala G, Masona G, Muyombe J, Mugisha D, Nalumansi E, Odongkara M, Lukwesa-Musyani C, Nakazwe R, Dondo V, Macharaga J, Weldegebriel GG, Mwenda JM, Serhan F, Cohen AL, Lessa FC, von Gottberg A.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S194-s203.
        BACKGROUND: As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa's regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). METHODS: From 2008 to 2017, CSF samples collected from children <5 years old with suspected meningitis underwent routine microbiology testing in-country, and 11 680 samples were submitted for HNS PCR at the regional reference laboratory. Unconditional logistic regression, with adjustment for geographic location, was performed to identify factors associated with PCR positivity. RESULTS: The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67-8.17) and xanthochromic (1.72; 1.29-2.28), had elevated white blood cell counts (6.13; 4.71-7.99) and high protein concentrations (5.80; 4.34-7.75), and were more often HNS culture positive (32.70; 23.18-46.12). CONCLUSION: PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.

      2. Antigen test performance among children and adults at a SARS-CoV-2 community testing siteexternal icon
        Ford L, Whaley MJ, Shah MM, Salvatore PP, Segaloff HE, Delaney A, Currie DW, Boyle-Estheimer L, O'Hegarty M, Morgan CN, Meece J, Ivacic L, Thornburg NJ, Tamin A, Harcourt JL, Folster JM, Medrzycki M, Jain S, Wong P, Goffard K, Gieryn D, Kahrs J, Langolf K, Zochert T, Tate JE, Hsu CH, Kirking HL.
        J Pediatric Infect Dis Soc. 2021 Sep 1.
        BACKGROUND: Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture. METHODS: Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR-positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults. RESULTS: About 1 in 10 included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR-positive. Cycle threshold values were similar among RT-PCR-positive specimens from children and adults (22.5 vs 21.3, P = .46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, P = .39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive values were 100% (27/27) and 94.9% (188/198), respectively. Virus was isolated from 51.4% (19/37) of RT-PCR-positive pediatric specimens; all 19 had positive antigen test results. CONCLUSIONS: With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.

      3. 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegaviralesexternal icon
        Kuhn JH, Adkins S, Agwanda BR, Al Kubrusli R, Alkhovsky Aльxoвcкий Cepгeй Bлaдимиpoвич SV, Amarasinghe GK, Avšič-Županc T, Ayllón MA, Bahl J, Balkema-Buschmann A, Ballinger MJ, Basler CF, Bavari S, Beer M, Bejerman N, Bennett AJ, Bente DA, Bergeron É, Bird BH, Blair CD, Blasdell KR, Blystad DR, Bojko J, Borth WB, Bradfute S, Breyta R, Briese T, Brown PA, Brown JK, Buchholz UJ, Buchmeier MJ, Bukreyev A, Burt F, Büttner C, Calisher CH, Cao 曹孟籍 M, Casas I, Chandran K, Charrel RN, Cheng Q, Chiaki 千秋祐也 Y, Chiapello M, Choi IR, Ciuffo M, Clegg JC, Crozier I, Dal Bó E, de la Torre JC, de Lamballerie X, de Swart RL, Debat H, Dheilly NM, Di Cicco E, Di Paola N, Di Serio F, Dietzgen RG, Digiaro M, Dolnik O, Drebot MA, Drexler JF, Dundon WG, Duprex WP, Dürrwald R, Dye JM, Easton AJ, Ebihara 海老原秀喜 H, Elbeaino T, Ergünay K, Ferguson HW, Fooks AR, Forgia M, Formenty PB, Fránová J, Freitas-Astúa J, Fu 付晶晶 J, Fürl S, Gago-Zachert S, Gāo 高福 GF, García ML, García-Sastre A, Garrison AR, Gaskin T, Gonzalez JJ, Griffiths A, Goldberg TL, Groschup MH, Günther S, Hall RA, Hammond J, Han 韩彤 T, Hepojoki J, Hewson R, Hong 洪健 J, Hong 洪霓 N, Hongo 本郷誠治 S, Horie 堀江真行 M, Hu JS, Hu T, Hughes HR, Hüttner F, Hyndman TH, Ilyas M, Jalkanen R, Jiāng 姜道宏 D, Jonson GB, Junglen S, Kadono 上遠野冨士夫 F, Kaukinen KH, Kawate M, Klempa B, Klingström J, Kobinger G, Koloniuk I, Kondō 近藤秀樹 H, Koonin EV, Krupovic M, Kubota 久保田健嗣 K, Kurath G, Laenen L, Lambert AJ, Langevin SL, Lee B, Lefkowitz EJ, Leroy EM, Li 李邵蓉 S, Li 李龙辉 L, Lǐ 李建荣 J, Liu 刘华珍 H, Lukashevich IS, Maes P, de Souza WM, Marklewitz M, Marshall SH, Marzano SL, Massart S, McCauley JW, Melzer M, Mielke-Ehret N, Miller KM, Ming TJ, Mirazimi A, Mordecai GJ, Mühlbach HP, Mühlberger E, Naidu R, Natsuaki 夏秋知英 T, Navarro JA, Netesov Heтёcoв Cepгeй Bиктopoвич SV, Neumann G, Nowotny N, Nunes MR, Olmedo-Velarde A, Palacios G, Pallás V, Pályi B, Papa Άννα Παπά A, Paraskevopoulou Σοφία Παρασκευοπούλου S, Park AC, Parrish CR, Patterson DA, Pauvolid-Corrêa A, Pawęska JT, Payne S, Peracchio C, Pérez DR, Postler TS, Qi 亓立莹 L, Radoshitzky SR, Resende RO, Reyes CA, Rima BK, Luna GR, Romanowski V, Rota P, Rubbenstroth D, Rubino L, Runstadler JA, Sabanadzovic S, Sall AA, Salvato MS, Sang R, Sasaya 笹谷孝英 T, Schulze AD, Schwemmle M, Shi 施莽 M, Shí 石晓宏 X, Shí 石正丽 Z, Shimomoto 下元祥史 Y, Shirako Y, Siddell SG, Simmonds P, Sironi M, Smagghe G, Smither S, Song 송진원 JW, Spann K, Spengler JR, Stenglein MD, Stone DM, Sugano J, Suttle CA, Tabata A, Takada 高田礼人 A, Takeuchi 竹内繁治 S, Tchouassi DP, Teffer A, Tesh RB, Thornburg NJ, Tomitaka 冨高保弘 Y, Tomonaga 朝長啓造 K, Tordo N, Torto B, Towner JS, Tsuda 津田新哉 S, Tu 涂长春 C, Turina M, Tzanetakis IE, Uchida J, Usugi 宇杉富雄 T, Vaira AM, Vallino M, van den Hoogen B, Varsani A, Vasilakis Νίκος Βασιλάκης N, Verbeek M, von Bargen S, Wada 和田治郎 J, Wahl V, Walker PJ, Wang 王林发 LF, Wang 王国平 G, Wang 王雁翔 Y, Wang 王亚琴 Y, Waqas M, Wèi 魏太云 T, Wen 温少华 S, Whitfield AE, Williams JV, Wolf YI, Wu 吴建祥 J, Xu 徐雷 L, Yanagisawa 栁澤広宣 H, Yang 杨彩霞 C, Yang 杨作坤 Z, Zerbini FM, Zhai 翟立峰 L, Zhang 张永振 YZ, Zhang 张松 S, Zhang 张靖国 J, Zhang 张哲 Z, Zhou 周雪平 X.
        Arch Virol. 2021 Aug 31.
        In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

      4. Triplex direct quantitative polymerase chain reaction for the identification of Streptococcus pneumoniae serotypesexternal icon
        Ouattara M, Tamboura M, Kambiré D, Lê KA, Van Phan T, Velusamy S, Nguyen HA, Trang DV, Lessa FC, Iijima M, Nguyen DT, Schwartz SB, McGee L, Traoré RO, Beall B.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S204-s208.
        The quantitative polymerase chain reaction (qPCR) method presented in this study allows the identification of pneumococcal capsular serotypes in cerebrospinal fluid without first performing DNA extraction. This testing approach, which saves time and resources, demonstrated similar sensitivity and a high level of agreement between cycle threshold values when it was compared side-by-side with the standard qPCR method with extracted DNA.

      5. Multiplex immunoassay to measure antibody response to nine HPV vaccine typesexternal icon
        Panicker G, Rajbhandari I, Pathak HN, Brady AM, Unger ER.
        J Immunol Methods. 2021 Aug 28:113136.
        Well-characterized HPV serology assays are required to evaluate performance of biosimilar candidate vaccines, reduced dosing schedules and novel administration methods. We report characterization of an expanded assay, M9ELISA, that detects antibodies to HPV virus-like particles (VLP) of nine types using direct IgG ELISA on the Meso Scale Discovery (MSD) electrochemiluminescence platform. The method is based on the previously published M4ELISA which detects antibodies to HPV6,11,16, and 18. It has been modified to add detection of antibodies to HPV31,33,45,52 and 58, and to streamline assay and reduce background. The M9ELISA plates were prepared with purified type specific L1 + L2 VLPs coated on 10-spot/well standard MSD microplates. Results of ELISA on three serial dilutions of serum were read on MSD imager, and titers calculated using the parallel line method. Evaluations included dynamic range, assay reproducibility, and stability over time. We compared M9ELISA results to those from a pseudovirion-based neutralization assay in sera from a mixed cohort of unvaccinated and vaccinated individuals (n = ~116) and to competitive Luminex immunoassay (cLIA) results in sera from a predominantly unvaccinated cohort (n = 4426). The linear range of the assay extended over 5 logs, with inter-assay reproducibility coefficient of variation ≤25% for all types. The pre-coated plates were stable for at least 2 years. Spearman correlation of antibody titers showed excellent correlation with PBNA (r = 0.86-0.97) and moderate correlation (r = 0.52-0.68) with cLIA. Thus, the M9ELISA can serve as a useful platform for high-throughput, sensitive and simultaneous quantitation of the antibody responses to nine HPV vaccine types.

      6. Modeling optimal laboratory testing strategies for bacterial meningitis surveillance in Africaexternal icon
        Walker J, Soeters HM, Novak R, Diallo AO, Vuong J, Bicaba BW, Medah I, Yaméogo I, Ouédraogo-Traoré R, Gamougame K, Moto DD, Dembélé AY, Guindo I, Coulibaly S, Issifou D, Zaneidou M, Assane H, Nikiema C, Sadji A, Fernandez K, Mwenda JM, Bita A, Lingani C, Tall H, Tarbangdo F, Sawadogo G, Paye MF, Wang X, McNamara LA.
        J Infect Dis. 2021 Sep 1;224(Supplement_3):S218-s227.
        Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa's meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.

    • Occupational Safety and Health
      1. Heat safety in the workplace: Modified Delphi consensus to establish strategies and resources to protect the US workersexternal icon
        Morrissey MC, Casa DJ, Brewer GJ, Adams WM, Hosokawa Y, Benjamin CL, Grundstein AJ, Hostler D, McDermott BP, McQuerry ML, Stearns RL, Filep EM, DeGroot DW, Fulcher J, Flouris AD, Huggins RA, Jacklitsch BL, Jardine JF, Lopez RM, McCarthy RB, Pitisladis Y, Pryor RR, Schlader ZJ, Smith CJ, Smith DL, Spector JT, Vanos JK, Williams WJ, Vargas NT, Yeargin SW.
        Geohealth. 2021 Aug;5(8):e2021GH000443.
        The purpose of this consensus document was to develop feasible, evidence-based occupational heat safety recommendations to protect the US workers that experience heat stress. Heat safety recommendations were created to protect worker health and to avoid productivity losses associated with occupational heat stress. Recommendations were tailored to be utilized by safety managers, industrial hygienists, and the employers who bear responsibility for implementing heat safety plans. An interdisciplinary roundtable comprised of 51 experts was assembled to create a narrative review summarizing current data and gaps in knowledge within eight heat safety topics: (a) heat hygiene, (b) hydration, (c) heat acclimatization, (d) environmental monitoring, (e) physiological monitoring, (f) body cooling, (g) textiles and personal protective gear, and (h) emergency action plan implementation. The consensus-based recommendations for each topic were created using the Delphi method and evaluated based on scientific evidence, feasibility, and clarity. The current document presents 40 occupational heat safety recommendations across all eight topics. Establishing these recommendations will help organizations and employers create effective heat safety plans for their workplaces, address factors that limit the implementation of heat safety best-practices and protect worker health and productivity.

    • Parasitic Diseases
      1. A framework for scabies controlexternal icon
        Engelman D, Marks M, Steer AC, Beshah A, Biswas G, Chosidow O, Coffeng LE, Lardizabal Dofitas B, Enbiale W, Fallah M, Gasimov E, Hopkins A, Jacobson J, Kaldor JM, Ly F, Mackenzie CD, McVernon J, Parnaby M, Rainima-Qaniuci M, Sokana O, Sankara D, Yotsu R, Yajima A, Cantey PT.
        PLoS Negl Trop Dis. 2021 Sep;15(9):e0009661.
        Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals.

    • Program Evaluation
      1. The Childhood Obesity Data Initiative: A case study in implementing clinical-community infrastructure enhancements to support health services research and public healthexternal icon
        King RJ, Heisey-Grove DM, Garrett N, Scott KA, Daley MF, Haemer MA, Podila P, Block JP, Carton T, Gregorowicz AJ, Mork KP, Porter RM, Chudnov DL, Jellison J, Kraus EM, Harrison MR, Sucosky MS, Armstrong S, Goodman AB.
        J Public Health Manag Pract. 2021 Aug 24.
        CONTEXT: We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process. PROGRAM: The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners. IMPLEMENTATION: CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020. EVALUATION: We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes. DISCUSSION: We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs.

      2. A governance framework to integrate longitudinal clinical and community data in a distributed data network: The Childhood Obesity Data Initiativeexternal icon
        Kraus EM, Scott KA, Zucker R, Heisey-Grove D, King RJ, Carton TW, Daley MF, Deakyne Davies SJ, Block JP, Haemer M, Goodman AB, Garrett N, Davidson AJ.
        J Public Health Manag Pract. 2021 Aug 24.
        CONTEXT: Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research. OBJECTIVE: A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems. PARTICIPANTS AND SETTING: Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research. DESIGN: A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement. RESULTS: A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications. CONCLUSION: CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts.

    • Zoonotic and Vectorborne Diseases
      1. A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxisexternal icon
        Kim PK, Ahn JS, Kim CM, Seo JM, Keum SJ, Lee HJ, Choo MJ, Kim MS, Lee JY, Maeng KE, Shin JY, Yi KS, Osinubi MO, Franka R, Greenberg L, Shampur M, Rupprecht CE, Lee SY.
        PLoS One. 2021 ;16(9):e0256779.
        Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

      2. Pathology and pathogenesis of Lassa fever: Novel immunohistochemical findings in fatal cases and clinico-pathologic correlationexternal icon
        Shieh WJ, Demby A, Jones T, Goldsmith CS, Rollin PE, Ksiazek TG, Peters CJ, Zaki SR.
        Clin Infect Dis. 2021 Aug 31.
        BACKGROUND: Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the "at risk" seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of three million, and fatalities up to 67,000, demonstrating the serious impact of the disease on the region and global health. METHODS: Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. RESULTS: Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. CONCLUSIONS: The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of LF is multifactorial and additional studies are needed.

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