Issue 4, January 25, 2022

CDC Science Clips: Volume 14, Issue 4, January 25, 2022

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Evaluation of effects of continued corticosteroid treatment on cardiac and pulmonary function in non-ambulatory males with Duchenne Muscular Dystrophy from MD STARnetexternal icon
        Butterfield RJ, Krikov S, Conway KM, Johnson N, Matthews D, Phan H, Cai B, Paramsothy P, Thomas S, Feldkamp ML.
        Muscle Nerve. 2022 Jan 7.
        INTRODUCTION/AIMS: Corticosteroids have been shown to improve muscle strength and delay loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD) and are considered standard of care despite significant side-effects. The objective of this study is to evaluate whether corticosteroid treatment after LOA is beneficial for cardiac or pulmonary functions among boys with DMD. METHODS: We used the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to characterize associations between corticosteroid use and onset of abnormal left ventricular (LV) function or abnormal percent predicted forced vital capacity (ppFVC) among 398 non-ambulatory boys with DMD. Kaplan-Meier curve estimation was used to compare time to onset by corticosteroid use groups; Cox proportional hazards modeling was used to estimate hazards ratios (HR)s and corresponding 95% confidence intervals. RESULTS: We found no differences in time to onset of abnormal LV function by corticosteroid use groups. We observed a longer time from LOA to first abnormal ppFVC in boys that were treated with corticosteroid ≥1 year beyond LOA compared to those with no corticosteroid use or those who stopped corticosteroid use within 1 year of LOA. DISCUSSION: Our findings show no association of corticosteroid use beyond LOA with the onset of abnormal LV function, but a significant association with a delay in onset of abnormal ppFVC. Prospective studies of corticosteroid use in boys with DMD who have lost ambulation may identify benefits and can better elucidate risks, allowing for more effective counseling of patients on continuing treatment after LOA.

    • Communicable Diseases
      1. Aging, trends in CD4/CD8 ratio and clinical outcomes with persistent HIV suppression in the HIV outpatient study (HOPS)external icon
        Novak RM, Armon C, Battalora L, Buchacz K, Li J, Ward D, Carlson K, Palella FJ.
        Aids. 2022 Jan 10.
        BACKGROUND: Age blunts CD4+ lymphocyte cell count/mm3 (CD4) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4/CD8 ratios (CD4/CD8). We studied CD4/CD8 over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression. METHODS: We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a VL < 200 copies/mL on or after January 1, 2000, and remained virally suppressed at least one year thereafter. We modeled associations of CD4/CD8 with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors. RESULTS: Of 2,480 eligible participants,1,145 (46%) were aged < 40 years, 835 (34%) 40-49 years, and 500 (20%) ≥ 50 years. At baseline, median CD4/CD8 was 0.53 (interquartile range: 0.30-0.84) and similar among all age groups (P = 0.18). CD4/CD8 values and percent of participants with CD4/CD8 ≥ 0.70 increased within each age group (P < 0.001 for all). CD4/CD8 increase was greatest for PWH aged < 40 years at baseline. In adjusted models, most recent CD4/CD8 < 1.00 and < 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively. CONCLUSIONS: Pre-treatment immune dysregulation may persist as indicated by CD4/CD8 < 0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity and mortality risk. Monitoring CD4/CD8 among ART-treated PWH with lower values provide a means to assess for mortality and co-morbidity risk.

      2. We analyzed a national pharmacy database to estimate the annual number of persons who abandoned their PrEP prescription and assessed the associated factors. About 9% of persons prescribed PrEP abandoned it in 2019, and PrEP abandonment was associated with sex, age, insurance type, black race/ethnicity, and drug copayment amount.

      3. BACKGROUND: Low global influenza circulation was reported during the coronavirus-19 pandemic. We explored relationships between non-pharmaceutical interventions (NPIs) and influenza in tropical Asian countries. METHODS: Using World Health Organization (WHO) surveillance data from 2015 to 2019 and the WHO shiny app, we constructed expected seasonal influenza epidemic curves from March 2020 to June 2021 and compared the timing, and average percent positivity with observed data. We used multivariate regression to test associations between ordinal NPI data (from the Oxford Stringency Index) 4 weeks before the expected 2020/21 epidemics and present adjusted incidence rate ratio (IRR) or relative proportion ratio (RPR) and 95% confidence intervals (CI). RESULTS: Data from nine countries predicted 18 seasonal epidemics; seven were observed. Five started 6-24 weeks later, and all were 4-21 weeks shorter than expected. Five epidemics had lower maximum peak values (percent positivity), and all but one had lower average percent positivity than expected. All countries implemented NPIs. Each increased level of school closure reduced risk of an epidemic by 43% (IRR = 0.57, CI: 0.34, 0.95). Each increased level of canceling public events reduced the average percent positivity across the season by 44% (RPR = 0.56, CI: 0.39, 0.82) and each increased level in restricting internal movements reduced it by 41% (RPR = 0.59, CI: 0.36, 0.96). Other NPIs were not associated with changes. CONCLUSIONS: Among nine countries, the 2020/21 seasonal epidemics were delayed, shorter, and less intense than expected. Although layered NPIs were difficult to tease apart, school closings, canceling public events, and restricting internal movements before influenza circulation seemed to reduce transmission.

    • Disaster Preparedness and Emergency Services
      1. ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Studyexternal icon
        Lane CJ, Bhatnagar M, Lutrick K, Maves RC, Weiner D, Rios Olvera D, Uyeki TM, Cobb JP, Brown JC.
        Crit Care Explor. 2022 Jan;4(1):e0606.
        OBJECTIVES: Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. DESIGN: Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. PARTICIPANTS: Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. SETTING: ICUs of 13 hospitals throughout the United States, 12 academic, and one community. INTERVENTIONS: ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018-April 2018). Responses were collected for 48 hours after each email query. MEASUREMENTS AND MAIN RESULTS: The average weekly response among the sites was 79% (range, 65-100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. CONCLUSIONS: This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

    • Drug Safety
      1. Using machine learning to examine drivers of inappropriate outpatient antibiotic prescribing in acute respiratory illnessesexternal icon
        King LM, Kusnetsov M, Filippoupolitis A, Arik D, Bartoces M, Roberts RM, Tsay SV, Kabbani S, Bizune D, Rathore AS, Valkova S, Eleftherohorinou H, Hicks LA.
        Infect Control Hosp Epidemiol. 2022 Jan 10:1-5.
        Using a machine-learning model, we examined drivers of antibiotic prescribing for antibiotic-inappropriate acute respiratory illnesses in a large US claims data set. Antibiotics were prescribed in 11% of the 42 million visits in our sample. The model identified outpatient setting type, patient age mix, and state as top drivers of prescribing.

    • Environmental Health
      1. Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Surveyexternal icon
        Cave MC, Pinkston CM, Rai SN, Wahlang B, Pavuk M, Head KZ, Carswell GK, Nelson GM, Klinge CM, Bell DA, Birnbaum LS, Chorley BN.
        Environ Health Perspect. 2022 Jan;130(1):17003.
        BACKGROUND: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress. OBJECTIVES: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort. METHODS: Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed. RESULTS: The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor α were well integrated within the top identified networks. DISCUSSION: These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies.

      2. Biomonitoring of exposure to Great Lakes contaminants among licensed anglers and Burmese refugees in Western New York: Toxic metals and persistent organic pollutants, 2010-2015external icon
        Hsu WH, Zheng Y, Savadatti SS, Liu M, Lewis-Michl EL, Aldous KM, Parsons PJ, Kannan K, Rej R, Wang W, Palmer CD, Wattigney WA, Irvin-Barnwell E, Hwang SA.
        Int J Hyg Environ Health. 2022 Jan 8;240:113918.
        Between 2010 and 2015, the New York State Department of Health (NYSDOH) conducted a biomonitoring program to gather exposure data on Great Lakes contaminants among licensed anglers and Burmese refugees living in western New York who ate locally caught fish. Four hundred and nine adult licensed anglers and 206 adult Burmese refugees participated in this program. Participants provided blood and urine samples and completed a detailed questionnaire. Herein, we present blood metal levels (cadmium, lead, and total mercury) and serum persistent organic pollutant concentrations [polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyldichloroethylene (DDE), and trans-nonachlor]. Multiple linear regression was applied to investigate the associations between analyte concentrations and indicators of fish consumption (locally caught fish meals, store-bought fish meals, and consuming fish/shellfish in the past week). Licensed anglers consumed a median of 16 locally caught fish meals and 22 store-bought fish meals while Burmese refugees consumed a median of 106 locally caught fish meals and 104 store-bought fish/shellfish meals in the past year. Compared to the general U.S. adult population, licensed anglers had higher blood lead and mercury levels; and Burmese refuges had higher blood cadmium, lead, and mercury, and higher serum DDE levels. Eating more locally caught fish was associated with higher blood lead, blood mercury, and serum ∑PCBs concentrations among licensed anglers. Licensed anglers and Burmese refugees who reported fish/shellfish consumption in the past week had elevated blood mercury levels compared with those who reported no consumption. Among licensed anglers, eating more store-bought fish meals was also associated with higher blood mercury levels. As part of the program, NYSDOH staff provided fish advisory outreach and education to all participants on ways to reduce their exposures, make healthier choices of fish to eat, and waters to fish from. Overall, our findings on exposure levels and fish consumption provide information to support the development and implementation of exposure reduction public health actions.

    • Epidemiology and Surveillance
      1. In the United States, COVID-19 has become a leading cause of death since 2020. However, the number of COVID-19 deaths reported from death certificates is likely to represent an underestimate of the total deaths related to SARS-CoV-2 infections. Estimating those deaths not captured through death certificates is important to understanding the full burden of COVID-19 on mortality. In this work, we explored enhancements to an existing approach by employing Bayesian hierarchical models to estimate unrecognized deaths attributed to COVID-19 using weekly state-level COVID-19 viral surveillance and mortality data in the United States from March 2020 to April 2021. We demonstrated our model using those aged   ≥ 85 years who died. First, we used a spatial-temporal binomial regression model to estimate the percent of positive SARS-CoV-2 test results. A spatial-temporal negative-binomial model was then used to estimate unrecognized COVID-19 deaths by exploiting the spatial-temporal association between SARS-CoV-2 percent positive and all-cause mortality counts using an excess mortality approach. Computationally efficient Bayesian inference was accomplished via the Polya-Gamma representation of the binomial and negative-binomial models. Among those aged   ≥ 85 years, we estimated 58,200 (95% CI: 51,300, 64,900) unrecognized COVID-19 deaths, which accounts for 26% (95% CI: 24%, 29%) of total COVID-19 deaths in this age group. Our modeling results suggest that COVID-19 mortality and the proportion of unrecognized deaths among deaths attributed to COVID-19 vary by time and across states.

    • Food Safety
      1. Outbreak of Multidrug-Resistant Salmonella Heidelberg Infections Linked to Dairy Calf Exposure, United States, 2015-2018external icon
        Nichols M, Gollarza L, Sockett D, Aulik N, Patton E, Francois Watkins LK, Gambino-Shirley KJ, Folster JP, Chen JC, Tagg KA, Stapleton GS, Trees E, Ellison Z, Lombard J, Morningstar-Shaw B, Schlater L, Elbadawi L, Klos R.
        Foodborne Pathog Dis. 2022 Jan 6.
        In August 2016, the Wisconsin Department of Health Services notified the U.S. Centers for Disease Control and Prevention of multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg infections in people who reported contact with dairy calves. Federal and state partners investigated this to identify the source and scope of the outbreak and to prevent further illnesses. Cases were defined as human Salmonella Heidelberg infection caused by a strain that had one of seven pulsed-field gel electrophoresis (PFGE) patterns or was related by whole genome sequencing (WGS), with illness onset from January 1, 2015, through July 2, 2018. Patient exposure and calf purchase information was collected and analyzed; calves were traced back from the point of purchase. Isolates obtained from animal and environmental samples collected on-farm were supplied by veterinary diagnostic laboratories and compared with patient isolates using PFGE and WGS. Antimicrobial susceptibility testing by standardized broth microdilution was performed. Sixty-eight patients from 17 states were identified. Forty (63%) of 64 patients noted cattle contact before illness. Thirteen (33%) of 40 patients with exposure to calves reported that calves were sick or had died. Seven individuals purchased calves from a single Wisconsin livestock market. One hundred forty cattle from 14 states were infected with the outbreak strain. WGS indicated that human, cattle, and environmental isolates from the livestock market were genetically closely related. Most isolates (88%) had resistance or reduced susceptibility to antibiotics of ≥5 antibiotic classes. This resistance profile included first-line antibiotic treatments for patients with severe salmonellosis, including ampicillin, ceftriaxone, and ciprofloxacin. In this outbreak, MDR Salmonella Heidelberg likely spread from sick calves to humans, emphasizing the importance of illness surveillance in animal populations to prevent future spillover of this zoonotic disease.

      2. Clostridium perfringens is a common foodborne pathogen, frequently associated with improper cooking, and cooling or reheating of animal products. The U.S. Food and Drug Administration Food Code outlines proper food preparation practices to prevent foodborne outbreaks; however, retail food establishments continue to have C. perfringens outbreaks. We qualitatively analyzed responses to two open-ended questions from the National Environmental Assessment Reporting System (NEARS) to understand patterns of unique circumstances in the retail food establishment that precede a C. perfringens outbreak. We identified three environmental antecedents, with three subcategories, to create nine operational antecedents to help explain why a C. perfringens outbreak occurred. Those antecedents included factors related to (1) people (a lack of adherence to food safety procedures, a lack of food safety culture, and no active managerial control), (2) processes (increased demand, a process change during food preparation, and new operations), and (3) equipment (not enough equipment, malfunctioning cold-holding equipment, and holding equipment not used as intended). We recommend that food establishments support food safety training and certification programs and adhere to a food safety management plan to reduce errors made by people and processes. Retail food establishments should conduct routine maintenance on equipment and use only properly working equipment for temperature control. They also should train workers on the purpose, use, and functionality of the equipment.

    • Genetics and Genomics
      1. The Need for a Tiered Registry for US Gene Drive Governanceexternal icon
        Warmbrod KL, Kobokovich AL, West R, Gronvall GK, Montague M.
        Health Secur. 2022 Jan 10.

    • Health Behavior and Risk
      1. Youth experiencing homelessness experience violence victimization, substance use, suicide risk, and sexual risk disproportionately, compared with their stably housed peers. Yet few large-scale assessments of these differences among high school students exist. The youth risk behavior survey (YRBS) is conducted biennially among local, state, and nationally representative samples of U.S. high school students in grades 9-12. In 2019, 23 states and 11 local school districts included a measure for housing status on their YRBS questionnaire. The prevalence of homelessness was assessed among states and local sites, and relationships between housing status and violence victimization, substance use, suicide risk, and sexual risk behaviors were evaluated using logistic regression. Compared with stably housed students, students experiencing homelessness were twice as likely to report misuse of prescription pain medicine, three times as likely to be threatened or injured with a weapon at school, and three times as likely to report attempting suicide. These findings indicate a need for intervention efforts to increase support, resources, and services for homeless youth.

      2. Impact of close interpersonal contact on COVID-19 incidence: Evidence from 1 year of mobile device dataexternal icon
        Crawford FW, Jones SA, Cartter M, Dean SG, Warren JL, Li ZR, Barbieri J, Campbell J, Kenney P, Valleau T, Morozova O.
        Sci Adv. 2022 Jan 7;8(1):eabi5499.
        [Figure: see text].

    • Health Disparities
      1. Rural-urban differences in maternal mortality ratios (MMR) in the United States have been difficult to measure in recent years due to the incremental adoption of a pregnancy status checkbox on death certificates. Using 1999-2017 mortality and birth data, we examined the impact of the pregnancy checkbox on MMRs by rural-urban residence (large urban, medium/small urban, rural), using log-binomial regression models to predict trends as if all states had adopted the checkbox as of 1999. Implementation of the checkbox resulted in an average estimated increase of 7.5 maternal deaths per 100,000 live births (95% CI: 6.3, 8.8) in large urban areas (76% increase), 11.6 (95% CI: 9.6, 13.6) in medium/small urban areas (113% increase), and 16.6 (95% CI: 12.9, 20.3) in rural areas (107% increase), compared with MMRs prior to the checkbox. Assuming all states had the checkbox as of 1999, demographic-adjusted predicted MMRs increased in rural, declined in large urban, and did not change in medium/small urban areas. However, trends and urban-rural differences were substantially attenuated when analyses were limited to direct/specific causes of maternal death, which are likely subject to less misclassification. Accurate ascertainment of maternal deaths, particularly in rural areas, is important for reducing disparities in maternal mortality.

      2. PURPOSE: This study estimates the rural-urban differences in outpatient service utilization and expenditures for depression, anxiety disorder, and substance use disorder, and the evolving mental health provider mix for privately insured US adults aged 18-64 during 2005-2018. METHODS: We used the IBM MarketScan Commercial Claims and Encounters Database for individuals covered by employer-sponsored health insurance, from 2005 to 2018, with a yearly total number of beneficiaries ranging from 17.5 to 53.1 million. Claims for nonelderly adults with mental health and substance abuse coverage are included. Outcomes include rates of outpatient service utilization for depression, anxiety disorder, and substance use disorder; counts of outpatient visits; expenditure and share of the out-of-pocket cost; and the mental health services provider mix. FINDINGS: Rural enrollees were less likely than urban enrollees to use outpatient mental health services for depression by 1.2% (percentage points) in 2005 and 0.6% in 2018. Among those who used outpatient mental health services, rural enrollees had fewer outpatient visits than their urban counterparts (difference: 1.8-2.4 visits for depression, 1.2-1.7 visits for anxiety disorder, and 0.7-2.1 visits for substance use disorder). Rural patients paid less per year for mental health outpatient visits of the 3 conditions but incurred a higher share of out-of-pocket expenses. Rural and urban patients differ in the mix of mental health providers, with rural enrollees relying more on primary care providers than urban enrollees. CONCLUSIONS: Rural-urban disparities in access to mental health services persist during 2005-2018 among a population with private insurance.

    • Health Economics
      1. Prenatal Syphilis Screening Among Medicaid Enrollees in 6 Southern Statesexternal icon
        Lanier P, Kennedy S, Snyder A, Smith J, Napierala E, Talbert J, Hammerslag L, Humble L, Myers E, Austin A, Blount T, Dowler S, Mobley V, Fede AL, Nguyen H, Bruce J, Grijalva CG, Krishnan S, Otter C, Horton K, Seiler N, Majors J, Pearson WS.
        Am J Prev Med. 2022 Jan 5.
        INTRODUCTION: The rates of syphilis among pregnant women and infants have increased in recent years, particularly in the U.S. South. Although state policies require prenatal syphilis testing, recent screening rates comparable across Southern states are not known. The purpose of this study is to measure syphilis screening among Medicaid enrollees with delivery in states in the U.S. South. METHODS: A total of 6 state-university research partnerships in the U.S. South developed a distributed research network to analyze Medicaid claims data using a common analytic approach for enrollees with delivery in fiscal years 2017-2018 and 2018-2019 (combined N=504,943). In 2020-2021, each state calculated the percentage of enrollees with delivery with a syphilis screen test during the first trimester, third trimester, and at any point during pregnancy. Percentages for those with first-trimester enrollment were compared with the percentages of those who enrolled in Medicaid later in pregnancy. RESULTS: Prenatal syphilis screening during pregnancy ranged from 56% to 91%. Screening was higher among those enrolled in Medicaid during the first trimester than in those enrolled later in pregnancy. CONCLUSIONS: Despite state laws requiring syphilis screening during pregnancy, screening was much lower than 100%, and states varied in syphilis screening rates among Medicaid enrollees. Findings indicate that access to Medicaid in the first trimester is associated with higher rates of syphilis screening and that efforts to improve access to screening in practice settings are needed.

      2. Costs associated with incorporation of network approaches into STD program activitiesexternal icon
        Williams AM, Eppink ST, Guy JN, Seña AC, Berruti AA.
        Sex Transm Dis. 2022 Jan 7;Online Ahead of Print.
        Network approaches can be used to study sociosexual partnerships and identify individuals at high risk of infection. Little is known about the cost structure of these services and their association with STD diagnoses. METHOD: We collected costs associated with using a peer network strategy to recruit MSM and transwomen of color in 4 counties in North Carolina: Guilford, Forsyth, Durham, and Wake from February through October 2019. We used a comprehensive costing approach to gather detailed retrospective information on the intervention cost, broken down by category and programmatic activity. RESULTS: The sociosexual networks collected consisted of 31 initial seeds (index cases) and 49 peers of those seeds. In peers, 5 cases of HIV and 10 cases of syphilis were identified. The cost per case (HIV or syphilis) identified was $7,325. Personnel costs accounted for 80% of total expenditures, followed by laboratory expenses (12%). Personnel cost was distributed between DIS patient navigators (51%), non-clinical (37%), and management (12%) staff. General administration was the costliest programmatic activity (37%), followed by case management and field services (37%), and study activities (11%). The estimated average cost per patient tested was $2,242. CONCLUSIONS: Finding positive peer cases in non-clinical settings is costly but may be crucial for limiting the spread of sexually transmitted diseases. The cost of staff was the major driver. This study demonstrates that using a network strategy can be a cost-effective way to identify, test, and refer patients at high-risk of syphilis and HIV infections to care.

    • Healthcare Associated Infections
      1. Antifungal Resistance Trends of Candida auris Clinical Isolates, New York-New Jersey, 2016-2020external icon
        Kilburn S, Innes G, Quinn M, Southwick K, Ostrowsky B, Greenko JA, Lutterloh E, Greeley R, Magleby R, Chaturvedi V, Chaturvedi S.
        Antimicrob Agents Chemother. 2022 Jan 10:aac0224221.
        About 55% of U.S. Candida auris clinical cases were reported from New York and New Jersey from 2016 through 2020. Nearly all New York-New Jersey clinical isolates (99.8%) were fluconazole resistant, and 50% were amphotericin B resistant. Echinocandin resistance increased from 0% to 4% and pan-resistance increased from 0 to <1% for New York C. auris clinical isolates but not for New Jersey, highlighting the regional differences.

      2. Prevalence of carbapenemase-producing organisms among hospitalized solid organ transplant recipients, five U.S. hospitals, 2019-2020external icon
        Chan JL, Nazarian E, Musser KA, Snavely EA, Fung M, Doernberg SB, Pouch SM, Leekha S, Anesi JA, Kodiyanplakkal RP, Turbett SE, Walters MS, Epstein L.
        Transpl Infect Dis. 2022 Jan 5.
        BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five U.S. hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert® Carba-R assay to identify carbapenemase genes (bla(KPC) , bla(NDM) , bla(VIM) , bla(IMP) , bla(OXA-48) ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of bla(IMP) and bla(OXA) variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: 4 bla(KPC) , 1 bla(NDM) , 2 blaOXA(-23) . CPOs were detected in 2 (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs. This article is protected by copyright. All rights reserved.

    • Immune System Disorders
      1. Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunityexternal icon
        Perelygina L, Faisthalab R, Abernathy E, Chen MH, Hao L, Bercovitch L, Bayer DK, Noroski LM, Lam MT, Cicalese MP, Al-Herz W, Nanda A, Hajjar J, Vanden Driessche K, Schroven S, Leysen J, Rosenbach M, Peters P, Raedler J, Albert MH, Abraham RS, Rangarjan HG, Buchbinder D, Kobrynski L, Pham-Huy A, Dhossche J, Cunningham Rundles C, Meyer AK, Theos A, Atkinson TP, Musiek A, Adeli M, Derichs U, Walz C, Krüger R, von Bernuth H, Klein C, Icenogle J, Hauck F, Sullivan KE.
        Front Immunol. 2021 ;12:796065.
        Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

    • Immunity and Immunization
      1. Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021external icon
        Lipkind HS, Vazquez-Benitez G, DeSilva M, Vesco KK, Ackerman-Banks C, Zhu J, Boyce TG, Daley MF, Fuller CC, Getahun D, Irving SA, Jackson LA, Williams JT, Zerbo O, McNeil MM, Olson CK, Weintraub E, Kharbanda EO.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):26-30.
        COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

      2. Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series - 465 Health Care Facilities, United States, December 2020-October 2021external icon
        Yek C, Warner S, Wiltz JL, Sun J, Adjei S, Mancera A, Silk BJ, Gundlapalli AV, Harris AM, Boehmer TK, Kadri SS.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):19-25.
        Vaccination against SARS-CoV-2, the virus that causes COVID-19, is highly effective at preventing COVID-19-associated hospitalization and death; however, some vaccinated persons might develop COVID-19 with severe outcomes(†) (1,2). Using data from 465 facilities in a large U.S. health care database, this study assessed the frequency of and risk factors for developing a severe COVID-19 outcome after completing a primary COVID-19 vaccination series (primary vaccination), defined as receipt of 2 doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or a single dose of JNJ-78436735 [Janssen (Johnson & Johnson)] ≥14 days before illness onset. Severe COVID-19 outcomes were defined as hospitalization with a diagnosis of acute respiratory failure, need for noninvasive ventilation (NIV), admission to an intensive care unit (ICU) including all persons requiring invasive mechanical ventilation, or death (including discharge to hospice). Among 1,228,664 persons who completed primary vaccination during December 2020-October 2021, a total of 2,246 (18.0 per 10,000 vaccinated persons) developed COVID-19 and 189 (1.5 per 10,000) had a severe outcome, including 36 who died (0.3 deaths per 10,000). Risk for severe outcomes was higher among persons who were aged ≥65 years, were immunosuppressed, or had at least one of six other underlying conditions. All persons with severe outcomes had at least one of these risk factors, and 77.8% of those who died had four or more risk factors. Severe COVID-19 outcomes after primary vaccination are rare; however, vaccinated persons who are aged ≥65 years, are immunosuppressed, or have other underlying conditions might be at increased risk. These persons should receive targeted interventions including chronic disease management, precautions to reduce exposure, additional primary and booster vaccine doses, and effective pharmaceutical therapy as indicated to reduce risk for severe COVID-19 outcomes. Increasing COVID-19 vaccination coverage is a public health priority.

      3. Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescentsexternal icon
        Olson SM, Newhams MM, Halasa NB, Price AM, Boom JA, Sahni LC, Pannaraj PS, Irby K, Walker TC, Schwartz SP, Maddux AB, Mack EH, Bradford TT, Schuster JE, Nofziger RA, Cameron MA, Chiotos K, Cullimore ML, Gertz SJ, Levy ER, Kong M, Cvijanovich NZ, Staat MA, Kamidani S, Chatani BM, Bhumbra SS, Bline KE, Gaspers MG, Hobbs CV, Heidemann SM, Maamari M, Flori HR, Hume JR, Zinter MS, Michelson KN, Zambrano LD, Campbell AP, Patel MM, Randolph AG.
        N Engl J Med. 2022 Jan 12.
        BACKGROUND: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age. METHODS: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative). RESULTS: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated. CONCLUSIONS: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).

      4. International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal diseaseexternal icon
        Gladstone RA, Siira L, Brynildsrud OB, Vestrheim DF, Turner P, Clarke SC, Srifuengfung S, Ford R, Lehmann D, Egorova E, Voropaeva E, Haraldsson G, Kristinsson KG, McGee L, Breiman RF, Bentley SD, Sheppard CL, Fry NK, Corander J, Toropainen M, Steens A.
        Vaccine. 2022 Jan 4.
        BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

      5. Retrospective Analysis of Six Years of Acute Flaccid Paralysis Surveillance and Polio Vaccine Coverage Reported by Italy, Serbia, Bosnia and Herzegovina, Montenegro, Bulgaria, Kosovo, Albania, North Macedonia, Malta, and Greeceexternal icon
        Fontana S, Buttinelli G, Fiore S, Amato C, Pataracchia M, Kota M, Aćimović J, Blažević M, Mulaomerović M, Nikolaeva-Glomb L, Mentis A, Voulgari-Kokota A, Gashi L, Kaçaniku-Gunga P, Barbara C, Melillo J, Protic J, Filipović-Vignjevic S, O’connor PM, D’alberto A, Orioli R, Siddu A, Saxentoff E, Stefanelli P.
        Vaccines. 2022 ;10(1).
        Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015–2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries’ vaccine coverage from 2015 to 2019. EV isolation, identification, and typing were performed by each country according to WHO protocols. Overall, a general AFP underreporting was observed. Non-Polio Enterovirus (NPEV) typing showed a high heterogeneity: over the years, several genotypes of coxsackievirus and echovirus have been identified. The polio vaccine coverage, for the data available, differs among countries. This evaluation allows for the collection, for the first time, of data from the countries of the Balkan area regarding AFP surveillance and polio vaccine coverage. The need, for some countries, to enhance the surveillance systems and to promote the polio vaccine uptake, in order to maintain the polio-free status, is evident. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Injury and Violence
      1. Strengthening Communities: A Qualitative Assessment of Opportunities for the Prevention of Adverse Childhood Experiences in the Wake of the Opioid Crisisexternal icon
        Matjasko JL, Chovnick G, Bradford J, Treves-Kagan S, Usher K, Vaughn E, Ingoldsby E.
        J Child Fam Stud. 2022 Jan 3:1-13.
        The opioid crisis is a significant challenge for health and human service systems that serve children, youth, and families across the United States. Between 2000 and 2017, the number of foster care entries, a type of adverse childhood experience (ACE), attributable to parental drug use increased by 147%. Nevertheless, there is variation in the burden of opioid overdose and foster care rates across the U.S., suggesting community supports and systems to support families affected by substance use also vary. This qualitative study sampled communities experiencing high and low rates of overdose mortality and foster care entries (i.e., a qualitative comparison group) to better understand what might protect some counties from high overdose mortality and foster care entries. The sample included six counties from three states that were selected based on their rates of opioid overdose mortality and foster care entries. Using purposive sampling within counties, interview and discussion group participants included multi-sector community partners, parents whose children had been removed due to parental substance use, and caregivers caring for children who had been removed from their homes. Across all counties, prevention was not front-of-mind. Yet, participants from communities experiencing high rates of overdose mortality and foster care entries identified several factors that might help lessen exposure to substance use and ACEs including more community-based prevention services for children and youth. Both parents and caregivers across all communities also described the need for additional supports and services. Participants also described the impact of COVID-19 on services, including greater utilization of mental health and substance use treatment services and the challenges with engaging children and youth on virtual platforms. The implications for prevention are discussed, including the need to encourage primary prevention programs in communities.

      2. Firearm Homicides and Suicides in Major Metropolitan Areas - United States, 2015-2016 and 2018-2019external icon
        Kegler SR, Stone DM, Mercy JA, Dahlberg LL.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):14-18.
        Firearm homicides and suicides represent an ongoing public health concern in the United States. During 2018-2019, a total of 28,372 firearm homicides (including 3,612 [13%] among youths and young adults aged 10-19 years [youths]) and 48,372 firearm suicides (including 2,463 [5%] among youths) occurred among U.S. residents (1). This report is the fourth in a series* that provides statistics on firearm homicides and suicides in major metropolitan areas. As with earlier reports, this report provides a special focus on youth violence, including suicide, recognizing the magnitude of the problem and the importance of early prevention efforts. Firearm homicide and suicide rates were calculated for the 50 most populous U.S. metropolitan statistical areas (MSAs)(†) for the periods 2015-2016 and 2018-2019, separated by a transition year (2017), using mortality data from the National Vital Statistics System (NVSS) and population data from the U.S. Census Bureau. Following a period of decreased firearm homicide rates among persons of all ages after 2006-2007 in large metropolitan areas collectively and nationally, by 2015-2016 rates had returned to levels comparable to those observed a decade earlier and remained nearly unchanged as of 2018-2019. Firearm suicide rates among persons aged ≥10 years have continued to increase in large MSAs collectively as well as nationally. Although the youth firearm suicide rate remained much lower than the overall rate, the youth rate nationally also continued to increase, most notably outside of large MSAs. The findings in this report underscore a continued and urgent need for a comprehensive approach to prevention. This includes efforts to prevent firearm homicide and suicide in the first place and support individual persons and communities at increased risk, as well as lessening harms after firearm homicide and suicide have occurred.

      3. Suicidal Thoughts and Behaviors Among Adults Aged ≥18 Years - United States, 2015-2019external icon
        Ivey-Stephenson AZ, Crosby AE, Hoenig JM, Gyawali S, Park-Lee E, Hedden SL.
        MMWR Surveill Summ. 2022 Jan 7;71(1):1-19.
        PROBLEM/CONDITION: Suicidal thoughts and behaviors are important public health concerns in the United States. In 2019, suicide was the 10th leading cause of death among persons aged ≥18 years (adults); in that year, 45,861 adults died as a result of suicide, and an estimated 381,295 adults visited hospital emergency departments for nonfatal, self-inflicted injuries. Regional- and state-level data on self-inflicted injuries are needed to help localities establish priorities and evaluate the effectiveness of suicide prevention strategies. PERIOD COVERED: 2015-2019. DESCRIPTION OF SYSTEM: The National Survey on Drug Use and Health (NSDUH) is an annual survey of a representative sample of the civilian, noninstitutionalized U.S. population aged ≥12 years. NSDUH collects data on the use of illicit drugs, alcohol, and tobacco; initiation of substance use; substance use disorders and treatment; health care; and mental health. This report summarizes data on responses to questions concerning suicidal thoughts and behaviors contained in the mental health section among sampled persons aged ≥18 years in all 50 states and the District of Columbia. This report summarizes 2015-2019 NSDUH data collected from 254,767 respondents regarding national-, regional-, and state-level prevalence of suicidal thoughts, planning, and attempts by age group, sex, race and ethnicity, region, state, education, marital status, poverty level, and health insurance status. RESULTS: Prevalence estimates of suicidal thoughts and behaviors varied by sociodemographic factors, region, and state. During 2015-2019, an estimated 10.6 million (annual average) adults in the United States (4.3% of the adult population) reported having had suicidal thoughts during the preceding year. The prevalence of having had suicidal thoughts ranged from 4.0% in the Northeast and South to 4.8% in the West and from 3.3% in New Jersey to 6.9% in Utah. An estimated 3.1 million adults (1.3% of the adult population) had made a suicide plan in the past year. The prevalence of having made suicide plans ranged from 1.0% in the Northeast to 1.4% in the Midwest and West and from 0.8% in Connecticut and New Jersey to 2.4% in Alaska. An estimated 1.4 million adults (0.6% of the adult population) had made a suicide attempt in the past year. The prevalence of suicide attempts ranged from 0.5% in the Northeast to 0.6% in the Midwest, South, and West and from 0.3% in Connecticut to 0.9% in West Virginia. Past-year prevalence of suicidal thoughts, suicide planning, and suicide attempts was higher among females than among males, higher among adults aged 18-39 years than among those aged ≥40 years, higher among noncollege graduates than college graduates, and higher among adults who had never been married than among those who were married, separated, divorced, or widowed. Prevalence was also higher among those living in poverty than among those with a family income at or above the federal poverty threshold and higher among those covered by Medicaid or the Children's Health Insurance Program than among those with other types of health insurance or no health insurance coverage. INTERPRETATION: The findings in this report highlight differences in the adult prevalence of suicidal thoughts, plans to attempt suicide, and attempted suicide during the 12 months preceding the survey at the national, regional, and state levels during 2015-2019. Geographic differences in suicidal thoughts and behavior varied by sociodemographic characteristics and might be attributable to sociodemographic composition of the population, selective migration, or the local cultural milieu. These findings underscore the importance of ongoing surveillance to collect locally relevant data on which to base prevention and intervention strategies. PUBLIC HEALTH ACTION: Understanding the patterns of and risk factors for suicide is essential for designing, implementing, and evaluating public health programs for suicide prevention and policies that reduce morbidity and mortality related to suicidal thoughts and behaviors. State health departments and federal agencies can use the results from this report to assess progress toward achieving national and state health objectives in suicide prevention. Strategies might include identifying and supporting persons at risk, promoting connectedness, and creating protective environments.

    • Laboratory Sciences
      1. A Trans-Governmental Collaboration to Independently Evaluate SARS-CoV-2 Serology Assaysexternal icon
        Pinto LA, Shawar RM, O'Leary B, Kemp TJ, Cherry J, Thornburg N, Miller CN, Gallagher PS, Stenzel T, Schuck B, Owen SM, Kondratovich M, Satheshkumar PS, Schuh A, Lester S, Cassetti MC, Sharpless NE, Gitterman S, Lowy DR.
        Microbiol Spectr. 2022 Jan 12:e0156421.
        The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (, and Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (, and

    • Maternal and Child Health
      1. OBJECTIVE: The objective of this article was to assess the impact on behavioral and socioemotional development, 4 to 6 years postintervention (depending on the curriculum), of Legacy for Children™, a public health approach to improve child developmental outcomes among families living in poverty. METHODS: Mothers who were recruited prenatally or at the time of childbirth participated in a set of Legacy parallel design randomized control trials between 2001 and 2009 in Miami, Florida, or Los Angeles, California. Of the initial 574 mother-child dyads, 364 completed at least 1 behavioral or socioemotional outcome measure at the third-grade follow-up. Intention-to-treat analyses compared Legacy and comparison groups on behavioral and socioemotional outcomes. RESULTS: Children of Legacy mothers in Los Angeles were at lower risk for externalizing behaviors and poor adaptive skills than children whose mothers did not participate in the intervention. No significant outcome differences by group assignment were found in Miami. CONCLUSION: Group-based positive parenting interventions such as Legacy may have a sustained impact on children's behavioral and socioemotional development several years after intervention completion.

      2. OBJECTIVE: To develop, implement, and assess implementation outcomes for a developmental monitoring and referral program for children in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Based on Centers for Disease Control and Prevention's Learn the Signs. Act Early. campaign, the program was developed and replicated in two phases at 20 demographically diverse WIC clinics in eastern Missouri. Parents were asked to complete developmental milestone checklists for their children, ages 2 months to 4 years, during WIC eligibility recertification visits; WIC staff referred children with potential concerns to their healthcare providers for developmental screening. WIC staff surveys and focus groups were used to assess initial implementation outcomes. RESULTS: In both phases, all surveyed staff (n = 46) agreed the program was easy to use. Most (≥ 80%) agreed that checklists fit easily into clinic workflow and required ≤ 5 min to complete. Staff (≥ 55%) indicated using checklists with ≥ 75% of their clients. 92% or more reported referring one or more children with potential developmental concerns. According to 80% of staff, parents indicated checklists helped them learn about development and planned to share them with healthcare providers. During the second phase, 18 of 20 staff surveyed indicated the program helped them learn when to refer children and how to support parents, and 19 felt the program promoted healthy development. Focus groups supported survey findings, and all clinics planned to sustain the program. CONCLUSIONS: Initial implementation outcomes supported this approach to developmental monitoring and referral in WIC. The program has potential to help low-income parents identify possible concerns and access support.

      3. OBJECTIVE: To assess variations in low-risk cesarean delivery rates in the United States using the Society for Maternal-Fetal Medicine (SMFM) definition of low-risk for cesarean delivery and to identify factors associated with low-risk cesarean deliveries. METHODS: From hospital discharge data in the 2018 National Inpatient Sample and State Inpatient Databases, we identified deliveries that were low-risk for cesarean delivery using the SMFM definition based on the International Classification of Diseases, Tenth Revision, Clinical Modification codes. We estimated national low-risk cesarean delivery rates overall and by patient characteristics, clinically relevant conditions not included in the SMFM definition, and hospital characteristics based on the nationally representative sample of hospital discharges in the National Inpatient Sample. Multivariate logistic regressions were estimated for the national sample to identify factors associated with low-risk cesarean delivery. We reported low-risk cesarean delivery rates for 27 states and the District of Columbia based on the annual state data that represented the universe of hospital discharges from participating states in the State Inpatient Databases. RESULTS: Of an estimated 3,634,724 deliveries in the 2018 National Inpatient Sample, 2,484,874 low-risk deliveries met inclusion criteria. The national low-risk cesarean delivery rate in 2018 was 14.6% (95% CI 14.4-14.8%). The rates varied widely by state (range 8.9-18.6%). Nationally, maternal age older than 40 years, non-Hispanic Black or Asian race, private insurance as primary payer, admission on weekday, obesity, diabetes, or hypertension, large metropolitan residence, and hospitals of the South census region were associated with low-risk cesarean delivery. CONCLUSION: Approximately one in seven low-risk deliveries was by cesarean in 2018 in the United States using the SMFM definition and the low-risk cesarean delivery rates varied widely by state.

    • Nutritional Sciences
      1. Adults Meeting Fruit and Vegetable Intake Recommendations - United States, 2019external icon
        Lee SH, Moore LV, Park S, Harris DM, Blanck HM.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):1-9.
        The 2020-2025 Dietary Guidelines for Americans* advise incorporating more fruits and vegetables into U.S. residents' diets as part of healthy dietary patterns. Adults should consume 1.5-2 cup-equivalents of fruits and 2-3 cup-equivalents of vegetables daily.(†) A healthy diet supports healthy immune function (1) and helps to prevent obesity, type 2 diabetes, cardiovascular diseases, and some cancers (2); having some of these conditions can predispose persons to more severe illness and death from COVID-19 (3). CDC used the most recent 2019 Behavioral Risk Factor Surveillance system (BRFSS) data to estimate the percentage of states' adult population who met intake recommendations overall and by sociodemographic characteristics for 49 states and the District of Columbia (DC). Overall, 12.3% of adults met fruit recommendations, ranging from 8.4% in West Virginia to 16.1% in Connecticut, and 10.0% met vegetable recommendations, ranging from 5.6% in Kentucky to 16.0% in Vermont. The prevalence of meeting fruit intake recommendations was highest among Hispanic adults (16.4%) and lowest among males (10.1%); meeting vegetable intake recommendations was highest among adults aged ≥51 years (12.5%) and lowest among those living below or close to the poverty level (income to poverty ratio [IPR] <1.25) (6.8%). Additional policies(§) and programs that will increase access to fruits and vegetables in places where U.S. residents live, learn, work, and play, might increase consumption and improve health.

    • Occupational Safety and Health
      1. Industrial hog operation (IHO) workers can be occupationally exposed to Staphylococcus aureus and may carry the bacteria in their nares. Workers may persistently carry S. aureus or transition between different states of nasal carriage over time: no nasal carriage, nasal carriage of a human-associated strain, and nasal carriage of a livestock-associated strain. We developed a mathematical model to predict the proportion of IHO workers in each nasal carriage state over time, accounting for IHO worker mask use. We also examined data sufficiency requirements to inform development of models that produce reliable predictions. We used nasal carriage data from a cohort of 101 IHO workers in North Carolina, sampled every two weeks for four months, to develop a three state Markov model that describes the transition dynamics of IHO worker nasal carriage status over the study period and at steady state. We also stratified models by mask use to examine its impact on worker transition dynamics. If conditions remain the same, our models predicted that 49.1% of workers will have no nasal carriage of S. aureus, 28.2% will carry livestock-associated S. aureus, and 22.7% will carry human-associated S. aureus at steady state. In stratified models, at steady state, workers who reported only occasional mask (<80% of the time) use had a higher predicted proportion of individuals with livestock-associated S. aureus nasal carriage (39.2%) compared to workers who consistently (≥80% of the time) wore a mask (15.5%). We evaluated the amount of longitudinal data that is sufficient to create a Markov model that accurately predicts future nasal carriage states by creating multiple models that withheld portions of the collected data and compared the model predictions to observed data. Our data sufficiency analysis indicated that models created with a small subset of the dataset (approximately 1/3 of observed data) perform similarly to models created using all observed data points. Markov models may have utility in predicting worker health status over time, even when limited longitudinal data are available.

      2. Perceptions of Work-Related Health and Cancer Risks Among Women Firefighters: A Qualitative Studyexternal icon
        Solle NS, Santiago KM, Louzado Feliciano P, Calkins MM, Fent K, Jahnke S, Parks N, Buren H, Grant C, Burgess JL, Caban-Martinez AJ.
        J Occup Environ Med. 2021 Dec 1;63(12):e846-e852.
        OBJECTIVES: We use a qualitative method to gain further insight into women firefighters' experiences, perceptions of cancer, health, and safety risks in the fire service. METHODS: We conducted six focus groups with U.S. women firefighters. Participants engaged in a 60 to 75-minute, semi-structured discussion and completed a sociodemographic questionnaire. A qualitative descriptive approach was used to inductively create themes. Data collection concluded when saturation was met. RESULTS: Forty-nine women firefighters participated. Qualitative results indicated the main health concerns include: occupational cancer risks including, risks related to hazardous exposures, sleep disruption and stress; and women's health concerns including, cancer, pregnancy and breastfeeding, and lack of resources. CONCLUSIONS: Women firefighters are concerned about their risk for cancer due to their occupation and identify a lack of resources specific to health and safety needs of women firefighters.

      3. Repeated noise exposure and occupational hearing loss are common health problems across industries and especially within the mining industry. Large mechanized processes, blasting, grinding, drilling, and work that is often in close quarters put many miners at an increased risk of noise overexposure. In stone, sand, and gravel mining, noise is generated from a variety of sources, depending on the type of ore being mined as well as the final consumer product provided by that mine. Depending on the source of noise generation, different strategies to reduce and avoid that noise should be implemented. The National Institute for Occupational Safety and Health (NIOSH) has evaluated the noise profile at three operational surface stone, sand, and gravel mines. A-weighted sound level meter data as well as phase array beamforming data were collected throughout the mines in areas with high noise exposure or high personnel foot or vehicle traffic. Sound level meter data collected on a grid pattern was used to develop sound profiles of the working areas. These sound contour maps as well as phase array beamforming plots were provided to the mines as well as guidance to modify work areas or personnel traffic to reduce noise exposure. © 2020, This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection.

      4. Focus on officer wellness: prevent struck-by incidents at crash scenesexternal icon
        Fowler ML, Knuth R.
        Police Chief Magazine. 2022 Jan:1-9.
        There are more than 800,000 state and local law enforcement officers (LEOs) in the United States. Officers that perform traffic-related duties are exposed to the risk of being struck by passing vehicles while working outside of their patrol cars. In the last decade, on average, one officer per week was killed on U.S. roads. Traffic-related incidents-vehicle crashes and being struck by moving vehicles while on foot-are a leading cause of death for officers. From 2011 to 2020, there were 1,762 officer line-of-duty deaths. Of that total, 367 officer line-of-duty deaths were due to vehicle crashes (21 percent of total), and 131 officer line-of-duty deaths were due to being struck by a vehicle (7 percent of total). The Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health (NIOSH) has been studying vehicle crashes and struck-by incidents among LEOs for nearly a decade. The NIOSH Fatality Assessment and Control Evaluation (FACE) Program investigates LEO line-of-duty deaths (LODDs) due to motor vehicle events. The investigators identify risk factors for vehicle crashes and struck-by LEO LODDs and develop prevention recommendations that can be applied in the field. NIOSH shares these recommendations with law enforcement agencies across the United States, with the goal of reducing LEO motor vehicle-related deaths. According to the National Highway Traffic Safety Administration's third quarter report for 2021, 44 officers were killed in traffic-related incidents during the first three quarters of 2021. Of these 44 traffic-related fatalities, 23 were struck-by fatalities, where officers on foot were struck and killed by vehicles. Many of these fatal struck-by crashes occurred while officers were investigating motor vehicle crashes or assisting motorists on the side of the road. Secondary crashes caused by distracted or impaired drivers continue to be the main circumstance for officers being struck and killed by vehicles. For the 70 struck-by events involving LEOs from 2015 to 2019, a third involved a &quot;Slow Down and Move Over&quot; violation, and almost half of the officers struck were engaged in some type of traffic enforcement.

    • Occupational Safety and Health - Mining
      1. Modern smart mining increasingly depends on the use of sophisticated electrical and electronic systems for improved safety and better productivity. With more electronic systems being introduced underground, the mining industry is facing electromagnetic compatibility (EMC) issues caused by electromagnetic energy emitted by one device adversely impacting the normal function of another. This paper provides an overview of EMC and electromagnetic interference (EMI) research for underground mining. The paper first starts with an overview of EMI in other industries applicable to mining, followed by a literature review on published EMI research pertaining to mining applications. Some representative EMI incidences and related EMI legislation in mining are reviewed. Finally, mitigation strategies that can be potentially used to cope with EMI issues are discussed and some practical considerations and best practices to overcome EMI in mining are provided. This paper is aimed at helping the mining industry to better understand the challenges posed by EMI and to promote EMC in underground coal mines. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

    • Public Health Leadership and Management
      1. Field epidemiology training programs contribute to COVID-19 preparedness and response globallyexternal icon
        Hu AE, Fontaine R, Turcios-Ruiz R, Abedi AA, Williams S, Hilmers A, Njoh E, Bell E, Reddy C, Ijaz K, Baggett HC.
        BMC Public Health. 2022 Jan 10;22(1):63.
        BACKGROUND: Field epidemiology training programs (FETPs) have trained field epidemiologists who strengthen global capacities for surveillance and response to public health threats. We describe how FETP residents and graduates have contributed to COVID-19 preparedness and response globally. METHODS: We conducted a cross-sectional survey of FETPs between March 13 and April 15, 2020 to understand how FETP residents or graduates were contributing to COVID-19 response activities. The survey tool was structured around the eight Pillars of the World Health Organization's (WHO) Strategic Preparedness and Response Plan for COVID-19. We used descriptive statistics to summarize quantitative results and content analysis for qualitative data. RESULTS: Among 88 invited programs, 65 (74%) responded and indicated that FETP residents and graduates have engaged in the COVID-19 response across all six WHO regions. Response efforts focused on country-level coordination (98%), surveillance, rapid response teams, case investigations (97%), activities at points of entry (92%), and risk communication and community engagement (82%). Descriptions of FETP contributions to COVID-19 preparedness and response are categorized into seven main themes: conducting epidemiological activities, managing logistics and coordination, leading risk communication efforts, providing guidance, supporting surveillance activities, training and developing the workforce, and holding leadership positions. CONCLUSIONS: Our findings demonstrate the value of FETPs in responding to public health threats like COVID-19. This program provides critical assistance to countries' COVID-19 response efforts but also enhances epidemiologic workforce capacity, public health emergency infrastructure and helps ensure global health security as prescribed in the WHO's International Health Regulations.

      2. BACKGROUND: Although supervision is a ubiquitous approach to support health programs and improve health care provider (HCP) performance in low- and middle-income countries (LMICs), quantitative evidence of its effects is unclear. The objectives of this study are to describe the effect of supervision strategies on HCP practices in LMICs and to identify attributes associated with greater effectiveness of routine supervision. METHODS: We performed a secondary analysis of data on HCP practice outcomes (e.g., percentage of patients correctly treated) from a systematic review on improving HCP performance. The review included controlled trials and interrupted time series studies. We described distributions of effect sizes (defined as percentage-point [%-point] changes) for each supervision strategy. To identify attributes associated with supervision effectiveness, we performed random-effects linear regression modeling and examined studies that directly compared different approaches of routine supervision. RESULTS: We analyzed data from 81 studies from 36 countries. For professional HCPs, such as nurses and physicians, primarily working at health facilities, routine supervision (median improvement when compared to controls: 10.7%-points; IQR: 9.9, 27.9) had similar effects on HCP practices as audit with feedback (median improvement: 10.1%-points; IQR: 6.2, 23.7). Two attributes were associated with greater mean effectiveness of routine supervision (p < 0.10): supervisors received supervision (by 8.8-11.5%-points), and supervisors participated in problem-solving with HCPs (by 14.2-20.8%-points). Training for supervisors and use of a checklist during supervision visits were not associated with effectiveness. The effects of supervision frequency (i.e., number of visits per year) and dose (i.e., the number of supervision visits during a study) were unclear. For lay HCPs, the effect of routine supervision was difficult to characterize because few studies existed, and effectiveness in those studies varied considerably. Evidence quality for all findings was low primarily because many studies had a high risk of bias. CONCLUSIONS: Although evidence is limited, to promote more effective supervision, our study supports supervising supervisors and having supervisors engage in problem-solving with HCPs. Supervision's integral role in health systems in LMICs justifies a more deliberate research agenda to identify how to deliver supervision to optimize its effect on HCP practices.

    • Substance Use and Abuse
      1. As part of the federal response to the opioid crisis, the Opioid Rapid Response Team project (2018-2019) was created to provide rapid short-term assistance to requesting US jurisdictions responding to an acute opioid-related event. The project used an approach that maximized overall value by leveraging existing federal resources and harnessing opportunities to meet project-specific objectives while also enhancing general response capacity at the federal, state, and local levels. This tandem capacity building for both opioid rapid response and general response focused on systems and operations, workforce readiness, technical assistance, and partnerships. In this article, we demonstrate the ancillary value that issue-specific response activities can contribute to broader public health response capacity.

      2. Alcohol Consumption and Binge Drinking During Pregnancy Among Adults Aged 18-49 Years - United States, 2018-2020external icon
        Gosdin LK, Deputy NP, Kim SY, Dang EP, Denny CH.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):10-13.
        There is no known safe amount of alcohol consumption during pregnancy; drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders and might increase the risk for miscarriage and stillbirth (1). The prevalence of drinking among pregnant women increased slightly during 2011-2018; however, more recent estimates are not yet reported (2). CDC estimated the prevalence of self-reported current drinking (at least one alcoholic drink in the past 30 days) and binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) among pregnant adults aged 18-49 years, overall and by selected characteristics, using 2018-2020 Behavioral Risk Factor Surveillance System (BRFSS) data. During 2018-2020, 13.5% of pregnant adults reported current drinking and 5.2% reported binge drinking: both measures were 2 percentage points higher than during 2015-2017. Pregnant adults with frequent mental distress were 2.3 and 3.4 times as likely to report current and binge drinking, respectively, compared with those without frequent mental distress. In addition, pregnant adults without a usual health care provider were 1.7 times as likely to report current drinking as were those with a current provider. Alcohol consumption during pregnancy continues to be a serious problem. Integration of mental health services into clinical care and improving access to care might help address alcohol consumption and mental distress during pregnancy to prevent associated adverse outcomes (3).

    • Veterinary Medicine
      1. Duration of antigen shedding and development of antibody titers in Malayan tigers (panthera tigris jacksoni) naturally infected with sars-cov-2external icon
        Cushing AC, Sawatzki K, Grome HN, Puryear WB, Kelly N, Runstadler J.
        J Zoo Wildl Med. 2021 Dec;52(4):1224-1228.
        Natural infection of three captive Malayan tigers (Panthera tigris jacksoni) with SARS-CoV-2 caused mild to moderate symptoms of lethargy, anorexia, and coughing. Each tiger was longitudinally sampled opportunistically via consciously obtained oral, nasal, and/or fecal samples during and after resolution of clinical signs, until 2 wk of negative results were obtained. Persistent shedding of SARS-CoV-2 genetic material was detected via reverse transcription-polymerase chain reaction in feces up to 29 d after initial onset of clinical signs, but not in nasal or oral samples. Tigers became resistant to behavioral training to obtain nasal samples but tolerated longitudinal oral sampling. Serum was obtained from two tigers, and antibody titers revealed a robust antibody response within 9 d of onset of clinical signs, which was sustained for at least 3 mon. The tigers were infected despite the use of masks and gloves by husbandry personnel. No known cause of the outbreak was identified, despite extensive investigational efforts by the regional health department. No forward cross-species transmission was observed in primates housed in nearby enclosures. The increasing regularity of reports of SARS-CoV-2 infection in nondomestic felids warrants further investigations into shedding and immunity.

      2. Fatal Toxoplasma gondii myocarditis in an urban pet dogexternal icon
        Dorsch MA, Cesar D, Bullock HA, Uzal FA, Ritter JM, Giannitti F.
        Vet Parasitol Reg Stud Reports. 2022 Jan;27:100659.
        A 70-day-old Boxer dog from a household in Montevideo, Uruguay, died after presenting neurologic, respiratory, and gastrointestinal signs for 6 days. Autopsy findings included lymphadenomegaly, ascites and hepatomegaly. Histopathology revealed severe widespread lymphohistiocytic and plasmacytic myocarditis with cardiomyocyte necrosis, mineralization and numerous intrasarcoplasmic protozoa immunoreactive with anti-Toxoplasma gondii antisera on immunohistochemistry. The protozoa were ultrastructurally confirmed as T. gondii by transmission electron microscopy. Other lesions included diffuse centrilobular hepatocellular necrosis, multifocal lymphohistiocytic portal hepatitis and interstitial nephritis. Other causes of myocarditis, including Neospora caninum, Trypanosoma cruzi, Sarcocystis neurona, canine distemper virus, and canine parvovirus were ruled out by immunohistochemistry. Toxoplasma gondii infections in dogs are usually subclinical; however, clinical disease with fatal outcome can occur. To our knowledge, this is the first report of fatal toxoplasmosis in a dog in Uruguay. This case raises awareness for dogs as sentinels and possible sources of human toxoplasmosis in urban settings in Uruguay.

    • Zoonotic and Vectorborne Diseases
      1. Notes from the Field: Three Human Rabies Deaths Attributed to Bat Exposures - United States, August 2021external icon
        Kunkel A, Minhaj FS, Whitehill F, Austin C, Hahn C, Kieffer AJ, Mendez L, Miller J, Tengelsen LA, Gigante CM, Orciari LA, Rao AK, Wallace RM.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71(1):31-32.

      2. The global epidemiology of chikungunya from 1999 to 2020: A systematic literature review to inform the development and introduction of vaccinesexternal icon
        Bettis AA, L'Azou Jackson M, Yoon IK, Breugelmans JG, Goios A, Gubler DJ, Powers AM.
        PLoS Negl Trop Dis. 2022 Jan 12;16(1):e0010069.
        Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus. Since its reemergence in 2004, the virus has spread throughout the tropical world and several subtropical areas affecting millions of people to become a global public health issue. Given the significant disease burden, there is a need for medical countermeasures and several vaccine candidates are in clinical development. To characterize the global epidemiology of chikungunya and inform vaccine development, we undertook a systematic literature review in MEDLINE and additional public domain sources published up to June 13, 2020 and assessed epidemiological trends from 1999 to 2020. Observational studies addressing CHIKV epidemiology were included and studies not reporting primary data were excluded. Only descriptive analyses were conducted. Of 3,883 relevant sources identified, 371 were eligible for inclusion. 46% of the included studies were published after 2016. Ninety-seven outbreak reports from 45 countries and 50 seroprevalence studies from 31 countries were retrieved, including from Africa, Asia, Oceania, the Americas, and Europe. Several countries reported multiple outbreaks, but these were sporadic and unpredictable. Substantial gaps in epidemiological knowledge were identified, specifically granular data on disease incidence and age-specific infection rates. The retrieved studies revealed a diversity of methodologies and study designs, reflecting a lack of standardized procedures used to characterize this disease. Nevertheless, available epidemiological data emphasized the challenges to conduct vaccine efficacy trials due to disease unpredictability. A better understanding of chikungunya disease dynamics with appropriate granularity and better insights into the duration of long-term population immunity is critical to assist in the planning and success of vaccine development efforts pre and post licensure.

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

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