Issue 41, November 9, 2021

CDC Science Clips: Volume 13, Issue 41, November 9, 2021

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

  1. 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
      • Trends in inpatient admissions and emergency department visits for heart failure in adults with versus without diabetes in the USA, 2006-2017external icon
        Harding JL, Benoit SR, Hora I, Sridharan L, Ali MK, Jagannathan R, Patzer RE, Narayan KM.
        BMJ Open Diabetes Res Care. 2021 Oct;9(1).
        INTRODUCTION: Heart failure (HF) is a major contributor to cardiovascular morbidity and mortality in people with diabetes. In this study, we estimated trends in the incidence of HF inpatient admissions and emergency department (ED) visits by diabetes status. RESEARCH DESIGN AND METHODS: Population-based age-standardized HF rates in adults with and without diabetes were estimated from the 2006-2017 National Inpatient Sample, Nationwide ED Sample and year-matched National Health Interview Survey, and stratified by age and sex. Trends were assessed using Joinpoint. RESULTS: HF inpatient admissions did not change in adults with diabetes between 2006 and 2013 (from 53.9 to 50.4 per 1000 persons; annual percent change (APC): -0.3 (95% CI -2.5 to 1.9) but increased from 50.4 to 62.3 between 2013 and 2017 (APC: 4.8 (95% CI 0.3 to 9.6)). In adults without diabetes, inpatient admissions initially declined (from 14.8 in 2006 to 12.9 in 2014; APC -2.3 (95% CI -3.2 to -1.2)) and then plateaued. Patterns were similar in men and women, but relative increases were greatest in young adults with diabetes. HF-related ED visits increased overall, in men and women, and in all age groups, but increases were greater in adults with (vs without) diabetes. CONCLUSIONS: Causes of increased HF rates in hospital settings are unknown, and more detailed data are needed to investigate the aetiology and determine prevention strategies, particularly among adults with diabetes and especially young adults with diabetes.

    • Communicable Diseases
      • Risk Factors for Severe COVID-19 in Childrenexternal icon
        Woodruff RC, Campbell AP, Taylor CA, Chai SJ, Kawasaki B, Meek J, Anderson EJ, Weigel A, Monroe ML, Reeg L, Bye E, Sosin DM, Muse A, Bennett NM, Billing LM, Sutton M, Talbot HK, McCaffrey K, Pham H, Patel K, Whitaker M, McMorrow M, Havers F.
        Pediatrics. 2021 Oct 22.

    • Disaster Preparedness and Emergency Services
      • OBJECTIVES: The adverse effects that racial and ethnic minority groups experience before, during, and after disaster events are of public health concern. The objective of this study was to examine disparities in the epidemiologic and geographic patterns of natural disaster and extreme weather mortality by race and ethnicity. METHODS: We used mortality data from the Centers for Disease Control and Prevention from January 1, 1999, through December 31, 2018. We defined natural disaster and extreme weather mortality based on International Classification of Diseases, 10th Revision codes X30-X39. We calculated age-adjusted mortality rates by race, ethnicity, and hazard type, and we calculated age-adjusted mortality rate ratios by race, ethnicity, and state. We used geographic mapping to examine age-adjusted mortality rate ratios by race, ethnicity, and state. RESULTS: Natural disasters and extreme weather caused 27 335 deaths in the United States during 1999-2018. Although non-Hispanic White people represented 68% of total natural disaster and extreme weather mortality, the mortality rate per 100 000 population among non-Hispanic Black people was 1.87 times higher (0.71) and among non-Hispanic American Indian/Alaska Native people was 7.34 times higher (2.79) than among non-Hispanic White people (0.38). For all racial and ethnic groups, exposure to extreme heat and cold were the 2 greatest causes of natural disaster and extreme weather mortality. Racial and ethnic disparities in natural disaster and extreme weather mortality were highest in the South, Southwest, Mountain West, and Upper Midwest. CONCLUSIONS: Racial and ethnic minority populations have a greater likelihood of mortality from natural disaster or extreme weather events than non-Hispanic White people. Our study strengthens the current knowledge base on these disparities and may inform and improve disaster preparedness and response efforts.

    • Environmental Health
      • Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefightersexternal icon
        Goodrich JM, Calkins MM, Caban-Martinez AJ, Stueckle T, Grant C, Calafat AM, Nematollahi A, Jung AM, Graber JM, Jenkins T, Slitt AL, Dewald A, Cook Botelho J, Beitel S, Littau S, Gulotta J, Wallentine D, Hughes J, Popp C, Burgess JL.
        Epigenomics. 2021 Oct;13(20):1619-1636.
        Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

    • Health Disparities
      • OBJECTIVES: HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. DESIGN: Systematic review and meta-analysis of peer-reviewed journal articles. METHODS: We searched multiple electronic databases and CDC's HIV Prevention Research Synthesis database for 2006-September 2018. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). RESULTS: Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Twenty-one studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care ≤3 months after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. CONCLUSIONS: HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.

    • Health Economics
      • BACKGROUND: The benefits of nonstandard work hours include increased production time and the number of jobs. While for some sectors, such as emergency services, around-the-clock work is a necessary and critical societal obligation, work outside of traditional daytime schedules has been associated with many occupational safety and health hazards and their associated costs. Thus, organizational- and policy-level decisions on nonstandard work hours can be difficult and are based on several factors including economic evaluation. However, there is a lack of systematic knowledge of economic benefits and costs associated with these schedules. METHODS: We conducted a scoping review of the methodology and data used to examine the economic benefits and costs of nonstandard work hours and related interventions to mitigate risks. RESULTS: Ten studies met all our inclusion criteria. Most studies used aggregation and analysis of national and other large datasets. Costs estimated include health-related expenses, productivity losses, and projections of future loss of earnings. Cost analyses of interventions were provided for an obstructive sleep apnea screening program, implementation of an employer-based educational program, and increased staffing to cover overtime hours. CONCLUSIONS: A paucity of studies assess nonstandard work hours using economic terms. Future studies are needed to expand economic evaluations beyond the employer level to include those at the societal level because impacts of nonstandard work go beyond the workplace and are important for policy analysis and formulation. We pose the opportunity for researchers and employers to share data and resources in the development of more analyses that fill these research gaps.

      • Estimating the Cost-Effectiveness of the Sodium Reduction in Communities Programexternal icon
        Yarnoff B, Teachout E, MacLeod KE, Whitehill J, Jordan J, Tayebali Z, Bates L.
        Public Health Nutr. 2021 Oct 25:1-29.
        OBJECTIVE: This study assessed the cost-effectiveness of the Centers for Disease Control and Prevention's (CDC's) Sodium Reduction in Communities Program (SRCP). DESIGN: We collected implementation costs and performance measure indicators from SRCP recipients and their partner food service organizations. We estimated the cost per person and per food service organization reached and the cost per menu item impacted. We estimated the short-term effectiveness of SRCP in reducing sodium consumption and used it as an input in the Prevention Impact Simulation Model to project the long-term impact on medical cost savings and quality adjusted life years gained due to a reduction in cardiovascular disease and estimate the cost-effectiveness of SRCP if sustained through 2025 and 2040. SETTING: CDC funded eight recipients as part of the 2016-2021 round of the Sodium Reduction in Communities Program (SRCP) to work with food service organizations in eight settings to increase the availability and purchase of lower-sodium food options. PARTICIPANTS: Eight SRCP recipients and 20 of their partners. RESULTS: At the recipient level, average cost per person reached was $10, and average cost per food service organization reached was $42,917. At the food service organization level, median monthly cost per food item impacted by recipe modification or product substitution was $684. Cost-effectiveness analyses showed that, if sustained, the program is cost saving (i.e. the reduction in medical costs is greater than the implementation costs) in the target population by $1.82 through 2025 and $2.09 through 2040. CONCLUSIONS: By providing evidence of the cost-effectiveness of a real-world sodium reduction initiative, this study can help inform decisions by public health organizations about related cardiovascular disease prevention interventions.

    • Immunity and Immunization
      • Progress and barriers towards maternal and neonatal tetanus elimination in the remaining 12 countries: a systematic reviewexternal icon
        Yusuf N, Raza AA, Chang-Blanc D, Ahmed B, Hailegebriel T, Luce RR, Tanifum P, Masresha B, Faton M, Omer MD, Farrukh S, Aung KD, Scobie HM, Tohme RA.
        Lancet Glob Health. 2021 Nov;9(11):e1610-e1617.
        This systematic review assessed the progress and barriers towards maternal and neonatal tetanus elimination in the 12 countries that are yet to achieve elimination, globally. Coverage of at least 80% (the coverage level required for elimination) was assessed among women of reproductive age for five factors: (1) at least two doses of tetanus toxoid-containing vaccine, (2) protection at birth, (3) skilled birth attendance, (4) antenatal care visits, and (5) health facility delivery. A scoping review of the literature and data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys provided insights into the barriers to attaining maternal and neonatal tetanus elimination. Findings showed that none of the 12 countries attained at least 80% coverage for women of reproductive age receiving at least two doses of tetanus toxoid-containing vaccine or protection at birth according to the data from Demographic and Health Surveys or Multiple Indicator Cluster Surveys. Barriers to maternal and neonatal tetanus elimination were mostly related to health systems and socioeconomic factors. Modification to existing maternal and neonatal tetanus elimination strategies, including innovations, will be required to accelerate maternal and neonatal tetanus elimination in these countries.

    • Laboratory Sciences
      • Short Communication: Evaluation of Antiretroviral Drug Concentrations in Minimally Invasive Specimens for Potential Development of Point-of-Care Drug Assaysexternal icon
        Haaland RE, Martin A, Mengesha M, Dinh C, Fountain J, Lupo LD, Hall L, Conway-Washington C, Kelley CF.
        AIDS Res Hum Retroviruses. 2021 Oct;37(10):744-747.
        Point-of-care (POC) tests for antiretroviral drugs (ARVs) could help improve individual adherence. This study sought to define the utility of urine, blood, and buccal swabs as minimally invasive specimens amenable to development of POC tests for ARVs. Urine, dried blood spots (DBS) and buccal swabs were collected from 35 HIV-negative men between 2 and 96 h after a single dose of tenofovir (TFV) alafenamide/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat and darunavir (DRV). ARV concentrations were measured by high-performance liquid chromatography-mass spectrometry. High concentrations of FTC, DRV, and TFV were detectable in urine at least 24 h after dosing. FTC, DRV, and EVG remained detectable in DBS at least 24 h postdose. FTC and DRV were detectable on buccal swabs up to 2 and 24 h postdose, respectively. TFV was not detectable in DBS or buccal swabs collected between 2 and 96 h after dosing. Variable distribution of ARVs in minimally invasive specimens highlights the challenge of developing POC assays for recent ARV exposure.

    • Nutritional Sciences
      • Dietary and complementary feeding practices of U.S. infants, 6-12 months: A narrative review of the Federal nutrition monitoring dataexternal icon
        Bailey RL, Stang JS, Davis TA, Naimi TS, Schneeman BO, Dewey KG, Donovan SM, Novotny R, Kleinman RE, Taveras EM, Bazzano L, Snetselaar LG, de Jesus J, Casavale KO, Stoody EE, Goldman JD, Moshfegh AJ, Rhodes DG, Herrick KA, Koegel K, Perrine CG, Pannucci T.
        J Acad Nutr Diet. 2021 Oct 21.
        Complementary foods and beverages (CFB) are key components of an infant's diet in the second 6 months of life. This manuscript summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFB sometime before 6 months. The primary mode of feeding (i.e., human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFB is associated with the timing of introduction and types of CFB reported. FMF infants (42%) are more likely to be introduced to CFB before 4 months compared to HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed including fruit, grains, dairy, proteins, and solid fats. Compared to HMF infants of the same age, FMF infants consume more total energy (845 vs. 631 kcal) and protein (22 vs. 12 g) from all sources, and more energy (345 vs. 204 kcal) and protein (11 vs. 6 g) from CFB alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs. 7%), zinc (54% vs. <3%), and protein (27% vs. <3%). FMF infants are more likely to have early introduction (<12 months) to fruit juice (45% vs. 20%) and cow's milk (36% vs. 24%). Dietitians and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could further refine findings from this analysis.

    • Occupational Safety and Health
      • Workplace Leave and Breastfeeding Duration Among Postpartum Women, 2016-2018external icon
        Kortsmit K, Li R, Cox S, Shapiro-Mendoza CK, Perrine CG, D'Angelo DV, Barfield WD, Shulman HB, Garfield CF, Warner L.
        Am J Public Health. 2021 Oct 22:e1-e10.
        Objectives. To examine associations of workplace leave length with breastfeeding initiation and continuation at 1, 2, and 3 months. Methods. We analyzed 2016 to 2018 data for 10 sites in the United States from the Pregnancy Risk Assessment Monitoring System, a site-specific, population-based surveillance system that samples women with a recent live birth 2 to 6 months after birth. Using multivariable logistic regression, we examined associations of leave length (< 3 vs ≥ 3 months) with breastfeeding outcomes. Results. Among 12 301 postpartum women who planned to or had returned to the job they had during pregnancy, 42.1% reported taking unpaid leave, 37.5% reported paid leave, 18.2% reported both unpaid and paid leave, and 2.2% reported no leave. Approximately two thirds (66.2%) of women reported taking less than 3 months of leave. Although 91.2% of women initiated breastfeeding, 81.2%, 72.1%, and 65.3% of women continued breastfeeding at 1, 2, and 3 months, respectively. Shorter leave length (< 3 months), whether paid or unpaid, was associated with lower prevalence of breastfeeding at 2 and 3 months compared with 3 or more months of leave. Conclusions. Women with less than 3 months of leave reported shorter breastfeeding duration than did women with 3 or more months of leave. (Am J Public Health. Published online ahead of print October 21, 2021:e1-e10.

    • Substance Use and Abuse
      • Effects of E-cigarette flavoring chemicals on human macrophages and bronchial epithelial cellsexternal icon
        Morris AM, Leonard SS, Fowles JR, Boots TE, Mnatsakanova A, Attfield KR.
        Int J Environ Res Public Health. 2021 ;18(21).
        E-cigarettes utilize a wide range of flavoring chemicals with respiratory health effects that are not well understood. In this study, we used pulmonary-associated cell lines to assess the in vitro cytotoxic effects of 30 flavoring chemicals. Human bronchial epithelial cells (BEAS-2B) and both naïve and activated macrophages (THP-1) were treated with 10, 100, and 1000 µM of flavoring chemicals and analyzed for changes in viability, cell membrane damage, reactive oxygen species (ROS) production, and inflammatory cytokine release. Viability was unaffected for all chemicals at the 10 and 100 µM concentrations. At 1000 µM, the greatest reductions in viability were seen with decanal, hexanal, nonanal, cinnamaldehyde, eugenol, vanillin, alpha-pinene, eugenol, and limo-nene. High amounts of ROS were elicited by vanillin, ethyl maltol, and the diketones (2,3-pentane-dione, 2,3-heptanedione, and 2,3-hexanedione) from both cell lines. Naïve THP-1 cells produced significantly elevated levels of IL-1β, IL-8, and TNF-α when exposed to ethyl maltol and hexanal. Activated THP-1 cells released increased IL-1β and TNF-α when exposed to ethyl maltol, but many flavoring chemicals had an apparent suppressive effect on inflammatory cytokines released by activated macrophages, some with varying degrees of accompanying cytotoxicity. The diketones, L-carvone, and linalool suppressed cytokine release in the absence of cytotoxicity. These findings pro-vide insight into lung cell cytotoxicity and inflammatory cytokine release in response to flavorings commonly used in e-cigarettes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Systematic Review of Self-Measured Blood Pressure Monitoring With Support: Intervention Effectiveness and Costexternal icon
        Shantharam SS, Mahalingam M, Rasool A, Reynolds JA, Bhuiya AR, Satchell TD, Chapel JM, Hawkins NA, Jones CD, Jacob V, Hopkins DP.
        Am J Prev Med. 2021 Oct 19.
        INTRODUCTION: Self-measured blood pressure monitoring with support is an evidence-based intervention that helps patients control their blood pressure. This systematic economic review describes how certain intervention aspects contribute to effectiveness, intervention cost, and intervention cost per unit of the effectiveness of self-measured blood pressure monitoring with support. METHODS: Papers published between data inception and March 2021 were identified from a database search and manual searches. Papers were included if they focused on self-measured blood pressure monitoring with support and reported blood pressure change and intervention cost. Papers focused on preeclampsia, kidney disease, or drug efficacy were excluded. Quality of estimates was assessed for effectiveness, cost, and cost per unit of effectiveness. Patient characteristics and intervention features were analyzed in 2021 to determine how they impacted effectiveness, intervention cost, and intervention cost per unit of effectiveness. RESULTS: A total of 22 studies were included in this review from papers identified in the search. Type of support was not associated with differences in cost and cost per unit of effectiveness. Lower cost and cost per unit of effectiveness were achieved with simple technologies such as interactive phone systems, smartphones, and websites and where providers interacted with patients only as needed. DISCUSSION: Some of the included studies provided only limited information on key outcomes of interest to this review. However, the strength of this review is the systematic collection and synthesis of evidence that revealed the associations between the characteristics of implemented interventions and their patients and the interventions' effectiveness and cost, a useful contribution to the fields of both research and implementation.

    • Communicable Diseases
      1. Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infectionexternal icon
        Wiemken TL, Furmanek SP, Carrico RM, Peyrani P, Hoft D, Fry AM, Ramirez JA.
        BMC Infect Dis. 2021 Oct 27;21(1):1106.
        BACKGROUND: Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. METHODS: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. RESULTS: A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%). CONCLUSIONS: This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); Identifier: NCT01248715

      2. Influenza clinical testing and oseltamivir treatment in hospitalized children with acute respiratory illness, 2015-2016external icon
        Hamdan L, Probst V, Haddadin Z, Rahman H, Spieker AJ, Vandekar S, Stewart LS, Williams JV, Boom JA, Munoz F, Englund JA, Selvarangan R, Staat MA, Weinberg GA, Azimi PH, Klein EJ, McNeal M, Sahni LC, Singer MN, Szilagyi PG, Harrison CJ, Patel M, Campbell AP, Halasa NB.
        Influenza Other Respir Viruses. 2021 Oct 26.
        BACKGROUND: Antiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children. METHODS: Hospitalized children <18 years of age with acute respiratory illness (ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed-effects models to identify factors associated with influenza testing and antiviral treatment. RESULTS: Of the 2299 hospitalized children with ARI enrolled during one influenza season, 51% (n = 1183) were tested clinically for influenza. Clinicians provided antiviral treatment for 61 of 117 (52%) patients with a positive influenza test versus 66 of 1066 (6%) with a negative or unknown test result. In multivariable analyses, factors associated with testing included neuromuscular disease (aOR = 5.35, 95% CI [3.58-8.01]), immunocompromised status (aOR = 2.88, 95% CI [1.66-5.01]), age (aOR = 0.93, 95% CI [0.91-0.96]), private only versus public only insurance (aOR = 0.78, 95% CI [0.63-0.98]), and chronic lung disease (aOR = 0.64, 95% CI [0.51-0.81]). Factors associated with antiviral treatment included neuromuscular disease (aOR = 1.86, 95% CI [1.04, 3.31]), immunocompromised state (aOR = 2.63, 95% CI [1.38, 4.99]), duration of illness (aOR = 0.92, 95% CI [0.84, 0.99]), and chronic lung disease (aOR = 0.60, 95% CI [0.38, 0.95]). CONCLUSION: Approximately half of children hospitalized with influenza during the 2015-2016 influenza season were treated with antivirals. Because antiviral treatment for influenza is associated with better health outcomes, further studies of subsequent seasons would help evaluate current use of antivirals among children and better understand barriers for treatment.

      3. Bedaquiline Drug Resistance Emergence Assessment in MDR-TB (DREAM): a 5-Year Prospective In-Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug-Susceptibility Testing in MDR-TB Isolatesexternal icon
        Kaniga K, Hasan R, Jou R, Vasiliauskienė E, Chuchottaworn C, Ismail N, Metchock B, Miliauskas S, Viet Nhung N, Rodrigues C, Shin S, Simsek H, Smithtikarn S, Ngoc AL, Boonyasopun J, Kazi M, Kim S, Kamolwat P, Musteikiene G, Sacopon CA, Tahseen S, Vasiliauskaitė L, Wu MH, Vally Omar S.
        J Clin Microbiol. 2021 Oct 27:Jcm0291920.
        Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant-tuberculosis (MDR-TB) (DREAM) was a 5-year (2015-2019) phenotypic drug-resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5036 MDR-TB isolates of bedaquiline-treatment-naïve patients to bedaquiline and other anti-tuberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) minimal inhibitory concentration (MIC) methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015-0.12 μg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cut-off values of 0.12 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or Intermediate category was set at 0.25 μg/ml and 0.5 μg/ml for BMD and AD, respectively. When applied to the 5036 MDR-TB isolates, bedaquiline-susceptible, intermediate and bedaquiline-resistant rates were 97.9%, 1.5% and 0.6%, respectively, for BMD, and 98.8%, 0.8% and 0.4% for AD. Resistance rates were: ofloxacin 35.1%, levofloxacin 34.2%, moxifloxacin 33.3%, 1.5% linezolid and 2% clofazimine. Phenotypic cross resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Co-resistance to bedaquiline and linezolid, and clofazimine and linezolid, were 0.1% and 0.3%, respectively, in MDR-TB, and 0.2% and 0.4% in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naïve population. No treatment-limiting patterns for cross-resistance and co-resistance have been identified with key TB drugs to date.

      4. A global call for talaromycosis to be recognised as a neglected tropical diseaseexternal icon
        Narayanasamy S, Dat VQ, Thanh NT, Ly VT, Chan JF, Yuen KY, Ning C, Liang H, Li L, Chowdhary A, Youngchim S, Supparatpinyo K, Aung NM, Hanson J, Andrianopoulos A, Dougherty J, Govender NP, Denning DW, Chiller T, Thwaites G, van Doorn HR, Perfect J, Le T.
        Lancet Glob Health. 2021 Nov;9(11):e1618-e1622.
        Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.

      5. Cryptococcus gattii Species Complex as an Opportunistic Pathogen: Underlying Medical Conditions Associated with the Infectionexternal icon
        Yang DH, England MR, Salvator H, Anjum S, Park YD, Marr KA, Chu LA, Govender NP, Lockhart SR, Desnos-Ollivier M, Chen S, Halliday C, Kan A, Chen J, Wollenberg KR, Zelazny A, Perfect JR, Chang YC, Bennett JE, Holland SM, Meyer W, Williamson PR, Kwon-Chung KJ.
        mBio. 2021 Oct 26;12(5):e0270821.
        The Cryptococcus gattii species complex has often been referred to as a primary pathogen due to its high infection frequency among apparently immunocompetent patients. In order to scrutinize the immune status of patients and the lineages of etiologic agents, we analyzed patient histories and the molecular types of etiologic agents from 135 global C. gattii cases. Eighty-six of 135 patients had been diagnosed as immunocompetent, although some of them had underlying medical issues, and 49 were diagnosed as immunocompromised with risk factors similar to those seen in Cryptococcus neoformans infection. We focused on the 86 apparently immunocompetent patients and were able to obtain plasma from 32 (37%) to analyze for the presence of autoantibodies against the granulocyte-macrophage colony-stimulating factor (GM-CSF) since these antibodies have been reported as a hidden risk factor for C. gattii infection. Among the 32 patients, 25 were free from any known other health issues, and 7 had various medical conditions at the time of diagnosis for cryptococcosis. Importantly, plasma from 19 (76%) of 25 patients with no recognized underlying medical condition showed the presence of GM-CSF autoantibodies, supporting this antibody as a major hidden risk factor for C. gattii infection. These data indicate that seemingly immunocompetent people with C. gattii infection warrant detailed evaluation for unrecognized immunologic risks. There was no relationship between molecular type and underlying conditions of patients. Frequency of each molecular type was related to its geographic origin exemplified by the overrepresentation of VGIV in HIV-positive (HIV+) patients due to its prevalence in Africa. IMPORTANCE The C. neoformans and C. gattii species complex causes cryptococcosis. The C. neoformans species complex is known as an opportunistic pathogen since it primarily infects immunocompromised patients. C. gattii species complex has been referred to as a primary pathogen due to its high infection frequency in apparently immunocompetent people. We analyzed 135 global cases of C. gattii infection with documented patient history. Eighty-six of 135 patients were originally diagnosed as immunocompetent and 49 as immunosuppressed with similar underlying conditions reported for C. neoformans infection. A significant number of C. gattii patients without known underlying conditions possessed autoantibodies against granulocytes-macrophage colony-stimulating factor (GM-CSF) in their plasma, supporting the presence of GM-CSF antibodies as a hidden risk factor for C. gattii infection. No relationship was found between C. gattii lineages and the underlying conditions except for overrepresentation of the molecular type VGIV among HIV+ patients due to the prevalence of VGIV in Africa.

      6. HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 23 Metropolitan Statistical Areas, United States, 2018external icon
        Handanagic S, Finlayson T, Burnett JC, Broz D, Wejnert C.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 22;70(42):1459-1465.
        In the United States, 10% of HIV infections diagnosed in 2018 were attributed to unsafe injection drug use or male-to-male sexual contact among persons who inject drugs (PWID) (1). In 2017, among PWID or men who have sex with men and who inject drugs (MSM-ID), 76% of those who received a diagnosis of HIV infection lived in urban areas* (2). To monitor the prevalence of HIV infection and associated behaviors among persons who reported injecting drugs in the past 12 months, including MSM-ID, CDC's National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing among populations of persons at high risk for HIV infection (MSM, PWID, and heterosexually active adults at increased risk for HIV infection) in selected metropolitan statistical areas (MSAs) (3). The estimated HIV infection prevalence among PWID in 23 MSAs surveyed in 2018 was 7%. Among HIV-negative PWID, an estimated 26% receptively shared syringes and 68% had condomless vaginal sex during the preceding 12 months. During the same period, 57% had been tested for HIV infection, and 55% received syringes from a syringe services program (SSP). While overall SSP use did not significantly change since 2015, a substantial decrease in SSP use occurred among Black PWID, and HIV prevalence among Black PWID was higher than that among Hispanic and White PWID. These findings underscore the importance of continuing and expanding HIV prevention programs and community-based strategies for PWID, such as those provided by SSPs, especially following service disruptions created by the COVID-19 pandemic (4). Efforts are needed to ensure that PWID have low-barrier access to comprehensive and integrated needs-based SSPs (where legally permissible) that include provision of sterile syringes and safe syringe disposal, HIV and hepatitis C virus (HCV) testing and referrals to HIV and HCV treatment, HIV preexposure prophylaxis, and treatment for substance use and mental health disorders.

      7. SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant resultsexternal icon
        Miller EM, Law EA, Ajeen R, Karasik J, Mendoza C, Abernathy H, Garrett H, King E, Wallace J, Zelek M, Edwards JK, Xiong K, Beatty C, Fleischauer AT, Ciccone EJ, Shook-Sa BE, Aiello AE, Boyce RM.
        PLoS One. 2021 ;16(10):e0259070.
        Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics.

      8. BACKGROUND: Human immunodeficiency virus (HIV) partner services (PS) are an essential component of comprehensive HIV prevention and care. We examined factors associated with partner notification, HIV testing, and HIV positivity among partners of HIV diagnosed persons (index persons) contacted by CDC-funded state and local health departments. METHODS: We analyzed PS data submitted to CDC by 61 state and local health departments from 2013-2017. Using multivariate Poisson regression-adjusted for clustering effects among partners reported by a common index person-we assessed association between three outcomes of interest (partner notification, HIV testing, and HIV positivity) and the demographic characteristics, risk behaviors, geographic region, and service year of index persons and their partners. RESULTS: A total of 51,368 sexual and/or needle-sharing partners were matched with 33,524 index persons. Of notifiable partners, 97.2% were notified of their potential HIV exposure, 52.3% were tested for HIV. Among 21,842 notified and tested partners, 23.8% were newly diagnosed with an HIV infection. Partner notification, HIV testing, and HIV positivity were associated with both partner and index person characteristics (individually and interactively), geographic region, and year of service. CONCLUSIONS: PS programs provided through CDC-funded health departments are effective in both partner notification and identification of undiagnosed HIV infection among partners. However, HIV testing rates among notified partners remains low. Implementing strategies to address gaps in HIV testing can contribute towards ending the HIV epidemic in the United States.

      9. Rotavirus infection among children under five years of age hospitalized with acute gastroenteritis in Myanmar during 2018-2020 - Multicentre surveillance before rotavirus vaccine introductionexternal icon
        Myat TW, Thu HM, Tate JE, Burnett E, Cates JE, Parashar UD, Kyaw YM, Khaing TE, Moh KM, Win NN, Khine WK, Kham MM, Kyaw T, Khine YY, Oo KK, Aung KM.
        Vaccine. 2021 Oct 23.
        BACKGROUND: Rotavirus gastroenteritis (RVGE) is a leading cause of severe diarrhea in children under-five worldwide, with the majority of mortality in lower -income countries. This study aimed to provide baseline information on epidemiology of rotavirus and circulating strains before rotavirus vaccine introduction in Myanmar. METHODS: Hospital-based, prospective surveillance was conducted from May 2018 to January 2020 at four sentinel sites; two hospitals in Lower Myanmar, one hospital each in Middle Myanmar and East Myanmar. Children under five years of age hospitalized for acute gastroenteritis were enrolled; demographic and clinical data were collected. Stool samples were screened by ELISA (ProSpecT™ Rotavirus, OXOID-UK) for rotavirus antigen and a subset of ELISA positive samples were genotyped by reverse transcription polymerase chain reaction. RESULTS: Rotavirus was detected in 45.7% (799/1750) of cases enrolled at three sites in May 2018-April 2019 and 42.5% (521/1227) at four sites in May 2019-January 2020. RVGE cases were predominantly male (58.7%; 775/1320) and 92.6% (1223/1320) of RVGE cases occurred in <2 years old. Rotavirus detection was higher in the cold and dry season (November-April). RVGE compared to non-RVGE cases had more frequent vomiting (78.3% Vs 68.1%, p < 0.01), fever (65.8% Vs 61.3%, p = 0.01), severe dehydration (3.6% Vs 2.1%, p < 0.01) and requirement of treatment by IV fluid (58.3% Vs 53.1%, p < 0.01). The most prevalent genotypes identified were G1P[6] (113/359, 31.5%), G1P[8] (94/359, 26.2%) and G2P[4] (33/359, 9.2%). CONCLUSIONS: This study confirms the persistent high prevalence of RVGE among children under-five admitted to hospitals in different parts of Myanmar and the diversity of rotavirus strains over time prior to vaccine introduction. The rotavirus vaccine was introduced nationwide in February 2020 in Myanmar and these data will be important baseline data for post-vaccination monitoring of vaccine impact and circulating strains.

    • Disaster Preparedness and Emergency Services
      1. Public health branch incident management and support as part of the Federal Government response during the emergency phase of Hurricanes Irma and Maria in Puerto Rico and the US Virgin Islandsexternal icon
        Cruz MA, Rivera-González LO, Irvin-Barnwell E, Cabrera-Marquez J, Ellis E, Ellis B, Qi B, Maniglier-Poulet C, Gerding JA, Shumate A, Andujar A, Yoder J, Laco J, Santana A, Bayleyegn T, Luna-Pinto C, Rodriguez LO, Roth J, Bermingham J, Funk RH, Raheem M.
        J Emerg Manag. 2021 ;19(8):63-77.
        On September 6 and 20, 2017, Hurricanes Irma and Maria made landfall as major hurricanes in the US Caribbean Territories of the Virgin Islands and Puerto Rico with devastating effects. As part of the initial response, a public health team (PHT) was initially deployed as part of the US Department of Health and Human Services Incident Response Coordination Team. As a result of increased demands for additional expertise and resources, a public health branch (PHB) was established for coordinating a broad spectrum of public health response activities in support of the affected territories. This paper describes the conceptual framework for organizing these activities; summarizes some key public health activities and roles; outlines partner support and coordination with key agencies; and defines best practices and areas for improvement in disaster future operations. © 2021 Weston Medical Publishing. All rights reserved.

      2. Notes from the Field: Deaths Related to Hurricane Ida Reported by Media - Nine States, August 29-September 9, 2021external icon
        Hanchey A, Schnall A, Bayleyegn T, Jiva S, Khan A, Siegel V, Funk R, Svendsen E.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1385-1386.

      3. Strengthening Pandemic Preparedness Through Noncommunicable Disease Strategiesexternal icon
        Kostova DA, Moolenaar RL, Van Vliet G, Lasu A, Mahar M, Richter P.
        Prev Chronic Dis. 2021 Oct 21;18:E93.

    • Disease Reservoirs and Vectors
      1. An Opportunistic Survey Reveals an Unexpected Coronavirus Diversity Hotspot in North Americaexternal icon
        Ip HS, Griffin KM, Messer JD, Winzeler ME, Shriner SA, Killian ML, K. Torchetti M, DeLiberto TJ, Amman BR, Cossaboom CM, Harvey RR, Wendling NM, Rettler H, Taylor D, Towner JS, Barton Behravesh C, Blehert DS.
        Viruses. 2021 Oct 7;13(10).
        In summer 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was detected on mink farms in Utah. An interagency One Health response was initiated to assess the extent of the outbreak and included sampling animals from on or near affected mink farms and testing them for SARS-CoV-2 and non-SARS coronaviruses. Among the 365 animals sampled, including domestic cats, mink, rodents, raccoons, and skunks, 261 (72%) of the animals harbored at least one coronavirus. Among the samples that could be further characterized, 127 alphacoronaviruses and 88 betacoronaviruses (including 74 detections of SARS-CoV-2 in mink) were identified. Moreover, at least 10% (n = 27) of the coronavirus-positive animals were found to be co-infected with more than one coronavirus. Our findings indicate an unexpectedly high prevalence of coronavirus among the domestic and wild free-roaming animals tested on mink farms. These results raise the possibility that mink farms could be potential hot spots for future trans-species viral spillover and the emergence of new pandemic coronaviruses.

    • Environmental Health
      1. Towards sustainable additive manufacturing: The need for awareness of particle and vapor releases during polymer recycling, making filament, and fused filament fabrication 3-D printingexternal icon
        Stefaniak AB, Bowers LN, Cottrell G, Erdem E, Knepp AK, Martin SB, Pretty J, Duling MG, Arnold ED, Wilson Z, Krider B, Fortner AR, LeBouf RF, Virji MA, Sirinterlikci A.
        Resour Conserv Recycl. 2022 ;176.
        Fused filament fabrication three-dimensional (FFF 3-D) printing is thought to be environmentally sustainable; however, significant amounts of waste can be generated from this technology. One way to improve its sustainability is via distributed recycling of plastics in homes, schools, and libraries to create feedstock filament for printing. Risks from exposures incurred during recycling and reuse of plastics has not been incorporated into life cycle assessments. This study characterized contaminant releases from virgin (unextruded) and recycled plastics from filament production through FFF 3-D printing. Waste polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS) plastics were recycled to create filament; virgin PLA, ABS, high and low density polyethylenes, high impact polystyrene, and polypropylene pellets were also extruded into filament. The release of particles and chemicals into school classrooms was evaluated using standard industrial hygiene methodologies. All tasks released particles that contained hazardous metals (e.g., manganese) and with size capable of depositing in the gas exchange region of the lung, i.e., granulation of waste PLA and ABS (667 to 714 nm) and filament making (608 to 711 nm) and FFF 3-D printing (616 to 731 nm) with waste and virgin plastics. All tasks released vapors, including respiratory irritants and potential carcinogens (benzene and formaldehyde), mucus membrane irritants (acetone, xylenes, ethylbenzene, and methyl methacrylate), and asthmagens (styrene, multiple carbonyl compounds). These data are useful for incorporating risks of exposure to hazardous contaminants in future life cycle evaluations to demonstrate the sustainability and circular economy potential of FFF 3-D printing in distributed spaces. © 2021

    • Genetics and Genomics
      1. Novel Candidate Genes Differentially Expressed in Glyphosate-Treated Horseweed (Conyza canadensis)external icon
        Yang Y, Gardner C, Gupta P, Peng Y, Piasecki C, Millwood RJ, Ahn TH, Stewart CN.
        Genes (Basel). 2021 Oct 14;12(10).
        The evolution of herbicide-resistant weed species is a serious threat for weed control. Therefore, we need an improved understanding of how gene regulation confers herbicide resistance in order to slow the evolution of resistance. The present study analyzed differentially expressed genes after glyphosate treatment on a glyphosate-resistant Tennessee ecotype (TNR) of horseweed (Conyza canadensis), compared to a susceptible biotype (TNS). A read size of 100.2 M was sequenced on the Illumina platform and subjected to de novo assembly, resulting in 77,072 gene-level contigs, of which 32,493 were uniquely annotated by a BlastX alignment of protein sequence similarity. The most differentially expressed genes were enriched in the gene ontology (GO) term of the transmembrane transport protein. In addition, fifteen upregulated genes were identified in TNR after glyphosate treatment but were not detected in TNS. Ten of these upregulated genes were transmembrane transporter or kinase receptor proteins. Therefore, a combination of changes in gene expression among transmembrane receptor and kinase receptor proteins may be important for endowing non-target-site glyphosate-resistant C. canadensis.

      2. ICTV Virus Taxonomy Profile: Herpesviridae 2021external icon
        Gatherer D, Depledge DP, Hartley CA, Szpara ML, Vaz PK, Benkő M, Brandt CR, Bryant NA, Dastjerdi A, Doszpoly A, Gompels UA, Inoue N, Jarosinski KW, Kaul R, Lacoste V, Norberg P, Origgi FC, Orton RJ, Pellett PE, Schmid DS, Spatz SJ, Stewart JP, Trimpert J, Waltzek TB, Davison AJ.
        J Gen Virol. 2021 Oct;102(10).
        Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at

      3. Next-Generation Sequencing of Human Respiratory Syncytial Virus Subgroups A and B Genomesexternal icon
        Wang L, Ng TF, Castro CJ, Marine RL, Magaña LC, Esona M, Peret TC, Thornburg NJ.
        J Virol Methods. 2021 Oct 18:114335.
        Human respiratory syncytial virus (HRSV) is a leading cause of acute respiratory illness in young children worldwide. Whole genome sequencing of HRSV offers enhanced resolution of strain variability for epidemiological surveillance and provides genomic information essential for antiviral and vaccine development. A 10-amplicon one-step RT-PCR assay and a 20-amplicon nested RT-PCR assay with enhanced sensitivity were developed to amplify whole HRSV genomes from samples containing high and low viral loads, respectively. Ninety-six HRSV-positive samples comprised of 58 clinical specimens and 38 virus isolates with C(t) values ≤ 24 were amplified successfully using the 10-amplicon one-step RT-PCR method and multiplexed in a single MiSeq run. Genome coverage exceeded 99.3% for all 96 samples. The 20-amplicon nested RT-PCR NGS method was used to generate >99.6% HRSV full-length genome for 72 clinical specimens with C(t) values ranging from 24 to 33. Phylogenetic analysis of the genome sequences obtained from the 130 clinical specimens revealed a wide diversity of HRSV genotypes demonstrating methodologic robustness.

    • Health Disparities
      1. BACKGROUND: American Indian and Alaska Native (AI/AN) populations have experienced regional variation and disparities in colorectal cancer incidence rates. METHODS: We examined colorectal cancer incidence (2013-2017) and colorectal cancer incidence trends (1999-2017) among AI/AN persons. Incidence data were linked to Indian Health Service enrollment records, and analyses were restricted to Purchased/Referred Care Delivery Areas. Incidence rates of colorectal cancer among AI/AN and White persons were analyzed in six geographic regions; Hispanic persons were excluded. Incidence trends were analyzed using linear modeling. RESULTS: During 2013-2017, colorectal cancer incidence was 41% higher among AI/AN than among White persons. AI/AN incidence rates per 100,000 varied regionally from 34.4 in the East to 96.1 in Alaska. Compared with White persons, AI/AN persons had higher colorectal cancer incidence rates among all age strata and were more likely to have late-stage diagnoses. Incidence rate trends indicated significant increases among both AI/AN and White persons ages <50 years and among AI/AN persons ages 50-64 years. The colorectal cancer incidence rate trend increased among AI/AN persons in the Southwest. CONCLUSIONS: The disparity of colorectal cancer incidence rates between AI/AN and White persons has widened since 2005-2009. AI/AN populations have higher colorectal cancer incidence compared with White populations, especially in the Alaska region. IMPACT: Our finding of increased colorectal cancer incidence disparities suggests that enhanced screening efforts and culturally appropriate clinical and public health interventions are needed among AI/AN persons overall, and especially in regions and age groups in which colorectal cancer rates are increasing.

      2. COVID-19 Vaccine Acceptability Among Clients and Staff of Homeless Shelters in Detroit, Michigan, February 2021external icon
        Meehan AA, Yeh M, Gardner A, DeFoe TL, Garcia A, Vander Kelen P, Montgomery MP, Tippins AE, Carmichael AE, Gibbs Chw R, Caidi H, Mosites E, Rehman N.
        Health Promot Pract. 2021 Oct 23:15248399211049202.
        Understanding COVID-19 vaccine acceptability among clients and staff of homeless shelters can inform public health efforts focused on communicating with and educating this population about COVID-19 vaccines and thus improve vaccine uptake. The objective of this study was to assess COVID-19 vaccine acceptability and uptake among people in homeless shelters in Detroit, Michigan. A cross-sectional study was conducted from February 9 to 23, 2021. Seventeen homeless shelters were surveyed: seven male-only, three male/female, and seven women and family shelters. All clients and staff aged ≥18 years and able to complete a verbal survey in English or with a translator were eligible to participate; of the 168 individuals approached, 26 declined, leaving a total sample of 106 clients and 36 staff participating in the study. The median client and staff ages were 44 and 54 years, respectively. Most participants (>80%) identified as non-Hispanic Black or African American. Sixty-one (57.5%) clients and 27 (75.5%) staff had already received or planned to receive a COVID-19 vaccination. Twelve (11.3%) clients and four (11.1%) staff were unsure, and 33 (31.1%) clients and five (13.9%) staff did not plan to get vaccinated. Reasons for hesitancy were concerns over side effects (29 clients [64.4%] and seven staff [77.8%]) and unknown long-term health impacts (26 clients [57.8%] and six staff [66.7%]). More than half of the clients had already received or planned to receive the vaccine. Continuing efforts such as vaccine education for hesitant clients and staff and having accessible vaccine events for this population may improve acceptability and uptake.

      3. Racial and Ethnic Disparities in Rates of COVID-19-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021external icon
        Acosta AM, Garg S, Pham H, Whitaker M, Anglin O, O'Halloran A, Milucky J, Patel K, Taylor C, Wortham J, Chai SJ, Kirley PD, Alden NB, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Openo KP, Weigel A, Monroe ML, Ryan P, Reeg L, Kohrman A, Lynfield R, Bye E, Torres S, Salazar-Sanchez Y, Muse A, Barney G, Bennett NM, Bushey S, Billing L, Shiltz E, Sutton M, Abdullah N, Talbot HK, Schaffner W, Ortega J, Price A, Fry AM, Hall A, Kim L, Havers FP.
        JAMA Netw Open. 2021 Oct 1;4(10):e2130479.
        IMPORTANCE: Racial and ethnic minority groups are disproportionately affected by COVID-19. OBJECTIVES: To evaluate whether rates of severe COVID-19, defined as hospitalization, intensive care unit (ICU) admission, or in-hospital death, are higher among racial and ethnic minority groups compared with non-Hispanic White persons. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 99 counties within 14 US states participating in the COVID-19-Associated Hospitalization Surveillance Network. Participants were persons of all ages hospitalized with COVID-19 from March 1, 2020, to February 28, 2021. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test within 14 days prior to or during hospitalization. MAIN OUTCOMES AND MEASURES: Cumulative age-adjusted rates (per 100 000 population) of hospitalization, ICU admission, and death by race and ethnicity. Rate ratios (RR) were calculated for each racial and ethnic group compared with White persons. RESULTS: Among 153 692 patients with COVID-19-associated hospitalizations, 143 342 (93.3%) with information on race and ethnicity were included in the analysis. Of these, 105 421 (73.5%) were 50 years or older, 72 159 (50.3%) were male, 28 762 (20.1%) were Hispanic or Latino, 2056 (1.4%) were non-Hispanic American Indian or Alaska Native, 7737 (5.4%) were non-Hispanic Asian or Pacific Islander, 40 806 (28.5%) were non-Hispanic Black, and 63 981 (44.6%) were White. Compared with White persons, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely to have higher cumulative age-adjusted rates of hospitalization, ICU admission, and death as follows: American Indian or Alaska Native (hospitalization: RR, 3.70; 95% CI, 3.54-3.87; ICU admission: RR, 6.49; 95% CI, 6.01-7.01; death: RR, 7.19; 95% CI, 6.47-7.99); Latino (hospitalization: RR, 3.06; 95% CI, 3.01-3.10; ICU admission: RR, 4.20; 95% CI, 4.08-4.33; death: RR, 3.85; 95% CI, 3.68-4.01); Black (hospitalization: RR, 2.85; 95% CI, 2.81-2.89; ICU admission: RR, 3.17; 95% CI, 3.09-3.26; death: RR, 2.58; 95% CI, 2.48-2.69); and Asian or Pacific Islander (hospitalization: RR, 1.03; 95% CI, 1.01-1.06; ICU admission: RR, 1.91; 95% CI, 1.83-1.98; death: RR, 1.64; 95% CI, 1.55-1.74). CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely than White persons to have a COVID-19-associated hospitalization, ICU admission, or in-hospital death during the first year of the US COVID-19 pandemic. Equitable access to COVID-19 preventive measures, including vaccination, is needed to minimize the gap in racial and ethnic disparities of severe COVID-19.

      4. Lifecourse socioeconomic position and diabetes incidence in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, 2003 to 2016external icon
        Martin KD, Beckles GL, Wu C, McClure LA, Carson AP, Bennett A, Bullard KM, Glymour M, Unverzagt F, Cunningham S, Imperatore G, Howard VJ.
        Prev Med. 2021 Oct 18:106848.
        Low socioeconomic position (SEP) across the lifecourse is associated with Type 2 diabetes (T2DM). We examined whether these economic disparities differ by race and sex. We included 5448 African American (AA) and white participants aged ≥45 years from the national (United States) REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort without T2DM at baseline (2003-07). Incident T2DM was defined by fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or using T2DM medications at follow-up (2013-16). Derived SEP scores in childhood (CSEP) and adulthood (ASEP) were used to calculate a cumulative (CumSEP) score. Social mobility was defined as change in SEP. We fitted race-stratified logistic regression models to estimate the association between each lifecourse SEP indicator and T2DM, adjusting for covariates; additionally, we tested SEP-sex interactions. Over a median of 9.0 (range 7-14) years of follow-up, T2DM incidence was 167.1 per 1000 persons among AA and 89.9 per 1000 persons among white participants. Low CSEP was associated with T2DM incidence among AA (OR = 1.61; 95%CI 1.05-2.46) but not white (1.06; 0.74-2.33) participants; this was attenuated after adjustment for ASEP. In contrast, low CumSEP was associated with T2DM incidence for both racial groups. T2DM risk was similar for stable low SEP and increased for downward mobility when compared with stable high SEP in both groups, whereas upward mobility increased T2DM risk among AAs only. No differences by sex were observed. Among AAs, low CSEP was not independently associated with T2DM, but CSEP may shape later-life experiences and health risks.

    • Health Economics
      1. Annual Report to the Nation on the Status of Cancer, Part 2: Patient Economic Burden Associated With Cancer Careexternal icon
        Yabroff KR, Mariotto A, Tangka F, Zhao J, Islami F, Sung H, Sherman RL, Henley SJ, Jemal A, Ward EM.
        J Natl Cancer Inst. 2021 Oct 26.
        BACKGROUND: The American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and North American Association of Central Cancer Registries provide annual information about cancer occurrence and trends in the United States. Part 1 of this annual report focuses on national cancer statistics. This study is part 2, which quantifies patient economic burden associated with cancer care. METHODS: We used complementary data sources, linked Surveillance, Epidemiology, and End Results-Medicare, and the Medical Expenditure Panel Survey to develop comprehensive estimates of patient economic burden, including out-of-pocket and patient time costs, associated with cancer care. The 2000-2013 Surveillance, Epidemiology, and End Results-Medicare data were used to estimate net patient out-of-pocket costs among adults aged 65 years and older for the initial, continuing, and end-of-life phases of care for all cancer sites combined and separately for the 21 most common cancer sites. The 2008-2017 Medical Expenditure Panel Survey data were used to calculate out-of-pocket costs and time costs associated with cancer among adults aged 18-64 years and 65 years and older. RESULTS: Across all cancer sites, annualized net out-of-pocket costs for medical services and prescriptions drugs covered through a pharmacy benefit among adults aged 65 years and older were highest in the initial ($2200 and $243, respectively) and end-of-life phases ($3823 and $448, respectively) and lowest in the continuing phase ($466 and $127, respectively), with substantial variation by cancer site. Out-of-pocket costs were generally higher for patients diagnosed with later-stage disease. Net annual time costs associated with cancer were $304.3 (95% confidence interval = $257.9 to $350.9) and $279.1 (95% confidence interval = $215.1 to $343.3) for adults aged 18-64 years and ≥65 years, respectively, with higher time costs among more recently diagnosed survivors. National patient economic burden, including out-of-pocket and time costs, associated with cancer care was projected to be $21.1 billion in 2019. CONCLUSIONS: This comprehensive study found that the patient economic burden associated with cancer care is substantial in the United States at the national and patient levels.

    • Healthcare Associated Infections
      1. This case study is part of a series centered on the Centers for Disease Control and Prevention's National Healthcare Safety Network's (NHSN) health care-associated infection (HAI) surveillance definitions. This is the first analytic case study published in AJIC since the CDC/ NHSN updated its HAI risk adjustment models and rebaselined the standardized infection ratios (SIRs) in 2015. This case describes a scenario that Infection Preventionists (IPs) have encountered during their analysis of surgical site infection (SSI) surveillance data. The case study is intended to illustrate how specific models can impact the SIR results by highlighting differences in the criteria for NHSN's older and newer risk models: the original versions and the updated models introduced in 2015. Understanding these differences provides insight into how SSI SIR calculations differ between the older and newer NHSN baseline models. NHSN plans to produce another set of HAI risk adjustment models in the future, using newer HAI incidence and risk factor data. While the timetable for these changes remains to be determined, the statistical methods used to produce future models and SIR calculations will continue the precedents that NHSN has established. An online survey link is provided where participants may confidentially answer questions related to the case study and receive immediate feedback in the form of correct answers, explanations, rationales, and summary of teaching points. Details of the case study, answers, and explanations have been reviewed and approved by NHSN staff. We hope that participants take advantage of this educational offering and thereby gain a greater understanding of the NHSN's HAI data analysis. There are 2 baselines available for SSI standardized infection ration (SIRs) in the National Healthcare Safety Network (NHSN); one based on the 2006-2008 national aggregate data and another based on the 2015 data. Each of the 2 baselines has a different set of inclusion criteria for the SSI data, which impact the calculation of the SIR. In this case study, we focused on the impact of the inclusion of PATOS in the calculation of the 2006-2008 baseline SSI SIR and the exclusion of PATOS from the calculation of the 2015 baseline SSI SIR. In the 2006-2008 baseline SSI SIRs, PATOS events and the procedures to which they are linked are included in the calculation of the SSI SIR whereas in the 2015 baseline SSI SIRs, PATOS events and the procedures to which they are linked are excluded from the calculation of the SSI SIR. Meaning, if we control for all other inclusion criteria other than PATOS data for both baselines, we will notice differences in the number of observed events as well as the number of predicted infections for the 2 baselines. For details of the 2015 baseline and risk adjustment calculation, please review the NHSN Guide to the SIR referenced below. For details of the 2006-2008 baseline4 and risk adjustment, please see the SHEA paper "Improving Risk-Adjusted Measures of Surgical Site Infection for the National Healthcare Safety Network" by author Yi Mu.

    • Immunity and Immunization
      1. Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosisexternal icon
        Muchtar E, Koehler AB, Johnson MJ, Rabe KG, Ding W, Call TG, Leis JF, Kenderian SS, Hayman SR, Wang Y, Hampel PJ, Holets MA, Darby HC, Slager SL, Kay NE, Miao C, Canniff J, Whitaker JA, Levin MJ, Schmid DS, Kennedy RB, Weinberg A, Parikh SA.
        Am J Hematol. 2021 Oct 26.
        Monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B cell disorders associated with increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by two months. Responses assessed at 3-months and 12-months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color IFN-γ and IL-2 FLUOROSPOT assays were compared to historic controls matched by age and sex. Sixty-two patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, P=0.03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs 36%, respectively, P=0.23). The CD4+ T cell response to vaccination was significantly lower in study participants compared to controls (54% vs 96%, P<0.001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs 73%, P=0.008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n=47), 24% had antibody titers below response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed. This article is protected by copyright. All rights reserved.

      2. Mycobacterium porcinum Skin and Soft Tissue Infections After Vaccinations - Indiana, Kentucky, and Ohio, September 2018-February 2019external icon
        Blau EF, Flinchum A, Gaub KL, Hartnett KP, Curran M, Allen VK, Napier A, Hesse EM, Hause AM, Cathey R, Feaster C, Mohr M, de Fijter S, Mitchell S, Moulton-Meissner HA, Benowitz I, Spicer KB, Thoroughman DA.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 22;70(42):1472-1477.
        During December 2018-February 2019, a multistate investigation identified 101 patients with vaccination-associated adverse events among an estimated 940 persons in Kentucky, Indiana, and Ohio who had received influenza; hepatitis A; pneumococcal; or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines at the workplace during September 11-November 28, 2018. These vaccines had been administered by staff members of a third-party health care company contracted by 24 businesses. Company A provided multiple vaccine types during workplace vaccination events across 54 locations in these adjoining states. Injection-site wound isolates from patients yielded Mycobacterium porcinum, a nontuberculous mycobacteria (NTM) species in the Mycobacterium fortuitum group; subtyping using pulsed-field gel electrophoresis of all 28 available isolates identified two closely related clusters. Site visits to company A and interviews with staff members identified inadequate hand hygiene, improper vaccine storage and handling, lack of appropriate medical record documentation, and lack of reporting to the Vaccine Adverse Event Reporting System (VAERS). Vaccination-associated adverse events can be prevented by training health care workers responsible for handling or administering vaccines in safe vaccine handling, administration, and storage practices, timely reporting of any suspected vaccination-associated adverse events to VAERS, and notifying public health authorities of any adverse event clusters.

      3. BACKGROUND: Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. METHODS: We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons. RESULTS: We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). CONCLUSION: We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

      4. BACKGROUND: Between September 2017 and June 2019, an outbreak of hepatitis A virus (HAV) occurred in Louisville, Kentucky, resulting in 501 cases and 6 deaths, predominantly among persons who experience homelessness or who use drugs (PEH/PWUD). The critical vaccination threshold (V(c)) required to achieve herd immunity in this population is unknown. We investigated V(c) and vaccination impact using epidemic modeling. METHODS: To determine which population subgroups had high infection risks, we employed a technique based on comparing the proportion of cases arising before and after the epidemic peak, across subgroups. We also developed a dynamic deterministic model of HAV transmission among PEH/PWUD to estimate the basic reproduction number (R(0)), herd immunity threshold, V(c) and the effect of timing of the vaccination intervention on epidemic and economic outcomes. RESULTS: Of the 501 confirmed or probable cases, 385 (76.8%) were among PEH/PWUD. Among PEH/PWUD and within the general population, homelessness was a significant risk factor for infection in the initial stages of the outbreak (odds ratios for homeless versus not homeless: 2.62; 95% confidence interval (CI): 1.62-4.25 for PEH/PWUD and 2.39; 95% CI: 1.51-3.78 for all detected cases). Our estimate for R(0) ranges between 2.85 and 3.54, corresponding to an estimate of 69% (95% CI: 65-72) for herd immunity threshold and 76% (95% CI: 72%-80%) for V(c)(,) assuming a vaccine with 90% efficacy. The observed vaccination program was estimated to have averted 30 hospitalizations (95% CI: 19-43), associated with over US$490 000 (95% CI: $310 000-700 000) in hospitalization cost. Greater impact was observed with earlier and faster vaccination implementation. CONCLUSIONS: Vaccination coverage of at least 77% is likely required to prevent outbreaks of HAV among PEH/PWUD in Louisville, assuming a 90% vaccine efficacy. Proactive hepatitis A vaccination programs among PEH/PWUD will maximize health and economic benefits of these programs and reduce the likelihood of another outbreak.

    • Laboratory Sciences
      1. Need for caution when interpreting Xpert(®) MTB/RIF results for rifampin resistance among childrenexternal icon
        Murithi W, Click ES, McCarthy KD, Okeyo E, Sitati R, Anyango I, Okumu A, McHembere W, Song R, Cain K.
        Int J Tuberc Lung Dis. 2021 Nov 1;25(11):911-916.
        BACKGROUND: Recommended by the World Health Organization as an initial diagnostic test for TB in children, Xpert(®) MTB/RIF is widely implemented in many countries, including Kenya.METHODS: Three hundred HIV-positive and negative children (<5 years) were enrolled in Kisumu County, Kenya, from October 2013 to August 2015. Multiple specimen types were collected from each child and tested using Xpert, liquid culture, and phenotypic drug susceptibility testing (DST). Samples positive for rifampin (RIF) resistance on Xpert were tested using line-probe assay and sequencing.RESULTS: Of 32 children with bacteriologically confirmed TB, 27 had positive Xpert results. Of these, 3/27 (11%, 95% CI 4-28) had RIF resistance detected on Xpert, but not by phenotypic DST, line-probe assay, or sequencing. For these three children, five Xpert tests showed RIF resistance; all five tests had semi-quantitative "very low" results and delay or absence of probe D signal, whereas no Xpert results with higher semi-quantitative results showed RIF resistance. All three children responded well to standard TB treatment.CONCLUSIONS: False RIF resistance may be detected in pediatric specimens. Further study is needed to determine if false RIF resistance is associated with low bacterial load.

      2. Performance characteristics of the Abbott BinaxNOW SARS-CoV-2 antigen test in comparison to real-time RT-PCR and viral culture in community testing sites during November 2020external icon
        Almendares O, Prince-Guerra JL, Nolen LD, Gunn JK, Dale AP, Buono SA, Deutsch-Feldman M, Suppiah S, Hao L, Zeng Y, Stevens VA, Knipe K, Pompey J, Atherstone C, Bui DP, Powell T, Tamin A, Harcourt JL, Petway M, Bohannon C, Folster JM, MacNeil A, Salerno R, Kuhnert-Tallman W, Tate JE, Thornburg N, Kirking HL, Sheiban K, Kudrna J, Cullen T, Komatsu KK, Villanueva JM, Rose DA, Neatherlin JC, Anderson M, Rota PA, Honein MA, Bower WA.
        J Clin Microbiol. 2021 Oct 27:Jcm0174221.
        Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse-transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease or exposure period and demographic variables are limited. During November 3(rd)-17(th), 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW (BinaxNOW) antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8-10 days post-exposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 hours for BinaxNOW and 26 hours for rRT-PCR. Point-of-care antigen tests have a shorter turn-around time compared to laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program.

      3. Comprehensive characterization of internal and cuticle surface microbiota of laboratory-reared F(1) Anopheles albimanus originating from different sitesexternal icon
        Dada N, Benedict AC, López F, Lol JC, Sheth M, Dzuris N, Padilla N, Lenhart A.
        Malar J. 2021 Oct 23;20(1):414.
        BACKGROUND: Research on mosquito-microbe interactions may lead to new tools for mosquito and mosquito-borne disease control. To date, such research has largely utilized laboratory-reared mosquitoes that typically lack the microbial diversity of wild populations. A logical progression in this area involves working under controlled settings using field-collected mosquitoes or, in most cases, their progeny. Thus, an understanding of how laboratory colonization affects the assemblage of mosquito microbiota would aid in advancing mosquito microbiome studies and their applications beyond laboratory settings. METHODS: Using high throughput 16S rRNA amplicon sequencing, the internal and cuticle surface microbiota of F(1) progeny of wild-caught adult Anopheles albimanus from four locations in Guatemala were characterized. A total of 132 late instar larvae and 135 2-5 day-old, non-blood-fed virgin adult females that were reared under identical laboratory conditions, were pooled (3 individuals/pool) and analysed. RESULTS: Results showed location-associated heterogeneity in both F(1) larval internal (p = 0.001; pseudo-F = 9.53) and cuticle surface (p = 0.001; pseudo-F = 8.51) microbiota, and only F(1) adult cuticle surface (p = 0.001; pseudo-F = 4.5) microbiota, with a more homogenous adult internal microbiota (p = 0.12; pseudo-F = 1.6) across collection sites. Overall, ASVs assigned to Leucobacter, Thorsellia, Chryseobacterium and uncharacterized Enterobacteriaceae, dominated F(1) larval internal microbiota, while Acidovorax, Paucibacter, and uncharacterized Comamonadaceae, dominated the larval cuticle surface. F(1) adults comprised a less diverse microbiota compared to larvae, with ASVs assigned to the genus Asaia dominating both internal and cuticle surface microbiota, and constituting at least 70% of taxa in each microbial niche. CONCLUSIONS: These results suggest that location-specific heterogeneity in filed mosquito microbiota can be transferred to F(1) progeny under normal laboratory conditions, but this may not last beyond the F(1) larval stage without adjustments to maintain field-derived microbiota. These findings provide the first comprehensive characterization of laboratory-colonized F(1) An. albimanus progeny from field-derived mothers. This provides a background for studying how parentage and environmental conditions differentially or concomitantly affect mosquito microbiome composition, and how this can be exploited in advancing mosquito microbiome studies and their applications beyond laboratory settings.

      4. Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarrayexternal icon
        Camerini D, Randall AZ, Trappl-Kimmons K, Oberai A, Hung C, Edgar J, Shandling A, Huynh V, Teng AA, Hermanson G, Pablo JV, Stumpf MM, Lester SN, Harcourt J, Tamin A, Rasheed M, Thornburg NJ, Satheshkumar PS, Liang X, Kennedy RB, Yee A, Townsend M, Campo JJ.
        Microbiol Spectr. 2021 Oct 27:e0141621.
        The rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the COVID-19 pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of various lengths, and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multicoronavirus arrays to identify specific antibody reactivity. High-level IgG, IgM, and IgA reactivity to structural proteins S, M, and N of SARS-CoV-2, as well as accessory proteins such as ORF3a and ORF7a, were observed that were specific to COVID-19 patients. Antibody reactivity against overlapping 100-, 50-, and 30-amino acid fragments of SARS-CoV-2 proteins was used to identify antigenic regions. Numerous proteins of SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and the endemic human coronaviruses HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM, and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. Whereas unexposed individuals had minimal reactivity against SARS-CoV-2 proteins that poorly correlated with reactivity against HCoV-NL63 and HCoV-OC43 S2 and N proteins, COVID-19 patient sera had higher correlation between SARS-CoV-2 and HCoV responses, suggesting that de novo antibodies against SARS-CoV-2 cross-react with HCoV epitopes. Array responses were compared with validated spike protein-specific IgG enzyme-linked immunosorbent assays (ELISAs), showing agreement between orthologous methods. SARS-CoV-2 microneutralization titers were low in the COVID-19 patient sera but correlated with array responses against S and N proteins. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients. IMPORTANCE With novel mutant SARS-CoV-2 variants of concern on the rise, knowledge of immune specificities against SARS-CoV-2 proteins is increasingly important for understanding the impact of structural changes in antibody-reactive protein epitopes on naturally acquired and vaccine-induced immunity, as well as broader topics of cross-reactivity and viral evolution. A multi-coronavirus protein microarray used to map the binding of COVID-19 patient antibodies to SARS-CoV-2 proteins and protein fragments as well as to the proteins of four other coronaviruses that infect humans has shown specific regions of SARS-CoV-2 proteins that are highly reactive with patient antibodies and revealed cross-reactivity of these antibodies with other human coronaviruses. These data and the multi-coronavirus protein microarray tool will help guide further studies of the antibody response to COVID-19 and to vaccination against this worldwide pandemic.

      5. Application of a Serial Antigen-Based Testing Strategy for Severe Acute Respiratory Syndrome Coronavirus 2 and Student Adherence in a University Setting: Wisconsin, October-November 2020external icon
        Bigouette JP, Ford L, Pray I, Langolf K, Kahrs J, Zochert T, Tate JE, Gieryn D, Kirking HL, Westergaard R, Killerby ME.
        Open Forum Infect Dis. 2021 Oct;8(10):ofab472.
        BACKGROUND: Serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing has been implemented at institutions of higher education (IHEs) and other settings. Testing strategies can include algorithms specifying confirmatory reverse-transcription polymerase chain reaction (RT-PCR) testing after an antigen test. It is unknown how testing strategies perform detecting SARS-CoV-2, including individual adherence to serial testing requirements. METHODS: Student serial testing adherence was defined as completing ≥80% of weekly tests from October 5, 2020 to November 14, 2020 and evaluated using logistic regression. Medical records were reviewed for all positive antigen test encounters and 10% of daily negative antigen test encounters during October 19-November 30, 2020. Results were used to estimate the proportion of individuals requiring only antigen tests, requiring and completing RT-PCR testing, and associated costs of tests. RESULTS: Two thirds (66.5%; 1166 of 1754) of eligible on-campus students adhered to weekly testing; female students were more adherent (adjusted odds ratio [aOR], 2.07; 95% confidence interval, 1.66-2.59) than male students. Of all antigen test encounters, 11.5% (1409 of 12 305) reported >1 COVID-19 symptoms. Of non-COVID-19-exposed antigen test encounters, 88% (10 386 of 11 769) did not require confirmatory RT-PCR testing. Only 28% (390 of 1387) of testing encounters had an associated recommended confirmatory RT-PCR test performed. We estimated the testing strategy captured 61% (235 of 389) of predicted RT-PCR-positive specimens. CONCLUSIONS: At this IHE, most students voluntarily adhered to serial testing. The majority of antigen test results did not require confirmatory RT-PCR testing, but when required, most students did not obtain it. Including strategies to increase the proportion of individuals obtaining indicated confirmatory testing might improve the testing program's performance.

    • Nutritional Sciences
      1. Temporal Trends in Dietary Sodium Intake Among Adults Aged ≥19 Years - United States, 2003-2016external icon
        Clarke LS, Overwyk K, Bates M, Park S, Gillespie C, Cogswell ME.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 22;70(42):1478-1482.
        Hypertension, which can be brought on by excess sodium intake, affects nearly one half of U.S. adults and is a major risk factor for heart disease, the leading cause of death in the United States (1). In 2019, the National Academies of Sciences, Engineering, and Medicine (NASEM) established the Chronic Disease Risk Reduction (CDRR) intake, a chronic-disease-specific recommendation for dietary sodium of 2,300 mg/day. Reducing daily sodium to CDRR intake is expected to reduce chronic disease risk among healthy persons, primarily by lowering blood pressure (2). Although the 2019 sodium CDRR intake is equivalent in number to the 2005 Tolerable Upper Limit (UL) released by NASEM (then known as the Institute of Medicine), the UL was intended to provide guidance on safe intake levels, not to serve as an intake goal (2). To describe excess sodium intake in the context of the CDRR intake goal, this report analyzed National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2016 to yield temporal trends in usual sodium intake >2,300 mg/day and in mean sodium intake, unadjusted and adjusted for total energy intake, among U.S. adults aged ≥19 years. The percentage of U.S. adults with sodium intake above CDRR intake was 87.0% during 2003-2004 and 86.7% during 2015-2016. Among U.S. adults overall, no significant linear trend was noted from 2003 to 2016 in unadjusted or energy intake-adjusted mean sodium intake. Small, significant declines were observed in mean usual sodium intake among some groups (adults aged 19-50 years, non-Hispanic White adults, adults experiencing obesity, and adults without hypertension). However, after energy adjustment, only adults aged ≥71 years and Mexican American adults demonstrated significant change in usual sodium intake. Many U.S. adults might be at risk for chronic disease associated with sodium intake above CDRR intake, and efforts to lower sodium intake could improve population cardiovascular health. The results of this report support enhanced efforts to reduce population sodium intake and cardiovascular disease risk, including the Food and Drug Administration's (FDA's) recently released guidance for the reduction of sodium in the commercially processed, packaged, and prepared food supply.

    • Occupational Safety and Health
      1. Load Asymmetry Angle Estimation Using Multiple-View Videosexternal icon
        Wang X, Hu YH, Lu M, Radwin R.
        IEEE Trans Hum Mach Syst. 2021 .
        A robust computer vision-based approach is developed to estimate the load asymmetry angle defined in the revised NIOSH lifting equation. The angle of asymmetry enables the computation of a recommended weight limit for repetitive lifting operations in a workplace to prevent lower back injuries. An open-source package OpenPose is applied to estimate the two-dimensional (2-D) locations of skeletal joints of the worker from two synchronous videos. Combining these joint location estimates, a computer vision correspondence and depth estimation method is developed to estimate the 3-D coordinates of skeletal joints during lifting. The angle of asymmetry is then deduced from a subset of these 3-D positions. Error analysis reveals unreliable angle estimates due to occlusions of upper limbs. A robust angle estimation method that mitigates this challenge is developed. We propose a method to flag unreliable angle estimates based on the average confidence level of 2-D joint estimates provided by OpenPose. An optimal threshold is derived that balances the percentage variance reduction of the estimation error and the percentage of angle estimates flagged. Tested with 360 lifting instances in a NIOSH-provided dataset, the standard deviation of angle estimation error is reduced from 10.13&#x00B0; to 4.99&#x00B0;. To realize this error variance reduction, 34&#x0025; of estimated angles are flagged and require further validation. IEEE

      2. Dissemination and implementation science approaches for occupational safety and health research: Implications for advancing total worker healthexternal icon
        Guerin RJ, Harden SM, Rabin BA, Rohlman DS, Cunningham TR, Tepoel MR, Parish M, Glasgow RE.
        Int J Environ Res Public Health. 2021 ;18(21).
        Total Worker Health® (TWH), an initiative of the U.S. National Institute for Occupational Safety and Health, is defined as policies, programs, and practices that integrate protection from work-related health and safety hazards by promoting efforts that advance worker well-being. Interventions that apply the TWH paradigm improve workplace health more rapidly than wellness programs alone. Evidence of the barriers and facilitators to the adoption, implementation, and long-term maintenance of TWH programs is limited. Dissemination and implementation (D&I) science, the study of methods and strategies for bridging the gap between public health research and practice, can help address these system-, setting-, and worker-level factors to increase the uptake, impact, and sustainment of TWH activities. The purpose of this paper is to draw upon a synthesis of existing D&I science literature to provide TWH researchers and practitioners with: (1) an overview of D&I science; (2) a plain language explanation of key concepts in D&I science; (3) a case study example of moving a TWH intervention down the research-to-practice pipeline; and (4) a discussion of future opportunities for conducting D&I science in complex and dynamic workplace settings to increase worker safety, health, and well-being. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Parasitic Diseases
      1. Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all agesexternal icon
        Sayre D, Steinhardt LC, Irinantenaina J, Dentinger C, Rasoanaivo TF, Kapesa L, Razafindrakoto J, Legrand A, Prada N, Gutman J, Lewis L, Mangahasimbola RT, Andriamananjara M, Ravaoarinosy AV, Ralemary N, Garchitorena A, Harimanana A.
        Malar J. 2021 Oct 26;20(1):422.
        BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.

    • Physical Activity
      1. Self-Management Education Class Attendance and Health Care Provider Counseling for Physical Activity Among Adults with Arthritis - United States, 2019external icon
        Duca LM, Helmick CG, Barbour KE, Guglielmo D, Murphy LB, Boring MA, Theis KA, Odom EL, Liu Y, Croft JB.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 22;70(42):1466-1471.
        Arthritis is a highly prevalent and disabling condition among U.S. adults (1); arthritis-attributable functional limitations and severe joint pain affect many aspects of health and quality of life (2). Self-management education (self-management) and physical activity can reduce pain and improve the health status and quality of life of adults with arthritis; however, in 2014, only 11.4% and 61.0% of arthritis patients reported engaging in each, respectively. To assess self-reported self-management class attendance and health care provider physical activity counseling among adults with doctor-diagnosed arthritis, CDC analyzed 2019 Behavioral Risk Factor Surveillance System (BRFSS) data. In 2019, an age-standardized state median of one in six (16.2%) adults with arthritis reported ever attending a self-management class, and 69.3% reported ever receiving health care provider counselling to be physically active. Prevalences of both differed by state and sociodemographic characteristics; decreased with lower educational attainment, joint pain severity, and urbanicity; and were lower in men than in women. Health care providers can play an important role in promoting self-management class attendance and physical activity by counseling arthritis patients about their benefits and referring patients to evidence-based programs (3).

    • Reproductive Health
      1. Predicting Emergence of Primary and Secondary Syphilis Among Women of Reproductive Age in U.S. Countiesexternal icon
        Kimball A, Torrone EA, Bernstein KT, Grey JA, Bowen VB, Rickless DS, Learner ER.
        Sex Transm Dis. 2021 Oct 22.
        BACKGROUND: Syphilis, a sexually transmitted infection that can cause severe congenital disease when not treated during pregnancy, is on the rise in the United States. Our objective was to identify U.S. counties with elevated risk for emergence of primary and secondary (P&S) syphilis among reproductive-aged women. METHODS: Using syphilis case reports, we identified counties with no cases of P&S syphilis among reproductive-aged women in 2017 and ≥ 1 case in 2018. Using county-level syphilis and sociodemographic data, we developed a model to predict counties with emergence of P&S syphilis among women and a risk score to identify counties at elevated risk. RESULTS: Of 2,451 counties with no cases of P&S syphilis among reproductive-aged women in 2017, 345 counties (14.1%) had documented emergence of syphilis in 2018. Emergence was predicted by the county's P&S syphilis rate among men; violent crime rate; proportions of Black, White, Asian, and Hawaiian/Pacific Islander persons; urbanicity; presence of a metropolitan area; population size; and having a neighboring county with P&S syphilis among women. A risk score of ≥20 identified 75% of counties with emergence. CONCLUSIONS: Jurisdictions can identify counties at elevated risk for emergence of syphilis in women and tailor prevention efforts. Prevention of syphilis requires multidisciplinary collaboration to address underlying social factors.

    • Substance Use and Abuse
      1. Lessons Learned From the E-cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) Outbreak Response, Minnesota, 2019-2020external icon
        Wiens T, Taylor J, Cole C, Saravia S, Peterson J, Lunda M, Margetta J, D'Heilly P, Holzbauer S, Lynfield R.
        Public Health Rep. 2021 Oct 25:333549211051394.
        OBJECTIVE: Electronic cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) is a novel noncommunicable disease with an unknown cause. The objective of this analysis was to describe the Minnesota Department of Health's (MDH's) outbreak response to EVALI, including challenges, successes, and lessons learned. METHODS: MDH began investigating EVALI cases in August 2019 and quickly coordinated an agencywide response. This response included activating the incident command system; organizing multidisciplinary teams to perform the epidemiologic investigation; laboratory testing of e-cigarette, or vaping, products (EVPs) and clinical specimens; and collaborating with partners to gather information and develop recommendations. RESULTS: MDH faced numerous investigational challenges during the outbreak response of EVALI, including the need to gather information on unregulated and illicit substances and their use and collecting information from minors and critically ill people. MDH laboratorians faced methodologic challenges in characterizing EVPs. Despite these challenges, MDH epidemiologists successfully collaborated with the MDH public health laboratory, law enforcement, partners with clinical and toxicology expertise, and local and national public health partners. PRACTICE IMPLICATIONS: Lessons learned included ensuring the state public health agency has legal authority to conduct noncommunicable disease outbreak investigations and the necessity of cultivating and using internal and external partnerships, specifically with laboratories that can analyze clinical specimens and unknown substances. The lessons learned may be useful to public health agencies responding to similar public health emergencies. To improve preparedness for the next outbreak of EVALI or other noncommunicable diseases, we recommend building and maintaining partnerships with internal and external partners.

      2. Background: Opioid misuse during pregnancy has been associated with adverse infant outcomes including preterm birth, stillbirth, and neonatal opioid withdrawal syndrome. The Pregnancy Risk Assessment Monitoring System (PRAMS) is an on-going state-based surveillance system of maternal behaviors, attitudes, and experiences prior to, during, and after pregnancy. Methods: We analyzed qualitative comments related to opioid use during pregnancy collected in 2016 from an open-ended prompt at the end of the PRAMS survey in 35 states (N = 40,408). Key word searches were conducted on the open-ended responses (n = 9,549) to identify opioid-related content with an automated function using Microsoft Excel. All responses from the initial screening (n = 1,035) were manually reviewed, and 69 responses were confirmed to relate to the respondent’s personal experience with opioid use during pregnancy. Content analysis was conducted by 3 independent coders; key themes were compiled, discussed, and finalized by the coding team. Results: Five key themes related to opioid use during pregnancy were identified: (1) gratitude for treatment, recovery, and healthy infants; (2) pregnancy as motivation to seek treatment; (3) difficulty finding prenatal care providers with training in substance use disorders; (4) concern about the effects of treatment on the infant; and (5) experiences of discrimination and stigma in the hospital around the time of delivery. Conclusions: Women may be aware of the potential impact of opioid use during pregnancy on the health of their infants and motivated to seek treatment. Findings may help inform new and ongoing initiatives designed to improve care and reduce stigma for women needing or seeking treatment. © 2021 Taylor & Francis Group, LLC.

    • Zoonotic and Vectorborne Diseases
      1. Salmonella Illness Outbreaks linked to Backyard Poultry Purchasing during the COVID-19 Pandemic - United States, 2020external icon
        Nichols M, Gollarza L, Palacios A, Stapleton GS, Basler C, Hoff C, Low M, McFadden K, Koski L, Leeper M, Brandenburg J, Tolar B.
        Epidemiol Infect. 2021 Oct 27:1-10.

      2. Evaluating Surveillance for and Estimating Administration of Rabies Postexposure Prophylaxis in the United States, 2012-2018external icon
        Whitehouse ER, Person MK, Brown CM, Slavinski S, Rao AK, Blanton JD.
        PLoS Negl Trop Dis. 2021 Oct 25;15(10):e0009878.
        BACKGROUND: An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. METHODOLOGY/PRINCIPLE FINDINGS: To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012-2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012-2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. CONCLUSIONS: Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment.

      3. Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018external icon
        Mercado-Reyes M, Gilboa SM, Valencia D, Daza M, Tong VT, Galang RR, Winfield CM, Godfred-Cato S, Benavides M, Villanueva JM, Thomas JD, Daniels J, Zaki S, Reagan-Steiner S, Bhatnagar J, Schiffer J, Steward-Clark E, Ricaldi JN, Osorio J, Sancken CL, Pardo L, Tinker SC, Anderson KN, Rico A, Burkel VK, Hojnacki J, Delahoy MJ, González M, Osorio MB, Moore CA, Honein MA, Ospina Martinez ML.
        Trop Med Infect Dis. 2021 Oct 12;6(4).
        Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy.

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