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Issue 43, November 23, 2021

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CDC Science Clips: Volume 13, Issue 43, November 23, 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.

The report consists of these components:

  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
      • The IARC Perspective on Cervical Cancer Screeningexternal icon
        Bouvard V, Wentzensen N, Mackie A, Berkhof J, Brotherton J, Giorgi-Rossi P, Kupets R, Smith R, Arrossi S, Bendahhou K, Canfell K, Chirenje ZM, Chung MH, Del Pino M, de Sanjosé S, Elfström M, Franco EL, Hamashima C, Hamers FF, Herrington CS, Murillo R, Sangrajrang S, Sankaranarayanan R, Saraiya M, Schiffman M, Zhao F, Arbyn M, Prendiville W, Indave Ruiz BI, Mosquera-Metcalfe I, Lauby-Secretan B.
        N Engl J Med. 2021 Nov 11;385(20):1908-1918.

    • Communicable Diseases
      • The shifting age distribution of people with HIV using antiretroviral therapy in the United States, 2020 to 2030external icon
        Althoff KN, Stewart CN, Humes E, Zhang J, Gerace L, Boyd CM, Wong C, Justice AC, Gebo K, Thorne JE, Rubtsova AA, Horberg MA, Silverberg MJ, Leng SX, Rebeiro PF, Moore RD, Buchacz K, Kasaie P.
        Aids. 2021 Nov 8.
        OBJECTIVE: To project the future age distribution of people with HIV using antiretroviral therapy (ART) in the US, under expected trends in HIV diagnosis and survival (baseline scenario) and achieving the Ending the HIV Epidemic (EHE) goals of a 75% reduction in HIV diagnoses from 2020-25 and sustaining levels to 2030 (EHE75% scenario). DESIGN: An agent-based simulation model with mathematical functions estimated from North American AIDS Cohort Collaboration on Research and Design data and parameters from the US Centers for Disease Control and Prevention's annual HIV surveillance reports. METHODS: The PEARL (ProjEcting Age, multimoRbidity, and poLypharmacy in adults with HIV) model simulated individuals in 15 subgroups of sex-and-HIV acquisition risk and race/ethnicity. Simulation outcomes from the baseline scenario are compared with outcomes from the EHE75% scenario. RESULTS: Under the baseline scenario, PEARL projects a substantial increase in number of ART-users over time, reaching a population of 909,638 [95%uncertaintyrange(UR):878,449-946,513] by 2030. The overall median age increased from 50 years (y) in 2020 to 52y in 2030, with 23% of ART-users age ≥65y in 2030. Under the EHE75% scenario, the projected number of ART-users was 718,348 [703,044-737,817] (median age=56y) in 2030, with a 70% relative reduction in ART-users <30y and a 4% relative reduction in ART-users age ≥65y compared to baseline, and persistent heterogeneities in projected numbers by sex-and-HIV acquisition risk group and race/ethnicity. CONCLUSIONS: It is critical to prepare healthcare systems to meet the impending demand of the US population aging with HIV.

    • Disaster Preparedness and Emergency Services
      • Lessons Learned from the Development and Demonstration of a PPE Inventory Monitoring System for US Hospitalsexternal icon
        Haas EJ, Casey ML, Furek A, Aldrich K, Ragsdale T, Crosswy S, Moore SM.
        Health Secur. 2021 Nov 9.
        An international system should be established to support personal protective equipment (PPE) inventory monitoring, particularly within the healthcare industry. In this article, the authors discuss the development and 15-week deployment of a proof-of-concept prototype that included the use of a Healthcare Trust Data Platform to secure and transmit PPE-related data. Seventy-eight hospitals participated, including 66 large hospital systems, 11 medium-sized hospital systems, and a single hospital. Hospitals reported near-daily inventory information for N95 respirators, surgical masks, and face shields, ultimately providing 159 different PPE model numbers. Researchers cross-checked the data to ensure the PPE could be accurately identified. In cases where the model number was inaccurately reported, researchers corrected the numbers whenever possible. Of the PPE model numbers reported, 74.2% were verified-60.5% of N95 respirators, 40.0% of face shields, and 84.0% of surgical masks. The authors discuss the need to standardize how PPE is reported, possible aspects of a PPE data standard, and standards groups who may assist with this effort. Having such PPE data standards would enable better communication across hospital systems and assist in emergency preparedness efforts during pandemics or natural disasters.

    • Environmental Health
      • BACKGROUND: The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. OBJECTIVES: To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. METHODS: We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26 weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12 years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. RESULTS: In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. DISCUSSION: In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

    • Health Economics
      • Preventing Leading Causes of Death: Systematic Review of Cost-Utility Literatureexternal icon
        Khushalani JS, Song S, Calhoun BH, Puddy RW, Kucik JE.
        Am J Prev Med. 2021 Nov 1.
        INTRODUCTION: Heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke are the 5 leading causes of death in the U.S. The objective of this review is to examine the economic value of prevention interventions addressing these 5 conditions. METHODS: Tufts Medical Center Cost-Effectiveness Analysis Registry data were queried from 2010 to 2018 for interventions that addressed any of the 5 conditions in the U.S. Results were stratified by condition, prevention stage, type of intervention, study sponsorship, and study perspective. The analyses were conducted in 2020, and all costs were reported in 2019 dollars. RESULTS: In total, 549 cost-effectiveness analysis studies examined interventions addressing these 5 conditions in the U.S. Tertiary prevention interventions were assessed in 61.4%, whereas primary prevention was assessed in 8.6% of the studies. Primary prevention studies were predominantly funded by government, whereas industry sources funded more tertiary prevention studies, especially those dealing with pharmaceutical interventions. The median incremental cost-effectiveness ratio for the 5 conditions combined was $68,500 per quality-adjusted life year. Median incremental cost-effectiveness ratios were lowest for primary prevention and highest for tertiary prevention. DISCUSSION: Primary prevention may be more cost effective than secondary and tertiary prevention interventions; however, research investments in primary prevention interventions, especially by industry, lag in comparison. These findings help to highlight the gaps in the cost-effectiveness analysis literature related to the 5 leading causes of death and identify understudied interventions and prevention stages for each condition.

    • Immunity and Immunization
      • Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severityexternal icon
        Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, Shapiro NI, Gibbs KW, Files DC, Hager DN, Shehu A, Prekker ME, Erickson HL, Exline MC, Gong MN, Mohamed A, Henning DJ, Steingrub JS, Peltan ID, Brown SM, Martin ET, Monto AS, Khan A, Hough CL, Busse LW, Ten Lohuis CC, Duggal A, Wilson JG, Gordon AJ, Qadir N, Chang SY, Mallow C, Rivas C, Babcock HM, Kwon JH, Halasa N, Chappell JD, Lauring AS, Grijalva CG, Rice TW, Jones ID, Stubblefield WB, Baughman A, Womack KN, Rhoads JP, Lindsell CJ, Hart KW, Zhu Y, Olson SM, Kobayashi M, Verani JR, Patel MM.
        Jama. 2021 Nov 4.
        IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). CONCLUSIONS AND RELEVANCE: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.

    • Injury and Violence
      • Alcohol-impaired driving among adults-USA, 2014-2018external icon
        Barry V, Schumacher A, Sauber-Schatz E.
        Inj Prev. 2021 Nov 5.
        INTRODUCTION: Alcohol-impaired driving (AID) crashes accounted for 10 511 deaths in the USA in 2018, or 29% of all motor vehicle-related crash deaths. This study describes self-reported AID in the USA during 2014, 2016 and 2018 and determines AID-related demographic and behavioural characteristics. METHODS: Data were from the nationally representative Behavioral Risk Factor Surveillance System. Adults were asked 'During the past 30 days, how many times have you driven when you have had perhaps too much to drink?' AID prevalence, episode counts and rates per 1000 population were estimated using annualised individual AID episodes and weighted survey population estimates. Results were stratified by characteristics including gender, binge drinking, seatbelt use and healthcare engagement. RESULTS: Nationally, 1.7% of adults engaged in AID during the preceding 30 days in 2014, 2.1% in 2016 and 1.7% in 2018. Estimated annual number of AID episodes varied across year (2014: 111 million, 2016: 186 million, 2018: 147 million) and represented 3.7 million, 4.9 million and 4.0 million adults, respectively. Corresponding yearly episode rates (95% CIs) were 452 (412-492) in 2014, 741 (676-806) in 2016 and 574 (491-657) in 2018 per 1000 population. Among those reporting AID in 2018, 80% were men, 86% reported binge drinking, 47% did not always use seatbelts and 60% saw physicians for routine check-ups within the past year. CONCLUSIONS: Although AID episodes declined from 2016 to 2018, AID was still prevalent and more common among men and those who binge drink. Most reporting AID received routine healthcare. Proven AID-reducing strategies exist.

    • Occupational Safety and Health
      • This study utilizes Gallup-ShareCare Well-being Index data to investigate the association between work-related well-being, i.e., job satisfaction, and overall subjective well-being among US workers. Subjective well-being is measured by i) daily positive and negative emotional experiences - happiness, smiles, enjoyment, sadness, anger, worry, and stress (hedonic well-being); and ii) current and future life evaluation (evaluative well-being). The study finds significant positive relationships between job satisfaction and subjective well-being both in terms of higher odds of positive hedonic experiences and increased life evaluation scores after controlling for covariates and other nonwork-related contributors to well-being. Job satisfaction accounted for a 14% increase in current and an 8% increase in future life evaluation scores. The results emphasize that not only the income generated by work but the quality of work is also important for worker well-being. In fact, those without a job had higher well-being than those workers who are dissatisfied at work. This is probably the first study that relates work-related well-being to overall well-being, using a nationally representative sample of US workers. Further, this is one of the few instances where the subjective measure of well-being is used in the occupational safety and health literature.

    • Parasitic Diseases
      • In 2010, the World Health Organization changed its guidance on malaria case management, recommending parasitological confirmation of all suspected cases before treatment with an antimalarial. This recommendation was in large part as a result of the availability of quality assured malaria rapid diagnostic tests (RDTs) that made it possible for malaria diagnosis to be performed by laboratory staff in all health facilities irrespective of the facility's place in the tiered health system. Community health workers and other non-laboratory health workers who traditionally did not perform malaria testing due to the technical and logistic demands of smear microscopy were now able to test for malaria. The use of RDTs has led to substantial increases in testing rates, improved quality of case management, as well as more accurate reporting of malaria cases. Although current RDTs have limitations, they remain one of the most important tools in contemporary malaria control. Further improvements to existing products, such as increased sensitivity for non-falciparum tests, diversification of Plasmodium falciparum antigen targets, along with strengthened health system support for current RDTs will further enhance their utility in malaria control and prevention.

    • Substance Use and Abuse
      • BACKGROUND: Deaths involving illicitly manufactured fentanyl (IMF) have increased since 2013 in the United States. Little research has examined individuals using IMF. This study aims to explore the characteristics of US adults who used IMF, heroin, or misused prescription opioids and examine the associations between demographic, clinical, psychosocial characteristics and IMF use. METHODS: A convenience sample of adults aged ≥ 18 years being assessed for substance use disorder (SUD) treatment was collected between January-December 2019 using the Addiction Severity Index-Multimedia Version instrument. We used a multivariable logistic regression model to examine the associations between demographic, clinical, psychosocial characteristics and IMF use. RESULTS: Adults reporting IMF as their primary lifetime substance use problem also reported using other substances-most often alcohol or heroin-both in the past 30 days and during their lifetime. Characteristics associated with increased odds of reporting IMF as the primary lifetime substance use problem included age 18-24 years (adjusted odds ratio (aOR) = 1.68; 95% confidence interval (CI) = 1.18-2.38) versus 45-54 years, non-Hispanic Black persons (aOR = 1.44; 95% CI = 1.11-1.85) versus non-Hispanic White persons, being assessed in Northeast (aOR = 15.46; 95% CI = 8.67-27.56) versus West, and having a history of at least one lifetime overdose (1 overdose (aOR = 1.91; 95% CI = 1.49-2.44); 2 overdoses (aOR = 1.95; 95% CI = 1.48-2.58); 3 or more overdoses (aOR = 2.27; 95% CI = 1.82-2.82)). CONCLUSIONS: These findings provide new insights into this high-risk population and help identify strategies to address increasing overdose death rates involving IMF. Opportunities for intervention include expanding naloxone distribution and harm reduction programs and connecting individuals with nonfatal overdoses to SUD treatment.

    • Veterinary Medicine
      • Determining the role of natural SARS-CoV-2 infection in the death of domestic pets: 10 cases (2020-2021)external icon
        Carpenter A, Ghai RR, Gary J, Ritter JM, Carvallo FR, Diel DG, Martins M, Murphy J, Schroeder B, Brightbill K, Tewari D, Boger L, Gabel J, Cobb R, Hennebelle J, Stanton JB, McCullough K, Mosley YC, Naikare HK, Radcliffe R, Parr B, Balsamo G, Robbins B, Smith D, Slavinski S, Williams C, Meckes D, Jones D, Frazier T, Steury K, Rooney J, Torchetti M, Wendling N, Currie D, Behravesh CB, Wallace RM.
        J Am Vet Med Assoc. 2021 Nov 1;259(9):1032-1039.
        OBJECTIVE: To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS: 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES: A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals' course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS: SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE: This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.


  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. Monitoring primary care providers' (PCP) attitudes and experiences with referrals of their patients with new-onset seizures or existing epilepsy/seizure disorders may help evaluate whether interventions to coordinate PCP and neurology care reduce treatment gaps and improve patient outcomes. To examine PCPs' attitudes toward, and experiences with, referral to specialty care of their patients with new-onset seizures or existing epilepsy/seizure disorders, we used cross-sectional 2018 DocStyles data to examine study outcomes. We selected a subsample of respondents who had a practice with at least 1% of patients with an epilepsy/seizure disorder and who answered questions about this disorder. We stratified provider actions, referral behavior, and referral enabling factors and barriers by epilepsy/seizure disorder caseload and provider type. We examined different patterns of responses by referral behavior and provider type. The final sample (n = 1284) included 422 family practitioners, 432 internists, 233 pediatricians, and 197 nurse practitioners. Most PCPs refer their patients with new-onset seizures to a neurologist, particularly to determine or confirm the diagnosis and appropriate treatment. Strikingly, about 40% of PCPs did not indicate a referral if their epilepsy/seizure disorder patient was unresponsive to treatment. Internists less likely referred their patients than pediatricians, nurse practitioners, or family practitioners. Less than one-third of all practitioners consulted seizure treatment guidelines. Prompt appointments, communication with the PCP, the patient's insurance, and referral back to primary care may facilitate referrals. Interventions that enhance enabling factors for guidelines-based care and that can increase opportunities for PCPs to consult with neurologists and/or refer their patients with uncontrolled seizures to specialty care are warranted.

      2. Linking the Paul Coverdell National Acute Stroke Program to commercial claims to establish a framework for real-world longitudinal stroke researchexternal icon
        Patorno E, Schneeweiss S, George MG, Tong X, Franklin JM, Pawar A, Mogun H, Moura L, Schwamm LH.
        Stroke Vasc Neurol. 2021 Nov 8.
        BACKGROUND: Non-interventional large-scale research on real-world patients who had a stroke requires the use of multiple data sources ensuring access to longitudinal data from large populations with clinically-detailed information. We sought to establish a framework for longitudinal research on patients hospitalised with stroke by linking information-rich, deidentified inpatient data from the Paul Coverdell National Acute Stroke Program (PCNASP) to commercial and Medicare Advantage longitudinal claims data. METHODS: All stroke admissions in PCNASP between 2008 and 2015 were evaluated for linkage to longitudinal claims from a commercial insurer using an algorithm based on six available common data fields (patient age, gender, admission date, discharge date, discharge diagnosis and state) and a hospital match. We evaluated the linkage quality (via the percentage of unique records in the linked dataset) and the representativeness of the linked population. We also described medical history, stroke severity and patterns of medication use among the PCNASP-claims linked cohort. RESULTS: The linkage produced uniqueness equal to 99.1%. We identified 5644 linked and 98 896 unlinked patients who had an ischaemic stroke hospitalisation in claims data. Linked patients were younger than unlinked (69.7 vs 72.5 years), but otherwise similar by medical history, prestroke medication use or lab values. Stroke severity was mild and most patients were discharged home. Prestroke and discharge use of antihypertensive and statins in the PCNASP were greater than their use as measured by filled prescriptions in claims. CONCLUSIONS: High-quality linkage between the PCNASP and commercial claims data is feasible. This linkage identified differences between reported or recommended versus actual out-of-hospital medication utilisation, highlighting the importance of longitudinal data availability for research aimed to improve the care of patients who had a stroke.

      3. Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patientsexternal icon
        Zhou M, Thompson TD, Lin HY, Chen VW, Karlitz JJ, Fontham ET, Theall KP, Zhang L, Hsieh MC, Pollack LA, Wu XC.
        Clin Colorectal Cancer. 2021 Oct 1.
        BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines have recommended tailored chemotherapy for stage III high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) colon cancer since 2018. Studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on stage III colon cancer survival, however, none has performed a stratified analysis by risk profiles. This study aims to identify the FOLFOX optimal RDI for high-risk and low-risk stage III colon cancer patients. METHODS: Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by 8 population-based cancer registries. Multivariable Cox model and Fine-Gray competing risks model were employed to explore Optimal RDI defined as the lowest RDI administered without significant differences in either overall or cause-specific death. RESULTS: Among the 168 high-risk patients, the optimal RDI cut-off was 70% (HR = 1.59 with 95% CI: 0.69-3.66 in overall mortality; HR = 1.24 with 95% CI: 0.42-3.64 in cause-specific mortality when RDI < 70% vs. RDI ≥ 70%). Among the 239 low-risk patients, none of the evaluated cut-offs were associated with significant differences in risk of death between comparison groups. The lowest assessed RDI was 45%, HR = 0.80; 95% CI: 0.24 to 2.73 for overall mortality and HR = 0.53; 95% CI: 0.06 to 4.95 for cause-specific mortality, when RDI <45% versus RDI ≥45%. CONCLUSIONS: There is no significant harm on the risk of death when reducing RDI by <30% for high-risk patients. For the low-risk patients, we found that RDI as low as 45% did not significantly affect the risk of death.

    • Communicable Diseases
      1. A literature review of severity scores for adults with influenza or community-acquired pneumonia - implications for influenza vaccines and therapeuticsexternal icon
        Adams K, Tenforde MW, Chodisetty S, Lee B, Chow EJ, Self WH, Patel MM.
        Hum Vaccin Immunother. 2021 Nov 10:1-15.
        Influenza vaccination and antiviral therapeutics may attenuate disease, decreasing severity of illness in vaccinated and treated persons. Standardized assessment tools, definitions of disease severity, and clinical endpoints would support characterizing the attenuating effects of influenza vaccines and antivirals. We review potential clinical parameters and endpoints that may be useful for ordinal scales evaluating attenuating effects of influenza vaccines and antivirals in hospital-based studies. In studies of influenza and community-acquired pneumonia, common physiologic parameters that predicted outcomes such as mortality, ICU admission, complications, and duration of stay included vital signs (hypotension, tachypnea, fever, hypoxia), laboratory results (blood urea nitrogen, platelets, serum sodium), and radiographic findings of infiltrates or effusions. Ordinal scales based on these parameters may be useful endpoints for evaluating attenuating effects of influenza vaccines and therapeutics. Factors such as clinical and policy relevance, reproducibility, and specificity of measurements should be considered when creating a standardized ordinal scale for assessment.

      2. HIV Prevention Program Eligibility Among Adolescent Girls and Young Women - Namibia, 2019external icon
        Agathis NT, Annor FB, Coomer R, Hegle J, Patel P, Forster N, O'Malley G, Ensminger AL, Kamuingona R, Andjamba H, Manyando M, Massetti GM.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 12;70(45):1570-1574.
        The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) relies on comprehensive and reliable population data to implement interventions to reduce HIV transmission in high-incidence areas among populations disproportionately affected by the HIV epidemic. Adolescent girls and young women in sub-Saharan Africa account for a disproportionate number of new HIV infections compared with their male peers (1). The DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe) program includes multisectoral, layered interventions aimed at reducing factors that contribute to vulnerability to HIV infection among adolescent girls and young women in PEPFAR-supported sub-Saharan African countries (1). Namibia, a southern African country with a population of approximately 2.55 million among whom approximately 8% live with HIV infection, had their DREAMS program first implemented in 2017* (2,3). Data from the 2019 Namibia Violence Against Children and Youth Survey (VACS), the most recent and comprehensive nationally representative data source available to study the epidemiology of violence and other HIV risk factors, were used to estimate the percentage of adolescent girls and young women aged 13-24 years who would be eligible for DREAMS program services. The prevalence of individual DREAMS eligibility criteria, which comprise known age-specific risk factors associated with HIV acquisition, were estimated by age group. Among all adolescent girls and young women in Namibia, 62% were eligible for DREAMS based on meeting at least one criterion. Common eligibility criteria included adverse childhood experiences, specifically exposure to physical, emotional, and sexual violence and being an orphan;(†) and high-risk behaviors, such as early alcohol use,(§) recent heavy alcohol use,(¶) and infrequent condom use.** Using VACS data to estimate the prevalence of HIV risk factors and identify adolescent girls and young women at elevated risk for HIV acquisition in countries like Namibia with high HIV-incidence can inform programs and policies aimed at improving the well-being of these adolescent girls and young women and help control the HIV epidemics in these countries.

      3. Population-Based Estimates of Coronavirus Disease 2019 (COVID-19)-like Illness, COVID-19 Illness, and Rates of Case Ascertainment, Hospitalizations, and Deaths-Noninstitutionalized New York City Residents, March-April 2020external icon
        Alroy KA, Crossa A, Dominianni C, Sell J, Bartley K, Sanderson M, Fernandez S, Levanon Seligson A, Lim S, Wang SM, Dumas SE, Perlman SE, Konty K, Olson DR, Gould LH, Greene SK.
        Clin Infect Dis. 2021 Nov 2;73(9):1707-1710.
        Using a population-based, representative telephone survey, ~930 000 New York City residents had COVID-19 illness beginning 20 March-30 April 2020, a period with limited testing. For every 1000 persons estimated with COVID-19 illness, 141.8 were tested and reported as cases, 36.8 were hospitalized, and 12.8 died, varying by demographic characteristics.

      4. Impact of isolation and exclusion as a public health strategy to contain measles virus transmission during a measles outbreakexternal icon
        Banerjee E, Paul P, Griffith J, Laine E, Como-Sabetti K, Gastañaduy PA.
        Clin Infect Dis. 2021 Nov 10.
        Responding to measles outbreaks in the United States puts a considerable strain on public health resources, and limited research exists about the effectiveness of containment strategies. In this paper we quantify the impact of isolation, contact tracing, and exclusion in reducing transmission during a measles outbreak in an under-vaccinated community.

      5. Treatment Practices for Adults With Candidemia at 9 Active Surveillance Sites-United States, 2017-2018external icon
        Gold JA, Seagle EE, Nadle J, Barter DM, Czaja CA, Johnston H, Farley MM, Thomas S, Harrison LH, Fischer J, Pattee B, Mody RK, Phipps EC, Davis SS, Tesini BL, Zhang AY, Markus TM, Schaffner W, Lockhart SR, Vallabhaneni S, Jackson BR, Lyman M.
        Clin Infect Dis. 2021 Nov 2;73(9):1609-1616.
        BACKGROUND: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. METHODS: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. RESULTS: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. CONCLUSIONS: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

      6. National Surveillance for Acute Flaccid Myelitis - United States, 2018-2020external icon
        Kidd S, Yee E, English R, Rogers S, Emery B, Getachew H, Routh JA, Lopez AS.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 5;70(44):1534-1538.
        Acute flaccid myelitis (AFM), a recognized complication of certain viral infections, is a serious neurologic condition that predominantly affects previously healthy children and can progress rapidly, leading to respiratory insufficiency and permanent paralysis. After national AFM surveillance began in 2014, peaks in AFM cases were observed in the United States in 2014, 2016, and 2018 (1). On the basis of this biennial pattern, an increase in AFM was anticipated in 2020. To describe the epidemiology of confirmed AFM cases since 2018, demographic, clinical, and laboratory information collected as part of national AFM surveillance was reviewed. In 2018, a total of 238 confirmed AFM cases were reported to CDC, compared with 47 cases in 2019 and 32 in 2020. Enterovirus D68 (EV-D68) was detected in specimens from 37 cases reported in 2018, one case in 2019 and none in 2020. Compared with 2018, cases reported during 2019-2020 occurred in older children and were less frequently associated with upper limb involvement, febrile or respiratory prodromal illness, or cerebrospinal fluid (CSF) pleocytosis. These findings suggest that the etiologies of AFM in 2019 and 2020 differed from those in 2018. The absence of an increase in cases in 2020 reflects a deviation from the previously observed biennial pattern, and it is unclear when the next increase in AFM should be expected. Clinicians should continue to maintain vigilance and suspect AFM in any child with acute flaccid limb weakness, particularly in the setting of recent febrile or respiratory illness.

      7. Assessment of SARS-CoV-2 Seroprevalence by Community Survey and Residual Specimens, Denver, Colorado, July-August 2020external icon
        Kugeler KJ, Podewils LJ, Alden NB, Burket TL, Kawasaki B, Biggerstaff BJ, Biggs HM, Zacks R, Foster MA, Lim T, McDonald E, Tate JE, Herlihy RK, Drobeniuc J, Cortese MM.
        Public Health Rep. 2021 Nov 9:333549211055137.
        OBJECTIVES: The number of SARS-CoV-2 infections is underestimated in surveillance data. Various approaches to assess the seroprevalence of antibodies to SARS-CoV-2 have different resource requirements and generalizability. We estimated the seroprevalence of antibodies to SARS-CoV-2 in Denver County, Colorado, via a cluster-sampled community survey. METHODS: We estimated the overall seroprevalence of antibodies to SARS-CoV-2 via a community seroprevalence survey in Denver County in July 2020, described patterns associated with seroprevalence, and compared results with cumulative COVID-19 incidence as reported to the health department during the same period. In addition, we compared seroprevalence as assessed with a temporally and geographically concordant convenience sample of residual clinical specimens from a commercial laboratory. RESULTS: Based on 404 specimens collected through the community survey, 8.0% (95% CI, 3.9%-15.7%) of Denver County residents had antibodies to SARS-CoV-2, an infection rate of about 7 times that of the 1.1% cumulative reported COVID-19 incidence during this period. The estimated infection-to-reported case ratio was highest among children (34.7; 95% CI, 11.1-91.2) and males (10.8; 95% CI, 5.7-19.3). Seroprevalence was highest among males of Black race or Hispanic ethnicity and was associated with previous COVID-19-compatible illness, a previous positive SARS-CoV-2 test result, and close contact with someone who had confirmed SARS-CoV-2 infection. Testing of 1598 residual clinical specimens yielded a seroprevalence of 6.8% (95% CI, 5.0%-9.2%); the difference between the 2 estimates was 1.2 percentage points (95% CI, -3.6 to 12.2 percentage points). CONCLUSIONS: Testing residual clinical specimens provided a similar seroprevalence estimate yet yielded limited insight into the local epidemiology of COVID-19 and might be less representative of the source population than a cluster-sampled community survey. Awareness of the limitations of various sampling strategies is necessary when interpreting findings from seroprevalence assessments.


      9. Temperature and Oxygen Saturation in SNF Residents Positive for SARS-CoV-2 Prior to Symptom Onsetexternal icon
        Lehnertz NB, Lifson A, Galloway E, Taylor J, Carter RJ, Kazazian L, Day K, Miller S, Mendez E, Lynfield R.
        J Am Geriatr Soc. 2021 Nov 9.
        BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spreads rapidly amongst residents of skilled nursing facilities (SNFs). The rapid transmission dynamics and high morbidity and mortality that occur in SNFs emphasize the need for early detection of cases. We hypothesized that residents of SNFs infected with SARS-CoV-2 would demonstrate an acute change in either temperature or oxygen saturation (SpO2) prior to symptom onset. The Minnesota Department of Health (MDH) conducted a retrospective analysis of both temperature and SpO2 at two separate SNFs to assess the utility of these quantitative markers to identify SARS-CoV-2 infection prior to the development of symptoms. METHODS: A retrospective analysis was conducted of 165 individuals positive for SARS-CoV-2 that were residents in in SNFs that experienced COVID-19 outbreaks during April-June 2020 in a metropolitan area of Minnesota. Age, sex, symptomology, temperature and SpO2 values, date of symptom onset and date of positive SARS-CoV-2 test were analyzed. Temperature and SpO2 values for the period 14 days before and after date of initial positive test were included. Descriptive analyses evaluated changes in temperature and SpO2, defined as either exceeding a set threshold or demonstrating an acute change between consecutive measurements. RESULTS: Two (1%) residents had a temperature value ≥100(o) F, and 30 (18%) had at least one value ≥99(o) F within 14 days before symptom development. One hundred and sixteen residents (70%) had at least one SpO2 value ≤94% while 131 (80%) had an acute decrease in SpO2 of ≥3% between consecutive values in the 14 days prior to symptom onset. CONCLUSIONS: Our results suggest that acute change in SpO2 might be useful in identification of SARS-CoV-2 infection prior to the development of symptoms among residents living in SNFs. Facilities may consider adding SpO2 to daily temperature and symptom screening checklists to improve early detection of residents of SNFs infected with SARS-CoV-2.

      10. PROBLEM: Sexually transmitted diseases (STDs) are a major cause of morbidity in the United States, with an estimated $15.9 billion in lifetime direct medical costs. Although the majority of STDs are diagnosed in the private sector, publicly funded STD clinics have an important role in providing comprehensive sexual health care services, including STD and HIV screening, for a broad range of patients. In certain cases, STD clinics often are the only source of sexual health care for patients, particularly among gay, bisexual, and other men who have sex with men (MSM). PERIOD COVERED: 2010-2018. DESCRIPTION OF THE SYSTEM: The STD Surveillance Network (SSuN) is an ongoing sentinel surveillance system for monitoring clinical information among patients attending STD clinics. SSuN is a collaboration of competitively selected state and city health departments that conduct facility-based sentinel surveillance in STD clinics. Information routinely collected through the course of patient encounters is obtained for all patients seeking care in the participating STD clinics. This information includes demographic, behavioral, and clinical characteristics (e.g., STD and HIV tests performed and STD and HIV diagnoses). This report presents 2010-2018 SSuN data from 14 STD clinics in five cities (Baltimore, Maryland; New York City, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington) to describe the patient populations seeking care in these STD clinics. Estimated numbers and percentages of patients receiving selected STD-related health services were calculated for each year by using an inverse variance weighted random-effects model, adjusting for heterogeneity among SSuN jurisdictions. Trends in receipt of selected STD-related health services were examined and included HIV screening after an acute STD diagnosis among persons not previously known to have HIV infection, annual chlamydia screening among adolescent and young females, and extragenital chlamydia and gonorrhea screening among MSM. RESULTS: During 2010-2018, the total number of annual visits made in the 14 participating STD clinics decreased 29.8% (from 145,728 to 102,275 visits), and the total number of unique patients examined in the clinics decreased 35.1% (from 94,281 to 61,172 patients). Decreases in the number of unique patients occurred both among men who have sex with women only (42.4%; from 37,842 in 2010 to 21,781 in 2018) and among females (51.4%; from 36,485 in 2010 to 17,721 in 2018). The decreases in the number of female patients were observed across all age groups, although they were more pronounced among females aged ≤24 years (66.4%; from 17,721 in 2010 to 5,962 in 2018). In contrast, the number of patients identified as MSM increased 44.0% (from 12,859 in 2010 to 18,512 in 2018), with the greatest increase among MSM aged ≥25 years (58.6%; from 9,918 in 2010 to 15,733 in 2018). Among visits during which an acute STD (defined as chlamydia, gonorrhea, or primary or secondary syphilis) was diagnosed, the percentage of visits during which an HIV test was performed within approximately 14 days of the STD diagnosis increased from 58.2% in 2010 to 70.2% in 2018. Among those patients tested, 1,672 HIV infections were identified, of which 84.0% were among MSM. Among females aged 15-24 years, the percentage screened for chlamydia in any calendar year increased from 88.6% in 2010 to 90.6% in 2018. However, because fewer females aged 15-24 years attended these clinics during the study period, the crude number of adolescent and young females tested for chlamydia decreased from 14,249 in 2010 to 4,507 in 2018. During 2010-2018, the percentage of females retested after their first positive chlamydia diagnosis during the same year ranged from 11.4% to 13.3%. During 2010-2018, the percentage of MSM tested for rectal chlamydia and rectal gonorrhea increased (from 54.7% to 57.8% and from 55.0% to 58.4%, respectively). During the same period, increases were noted in the percentage of MSM with diagnosed rectal chlamydia (from 15.5% in 2010 to 17.7% in 2018) and rectal gonorrhea (from 13.3% in 2010 to 17.1% in 2018). In contrast with pharyngeal chlamydia, pharyngeal gonorrhea screening was more common (from 69.5% in 2010 to 74.6% in 2018), and the percentage positive doubled during the study period (from 7.3% in 2010 to 14.8% in 2018). Pharyngeal chlamydia testing also increased (from 50.3% in 2010 to 72.9% in 2018), with concurrent decreases in positivity (from 4.2% in 2010 to 2.6% in 2018). INTERPRETATION: During 2010-2018, changes occurred in the demographic composition of patients attending STD clinics participating in SSuN. Understanding trends in the demographic profile of STD patients and services provided can help identify addressable gaps in STD control efforts and direct public health action. Overall, fewer females, especially those aged 15-24 years, accessed care in these STD clinics during the study period. Untreated STDs among adolescent and young females can have serious consequences, including pelvic inflammatory disease and infertility. Additional efforts to monitor where adolescent and young females seek care and to ensure they are receiving quality STD-related health services are needed, especially considering increases in reported cases of STDs among females. Increases in the number of MSM attending STD clinics present a unique opportunity to reach this population with STD and HIV prevention services. Although a large percentage of STD cases are diagnosed outside of STD clinics, publicly funded STD clinics are an important safety-net provider of STD-related health services and provide vital STD-related health services for patient populations at risk for the consequences of STDs and HIV infection. PUBLIC HEALTH ACTIONS: STD-related health services represent effective strategies for preventing STD and HIV transmission and acquisition or STD-related sequelae. Ensuring that all persons receive quality HIV and STD prevention and treatment services is vital for an effective public health approach to reducing STDs. STD clinics provide crucial safety-net services for preventing STD-related morbidity, including timely identification and treatment of curable STDs such as chlamydia, gonorrhea, and syphilis. Increases in the numbers of MSM attending STD clinics participating in SSuN provide additional opportunities for linking patients to high-impact HIV preventive services (e.g., pre-exposure prophylaxis), and the clinics are positioned to facilitate initiation or resumption of treatment among persons living with HIV.

      11. A socio-ecological analysis of factors influencing HIV treatment initiation and adherence among key populations in Papua New Guineaexternal icon
        Mitchell E, Hakim A, Nosi S, Kupul M, Boli-Neo R, Aeno H, Redman-Maclaren M, Ase S, Amos A, Hou P, Narokobi R, Willie B, Vallely AJ, Kaldor JM, Badman SG, Kelly-Hanku A.
        BMC Public Health. 2021 Nov 4;21(1):2003.
        BACKGROUND: In Papua New Guinea (PNG) members of key populations, including female sex workers (FSW), men who have sex with men (MSM) and transgender women (TGW), have higher rates of HIV compared to the general adult population and low engagement in HIV care. This paper examines the socio-ecological factors that encourage or hinder HIV treatment initiation and adherence among HIV positive members of key populations in PNG. METHODS: As part of a larger biobehavioural survey of key populations in PNG, 111 semi-structured interviews were conducted with FSW, MSM and TGW, of whom 28 identified as living with HIV. Interviews from 28 HIV positive participants are used in this analysis of the influences that enabled or inhibited HIV treatment initiation and treatment adherence. RESULTS: Enablers included awareness of the biomedical benefits of treatment; experiences of the social, familial and health benefits of early treatment initiation and adherence; support provided by family and friends; and non-judgmental and supportive HIV service provision. Factors that inhibited treatment initiation and adherence included perception of good health and denial of HIV diagnosis; poor family support following positive diagnosis; and anonymity and stigma concerns in HIV care services. CONCLUSION: Exploring health promotion messages that highlight the positive health impacts of early treatment initiation and adherence; providing client-friendly services and community-based treatment initiation and supply; and rolling out HIV viral load testing across the country could improve health outcomes for these key populations.

      12. Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenyaexternal icon
        Neary J, Langat A, Singa B, Kinuthia J, Itindi J, Nyaboe E, Ng'anga LW, Katana A, John-Stewart GC, McGrath CJ.
        Aids. 2021 Nov 8.
        BACKGROUND: With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children. METHODS: We analyzed data from a population-level survey enrolling mother-infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ<-2), stunting (LAZ<-2), and microcephaly (HCAZ<-2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models. RESULTS: Among 2,457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy and 22% were on antiretroviral prophylaxis during pregnancy. At 9-months, 72% of HEU and 98% of HUU were breastfeeding. At 6-weeks, HEU had lower mean WAZ (-0.41 vs. -0.09; p < 0.001) and LAZ (-0.99 vs. -0.31; p = 0.001) than HUU. Stunting was higher in HEU than HUU at 6-weeks (34% vs 18%, p < 0.001) and 9-months (20% vs 10%, p < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6-weeks (-0.67, 95%CI: -1.07, -0.26) and 9-months (-0.57, 95%CI: -0.92, -0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95%CI: 1.35, 2.63; month-9 aPR: 2.10, 95%CI: 1.41, 3.13). HEU had lower mean head circumference (-0.49, 95%CI: -0.91, -0.07) and higher prevalence of microcephaly (aPR: 2.21, 95%CI: 1.11, 4.41) at 9-months. CONCLUSION: Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.

      13. Repeat Syphilis Among HIV-Infected Men in Florida and Louisiana 2000-2018: Implications for Screening Recommendationsexternal icon
        Newman DR, Matthias J, Rahman MM, Brantley A, Peterman TA.
        AIDS Patient Care STDS. 2021 Nov;35(11):435-440.
        Syphilis rates have continued to rise in the United States. Florida and Louisiana consistently report high numbers of cases. We evaluated rates of reinfection to see if frequent rescreening might lead to earlier treatment and prevent infections. All syphilis records of all stages for males and females aged 15-70 years from the Florida and Louisiana Departments of Health surveillance databases 2000-2018 were evaluated. The first episode of syphilis during this period was considered the initial diagnosis for each person. Demographics of cases and repeaters (individuals reported with two or more cases of syphilis) were examined. Percentages of syphilis cases from repeaters by year were calculated as were percentages from HIV+ males. During 2000-2018, 124,827 syphilis cases were reported from 107,405 individuals: 73,811 (68.7%) males; 33,594 (31.3%) females. There were 12,545 individuals (repeaters) with two or more syphilis diagnoses (n = 17,422 cases; range, 2-10). From 2010 to 2018, repeaters accounted for steadily increasing percentage of all syphilis reported: 2010 (11%), 2013 (16%), 2015 (20%), and 2018 (26%). Among HIV+ male cases the percentage from repeaters also increased: 2010 (28%), 2013 (35%), 2015 (42%), and 2018 (50%). In 2018, 19% of all cases (n = 2455) were from HIV+ males who had a previous syphilis diagnosis. Among HIV+ males diagnosed with syphilis in 2015, 34% had a repeat syphilis diagnosis within 3 years. Most syphilis diagnosed in Florida and Louisiana was among persons infected for the first time. However, some subgroups could possibly benefit from more frequent screening. Males living with HIV who had a prior syphilis diagnosis were at very high risk of repeat infection.

      14. Respiratory Illness Caused by Corynebacterium diphtheriae and C. ulcerans, and Use of Diphtheria Antitoxin in the United States, 1996-2018external icon
        Otshudiema JO, Acosta AM, Cassiday PK, Hadler SC, Hariri S, Tiwari TS.
        Clin Infect Dis. 2021 Nov 2;73(9):e2799-e2806.
        BACKGROUND: Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by Corynebacterium ulcerans, a zoonotic bacterium that can also produce diphtheria toxin. In the United States, respiratory diphtheria is nationally notifiable: specimens from suspected cases are submitted to the Centers for Disease Control and Prevention (CDC) for species and toxin confirmation, and diphtheria antitoxin (DAT) is obtained from CDC for treatment. We summarize the epidemiology of respiratory diphtheria and diphtheria-like illness and describe DAT use during 1996-2018 in the United States. METHODS: We described respiratory diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and C. ulcerans-related diphtheria-like illness identified through specimen submissions to CDC during 1996-2018. We reviewed DAT requests from 1997 to 2018. RESULTS: From 1996 to 2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were nontoxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but polymerase chain reaction (PCR)-positive for diphtheria toxin gene, 1 was culture-positive without further testing, and the remaining 3 were either not tested or tested negative. Five cases of respiratory diphtheria-like illness caused by toxigenic C. ulcerans were identified. DAT was requested by healthcare providers for 151 suspected diphtheria cases between 1997 and 2018, with an average of 11 requests per year from 1997 to 2007, and 3 per year from 2008 to 2018. CONCLUSIONS: Respiratory diphtheria remains rare in the United States, and requests for DAT have declined. Incidental identification of C. ulcerans-related diphtheria-like illness suggests surveillance of this condition might be warranted.


      16. Lack of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Large Cohort of Previously Infected Personsexternal icon
        Petersen LR, Sami S, Vuong N, Pathela P, Weiss D, Morgenthau BM, Henseler RA, Daskalakis DC, Atas J, Patel A, Lukacs S, Mackey L, Grohskopf LA, Thornburg N, Akinbami LJ.
        Clin Infect Dis. 2021 Nov 2;73(9):e3066-e3073.
        BACKGROUND: Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable immunoglobulin G (IgG) antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2. METHODS: We analyzed serologic data collected from healthcare workers and first responders in New York City and the Detroit metropolitan area with a history of a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset. RESULTS: Of 2547 persons with previously confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (P = .06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons who took immunosuppressive medications were more likely to be seronegative (31.9%; 95% confidence interval [CI], 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (vs non-Hispanic White; 2.7%; 95% CI, 1.5%-4.8%), with severe obesity (vs under/normal weight; 3.9%; 95% CI, 1.7%-8.6%), or with more symptoms were less likely to be seronegative. CONCLUSIONS: In our population with previous RT-PCR-confirmed infection, approximately 1 in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.

      17. BACKGROUND AND AIMS: In the United States, respiratory infections due to respiratory syncytial virus (RSV) cause an estimated 57 000 hospitalizations annually among children aged <5 years and 177 000 hospitalizations among adults aged ≥65 years. RSV-associated deaths are less well described. It will be important to establish a baseline of RSV-coded deaths prior to the introduction of vaccines, immunoprophylaxis products, and anti-viral therapies currently in development. METHODS: US death certificate data for all ages from 2005 through 2016 were compiled through the National Center for Health Statistics. Deaths with International Classification of Diseases codes of J12.1 (RSV-pneumonia), J20.5 (RSV-bronchitis), or J21.0 (RSV-bronchiolitis) assigned as either the underlying cause of death or a contributing cause of death were considered "RSV-associated" for this analysis. RESULTS: Among 30.5 million deaths, 1001 (.003%) were assigned an RSV-associated cause of death as follows: 697 (69.6%) RSV-pneumonia, 277 (27.7%) RSV-bronchiolitis, 17 (1.7%) RSV-bronchitis, and 10 (1.0%) with multiple RSV-associated causes. Most deaths were among children <5 (47.8%) and adults ≥50 (40.4%) years of age. Almost half (46.8%) had an RSV-associated cause as the primary underlying cause of death. The average annual number of RSV-associated deaths did not significantly change among those aged <5 and 5 to 49 years. However, RSV-pneumonia deaths among adults aged ≥50 years increased from 17.6 in 2005 to 2012 to 57.3 in 2013 to 2016 (P value <.0001). CONCLUSIONS: From 2005 to 2016, the number of recorded RSV-associated deaths increased, primarily due to greater RSV-associated pneumonia deaths among older adults since 2013. The reasons for this increase are not clear but likely reflect increased testing for RSV among adults. The number of RSV-associated deaths according to death certificates compared with estimates derived from active, laboratory-confirmed surveillance and models using hospital administrative data suggests that counts from death certificates are a large underestimation, particularly among adults.

      18. BACKGROUND: Shigellosis, an acute diarrheal disease, is the third most common bacterial infection in the United States. Shigellosis most commonly affects children under the age of 5; however, clusters and outbreaks of shigellosis have been reported among gay, bisexual, and other men who have sex with men (MSM). Evidence suggests that knowledge of shigellosis among MSM is low, indicating health promotion outreach is needed for this population. METHODS: To inform the development of shigellosis-related health communication materials and strategies, six focus groups were conducted in 2017, in Atlanta, Georgia among 24 self-identified gay and bisexual men. Participants were asked about their preferences and recommendations for health communication materials. RESULTS: Participants indicated they would prefer a range of physical and virtual materials placed in diverse locations where the community would see them. Respondents recommended health messages be simple, quick to read, and concise and have limited word counts. Participants also advised the use of diverse images that were inclusive of couples of varying sexual orientations to reduce stigma. Participants advocated for the use of humor and provocative images to increase user engagement. CONCLUSIONS: The results emphasize the potential benefits of conducting formative research when designing health communication materials. Incorporating messaging preferences of MSM in the development of shigellosis-related health communication materials could enhance their relevance for the target population, while also avoiding unintended consequences associated with stigmatizing MSM.

      19. Identification of a Human Immunodeficiency Virus Type 1 and Neurosyphilis Cluster in Vermontexternal icon
        Singh D, Switzer WM, Belcher R, Daltry D, Read JS.
        Clin Infect Dis. 2021 Nov 2;73(9):e3244-e3249.
        BACKGROUND: Rates of syphilis in the United States have more than doubled over the last several decades, largely among men who have sex with men (MSM). Our study characterizes a cluster of neurosyphilis cases among people with human immunodeficiency virus 1 (HIV-1) in Vermont in 2017-2018. METHODS: Vermont Department of Health disease intervention specialists conduct interviews with newly diagnosed HIV-1 cases and pursue sexual networking analyses. Phylogenetic and network analyses of available Vermont HIV-1 polymerase (pol) sequences identified clusters of infection. Fishers-exact and independent t-tests were used to compare people with HIV-1 within or outside an identified cluster. RESULTS: Between 1 January 2017 and 31 December 2018, 38 residents were diagnosed with HIV-1 infection. The mean age was 35.5 years, 79% were male and 82% were White. Risk factors for HIV-1 included MSM status (79%) and methamphetamine use (21%). Eighteen cases (49%) had HIV-1 viral loads (VLs) >100 000 copies/mL and 47% had CD4 cell counts <200/mm3. Eleven of the 38 (29%) had positive syphilis serology, including four (36%) with neurosyphilis. Sexual networking analysis revealed a ten-person cluster with higher VLs at diagnosis (90% with VLs > 100 000 copies/mL vs 33%, P = 0.015). Phylogenetic analysis of pol sequences showed a cluster of 14 cases with sequences that shared 98%-100% HIV-1 nucleotide identity. CONCLUSIONS: This investigation of newly infected HIV-1 cases in Vermont led to identification of a cluster that appeared more likely to have advanced HIV-1 disease and neurosyphilis, supported by phylogenetic and network analyses.

      20. Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidityexternal icon
        Thomas AS, Moreau Y, Jiang W, Isaac JE, Ewing A, White LF, Kourtis AP, Sagar M.
        Cell Rep Med. 2021 Oct 19;2(10):100412.
        In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother's strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity.

      21. Influenzaexternal icon
        Uyeki TM.
        Ann Intern Med. 2021 Nov 9.
        Seasonal influenza epidemics of variable severity pose challenges to public health. Annual vaccination is the primary way to prevent influenza, and a wide range of vaccines are available, including inactivated or live attenuated standard-dose, recombinant vaccines, as well as adjuvanted or high-dose vaccines for persons aged 65 years or older. Persons at increased risk for influenza complications include young children, persons with underlying medical conditions, and older adults. Prompt diagnosis of influenza can facilitate early initiation of antiviral treatment that provides the greatest clinical benefit. This article summarizes recommendations for providers on influenza vaccination, diagnostic testing, and antiviral treatment.

      22. Coronavirus Disease 2019 (COVID-19) Prevalences Among People Experiencing Homelessness and Homelessness Service Staff During Early Community Transmission in Atlanta, Georgia, April-May 2020external icon
        Yoon JC, Montgomery MP, Buff AM, Boyd AT, Jamison C, Hernandez A, Schmit K, Shah S, Ajoku S, Holland DP, Prieto J, Smith S, Swancutt MA, Turner K, Andrews T, Flowers K, Wells A, Marchman C, Laney E, Bixler D, Cavanaugh S, Flowers N, Gaffga N, Ko JY, Paulin HN, Weng MK, Mosites E, Morris SB.
        Clin Infect Dis. 2021 Nov 2;73(9):e2978-e2984.
        BACKGROUND: In response to reported coronavirus disease 2019 (COVID-19) outbreaks among people experiencing homelessness (PEH) in other US cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and associated symptoms, and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during 7 April-6 May 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2875 individuals at 24 shelters and 9 unsheltered outreach events underwent SARS-CoV-2 testing, and 2860 (99.5%) had conclusive test results. The SARS-CoV-2 prevalences were 2.1% (36/1684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases, compared with RT-PCR. Prevalences by shelter ranged 0-27.6%. Repeat testing 3-4 weeks later at 4 shelters documented decreased SARS-CoV-2 prevalences (0-3.9%). Of 24 shelters, 9 completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced a higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for the identification and isolation of COVID-19 cases, and is an important strategy to interrupt SARS-CoV-2 transmission.

    • Disease Reservoirs and Vectors
      1. Use of Cervid Serosurveys to Monitor Eastern Equine Encephalitis Virus Activity in Northern New England, United States, 2009-2017external icon
        Mutebi JP, Mathewson AA, Elias SP, Robinson S, Graham AC, Casey P, Lubelczyk CB.
        J Med Entomol. 2021 Nov 4.
        Vertebrate surveillance for eastern equine encephalitis virus (EEEV) activity usually focuses on three types of vertebrates: horses, passerine birds, and sentinel chicken flocks. However, there is a variety of wild vertebrates that are exposed to EEEV infections and can be used to track EEEV activity. In 2009, we initiated a pilot study in northern New England, United States, to evaluate the effectiveness of using wild cervids (free-ranging white-tailed deer and moose) as spatial sentinels for EEEV activity. In Maine, New Hampshire, and Vermont during 2009-2017, we collected blood samples from hunter-harvested cervids at tagging stations and obtained harvest location information from hunters. U.S. Centers for Disease Control and Prevention processed the samples for EEEV antibodies using plaque reduction neutralization tests (PRNTs). We detected EEEV antibodies in 6 to 17% of cervid samples in the different states and mapped cervid EEEV seropositivity in northern New England. EEEV antibody-positive cervids were the first detections of EEEV activity in the state of Vermont, in northern Maine, and northern New Hampshire. Our key result was the detection of the antibodies in areas far outside the extent of documented wild bird, mosquito, human case, or veterinary case reports of EEEV activity in Maine, New Hampshire, and Vermont. These findings showed that cervid (deer and moose) serosurveys can be used to characterize the geographic extent of EEEV activity, especially in areas with low EEEV activity or with little or no EEEV surveillance. Cervid EEEV serosurveys can be a useful tool for mapping EEEV activity in areas of North America in addition to northern New England.

    • Drug Safety
      1. US Emergency Department Visits for Acute Harms from Over-the-Counter Cough and Cold Medications, 2017-2019external icon
        Mital R, Lovegrove MC, Moro RN, Geller AI, Weidle NJ, Lind JN, Budnitz DS.
        Pharmacoepidemiol Drug Saf. 2021 Nov 10.
        BACKGROUND AND PURPOSE: Characterization of emergency department (ED) visits for acute harms related to use of over-the-counter cough and cold medications (CCMs) by patient demographics, intent of CCM use, concurrent substance use, and clinical manifestations can help guide prevention of medication harms. METHODS: Public health surveillance data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used to estimate numbers and population rates of ED visits from 2017-2019. RESULTS: Based on 1,396 surveillance cases, there were an estimated 26,735 (95% CI, 21,679-31,791) US ED visits for CCM-related harms annually, accounting for 1.3% (95% CI, 1.2%-1.5%) of all ED visits for medication adverse events. Three fifths (61.4%, 95% CI, 55.6%-67.2%) of these visits were attributed to non-therapeutic CCM use (nonmedical use, self-harm, unsupervised pediatric exposures). Most visits by children aged <4 years (74.0%, 95% CI, 59.7%-88.3%) were for unsupervised CCM exposures. Proportion hospitalized was higher for visits for self-harm (76.5%, 95% CI, 68.9%-84.2%) than for visits for nonmedical use (30.3%, 95% CI, 21.1%-39.6%) and therapeutic use (8.8%, 95% CI, 5.9%-11.8%). Overall, estimated population rates of ED visits for CCM-related harms were higher for patients aged 12-34 years (16.5 per 100,000, 95% CI, 13.0-20.0) compared with patients aged <12 years (5.1 per 100,000, 95% CI, 3.6-6.5) and ≥35 years (4.3 per 100,000, 95% CI, 3.4-5.1). Concurrent use of other medications, illicit drugs, or alcohol was frequent in ED visits for nonmedical use (61.3%) and self-harm (75.9%). CONCLUSIONS: Continued national surveillance of CCM-related harms can assess progress toward safer use.

    • Food Safety
      1. Genome-Enabled Molecular Subtyping and Serotyping for Shiga Toxin-Producing Escherichia coliexternal icon
        Im SB, Gupta S, Jain M, Chande AT, Carleton HA, Jordan IK, Rishishwar L.
        Frontiers in Sustainable Food Systems. 2021 ;5.
        Foodborne pathogens are a major public health burden in the United States, leading to 9.4 million illnesses annually. Since 1996, a national laboratory-based surveillance program, PulseNet, has used molecular subtyping and serotyping methods with the aim to reduce the burden of foodborne illness through early detection of emerging outbreaks. PulseNet affiliated laboratories have used pulsed-field gel electrophoresis (PFGE) and immunoassays to subtype and serotype bacterial isolates. Widespread use of serotyping and PFGE for foodborne illness surveillance over the years has resulted in the accumulation of a wealth of routine surveillance and outbreak epidemiological data. This valuable source of data has been used to understand seasonal frequency, geographic distribution, demographic information, exposure information, disease severity, and source of foodborne isolates. In 2019, PulseNet adopted whole genome sequencing (WGS) at a national scale to replace PFGE with higher-resolution methods such as the core genome multilocus sequence typing. Consequently, PulseNet's recent shift to genome-based subtyping methods has rendered the vast collection of historic surveillance data associated with serogroups and PFGE patterns potentially unusable. The goal of this study was to develop a bioinformatics method to associate the WGS data that are currently used by PulseNet for bacterial pathogen subtyping to previously characterized serogroup and PFGE patterns. Previous efforts to associate WGS to PFGE patterns relied on predicting DNA molecular weight based on restriction site analysis. However, these approaches failed owing to the non-uniform usage of genomic restriction sites by PFGE restriction enzymes. We developed a machine learning approach to classify isolates to their most probable serogroup and PFGE pattern, based on comparisons of genomic k-mer signatures. We applied our WGS classification method to 5,970 Shiga toxin-producing Escherichia coli (STEC) isolates collected as part of PulseNet's routine foodborne surveillance activities between 2003 and 2018. Our machine learning classifier is able to associate STEC WGS to higher-level serogroups with very high accuracy and lower-level PFGE patterns with somewhat lower accuracy. Taken together, these classifications support the ability of public health investigators to associate currently generated WGS data with historical epidemiological knowledge linked to serogroups and PFGE patterns in support of outbreak surveillance for food safety and public health. © Copyright © 2021 Im, Gupta, Jain, Chande, Carleton, Jordan and Rishishwar.

    • Genetics and Genomics
      1. Complete Genome Sequence of Rickettsia parkeri Strain Black Gapexternal icon
        Karpathy SE, Paddock CD, Grizzard SL, Batra D, Rowe LA, Gauthier DT.
        Microbiol Resour Announc. 2021 Nov 4;10(44):e0062321.
        A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%.

    • Health Disparities
      1. BACKGROUND: While unemployment has been associated with poor health, few recent studies in the United States have comprehensively assessed associations between employment status (including duration unemployed) and healthcare access, health-related behaviors, and specific health outcomes. METHODS: We assessed health-related metrics by employment status in 2018-2019 Behavioral Risk Factor Surveillance System respondents ages 25-54. We calculated the unadjusted prevalence and adjusted prevalence ratios to compare employed workers to respondents who were self-employed, short-term (<12 months) unemployed, long-term unemployed, and unable to work. RESULTS: Adverse health outcomes increased with unemployment duration and were highest for those unable to work. Non-Hispanic Blacks were most likely to be unemployed or unable to work. Short-term unemployment and self-employment were associated with poor healthcare access. Health behaviors and outcomes declined with increasing duration of unemployment and were worst for those unable to work. CONCLUSIONS: In the United States, access to affordable healthcare is problematic for both the self-employed and the short-term unemployed. Short-term unemployment is a particularly important locus for intervention and provision of resources to prevent health declines that may hinder re-employment.

    • Health Economics
      1. The economic burden of rotavirus hospitalization among children < 5 years of age in selected hospitals in Bangladeshexternal icon
        Ahmed S, Dorin F, Satter SM, Sarker AR, Sultana M, Gastanaduy PA, Parashar U, Tate JE, Heffelfinger JD, Gurley ES, Khan JA.
        Vaccine. 2021 Oct 29.
        BACKGROUND: Rotavirus is a common cause of severe acute gastroenteritis among young children. Estimation of the economic burden would provide informed decision about investment on prevention strategies (e.g., vaccine and/or behavior change), which has been a potential policy discussion in Bangladesh for several years. METHODS: We estimated the societal costs of children <5 years for hospitalization from rotavirus gastroenteritis (RVGE) and incidences of catastrophic health expenditure. A total of 360 children with stool specimens positive for rotavirus were included in this study from 6 tertiary hospitals (3 public and 3 private). We interviewed the caregiver of the patient and hospital staff to collect cost from patient and health facility perspectives. We estimated the economic cost considering 2015 as the reference year. RESULTS: The total societal per-patient costs to treat RVGE in the public hospital were 126 USD (95% CI: 116-136) and total household costs were 161 USD (95% CI: 145-177) in private facilities. Direct costs constituted 38.1% of total household costs. The out-of-pocket payments for RVGE hospitalization was 23% of monthly income and 76% of households faced catastrophic healthcare expenditures due to this expense. The estimated total annual household treatment cost for the country was 10 million USD. CONCLUSIONS: A substantial economic burden of RVGE in Bangladesh was observed in this study. Any prevention of RVGE through cost-effective vaccination or/and behavioural change would contribute to substantial economic benefits to Bangladesh.

      2. INTRODUCTION: Of the 22.8 million coronavirus disease 2019 (COVID-19) cases recorded in the United States as of March 21, 2021 with age information, three-fourths were in the workingage group, indicating the potentially high economic impact of the pandemic. This study estimates the cost of lost work hours associated with the COVID-19 pandemic between March 2020 through February 2021. METHOD: I used a before-and-after analysis of data from the 2017-2021 Current Population Survey to estimate the costs of lost work hours due to economic, workers' own health, and other reasons, from the COVID-19 pandemic. RESULTS: Across March 2020 through February 2021 (a year since the start of the pandemic in the United States), the estimated cost of lost work hours associated with the COVID-19 pandemic among US full-time workers was $138 billion (95% confidence interval [CI]: $73.4 billion-$202.46 billion). Shares of the costs attributed to economic, workers' own health, and other reasons were 33.7%, 13.7%, and 52.6%, respectively. CONCLUSION: The $138 billion cost of lost work hours associated with the COVID-19 pandemic during March 2020 through February 2021 highlights the economic consequences of the pandemic, as well as indicating the potential benefit of public health and safety interventions used to mitigate COVID-19 spread.

      3. Cost-Effectiveness and Impact of a Targeted Age- and Incidence-based West Nile Virus Vaccine Strategyexternal icon
        Curren EJ, Shankar MB, Fischer M, Meltzer MI, Erin Staples J, Gould CV.
        Clin Infect Dis. 2021 Nov 2;73(9):1565-1570.
        BACKGROUND: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost-effective than universal vaccination, but costs remained high. METHODS: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100 000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100 000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life-years (QALYs) saved. RESULTS: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100 000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively. CONCLUSIONS: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.


    • Healthcare Associated Infections
      1. Incidence, Etiology, and Severity of Acute Gastroenteritis Among Prospectively Enrolled Patients in 4 Veterans Affairs Hospitals and Outpatient Centers, 2016-2018external icon
        Cardemil CV, Balachandran N, Kambhampati A, Grytdal S, Dahl RM, Rodriguez-Barradas MC, Vargas B, Beenhouwer DO, Evangelista KV, Marconi VC, Meagley KL, Brown ST, Perea A, Lucero-Obusan C, Holodniy M, Browne H, Gautam R, Bowen MD, Vinjé J, Parashar UD, Hall AJ.
        Clin Infect Dis. 2021 Nov 2;73(9):e2729-e2738.
        BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California), collectively serving >320 000 patients annually. METHODS: From 1 July 2016 to 30 June 2018, we actively identified inpatient AGE case patients and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatients with AGE through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens by means of multiplex gastrointestinal polymerase chain reaction panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatients with AGE, 394 non-AGE inpatient controls, and 506 outpatients with AGE. Clostridioides difficile and norovirus were most frequently detected among inpatients (for AGE case patients vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; P < .01 for both) and outpatients (norovirus, 10.7%; C. difficile, 10.5%). The incidence per 100 000 population was highest among outpatients (AGE, 2715; C. difficile, 285; norovirus, 291) and inpatients ≥65 years old (AGE, 459; C. difficile, 91; norovirus, 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/enteroinvasive Escherichia coli cases. Overall, 12% of inpatients with AGE had intensive care unit stays, and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

      2. A Pseudo-outbreak of Burkholderia cepacia Complex in a Kentucky Hospitalexternal icon
        Eldridge CC, Flinchum AH, Thoroughman D, Spicer KB.
        Am J Infect Control. 2021 Nov 3.
        A cluster of Burkholderia cepacia complex cases from January to October 2020 among outpatients undergoing urologic procedures within a Kentucky hospital's operating rooms was investigated. This investigation included a laboratory look-back, chart reviews, exposure tracing, staff interviews, and direct observation of infection prevention and control practices. A significant protocol breach in a laboratory procedure led to contamination of surgical specimens submitted for culture with non-sterile saline. Pseudo-outbreaks often highlight gaps in infection control processes. Healthcare facilities can make substantial improvements in patient care quality and safety as they respond to identified gaps and improve systems and protocols.

    • Immunity and Immunization
      1. Strategies associated with COVID-19 vaccine coverage among nursing home staffexternal icon
        Berry SD, Baier RR, Syme M, Gouskova N, Bishnoi C, Patel U, Leitson M, Gharpure R, Stone ND, Link-Gelles R, Gifford DR.
        J Am Geriatr Soc. 2021 Nov 6.
        BACKGROUND: After the first of three COVID-19 vaccination clinics in U.S. nursing homes (NHs), the median vaccination coverage of staff was 37.5%, indicating the need to identify strategies to increase staff coverage. We aimed to compare the facility-level activities, policies, incentives, and communication methods associated with higher staff COVID-19 vaccination coverage. METHODS: Design Case-control analysis. Setting Nationally stratified random sample of 1,338 U.S. NHs participating in the Pharmacy Partnership for Long-Term Care Program. Participants Nursing home leadership Measurement During February 4-March 2, 2021, we surveyed NHs with low (<35%), medium (40%-60%) and high (>75%) staff vaccination coverage, to collect information on facility strategies used to encourage staff vaccination. Cases were respondents with medium and high vaccination coverage, whereas controls were respondents with low coverage. We used logistic regression modeling, adjusted for county and NH characteristics, to identify strategies associated with facility-level vaccination coverage. RESULTS: We obtained responses from 413 of 1,338 NHs (30.9%). Compared with facilities with lower staff vaccination coverage, facilities with medium or high coverage were more likely to have designated frontline staff champions (medium: adjusted odds ratio [aOR] 3.6, 95% CI 1.3-10.3; high: aOR 2.9, 95% CI 1.1-7.7) and set vaccination goals (medium: aOR 2.4, 95% 1.0-5.5; high: aOR 3.7, 95% CI 1.6-8.3). NHs with high vaccination coverage were more likely to have given vaccinated staff rewards such as T-shirts compared with NHs with low coverage (aOR 3.8, 95% CI 1.3-11.0). Use of multiple strategies was associated with greater likelihood of facilities having medium or high vaccination coverage: for example, facilities that used ≥9 strategies were three times more likely to have high staff vaccination coverage than facilities using <6 strategies (aOR 3.3, 95% CI 1.2-8.9). CONCLUSIONS: Use of designated champions, setting targets, and use of non-monetary awards, were associated with high NH staff COVID-19 vaccination coverage. This article is protected by copyright. All rights reserved.

      2. Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19-Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity - Nine States, January-September 2021external icon
        Bozio CH, Grannis SJ, Naleway AL, Ong TC, Butterfield KA, DeSilva MB, Natarajan K, Yang DH, Rao S, Klein NP, Irving SA, Dixon BE, Dascomb K, Liao IC, Reynolds S, McEvoy C, Han J, Reese SE, Lewis N, Fadel WF, Grisel N, Murthy K, Ferdinands J, Kharbanda AB, Mitchell PK, Goddard K, Embi PJ, Arndorfer J, Raiyani C, Patel P, Rowley EA, Fireman B, Valvi NR, Griggs EP, Levy ME, Zerbo O, Porter RM, Birch RJ, Blanton L, Ball SW, Steffens A, Olson N, Williams J, Dickerson M, McMorrow M, Schrag SJ, Verani JR, Fry AM, Azziz-Baumgartner E, Barron M, Gaglani M, Thompson MG, Stenehjem E.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 5;70(44):1539-1544.
        Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.

      3. The immediate impact of the COVID-19 pandemic on polio immunization and surveillance activitiesexternal icon
        Burkholder B, Wadood Z, Kassem AM, Ehrhardt D, Zomahoun D.
        Vaccine. 2021 Oct 22.
        In addition to affecting individual health the COVID-19 pandemic has disrupted efforts to deliver essential health services around the world. In this article we present an overview of the immediate programmatic and epidemiologic impact of the pandemic on polio eradication as well as the adaptive strategic and operational measures taken by the Global Polio Eradication Initiative (GPEI) from March through September 2020. Shortly after the World Health Organization (WHO) declared a global pandemic on 11 March 2020, the GPEI initially redirected the programme's assets to tackle COVID-19 and suspended house-to-house supplementary immunization activities (SIAs) while also striving to continue essential poliovirus surveillance functions. From March to May 2020, 28 countries suspended a total of 62 polio vaccine SIAs. In spite of efforts to continue poliovirus surveillance, global acute flaccid paralysis (AFP) cases reported from January-July 2020 declined by 34% compared with the same period in 2019 along with decreases in the mean number of environment samples collected per active site in the critical areas of the African and Eastern Mediterranean regions. The GPEI recommended countries should resume planning and implementation of SIAs starting in July 2020 and released guidelines to ensure these could be done safely for front line workers and communities. By the end of September 2020, a total of 14 countries had implemented circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreak response vaccination campaigns and Afghanistan and Pakistan restarted SIAs to stop ongoing wild poliovirus type 1 (WPV1) transmission. The longer-term impacts of disruptions to eradication efforts remain to be determined, especially in terms of the effect on poliovirus epidemiology. Adapting to the pandemic situation has imposed new considerations on program implementation and demonstrated not only GPEI's contribution to global health security, but also identified potential opportunities for coordinated approaches across immunization and health services.

      4. Progress Toward Regional Measles Elimination - Worldwide, 2000-2020external icon
        Dixon MG, Ferrari M, Antoni S, Li X, Portnoy A, Lambert B, Hauryski S, Hatcher C, Nedelec Y, Patel M, Alexander JP, Steulet C, Gacic-Dobo M, Rota PA, Mulders MN, Bose AS, Rosewell A, Kretsinger K, Crowcroft NS.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 12;70(45):1563-1569.
        In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan,* with the objective of eliminating measles(†) in five of the six World Health Organization (WHO) regions by 2020 (1). The Immunization Agenda 2021-2030 (IA2030)(§) uses measles incidence as an indicator of the strength of immunization systems. The Measles-Rubella Strategic Framework 2021-2030(¶) and the Measles Outbreaks Strategic Response Plan 2021-2023** are aligned with the IA2030 and highlight robust measles surveillance systems to document immunity gaps, identify root causes of undervaccination, and develop locally tailored solutions to ensure administration of 2 doses of measles-containing vaccine (MCV) to all children. This report describes progress toward World Health Assembly milestones and measles elimination objectives during 2000-2020 and updates a previous report (2). During 2000-2010, estimated MCV first dose (MCV1) coverage increased globally from 72% to 84%, peaked at 86% in 2019, but declined to 84% in 2020 during the COVID-19 pandemic. All countries conducted measles surveillance, although fewer than one third achieved the sensitivity indicator target of ≥2 discarded(††) cases per 100,000 population in 2020. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, rebounded to 120 in 2019, before falling to 22 in 2020. During 2000-2020, the annual number of estimated measles deaths decreased 94%, from 1,072,800 to 60,700, averting an estimated 31.7 million measles deaths. To achieve regional measles elimination targets, enhanced efforts are needed to reach all children with 2 MCV doses, implement robust surveillance, and identify and close immunity gaps.

      5. Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults - Nine States, January-September 2021external icon
        Embi PJ, Levy ME, Naleway AL, Patel P, Gaglani M, Natarajan K, Dascomb K, Ong TC, Klein NP, Liao IC, Grannis SJ, Han J, Stenehjem E, Dunne MM, Lewis N, Irving SA, Rao S, McEvoy C, Bozio CH, Murthy K, Dixon BE, Grisel N, Yang DH, Goddard K, Kharbanda AB, Reynolds S, Raiyani C, Fadel WF, Arndorfer J, Rowley EA, Fireman B, Ferdinands J, Valvi NR, Ball SW, Zerbo O, Griggs EP, Mitchell PK, Porter RM, Kiduko SA, Blanton L, Zhuang Y, Steffens A, Reese SE, Olson N, Williams J, Dickerson M, McMorrow M, Schrag SJ, Verani JR, Fry AM, Azziz-Baumgartner E, Barron MA, Thompson MG, DeSilva MB.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 5;70(44):1553-1559.
        Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the U.S. adult population (1). Immunocompromised adults are at increased risk for severe COVID-19 outcomes (2) and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network* on hospitalizations among persons aged ≥18 years with COVID-19-like illness from 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses,(†) VE against COVID-19-associated hospitalization conferred by completing a 2-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date(§) (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of 2 doses of mRNA COVID-19 vaccine against COVID-19-associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%-80%) than among immunocompetent patients (90%; 95% CI = 89%-91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.

      6. How Australia's measles control activities catalysed rubella eliminationexternal icon
        Glynn-Robinson A, Knapp JK, Durrheim DN.
        Int J Infect Dis. 2021 Nov 5.
        BACKGROUND: Australia was verified to have eliminated rubella in 2017. This success is attributed to Australia's longstanding national immunisation programme and two enhanced measles immunisation activities using measles, mumps, and rubella (MMR) vaccines - Measles Control Campaign (MCC) and Young Adult MMR Campaign (YAC). The impact of these activities on rubella incidence and its elimination in Australia is described. METHODS: Aggregate national serological survey data were assigned to birth cohorts and mean, median and age-group estimates calculated and analysed against MMR immunisation coverage estimates (1998-2018) and rubella notifications (1993-2018). Three-year cumulative incidences were calculated by birth cohort. RESULTS: Serological surveys revealed high stable levels of rubella immunity among females but estimates for three male cohorts were lower. Since 2007, MMR immunisation coverage among children aged 24-27 months has remained above 90% for both doses. The three-year cumulative incidence of rubella declined across all birth cohorts following the MCC and the YAC. DISCUSSION: Using MMR vaccines to address measles immunity gaps had a symbiotic benefit in controlling rubella in Australia. Both the MCC and YAC shifted rubella epidemiology, accelerating the interruption of endemic transmission. Countries should consider combined measles and rubella vaccines for all catch-up activities.

      7. The Advisory Committee on Immunization Practices' Interim Recommendations for Additional Primary and Booster Doses of COVID-19 Vaccines - United States, 2021external icon
        Mbaeyi S, Oliver SE, Collins JP, Godfrey M, Goswami ND, Hadler SC, Jones J, Moline H, Moulia D, Reddy S, Schmit K, Wallace M, Chamberland M, Campos-Outcalt D, Morgan RL, Bell BP, Brooks O, Kotton C, Talbot HK, Lee G, Daley MF, Dooling K.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 5;70(44):1545-1552.
        Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.

      8. Estimating the early impact of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older: an ecological analysis of national surveillance dataexternal icon
        McNamara LA, Wiegand RE, Burke RM, Sharma AJ, Sheppard M, Adjemian J, Ahmad FB, Anderson RN, Barbour KE, Binder AM, Dasgupta S, Dee DL, Jones ES, Kriss JL, Lyons BC, McMorrow M, Payne DC, Reses HE, Rodgers LE, Walker D, Verani JR, Schrag SJ.
        Lancet. 2021 Nov 3.
        BACKGROUND: In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older. METHODS: We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods. FINDINGS: The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI -14 to 69 among adults aged 65-74 years and by 30%, -47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear. INTERPRETATION: The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults. FUNDING: None.

      9. Monitoring the safety of COVID-19 vaccines in pregnancy in the USexternal icon
        Moro PL, Panagiotakopoulos L, Oduyebo T, Olson CK, Myers T.
        Hum Vaccin Immunother. 2021 Nov 10:1-9.
        Pregnant persons are at increased risk of severe illness from COVID-19. The first COVID-19 vaccines in the U.S. were authorized for emergency use in December 2020 and pregnant persons were eligible and could get vaccinated despite scarce safety data in this population. To monitor the safety of COVID-19 vaccination during pregnancy, four surveillance systems are used by the Centers for Disease Control and Prevention (CDC). The Vaccine Adverse Event Reporting System is a national, passive system that captures reports of potential adverse events. V-safe is a novel, active system that uses text messaging and web-based surveys to provide health check-ins after vaccination; and enrolls eligible v-safe participants in the v-safe pregnancy registry. The Vaccine Safety Datalink is a collaboration between the CDC and nine integrated health care organizations which performs near-real time surveillance and traditional epidemiologic studies on pregnant vaccine recipients. The CDC is committed to timely and comprehensive monitoring of COVID-19 vaccine safety in pregnancy.

      10. US Primary Care Providers' Experiences and Practices Related to Routine Pediatric Vaccination During the COVID-19 Pandemicexternal icon
        O'Leary ST, Cataldi J, Lindley MC, Beaty BL, Hurley LP, Crane LA, Brtnikova M, Gorman C, Vogt T, Kang Y, Kempe A.
        Acad Pediatr. 2021 Oct 28.
        OBJECTIVE: To describe, among pediatricians (Peds) and family physicians (FPs), 1) changes made to routine childhood vaccination delivery as a result of the pandemic, and 2) perceived barriers to delivering vaccinations from March 2020 through the time of the survey. METHODS: A nationally representative survey among Peds and FPs was administered by mail or Internet in October-December 2020. RESULTS: Response rate was 64% (579/909). For children aged 0-2 years, among those who vaccinated that age group pre-pandemic (Peds n=265, FPs n=222), 5% of Peds and 15% of FPs reported they had stopped vaccinating these children at any time. For children aged 4-6 years (Peds n=264, FPs n=229), 19% of Peds and 17% of FPs reported they had stopped vaccinating at any time. For children aged 11-18 years (Peds n=265, FPs n=251), 24% of Peds and 19% of FPs reported they had stopped vaccinating at any time. Nearly all reported returning to pre-pandemic vaccination services at the time of the survey. Factors most frequently reported as major/moderate barriers to providing vaccinations included fewer in-person visits because patients/parents were concerned about risk of SARS-CoV-2 infection (Peds, 52%; FPs, 54%), fewer in-person visits for sports clearance (Peds, 39%; FPs, 44%), and fewer back-to-school in-person visits because some children were in virtual learning (Peds, 25%; FPs, 33%). CONCLUSIONS: Although some physicians reported interrupting vaccination services at some point during the pandemic, the majority reported continuing to provide vaccinations throughout, with essentially all returning to pre-pandemic vaccination services by end of 2020.

      11. Influenza Vaccinations During the COVID-19 Pandemic - 11 U.S. Jurisdictions, September-December 2020external icon
        Roman PC, Kirtland K, Zell ER, Jones-Jack N, Shaw L, Shrader L, Sprague C, Schultz J, Le Q, Nalla A, Kuramoto S, Cheng I, Woinarowicz M, Robison S, Robinson S, Meder K, Murphy A, Gibbs-Scharf L, Harris L, Murthy BP.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 12;70(45):1575-1578.
        Influenza causes considerable morbidity and mortality in the United States. Between 2010 and 2020, an estimated 9-41 million cases resulted in 140,000-710,000 hospitalizations and 12,000-52,000 deaths annually (1). As the United States enters the 2021-22 influenza season, the potential impact of influenza illnesses is of concern given that influenza season will again coincide with the ongoing COVID-19 pandemic, which could further strain overburdened health care systems. The Advisory Committee on Immunization Practices (ACIP) recommends routine annual influenza vaccination for the 2021-22 influenza season for all persons aged ≥6 months who have no contraindications (2). To assess the potential impact of the COVID-19 pandemic on influenza vaccination coverage, the percentage change between administration of at least 1 dose of influenza vaccine during September-December 2020 was compared with the average administered in the corresponding periods in 2018 and 2019. The data analyzed were reported from 11 U.S. jurisdictions with high-performing state immunization information systems.* Overall, influenza vaccine administration was 9.0% higher in 2020 compared with the average in 2018 and 2019, combined. However, in 2020, the number of influenza vaccine doses administered to children aged 6-23 months and children aged 2-4 years, was 13.9% and 11.9% lower, respectively than the average for each age group in 2018 and 2019. Strategic efforts are needed to ensure high influenza vaccination coverage among all age groups, especially children aged 6 months-4 years who are not yet eligible to receive a COVID-19 vaccine. Administration of influenza vaccine and a COVID-19 vaccine among eligible populations is especially important to reduce the potential strain that influenza and COVID-19 cases could place on health care systems already overburdened by COVID-19.

      12. Predictors of HPV vaccination in the southern US: A survey of caregivers from 13 statesexternal icon
        Vasudevan L, Ostermann J, Wang Y, Harrison SE, Yelverton V, McDonald JA, Fish LJ, Williams C, Walter EB.
        Vaccine. 2021 Nov 3.
        BACKGROUND AND OBJECTIVES: Despite a high burden of human papillomavirus (HPV)-attributable cancers, the southern US lags other regions in HPV vaccination coverage. This study sought to characterize and contextualize predictors of HPV vaccination in the southern US. METHODS: From December 2019 - January 2020, parents of adolescents (ages 9-17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel and completed a cross-sectional survey. The primary study outcome was initiation of HPV vaccination. RESULTS: Of 1105 parents who responded to the survey, most were ≥35 years of age and of female gender. HPV vaccination initiation was reported only among 37.3% of adolescents and was highest at age 12. Cumulative HPV vaccination coverage was highest at age 15 (52%) but lower than coverage for tetanus-diphtheria-acellular pertussis (Tdap, 79.3%) and Meningococcal vaccines (MenACWY, 67.3%). Provider recommendation was strongly associated with higher odds of HPV vaccination (aOR: 49.9, 95 %CI: 23.1-107.5). In alternative predictive models, home/online (vs. public) schooling and parents' working status were associated with lower odds of vaccination; health care visits in the past 12 months and shorter travel times to adolescents' usual health care provider were associated with greater odds of vaccination. CONCLUSIONS: Our findings suggest missed opportunities for HPV vaccination in the southern US and support strengthening provider recommendation for on-time initiation of HPV vaccination among adolescents. Other strategies to increase HPV vaccinations may include encouraging co-administration with other adolescent vaccines, increasing vaccine access, and promoting vaccinations for home/online-school students.

      13. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Children Aged 5-11 Years - United States, November 2021external icon
        Woodworth KR, Moulia D, Collins JP, Hadler SC, Jones JM, Reddy SC, Chamberland M, Campos-Outcalt D, Morgan RL, Brooks O, Talbot HK, Lee GM, Bell BP, Daley MF, Mbaeyi S, Dooling K, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 12;70(45):1579-1583.
        The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 μg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 μg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework(§) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.

    • Injury and Violence
      1. Suicide Risk and Protective Factors in Online Support Forum Posts: Annotation Scheme Development and Validation Studyexternal icon
        Chancellor S, Sumner SA, David-Ferdon C, Ahmad T, De Choudhury M.
        JMIR Ment Health. 2021 Nov 8;8(11):e24471.
        BACKGROUND: Online communities provide support for individuals looking for help with suicidal ideation and crisis. As community data are increasingly used to devise machine learning models to infer who might be at risk, there have been limited efforts to identify both risk and protective factors in web-based posts. These annotations can enrich and augment computational assessment approaches to identify appropriate intervention points, which are useful to public health professionals and suicide prevention researchers. OBJECTIVE: This qualitative study aims to develop a valid and reliable annotation scheme for evaluating risk and protective factors for suicidal ideation in posts in suicide crisis forums. METHODS: We designed a valid, reliable, and clinically grounded process for identifying risk and protective markers in social media data. This scheme draws on prior work on construct validity and the social sciences of measurement. We then applied the scheme to annotate 200 posts from r/SuicideWatch-a Reddit community focused on suicide crisis. RESULTS: We documented our results on producing an annotation scheme that is consistent with leading public health information coding schemes for suicide and advances attention to protective factors. Our study showed high internal validity, and we have presented results that indicate that our approach is consistent with findings from prior work. CONCLUSIONS: Our work formalizes a framework that incorporates construct validity into the development of annotation schemes for suicide risk on social media. This study furthers the understanding of risk and protective factors expressed in social media data. This may help public health programming to prevent suicide and computational social science research and investigations that rely on the quality of labels for downstream machine learning tasks.

      2. Traumatic Brain Injury-Related Hospitalizations and Deaths in Urban and Rural Counties-2017external icon
        Daugherty J, Sarmiento K, Waltzman D, Xu L.
        Ann Emerg Med. 2021 Nov 3.
        STUDY OBJECTIVE: A better understanding of differences in traumatic brain injury incidence by geography may help inform resource needs for local communities. This paper presents estimates on traumatic brain injury-related hospitalizations and deaths by urban and rural county of residence. METHODS: To estimate the incidence of traumatic brain injury-related hospitalizations, data from the 2017 Healthcare Cost and Utilization Project's National Inpatient Sample were analyzed (n=295,760). To estimate the incidence of traumatic brain injury-related deaths, the Centers for Disease Control and Prevention's National Vital Statistics System multiple-cause-of-death files were analyzed (n=61,134). Datasets were stratified by residence, sex, principal mechanism of injury, and age group. Traumatic brain injury-related hospitalizations were also stratified by insurance status and hospital location. RESULTS: The rate of traumatic brain injury-related hospitalizations was significantly higher among urban (70.1 per 100,000 population) than rural residents (61.0), whereas the rate of traumatic brain injury-related deaths was significantly higher among rural (27.5) than urban residents (17.4). These patterns held for both sexes, individuals age 55 and older, and within the leading mechanisms of injury (ie, suicide, unintentional falls). Among patients with Medicare or Medicaid, the rate of traumatic brain injury-related hospitalizations was higher among urban residents; there was no urban/rural difference with other types of insurance. Nearly all (99.6%) urban residents who were hospitalized for a traumatic brain injury received care in an urban hospital. Additionally, approximately 80.3% of rural residents were hospitalized in an urban hospital. CONCLUSION: Urban residents had a higher rate of traumatic brain injury-related hospitalizations, whereas rural residents had a higher rate of traumatic brain injury-related deaths. This disparity deserves further study using additional databases that assess differences in mechanisms of injury and strategies to improve access to emergency care among rural residents.

      3. Associations between adverse childhood experiences and contraceptive use among young adults in Hondurasexternal icon
        Huber-Krum S, Miedema SS, Shortt JW, Villaveces A, Kress H.
        Child Abuse Negl. 2021 Nov 6;123:105381.
        OBJECTIVE: Research on adverse childhood experiences (ACEs) and use of modern contraception is limited in Honduras. The government has made substantial gains in promoting modern contraception. Young adults experience high rates of violence. The aim of this study was to assess the relationship between ACEs and contraceptive behaviors among young women and men. METHODS: We used data from 810 women and 753 men aged 18-24 years from the 2017 Honduras Violence against Children Survey, a cross-sectional, nationally representative household survey of childhood adversity. We assessed associations between ACEs and three contraceptive use outcomes: use versus nonuse of modern contraceptives; use of methods requiring medium/high or low programmatic support among current contraceptive users; and frequent versus infrequent condom use. FINDINGS: Exposure to physical or emotional abuse and witnessing violence in the home was not significantly associated with the three contraceptive use outcomes for men or women. Sexual abuse and parental separation reduced odds of contraceptive use among women (Odds Ratio (OR) < 0.60) but not among men. In contrast, orphan status increased odds of modern contraception use among men (OR 1.93) and frequent condom use among women (OR 2.22). CONCLUSION: The inconsistent direction and magnitude of associations between ACEs and modern contraceptive use among young men and women suggests divergent relationships between ACEs and sexual and reproductive health behaviors. Results may highlight the strength of norms around contraceptive use and/or widespread access to community-based family planning programs and comprehensive sexuality education, irrespective of exposure to ACEs in Honduras.

    • Laboratory Sciences
      1. Comparison of Estimated Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence Through Commercial Laboratory Residual Sera Testing and a Community Surveyexternal icon
        Bajema KL, Dahlgren FS, Lim TW, Bestul N, Biggs HM, Tate JE, Owusu C, Szablewski CM, Drenzek C, Drobeniuc J, Semenova V, Li H, Browning P, Desai R, Epperson M, Jia LT, Thornburg NJ, Edens C, Fry AM, Hall AJ, Schiffer J, Havers FP.
        Clin Infect Dis. 2021 Nov 2;73(9):e3120-e3123.
        We compared severe acute respiratory syndrome coronavirus 2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April and May 2020 and found these 2 estimates to be similar (4.94% vs 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence.

      2. A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemiaexternal icon
        Brindle E, Lillis L, Barney R, Bansil P, Hess SY, Wessells KR, Ouédraogo CT, Arredondo F, Barker MK, Craft NE, Fischer C, Graham JL, Havel PJ, Karakochuk CD, Zhang M, Mussai EX, Mapango C, Randolph JM, Wander K, Pfeiffer CM, Murphy E, Boyle DS.
        PLoS One. 2021 ;16(11):e0259509.
        A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential.

      3. A system to differentiate and quantify liquid and headspace vapor leaks from closed system drug-transfer devices (CSTDs) is presented. CSTDs are designed to reduce or eliminate hazardous drug (HD) exposure risk when compounding and administering HDs. CSTDs may leak liquid, headspace, or a mixture of the two. The amount of HD contained in liquid and headspace leaks may be substantially different. Use of a test solution containing two VOCs with differences in ratios of VOC concentrations in the headspace and liquid enables source apportionment of leaked material. SIFT-MS was used to detect VOCs from liquid and headspace leaks in the vapor phase. Included in this report is a novel method to determine the origin and magnitude of leaks from CSTDs. A limit of leak detection of 24 μL of headspace vapor and 0.14 μL of test liquid were found using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

      4. Diagnostic accuracy of dried plasma spot specimens for HIV-1 viral load testing: a systematic review and meta-analysisexternal icon
        Fong Y, Markby J, Andreotti M, Beck I, Bourlet T, Brambilla D, Frenkel L, Lira R, Nelson JA, Pollakis G, Reigadas S, Richman D, Sawadogo S, Waters L, Yang C, Zeh C, Doherty M, Vojnov L.
        J Acquir Immune Defic Syndr. 2021 Nov 2.
        BACKGROUND: Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood. METHODS: Standard databases (PubMed and Medline), conferences, and grey literature were searched until January 2019. The quality of evidence was evaluated using STARD and QUADAS-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology and to account for between-study variation. RESULTS: We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots to plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1,847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared to plasma was 0.28 log10 copies/ml, while the difference in median viral load was 2.25 log10 copies/ml. More dried plasma spot values were undetectable compared to plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens was >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds. DISCUSSION: Overall, dried plasma spot specimens performed relatively well compared to plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.

      5. Culture-Independent Detection of Poliovirus in Stool Samples by Direct RNA Extractionexternal icon
        Harrington C, Sun H, Jeffries-Miles S, Gerloff N, Mandelbaum M, Pang H, Collins N, Burns CC, Vega E.
        Microbiol Spectr. 2021 Nov 10:e0066821.
        Laboratory surveillance for poliovirus (PV) relies on virus isolation by cell culture to identify PV in stool specimens from acute flaccid paralysis (AFP) cases. Although this method successfully identifies PV, it is time-consuming and necessitates the additional biorisk of growing live virus in an increasingly polio-free world. To reduce the risk of culturing PV, the Global Polio Laboratory Network (GPLN) must switch to culture-independent diagnostic methods with sensitivity at least equivalent to that of cell culture procedures. Five commercial nucleic acid extraction kits and one enrichment method were tested for PV extraction efficiency. RNA yield was measured using real-time reverse transcription (RT)-PCR. Based on greater RNA yield, compared with the other kits, the Quick-RNA viral kit was selected for further testing and was optimized using an RNA extraction procedure for stool suspensions. RNA extraction was retrospectively tested with 182 stool samples that had previously tested positive for PVs, in parallel with the standard GPLN virus isolation algorithm. After virus isolation or RNA extraction, real-time RT-PCR assays were performed. RNA extraction was significantly more sensitive than virus isolation (McNemar's test, P < 0.001). Thereafter, the RNA extraction method was tested in parallel for 202 prospective samples; RNA extraction and virus isolation were not significantly different from each other (McNemar's test, P = 0.13). Direct RNA extraction was noninferior to current cell culture methods for detecting PV in stool samples. Our results show that direct RNA extraction can make downstream manipulation safer and can reduce the risk of accidental posteradication viral release. The method is amenable to implementation in a wide variety of polio laboratories. IMPORTANCE Successfully identifying poliovirus from acute flaccid paralysis (AFP) cases is a vital role of the Global Polio Laboratory Network to achieve the goals of the Global Polio Eradication Initiative. Currently, laboratory surveillance relies on virus isolation by cell culture to test for PV present in stool samples. Although this method can identify polioviruses, laboratories must switch to culture-independent methods to reduce the risk associated with growing live viruses in a soon-to-be polio-free world. By implementing this streamlined method, in combination with real-time RT-PCR, laboratories can quickly screen for and type polioviruses of programmatic importance to support the final stages of global polio eradication.

      6. Molecular identification and characterization of novel or re-emerging infectious pathogens is critical for disease surveillance and outbreak investigations. Next generation sequencing (NGS) using Sequence-Independent, Single-Primer Amplification (SISPA) is being used extensively in sequencing of viral genomes but it requires an expensive library preparation step. We developed a simple, low-cost method that enriches nucleic acids followed by a ligation-free (LF) 2-step Polymerase Chain Reaction (PCR) procedure for library preparation. A pan-chimeric universal primer (JS15N14) containing 15 nucleotides with a random tetradecamer (14N) attached to the 3'-end was designed. The complimentary primer (JS15) was used for nucleic acid enrichment in a first round PCR. A second PCR was designed to create Illumina sequencer-compatible sequencing-ready libraries for NGS. The new LF-SISPA protocol was tested using six RNA and DNA viral genomes (10.8-229.4 kilobases, kb) from an ATCC virome nucleic acid mix (ATCC® MSA-1008™) followed by analysis using One Codex, an online identification tool. In addition, a human stool sample known to be positive for norovirus GII was sequenced, and de novo assembly was performed using the Genome Detective Virus Tool allowing for near complete genome identification in less than 24 h. The LF-SISPA method does not require prior knowledge of target sequences and does not require an expensive enzymatic library preparation kit, thereby providing a simple, fast, low-cost alternative for the identification of unknown viral pathogens.

      7. Evaluation of the Point-of-Care Circulating Cathodic Antigen Assay for Monitoring Mass Drug Administration in a Schistosoma mansoni Control Program in Western Kenyaexternal icon
        Straily A, Kavere EA, Wanja D, Wiegand RE, Montgomery SP, Mwaki A, Eleveld A, Secor WE, Odiere MR.
        Am J Trop Med Hyg. 2021 Nov 8.
        The WHO guidelines for monitoring and evaluating Schistosoma mansoni control programs are based on the Kato-Katz (KK) fecal examination method; however, there are limitations to its use, particularly in low prevalence areas. The point-of-care urine circulating cathodic antigen (POC-CCA) assay has emerged as a useful tool for mapping schistosomiasis prevalence, but its use in monitoring and evaluating control programs has not been evaluated. Before POC-CCA can be used for these programs, it must be determined how previous guidance based on the KK method can be translated to the POC-CCA assay; furthermore, its performance in different endemicity settings must be evaluated. Urine and stool specimens were collected from students attending public primary schools in western Kenya before mass treatment with praziquantel at baseline (51 schools), year 1 (45 schools), year 2 (34 schools), and year 3 (20 schools). Prevalence and infection intensity were determined by the KK method and POC-CCA assay. Changes in prevalence and intensity were compared within the strata of schools grouped according to the baseline prevalence determined by the KK method (0-10%, > 10-20%, > 20%). The prevalence determined by the POC-CCA assay was higher than that determined by the KK method at all time points for all strata. The prevalence determined by the KK method decreased from baseline to 2 and 3 years, as did infection intensity (with one exception). A corresponding decrease was not always replicated by the POC-CCA assay results. The POC-CCA assay did not perform as expected, and the concordance of results of the two tests was poor. Furthermore, there are emerging concerns regarding the specificity of the POC-CCA assay. Therefore, it is impossible to translate historical data and programmatic guidelines based on the KK method results to the POC-CCA assay.

    • Maternal and Child Health
      1. Towards a newborn screening common data model: The Utah newborn screening data modelexternal icon
        Jones D, Shao J, Wallis H, Johansen C, Hart K, Pasquali M, Gouripeddi R, Rohrwasser A.
        International Journal of Neonatal Screening. 2021 December;7(4) (no pagination).
        As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and follow-up care to the LOINC, SNOMED CT, ICD-10-CM, and HL7 healthcare standards. The described framework lays the foundation for the implementation of standardized electronic data exchange across newborn screening programs, leading to greater data interoperability. The use of this model can accelerate the implementation of electronic data exchange between healthcare providers and newborn screening programs, which would ultimately improve health outcomes for all newborns and standardize data exchange across programs. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      2. Health Profile of Preterm Males With Duchenne Muscular Dystrophyexternal icon
        Soim A, Wallace B, Whitehead N, Smith MG, Mann JR, Thomas S, Ciafaloni E.
        J Child Neurol. 2021 Oct;36(12):1095-1102.
        In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.

    • Occupational Safety and Health
      1. How effective are Fatigue Risk Management Systems (FRMS)? A reviewexternal icon
        Sprajcer M, Thomas MJ, Sargent C, Crowther ME, Boivin DB, Wong IS, Smiley A, Dawson D.
        Accid Anal Prev. 2021 Oct 28:106398.
        OBJECTIVE: Fatigue Risk Management Systems (FRMS) are a data-driven set of management practices for identifying and managing fatigue-related safety risks. This approach also considers sleep and work time, and is based on ongoing risk assessment and monitoring. This narrative review addresses the effectiveness of FRMS, as well as barriers and enablers in the implementation of FRMS. Furthermore, this review draws on the literature to provide evidence-based policy guidance regarding FRMS implementation. METHODS: Seven databases were drawn on to identify relevant peer-reviewed literature. Relevant grey literature was also reviewed based on the authors' experience in the area. In total, 2129 records were screened based on the search strategy, with 231 included in the final review. RESULTS: Few studies provide an evidence-base for the effectiveness of FRMS as a whole. However, FRMS components (e.g., bio-mathematical models, self-report measures, performance monitoring) have improved key safety and fatigue metrics. This suggests FRMS as a whole are likely to have positive safety outcomes. Key enablers of successful implementation of FRMS include organisational and worker commitment, workplace culture, and training. CONCLUSIONS: While FRMS are likely to be effective, in organisations where safety cultures are insufficiently mature and resources are less available, these systems may be challenging to implement successfully. We propose regulatory bodies consider a hybrid model of FRMS, where organisations could choose to align with tight hours of work (compliance) controls. Alternatively, where organisational flexibility is desired, a risk-based approach to fatigue management could be implemented.

    • Parasitic Diseases
      1. Assessing an Adaptation of the Universal Parasite Diagnostic Assay for Bloodborne Parasites in a US State Public Health Laboratoryexternal icon
        Clemons B, Barratt J, Lane M, Qvarnstrom Y, Teal AE, Zayas G, Madison-Antenucci S.
        Am J Trop Med Hyg. 2021 Nov 8.
        For complex clinical cases where a parasitic infection is suspected, it can be difficult for clinicians to recommend an appropriate laboratory test. These tests are usually pathogen-specific and require a certain degree of suspicion for the precise etiology. Recently, Flaherty et al. (2021) described an assay, the universal parasite diagnostic (UPDx) that can potentially provide a diagnosis of any parasite present in a specimen. Using primers that amplify DNA from all eukaryotes, UPDx differentiates several parasitic infections in blood by amplicon-based next-generation sequencing (NGS) of the 18S rDNA locus. As the state's public health reference laboratory, the Parasitology Laboratory at the Wadsworth Center (New York, NY) receives specimens from patients who have potentially encountered a wide variety of parasites. As such, the ability to differentiate several blood parasites using a single assay is of interest. We assessed UPDx for its ability to confirm parasitic infections for 20 specimens that were previously identified by real-time PCR (RT-PCR). This included specimens positive for Babesia microti, Trypanosoma cruzi, Leishmania tropica, various Plasmodium species, and specimens comprising mixed Plasmodium sp. infections. Results obtained using UPDx were largely concordant with the RT-PCR assays. A T. cruzi positive specimen was negative by UPDx and for two mixed Plasmodium sp. infections only one species was detected. The results obtained for other specimens were concordant. We conclude that UPDx shows promise for the detection of blood parasites in diagnostic laboratories. As NGS becomes cheaper, assays like UPDx will become increasingly amenable to use in clinical settings.

      2. Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018external icon
        Dentinger CM, Rakotomanga TA, Rakotondrandriana A, Rakotoarisoa A, Rason MA, Moriarty LF, Steinhardt LC, Kapesa L, Razafindrakoto J, Svigel SS, Lucchi NW, Udhayakumar V, Halsey ES, Ratsimbasoa CA.
        Malar J. 2021 Nov 3;20(1):432.
        BACKGROUND: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. METHODS: Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. RESULTS: Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76. CONCLUSION: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

      3. Intermittent screening and treatment with artemisinin-combination therapy versus intermittent preventive treatment with sulphadoxine-pyrimethamine for malaria in pregnancy: a systematic review and individual participant data meta-analysis of randomised clinical trialsexternal icon
        Gutman JR, Khairallah C, Stepniewska K, Tagbor H, Madanitsa M, Cairns M, L'Lanziva A J, Kalilani L, Otieno K, Mwapasa V, Meshnick S, Kariuki S, Chandramohan D, Desai M, Taylor SM, Greenwood B, Ter Kuile FO.
        EClinicalMedicine. 2021 Nov;41:101160.
        BACKGROUND: In sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections. METHODS: We searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental Plasmodium falciparum at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789. FINDINGS: Five trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I(2)=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I(2)=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I(2)=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I(2)=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57). INTERPRETATION: ISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections. FUNDING: Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.

      4. Progress Toward Global Eradication of Dracunculiasis, January 2020-June 2021external icon
        Hopkins DR, Weiss AJ, Roy SL, Yerian S, Cama VA.
        MMWR Morb Mortal Wkly Rep. 2021 Nov 5;70(44):1527-1533.
        Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is traditionally acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae, but in recent years also appears increasingly to be transmitted by eating fish or other aquatic animals. The worm typically emerges through the skin on a lower limb of the host 1 year after infection, causing pain and disability (1). There is no vaccine or medicine to prevent or medicine to treat dracunculiasis; eradication relies on case containment* to prevent water contamination and other interventions to prevent infection: health education, water filtration, treatment of unsafe water with temephos (an organophosphate larvicide), and provision of safe drinking water (1,2). The eradication campaign began in 1980 at CDC (1). In 1986, with an estimated 3.5 million cases(†) occurring annually in 20 African and Asian countries(§) (3), the World Health Assembly called for dracunculiasis elimination (4). The Guinea Worm Eradication Program (GWEP), led by The Carter Center and supported by the World Health Organization (WHO), UNICEF, CDC, and other partners, began assisting ministries of health in countries with endemic disease. With 27 cases in humans reported in 2020, five during January-June 2021, and only six countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, South Sudan, and importations into Cameroon), achievement of eradication appears to be close. However, dracunculiasis eradication is challenged by civil unrest, insecurity, and epidemiologic and zoologic concerns. Guinea worm infections in dogs were first reported in Chad in 2012. Animal infections have now overtaken human cases, with 1,601 reported animal infections in 2020 and 443 during January-June 2021. Currently, all national GWEPs remain fully operational, with precautions taken to ensure safety of program staff and community members in response to the COVID-19 pandemic. Because of COVID-19, The Carter Center convened the 2020 and 2021 annual GWEP Program Managers meetings virtually, and WHO's International Commission for the Certification of Dracunculiasis Eradication met virtually in October 2020. Since 1986, WHO has certified 199 countries, areas, and territories dracunculiasis-free. Six countries are still affected: five with endemic disease and importations into Cameroon. Seven countries (five with endemic dracunculiasis, Democratic Republic of the Congo, and Sudan) still lack certification (4). The existence of infected dogs, especially in Chad, and impeded access because of civil unrest and insecurity in Mali and South Sudan are now the greatest challenges to interrupting transmission. This report describes progress during January 2020-June 2021 and updates previous reports (2,4,5).

    • Substance Use and Abuse
      1. Characteristics of an Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury-North Carolina, 2019external icon
        Tanz LJ, Christensen A, Knuth KB, Hoffman MN, Dandeneau D, Koehler K, Moore Z, Herndon S, Davidson K, Fleischauer A.
        N C Med J. 2021 Nov-Dec;82(6):384-392.
        BACKGROUND In August 2019, the North Carolina Division of Public Health (NCDPH) began investigating e-cigarette, or vaping, product use-associated lung injury (EVALI) cases as part of a national response. We describe clinical, epidemiologic, and laboratory findings of North Carolina EVALI patients.METHODS NCDPH requested that physicians report cases of respiratory illness or bilateral pulmonary infiltrates or opacities in patients who reported using e-cigarette, or vaping, products and had no infection or alternative plausible diagnoses. We reviewed medical records, interviewed patients, and tested vaping products for substances.RESULTS During August 13, 2019-February 18, 2020, 78 EVALI cases were reported in North Carolina. Median age of cases was 24 years (range: 13-72 years); 49 (63%) patients were male. Symptoms included cough (n = 70; 90%), shortness of breath (n = 66; 85%), and gastrointestinal symptoms (n = 63; 81%). Seventy-five patients (96%) were hospitalized, 32 (41%) required intensive care, and 12 (16%) required mechanical ventilation; none died. Among 20 patients interviewed, most reported using tetrahydrocannabinol (THC) (n = 16; 80%) or nicotine-containing products (n = 14; 70%). All obtained THC-containing products from informal sources, such as family, friends, or dealers, as THC is illegal in North Carolina. Among 82 products tested, 74 (90%) contained THC, cannabidiol, or cannabinol; 54 (66%) contained vitamin E acetate.LIMITATIONS In North Carolina, EVALI is not reportable by law, and THC is illegal. Thus, cases and exposures are likely underreported.CONCLUSIONS THC-containing products, particularly those containing vitamin E acetate, are associated with EVALI. Persons should not use these products, particularly from informal sources. Continued communication of health risks to persons who use e-cigarette, or vaping, products is essential.

    • Zoonotic and Vectorborne Diseases
      1. Tick-borne encephalitis among US travellers, 2010-20external icon
        Hills SL, Broussard KR, Broyhill JC, Shastry LG, Cossaboom CM, White JL, Machesky KD, Kosoy O, Girone K, Klena JD, Backenson BP, Gould CV, Lind L, Hieronimus A, Gaines DN, Wong SJ, Choi MJ, Laven JJ, Staples JE, Fischer M.
        J Travel Med. 2021 Nov 6.
        BACKGROUND: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas. METHODS: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection. RESULTS: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite. CONCLUSIONS: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported.

      2. Economic evaluation of Zika Contraception Access Network in Puerto Rico during the 2016-17 Zika virus outbreakexternal icon
        Li R, Ellington SR, Galang RR, Grosse SD, Mendoza Z, Hurst S, Vale Y, Lathrop E, Romero L.
        Contraception. 2021 Nov 5.
        OBJECTIVE: During the 2016-2017 Zika virus (ZIKV) outbreak, the prevention of unintended pregnancies was identified as a primary strategy to prevent birth defects. This study estimated the cost-effectiveness of the Zika Contraception Access Network (Z-CAN), an emergency response intervention that provided women in Puerto Rico with access to the full range of reversible contraception at no cost and compared results with a pre-implementation hypothetical cost-effectiveness analysis (CEA). STUDY DESIGN: We evaluated costs and outcomes of Z-CAN from a health sector perspective compared to no intervention using a decision tree model. Number of people served, contraception methods mix, and costs under Z-CAN were from actual program data and other input parameters were from the literature. Health outcome measures included the number of Zika-associated microcephaly (ZAM) cases and unintended pregnancies. The economic benefits of the Z-CAN intervention were ZIKV-associated direct costs avoided, including lifetime medical and supportive costs associated with ZAM cases, costs of monitoring ZIKV-exposed pregnancies and infants born from Zika-virus infected mothers, and the costs of unintended pregnancies prevented during the outbreak as a result of increased contraception use through the Z-CAN intervention. RESULTS: The Z-CAN intervention cost a total of $26.1 million, including costs for the full range of reversible contraceptive methods, contraception related services, and programmatic activities. The program is estimated to have prevented 85% of cases of estimated ZAM cases and unintended pregnancies in the absence of Z-CAN. The intervention cost was projected to have been more than offset by $79.9 million in ZIKV-associated costs avoided, 96% of which were lifetime ZAM-associated costs, as well as $137.0 million from avoided unintended pregnancies, with total net savings in one year of $216.9 million. The results were consistent with the previous CEA study. CONCLUSION: Z-CAN was likely cost-saving in the context of a public health emergency response setting.

      3. Rickettsiosis subcommittee report to the tick-borne disease working groupexternal icon
        Walker DH, Myers CT, Blanton LS, Bloch KC, Fowler VG, Gaines DN, Paddock CD, Yaglom HD.
        Ticks Tick Borne Dis. 2021 Oct 29;13(1):101855.
        Tick-borne rickettsial infections are serious, common, and difficult to diagnose. Among the most important factors leading to failure to diagnose and treat tick-borne rickettsioses effectively is a lack of consideration of the potential diagnosis by primary caregivers and emergency department physicians in patients presenting with undifferentiated acute febrile illness during tick season. This situation exists because of insufficient primary and continuing medical education of medical students, primary care and emergency medicine residents, and practicing physicians regarding tick-borne rickettsioses specific to the region where they practice. Delayed initiation of treatment with an appropriate antibiotic is associated with adverse outcomes including increased rates of hospitalization, admission to an intensive care unit, and mortality. The earliest symptoms are nonspecific, consisting of fever, headache, myalgias, and nausea and/or vomiting. Laboratory abnormalities are typically absent at this time when the therapeutic response to an appropriate antibiotic would be optimal. There is a mistaken idea among a substantial portion of physicians that the best antibiotic available, doxycycline, should not be administered to children 8 years of age or younger or during pregnancy. For all of the above reasons, there is unnecessary morbidity and mortality caused by tick-borne rickettsioses. This report proposes measures to address these critical issues regarding tick-borne rickettsioses.


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