Issue 35, September 28, 2021

CDC Science Clips: Volume 13, Issue 35, September 28, 2021

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Trends in the use of cervical cancer screening tests in a large medical claims database, United States, 2013-2019external icon
        Qin J, Shahangian S, Saraiya M, Holt H, Gagnon M, Sawaya GF.
        Gynecol Oncol. 2021 Sep 7.
        OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: The study population included women of all ages with continuous enrollment each year in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9-9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression. RESULTS: Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21-29 years (P < .0001). Among women aged 30-64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%-13.6% of women aged 18-20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends. CONCLUSIONS: Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.

    • Communicable Diseases
    • Environmental Health
      • Personal interventions for reducing exposure and risk for outdoor air pollution: An official American Thoracic Society Workshop reportexternal icon
        Laumbach RJ, Cromar KR, Adamkiewicz G, Carlsten C, Charpin D, Chan WR, de Nazelle A, Forastiere F, Goldstein J, Gumy S, Hallman WK, Jerrett M, Kipen HM, Pirozzi CS, Polivka BJ, Radbel J, Shaffer RE, Sin DD, Viegi G.
        Ann Am Thorac Soc. 2021 Sep;18(9):1435-1443.
        Poor air quality affects the health and wellbeing of large populations around the globe. Although source controls are the most effective approaches for improving air quality and reducing health risks, individuals can also take actions to reduce their personal exposure by staying indoors, reducing physical activity, altering modes of transportation, filtering indoor air, and using respirators and other types of face masks. A synthesis of available evidence on the efficacy, effectiveness, and potential adverse effects or unintended consequences of personal interventions for air pollution is needed by clinicians to assist patients and the public in making informed decisions about use of these interventions. To address this need, the American Thoracic Society convened a workshop in May of 2018 to bring together a multidisciplinary group of international experts to review the current state of knowledge about personal interventions for air pollution and important considerations when helping patients and the general public to make decisions about how best to protect themselves. From these discussions, recommendations were made regarding when, where, how, and for whom to consider personal interventions. In addition to the efficacy and safety of the various interventions, the committee considered evidence regarding the identification of patients at greatest risk, the reliability of air quality indices, the communication challenges, and the ethical and equity considerations that arise when discussing personal interventions to reduce exposure and risk from outdoor air pollution.

    • Health Disparities
      • How right now: The role of social determinants of health as they relate to emotional well-being amidst the COVID-19 pandemicexternal icon
        Burke-Garcia A, Johnson-Turbes A, Mitchell EW, Vallery Verlenden JM, Puddy R, Mercado MC, Nelson P, Thomas C, Crick C, Leeb R, Rabinowitz L, McCutchan L, Xia K, Wagstaff L, Feng M, Caicedo L, Tolbert E.
        J Emerg Manage. 2021 ;19(9):17-62.
        Pandemics are stressful times, full of uncertainty and fear. During the COVID-19 pandemic, many Americans have experienced feelings of stress, grief, and loss. How Right Now (HRN) – and its Spanish-language counterpart, Qué Hacer Ahora (QHA) – is an evidence-based, culturally-relevant communication campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by the COVID-19 pandemic and beyond. Developed by the Centers for Disease Control and Prevention (CDC) with support from the CDC Foundation, the campaign aims to help all Americans but has a specific focus on some of the disproportionately affected groups, including adults over 65 and their caregivers, individuals with pre-existing physical and mental health conditions, people experiencing violence, and those experiencing economic distress. Based on rapid, but robust, formative research, HRN offers audience-centric messages representing the real, everyday experiences and emotions that these audiences are having and addresses them in actionable ways. These include messages that address the social and structural barrier that disproportionately-affected groups have been facing long before the pandemic — and which are felt more acutely now. This paper provides an overview of the rapid, mixed-method, culturally-responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN’s disproportionately-affected audiences describe and discuss their emotiona well-being during COVID-19 through the lens of Social Determinants of Health (SDOH). We introduce a secondary theory, Vital Conditions for Health and Well-Being (VCHW), which conceptualizes holistic well-being and the conditions that give rise to it and identifies levers for community change and improvement. Data collection methods included an environmental scan (n≥700 publications); social listening (n≥1 million social media posts); partner needs-assessment calls (n=16); partner-convened listening sessions with community members (n=29), online focus groups (n=10), and a national probability survey (n=731), all in English and Spanish. Findings suggest that HRN’s priority audiences’ emotional well-being and SDOH are interconnected. Disruptions in SDOH du to the COVID-19 pandemic can lead to emotional well-being challenges (e.g., anxiety) for HRN’s priority audiences. While some disruptions may lead some people to adapt, connect with others, and be more resilient, there is a disparate impact of emotional well-being amid COVID-19 for those already experiencing disparities linked to SDOH. Understanding the perspectives and experiences of disproportionately affected populations through the lens of SDOH is vital to identifying the kinds of supports and services – like How Right Now/Qué Hacer Ahora – required for these populations. © 2021 Weston Medical Publishing. All rights reserved.

    • Immunity and Immunization
      • Lower cognitive scores among toddlers in birth cohorts with acute respiratory illnesses, fevers, and laboratory-confirmed influenzaexternal icon
        Azziz-Baumgartner E, Gonzalez R, Davis W, Calvo A, Olson N, Grant L, Hess-Holtz M, Veguilla V, Rauda R, Kaydos-Daniels SC, Sosa N, Aedo Ruíz EI, Armero Guardado J, Porter R, Franco D, Pascale JM, Peacock G.
        Influenza Other Respir Viruses. 2021 Sep 14.
        BACKGROUND: We established cohorts to assess associations between viral influenza and cognitive development to inform the value proposition of vaccination. METHODS: From 2014 through 2017, we called women seeking care at four prenatal clinics in Panama and El Salvador to identify acute respiratory illnesses (ARIs). Within 2 weeks of childbirth, mothers were asked to enroll their neonates in the cognitive development study. Staff obtained nasopharyngeal swabs from children with febrile ARIs for real-time reverse transcription polymerase chain reaction (rtPCR) detection of viral RNA. Toddlers were administered Bayley developmental tests at ages 12 and 18-24 months. We used multilevel linear regression to explore associations between Bayley scores, ARIs, fever, and laboratory-confirmed influenza, controlling for maternal respiratory or Zika illnesses, infant influenza vaccination, birth during influenza epidemics, and the number of children in households. RESULTS: We enrolled 1567 neonates of which 68% (n = 1062) underwent developmental testing once and 40% (n = 623) twice. Children with previous ARIs scored an average of 3 points lower on their cognitive scores than children without ARIs (p = 0.001). Children with previous fevers scored an average of 2.1 points lower on their cognitive scores than afebrile children (p = 0.02). In the second year, children with previous laboratory-confirmed influenza scored 4 points lower on their cognitive scores than children without influenza (p = 0.04, after controlling for first Bayley cognitive scores). CONCLUSIONS: ARIs and fever during infancy were associated with lower Bayley scores at 12 months, and laboratory-confirmed influenza was associated with lower cognitive scores at 24 months suggesting the potential value of vaccination to prevent non-respiratory complications of influenza.

    • Occupational Safety and Health
      • Cancer incidence in World Trade Center-exposed and non-exposed male firefighters, as compared with the US adult male population: 2001-2016external icon
        Webber MP, Singh A, Zeig-Owens R, Salako J, Skerker M, Hall CB, Goldfarb DG, Jaber N, Daniels RD, Prezant DJ.
        Occup Environ Med. 2021 Oct;78(10):707-714.
        OBJECTIVE: To compare cancer incidence in Fire Department of the City of New York (FDNY) firefighters who worked at the World Trade Center (WTC) site to incidence in a population of non-WTC-exposed firefighters, the Career Firefighter Health Study (CFHS) cohort, and to compare rates from each firefighter cohort to rates in demographically similar US males. METHODS: FDNY (N=10 786) and CFHS (N=8813) cohorts included male firefighters who were active on 11 September 2001 (9/11) and were followed until death or 31 December 2016. Cases were identified from 15 state cancer registries. Poisson regression models assessed cancers in each group (FDNY and CFHS) versus US males, and associations between group and cancer rates; these models estimated standardised incidence ratios (SIRs) and adjusted relative rates (RRs), respectively. Secondary analyses assessed surveillance bias and smoking history. RESULTS: We identified 915 cancer cases in 841 FDNY firefighters and 1002 cases in 909 CFHS firefighters. FDNY had: higher rates for all cancers (RR=1.13; 95% CI 1.02 to 1.25), prostate (RR=1.39; 95% CI 1.19 to 1.63) and thyroid cancer (RR=2.53; 95% CI 1.37 to 4.70); younger median ages at diagnosis (55.6 vs 59.4; p<0.001, all cancers); and more cases with localised disease when compared with CFHS. Compared with US males, both firefighter cohorts had elevated SIRs for prostate cancer and melanoma. Control for surveillance bias in FDNY reduced most differences. CONCLUSIONS: Excess cancers occurred in WTC-exposed firefighters relative to each comparison group, which may partially be explained by heightened surveillance. Two decades post-9/11, clearer understanding of WTC-related risk requires extended follow-up and modelling studies (laboratory or animal based) to identify workplace exposures in all firefighters.

    • Parasitic Diseases
      • Neglected parasitic infections: What family physicians need to know-a CDC updateexternal icon
        Cantey PT, Montgomery SP, Straily A.
        Am Fam Physician. 2021 Sep 1;104(3):277-287.
        Chagas disease, cysticercosis, and toxoplasmosis affect millions of people in the United States and are considered neglected parasitic diseases. Few resources are devoted to their surveillance, prevention, and treatment. Chagas disease, transmitted by kissing bugs, primarily affects people who have lived in Mexico, Central America, and South America, and it can cause heart disease and death if not treated. Chagas disease is diagnosed by detecting the parasite in blood or by serology, depending on the phase of disease. Antiparasitic treatment is indicated for most patients with acute disease. Treatment for chronic disease is recommended for people younger than 18 years and generally recommended for adults younger than 50 years. Treatment decisions should be individualized for all other patients. Cysticercosis can manifest in muscles, the eyes, and most critically in the brain (neurocysticercosis). Neurocysticercosis accounts for 2.1% of all emergency department visits for seizures in the United States. Diagnosing neurocysticercosis involves serology and neuroimaging. Treatment includes symptom control and antiparasitic therapy. Toxoplasmosis is estimated to affect 11% of people older than six years in the United States. It can be acquired by ingesting food or water that has been contaminated by cat feces; it can also be acquired by eating undercooked, contaminated meat. Toxoplasma infection is usually asymptomatic; however, people who are immunosuppressed can develop more severe neurologic symptoms. Congenital infection can result in miscarriage or adverse fetal effects. Diagnosis is made with serologic testing, polymerase chain reaction testing, or parasite detection in tissue or fluid specimens. Treatment is recommended for people who are immunosuppressed, pregnant patients with recently acquired infection, and people who are immunocompetent with visceral disease or severe symptoms.

      • Safety, immunogenicity and efficacy of PfSPZ vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trialexternal icon
        Oneko M, Steinhardt LC, Yego R, Wiegand RE, Swanson PA, Kc N, Akach D, Sang T, Gutman JR, Nzuu EL, Dungani A, Kim Lee Sim B, Oloo PN, Otieno K, Bii DK, Billingsley PF, James ER, Kariuki S, Samuels AM, Jongo S, Chebore W, Abdulla S, Daubenberger C, Mpina M, Styers D, Potter GE, Abarbanell G, Richie TL, Hoffman SL, Seder RA.
        Nat Med. 2021 Sep;27(9):1636-1645.
        The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10(5), 9.0 × 10(5) or 1.8 × 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10(5) dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2(+)Vγ9(+) T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2(+)Vγ9(+) T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.

    • Physical Activity
      • Priorities and indicators for economic evaluation of built environment interventions to promote physical activityexternal icon
        Cradock AL, Buchner D, Zaganjor H, Thomas JV, Sallis JF, Rose K, Meehan L, Lawson M, Lavinghouze R, Fenton M, Devlin HM, Carlson SA, Bhattacharya T, Fulton JE.
        J Phys Act Health. 2021 Jul 9:1-9.
        BACKGROUND: Built environment approaches to promoting physical activity can provide economic value to communities. How best to assess this value is uncertain. This study engaged experts to identify a set of key economic indicators useful for evaluation, research, and public health practice. METHODS: Using a modified Delphi process, a multidisciplinary group of experts participated in (1) one of 5 discussion groups (n = 21 experts), (2) a 2-day facilitated workshop (n = 19 experts), and/or (3) online surveys (n = 16 experts). RESULTS: Experts identified 73 economic indicators, then used a 5-point scale to rate them on 3 properties: measurement quality, feasibility of use by a community, and influence on community decision making. Twenty-four indicators were highly rated (≥3.9 on all properties). The 10 highest-rated "key" indicators were walkability score, residential vacancy rate, housing affordability, property tax revenue, retail sales per square foot, number of small businesses, vehicle miles traveled per capita, employment, air quality, and life expectancy. CONCLUSION: This study identified key economic indicators that could characterize the economic value of built environment approaches to promoting physical activity. Additional work could demonstrate the validity, feasibility, and usefulness of these key indicators, in particular to inform decisions about community design.

    • Public Health Leadership and Management
    • Reproductive Health
      • Changes in U.S. healthcare provider practices related to emergency contraceptionexternal icon
        Pagano HP, Zapata LB, Curtis KM, Whiteman MK.
        Womens Health Issues. 2021 Sep 9.
        INTRODUCTION: Emergency contraception (EC), including EC pills (ECPs) and the copper intrauterine device, can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), initially released in 2013, provides evidence-based clinical recommendations on the provision of EC. The objective of this analysis was to assess the percentage of health care providers reporting frequent provision of select EC practices around the time of and after the release of the U.S. SPR. METHODS: We conducted two cross-sectional mailed surveys using different nationwide samples of office-based physicians and public-sector providers in 2013 and 2014 (n = 2,060) and 2019 (n = 1,420). We compared the percentage of providers reporting frequent provision of select EC practices by time period, overall, and by provider type. RESULTS: In 2019, few providers frequently provided an advance prescription for ECPs (16%), an advance supply of ECPs (7%), or the copper intrauterine device as EC (8%), although 41% frequently provided or prescribed regular contraception at the same time as providing ECPs. Providers in 2019 were more likely than providers in 2013 and 2014 to provide or prescribe contraception at the same time as providing ECPs (adjusted prevalence ratio, 1.26; 95% confidence interval, 1.001-1.59) and to provide a copper intrauterine device as EC (adjusted prevalence ratio, 3.87; 95% confidence interval 2.10-7.15); there were no other significant differences by time period. CONCLUSIONS: Few providers report frequent provision of recommended EC practices. Understanding the barriers faced by providers and clinics in implementing these practices may improve access to EC.

    • Zoonotic and Vectorborne Diseases
      • Ongoing outbreak of extensively drug-resistant Campylobacter jejuni infections associated with US pet store puppies, 2016-2020external icon
        Francois Watkins LK, Laughlin ME, Joseph LA, Chen JC, Nichols M, Basler C, Breazu R, Bennett C, Koski L, Montgomery MP, Hughes MJ, Robertson S, Lane CG, Singh AJ, Stanek D, Salehi E, Brandt E, McGillivary G, Mowery J, DeMent J, Aubert RD, Geissler AL, de Fijter S, Williams IT, Friedman CR.
        JAMA Netw Open. 2021 Sep 1;4(9):e2125203.
        IMPORTANCE: Extensively drug-resistant Campylobacter jejuni infections cannot be treated with any commonly recommended antibiotics and pose an increasing public health threat. OBJECTIVES: To investigate cases of extensively drug-resistant C jejuni associated with pet store puppies and describe the epidemiologic and laboratory characteristics of these infections. DESIGN, SETTING, AND PARTICIPANTS: In August 2017, health officials identified, via survey, patients with C jejuni infections who reported contact with puppies sold by pet stores. In conjunction with state and federal partners, the Centers for Disease Control and Prevention investigated cases of culture-confirmed C jejuni infections in US patients with an epidemiologic or molecular association with pet store puppies between January 1, 2016, and February 29, 2020. Available records from cases occurring before 2016 with genetically related isolates were also obtained. MAIN OUTCOMES AND MEASURES: Patients were interviewed about demographic characteristics, health outcomes, and dog exposure during the 7 days before illness onset. Core genome multilocus sequence typing was used to assess isolate relatedness, and genomes were screened for resistance determinants to predict antibiotic resistance. Isolates resistant to fluoroquinolones, macrolides, and 3 or more additional antibiotic classes were considered to be extensively drug resistant. Cases before 2016 were identified by screening all sequenced isolates submitted for surveillance using core genome multilocus sequence typing. RESULTS: A total of 168 patients (median [interquartile range] age, 37 [19.5-51.0] years; 105 of 163 female [64%]) with an epidemiologic or molecular association with pet store puppies were studied. A total of 137 cases occurred from January 1, 2016, to February 29, 2020, with 31 additional cases dating back to 2011. Overall, 117 of 121 patients (97%) reported contact with a dog in the week before symptom onset, of whom 69 of 78 (88%) with additional information reported contact with a pet store puppy; 168 isolates (88%) were extensively drug resistant. Traceback investigation did not implicate any particular breeder, transporter, distributer, store, or chain. CONCLUSIONS AND RELEVANCE: Strains of extensively drug-resistant C jejuni have been circulating since at least 2011 and are associated with illness among pet store customers, employees, and others who come into contact with pet store puppies. The results of this study suggest that practitioners should ask about puppy exposure when treating patients with Campylobacter infection, especially when they do not improve with routine antibiotics, and that the commercial dog industry should take action to help prevent the spread of extensively drug-resistant C jejuni from pet store puppies to people.

  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. Longitudinal trends in body mass index before and during the COVID-19 pandemic among persons aged 2-19 years - United States, 2018-2020external icon
        Lange SJ, Kompaniyets L, Freedman DS, Kraus EM, Porter R, Blanck HM, Goodman AB.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1278-1283.
        Obesity is a serious health concern in the United States, affecting more than one in six children (1) and putting their long-term health and quality of life at risk.* During the COVID-19 pandemic, children and adolescents spent more time than usual away from structured school settings, and families who were already disproportionally affected by obesity risk factors might have had additional disruptions in income, food, and other social determinants of health.(†) As a result, children and adolescents might have experienced circumstances that accelerated weight gain, including increased stress, irregular mealtimes, less access to nutritious foods, increased screen time, and fewer opportunities for physical activity (e.g., no recreational sports) (2,3). CDC used data from IQVIA's Ambulatory Electronic Medical Records database to compare longitudinal trends in body mass index (BMI, kg/m(2)) among a cohort of 432,302 persons aged 2-19 years before and during the COVID-19 pandemic (January 1, 2018-February 29, 2020 and March 1, 2020-November 30, 2020, respectively). Between the prepandemic and pandemic periods, the rate of BMI increase approximately doubled, from 0.052 (95% confidence interval [CI] = 0.051-0.052 to 0.100 (95% CI = 0.098-0.101) kg/m(2)/month (ratio = 1.93 [95% CI = 1.90-1.96]). Persons aged 2-19 years with overweight or obesity during the prepandemic period experienced significantly higher rates of BMI increase during the pandemic period than did those with healthy weight. These findings underscore the importance of efforts to prevent excess weight gain during and following the COVID-19 pandemic, as well as during future public health emergencies, including increased access to efforts that promote healthy behaviors. These efforts could include screening by health care providers for BMI, food security, and social determinants of health, increased access to evidence-based pediatric weight management programs and food assistance resources, and state, community, and school resources to facilitate healthy eating, physical activity, and chronic disease prevention.

      2. Baby boomers who provide informal care for people living with dementia in the communityexternal icon
        Miyawaki CE, Bouldin ED, Taylor CA, McGuire LC.
        Int J Environ Res Public Health. 2021 ;18(18).
        One in four Baby Boomers fills the informal caregiver role in the United States. The objectives of this study were to estimate the prevalence of Baby Boomers who are informal caregivers for people living with dementia and compare their physical and mental health status to caregivers for persons with conditions other than dementia using 2015–2018 Behavioral Risk Factor Surveillance System data (n = 10,602). We identified caregiving status (assisting a family member/friend with a long-term illness or disability in the past month, managing personal care, and not caring for a child/grandchild) and whether the care recipient’s major health condition was dementia. We calculated weighted estimates and used chi-square tests and log-binomial regression for comparisons of selected characteristics. Among Baby Boomer caregivers, 15.4% were caring for someone with dementia. Dementia caregivers were more likely to be female, caring for a parent/parent-in-law, and providing care longer than caregivers for persons without dementia. After adjusting for sociodemographic and caregiving characteristics, the prevalence of fair/poor health, frequent mental distress, and chronic conditions were similar across types of caregivers. Although no differences in caregiver’s physical and mental health by care recipient’s dementia status were found, we should underscore the importance of maintaining Baby Boomer caregivers’ health and well-being. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      3. Asthma surveillance - United States, 2006-2018external icon
        Pate CA, Zahran HS, Qin X, Johnson C, Hummelman E, Malilay J.
        MMWR Surveill Summ. 2021 Sep 17;70(5):1-32.
        PROBLEM: Asthma is a chronic disease of the airways that requires ongoing medical management. Socioeconomic and demographic factors as well as health care use might influence health patterns in urban and rural areas. Persons living in rural areas tend to have less access to health care and health resources and worse health outcomes. Characterizing asthma indicators (i.e., prevalence of current asthma, asthma attacks, emergency department and urgent care center [ED/UCC] visits, and asthma-associated deaths) and determining how asthma exacerbations and health care use vary across the United States by geographic area, including differences between urban and rural areas, and by sociodemographic factors can help identify subpopulations at risk for asthma-related complications. REPORTING PERIOD: 2006-2018. DESCRIPTION OF SYSTEM: The National Health Interview Survey (NHIS) is an annual cross-sectional household health survey among the civilian noninstitutionalized population in the United States. NHIS data were used to produce estimates for current asthma and among them, asthma attacks and ED/UCC visits. National Vital Statistics System (NVSS) data were used to estimate asthma deaths. Estimates of current asthma, asthma attacks, ED/UCC visits, and asthma mortality rates are described by demographic characteristics, poverty level (except for deaths), and geographic area for 2016-2018. Trends in asthma indicators by metropolitan statistical area (MSA) category for 2006-2018 were determined. Current asthma and asthma attack prevalence are provided by MSA category and state for 2016-2018. Detailed urban-rural classifications (six levels) were determined by merging 2013 National Center for Health Statistics (NCHS) urban-rural classification data with 2016-2018 NHIS data by county and state variables. All subregional estimates were accessed through the NCHS Research Data Center. RESULTS: Current asthma was higher among boys aged <18 years, women aged ≥18 years, non-Hispanic Black (Black) persons, non-Hispanic multiple-race (multiple-race) persons, and Puerto Rican persons. Asthma attacks were more prevalent among children, females, and multiple-race persons. ED/UCC visits were more prevalent among children, women aged ≥18 years, and all racial and ethnic groups (i.e., Black, non-Hispanic Asian, multiple race, and Hispanic, including Puerto Rican, Mexican, and other Hispanic) except American Indian and Alaska Native persons compared with non-Hispanic White (White) persons. Asthma deaths were higher among adults, females, and Black persons. All pertinent asthma outcomes were also more prevalent among persons with low family incomes. Current asthma prevalence was higher in the Northeast than in the South and the West, particularly in small MSA areas. The prevalence was also higher in small and medium metropolitan areas than in large central metropolitan areas. The prevalence of asthma attacks differed by MSA category in four states. The prevalence of ED/UCC visits was higher in the South than the Northeast and the Midwest and was also higher in large central metropolitan areas than in micropolitan and noncore areas. The asthma mortality rate was highest in non-MSAs, specifically noncore areas. The asthma mortality rate was also higher in the Northeast, Midwest, and West than in the South. Within large MSAs, asthma deaths were higher in the Northeast and Midwest than the South and West. INTERPRETATION: Despite some improvements in asthma outcomes over time, the findings from this report indicate that disparities in asthma indicators persist by demographic characteristics, poverty level, and geographic location. PUBLIC HEALTH ACTION: Disparities in asthma outcomes and health care use in rural and urban populations identified from NHIS and NVSS can aid public health programs in directing resources and interventions to improve asthma outcomes. These data also can be used to develop strategic goals and achieve CDC's Controlling Childhood Asthma and Reducing Emergencies (CCARE) initiative to reduce childhood asthma hospitalizations and ED visits and prevent 500,000 asthma-related hospitalizations and ED visits by 2024.

      4. Tubular injury in diabetic ketoacidosis: Results from the Diabetic Kidney Alarm Studyexternal icon
        Piani F, Melena I, Severn C, Chung LT, Vinovskis C, Cherney D, Pyle L, Roncal-Jimenez CA, Lanaspa MA, Rewers A, van Raalte DH, Obeid W, Parikh C, Nelson RG, Pavkov ME, Nadeau KJ, Johnson RJ, Bjornstad P.
        Pediatr Diabetes. 2021 Aug 26.
        OBJECTIVE: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0-8 and 12-24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). RESULTS: Serum NGAL, KIM-1, and IL-18 were highest at 0-8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0-8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. CONCLUSIONS: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.

      5. Comprehensive search for novel circulating miRNAs and axon guidance pathway proteins associated with risk of ESKD in diabetesexternal icon
        Satake E, Saulnier PJ, Kobayashi H, Gupta MK, Looker HC, Wilson JM, Md Dom ZI, Ihara K, O'Neil K, Krolewski B, Pipino C, Pavkov ME, Nair V, Bitzer M, Niewczas MA, Kretzler M, Mauer M, Doria A, Najafian B, Kulkarni RN, Duffin KL, Pezzolesi MG, Kahn CR, Nelson RG, Krolewski AS.
        J Am Soc Nephrol. 2021 Sep;32(9):2331-2351.
        BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

    • Communicable Diseases
      1. Data on use of and barriers to HIV ancillary care services among people who inject drugs (PWID) with HIV can inform interventions intended to improve access to care, but national estimates are lacking. We analyzed data on PWID with HIV from the CDC Medical Monitoring Project. Overall, 79% had an unmet need for ≥1 service. Services with the highest unmet need included: dental care (38%), drug/alcohol treatment (20%), transportation assistance (20%), and HIV peer group support (20%). Unmet needs for mental health services (13% vs. 23%) and HIV peer group support (15% vs. 29%) were lower among persons attending Ryan White HIV/AIDS Program (RWHAP)-funded facilities for HIV care. Barriers to care services varied by service type. Modeling components of the RWHAP structure in non-RWHAP funded facilities, including integration of support services and use of patient navigation services in the HIV medical care setting, may improve outcomes among PWID with HIV. ©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

      2. HIV incidence by male circumcision status from the population-based HIV impact assessment surveys-eight sub-Saharan African countries, 2015-2017external icon
        Hines JZ, Sachathep K, Pals S, Davis SM, Toledo C, Bronson M, Parekh B, Carrasco M, Xaba S, Mandisarisa J, Kamobyi R, Chituwo O, Kirungi WL, Alamo S, Kabuye G, Awor AC, Mmbando S, Simbeye D, Aupokolo MA, Zemburuka B, Nyirenda R, Msungama W, Tarumbiswa T, Manda R, Nuwagaba-Biribonwoha H, Kiggundu V, Thomas AG, Watts H, Voetsch AC, Williams DB.
        J Acquir Immune Defic Syndr. 2021 Aug 1;87(Suppl 1):S89-s96.
        BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally representative samples. Data from the population-based HIV impact assessments were used to compare HIV incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from population-based HIV impact assessments conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2017. Incidence was measured using a recent infection testing algorithm and analyzed by self-reported MC status distinguishing between medical and nonmedical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random-effects logistic regression model using pooled survey weights. Analyses were age stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men [0.04% (95% CI: 0.00% to 0.10%) versus 0.34% (95% CI: 0.10% to 0.57%), respectively; P value = 0.01]; whereas among men 35-59 years, there was no significant incidence difference [1.36% (95% CI: 0.32% to 2.39%) versus 0.55% (95% CI: 0.14% to 0.67%), respectively; P value = 0.14]. DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa.

      3. Trade-offs between individual and ensemble forecasts of an emerging infectious diseaseexternal icon
        Oidtman RJ, Omodei E, Kraemer MU, Castañeda-Orjuela CA, Cruz-Rivera E, Misnaza-Castrillón S, Cifuentes MP, Rincon LE, Cañon V, Alarcon P, España G, Huber JH, Hill SC, Barker CM, Johansson MA, Manore CA, Reiner RC, Rodriguez-Barraquer I, Siraj AS, Frias-Martinez E, García-Herranz M, Perkins TA.
        Nat Commun. 2021 Sep 10;12(1):5379.
        Probabilistic forecasts play an indispensable role in answering questions about the spread of newly emerged pathogens. However, uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among alternative model structures and assumptions. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about human mobility, spatiotemporal variation in transmission potential, and the number of virus introductions. We found that which model assumptions had the most ensemble weight changed through time. We additionally identified a trade-off whereby some individual models outperformed ensemble models early in the epidemic, but on average the ensembles outperformed all individual models. Our results suggest that multiple models spanning uncertainty across alternative assumptions are necessary to obtain robust forecasts for emerging infectious diseases.

      4. Informing the future of PrEP navigation: Findings from a five-site cluster evaluationexternal icon
        Salabarría-Peña Y, Douglas C, Brantley M, Johnson AK.
        Eval Program Plann. 2021 Sep 2:101999.
        The PrEP (pre-exposure prophylaxis) Implementation, Data to Care and Evaluation (PrIDE) demonstration project funded 12 health departments (HD) (2016-2019) to scale up PrEP among sexual minorities at risk for HIV. Each health department (HD) conducted an evaluation of at least one local strategy, and, to maximize crossvalidation, an adapted cluster evaluation approach was employed. As a result, five HDs with similar evaluation questions regarding PrEP navigation were identified. Overall, PrEP navigation fit in well with HD clinics and community-based organizations. A hybrid model of patient, peer, and systems navigation linking clients to PrEP and social services was commonly used. Although there were no differences by setting regarding linking clients to PrEP providers, one HD demonstrated that having all PrEP services in the same location contributed the most to PrEP uptake. Navigator skill for case management and rapport building facilitated navigation, whereas staff turnover and lack of client health insurance were challenges. While one HD in a non-Medicaid expansion state was affected by health insurance issues the most, another HD demonstrated that providing payment assistance increased client PrEP use. The findings pinpoint PrEP navigation hybrid modality and having health insurance as promising strategies to increase PrEP uptake among priority groups.

      5. Going beyond performance measures in HIV-prevention: A funder-recipient expeditionexternal icon
        Salabarría-Peña Y, Robinson WT.
        Eval Program Plann. 2021 Sep 2:101996.
        Project PrIDE (PrEP Implementation, Data to Care, and Evaluation) was a multi-site demonstration project implemented in 12 health departments (HDs) from 2016 to 2019. In Project PrIDE, there were two monitoring and evaluation components: crossjurisdictional performance monitoring (CJPM) and local program evaluation (LE). Project PrIDE was innovative in that a portion of funds were allocated for LE in order to support robust process and outcome evaluations. The purpose of this article is threefold: to describe Project PrIDE LE conceptualization, to share lessons learned about LE development and implementation processes that may benefit other programs and evaluation initiatives, and to introduce the Special Issue. This experience highlights the importance of using a health equity lens in future evaluation efforts in HIV prevention involving historically marginalized populations to ensure that priority groups are treated as equal partners of and benefit from the evaluations.

      6. Trends in HIV prevalence by self-report among MSM diagnosed and 1 reported with gonorrhea in six U.S. jurisdictions, 2010-2019external icon
        Stenger MR, Pathela P, Schumacher C, Burghardt N, Amiya R, Madera R, Nguyen TQ, Torrone E.
        Aids. 2021 Sep 10.
        BACKGROUND: HIV co-infection among persons diagnosed with gonorrhea is not well characterized. Trends in HIV prevalence among persons diagnosed with gonorrhea may have significant implications for HIV prevention interventions, especially for MSM. MSM are increasing and disproportionately represented among incident gonorrhea cases reported in a multi-state sentinel surveillance network. Using data from this network, we estimated HIV prevalence among MSM by self-report and explored trends in co-infection by key demographics. DESIGN: Observational study using enhanced surveillance data. METHODS: Six geographically diverse jurisdictions in the STD Surveillance Network (SSuN) 2010 - 2019 randomly sampled laboratory-confirmed gonorrhea cases. Enhanced investigations on sampled cases included patient interviews eliciting demographic, behavioral and HIV testing history. These data were weighted to adjust for study design and non-response to estimate trends in HIV prevalence. RESULTS: Of 653,522 reported cases, 28,979 were sampled and investigated. The proportion of cases reporting living with diagnosed HIV at the time of their gonorrhea diagnosis increased 61% across the study period from 6.6% in 2010 to 10.8% in 2019. The observed increase in HIV prevalence is concurrent with an increase in the proportion of gonorrhea cases attributable to MSM. HIV prevalence among MSM decreased in two jurisdictions and increasing trends were observed among Non-Hispanic Black and Hispanic MSM. HIV prevalence decreased among non-Hispanic White MSM, MSM under 20 and those 40 years of age or older. CONCLUSIONS: Diagnosis with gonorrhea, especially among MSM, should be a sentinel event triggering screening for HIV, referral to high-impact HIV prevention interventions or to HIV primary care.

    • Community Health Services
      1. Pre-emptive school closures are frontline community mitigation measures recommended by the US Centers for Disease Control and Prevention (CDC) for implementation during severe pandemics. This study describes the spatiotemporal patterns of publicly announced school closures implemented in response to the coronavirus disease 2019 (COVID-19) pandemic and assesses how public K-12 districts adjusted their methods of education delivery and provision of subsidized meals. During February 18-June 30, 2020, we used daily systematic media searches to identify publicly announced COVID-19-related school closures lasting ≥1 day in the United States (US). We also collected statewide school closure policies from state government websites. Data on distance learning and subsidized meal programs were collected from a stratified sample of 600 school districts. The first COVID-19-associated school closure occurred on February 27, 2020 in Washington state. By March 30, 2020, all but one US public school districts were closed, representing the first-ever nearly synchronous nationwide closure of public K-12 schools in the US. Approximately 100,000 public schools were closed for ≥8 weeks because of COVID-19, affecting >50 million K-12 students. Of 600 districts sampled, the vast majority offered distance learning (91.0%) and continued provision of subsidized meal programs (78.8%) during the closures. Despite the sudden and prolonged nature of COVID-19-associated school closures, schools demonstrated flexibility by implementing distance learning and alternate methods to continue subsidized meal programs.

    • Disaster Control and Emergency Services
      1. World Trade Center Health Program: 20 years after 9/11external icon
        Calvert GM, Reissman D, Howard J.
        Occup Environ Med. 2021 Oct;78(10):697-698.

      2. How do I… facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?external icon
        Miller MJ, Skrzekut A, Kracalik I, Jones JM, Lofy KH, Konkle BA, Haley NR, Duvenhage M, Bonnett T, Holbrook M, Higgs E, Basavaraju SV, Paranjape S.
        Transfusion. 2021 Sep 12.
        In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.

    • Environmental Health
      1. Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohortexternal icon
        Jedynak P, Tost J, Calafat AM, Bourova-Flin E, Busato F, Forhan A, Heude B, Jakobi M, Rousseaux S, Schwartz J, Slama R, Vaiman D, Philippat C, Lepeule J.
        Environ Pollut. 2021 Aug 21;290:118024.
        In utero exposure to environmental chemicals, such as synthetic phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary biomarker concentrations of synthetic phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary phenol concentrations and DNA methylation. We identified 46 significant DMRs (≥5 CpGs) associated with triclosan (37 DMRs), 2,4-dichlorophenol (3), benzophenone-3 (3), methyl- (2) and propylparaben (1). All but 2 DMRs were positively associated with phenol concentrations. Out of the 46 identified DMRs, 7 (6 for triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding transcription factors, histones, tumor suppressors, genes involved in tumorigenesis and several cancer risk biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to triclosan, could affect fetal development.

    • Food Safety
      1. Mild botulism from illicitly brewed alcohol in a large prison outbreak in Mississippiexternal icon
        Marlow M, Edwards L, McCrickard L, Francois Watkins LK, Anderson J, Hand S, Taylor K, Dykes J, Byers P, Chatham-Stephens K.
        Front Public Health. 2021 ;9:716615.
        Botulism is typically described as a rapidly progressing, severe neuroparalytic disease. Foodborne botulism is transmitted through consuming food or drink that has been contaminated with botulinum toxin. During a botulism outbreak linked to illicitly brewed alcohol (also known as "hooch" or "pruno") in a prison, 11 (35%) of 31 inmates that consumed contaminated hooch had mild illnesses. This includes 2 inmates with laboratory confirmed botulism. The most frequently reported signs and symptoms among the 11 patients with mild illness included dry mouth (91%), hoarse voice (91%), difficulty swallowing (82%), fatigue (82%), and abdominal pain (82%). Foodborne botulism is likely underdiagnosed and underreported in patients with mild illness. Botulism should be considered on the differential diagnosis for patients with cranial nerve palsies.

      2. Assessment of genetic stability during serial in vitro passage and in vivo carriageexternal icon
        Sabol A, Joung YJ, VanTubbergen C, Ale J, Ribot EM, Trees E.
        Foodborne Pathog Dis. 2021 Sep 14.
        In this study, our objective was to evaluate the genetic stability of foodborne bacterial pathogens during serial passage in vitro and persistent in vivo carriage. Six strains of Listeria, Campylobacter, Escherichia, Salmonella, and Vibrio were serially passaged 20 times. Three colonies were picked for whole-genome sequencing (WGS) from passes P0, P5, P10, P15, and P20. In addition, isolates of Salmonella and Escherichia from three patients with persistent infections were sequenced. Genetic stability was evaluated in terms of variations detected in high-quality single-nucleotide polymorphism (hqSNP), core genome multilocus sequence typing (cgMLST), seven-gene MLST, and determinants encoding serotype, antimicrobial resistance (AMR), and virulence. During serial passage, increasing diversity was observed in Listeria, Salmonella, and Vibrio as measured by hqSNPs (from median of 0 SNPs to median of 3-5 SNPs, depending on the organism) and to a lesser extent with cgMLST (from median of 0 alleles to median of 0-5 alleles), while Escherichia and Campylobacter genomes showed minimal variation. The serotype, AMR, and virulence markers remained stable in all organisms. Isolates from persistent infections lasting up to 10 weeks remained genetically stable. However, isolates from a persistent Salmonella enterica ser. Montevideo infection spanning 9 years showed early heterogeneity leading to the emergence of one predominant genotype that continued to evolve over the years, including gains and losses of AMR markers. While the hqSNP and cgMLST variation observed during the serial passage was minimal, culture passages should be limited to as few times as possible before WGS. Our WGS data show that in vivo carriage lasting for a few weeks did not appear to alter the genotype. Longer persistent infections spanning for years, particularly in the presence of selective pressure, may cause changes in the genotype making it challenging to differentiate persistent infections from reinfections.

    • Genetics and Genomics
      1. Comparative genomic analysis of genogroup 1 and genogroup 2 rotaviruses circulating in seven US cities, 2014-2016external icon
        Esona MD, Gautam R, Katz E, Jaime J, Ward ML, Wikswo ME, Betrapally NS, Rustempasic SM, Selvarangan R, Harrison CJ, Boom JA, Englund J, Klein EJ, Staat MA, McNeal MM, Halasa N, Chappell J, Weinberg GA, Payne DC, Parashar UD, Bowen MD.
        Virus Evol. 2021 Jan;7(1):veab023.
        For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix(®) vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2-11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.

    • Health Disparities
      1. BACKGROUND: Approximately 20,000 people died from influenza in the US in the 2019 - 2020 season. The best way to prevent influenza is to receive the influenza vaccine. Persons who are foreign-born experience disparities in access to, and utilization of, preventative healthcare, including vaccination. METHODS: National Health Interview Survey (NHIS) data were analyzed to assess differences in influenza vaccination coverage during the 2012-13 through 2017-18 influenza seasons among adults by nativity, citizenship status of foreign-born persons, race/ethnicity, and language of the interview. RESULTS: Influenza vaccination coverage increased significantly during the study period for US-born adults but did not change significantly among foreign-born racial/ethnic groups except for increases among foreign-born Hispanic adults. Coverage for foreign-born adults, those who completed an interview in a non-English language, and non-US citizens, had lower vaccination coverage during most influenza seasons studied, compared with US-born, English-interviewed, and US-citizen adults, respectively. CONCLUSION: Strategies to improve influenza vaccination uptake must consider foreign-born adults as an underserved population in need of focused, culturally-tailored outreach. Achieving high influenza vaccination coverage among the foreign-born population will help reduce illness among the essential workforce, achieve national vaccination goals, and reduce racial and ethnic disparities in vaccination coverage in the US.

      2. Disaggregating data to measure racial disparities in COVID-19 outcomes and guide community response - Hawaii, March 1, 2020-February 28, 2021external icon
        Quint JJ, Van Dyke ME, Maeda H, Worthington JK, Dela Cruz MR, Kaholokula JK, Matagi CE, Pirkle CM, Roberson EK, Sentell T, Watkins-Victorino L, Andrews CA, Center KE, Calanan RM, Clarke KE, Satter DE, Penman-Aguilar A, Parker EM, Kemble S.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1267-1273.
        Native Hawaiian and Pacific Islander populations have been disproportionately affected by COVID-19 (1-3). Native Hawaiian, Pacific Islander, and Asian populations vary in language; cultural practices; and social, economic, and environmental experiences,(†) which can affect health outcomes (4).(§) However, data from these populations are often aggregated in analyses. Although data aggregation is often used as an approach to increase sample size and statistical power when analyzing data from smaller population groups, it can limit the understanding of disparities among diverse Native Hawaiian, Pacific Islander, and Asian subpopulations(¶) (4-7). To assess disparities in COVID-19 outcomes among Native Hawaiian, Pacific Islander, and Asian populations, a disaggregated, descriptive analysis, informed by recommendations from these communities,** was performed using race data from 21,005 COVID-19 cases and 449 COVID-19-associated deaths reported to the Hawaii State Department of Health (HDOH) during March 1, 2020-February 28, 2021.(††) In Hawaii, COVID-19 incidence and mortality rates per 100,000 population were 1,477 and 32, respectively during this period. In analyses with race categories that were not mutually exclusive, including persons of one race alone or in combination with one or more races, Pacific Islander persons, who account for 5% of Hawaii's population, represented 22% of COVID-19 cases and deaths (COVID-19 incidence of 7,070 and mortality rate of 150). Native Hawaiian persons experienced an incidence of 1,181 and a mortality rate of 15. Among subcategories of Asian populations, the highest incidences were experienced by Filipino persons (1,247) and Vietnamese persons (1,200). Disaggregating Native Hawaiian, Pacific Islander, and Asian race data can aid in identifying racial disparities among specific subpopulations and highlights the importance of partnering with communities to develop culturally responsive outreach teams(§§) and tailored public health interventions and vaccination campaigns to more effectively address health disparities.

    • Healthcare Associated Infections
      1. Feasibility of a nursing home antibiotic stewardship interventionexternal icon
        Baier RR, Jump RL, Zhang T, Kabbani S, Gifford DR, Gravenstein S.
        J Am Med Dir Assoc. 2021 Sep 7.
        OBJECTIVE: To evaluate a bundled electronic intervention to improve antibiotic prescribing practices in US nursing homes. DESIGN: Prospective mixed-methods quality improvement intervention. SETTING AND PARTICIPANTS: Nursing staff and residents in 13 nursing homes, and residents in 8 matched-control facilities (n = 21 facilities total, from 2 corporations). METHODS: This study involved a 2-month design period (n = 5 facilities) focused on the acceptability and feasibility of a bundled electronic intervention consisting of 3 tools, followed by a 15-month implementation period (n = 8 facilities) during which we used rapid-cycle quality improvement methods to refine and add to the bundle. We used mixed-methods data from providers, intervention tools, and health records to assess feasibility and conduct a difference-in-difference analysis among the 8 intervention sites and 8 pair-matched controls. RESULTS: Nurses at 5 pilot sites reported that initial versions of the electronic tools were acceptable and feasible, but barriers emerged when 8 different facilities began implementing the tools, prompting iterative revisions to the training and bundle. The final bundle consisted of 3 electronic tools and training that standardized digital documentation to document and track a change in resident condition, infections, antibiotic prescribing, and antibiotic follow-up. By the end of the implementation phase, all 8 facilities were using at least 1 of the 3 tools. Early antibiotic discontinuation increased 10.5% among intervention sites, but decreased 10.8% among control sites. CONCLUSIONS AND IMPLICATIONS: The 3 tools in our bundled electronic intervention capture clinical and prescribing data necessary to assess changes in antibiotic use and were feasible for nurses to adopt. Achieving this required modifying the tools and training before the intervention reached its final form. Comparisons of rates of antibiotic use at intervention and control facilities showed promising improvement in antibiotic discontinuation, demonstrating that the intervention could be evaluated using secondary electronic health record data.

      2. Norovirus outbreaks in long-term care facilities in the United States, 2009-2018: a decade of surveillanceexternal icon
        Calderwood LE, Wikswo ME, Mattison CP, Kambhampati AK, Balachandran N, Vinjé J, Barclay L, Hall AJ, Parashar U, Mirza SA.
        Clin Infect Dis. 2021 Sep 15.
        BACKGROUND: In the US, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). METHODS: CDC collects epidemiologic and laboratory data on norovirus outbreaks from U.S. health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009-2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. RESULTS: During 2009-2018, 50 states, Washington D.C., and Puerto Rico reported 13,092 norovirus outbreaks and 416,284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009-2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (IQR: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%) and 75% occurred during December-March. Genogroup was reported for 7,292 outbreaks with 862 (11.8%) positive for GI and 6,370 (87.3%) for GII. Among 4,425 GII outbreaks with typing data, 3,618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% versus 10.9%; p<0.001). For every 1,000 cases, there were 21.6 hospitalizations and 2.3 deaths. CONCLUSIONS: LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains.

      3. Carbapenemase production among less-common Enterobacterales genera: 10 US sites, 2018external icon
        Shugart A, Mahon G, Huang JY, Karlsson M, Valley A, Lasure M, Gross A, Pattee B, Vaeth E, Brooks R, Maruca T, Dominguez CE, Torpey D, Francis D, Bhattarai R, Kainer MA, Chan A, Dubendris H, Greene SR, Blosser SJ, Shannon DJ, Jones K, Brennan B, Hun S, D'Angeli M, Murphy CN, Tierney M, Reese N, Bhatnagar A, Kallen A, Brown AC, Spalding Walters M.
        JAC Antimicrob Resist. 2021 Sep;3(3):dlab137.
        BACKGROUND: Historically, United States' carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: Escherichia, Klebsiella, and Enterobacter (EsKE); however, other genera can harbour mobile carbapenemases associated with CRE spread. OBJECTIVES: From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE. METHODS: State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory. SPHLs performed species identification, phenotypic carbapenemase production testing, and molecular testing for carbapenemases to identify CP-CRE. Isolates were categorized as CP if they demonstrated phenotypic carbapenemase production and ≥1 carbapenemase gene (bla (KPC), bla (NDM), bla (VIM), bla (IMP), or bla (OXA-48-like)) was detected. RESULTS: SPHLs tested 868 CRE isolates, 127 (14.6%) were from eight LCG. Overall, 195 (26.3%) EsKE isolates were CP-CRE, compared with 24 (18.9%) LCG isolates. LCG accounted for 24 (11.0%) of 219 CP-CRE identified. Citrobacter spp. was the most common CP-LCG; the proportion of Citrobacter that were CP (11/42, 26.2%) was similar to the proportion of EsKE that were CP (195/741, 26.3%). Five of 24 (20.8%) CP-LCG had a carbapenemase gene other than bla (KPC). CONCLUSIONS: Participating sites would have missed approximately 1 in 10 CP-CRE if isolate submission had been limited to EsKE genera. Expanding mechanism testing to additional genera could improve detection and prevention efforts.

    • Immunity and Immunization
      1. Effectiveness of COVID-19 mRNA vaccines against COVID-19-associated hospitalization - five Veterans Affairs Medical Centers, United States, February 1-August 6, 2021external icon
        Bajema KL, Dahl RM, Prill MM, Meites E, Rodriguez-Barradas MC, Marconi VC, Beenhouwer DO, Brown ST, Holodniy M, Lucero-Obusan C, Rivera-Dominguez G, Morones RG, Whitmire A, Goldin EB, Evener SL, Tremarelli M, Tong S, Hall AJ, Schrag SJ, McMorrow M, Kobayashi M, Verani JR, Surie D.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1294-1299.
        COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19-associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination.

      2. An evaluation of an influenza vaccination campaign targeting pregnant women in 27 clinics in two provinces of South Africa, 2015 - 2018external icon
        Bishop K, McMorrow M, Meiring S, Walaza S, Rossi L, Mhlanga S, Tempia S, Mathunjwa A, Kleynhans J, Appiah GD, McAnerney JM, Zar HJ, Cohen C.
        BMC Health Serv Res. 2021 Sep 9;21(1):941.
        INTRODUCTION: Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women. METHODS: From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. RESULTS: We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p < 0.001). Women aged 25-29 and > 35 years were less likely to be vaccinated than women aged 18-24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489). CONCLUSION: Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.

      3. COVID-19 vaccine uptake among residents and staff members of assisted living and residential care communities-Pharmacy Partnership for Long-Term Care Program, December 2020-April 2021external icon
        Gharpure R, Yi SH, Li R, Jacobs Slifka KM, Tippins A, Jaffe A, Guo A, Kent AG, Gouin KA, Whitworth JC, Vlachos N, Patel A, Stuckey MJ, Link-Gelles R.
        J Am Med Dir Assoc. 2021 Aug 25.
        OBJECTIVES: In December 2020, CDC launched the Pharmacy Partnership for Long-Term Care Program to facilitate COVID-19 vaccination of residents and staff in long-term care facilities (LTCFs), including assisted living (AL) and other residential care (RC) communities. We aimed to assess vaccine uptake in these communities and identify characteristics that might impact uptake. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: AL/RC communities in the Pharmacy Partnership for Long-Term Care Program that had ≥1 on-site vaccination clinic during December 18, 2020-April 21, 2021. METHODS: We estimated uptake by using the cumulative number of doses of COVID-19 vaccine administered and normalizing by the number of AL/RC community beds. We estimated the percentage of residents vaccinated in 3 states using AL census counts. We linked community vaccine administration data with county-level social vulnerability index (SVI) measures to calculate median vaccine uptake by SVI tertile. RESULTS: In AL communities, a median of 67 residents [interquartile range (IQR): 48-90] and 32 staff members (IQR: 15-60) per 100 beds received a first dose of COVID-19 vaccine at the first on-site clinic; in RC, a median of 8 residents (IQR: 5-10) and 5 staff members (IQR: 2-12) per 10 beds received a first dose. Among 3 states with available AL resident census data, median resident first-dose uptake at the first clinic was 93% (IQR: 85-108) in Connecticut, 85% in Georgia (IQR: 70-102), and 78% (IQR: 56-91) in Tennessee. Among both residents and staff, cumulative first-dose vaccine uptake increased with increasing social vulnerability related to housing type and transportation. CONCLUSIONS AND IMPLICATIONS: COVID-19 vaccination of residents and staff in LTCFs is a public health priority. On-site clinics may help to increase vaccine uptake, particularly when transportation may be a barrier. Ensuring steady access to COVID-19 vaccine in LTCFs following the conclusion of the Pharmacy Partnership is critical to maintaining high vaccination coverage among residents and staff.

      4. Data on COVID-19 vaccine effectiveness (VE) since the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States are limited (1-3). CDC used the VISION Network* to examine medical encounters (32,867) from 187 hospitals and 221 emergency departments (EDs) and urgent care (UC) clinics across nine states during June-August 2021, beginning on the date the Delta variant accounted for >50% of sequenced isolates in each medical facility's state. VISION Network methods have been published (4).

      5. Monitoring incidence of COVID-19 cases, hospitalizations, and deaths, by vaccination status - 13 U.S. jurisdictions, April 4-July 17, 2021external icon
        Scobie HM, Johnson AG, Suthar AB, Severson R, Alden NB, Balter S, Bertolino D, Blythe D, Brady S, Cadwell B, Cheng I, Davidson S, Delgadillo J, Devinney K, Duchin J, Duwell M, Fisher R, Fleischauer A, Grant A, Griffin J, Haddix M, Hand J, Hanson M, Hawkins E, Herlihy RK, Hicks L, Holtzman C, Hoskins M, Hyun J, Kaur R, Kay M, Kidrowski H, Kim C, Komatsu K, Kugeler K, Lewis M, Lyons BC, Lyons S, Lynfield R, McCaffrey K, McMullen C, Milroy L, Meyer S, Nolen L, Patel MR, Pogosjans S, Reese HE, Saupe A, Sell J, Sokol T, Sosin D, Stanislawski E, Stevens K, Vest H, White K, Wilson E, MacNeil A, Ritchey MD, Silk BJ.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1284-1290.
        COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

      6. Influenza vaccine effectiveness within prospective cohorts of healthcare personnel in Israel and Peru 2016-2019external icon
        Thompson MG, Soto G, Perez A, Newes-Adeyim G, Yoo YM, Hirsch A, Katz M, Tinoco Y, Shemer Avni Y, Ticona E, Malosh R, Martin E, Matos E, Reynolds S, Wesley M, Ferdinands J, Cheung A, Levine M, Bravo E, Arriola CS, Ester Castillo M, Carlos Castro J, Dawood F, Goldberg D, Manuel Neyra Quijandría J, Azziz-Baumgartner E, Monto A, Balicer R.
        Vaccine. 2021 Sep 8.
        BACKGROUND: There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). METHODS: HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016-2017 to 2018-2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018-2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). RESULTS: Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = -30%, 25%) in Israel and 12% (95% CI = -61%, 52%) in Peru. CONCLUSION: Estimates of IVE were null using person-time models during six study seasons in Israel and Peru.

    • Injury and Violence
      1. Developing indicators to evaluate systems thinking and application in state injury and violence prevention programsexternal icon
        Wilkins NJ, Kossover-Smith RA, Hogan SA, Espinosa R, Wilson LF.
        New Dir Eval. 2021 ;2021(170):67-80.
        Systems thinking principles are increasingly recognized as an important part of public health research and practice. However, the extent to which systems thinking is being integrated into public health practice, and its impact on health outcomes, is largely unknown. This is in part due to the paucity of options for measuring systems thinking at the organizational level and in the context of public health practice. Building on existing frameworks of public health competencies, infrastructure, and systems thinking principles, this article proposes a conceptual model and corresponding indicators for measuring organizational systems thinking and application within state public health departments. We describe our process for developing this model and indicators, drawing from both research and practice-based evidence on systems thinking, and offer a set of indicators for measuring organizational-level systems thinking in the context of public health practice. © 2021 American Evaluation Association and Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

    • Laboratory Sciences
      1. Dermal exposure to the immunomodulatory antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in miceexternal icon
        Baur R, Gandhi J, Marshall NB, Lukomska E, Weatherly LM, Shane HL, Hu G, Anderson SE.
        Toxicol Sci. 2021 Sep 13.
        Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5-2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5-7 days on the skin was shown to increase trans-epidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.

      2. Escaping the fate of Sisyphus: assessing resistome hybridization baits for antimicrobial resistance gene captureexternal icon
        Beaudry MS, Thomas JC, Baptista RP, Sullivan AH, Norfolk W, Devault A, Enk J, Kieran TJ, Rhodes OE, Perry-Dow KA, Rose LJ, Bayona-Vásquez NJ, Oladeinde A, Lipp EK, Sanchez S, Glenn TC.
        Environ Microbiol. 2021 Sep 14.
        Finding, characterizing and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19 933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement.

      3. OBJECTIVE: In 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. The aim of this study was to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. METHODS: Serum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. RESULTS: Of 19 samples, 13 (68%) were conclusive with classification of BCs and 6 (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (7 or 54%), secondary vaccine failures (4 or 31%) and 2 (15%) could not be classified. CONCLUSIONS: In measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM and RNA detection) including IgG avidity and PRN results, when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.

      4. Coxiella burnetii infections in mice: Immunological responses to contemporary genotypes found in the USexternal icon
        Priestley RA, Smith CB, Miller HK, Kersh GJ.
        Virulence. 2021 Dec;12(1):2461-2473.
        Coxiella burnetii is an obligate intracellular bacterium that causes the human disease Q fever, which can manifest as an acute flu-like illness or a long-term chronic illness, such as endocarditis. Three genotypes (ST8, ST16, and ST20) of Coxiella burnetii are commonly found in the contemporary US and are associated with specific animal hosts. Although all three genotypes have been isolated from humans with Q fever, studies comparing virulence between C. burnetii sequence types have been rare. Here, groups of mice were infected via aerosol inoculation with isolates derived from cow's milk, environmental, animal, and human samples. Mice were monitored for weight loss and blood samples were takenweekly. Animals were euthanized at 2- and 12-weeks post-infection, and bacterial burden was determined for tissues by real-time PCR. The levels of anti-Coxiella antibodies and selected inflammatory cytokines were determined for serum samples. Weight loss and splenomegaly were observed in mice infected with ST20 and ST16 isolates but were absent in the mice infected with ST8 isolates. Bacterial concentrations in the tissues were lower in the ST8 isolates at 2 weeks post-infection relative to all other isolates. ST16 and ST20 isolates induced robust antibody and cytokine responses, while ST8 isolates produced significantly lower anti-C. burnetii titers early in the infection but saw increased titers in some animals several weeks post-infection. The data suggest that the ST8 isolates are less virulent in this mouse model, as they produce less robust antibody responses that are slow to develop, relative to the ST16 and ST20 isolates.

    • Maternal and Child Health
      1. Maternal smoking and congenital heart defects, National Birth Defects Prevention Study, 1997-2011external icon
        Bolin EH, Gokun Y, Romitti PA, Tinker SC, Summers AD, Roberson PK, Hobbs CA, Malik S, Botto LD, Nembhard WN.
        J Pediatr. 2021 Sep 8.
        OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n=8,339) and non-malformed controls (n=11,020) children from all years (1997-2011) of the National Birth Defects Prevention Study. Maternal self-reported smoking one month before through three months after conception was evaluated as a binary (none, any) and categorical (light, medium, heavy) exposure. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals. Stratified analyses were performed for septal defects according to maternal age, pre-pregnancy body mass index, and maternal race/ethnicity. RESULTS: Multiple CHDs displayed modest associations with any level of maternal periconceptional smoking independent of potential confounders; the strongest associations were for aggregated septal defects (OR 1.5 [1.3-1.7]), tricuspid atresia (OR 1.7 [1.0-2.7]), and double outlet right ventricle (DORV) (1.5 [1.1-2.1]). TA and DORV also displayed dose-response relationships. Among heavy smokers, the highest odds were again observed for TA (aOR 3.0 [1.5-6.1]) and DORV (aOR 1.5 [1.1-2.2]). Heavy smokers ≥35 years old more frequently had a child with a septal defect when compared with similarly aged non-smokers (aOR 2.3 [1.4-3.9]). CONCLUSIONS: Maternal periconceptional smoking is most strongly associated with septal defects, TA and DORV; the risk for septal defects is modified by maternal age.

    • Occupational Safety and Health

    • Parasitic Diseases
      1. Investigation of US Cyclospora cayetanensis outbreaks in 2019 and evaluation of an improved Cyclospora genotyping system against 2019 cyclosporiasis outbreak clustersexternal icon
        Barratt J, Houghton K, Richins T, Straily A, Threlkel R, Bera B, Kenneally J, Clemons B, Madison-Antenucci S, Cebelinski E, Whitney BM, Kreil KR, Cama V, Arrowood MJ, Qvarnstrom Y.
        Epidemiol Infect. 2021 Sep 13:1-39.

      2. Partial indoor residual spraying with pirimiphos-methyl as an effective and cost-saving measure for the control of Anopheles gambiae s.l. in northern Ghanaexternal icon
        Coleman S, Yihdego Y, Sherrard-Smith E, Thomas CS, Dengela D, Oxborough RM, Dadzie SK, Boakye D, Gyamfi F, Obiri-Danso K, Johns B, Siems LV, Lucas B, Tongren JE, Zigirumugabe S, Dery D, Fornadel C, George K, Belemvire A, Carlson J, Irish SR, Armistead JS, Seyoum A.
        Sci Rep. 2021 Sep 10;11(1):18055.
        The scale up of indoor residual spraying (IRS) and insecticide treated nets have contributed significantly to global reductions in malaria prevalence over the last two decades. However, widespread pyrethroid resistance has necessitated the use of new and more expensive insecticides for IRS. Partial IRS with pirimiphos-methyl in experimental huts and houses in a village-wide trial was evaluated against Anopheles gambiae s.l. in northern Ghana. Four different scenarios in which either only the top or bottom half of the walls of experimental huts were sprayed, with or without also spraying the ceiling were compared. Mortality of An. gambiae s.l. on partially sprayed walls was compared with the standard procedures in which all walls and ceiling surfaces are sprayed. A small-scale trial was then conducted to assess the effectiveness, feasibility, and cost of spraying only the upper walls and ceiling as compared to full IRS and no spraying in northern Ghana. Human landing catches were conducted to estimate entomological indices and determine the effectiveness of partial IRS. An established transmission dynamics model was parameterized by an analysis of the experimental hut data and used to predict the epidemiological impact and cost effectiveness of partial IRS for malaria control in northern Ghana. In the experimental huts, partial IRS of the top (IRR 0.89, p = 0.13) or bottom (IRR 0.90, p = 0.15) half of walls and the ceiling was not significantly less effective than full IRS in terms of mosquito mortality. In the village trial, the annual entomological inoculation rate was higher for the unsprayed control (217 infective bites/person/year (ib/p/yr)) compared with the fully and partially sprayed sites, with 28 and 38 ib/p/yr, respectively. The transmission model predicts that the efficacy of partial IRS against all-age prevalence of malaria after six months would be broadly equivalent to a full IRS campaign in which 40% reduction is expected relative to no spray campaign. At scale, partial IRS in northern Ghana would have resulted in a 33% cost savings ($496,426) that would enable spraying of 36,000 additional rooms. These findings suggest that partial IRS is an effective, feasible, and cost saving approach to IRS that could be adopted to sustain and expand implementation of this key malaria control intervention.

      3. A comparison of PCR and ELISA methods to detect different stages of Plasmodium vivax in Anopheles arabiensisexternal icon
        Hendershot AL, Esayas E, Sutcliffe AC, Irish SR, Gadisa E, Tadesse FG, Lobo NF.
        Parasit Vectors. 2021 Sep 15;14(1):473.
        BACKGROUND: In characterizing malaria epidemiology, measuring mosquito infectiousness informs the entomological inoculation rate, an important metric of malaria transmission. PCR-based methods have been touted as more sensitive than the current "gold-standard" circumsporozoite (CSP) ELISA. Wider application of PCR-based methods has been limited by lack of specificity for the infectious sporozoite stage. We compared a PCR method for detecting the parasite's mitochondrial (mt) cytochrome oxidase I (COX-I) gene with ELISA for detecting circumsporozoite protein for identification of different life stages of the parasite during development within a mosquito. METHODS: A PCR-based method targeting the Plasmodium mt COX-I gene was compared with the CSP ELISA method to assess infectivity in Anopheles arabiensis colony mosquitoes fed on blood from patients infected with Plasmodium vivax. Mosquitoes were tested at six post-infection time points (days 0.5, 1, 6, 9, 12, 15). The head and thorax and the abdomen for each specimen were tested separately with each method. Agreement between methods at each infection stage was measured using Cohen's kappa measure of test association. RESULTS: Infection status of mosquitoes was assessed in approximately 90 head/thorax and 90 abdomen segments at each time point; in total, 538 head/thorax and 534 abdomen segments were tested. In mosquitoes bisected after 0.5, 1, and 6 days post-infection (dpi), the mt COX-I PCR detected Plasmodium DNA in both the abdomen (88, 78, and 67%, respectively) and head/thorax segments (69, 60, and 44%, respectively), whilst CSP ELISA detected sporozoites in only one abdomen on day 6 post-infection. PCR was also more sensitive than ELISA for detection of Plasmodium in mosquitoes bisected after 9, 12, and 15 dpi in both the head and thorax and abdomen. There was fair agreement between methods for time points 9-15 dpi (κ = 0.312, 95% CI: 0.230-0.394). CONCLUSIONS: The mt COX-I PCR is a highly sensitive, robust method for detecting Plasmodium DNA in mosquitoes, but its limited Plasmodium life-stage specificity cannot be overcome by bisection of the head and thorax from the abdomen prior to PCR. Thus, the mt COX-I PCR is a poor candidate for identifying infectious mosquitoes.

    • Reproductive Health
      1. Increasing access to contraception in the United States: Assessing achievement and sustainabilityexternal icon
        DeSisto CL, Estrich CG, Kroelinger CD, Pliska E, Akbarali S, Romero L, Cox S, Velonis A.
        J Womens Health (Larchmt). 2021 Sep;30(9):1217-1224.
        Background: During October 2016 through May 2018, a learning community was convened to focus on policies and programs to increase access to the full range of contraceptive options for women of reproductive age. The Increasing Access to Contraception (IAC) Learning Community included 27 jurisdictions, with teams from each jurisdiction consisting of state health department leaders, program staff, and provider champions. At the kick-off meeting, teams from each jurisdiction created action plans that outlined their goals. Methods: We contacted jurisdictions during May-June 2019, 1 year after the learning community ended, and invited them to complete a post-assessment of goal achievement and sustainment through semi-structured interviews over the telephone or via email. Results: Follow-up information was collected from 26 jurisdictions (96%) that participated in the learning community. The teams from these jurisdictions had created 79 total goals. At the time of the learning community closing meeting in May 2018, 35 goals (44%) had been achieved. Three jurisdictions achieved all their goals by the close of the learning community. At the time of the post-assessment 1 year later, jurisdictions were sustaining efforts for 69 (87%) of the total goals. In every jurisdiction, work on at least one goal that originated in the learning community was sustained. Conclusions: The jurisdictions that participated in the IAC Learning Community continued the work of their action plan goals 1 year after the formal closure of the learning community, indicating sustainability of the learning community activities, beyond what jurisdictions accomplished during formal participation.

    • Substance Use and Abuse
      1. Notes from the field: Xylazine detection and involvement in drug overdose deaths - United States, 2019external icon
        Kariisa M, Patel P, Smith H, Bitting J.
        MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1300-1302.

      2. The impact of community-level prevention strategies on high-dose opioid dispensing rates: 2014-2019external icon
        Underwood N, Cremer L, Cance JD, Williams J, Guy GP, Zule W.
        Drug Alcohol Depend. 2021 Aug 27;227:108988.
        BACKGROUND: Prescription opioids played a major role in the current opioid overdose epidemic. High rates of opioid prescribing and dispensing exposed many people to opioids, and high-dose opioid prescriptions (e.g., 90 morphine milligram equivalents [MME] per day) contributed to increases in opioid overdoses. The Centers for Disease Control and Prevention (CDC) Prevention for States (PfS) program provided funding to jurisdictions ("PfS recipients") with a high burden of opioid-involved overdoses. This paper examines associations between strategies addressing high-dose opioid prescribing and changes in high-dose opioid dispensing. METHODS: Monthly opioid dispensing data (2014-2019) from IQVIA Xponent were analyzed using longitudinal growth models (LGM) to compare high-dose opioid dispensing rates in the 29 jurisdictions that participated in PfS with rates in non-PfS jurisdictions. Additional models examined associations between specific PfS activities and changes in high-dose dispensing among PfS recipients. RESULTS: High-dose dispensing rates decreased significantly in both PfS and non-PfS jurisdictions from 2014 to 2019. Rates of high-dose opioid dispensing rates in PfS jurisdictions were not significantly different than those in non-PfS jurisdictions (p = 0.07). Among PfS recipients, multiple activities were associated with decreases in high-dose dispensing rates over time, including moving towards real-time prescription drug monitoring program (PDMP) reporting (p < 0.001) and implementation of opioid dispensing interventions for insurers/ health systems (p < 0.05). CONCLUSIONS: High-dose opioid dispensing rates decreased throughout the United States from 2014-2019. As the drug epidemic continues to evolve, implementation of prevention activities by state and local partners is important. These findings highlight two potential prevention strategies and activities that jurisdictions can utilize.

    • Zoonotic and Vectorborne Diseases
      1. This study assessed the duration of tick attachment necessary for a successful transmission of Anaplasma phagocytophilum by an infected I. scapularis nymph. Individual nymphs were placed upon BALB/c mice and allowed to feed for predetermined time intervals of 4 to 72 h. Ticks removed from mice at predetermined intervals were tested by PCR for verification of infection and evaluation of the bacterial load. The success of pathogen transmission to mice was assessed by blood-PCR at 7, 14 and 21 days postinfestation, and IFA at 21 days postinfestation. Anaplasma phagocytophilum infection was documented in 10-30 % of mice, from which ticks were removed within the first 20 h of feeding. However, transmission success was ≥70% if ticks remained attached for 36 h or longer. Notably, none of the PCR-positive mice that were exposed to infected ticks for 4 to 8 h and only half of PCR-positive mice exposed for 24 h developed antibodies within 3 weeks postinfestation. On the other hand, all mice with detectable bacteremia after being infested for 36 h seroconverted. This suggests that although some of the ticks removed prior to 24 h of attachment succeed in injecting a small amount of A. phagocytophilum, this amount is insufficient for stimulating humoral immunity and perhaps for establishing disseminated infection in BALB/c mice. Although A. phagocytophilum may be present in salivary glands of unfed I. scapularis nymphs, the amount of A. phagocytophilum initially contained in saliva appears insufficient to cause sustainable infection in a host. Replication and, maybe, reactivation of the agent for 12-24 h in a feeding tick is required before a mouse can be consistently infected.

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