Volume 11, Issue 42 October 22, 2019

CDC Science Clips: Volume 11, Issue 42, October 22, 2019

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!

This week, Science Clips is pleased to feature a selection of publications related to the Global Tobacco Surveillance System (GTSS), on the occasion of its twentieth anniversary.

GTSS is one of the world’s largest surveillance systems. GTSS aims to enhance country capacity to design, implement, and evaluate tobacco control interventions. GTSS currently includes the collection of data through three surveys: The Global Youth Tobacco Survey (GYTS), the Global Adult Tobacco Survey (GATS), and Tobacco Questions for Surveys (TQS). In the past 20 years, CDC and global partners have assisted many countries in tobacco surveillance. These data have helped inform tobacco control and prevention strategies around the world.

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Substance Use and Abuse – Global Tobacco Surveillance System
      1. Tobacco use and tobacco-related behaviors – 11 countries, 2008-2017external icon
        Ahluwalia IB, Arrazola RA, Zhao L, Shi J, Dean A, Rainey E, Palipudi K, Twentyman E, Armour BS.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 18;68(41):928-933.
        Each year, tobacco use is responsible for approximately 8 million deaths worldwide, including 7 million deaths among persons who use tobacco and 1.2 million deaths among nonsmokers exposed to secondhand smoke (SHS) (1). Approximately 80% of the 1.1 billion persons who smoke tobacco worldwide reside in low- and middle-income countries (2,3). The World Health Organization’s (WHO’s) Framework Convention on Tobacco Control (FCTC) provides the foundation for countries to implement and manage tobacco control through the MPOWER policy package,* which includes monitoring tobacco use, protecting persons from SHS, warning them about the danger of tobacco, and enforcing bans on tobacco advertising, promotion, or sponsorship (tobacco advertising) (4). CDC analyzed data from 11 countries that completed two or more rounds of the Global Adult Tobacco Survey (GATS) during 2008-2017. Tobacco use and tobacco-related behaviors that were assessed included current tobacco use, SHS exposure, thinking about quitting because of warning labels, and exposure to tobacco advertising. Across the assessed countries, the estimated percentage change in tobacco use from the first round to the most recent round ranged from -21.5% in Russia to 1.1% in Turkey. Estimated percentage change in SHS exposure ranged from -71.5% in Turkey to 72.9% in Thailand. Estimated percentage change in thinking about quitting because of warning labels ranged from 77.4% in India to -33.0% in Turkey. Estimated percentage change in exposure to tobacco advertising ranged from -66.1% in Russia to 44.2% in Thailand. Continued implementation and enforcement of proven tobacco control interventions and strategies at the country level, as outlined in MPOWER, can help reduce tobacco-related morbidity and mortality worldwide (3,5,6).

      2. The Global Tobacco Surveillance System (GTSS) African Region Atlasexternal icon
        CDC Foundation.
        CDC Foundation; Atlanta, GA, USA. 2018.
        This Atlas presents estimates of tobacco use and key tobacco control measures in a visual format from countries within the World Health Organization (WHO) African Region who have completed the Global Adult Tobacco Survey (GATS), the Global Youth Tobacco Survey (GYTS), or both. Following the MPOWER measures, and in line with the WHO Framework Convention on Tobacco Control Articles, the Atlas describes the range of tobacco product use across various countries in the WHO African Region and provides estimates on tobacco use; secondhand smoke exposure; cessation; warnings about the dangers of tobacco; bans on advertising, promotion and sponsorship; and tobacco taxes. Progress and opportunities for further tobacco prevention and control efforts in these countries are also highlighted. This Atlas can serve as a resource for decision makers, public health professionals, the media, researchers, and the general public to inform tobacco prevention and control efforts to end the tobacco epidemic.

      3. Exposure to anti- and pro-tobacco advertising, promotions or sponsorships: Turkey, 2008external icon
        Erguder T, Bilir N, Ozcebe H, Irmak H, Tasti E, Ilter H, Palipudi KM, Andes LJ, Asma S, Khoury RN, Talley B.
        Glob Health Promot. 2016 Jun;23(2 Suppl):58-67.
        INTRODUCTION: In 2008, Turkey became one of 26 countries with a complete ban on all forms of direct and indirect tobacco marketing. We assessed the level of exposure to anti- and pro-cigarette advertising and to cigarette promotions and sponsorships among various demographic groups in Turkey. METHODS: We used the data from the Global Adult Tobacco Survey (GATS), conducted in November 2008 in Turkey. The data consist of answers to GATS questions by 9030 respondents from a nationally representative, multistage probability sample of adults 15 years of age or older. To find differences in exposure to the advertising by sex, age, education level and smoking status, we analyzed responses to GATS questions about cigarette advertisements and anti-cigarette smoking information in various forms and through various advertising channels, during the 30 days before the survey, using bivariate analysis. RESULTS: Overall, 13.3% of respondents aged 15 years or older noticed some type of cigarette marketing during the 30 days before the survey: 7.1% saw advertisements, 5.3% saw promotions and 3.3% saw sports sponsorships. Men were more likely than women to have seen cigarette promotions (7.8% versus 3.0%) and sports sponsorships (5.3% versus 1.4%). Respondents aged 15-24 years were more likely than those aged 25 years or older to have seen cigarette advertisements (10.2% versus 6.2%), promotions (8.7% versus 4.4%) and sponsorships (6.6% versus 2.3%), respectively. Respondents were most likely to have seen cigarette advertisements on television (3.4%) or in shops (2.7%). In addition, 2.8% of respondents reported seeing a clothing item with a brand name or logo, 2.5% reported that they received free samples of cigarettes and 0.3% received gifts along with the purchase of cigarettes. Almost 9 of 10 survey respondents (88.8%) reported having noticed some anti-cigarette information during the 30 days before the survey. Most anti-cigarette information was seen on television (85.5%). The anti-cigarette information was seen by slightly more cigarette smokers (91.6%) than nonsmokers (87.6%). Persons with less than a primary education were less likely to notice anti-cigarette information than those with a higher level of education, in all examined media channels. CONCLUSIONS: Our findings showed a low prevalence of noticing cigarette marketing, which indicates high compliance with the Turkish law banning such marketing. GATS data provide an in-depth understanding of the level of exposure to pro- and anti-cigarette information in 2008 and they are of practical assistance to those who implement policies to reduce the demand for tobacco. The challenge now is to maintain rigorous enforcement. To do so requires ongoing surveillance to produce data on the effectiveness of the enforcement efforts.

      4. Tobacco Control in Africa (supplement)external icon
        Franco EL (editor in chief) .
        Prev Med. 2016 Oct;91[Supplement]:S1-S40.
        The articles in this supplement focus on a number of important areas for tobacco prevention and control, using surveillance data collected by various countries in Africa. The papers provide an overall status of FCTC, including demand reduction strategies implemented, and identify opportunities for enhancing programs and policies that protect people from the harms of tobacco use and secondhand smoke exposure. GYTS data are presented on multiple topics throughout the supplement, including youth tobacco use and access to cigarettes, marketing of tobacco products to youths, and the relationship between secondhand smoke exposure and youth susceptibility to tobacco use. The studies in this supplement are poised to fill an important gap in the literature and point to the future work that can help combat tobacco use on a continent with a young, vibrant population and growing economies. Reducing tobacco use in Africa is an urgent public health priority, and tobacco use prevention and control strategies are a best buy in public health. The WHO FCTC and its guidelines, as well as the package of demand reduction measures developed by WHO, provide concrete steps to equip countries to address tobacco use and secondhand smoke exposure in Africa.

      5. Tobacco use among youths–Argentina, 2007 and 2012external icon
        Konfino J, Ferrante D, Goldberg L, Caixeta R, Palipudi KM.
        MMWR Morb Mortal Wkly Rep. 2014 Jul 11;63(27):588-90.
        Tobacco use is the leading preventable cause of deaths worldwide. The MPOWER package, the six recommended policies of the World Health Organization (WHO) to reverse the tobacco epidemic, strongly recommends monitoring tobacco use trends. Because evidence indicates that smoking addiction often starts before the age of 18 years, there is a need to monitor tobacco use among youths. During 2011, a National Tobacco Control Law was enacted in Argentina that included implementation of 100% smoke-free environments, a comprehensive advertising ban (prohibiting advertising, promotion, and sponsorship of cigarettes or tobacco products through any media or communications outlets), pictorial health warnings, and a prohibition against the sale of tobacco products through any means to persons aged <18 years. To ascertain trends in tobacco use among youths in Argentina, the Argentina Ministry of Health and CDC analyzed data from the Global Youth Tobacco Survey (GYTS) for 2007 and 2012 (the next year that it was administered in Argentina). The findings indicated that the overall proportion of youths aged approximately 13-15 years who reported ever smoking a cigarette declined from 52.0% in 2007 to 41.9% in 2012 with significant decreases among both males and females. In 2012, 52.5% of youths in Argentina reported secondhand smoke (SHS) exposure in their homes and 47.5% in enclosed public places in the 7 days preceding the survey. Increased public education and tobacco control efforts will be important to discouraging tobacco use and decreasing SHS exposure among youths in Argentina.

      6. Secondhand smoke exposure at home among one billion children in 21 countries: findings from the Global Adult Tobacco Survey (GATS)external icon
        Mbulo L, Palipudi KM, Andes L, Morton J, Bashir R, Fouad H, Ramanandraibe N, Caixeta R, Dias RC, Wijnhoven TM, Kashiwabara M, Sinha DN, Tursan d’Espaignet E.
        Tob Control. 2016 Dec;25(e2):e95-e100.
        OBJECTIVE: Children are vulnerable to secondhand smoke (SHS) exposure because of limited control over their indoor environment. Homes remain the major place where children may be exposed to SHS. Our study examines the magnitude, patterns and determinants of SHS exposure in the home among children in 21 countries (19 low-income and middle-income countries and 2 high-income countries). METHODS: Global Adult Tobacco Survey (GATS) data, a household survey of people 15 years of age or older. Data collected during 2009-2013 were analysed to estimate the proportion of children exposed to SHS in the home. GATS estimates and 2012 United Nations population projections for 2015 were also used to estimate the number of children exposed to SHS in the home. RESULTS: The proportion of children younger than 15 years of age exposed to SHS in the home ranged from 4.5% (Panama) to 79.0% (Indonesia). Of the approximately one billion children younger than 15 years of age living in the 21 countries under study, an estimated 507.74 million were exposed to SHS in the home. China, India, Bangladesh, Indonesia and the Philippines accounted for almost 84.6% of the children exposed to SHS. The prevalence of SHS exposure was higher in countries with higher adult smoking rates and was also higher in rural areas than in urban areas, in most countries. CONCLUSIONS: A large number of children were exposed to SHS in the home. Encouraging of voluntary smoke-free rules in homes and cessation in adults has the potential to reduce SHS exposure among children and prevent SHS-related diseases and deaths.

      7. Socioeconomic patterns of smoking cessation behavior in low and middle-income countries: Emerging evidence from the Global Adult Tobacco Surveys and International Tobacco Control Surveysexternal icon
        Nargis N, Yong HH, Driezen P, Mbulo L, Zhao L, Fong GT, Thompson ME, Borland R, Palipudi KM, Giovino GA, Thrasher JF, Siahpush M.
        PLoS One. 2019 ;14(9):e0220223.
        INTRODUCTION: Tobacco smoking is often more prevalent among those with lower socio-economic status (SES) in high-income countries, which can be driven by the inequalities in initiation and cessation of smoking. Smoking is a leading contributor to socio-economic disparities in health. To date, the evidence for any socio-economic inequality in smoking cessation is lacking, especially in low- and middle-income countries (LMICs). This study examined the association between cessation behaviours and SES of smokers from eight LMICs. METHODS: Data among former and current adult smokers aged 18 and older came from contemporaneous Global Adult Tobacco Surveys (2008-2011) and the International Tobacco Control Surveys (2009-2013) conducted in eight LMICs (Bangladesh, Brazil, China, India, Mexico, Malaysia, Thailand and Uruguay). Adjusted odds ratios (AORs) of successful quitting in the past year by SES indicators (household income/wealth, education, employment status, and rural-urban residence) were estimated using multivariable logistic regression controlling for socio-demographics and average tobacco product prices. A random effects meta-analysis was used to combine the estimates of AORs pooled across countries and two concurrent surveys for each country. RESULTS: Estimated quit rates among smokers (both daily and occasional) varied widely across countries. Meta-analysis of pooled AORs across countries and data sources indicated that there was no clear evidence of an association between SES indicators and successful quitting. The only exception was employed smokers, who were less likely to quit than their non-employed counterparts, which included students, homemakers, retirees, and the unemployed (pooled AOR approximately 0.8, p<0.10). CONCLUSION: Lack of clear evidence of the impact of lower SES on adult cessation behaviour in LMICs suggests that lower-SES smokers are not less successful in their attempts to quit than their higher-SES counterparts. Specifically, lack of employment, which is indicative of younger age and lower nicotine dependence for students, or lower personal disposable income and lower affordability for the unemployed and the retirees, may be associated with quitting. Raising taxes and prices of tobacco products that lowers affordability of tobacco products might be a key strategy for inducing cessation behaviour among current smokers and reducing overall tobacco consumption. Because low-SES smokers are more sensitive to price increases, tobacco taxation policy can induce disproportionately larger decreases in tobacco consumption among them and help reduce socio-economic disparities in smoking and consequent health outcomes.

      8. Smokeless Tobacco and Public Health: A Global Perspectiveexternal icon
        National Cancer Institute , Centers for Disease Control and Prevention .
        Bethesda, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health, National Cancer Institute. 2014 ;NIH Publication No. 14-7983.
        Smokeless Tobacco and Public Health: A Global Perspective provides a snapshot of current knowledge and data sources on smokeless tobacco (ST) use, characteristics of products, and related policy efforts. It outlines what is currently known about the changing ST product market, industry marketing efforts, and economic and policy factors; and provides an overview of the current state of scientific knowledge, public health information, and policy initiatives focused on ST in each major region of the world. The report aims to identify gaps and needs related to monitoring and surveillance of ST products and other information collection, and make recommendations for strengthening international collaboration and building a scientific basis for ST product control and regulation.

      9. Awareness and current use of electronic cigarettes in Indonesia, Malaysia, Qatar, and Greece: Findings From 2011-2013 Global Adult Tobacco Surveysexternal icon
        Palipudi KM, Mbulo L, Morton J, Mbulo L, Bunnell R, Blutcher-Nelson G, Kosen S, Tee GH, Abdalla AM, Mutawa KA, Barbouni A, Antoniadou E, Fouad H, Khoury RN, Rarick J, Sinha DN, Asma S.
        Nicotine Tob Res. 2016 Apr;18(4):501-7.
        INTRODUCTION: Increases in electronic cigarette (e-cigarette) awareness and current use have been documented in high income countries but less is known about middle and low income countries. METHODS: Nationally representative household survey data from the first four Global Adult Tobacco Surveys to assess e-cigarettes were analyzed, including Indonesia (2011), Malaysia (2011), Qatar (2013), and Greece (2013). Correlates of e-cigarette awareness and current use were calculated. Sample sizes for Greece and Qatar allowed for further analysis of e-cigarette users. RESULTS: Awareness of e-cigarettes was 10.9% in Indonesia, 21.0% in Malaysia, 49.0% in Qatar, and 88.5% in Greece. In all four countries, awareness was higher among male, younger, more educated, and wealthier respondents. Current e-cigarette use among those aware of e-cigarettes was 3.9% in Malaysia, 2.5% in Indonesia, 2.2% in Greece and 1.8% in Qatar. Across these four countries, an estimated 818 500 people are currently using e-cigarettes. Among current e-cigarette users, 64.4% in Greece and 84.1% in Qatar also smoked cigarettes, and, 10.6% in Greece and 6.0% in Qatar were never-smokers. CONCLUSIONS: E-cigarette awareness and use was evident in all four countries. Ongoing surveillance and monitoring of awareness and use of e-cigarettes in these and other countries could help inform tobacco control policies and public health interventions. Future surveillance should monitor use of e-cigarettes among current smokers and uptake among never-smokers and relapsing former smokers.

      10. Smokeless tobacco use: a meta-analysis of risk and attributable mortality estimates for Indiaexternal icon
        Sinha DN, Palipudi KM, Gupta PC, Singhal S, Ramasundarahettige C, Jha P, Indrayan A, Asma S, Vendhan G.
        Indian J Cancer. 2014 Dec;51 Suppl 1:S73-7.
        BACKGROUND: Use of smokeless tobacco (SLT) is widely prevalent in India and Indian subcontinent. Cohort and case-control studies in India and elsewhere report excess mortality due to its use. OBJECTIVE: The aim was to estimate the SLT use-attributable deaths in males and females, aged 35 years and older, in India. MATERIALS AND METHODS: Prevalence of SLT use in persons aged 35 years and older was obtained from the Global Adult Tobacco Survey in India and population size and deaths in the relevant age-sex groups were obtained from UN estimates (2010 revision) for 2008. A meta-relative risk (RR) based population attributable fraction was used to estimate attributable deaths in persons aged 35 years and older. A random effects model was used in the meta-analysis on all-cause mortality from SLT use in India including four cohort and one case-control study. The studies included in the meta-analysis were adjusted for smoking, age and education. RESULTS: The prevalence of SLT use in India was 25.2% for men and 24.5% for women aged 35 years and older. RRs for females and males were 1.34 (1.27-1.42) and 1.17 (1.05-1.42), respectively. The number of deaths attributable to SLT use in India is estimated to be 368127 (217,076 women and 151,051 men), with nearly three-fifth (60%) of these deaths occurring among women. CONCLUSION: SLT use caused over 350,000 deaths in India in 2010, and nearly three-fifth of SLT use-attributable deaths were among women in India. This calls for targeted public health intervention focusing on SLT products especially among women.

      11. Influence of tobacco industry advertisements and promotions on tobacco use in India: findings from the Global Adult Tobacco Survey 2009-2010external icon
        Sinha DN, Palipudi KM, Oswal K, Gupta PC, Andes LJ, Asma S.
        Indian J Cancer. 2014 Dec;51 Suppl 1:S13-8.
        INTRODUCTION: The developing world, including countries like India, has become a major target for the tobacco industry to market its products. This study examines the influence of the marketing (advertising and promotion) of tobacco products on the use of tobacco by adults (ages 15 and over) in India. METHOD: Data from Global Adult Tobacco Survey 2009-2010 was analyzed using methods for complex (clustered) sample designs. Multivariate logistic regression was employed to predict the use of different tobacco products by level of exposure to tobacco marketing using adults who have never used tobacco as the reference category. Odds ratios (ORs) were adjusted for education, gender, age, state of residence, wealth index, and place of residence (urban/rural). RESULTS: Adults in India were almost twice as likely to be current smokers (versus never users) when they were exposed to a moderate level of bidi or cigarette marketing. For bidis, among adults with high exposure, the OR for current use was 4.57 (95% confidence interval [CI]: 1.6, 13.0). Adults were more likely to be current users of smokeless tobacco (SLT) with even a low level of exposure to SLT marketing (OR = 1.24 [95% CI: 1.1, 1.4]). For SLT, the ORs showed an increasing trend (P for trend < 0.001) with greater level of exposure (moderate, OR = 1.55 [95% CI: 1.1, 2.2]; high, OR = 2.05 [95% CI: 0.8, 5.1]). The risk of any current tobacco use rose with increasing level of exposure to any marketing (minimum, OR = 1.25 [1.1-1.4]; moderate, OR = 1.38 [1.1-1.8]; and high, OR = 2.73 [1.8-4.2]), with the trend highly significant (P < 0.001). CONCLUSION: Exposure to the marketing of tobacco products, which may take the form of advertising at the point of sale, sales or a discounted price, free coupons, free samples, surrogate advertisements, or any of several other modalities, increased prevalence of tobacco use among adults. An increasing level of exposure to direct and indirect advertisement and promotion is associated with an increased likelihood of tobacco use.

      12. Tracking MPOWER in 14 countries: results from the Global Adult Tobacco Survey, 2008-2010external icon
        Song Y, Zhao L, Palipudi KM, Asma S, Morton J, Talley B, Hsia J, Ramanandraibe N, Caixeta R, Fouad H, Khoury R, Sinha D, Rarick J, Bettcher D, Peruga A, Deland K, D’Espaignet ET.
        Glob Health Promot. 2016 Jun;23(2 Suppl):24-37.
        BACKGROUND: The World Health Organization (WHO) MPOWER is a technical package of six tobacco control measures that assist countries in meeting their obligations of the WHO Framework Convention Tobacco Control and are proven to reduce tobacco use. The Global Adult Tobacco Survey (GATS) systematically monitors adult tobacco use and tracks key tobacco control indicators. METHODS: GATS is a nationally representative household survey of adults aged 15 and older, using a standard and consistent protocol across countries; it includes information on the six WHO MPOWER measures. GATS Phase I was conducted from 2008-2010 in 14 high-burden low- and middle-income countries. We selected one key indicator from each of the six MPOWER measures and compared results across 14 countries. RESULTS: Current tobacco use prevalence rates ranged from 16.1% in Mexico to 43.3% in Bangladesh. We found that the highest rate of exposure to secondhand smoke in the workplace was in China (63.3%). We found the highest ‘smoking quit attempt’ rates in the past 12 months among cigarette smokers in Viet Nam (55.3%) and the lowest rate was in the Russian Federation (32.1%). In five of the 14 countries, more than one-half of current smokers in those 5 countries said they thought of quitting because of health warning labels on cigarette packages. The Philippines (74.3%) and the Russian Federation (68.0%) had the highest percentages of respondents noticing any cigarette advertising, promotion and sponsorship. Manufactured cigarette affordability ranged from 0.6% in Russia to 8.0% in India. CONCLUSIONS: Monitoring tobacco use and tobacco control policy achievements is crucial to managing and implementing measures to reverse the epidemic. GATS provides internationally-comparable data that systematically monitors and tracks the progress of the other five MPOWER measures.

  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. OBJECTIVE: Informal caregiving may likely increase as the number of cancer survivors grows. Caregiving responsibilities can impact caregivers’ quality of life (QOL). Understanding the current state of the science regarding caregiving QOL could help inform future research and intervention development. METHODS: A systematic literature review in PubMed/Medline examined research on QOL among informal cancer caregivers and related psychosocial health outcomes. Original research articles in English, published between 2007 and 2017 about caregivers (aged >18 years) of adult cancer patients in the United States were included. Abstracted articles were categorized according to caregiving recipient’s phase of survivorship (acute, middle to long-term, end of life/bereavement). RESULTS: Of 920 articles abstracted, 60 met inclusion criteria. Mean caregiver age ranged from 37 to 68 with the majority being female, non-Hispanic white, with at least a high school degree, and middle income. Almost half of the studies focused on caregivers who provided care for survivors from diagnosis through the end of active treatment. Studies examined physical health, spirituality, psychological distress, and social support. Differences in QOL were noted by caregiver age, sex, and employment status. SIGNIFICANCE OF RESULTS: Additional research includes the examination of the needs of diverse cancer caregivers and determines how additional caregiver characteristics (e.g., physical functioning, financial burden, etc.) affect QOL. This includes studies examining caregiver QOL in the phases following the cessation of active treatment and assessments of health systems, support services, and insurance to determine barriers and facilitators needed to meet the immediate and long-term needs of cancer caregivers.

    • Communicable Diseases
      1. Acute flaccid myelitis in the United States: 2015-2017external icon
        Ayers T, Lopez A, Lee A, Kambhampati A, Nix WA, Henderson E, Rogers S, Weldon WC, Oberste MS, Sejvar J, Hopkins SE, Pallansch MA, Routh JA, Patel M.
        Pediatrics. 2019 Oct 7.
        BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm(3) in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age </=21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition.

      2. Update: Influenza Activity – United States and Worldwide, May 19-September 28, 2019, and Composition of the 2020 Southern Hemisphere Influenza Vaccineexternal icon
        Epperson S, Davis CT, Brammer L, Abd Elal AI, Ajayi N, Barnes J, Budd AP, Burns E, Daly P, Dugan VG, Fry AM, Jang Y, Johnson SJ, Kniss K, Kondor R, Grohskopf LA, Gubareva L, Merced-Morales A, Sessions W, Stevens J, Wentworth DE, Xu X, Jernigan D.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):880-884.
        During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged >/=6 months who do not have contraindications to vaccination (1).

      3. Hospitalizations associated with respiratory syncytial virus and influenza in children, including children diagnosed with asthmaexternal icon
        Goldstein E, Finelli L, O’Halloran A, Liu P, Karaca Z, Steiner CA, Viboud C, Lipsitch M.
        Epidemiology. 2019 Nov;30(6):918-926.
        BACKGROUND: There is uncertainty about the burden of hospitalization associated with respiratory syncytial virus (RSV) and influenza in children, including those with underlying medical conditions. METHODS: We applied previously developed methodology to Health Care Cost and Utilization Project hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003 and 2010. RESULTS: The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2,381 (95% CI(2252,2515)) in children <1 year of age; 710.6 (609.1, 809.2) (1 y old); 395 (327.7, 462.4) (2 y old); 211.3 (154.6, 266.8) (3 y old); 111.1 (62.4, 160.1) (4 y old); 72.3 (29.3, 116.4) (5-6 y of age); 35.6 (9.9,62.2) (7-11 y of age); and 39 (17.5, 60.6) (12-17 y of age). The corresponding rates of influenza-associated hospitalization were lower, ranging from 181 (142.5, 220.3) in <1 year old to 17.9 (11.7, 24.2) in 12-17 years of age. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups <5 y ranged between 3.1 (2.1, 4.7) (<1 y old) and 6.7 (4.2, 11.8) (2 y old; the corresponding risks for influenza-related hospitalization ranged from 2.8 (2.1, 4) (<1y old) to 4.9 (3.8, 6.4) (3 y old). CONCLUSION: RSV-associated hospitalization rates in young children are high and decline rapidly with age. There are additional risks for both RSV and influenza hospitalization associated with a prior diagnosis of asthma, with the rates of RSV-related hospitalization in the youngest children diagnosed with asthma being particularly high.

      4. [No abstract]

      5. Vital signs: Burden and prevention of influenza and pertussis among pregnant women and infants – United Statesexternal icon
        Lindley MC, Kahn KE, Bardenheier BH, D’Angelo DV, Dawood FS, Fink RV, Havers F, Skoff TH.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):885-892.
        INTRODUCTION: Vaccinating pregnant women with influenza vaccine and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) can reduce influenza and pertussis risk for themselves and their infants. METHODS: Surveillance data were analyzed to ascertain influenza-associated hospitalization among pregnant women and infant hospitalization and death associated with influenza and pertussis. An Internet panel survey was conducted during March 27-April 8, 2019, among women aged 18-49 years who reported being pregnant any time since August 1, 2018. Influenza vaccination before or during pregnancy was assessed among respondents with known influenza vaccination status who were pregnant any time during October 2018-January 2019 (2,097). Tdap receipt during pregnancy was assessed among respondents with known Tdap status who reported a live birth by their survey date (817). RESULTS: From 2010-11 to 2017-18, pregnant women accounted for 24%-34% of influenza-associated hospitalizations per season among females aged 15-44 years. From 2010 to 2017, a total of 3,928 pertussis-related hospitalizations were reported among infants aged <2 months (annual range = 262-743). Maternal influenza and Tdap vaccination coverage rates reported as of April 2019 were 53.7% and 54.9%, respectively. Among women whose health care providers offered vaccination or provided referrals, 65.7% received influenza vaccine and 70.5% received Tdap. The most commonly reported reasons for nonvaccination were believing the vaccine is not effective (influenza; 17.6%) and not knowing that vaccination is needed during each pregnancy (Tdap; 37.9%), followed by safety concerns for the infant (influenza =15.9%; Tdap = 17.1%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Many pregnant women do not receive the vaccines recommended to protect themselves and their infants, even when vaccination is offered. CDC and provider organizations’ resources are available to help providers convey strong, specific recommendations for influenza and Tdap vaccination that are responsive to pregnant women’s concerns.

      6. Deaths associated with hepatitis C virus infection among residents in 50 states and the District of Columbia, 2016-2017external icon
        Ly KN, Minino AM, Liu SJ, Roberts H, Hughes EM, Ward JW, Jiles RB.
        Clin Infect Dis. 2019 Oct 5.
        BACKGROUND: Hepatitis C virus (HCV)-associated mortality is well-documented nationally, but examination across regions and jurisdictions may inform healthcare planning. METHODS: To document HCV-associated deaths sub-nationally, we calculated age-adjusted HCV-associated death rates, compared death rate ratios (DRR) for ten US regions, 50 states, and District of Columbia (DC) with the national rate and described rate changes between 2016 and 2017 to determine variability. We examined mean age at HCV-associated death and rates and proportions by sex, race/ethnicity, and birth year. RESULTS: In 2017, there were 17,253 HCV-associated deaths, representing 4.13 (95% CI, 4.07-4.20) deaths/100,000 standard population, a significant 6.56% rate decline from 4.42 in 2016. Age-adjusted death rates significantly surpassed the US rate for the following jurisdictions: Oklahoma, DC, Oregon, New Mexico, Louisiana, Texas, Colorado, California, Kentucky, Tennessee, Arizona, and Washington (DRR, 2.87, 2.77, 2.24, 1.62, 1.57, 1.46, 1.36, 1.35, 1.35, 1.35, 1.32, 1.32, respectively) (P<0.05). Death rates ranged from a low of 1.60 (95% CI, 1.07-2.29) in Maine to a high of 11.84 (95% CI, 10.82-12.85) in Oklahoma. Death rates were highest among non-Hispanic American Indians/Alaska Natives and non-Hispanic blacks nationally and regionally. Mean age at death was 61.4 years (range, 56.6 years in West Virginia to 64.1 years in DC); 78.6% of deaths were born during 1945-1965. CONCLUSION: In 2016-2017, national HCV-associated mortality declined but remained high in western and southern regions, DC, non-Hispanic American Indians/Alaska Natives, non-Hispanic blacks, and Baby Boomers. These data can inform local prevention and control programs to reduce the HCV mortality burden.

      7. Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of Americaexternal icon
        Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG.
        Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.
        Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

      8. Sex work, discrimination, drug use and violence: a pattern for HIV risk among transgender sex workers compared to MSM sex workers and other MSM in Guatemalaexternal icon
        Miller WM, Miller WC, Barrington C, Weir SS, Chen SY, Emch ME, Pettifor AE, Paz-Bailey G.
        Glob Public Health. 2019 Oct 10:1-13.
        The risk of HIV infection is higher among transgender women and cisgender men who have sex with men (MSM) compared to the general population due in part to social and contextual factors. This study aimed to determine the prevalence and association of alcohol and drug abuse, discrimination and violence among transgender sex workers compared to cisgender male sex workers and cisgender men who had not received money for sex in Guatemala City. In 2010, transgender women and cisgender men who had had sex with men or transgender women were recruited into a cross-sectional behavioural survey. Among transgender women, 86% received money for sex in the past year. Transgender sex workers were more likely to use drugs and binge drink, three times as likely to be discriminated against and eight times as likely to be forced to have sex compared to non-sex worker men. Male sex workers were twice as likely to use illicit drugs or experience physical violence and six times as likely to experience forced sex compared to non-sex worker men. Transgender and male sex workers would benefit from harm reduction for substance use, violence prevention, response and strategies to mitigate discrimination.

      9. Trends in HIV testing among US adults, aged 18-64 years, 2011-2017external icon
        Patel D, Johnson CH, Krueger A, Maciak B, Belcher L, Harris N, DiNenno EA.
        AIDS Behav. 2019 Oct 8.
        In 2006, Centers for Disease Control and Prevention (CDC) recommended HIV screening in healthcare or clinical settings for all persons aged 13-64 years and annual rescreening for populations at high risk for HIV. We used the Behavioral Risk Factor Surveillance System to describe the prevalence and trends of ever tested for HIV and tested for HIV in the past 12 months among US adults. The percentage of ever tested increased from 42.9% in 2011 to 45.9% in 2017; testing in the past 12 months increased from 13.2% in 2011 to 14.8% in 2017. Despite these increases, less than half of US adults have ever been tested for HIV over ten years after CDC’s recommendations. Increasing the prevalence of routine HIV screening and rescreening among individuals at high risk will reduce the number of undiagnosed persons with HIV infection and thus prevent new HIV infections-a key strategy in the Ending the HIV Epidemic initiative.

      10. National update on measles cases and outbreaks – United States, January 1-October 1, 2019external icon
        Patel M, Lee AD, Clemmons NS, Redd SB, Poser S, Blog D, Zucker JR, Leung J, Link-Gelles R, Pham H, Arciuolo RJ, Rausch-Phung E, Bankamp B, Rota PA, Weinbaum CM, Gastanaduy PA.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):893-896.
        During January 1-October 1, 2019, a total of 1,249 measles cases and 22 measles outbreaks were reported in the United States. This represents the most U.S. cases reported in a single year since 1992 (1), and the second highest number of reported outbreaks annually since measles was declared eliminated* in the United States in 2000 (2). Measles is an acute febrile rash illness with an attack rate of approximately 90% in susceptible household contacts (3). Domestic outbreaks can occur when travelers contract measles outside the United States and subsequently transmit infection to unvaccinated persons they expose in the United States. Among the 1,249 measles cases reported in 2019, 1,163 (93%) were associated with the 22 outbreaks, 1,107 (89%) were in patients who were unvaccinated or had an unknown vaccination status, and 119 (10%) measles patients were hospitalized. Closely related outbreaks in New York City (NYC) and New York State (NYS; excluding NYC), with ongoing transmission for nearly 1 year in large and close-knit Orthodox Jewish communities, accounted for 934 (75%) cases during 2019 and threatened the elimination status of measles in the United States. Robust responses in NYC and NYS were effective in controlling transmission before the 1-year mark; however, continued vigilance for additional cases within these communities is essential to determine whether elimination has been sustained. Collaboration between public health authorities and undervaccinated communities is important for preventing outbreaks and limiting transmission. The combination of maintenance of high national vaccination coverage with measles, mumps, and rubella vaccine (MMR) and rapid implementation of measles control measures remains the cornerstone for preventing widespread measles transmission (4).

      11. Client perspectives and experiences with HIV patient navigation in the United States: A qualitative meta-synthesisexternal icon
        Roland KB, Higa DH, Leighton CA, Mizuno Y, DeLuca JB, Koenig LJ.
        Health Promot Pract. 2019 Oct 9:1524839919875727.
        Patient navigation is increasingly utilized to link and (re)engage persons with HIV to care. Understanding client experiences with HIV patient navigation can facilitate intervention design and translation of evidence to practice. We conducted a qualitative meta-synthesis of client experiences with HIV patient navigation. Data were analyzed using thematic synthesis. We identified seven relevant studies; all collected data via in-depth interviews with persons with HIV who participated in HIV patient navigation. Four interrelated themes emerged from analysis that pertain to (1) the complexity of the health and social service environment and the holistic approaches taken by the navigator, (2) the profound significance of the client-navigator relationship, (3) client reluctance to end the navigation program, and (4) client self-efficacy and feelings of hope and psychological change as a result of their navigation experience. The unifying theme across all studies was the value and impact of the client-navigator relationship on client experience and quality of life. Programs should consider hiring navigators who possess strong relational skills and are peers of the clients, and clearly delineating the role of the navigator. Research should examine the impact of the client-navigator relationship on client outcomes and further investigate how participating in patient navigation affects client self-efficacy, client resiliency, and the role of posttraumatic growth to achieve improved HIV outcomes. This review underscores the significance of the relationship within intensive, multilevel interventions for individuals and communities marginalized and isolated from health and social service systems.

      12. Should you follow the better-hearing ear for congenital cytomegalovirus infection and isolated sensorineural hearing loss?external icon
        Torrecillas V, Allen CM, Greene T, Park A, Chung W, Lanzieri TM, Demmler-Harrison G.
        Otolaryngol Head Neck Surg. 2019 Oct 8:194599819880348.
        OBJECTIVE: To describe the progression of sensorineural hearing loss (SNHL) in the better- and poorer-hearing ears in children with asymptomatic congenital cytomegalovirus (CMV) infection with isolated SNHL. STUDY DESIGN: Longitudinal prospective cohort study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: We analyzed hearing thresholds of the better- and poorer-hearing ears of 16 CMV-infected patients with isolated congenital/early-onset or delayed-onset SNHL identified through hospital-based CMV screening of >30,000 newborns from 1982 to 1992. RESULTS: By 12 months of age, 4 of 7 patients with congenital/early-onset SNHL developed worsening thresholds in the poorer-hearing ear, and 1 had an improvement in the better-hearing ear. By 18 years of age, all 7 patients had worsening thresholds in the poorer-hearing ear and 3 patients had worsening thresholds in the better-hearing ear. Hearing loss first worsened at a mean age of 2 and 6 years in the poorer- and better-hearing ears, respectively. Nine patients were diagnosed with delayed-onset SNHL (mean age of 9 years vs 12 years for the poorer- and better-hearing ears), 6 of whom had worsening thresholds in the poorer-hearing ear and 1 in both ears. CONCLUSION: In most children with congenital CMV infection and isolated SNHL, the poorer-hearing ear worsened earlier and more precipitously than the better-hearing ear. This study suggests that monitoring individual hearing thresholds in both ears is important for appropriate interventions and future evaluation of efficacy of antiviral treatment.

      13. Clustering of hepatitis C virus antibody positivity within households and communities in Punjab, Indiaexternal icon
        Trickey A, Sood A, Midha V, Thompson W, Vellozzi C, Shadaker S, Surlikar V, Kanchi S, Vickerman P, May MT, Averhoff F.
        Epidemiol Infect. 2019 Oct 7;147:e283.
        To better understand hepatitis C virus (HCV) epidemiology in Punjab state, India, we estimated the distribution of HCV antibody positivity (anti-HCV+) using a 2013-2014 HCV household seroprevalence survey. Household anti-HCV+ clustering was investigated (a) by individual-level multivariable logistic regression, and (b) comparing the observed frequency of households with multiple anti-HCV+ persons against the expected, simulated frequency assuming anti-HCV+ persons are randomly distributed. Village/ward-level clustering was investigated similarly. We estimated household-level associations between exposures and the number of anti-HCV+ members in a household (N = 1593 households) using multivariable ordered logistic regression. Anti-HCV+ prevalence was 3.6% (95% confidence interval 3.0-4.2%). Individual-level regression (N = 5543 participants) found an odds ratio of 3.19 (2.25-4.50) for someone being anti-HCV+ if another household member was anti-HCV+. Thirty households surveyed had 2 anti-HCV+ members, whereas 0/1000 (P < 0.001) simulations had 30 such households. Excess village-level clustering was evident: 10 villages had 6 anti-HCV+ members, occurring in 31/1000 simulations (P = 0.031). The household-level model indicated the number of household members, living in southern Punjab, lower socio-economic score, and a higher proportion having ever used opium/bhuki were associated with a household’s number of anti-HCV+ members. Anti-HCV+ clusters within households and villages in Punjab, India. These data should be used to inform screening efforts.

      14. Trends in sexual risk behaviors among Hispanic/Latino men who have sex with men – 19 urban areas, 2011-2017external icon
        Trujillo L, Chapin-Bardales J, German EJ, Kanny D, Wejnert C.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):873-879.
        Correct and consistent condom use and human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) are protective against sexual transmission of HIV (1,2). The incidence of HIV infection among Hispanic/Latino men who have sex with men (MSM) in the United States is increasing (3). HIV risk among Hispanic/Latino MSM differs based on their place of birth and years of U.S. residence (4). Data from CDC’s National HIV Behavioral Surveillance (NHBS)* for 2011-2017 were analyzed to assess changes in sexual risk behaviors among Hispanic/Latino MSM by place of birth and years of U.S. residence. Overall, condomless anal sex during the previous 12 months increased from 63% in 2011 to 74% in 2017, and PrEP use during the previous 12 months increased from 3% in 2014 to 24% in 2017. Regardless of place of birth, nearly 75% of Hispanic/Latino MSM reported condomless anal sex during 2017. However, because of PrEP use, <60% of non-U.S.-born Hispanic/Latino MSM and <50% of U.S.-born Hispanic/Latino MSM reported unprotected anal sex (condomless anal sex and no PrEP use) during 2017. Results indicate that PrEP can be a vital tool for reducing HIV transmission among Hispanic/Latino MSM, especially those who have condomless anal sex. Interventions to prevent HIV acquisition, including increasing PrEP uptake, could address cultural and linguistic needs of Hispanic/Latino MSM, as well as other barriers to prevention of HIV infection typically faced by all MSM.

      15. Descriptive epidemiology of rubella disease and associated virus strains in Ugandaexternal icon
        Tushabe P, Bwogi J, Abernathy E, Birungi M, Eliku JP, Seguya R, Bukenya H, Namuwulya P, Kakooza P, Suppiah S, Kabaliisa T, Tibanagwa M, Ampaire I, Kisakye A, Bakainaga A, Byabamazima CR, Icenogle JP, Bakamutumaho B.
        J Med Virol. 2019 Oct 9.
        Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data prior to vaccine introduction. Sera collected during case-based measles surveillance from January 2005 to July 2018 were tested for rubella IgM antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real-time RT-PCR; for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23,196 suspected measles cases serologically tested in parallel for measles and rubella, 5,334 (23%) were rubella IgM positive of which 2,710 (50.8%) cases were females with 2,609 (96.3%) below 15 years of age. Rubella IgM positive cases were distributed throughout the country and the highest number detected in April, August and November. Eighteen (18%) of the 100 sera screened were real-time RT-PCR positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves towards control and elimination of rubella and CRS. This article is protected by copyright. All rights reserved.

    • Disease Reservoirs and Vectors
      1. Environmental conditions for Jamestown Canyon virus correlated with population-level resource selection by white-tailed deer in a suburban landscapeexternal icon
        Hollis-Etter KM, Montgomery RA, Etter DR, Anchor CL, Chelsvig JE, Warner RE, Grimstad PR, Lovin DD, Godsey MS.
        PLoS One. 2019 ;14(10):e0223582.
        Suburban landscapes can alter spatial patterns by white-tailed deer (Odocoileus virginianus) and increase animal contact with vectors, pathogens, and humans. Close-contact relationships at a landscape level can have broad implications for disease epidemiology. From 1995-1999, we captured and radio-collared 41 deer in two suburban forest preserves in Chicago, Illinois. We collected blood to determine if animals were seronegative or seropositive for Jamestown Canyon virus and tracked deer movements within suburban habitats. We developed utilization distributions at the population-level and evaluated resource selection for seronegative and seropositive deer. We used maximum likelihood estimation for model selection via Akaike information criterion and then restricted maximum likelihood estimation to attain unbiased estimates of the parameters in the top-ranking models. The top-ranking model describing the resource selection of seronegative deer received almost the full weight of evidence (Akaike information criterion omegai = 0.93), and included the proportion of wetlands, precipitation in year t, and an interaction of the proportion of wetlands and precipitation in year t. The top-ranking model describing resource selection of seropositive deer received the full weight of evidence (Akaike information criterion omegai = 1.00). The model included distance to nearest populated place, distance to nearest river, length of road in each grid cell, precipitation in year t, and an interaction of the length of road in each grid cell and precipitation in year t. These results are valuable for mapping the spatial configuration of hotspots for Jamestown Canyon virus and could be used to educate local residents and recreationalists to reduce human exposure.

      2. Consensus and uncertainty in the geographic range of Aedes aegypti and Aedes albopictus in the contiguous United States: Multi-model assessment and synthesisexternal icon
        Monaghan AJ, Eisen RJ, Eisen L, McAllister J, Savage HM, Mutebi JP, Johansson MA.
        PLoS Comput Biol. 2019 Oct;15(10):e1007369.
        Aedes (Stegomyia) aegypti (L.) and Ae. (Stegomyia) albopictus (Skuse) mosquitoes can transmit dengue, chikungunya, yellow fever, and Zika viruses. Limited surveillance has led to uncertainty regarding the geographic ranges of these vectors globally, and particularly in regions at the present-day margins of habitat suitability such as the contiguous United States. Empirical habitat suitability models based on environmental conditions can augment surveillance gaps to describe the estimated potential species ranges, but model accuracy is unclear. We identified previously published regional and global habitat suitability models for Ae. aegypti (n = 6) and Ae. albopictus (n = 8) for which adequate information was available to reproduce the models for the contiguous U.S. Using a training subset of recently updated county-level surveillance records of Ae. aegypti and Ae. albopictus and records of counties conducting surveillance, we constructed accuracy-weighted, probabilistic ensemble models from these base models. To assess accuracy and uncertainty we compared individual and ensemble model predictions of species presence or absence to both training and testing data. The ensemble models were among the most accurate and also provided calibrated probabilities of presence for each species. The quantitative probabilistic framework enabled identification of areas with high uncertainty and model bias across the U.S. where improved models or additional data could be most beneficial. The results may be of immediate utility for counties considering surveillance and control programs for Ae. aegypti and Ae. albopictus. Moreover, the assessment framework can drive future efforts to provide validated quantitative estimates to support these programs at local, national, and international scales.

    • Environmental Health
      1. Exposure to particulate matter (PM) in school environments has been associated with respiratory illnesses among children. Although using air cleaners was reported to reduce PM exposure and improve residents’ health in homes, their effects in classrooms are not well understood. We examined how the use of air cleaners in classrooms and school/classroom characteristics affect the levels of indoor PM. Our environmental study included 102 classrooms from 34 elementary schools located on the mainland peninsula and an island in Korea. Indoor and outdoor PM were monitored simultaneously with portable aerosol spectrometers, and indoor gravimetric PM levels were measured with low volume, size-selective samplers during the class hours. Correlations among PM measurements were computed and final multiple regression models for indoor PM were constructed with a model building procedure. Correlation between indoor and outdoor PM2.5 (PM < 2.5 microm in aerodynamic diameter) was higher (r = 0.78, p < 0.01) than that of PM10 (PM < 10 microm) (r = 0.49, p < 0.01). School location, classroom occupant density, and ambient PM levels significantly (p-values<0.05) affected classroom PM concentrations. The adjusted PM levels in classrooms using air cleaners were significantly (p-values<0.01) lower by approximately 35% than in classrooms not using them. However, air cleaners appeared to remove PM2.5 more effectively than PM10, perhaps because coarse particles settle more rapidly than fine particles on surfaces, or their resuspension and generation rate by occupants exceeds the removal rate by air cleaners. Our study suggests that routine cleaning to remove surface dust along with the use of air cleaners might be required to effectively reduce occupants’ exposure in classrooms.

    • Food Safety
      1. Incubation periods of enteric illnesses in foodborne outbreaks, United States, 1998-2013external icon
        Chai SJ, Gu W, O’Connor KA, Richardson LC, Tauxe RV.
        Epidemiol Infect. 2019 Oct 7;147:e285.
        Early in a foodborne disease outbreak investigation, illness incubation periods can help focus case interviews, case definitions, clinical and environmental evaluations and predict an aetiology. Data describing incubation periods are limited. We examined foodborne disease outbreaks from laboratory-confirmed, single aetiology, enteric bacterial and viral pathogens reported to United States foodborne disease outbreak surveillance from 1998-2013. We grouped pathogens by clinical presentation and analysed the reported median incubation period among all illnesses from the implicated pathogen for each outbreak as the outbreak incubation period. Outbreaks from preformed bacterial toxins (Staphylococcus aureus, Bacillus cereus and Clostridium perfringens) had the shortest outbreak incubation periods (4-10 h medians), distinct from that of Vibrio parahaemolyticus (17 h median). Norovirus, salmonella and shigella had longer but similar outbreak incubation periods (32-45 h medians); campylobacter and Shiga toxin-producing Escherichia coli had the longest among bacteria (62-87 h medians); hepatitis A had the longest overall (672 h median). Our results can help guide diagnostic and investigative strategies early in an outbreak investigation to suggest or rule out specific etiologies or, when the pathogen is known, the likely timeframe for exposure. They also point to possible differences in pathogenesis among pathogens causing broadly similar syndromes.

    • Genetics and Genomics
      1. A global genotyping survey of Strongyloides stercoralis and Strongyloides fuelleborni using deep amplicon sequencingexternal icon
        Barratt JL, Lane M, Talundzic E, Richins T, Robertson G, Formenti F, Pritt B, Verocai G, Nascimento de Souza J, Mato Soares N, Traub R, Buonfrate D, Bradbury RS.
        PLoS Negl Trop Dis. 2019 Sep;13(9):e0007609.
        Strongyloidiasis is a neglected tropical disease caused by the human infective nematodes Strongyloides stercoralis, Strongyloides fuelleborni fuelleborni and Strongyloides fuelleborni kellyi. Previous large-scale studies exploring the genetic diversity of this important genus have focused on Southeast Asia, with a small number of isolates from the USA, Switzerland, Australia and several African countries having been genotyped. Consequently, little is known about the global distribution of geographic sub-variants of these nematodes and the genetic diversity that exists within the genus Strongyloides generally. We extracted DNA from human, dog and primate feces containing Strongyloides, collected from several countries representing all inhabited continents. Using a genotyping assay adapted for deep amplicon sequencing on the Illumina MiSeq platform, we sequenced the hyper-variable I and hyper-variable IV regions of the Strongyloides 18S rRNA gene and a fragment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene from these specimens. We report several novel findings including unique S. stercoralis and S. fuelleborni genotypes, and the first identifications of a previously unknown S. fuelleborni infecting humans within Australia. We expand on an existing Strongyloides genotyping scheme to accommodate S. fuelleborni and these novel genotypes. In doing so, we compare our data to all 18S and cox1 sequences of S. fuelleborni and S. stercoralis available in GenBank (to our knowledge), that overlap with the sequences generated using our approach. As this analysis represents more than 1,000 sequences collected from diverse hosts and locations, representing all inhabited continents, it allows a truly global understanding of the population genetic structure of the Strongyloides species infecting humans, non-human primates, and domestic dogs.

      2. Pathogen surveillance in the informal settlement, Kibera, Kenya, using a metagenomics approachexternal icon
        Hendriksen RS, Lukjancenko O, Munk P, Hjelmso MH, Verani JR, Ng’eno E, Bigogo G, Kiplangat S, Oumar T, Bergmark L, Roder T, Neatherlin JC, Clayton O, Hald T, Karlsmose S, Pamp SJ, Fields B, Montgomery JM, Aarestrup FM.
        PLoS One. 2019 ;14(10):e0222531.
        BACKGROUND: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate. METHOD: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance. RESULTS: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time. CONCLUSION: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care.

      3. Phylogenetic methods inconsistently predict the direction of HIV transmission among heterosexual pairs in the HPTN 052 cohortexternal icon
        Rose R, Hall M, Redd AD, Lamers S, Barbier AE, Porcella SF, Hudelson SE, Piwowar-Manning E, McCauley M, Gamble T, Wilson EA, Kumwenda J, Hosseinipour MC, Hakim JG, Kumarasamy N, Chariyalertsak S, Pilotto JH, Grinsztejn B, Mills LA, Makhema J, Santos BR, Chen YQ, Quinn TC, Fraser C, Cohen MS, Eshleman SH, Laeyendecker O.
        J Infect Dis. 2019 Sep 26;220(9):1406-1413.
        BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, “index patients”) and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, “SC samples”); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, “early index samples”) were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees. RESULTS: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

    • Health Economics
      1. Billing and payment of commercial and Medicaid health plan adult vaccination claims in Michigan since the Affordable Care Actexternal icon
        Goodman RM, Bridges CB, Kim D, Pike J, Rose A, Prosser LA, Hutton DW.
        Vaccine. 2019 Oct 23;37(45):6803-6813.
        BACKGROUND: Provider concern regarding insurance non-payment for vaccines is a common barrier to provision of adult immunizations. We examined current adult vaccination billing and payment associated with two managed care populations to identify reasons for non-payment of immunization insurance claims. METHODS: We assessed administrative data from 2014 to 2015 from Blue Care Network of Michigan, a nonprofit health maintenance organization, and Blue Cross Complete of Michigan, a Medicaid managed care plan, to determine rates of and reasons for non-payment of adult vaccination claims across patient-care settings, insurance plans, and vaccine types. We compared commercial and Medicaid payment rates to Medicare payment rates and examined patient cost sharing. RESULTS: Pharmacy-submitted claims for adult vaccine doses were almost always paid (commercial 98.5%; Medicaid 100%). As the physician office accounted for the clear majority (79% commercial; 69% Medicaid) of medical (non-pharmacy) vaccination services, we limited further analyses of both commercial and Medicaid medical claims to the physician office setting. In the physician office setting, rates of payment were high with commercial rates of payment (97.9%) greater than Medicaid rates (91.6%). Reasons for non-payment varied, but generally related to the complexity of adult vaccine recommendations (patient diagnosis does not match recommendations) or insurance coverage (complex contracts, multiple insurance payers). Vaccine administration services were also generally paid. Commercial health plan payments were greater for both vaccine dose and vaccine administration than Medicare payments; Medicaid paid a higher amount for the vaccine dose, but less for vaccine administration than Medicare. Patients generally had very low (commercial) or no (Medicaid) cost-sharing for vaccination. CONCLUSIONS: Adult vaccine dose claims were usually paid. Medicaid generally had higher rates of non-payment than commercial insurance.

      2. Our objective was to develop comprehensive national estimates of the total burden of HZ among US adults, including direct (ie, medical costs) and indirect (ie, productivity losses) costs, as well as its psychosocial impact (ie, quality of life losses).Using a patient-level microsimulation model, we projected health and economic outcomes among US adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015.Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually.Projected QALY-losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN.The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.

      3. PURPOSE: The purpose of this paper is to provide a brief overview of economic analysis methods used in estimating the costs and benefits of public health programs and systematically review the application of these methods to the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). METHODS: Published literature on economic analyses of the NBCCEDP was systematically reviewed. The Consensus on Health Economic Criteria checklist was used to assess methodological quality of the included studies. RESULTS: Methods available for economic analysis of public health programs include program cost, cost-effectiveness, cost-utility, cost-benefit analysis, and budget impact analysis. Of these, program cost analysis, cost-effectiveness analysis, and cost-utility analysis have been applied to the NBCCEDP in previously published literature. CONCLUSION: While there have been multiple program cost analyses, there are relatively fewer cost-effectiveness and cost-utility studies and no cost-benefit and budget impact analysis studies to evaluate the NBCCEDP. Addressing these gaps will inform implementation of effective public health programs with equitable resource allocation to all population subgroups.

    • Healthcare Associated Infections
      1. Sample size estimates for cluster-randomized trials in hospital infection control and antimicrobial stewardshipexternal icon
        Blanco N, Harris AD, Magder LS, Jernigan JA, Reddy SC, O’Hagan J, Hatfield KM, Pineles L, Perencevich E, O’Hara LM.
        JAMA Netw Open. 2019 Oct 2;2(10):e1912644.
        Importance: An important step in designing, executing, and evaluating cluster-randomized trials (CRTs) is understanding the correlation and thus nonindependence that exists among individuals in a cluster. In hospital epidemiology, there is a shortage of CRTs that have published their intraclass correlation coefficient or coefficient of variation (CV), making prospective sample size calculations difficult for investigators. Objectives: To estimate the number of hospitals needed to power parallel CRTs of interventions to reduce health care-associated infection outcomes and to demonstrate how different parameters such as CV and expected effect size are associated with the sample size estimates in practice. Design, Setting, and Participants: This longitudinal cohort study estimated parameters for sample size calculations using national rates developed by the Centers for Disease Control and Prevention for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, central-line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and Clostridium difficile infections (CDI) from 2016. For MRSA and vancomycin-resistant enterococci (VRE) acquisition, outcomes were estimated using data from 2012 from the Benefits of Universal Glove and Gown study. Data were collected from June 2017 through September 2018 and analyzed from September 2018 through January 2019. Main Outcomes and Measures: Calculated number of clusters needed for adequate power to detect an intervention effect using a 2-group parallel CRT. Results: To study an intervention with a 30% decrease in daily rates, 73 total clusters were needed (37 in the intervention group and 36 in the control group) for MRSA bacteremia, 82 for CAUTI, 60 for CLABSI, and 31 for CDI. If a 10% decrease in rates was expected, 768 clusters were needed for MRSA bacteremia, 875 for CAUTI, 631 for CLABSI, and 329 for CDI. For MRSA or VRE acquisition, 50 or 40 total clusters, respectively, were required to observe a 30% decrease, whereas 540 or 426 clusters, respectively, were required to detect a 10% decrease. Conclusions and Relevance: This study suggests that large sample sizes are needed to appropriately power parallel CRTs targeting infection prevention outcomes. Sample sizes are most associated with expected effect size and CV of hospital rates.

    • Immunity and Immunization
      1. Estimating population immunity to poliovirus in Jordan’s high-risk areasexternal icon
        Farag NH, Wannemuehler K, Weldon W, Arbaji A, Belbaisi A, Khuri-Bulos N, Ehrhardt D, Surour MR, ElhajQasem NS, Al-Abdallat MM.
        Hum Vaccin Immunother. 2019 Oct 4.
        A community-based serosurvey was conducted among children ages 6-59 to assess population immunity in Jordan’s high-risk areas following the Middle East polio outbreak response. The survey was a two-stage cluster-quota sample with high risk areas as the primary sampling units. High-risk areas included border and hard-to-reach areas, and areas with a high proportion of refugees, mobile communities and/or low coverage during previous immunization campaigns. Population immunity to poliovirus was high overall. In high-risk areas, Type 1 seroprevalence = 98% (95% CI = 96, 99), Type 2= 98 (95% CI = 96, 99) and Type 3= 96 (95% CI = 94, 98). Seroprevalence was higher in the refugee camps: Type 1 seroprevalence = 99.6 (95% CI = 97.9, 100); Type 2: 99.6 (95% CI = 97.9, 99.9), and Type 3: 100 (95% CI = 100,100). The vigilance that the Jordan Ministry of Health has placed on locating and vaccinating high-risk populations has been successful in maintaining high population immunity and averting polio outbreaks despite the influx of refugees from Syria.

      2. Inactivated rabies virus-based Ebola vaccine preserved by vaporization is heat-stable and immunogenic against Ebola and protects against rabies challengeexternal icon
        Kurup D, Fisher CR, Smith TG, Abreu-Mota T, Yang Y, Jackson FR, Gallardo-Romero N, Franka R, Bronshtein V, Schnell MJ.
        J Infect Dis. 2019 Sep 26;220(9):1521-1528.
        BACKGROUND: Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage. METHODS: We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4 degrees C to 50 degrees C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV). RESULTS: Syrian hamsters immunized with FiloRab1 PBV-processed vaccines stored at temperatures of 4 degrees C and 37 degrees C for 6 months, and at 50 degrees C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model. CONCLUSIONS: We successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4 degrees C to 37 degrees C and for up to 2 weeks at 50 degrees C.

      3. The 2016 and 2017 National Immunization Surveys-Teen (NIS-Teen) highlighted disparities in human papillomavirus (HPV) vaccination coverage by metropolitan statistical area (MSA) status. Coverage with >/=1 dose of HPV vaccine was significantly lower among teens in suburban and mostly- rural areas than it was among those in mostly-urban areas. Reasons underlying this disparity are poorly understood; this analysis sought to identify sociodemographic factors associated with not initiating the HPV vaccine series and to determine whether these factors differed by MSA status. Using NIS-Teen data for a sample of 41,424 adolescents from the 2016 and 2017 survey years, multivariate logistic regression was utilized to assess associations between various sociodemographic factors and non-initiation of the HPV vaccine series by MSA status. Adjusted prevalence ratios and 95% confidence intervals are reported. A secondary analysis assessed missed opportunities for HPV vaccination by MSA status and estimated what coverage could be if these missed opportunities had not occurred. Most factors associated with not receiving HPV vaccine were similar across all three MSAs, including living in the South, having a mother with some college education, not having an 11-12 year old well-child visit, and not receiving a provider recommendation for vaccination. Others were associated with non-initiation of the HPV vaccine series in only specific MSAs. Teens in suburban areas (82.2%) were more likely to miss opportunities for HPV vaccination than those in mostly-urban (79.3%) areas. Coverage with >/=1 dose of HPV vaccine in all three MSAs would be substantially higher if these missed opportunities had been eliminated.

      4. Review of the status and challenges associated with increasing influenza vaccination coverage among pregnant women in Chinaexternal icon
        Zhou S, Greene CM, Song Y, Zhang R, Rodewald LE, Feng L, Millman AJ.
        Hum Vaccin Immunother. 2019 Oct 7:1-10.
        Influenza vaccination coverage in pregnant women in China remains low. In this review, we first provide an overview of the evidence for the use of influenza vaccination during pregnancy. Second, we discuss influenza vaccination policy and barriers to increased seasonal influenza vaccination coverage in pregnant women in China. Third, we provide case studies of successes and challenges of programs for increasing seasonal influenza vaccination in pregnant women from other parts of Asia with lessons learned for China. Finally, we assess opportunities and challenges for increasing influenza vaccination coverage among pregnant women in China.

    • Laboratory Sciences
      1. Building biosafety capacity in our nation’s laboratoriesexternal icon
        Chung CL, Bellis KS, Pullman A, O’Connor A, Shultz A.
        Health Secur. 2019 Sep/Oct;17(5):353-363.
        The 2014 Ebola outbreak revealed biosafety vulnerabilities across the United States. We distributed $24.1 million to health departments to support public health laboratories (PHLs) and sentinel clinical laboratory partners to improve biosafety practices. We used 9 indicators to evaluate PHLs and associated clinical laboratories from March 2015 through April 2018 using descriptive statistics. On average, over 6 reporting periods, 59 awardee PHLs and 4,040 clinical laboratories responded. By April 2018, 92% (57 of 62) of PHLs had conducted at least 1 risk assessment for work with Ebola and another highly infectious disease. The number of PHLs having a policy for risk assessments increased from 32 of 61 (52%) to 49 of 54 (91%). The percentage of awardees meeting the target (80%) for associated clinical laboratories with staff certifications to package/ship rose from 32% (19 of 60) to 46% (25 of 54). The percentage of awardees meeting the target (70%) for associated clinical laboratories with risk assessment policies increased from 18% (8 of 44) to 28% (15 of 54). Awardees reported improvement among Ebola treatment centers/Ebola assessment hospitals with policies to perform risk assessments from 48% (20 of 42) to 67% (34 of 51). Public health laboratories and their clinical partners made progress on their abilities to address biosafety concerns and implement consistent biosafety practices, improving their ability to work safely with biological threats. More attention is needed to address gaps in the clinical community. Support for biosafety activities is critical to continuing to achieve progress.

      2. Use of live Variola virus to determine whether CAST/EiJ mice are a suitable surrogate animal model for human smallpoxexternal icon
        Gallardo-Romero NF, Hutson CL, Carroll D, Kondas AV, Salzer JS, Dietz-Ostergaard S, Smith S, Hudson P, Olson V, Damon I.
        Virus Res. 2019 Oct 5:197772.
        Numerous animal models of systemic orthopoxvirus disease have been developed to evaluate therapeutics against variola virus (VARV), the causative agent of smallpox. These animal models do not resemble the disease presentation in human smallpox and most used surrogate Orthopoxviruses. A rodent model using VARV has a multitude of advantages, and previous investigations identified the CAST/EiJ mouse as highly susceptible to monkeypox virus infection, making it of interest to determine if these rodents are also susceptible to VARV infection. In this study, we inoculated CAST/EiJ mice with a range of VARV doses (10(2)-10(6) plaque forming units). Some animals had detectable viable VARV from the oropharynx between days 3 and 12 post inoculation. Despite evidence of disease, the CAST/EiJ mouse does not provide a model for clinical smallpox due to mild signs of morbidity and limited skin lesions. However, in contrast to previous rodent models using VARV challenge (i.e. prairie dogs and SCID mice), a robust immune response was observed in the CAST/EiJ mice (measured by Immunoglobulin G enzyme-linked immunosorbent assay). This is an advantage of this model for the study of VARV and presents a unique potential for the study of the immunomodulatory pathways following VARV infection.

      3. Recently, the IL-36 cytokines were shown to be elevated in women with non-Lactobacillus-dominated vaginal microbiomes. Here, we evaluated IL36G expression in clinical samples from women with and without bacterial vaginosis (BV) and a human 3-D cervical epithelial cell model. IL36G expression was significantly elevated in cervicovaginal epithelial cells isolated from BV-positive women and corresponded with increased neutrophil counts relative to BV-negative women. Additionally, specific BV-associated bacterial species as well as a polymicrobial cocktail significantly induced IL36G expression in vitro. These findings suggest that IL-36gamma may exhibit an important function in the host response to BV and other sexually transmitted infections.

      4. Analysis of toxic metals in electronic cigarette aerosols using a novel trap designexternal icon
        Halstead M, Gray N, Gonzalez-Jimenez N, Fresquez M, Valentin-Blasini L, Watson C, Pappas RS.
        J Anal Toxicol. 2019 Oct 4.
        Since 2006 the domestic popularity and sales of electronic cigarettes (i.e., electronic nicotine delivery systems or ENDS) have grown rapidly. Although the constituents of the aerosol produced by ENDS have been previously investigated, differences in puff regimens and aerosol trapping schema in published literature often complicate result comparisons and data interpretation. As the ENDS product designs continue to evolve, there is a critical need to develop and validate robust methodologies for laboratory testing, appropriate aerosol generation and trapping media required for accurate determinations of ENDS aerosol metals deliveries. A simple, high metals purity, fluoropolymer trap was developed and validated that meets standard machine puffing regimen (CORESTA Recommended Method 81) specifications and exhibits negligible acid extractable metal backgrounds. Using a standard machine puffing regimen in combination with a fluoropolymer condensation trap, aerosol was generated and collected from select ENDS devices for analysis of chromium, nickel, copper, zinc, cadmium, tin, and lead with triple quadrupole inductively coupled plasma mass spectrometry. Devices tested spanned a range of commercial products, including flavored variants of JUUL pods, refillable tank systems, rechargeable cartridges, and single-use ENDs devices. Results showed that for aerosols generated under a fixed puffing regimen (50 puffs/collection), metal concentrations ranged from below the detection limits (LOD) to 614 ng copper and 339 ng zinc per 10 puffs. Cadmium concentrations were below LOD for all devices tested. Device specific aerosol levels of Sn and Pb ranged from below LOD to low nanogram levels. Cr and Ni were transported in aerosols at levels equivalent to, or slightly higher than in mainstream cigarette smoke using a standard smoking regimen. The generally lower levels of specific metals, Cd and Pb, transmitted in ENDS aerosols compared to mainstream cigarette smoke reflect possible reduction of harm for smokers who substitute the use of ENDS as cessation devices in place of smoking cigarettes.

      5. Feasibility of a point-of-care test based on quantum dots with a mobile phone reader for detection of antibody responsesexternal icon
        Lee C, Noh J, O’Neal SE, Gonzalez AE, Garcia HH, Handali S.
        PLoS Negl Trop Dis. 2019 Oct 7;13(10):e0007746.
        We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru that conducted under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the specimen was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95-100%) while assay sensitivity was 89% (79-95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection.

      6. Correlation between Etest and reference broth microdilution for antimicrobial susceptibility testing of Burkholderia pseudomalleiexternal icon
        Lonsway DR, Elrod MG, Kendrick N, Tiller R, Sullivan MM, Edwards JR, Blaney DD, Karlsson M.
        Microb Drug Resist. 2019 Oct 9.
        A three-center study was performed to see if Etest gradient diffusion minimum inhibitory concentration (MIC) methodology correlated with reference broth microdilution (BMD) for antimicrobial susceptibility testing of Burkholderia pseudomallei against six antimicrobial agents known to be usually effective against B. pseudomallei. This study was performed to assist in the decision-making process for possible deployment of the Etest method for antimicrobial susceptibility testing of B. pseudomallei into several regional public health laboratories in the United States. Three laboratories each tested a challenge set of 30 genotypically diverse isolates collected from 15 different countries. MICs were performed by both Etest gradient diffusion and reference BMD for amoxicillin/clavulanate, ceftazidime, doxycycline, imipenem, tetracycline, and trimethoprim/sulfamethoxazole. Etest results for amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem correlated well with reference BMD by both category interpretation (>/=97%) and essential agreement of MIC (>/=93%). Tetracycline and trimethoprim/sulfamethoxazole Etests yielded poor correlation with BMD by category interpretation (80%) and essential agreement (70%), respectively. In conclusion, Etest gradient diffusion represents a valid option for antimicrobial susceptibility testing of B. pseudomallei against amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem. Tetracycline and trimethoprim/sulfamethoxazole Etest results showed some concerning lack of correlation with the corresponding reference BMD results.

      7. OBJECTIVES: To demonstrate the performance of 53 laboratories required to submit 90% or more of their pulsed-field gel electrophoresis (PFGE) subtyping results for Escherichia coli O157:H7 (E coli O157:H7) and Listeria monocytogenes (L monocytogenes) to the PulseNet national databases at the Centers for Disease Control and Prevention (CDC) within 4 working days of receiving isolates. METHODS: We examined data from 53 laboratories during 2013-2017 to ascertain whether E. coli O157:H7 and L monocytogenes PFGE data were reported to the PulseNet national databases within 4 working days. RESULTS: In the study period, 45 laboratories that submitted reports during the period (86.8%) met the target for timely submission of 10 606 (94.85%) E coli O157:H7 isolates into the PulseNet national database. For L monocytogenes isolates, 32 laboratories submitted reports (76.95%) that achieved timely submission of 3119 (93.35%) isolates. CONCLUSIONS: This study uncovered areas for improvement to advance public health in the CDC-funded laboratories.

      8. Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cellsexternal icon
        Siegrist KJ, Reynolds SH, Porter DW, Mercer RR, Bauer AK, Lowry D, Cena L, Stueckle TA, Kashon ML, Wiley J, Salisbury JL, Mastovich J, Bunker K, Sparrow M, Lupoi JS, Stefaniak AB, Keane MJ, Tsuruoka S, Terrones M, McCawley M, Sargent LM.
        Part Fibre Toxicol. 2019 Oct 7;16(1):36.
        BACKGROUND: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). RESULTS: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 mug/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 mug/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 mug/mL MWCNT-HT & ND. CONCLUSIONS: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

      9. Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015external icon
        Tamin A, Queen K, Paden CR, Lu X, Andres E, Sakthivel SK, Li Y, Tao Y, Zhang J, Kamili S, Assiri AM, Alshareef A, Alaifan TA, Altamimi AM, Jokhdar H, Watson JT, Gerber SI, Tong S, Thornburg NJ.
        J Gen Virol. 2019 Oct 8.
        Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5’UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5’UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.

    • Maternal and Child Health
      1. Overview and development of the Child Health and Mortality Prevention Surveillance Determination of Cause of Death (DeCoDe) Process and DeCoDe Diagnosis Standardsexternal icon
        Blau DM, Caneer JP, Philipsborn RP, Madhi SA, Bassat Q, Varo R, Mandomando I, Igunza KA, Kotloff KL, Tapia MD, Johnstone S, Chawana R, Rahman A, El Arifeen S, Onyango D, Kaiser R, Seale AC, Assefa N, Morris T, Raghunathan PL, Breiman RF.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S333-s341.
        Mortality surveillance and cause of death data are instrumental in improving health, identifying diseases and conditions that cause a high burden of preventable deaths, and allocating resources to prevent these deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) network uses a standardized process to define, assign, and code causes of stillbirth and child death (<5 years of age) across the CHAMPS network. A Determination of Cause of Death (DeCoDe) panel composed of experts from a local CHAMPS site analyzes all available individual information, including laboratory, histopathology, abstracted clinical records, and verbal autopsy findings for each case and, if applicable, also for the mother. Using this information, the site panel ascertains the underlying cause (event that precipitated the fatal sequence of events) and other antecedent, immediate, and maternal causes of death in accordance with the International Classification of Diseases, Tenth Revision and the World Health Organization death certificate. Development and use of the CHAMPS diagnosis standards-a framework of required evidence to support cause of death determination-assures a homogenized procedure leading to a more consistent interpretation of complex data across the CHAMPS network. This and other standardizations ensures future comparability with other sources of mortality data produced externally to this project. Early lessons learned from implementation of DeCoDe in 5 CHAMPS sites in sub-Saharan Africa and Bangladesh have been incorporated into the DeCoDe process, and the implementation of DeCoDe has the potential to spur health systems improvements and local public health action.

      2. Using participatory workshops to assess alignment or tension in the Community for Minimally Invasive Tissue Sampling Prior to Start of Child Mortality Surveillance: Lessons from 5 sites across the CHAMPS Networkexternal icon
        Blevins J, O’Mara Sage E, Kone A, Maixenchs M, Raghunathan PL, Guilaze RA, Cossa S, Girma Z, Zegeye Y, Ackley C, Hussain F, Islam S, Myburgh N, Ngwenya N, Madhi SA, Otieno P, Ochola K, Munguambe K, Breiman RF.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S280-s290.
        The Child Health and Mortality Prevention Surveillance (CHAMPS) program is a 7-country network (as of December 2018) established by the Bill & Melinda Gates Foundation to identify the causes of death in children in communities with high rates of under-5 mortality. The program carries out both mortality and pregnancy surveillance, and mortality surveillance employs minimally invasive tissue sampling (MITS) to gather small samples of body fluids and tissue from the bodies of children who have died. While this method will lead to greater knowledge of the specific causes of childhood mortality, the procedure is in tension with cultural and religious norms in many of the countries where CHAMPS works-Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. Participatory Inquiry Into Community Knowledge of Child Health and Mortality Prevention (PICK-CHAMP) is a community entry activity designed to introduce CHAMPS to communities and gather initial perspectives on alignments and tensions between CHAMPS activities and community perceptions and priorities. Participants’ responses revealed medium levels of overall alignment in all sites (with the exception of South Africa, where alignment was high) and medium levels of tension (with the exception of Ethiopia, where tension was high). Alignment was high and tension was low for pregnancy surveillance across all sites, whereas Ethiopia reflected low alignment and high tension for MITS. Participants across all sites indicated that support for MITS was possible only if the procedure did not interfere with burial practices and rituals.

      3. Potential of minimally invasive tissue sampling for attributing specific causes of childhood deaths in South Africa: A pilot, epidemiological studyexternal icon
        Chawana R, Baillie V, Izu A, Solomon F, Bassat Q, Blau DM, Breiman RF, Hale M, Houpt ER, Lala SG, Martines RB, Mathunjwa A, Nzenze S, Pathirana J, Petersen KL, Raghunathan PL, Ritter JM, Wadula J, Zaki SR, Madhi SA.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S361-s373.
        BACKGROUND: Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. METHODS: MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. CONCLUSIONS: MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.

      4. Health and demographic surveillance systems within the Child Health and Mortality Prevention Surveillance Networkexternal icon
        Cunningham SA, Shaikh NI, Nhacolo A, Raghunathan PL, Kotloff K, Naser AM, Mengesha MM, Adedini SA, Misore T, Onuwchekwa UU, Worrell MC, El Arifeen S, Assefa N, Chowdhury AI, Kaiser R, Madhi SA, Mehta A, Obor D, Sacoor C, Sow SO, Tapia MD, Wilkinson AL, Breiman RF.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S274-s279.
        Health and demographic surveillance systems (HDSSs) provide a foundation for characterizing and defining priorities and strategies for improving population health. The Child Health and Mortality Prevention Surveillance (CHAMPS) project aims to inform policy to prevent child deaths through generating causes of death from surveillance data combined with innovative diagnostic and laboratory methods. Six of the 7 sites that constitute the CHAMPS network have active HDSSs: Mozambique, Mali, Ethiopia, Kenya, Bangladesh, and South Africa; the seventh, in Sierra Leone, is in the early planning stages. This article describes the network of CHAMPS HDSSs and their role in the CHAMPS project. To generate actionable health and demographic data to prevent child deaths, the network depends on reliable demographic surveillance, and the HDSSs play this crucial role.

      5. Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratoriesexternal icon
        Diaz MH, Waller JL, Theodore MJ, Patel N, Wolff BJ, Benitez AJ, Morris T, Raghunathan PL, Breiman RF, Whitney CG, Blau DM, Winchell JM.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S311-s321.
        Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30-45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories.

      6. An observational pilot study evaluating the utility of minimally invasive tissue sampling to determine the cause of stillbirths in South African womenexternal icon
        Madhi SA, Pathirana J, Baillie V, Cutland C, Adam Y, Izu A, Bassat Q, Blau DM, Breiman RF, Hale M, Johnstone S, Martines RB, Mathunjwa A, Nzenze S, Ordi J, Raghunathan PL, Ritter JM, Solomon F, Wadula J, Zaki SR, Chawana R.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S342-s350.
        BACKGROUND: Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. METHODS: This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization’s International Classification of Diseases, Tenth Revision application to perinatal deaths. RESULTS: A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). CONCLUSIONS: In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.

      7. Unraveling specific causes of neonatal mortality using minimally invasive tissue sampling: An observational studyexternal icon
        Madhi SA, Pathirana J, Baillie V, Izu A, Bassat Q, Blau DM, Breiman RF, Hale M, Mathunjwa A, Martines RB, Nakwa FL, Nzenze S, Ordi J, Raghunathan PL, Ritter JM, Solomon F, Velaphi S, Wadula J, Zaki SR, Chawana R.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S351-s360.
        BACKGROUND: Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. METHODS: This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12-15 medical specialists. RESULTS: We enrolled 153 neonatal deaths, 106 aged 3-28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause. CONCLUSIONS: MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths.

      8. Pathology and telepathology methods in the Child Health and Mortality Prevention Surveillance Networkexternal icon
        Martines RB, Ritter JM, Gary J, Shieh WJ, Ordi J, Hale M, Carrilho C, Ismail M, Traore CB, Ndibile BE, Sava S, Arjuman F, Kamal M, Rahman MM, Blau DM, Zaki SR.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S322-s332.
        This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.

      9. Early life exposure to air pollution and autism spectrum disorder: Findings from a multisite case-control studyexternal icon
        McGuinn LA, Windham GC, Kalkbrenner AE, Bradley C, Di Q, Croen LA, Fallin MD, Hoffman K, Ladd-Acosta C, Schwartz J, Rappold AG, Richardson DB, Neas LM, Gammon MD, Schieve LA, Daniels JL.
        Epidemiology. 2019 Oct 1.
        BACKGROUND: Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. OBJECTIVES: We examined associations between early life exposure to PM2.5 and ozone in association with ASD across multiple US regions. METHODS: Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. RESULTS: The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life [OR = 1.3 (95% CI: 1.0, 1.6) per 1.6 microg/m increase in PM2.5]. CONCLUSIONS: Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods.

      10. Investigating the feasibility of child mortality surveillance with postmortem tissue sampling: Generating constructs and variables to strengthen validity and reliability in qualitative researchexternal icon
        O’Mara Sage E, Munguambe KR, Blevins J, Guilaze R, Kosia B, Maixenchs M, Bassat Q, Mandomando I, Kaiser R, Kone A, Jambai A, Myburgh ND, Ngwenya N, Madhi SA, Degefa K, Ackley C, Breiman RF, Raghunathan PL.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S291-s301.
        BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged <5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS. METHODS: Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting. RESULTS: Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability. CONCLUSIONS: These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS.

      11. Illuminating child mortality: Discovering why children dieexternal icon
        Raghunathan PL, Madhi SA, Breiman RF.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S257-s259.
        Current understanding of the causes of under-5 childhood deaths in low- and middle-income countries relies heavily on country-level vital registration data and verbal autopsies. Reliable data on specific causes of deaths are crucial to target interventions more effectively and achieve rapid reductions in under-5 mortality. The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to systematically describe causes of child death and stillbirth in low- and middle-income countries using minimally invasive tissue sampling. The articles in this supplement introduce the set of foundational epidemiologic, demographic surveillance, social behavioral science, and laboratory methods. Undergirding the CHAMPS surveillance system designed to determine causes of child mortality.

      12. Standardization of minimally invasive tissue sampling specimen collection and pathology training for the Child Health and Mortality Prevention Surveillance Networkexternal icon
        Rakislova N, Fernandes F, Lovane L, Jamisse L, Castillo P, Sanz A, Marimon L, Jesri S, Ferrando M, Delgado V, Novela O, Muiuane V, Ismail MR, Lorenzoni C, Blau DM, Bassat Q, Menendez C, Zaki SR, Carrilho C, Ordi J.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S302-s310.
        BACKGROUND: Minimally invasive tissue sampling (MITS) is a simplified postmortem examination technique that has shown to be an adequate approach for cause of death investigation in low-resource settings. It requires relatively low level of infrastructures and can be performed by health professionals with no background in pathology. A training program has been developed for the Child Health and Mortality Prevention Surveillance (CHAMPS) network to guarantee standardization of specimen collection techniques, procedures, and laboratory methods. METHODS: The training program has included assessment of the site capacities and training on a standardized protocol of MITS sampling and histological processing. The project has also introduced a program of training for trainers for the personnel from Mozambique. To guarantee the adequacy of the procedure in each site, a trainer accompanied the local teams when the activities started. Training outcomes were assessed by evaluating the quality of the samples obtained and the quality of the slides produced locally. RESULTS: Between June 2016 and October 2018, the laboratories of 7 sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) have been evaluated and upgraded. Training has been delivered to 63 staff members from all sites. More than 600 MITS procedures have been performed. The quantity of tissue obtained in the MITS by the local teams was sufficient or abundant in 73%, and 87% of the slides were considered as technically acceptable or excellent. CONCLUSIONS: Satisfactory standardization of MITS and histology procedures has been achieved across all CHAMPS sites through organized capacity-building plans.

      13. Mortality surveillance methods to identify and characterize deaths in Child Health and Mortality Prevention Surveillance Network sitesexternal icon
        Salzberg NT, Sivalogan K, Bassat Q, Taylor AW, Adedini S, El Arifeen S, Assefa N, Blau DM, Chawana R, Cain CJ, Cain KP, Caneer JP, Garel M, Gurley ES, Kaiser R, Kotloff KL, Mandomando I, Morris T, Nyamthimba Onyango P, Sazzad HM, Scott JA, Seale AC, Sitoe A, Sow SO, Tapia MD, Whitney EA, Worrell MC, Zielinski-Gutierrez E, Madhi SA, Raghunathan PL, Koplan JP, Breiman RF.
        Clin Infect Dis. 2019 Oct 9;69(Supplement_4):S262-s273.
        Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.

    • Occupational Safety and Health
      1. Policy brief: Nurse fatigue, sleep, and health, and ensuring patient and public safetyexternal icon
        Caruso CC, Baldwin CM, Berger A, Chasens ER, Edmonson JC, Gobel BH, Landis CA, Patrician PA, Redeker NS, Scott LD, Todero C, Trinkoff A, Tucker S.
        Nurs Outlook. 2019 Sep – Oct;67(5):615-619.

        [No abstract]

      2. Workplace interventions for treatment of occupational asthmaexternal icon
        Henneberger PK, Patel JR, de Groene GJ, Beach J, Tarlo SM, Pal TM, Curti S.
        Cochrane Database Syst Rev. 2019 Oct 8;10:Cd006308.
        BACKGROUND: The impact of workplace interventions on the outcome of occupational asthma is not well understood. OBJECTIVES: To evaluate the effectiveness of workplace interventions on occupational asthma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); EMBASE(Ovid); NIOSHTIC-2; and CISILO (CCOHS) up to July 31, 2019. SELECTION CRITERIA: We included all eligible randomized controlled trials, controlled before and after studies and interrupted time-series of workplace interventions for occupational asthma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and risk of bias, and extracted data. MAIN RESULTS: We included 26 non-randomized controlled before and after studies with 1,695 participants that reported on three comparisons: complete removal from exposure and reduced exposure compared to continued exposure, and complete removal from exposure compared to reduced exposure. Reduction of exposure was achieved by limiting use of the agent, improving ventilation, or using protective equipment in the same job; by changing to another job with intermittent exposure; or by implementing education programs. For continued exposure, 56 per 1000 workers reported absence of symptoms at follow-up, the decrease in forced expiratory volume in one second as a percentage of a reference value (FEV1 %) was 5.4% during follow-up, and the standardized change in non-specific bronchial hyperreactivity (NSBH) was -0.18.In 18 studies, authors compared removal from exposure to continued exposure. Removal may increase the likelihood of reporting absence of asthma symptoms, with risk ratio (RR) 4.80 (95% confidence interval (CI) 1.67 to 13.86), and it may improve asthma symptoms, with RR 2.47 (95% CI 1.26 to 4.84), compared to continued exposure. Change in FEV1 % may be better with removal from exposure, with a mean difference (MD) of 4.23 % (95% CI 1.14 to 7.31) compared to continued exposure. NSBH may improve with removal from exposure, with standardized mean difference (SMD) 0.43 (95% CI 0.03 to 0.82).In seven studies, authors compared reduction of exposure to continued exposure. Reduction of exposure may increase the likelihood of reporting absence of symptoms, with RR 2.65 (95% CI 1.24 to 5.68). There may be no considerable difference in FEV1 % between reduction and continued exposure, with MD 2.76 % (95% CI -1.53 to 7.04) . No studies reported or enabled calculation of change in NSBH.In ten studies, authors compared removal from exposure to reduction of exposure. Following removal from exposure there may be no increase in the likelihood of reporting absence of symptoms, with RR 6.05 (95% CI 0.86 to 42.34), and improvement in symptoms, with RR 1.11 (95% CI 0.84 to 1.47), as well as no considerable change in FEV1 %, with MD 2.58 % (95% CI -3.02 to 8.17). However, with all three outcomes, there may be improved results for removal from exposure in the subset of patients exposed to low molecular weight agents. No studies reported or enabled calculation of change in NSBH.In two studies, authors reported that the risk of unemployment after removal from exposure may increase compared with reduction of exposure, with RR 14.28 (95% CI 2.06 to 99.16). Four studies reported a decrease in income of 20% to 50% after removal from exposure.The quality of the evidence is very low for all outcomes. AUTHORS’ CONCLUSIONS: Both removal from exposure and reduction of exposure may improve asthma symptoms compared with continued exposure. Removal from exposure, but not reduction of exposure, may improve lung function compared to continued exposure. When we compared removal from exposure directly to reduction of exposure, the former may improve symptoms and lung function more among patients exposed to low molecular weight agents. Removal from exposure may also increase the risk of unemployment. Care providers should balance the potential clinical benefits of removal from exposure or reduction of exposure with potential detrimental effects of unemployment. Additional high-quality studies are needed to evaluate the effectiveness of workplace interventions for occupational asthma.

    • Occupational Safety and Health – Mining
      1. An ignition of methane and air can generate enough air flow to raise mixtures of combustible coal and rock dust. The expanding high temperature combustion products ignite the suspended dust mixture and will continue to propagate following the available combustible fuel supply. If the concentration of the dispersed rock dust is sufficient, the flame will stop propagating. Large-scale explosion tests were conducted within the National Institute for Occupational Safety and Health (NIOSH) Lake Lynn Experimental Mine (LLEM) to measure the dynamic pressure history and the post-explosion dust scour depth. The aim of this effort is to provide quantitative data on depth of dust removal during the early stages of explosion development and its relationship to the depth of floor dust collected for assessing the incombustible content most likely to participate in the combustion process. This experimental work on dust removal on is not only important for coal mine safety but also for industrial dust explosions.

      2. This paper reports the influence of antennas on radio signal propagation in tunnels and underground mines. Radio signal propagation measurement results in a concrete tunnel and underground mines using antenna types with various radiation patterns, i.e., omnidirectional, Yagi, patch, and circular, are reported. Extensive measurements were taken in various scenarios which include vertical, horizontal, and circular polarization for line-of-sight (LoS) radio signal propagation at four frequencies (455, 915, 2450, and 5800 MHz) that are common to many voice and data transport radio systems used in underground mines. The results show that antenna pattern has a strong influence on the uniformity of radio signal propagation gain in the near zone and typically does not significantly influence behavior in the far zone, except for a constant gain offset.

      3. Effects of light spectrum on luminance measurements in underground coal minesexternal icon
        Martell MJ, Sammarco J, Macdonald B.
        IEEE Trans Ind Appl. 2019 .
        Lighting regulations for luminance in U. S. coal mines are verified in the field by using a luminance photometer calibrated to the Standard Illuminant A light source. Significant measurement errors can exist when measuring light sources that are dissimilar to light sources used to calibrate the photometer. This paper quantifies the measurement errors when measuring these dissimilar light sources commonly used in U.S. underground coal mines-an LED, a CFL with a clear cover, a CFL with an amber cover, and a tungsten halogen. The impact of photometer quality was also evaluated. Three different luminance measuring instruments of high, medium, and low quality were compared-a PR-650, LS-100, and PMEX, respectively. The PMEX was under evaluation for measuring luminance compliance in U.S. underground coal mines. The PR-650 was used as the referent to which the other photometers were compared. The PMEX error ranged from -17.0% to -26.5% with the highest error for the amber CFL. The LS-100 closely matched the luminance measurement for the LED and halogen; however, it had a percent error of -10.4% for the amber CFL. After the initial experiment, MSHA made improvements to the PMEX resulting in the PMEX-MSHA. The experiment was replicated using the new photometer and the newer PR-670. After repeating the experiment, the measurement errors ranged from -16% to -19% for the PMEX-MSHA, thus indicating an improvement over the PMEX. These results show that the spectral content of a light source and the photometer quality can greatly impact the accuracy of luminance measurement.

      4. Mine explosions are caused by the ignition of excessive accumulations of combustible dust and/or flammable gas mixed with air in the presence of an ignition source. Rock dusting (limestone dust) is a primary measure to prevent propagating coal dust explosions in underground coal mines in the United States. Although rock dust is considered a nuisance dust, Continuous Personal Dust Monitors (CPDMs) do not distinguish between the coal dust and rock dust and assess the total dust exposure. During application, the <10 microm limestone particles and coal dust particles can become suspended and carried by the ventilating air for long distances and can be measured by the CPDMs. There is a concern in the mining industry that rock dust can be included in the CPDM measurements and make the samples noncompliant. Research conducted by the National Institute for Occupational Safety and Health (NIOSH) has found that all rock dust (RD) cakes after being wetted and then dried. To prevent rock dust from caking, several rock dust manufacturers have developed anti-caking rock dusts. The anti-caking additives used are typically fatty acids that make the rock dust hydrophobic and are added in very low quantities (<1%). While this development will add to the rock dust fluidity, an inevitable problem may be the increased airborne re-entrainment of rock dust due to vehicle movement and foot traffic in the area. Thus, one consideration to reduce such exposure from rock dust is to remove the respirable size fraction (<10 microm) of the applied rock dust. This paper presents the results of experiments that were conducted to determine if a rock dust can still inert a coal dust explosion when the respirable (<10 microm) or inhalable (<20 microm) component of the particle size distribution is removed. Three different untreated rock dusts (untreated A, B, and C) with their treated counterparts (treated A, B, and C) were classified using mechanical sieves into several different-sized fractions, including < 10, 10-20, 20-38, 38-53 and > 75 microm. The relative inerting effectiveness of these size fractions were determined using the United States Bureau of Mines (USBM) 20-L explosion chamber.

      5. Underground mine refuge alternatives heat mitigationexternal icon
        Yan L, Yantek D, Lutz T, Yonkey J, Srednicki J.
        J Thermal Sci Eng Appl. 2020 Apr;12(2):021019 .
        In case of an emergency in an underground coal mine, miners who fail to escape from the mine can enter a refuge alternative (RA) for protection from adverse conditions, such as high carbon monoxide levels. One of the main concerns with the use of both portable and built-in-place (BIP) RAs, especially for hot or deep mines, is the interior temperature rise due to the occupants’ metabolic heat and the heat released by devices such as the carbon dioxide (CO2) scrubbing system. The humidity within the RA will also increase through occupants’ respiration and perspiration and from the chemical reaction within the CO2 scrubbing system. Heat and humidity buildup can subject the occupants to hazardous thermal conditions. To protect RA occupants, Mine Safety and Health Administration regulations mandate a maximum apparent temperature of 95F within an occupied RA. The National Institute for Occupational Safety and Health (NIOSH) tested both an air-conditioned borehole air supply (BAS) and a cryogenic air supply for RAs in the NIOSH Experimental Mine in Bruceton, Pennsylvania. The BAS was tested on a 60-person BIP RA, while the cryogenic air supply was tested on a 30-person BIP RA and a portable 23-person tent-type RA. Multiple tests were conducted with both air supplies to assess their ability to cool RAs. The test results show that the BAS and the cryogenic air supply were able to maintain the apparent temperature within the tested RAs under the 95F limit. The BAS and the cryogenic air supply are potential RA heat mitigation strategies that mines could use to prevent heat/humidity buildup within RAs.

    • Parasitic Diseases
      1. The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysisexternal icon
        Commons RJ, Simpson JA, Thriemer K, Abreha T, Adam I, Anstey NM, Assefa A, Awab GR, Baird JK, Barber BE, Chu CS, Dahal P, Daher A, Davis TM, Dondorp AM, Grigg MJ, Humphreys GS, Hwang J, Karunajeewa H, Laman M, Lidia K, Moore BR, Mueller I, Nosten F, Pasaribu AP, Pereira DB, Phyo AP, Poespoprodjo JR, Sibley CH, Stepniewska K, Sutanto I, Thwaites G, Hien TT, White NJ, William T, Woodrow CJ, Guerin PJ, Price RN.
        PLoS Med. 2019 Oct;16(10):e1002928.
        BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis.

    • Public Health Leadership and Management
      1. CONTEXT: Public health has a responsibility to ensure the ability of its workforce to deliver essential services, including mastering the core public health competencies. PROGRAM: The Division of Scientific Education and Professional Development (DSEPD) of the Centers for Disease Control and Prevention has a mission to improve health outcomes through a competent, sustainable, and empowered public health workforce. The DSEPD programs offer fellowships and other training opportunities, develop and disseminate quality public health training, and advance public health workforce development science. EVALUATION: The DSEPD developed a unified division logic model to describe the combined activities and intended outcomes of all DSEPD programs and their intended contribution to a robust public health workforce and to support ongoing program planning and evaluation. The logic model has 4 streams of work that include (1) producing and disseminating quality learning products; (2) implementing and managing fellowship programs that support learning; (3) providing public health service through fellows; and (4) advancing workforce development science through collaboration with other public health leaders.The underlying program theory is that a robust workforce has sufficient workforce, organizational, and systems capacity to deliver public health essential services and, therefore, to protect the public’s health. Three scientific theories support the program theory: the quality of learning; the accepted practice of competency-based programs and the service-learning model; and use of evidence-guided decision making in workforce development programs. DISCUSSION: A unified division logic model allows DSEPD to describe its combined approaches to workforce development as a coherent portfolio with well-defined goals and measureable outcomes. The logic model effectively communicates the relationship among division programs, their shared outcomes, and their combined contributions to developing and maintaining a robust public health workforce. A unified logic model can serve as effective frame of reference for division evaluation and as evidence in public health workforce development science.

    • Substance Use and Abuse
      1. Cannabis use disorders among adults in the United States during a time of increasing use of cannabisexternal icon
        Compton WM, Han B, Jones CM, Blanco C.
        Drug Alcohol Depend. 2019 Sep 12;204:107468.
        BACKGROUND: Using U.S. National Surveys on Drug Use and Health (NSDUH) data, researchers found that prevalence of cannabis use among adults increased in recent years, but prevalence of DSM-IV cannabis use disorder (CUD) was stable. Examining trends of all individual CUD criteria and of CUD severity may elucidate reasons for the lack of increases in CUD. METHODS: Data were from 749,500 persons aged 18 or older who participated in the 2002-2017 NSDUH. Descriptive analyses and logistic regressions were applied. RESULTS: Among adults during 2002-2017, past-year prevalence of DSM-IV CUD remained stable at 1.5% to 1.4%, but cannabis use increased from 10.4% to 15.3%, daily/near daily use increased from 1.9% to 4.2%, and mild DSM-5 CUD increased from 1.4% to 1.9%. Among adult cannabis users, past-year prevalence of DSM-IV CUD decreased from 14.8% to 9.3%, daily/near daily use increased from 18.0% to 27.2%, and DSM-5 moderate (4-5 criteria) and severe (6+ criteria) CUD decreased from 4.3% to 3.1% and from 2.4% to 1.3%, respectively. Examining trends in individual CUD criteria during 2002-2017 among adults overall revealed increases in two criteria (tolerance; spending a lot of time getting/using cannabis or getting over cannabis effects) and decreases/no changes in other criteria; among adult cannabis users, there was no change in one criterion (tolerance) and decreases in other criteria. CONCLUSIONS: DSM-5’s single dimension CUD measure may be more sensitive to diagnosis prevalence changes than the separate DSM-IV cannabis dependence and abuse categories. Future diagnostic approaches to assessing CUD may benefit from quantitatively oriented criteria.

      2. [No abstract]

      3. Evidence for state, community and systems-level prevention strategies to address the opioid crisisexternal icon
        Haegerich TM, Jones CM, Cote PO, Robinson A, Ross L.
        Drug Alcohol Depend. 2019 Sep 19;204:107563.
        BACKGROUND: Practitioners and policy makers need evidence to facilitate the selection of effective prevention interventions that can address the ongoing opioid overdose epidemic in the United States. METHODS: We conducted a systematic review of publications reporting on rigorous evaluations of systems-level interventions to address provider and patient/public behavior and prevent prescription and illicit opioid overdose. A total of 251 studies were reviewed. Interventions studied included 1) state legislation and regulation, 2) prescription drug monitoring programs (PDMPs), 3) insurance strategies, 4) clinical guideline implementation, 5) provider education, 6) health system interventions, 7) naloxone education and distribution, 8) safe storage and disposal, 9) public education, 10) community coalitions, and 11) interventions employing public safety and public health collaborations. RESULTS: The quality of evidence supporting selected interventions was low to moderate. Interventions with the strongest evidence include PDMP and pain clinic legislation, insurance strategies, motivational interviewing in clinical settings, feedback to providers on opioid prescribing behavior, intensive school and family-based programs, and patient education in the clinical setting. CONCLUSIONS: Although evidence is growing, further high-quality research is needed. Investigators should aim to identify strategies that can prevent overdose, as well as influence public, patient, and provider behavior. Identifying which strategies are most effective at addressing prescription compared to illicit opioid misuse and overdose could be fruitful, as well as investigating synergistic effects and unintended consequences.

      4. Marijuana and alcohol use among injured drivers evaluated at level I trauma centers in Arizona, 2008-2014external icon
        Jones JM, Shults RA, Robinson B, Komatsu KK, Sauber-Schatz EK.
        Drug Alcohol Depend. 2019 Aug 30;204:107539.
        BACKGROUND: We examined marijuana and alcohol use trends among drivers aged >/=16 years evaluated at Level I trauma centers before and after Arizona legalized medical marijuana in April 2011. METHODS: We conducted interrupted time series (ITS) analysis of urine drug screens for marijuana metabolites and blood alcohol concentration (BAC) data from the 2008-2014 Arizona State Trauma Registry. RESULTS: Among 30,083 injured drivers, 14,710 had marijuana test results, and 2590 were positive for marijuana; of these, 1087 (42%) also tested positive for alcohol. Among 23,186 drivers with BAC results, 5266 exceeded the legal limit for their age. Compared with prelaw trends (models if law had not been enacted), postlaw models showed small but significant annual increases in the proportions of drivers testing positive for either substance. By the end of 2014, the proportion of drivers testing positive for marijuana was 9.6% versus a projected 5.6% if the law had not been enacted, and the proportion of drivers with illegal BACs was 15.7% versus a projected 8.2%. When ITS was restricted to only substance-tested drivers, no significant differences were detected. CONCLUSIONS: Despite the small annual postlaw increases in the proportion of marijuana-positive drivers compared with the prelaw trend, alcohol-impaired driving remains a more prevalent threat to road safety in Arizona.

    • Zoonotic and Vectorborne Diseases
      1. The Check and Report Ebola (CARE+) Program to monitor travelers for Ebola after arrival to the United States, 2014-2016external icon
        Joseph HA, Wojno AE, Winter K, Grady-Erickson O, Hawes E, Benenson GA, Lee A, Cetron M.
        Public Health Rep. 2019 Oct 10.
        The 2014-2016 Ebola epidemic in West Africa influenced how public health officials considered migration and emerging infectious diseases. Responding to the public’s concerns, the US government introduced enhanced entry screening and post-arrival monitoring by public health authorities to reduce the risk of importation and domestic transmission of Ebola while continuing to allow travel from West Africa. This case study describes a new initiative, the Check and Report Ebola (CARE+) program that engaged travelers arriving to the United States from countries with Ebola outbreaks. The Centers for Disease Control and Prevention employed CARE ambassadors, who quickly communicated with incoming travelers and gave them practical resources to boost their participation in monitoring for Ebola. The program aimed to increase travelers’ knowledge of Ebola symptoms and how to seek medical care safely, increase travelers’ awareness of monitoring requirements, reduce barriers to monitoring, and increase trust in the US public health system. This program could be adapted for use in future outbreaks that involve the potential importation of disease and require the education and active engagement of travelers to participate in post-arrival monitoring.

      2. A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concernexternal icon
        Kobres PY, Chretien JP, Johansson MA, Morgan JJ, Whung PY, Mukundan H, Del Valle SY, Forshey BM, Quandelacy TM, Biggerstaff M, Viboud C, Pollett S.
        PLoS Negl Trop Dis. 2019 Oct 4;13(10):e0007451.
        INTRODUCTION: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. METHODS: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. RESULTS: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barre Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. CONCLUSIONS: Many ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics.

      3. Influencing factors in the development of state-level movement restriction and monitoring policies in response to Ebola, United States, 2014-15external icon
        Sell TK, Shearer MP, Meyer D, Leinhos M, Carbone EG, Thomas E.
        Health Secur. 2019 Sep/Oct;17(5):364-371.
        During the 2014-15 domestic Ebola response, US states developed monitoring and movement restriction policies for potentially exposed individuals. We describe decision-making processes and factors in the development of these policies. Results may help health officials anticipate potential concerns and policy influencers in future infectious disease responses. Thirty individuals with knowledge of state-level Ebola policy development participated in semi-structured interviews conducted from January to May 2017. Interviewees represented 18 jurisdictions from diverse census regions, state political affiliations, and public health governance structures as well as the US Centers for Disease Control and Prevention (CDC). Limited and/or changing guidance and unique state-level public health, legal, and operational environments resulted in variation in policy responses. Federal guidance developed by the CDC was an important information source influencing state-level policy responses, as was available scientific evidence; however, other external factors, such as local events, contributing experts, political environment, public concern, news media, and the influence of neighboring states, contributed to additional variation. Improvements in timing, consistency, and communication of federal guidance for monitoring and movement restrictions at the state level-along with balanced approaches to addressing ethical concerns, scientific evidence, and public concern at the state level-are considerations for policy development for future disease responses.

      4. Diaphragmatic paralysis: Evaluation in infants with congenital Zika syndromeexternal icon
        van der Linden V, Lins OG, Petribu NC, de Melo A, Moore J, Rasmussen SA, Moore CA.
        Birth Defects Res. 2019 Oct 9.
        BACKGROUND: Paralysis of the diaphragm in newborn infants can lead to recurrent infections and life-threatening respiratory insufficiency. The clinical diagnosis of unilateral diaphragmatic paralysis has been reported in infants with laboratory evidence of congenital Zika virus infection and/or the congenital Zika syndrome (CZS) phenotype but no evaluation of phrenic nerve function has been described. All reported infants have had accompanying arthrogryposis. High infant mortality is reported. METHODS: The causal mechanism of congenital diaphragmatic paralysis was evaluated in three infants with arthrogryposis as a manifestation of CZS (two of the three infants had laboratory evidence of ZIKV infection shortly after birth; the remaining infant had negative serology for ZIKV when first tested at 7 months of age). Electromyography and phrenic nerve compound muscle action potential (CMAP) were performed in all infants with diaphragmatic paralysis demonstrated on imaging studies. RESULTS: All infants had evidence of moderate chronic involvement of peripheral motor neurons. Phrenic nerve CMAP was reduced on the side of the diaphragmatic paralysis in two infants and reduced bilaterally in the remaining infant who had primarily anterior involvement of the diaphragm. All three infants had multiple medical complications and one infant died at 18 months of age. CONCLUSION: Evaluation of three infants with CZS and diaphragmatic paralysis demonstrated phrenic nerve dysfunction. In these and other affected infants, arthrogryposis appears to be a constant co-occurring condition and health problems are significant; both conditions are likely due to involvement of the peripheral nervous system in some infants with CZS.

      5. Lassa virus circulating in Liberia: a retrospective genomic characterisationexternal icon
        Wiley MR, Fakoli L, Letizia AG, Welch SR, Ladner JT, Prieto K, Reyes D, Espy N, Chitty JA, Pratt CB, Di Paola N, Taweh F, Williams D, Saindon J, Davis WG, Patel K, Holland M, Negron D, Stroher U, Nichol ST, Sozhamannan S, Rollin PE, Dogba J, Nyenswah T, Bolay F, Albarino CG, Fallah M, Palacios G.
        Lancet Infect Dis. 2019 Oct 3.
        BACKGROUND: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. METHODS: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. FINDINGS: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. INTERPRETATION: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics. FUNDING: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section.

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

Page last reviewed: October 28, 2019, 12:00 AM