Volume 10, Issue 25, July 10, 2018

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CDC Science Clips: Volume 10, Issue 25, July 10, 2018

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions

      1. Urinary cadmium concentration and the risk of ischemic strokeExternal
        Chen C, Xun P, Tsinovoi C, McClure LA, Brockman J, MacDonald L, Cushman M, Cai J, Kamendulis L, Mackey J, He K.
        Neurology. 2018 Jun 22.

        OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) mug/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

      2. Quality-adjusted life years (QALY) for 15 chronic conditions and combinations of conditions among US adults aged 65 and olderExternal
        Jia H, Lubetkin EI, Barile JP, Horner-Johnson W, DeMichele K, Stark DS, Zack MM, Thompson WW.
        Med Care. 2018 Jun 22.

        BACKGROUND: Although the life expectancy for the US population has increased, a high proportion of this population has lived with >/=1 chronic conditions. We have quantified the burden of disease associated with 15 chronic conditions and combinations of conditions by estimating quality-adjusted life years (QALYs) for older US adults. RESEARCH DESIGN: Data were from the Medicare Health Outcomes Survey Cohort 15 (baseline survey in 2012, follow-up survey 2014, with mortality follow-up through January 31, 2015). We included individuals aged 65 years and older (n=96,481). We estimated mean QALY throughout the remainder of the lifetime according to the occurrence of these conditions. RESULTS: The age-adjusted QALY was 5.8 years for men and 7.8 years for women. Over 90% respondents reported at least 1 condition and 72% reported multiple conditions. Respondents with depression and congestive heart failure had the lowest age-adjusted QALY (1.1-1.5 y for men and 1.5-2.2 y for women), whereas those with hypertension, arthritis, and sciatica had higher QALY (4.2-5.4 and 6.4-7.2 y, respectively). Having either depression or congestive heart failure and any 1 or 2 of the other 13 conditions was associated with the lowest QALY among the possible dyads and triads of chronic conditions. Dyads and triads with hypertension or arthritis were more prevalent, but had higher QALY. CONCLUSIONS: Understanding the burden of disease for common chronic conditions and for combinations of these conditions is useful for delivering high-quality primary care that could be tailored for individuals with combinations of chronic conditions.

      3. State-level estimation of diabetes and prediabetes prevalence: Combining national and local survey data and clinical dataExternal
        Marker DA, Mardon R, Jenkins F, Campione J, Nooney J, Li J, Saydeh S, Zhang X, Shrestha S, Rolka D.
        Stat Med. 2018 Jun 22.

        Many statisticians and policy researchers are interested in using data generated through the normal delivery of health care services, rather than carefully designed and implemented population-representative surveys, to estimate disease prevalence. These larger databases allow for the estimation of smaller geographies, for example, states, at potentially lower expense. However, these health care records frequently do not cover all of the population of interest and may not collect some covariates that are important for accurate estimation. In a recent paper, the authors have described how to adjust for the incomplete coverage of administrative claims data and electronic health records at the state or local level. This article illustrates how to adjust and combine multiple data sets, namely, national surveys, state-level surveys, claims data, and electronic health record data, to improve estimates of diabetes and prediabetes prevalence, along with the estimates of the method’s accuracy. We demonstrate and validate the method using data from three jurisdictions (Alabama, California, and New York City). This method can be applied more generally to other areas and other data sources.

      4. Primary care providers’ prediabetes screening, testing, and referral behaviorsExternal
        Nhim K, Khan T, Gruss SM, Wozniak G, Kirley K, Schumacher P, Luman ET, Albright A.
        Am J Prev Med. 2018 Jun 19.

        INTRODUCTION: Intensive behavioral counseling is effective in preventing type 2 diabetes, and insurance coverage for such interventions is increasing. Although primary care provider referrals are not required for entry to the Centers for Disease Control and Prevention (CDC)-recognized National Diabetes Prevention Program lifestyle change program, referral rates remain suboptimal. This study aims to assess the association between primary care provider behaviors regarding prediabetes screening, testing, and referral and awareness of the CDC-recognized lifestyle change program and the Prevent Diabetes STAT: Screen, Test, and Act Today() toolkit. Awareness of the lifestyle change program and the STAT toolkit, use of electronic health records, and the ratio of lifestyle change program classes to primary care physicians were hypothesized to be positively associated with primary care provider prediabetes screening, testing, and referral behaviors. METHODS: Responses from primary care providers (n=1,256) who completed the 2016 DocStyles cross-sectional web-based survey were analyzed in 2017 to measure self-reported prediabetes screening, testing, and referral behaviors. Multivariate logistic regression was used to estimate the effects of primary care provider awareness and practice characteristics on these behaviors, controlling for provider characteristics. RESULTS: Overall, 38% of primary care providers were aware of the CDC-recognized lifestyle change program, and 19% were aware of the STAT toolkit; 27% screened patients for prediabetes using a risk test; 97% ordered recommended blood tests; and 23% made referrals. Awareness of the lifestyle change program and the STAT toolkit was positively associated with screening and referring patients. Primary care providers who used electronic health records were more likely to screen, test, and refer. Referring was more likely in areas with more lifestyle change program classes. CONCLUSIONS: This study highlights the importance of increasing primary care provider awareness of and referrals to the CDC-recognized lifestyle change program.

      5. A taxonomic signature of obesity in a large study of American adultsExternal
        Peters BA, Shapiro JA, Church TR, Miller G, Trinh-Shevrin C, Yuen E, Friedlander C, Hayes RB, Ahn J.
        Sci Rep. 2018 Jun 27;8(1):9749.

        Animal models suggest that gut microbiota contribute to obesity; however, a consistent taxonomic signature of obesity has yet to be identified in humans. We examined whether a taxonomic signature of obesity is present across two independent study populations. We assessed gut microbiome from stool for 599 adults, by 16S rRNA gene sequencing. We compared gut microbiome diversity, overall composition, and individual taxon abundance for obese (BMI >/= 30 kg/m(2)), overweight (25 </= BMI < 30), and healthy-weight participants (18.5 </= BMI < 25). We found that gut species richness was reduced (p = 0.04), and overall composition altered (p = 0.04), in obese (but not overweight) compared to healthy-weight participants. Obesity was characterized by increased abundance of class Bacilli and its families Streptococcaceae and Lactobacillaceae, and decreased abundance of several groups within class Clostridia, including Christensenellaceae, Clostridiaceae, and Dehalobacteriaceae (q < 0.05). These findings were consistent across two independent study populations. When random forest models were trained on one population and tested on the other as well as a previously published dataset, accuracy of obesity prediction was good (~70%). Our large study identified a strong and consistent taxonomic signature of obesity. Though our study is cross-sectional and causality cannot be determined, identification of microbes associated with obesity can potentially provide targets for obesity prevention and treatment.

      6. PROBLEM: Chronic conditions and disorders (e.g., diabetes, cardiovascular diseases, arthritis, and depression) are leading causes of morbidity and mortality in the United States. Healthy behaviors (e.g., physical activity, avoiding cigarette use, and refraining from binge drinking) and preventive practices (e.g., visiting a doctor for a routine check-up, tracking blood pressure, and monitoring blood cholesterol) might help prevent or successfully manage these chronic conditions. Monitoring chronic diseases, health-risk behaviors, and access to and use of health care are fundamental to the development of effective public health programs and policies at the state and local levels. REPORTING PERIOD: January-December 2015. DESCRIPTION OF THE SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing, state-based, random-digit-dialed landline- and cellular-telephone survey of noninstitutionalized adults aged >/=18 years residing in the United States. BRFSS collects data on health-risk behaviors, chronic diseases and conditions, access to and use of health care, and use of preventive health services related to the leading causes of death and disability. This report presents results for all 50 states, the District of Columbia, the Commonwealth of Puerto Rico (Puerto Rico), and Guam and for 130 metropolitan and micropolitan statistical areas (MMSAs) (N = 441,456 respondents) for 2015. RESULTS: The age-adjusted prevalence estimates of health-risk behaviors, self-reported chronic health conditions, access to and use of health care, and use of preventive health services varied substantially by state, territory, and MMSA in 2015. Results are summarized for selected BRFSS measures. Each set of proportions refers to the median (range) of age-adjusted prevalence estimates for health-risk behaviors, self-reported chronic diseases or conditions, or use of preventive health care services by geographic jurisdiction, as reported by survey respondents. Adults with good or better health: 84.6% (65.9%-88.8%) for states and territories and 85.2% (66.9%-91.3%) for MMSAs. Adults with >/=14 days of poor physical health in the past 30 days: 10.9% (8.2%-17.2%) for states and territories and 10.9% (6.6%-19.1%) for MMSAs. Adults with >/=14 days of poor mental health in the past 30 days: 11.3% (7.3%-15.8%) for states and territories and 11.4% (5.6%-20.5%) for MMSAs. Adults aged 18-64 years with health care coverage: 86.8% (72.0%-93.8%) for states and territories and 86.8% (63.2%-95.7%) for MMSAs. Adults who received a routine physical checkup during the preceding 12 months: 69.0% (58.1%-79.8%) for states and territories and 69.4% (57.1%-81.1%) for MMSAs. Adults who ever had their blood cholesterol checked: 79.1% (73.3%-86.7%) for states and territories and 79.5% (65.1%-87.3%) for MMSAs. Current cigarette smoking among adults: 17.7% (9.0%-27.2%) for states and territories and 17.3% (4.5%-29.5%) for MMSAs. Binge drinking among adults during the preceding 30 days: 17.2% (11.2%-26.0%) for states and territories and 17.4% (5.5%-24.5%) for MMSAs. Adults who reported no leisure-time physical activity during the preceding month: 25.5% (17.6%-47.1%) for states and territories and 24.5% (16.1%-47.3%) for MMSAs. Adults who reported consuming fruit less than once per day during the preceding month: 40.5% (33.3%-55.5%) for states and territories and 40.3% (30.1%-57.3%) for MMSAs. Adults who reported consuming vegetables less than once per day during the preceding month: 22.4% (16.6%-31.3%) for states and territories and 22.3% (13.6%-32.0%) for MMSAs. Adults who have obesity: 29.5% (19.9%-36.0%) for states and territories and 28.5% (17.8%-41.6%) for MMSAs. Adults aged >/=45 years with diagnosed diabetes: 15.9% (11.2%-26.8%) for states and territories and 15.7% (10.5%-27.6%) for MMSAs. Adults aged >/=18 years with a form of arthritis: 22.7% (17.2%-33.6%) for states and territories and 23.2% (12.3%-33.9%) for MMSAs. Adults having had a depressive disorder: 19.0% (9.6%-27.0%) for states and territories and 19.2% (9.9%-27.2%) for MMSAs. Adults with high blood pressure: 29.1% (24.2%-39.9%) for states and territories and 29.0% (19.7%-41.0%) for MMSAs. Adults with high blood cholesterol: 31.8% (27.1%-37.3%) for states and territories and 31.4% (23.2%-42.0%) for MMSAs. Adults aged >/=45 years who have had coronary heart disease: 10.3% (7.2%-16.8%) for states and territories and 10.1% (4.7%-17.8%) for MMSAs. Adults aged >/=45 years who have had a stroke: 4.9% (2.5%-7.5%) for states and territories and 4.7% (2.1%-8.4%) for MMSAs. INTERPRETATION: The prevalence of health care access and use, health-risk behaviors, and chronic health conditions varied by state, territory, and MMSA. The data in this report underline the importance of continuing to monitor chronic diseases, health-risk behaviors, and access to and use of health care in order to assist in the planning and evaluation of public health programs and policies at the state, territory, and MMSA level. PUBLIC HEALTH ACTION: State and local health departments and agencies and others interested in health and health care can continue to use BRFSS data to identify groups with or at high risk for chronic conditions, unhealthy behaviors, and limited health care access and use. BRFSS data also can be used to help design, implement, monitor, and evaluate health-related programs and policies.

      7. The Chinese Children and Families Cohort Study: The Nutrition, Physical Activity, and Ultraviolet Radiation Data CollectionExternal
        Potischman N, Fang L, Hao L, Bailey RR, Berrigan D, Berry RJ, Brodie A, Chao A, Chen J, Dodd K, Feng Y, Ma G, He Y, Fan J, Kimlin M, Kitahara C, Linet M, Li Z, Liu A, Liu Y, Sampson J, Su J, Sun J, Tasevska N, Yang L, Yang R, Zhang Q, Wang N, Wang L, Yu W.
        Nutr Today. 2018 May-Jun;53(3):104-114.

        This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

      8. Geographic variation in pediatric cancer incidence – United States, 2003-2014External
        Siegel DA, Li J, Henley SJ, Wilson RJ, Lunsford NB, Tai E, Van Dyne EA.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 29;67(25):707-713.

        Approximately 15,000 persons aged <20 years receive a cancer diagnosis each year in the United States (1). National surveillance data could provide understanding of geographic variation in occurrence of new cases to guide public health planning and investigation (2,3). Past research on pediatric cancer incidence described differences by U.S. Census region but did not provide state-level estimates (4). To adequately describe geographic variation in cancer incidence among persons aged <20 years in the United States, CDC analyzed data from United States Cancer Statistics (USCS) during 2003-2014 and identified 171,432 cases of pediatric cancer during this period (incidence = 173.7 cases per 1 million persons). The cancer types with the highest incidence rates were leukemias (45.7), brain tumors (30.9), and lymphomas (26.2). By U.S. Census region, pediatric cancer incidence was highest in the Northeast (188.0) and lowest in the South (168.0), whereas by state (including the District of Columbia [DC]), rates were highest in New Hampshire, DC, and New Jersey. Among non-Hispanic whites (whites) and non-Hispanic blacks (blacks), pediatric cancer incidence was highest in the Northeast, and the highest rates among Hispanics were in the South. The highest rates of leukemia were in the West, and the highest rates of lymphoma and brain tumors were in the Northeast. State-based differences in pediatric cancer incidence could guide interventions related to accessing care (e.g., in states with large distances to pediatric oncology centers), clinical trial enrollment, and state or regional studies designed to further explore variations in cancer incidence.

    • Communicable Diseases

      1. Pneumococcal carriage and serotype distribution among children with and without pneumonia in Mozambique, 2014-2016External
        Adebanjo T, Lessa FC, Mucavele H, Moiane B, Chauque A, Pimenta F, Massora S, Carvalho MD, Whitney CG, Sigauque B.
        PLoS One. 2018 ;13(6):e0199363.

        BACKGROUND: Pneumococcal colonization is a precursor to pneumonia, and pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT) colonization. Pneumococcal colonization studies are traditionally done among healthy children in the community; however, VT colonization prevalence may differ between these children and those with pneumonia. We assessed overall and VT pneumococcal colonization and factors associated with colonization among children with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in 2013. METHODS: We used data from ongoing pneumonia surveillance in children aged <5 years and from cross-sectional nasopharyngeal colonization surveys conducted in October 2014 -April 2015 and October 2015 -May 2016. Pneumonia was defined using WHO standard criteria for radiologically confirmed pneumonia. Children with pneumonia enrolled from January 2014 -April 2016 were compared to children without pneumonia enrolled from the cross-sectional surveys. Clinical data and nasopharyngeal (NP) swabs were collected from each child. NP specimens were cultured for pneumococci, and culture-negative specimens from children with pneumonia underwent polymerase chain reaction (PCR). RESULTS: Of 778 and 927 children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics before swab collection, respectively. Based on culture, pneumococcal colonization was 45.1% for children with and 84.5% for children without pneumonia (P<0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (P = 0.02). The addition of PCR in children with pneumonia increased overall and VT-pneumococcal colonization to 79.2% and 31.1%, respectively. In multivariable analysis including PCR results, pneumonia was associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10-1.78). CONCLUSION: Vaccine-type pneumococcal colonization remains common among children with and without pneumonia post-PCV10 introduction in Mozambique. In a population of children with high antibiotic exposure, the use of PCR for culture-negative NP swabs can improve assessment of pneumococcal colonization and circulating serotypes.

      2. Update of recommendations for use of once-weekly isoniazid-rifapentine regimen to treat latent Mycobacterium tuberculosis infectionExternal
        Borisov AS, Bamrah Morris S, Njie GJ, Winston CA, Burton D, Goldberg S, Yelk Woodruff R, Allen L, LoBue P, Vernon A.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 29;67(25):723-726.

        Treatment of latent tuberculosis infection (LTBI) is critical to the control and elimination of tuberculosis disease (TB) in the United States. In 2011, CDC recommended a short-course combination regimen of once-weekly isoniazid and rifapentine for 12 weeks (3HP) by directly observed therapy (DOT) for treatment of LTBI, with limitations for use in children aged <12 years and persons with human immunodeficiency virus (HIV) infection (1). CDC identified the use of 3HP in those populations, as well as self-administration of the 3HP regimen, as areas to address in updated recommendations. In 2017, a CDC Work Group conducted a systematic review and meta-analyses of the 3HP regimen using methods adapted from the Guide to Community Preventive Services. In total, 19 articles representing 15 unique studies were included in the meta-analysis, which determined that 3HP is as safe and effective as other recommended LTBI regimens and achieves substantially higher treatment completion rates. In July 2017, the Work Group presented the meta-analysis findings to a group of TB experts, and in December 2017, CDC solicited input from the Advisory Council for the Elimination of Tuberculosis (ACET) and members of the public for incorporation into the final recommendations. CDC continues to recommend 3HP for treatment of LTBI in adults and now recommends use of 3HP 1) in persons with LTBI aged 2-17 years; 2) in persons with LTBI who have HIV infection, including acquired immunodeficiency syndrome (AIDS), and are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine; and 3) by DOT or self-administered therapy (SAT) in persons aged >/=2 years.

      3. Use of multiple imputation to estimate the proportion of respiratory virus detections among patients hospitalized with community-acquired pneumoniaExternal
        Bozio CH, Flanders WD, Finelli L, Bramley AM, Reed C, Gandhi NR, Vidal JE, Erdman D, Levine MZ, Lindstrom S, Ampofo K, Arnold SR, Self WH, Williams DJ, Grijalva CG, Anderson EJ, McCullers JA, Edwards KM, Pavia AT, Wunderink RG, Jain S.
        Open Forum Infect Dis. 2018 Apr;5(4):ofy061.

        Background: Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. Methods: Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. Results: Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%-4.4% and 0.8%-2.8% in children and adults, respectively; relative differences were 1.1-3.0 times higher. Conclusions: Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.

      4. BACKGROUND: Congenital syphilis occurs when a pregnant woman with syphilis is not diagnosed or treated and the infection is passed in utero, causing severe infant morbidity and mortality. Congenital syphilis is easily prevented if women receive timely and adequate prenatal care. Cases of congenital syphilis are considered indicators of problems in the safety net. However, maternal social and behavioral factors can impede women’s care, even when providers follow guidelines. METHODS: We reviewed case interviews and maternal records for 23 congenital syphilis cases reported to the Centers for Disease Control and Prevention from Indiana between 2014 and 2016. We used qualitative methods to analyze narrative notes from maternal interviews to learn more about factors that potentially contributed to congenital syphilis cases. RESULTS: All providers followed Centers for Disease Control and Prevention and state recommendations for screening and treatment for pregnant women with syphilis. Twenty-one of 23 women had health insurance. The number of prenatal care visits women had was suboptimal; more than one third of women had no prenatal care. Nearly one third of women’s only risk factor was sex with a primary male sex partner. The majority of women suffered social vulnerabilities, including homelessness, substance abuse, and incarceration. CONCLUSIONS: Despite provider adherence to guidelines and health insurance availability, some pregnant women with syphilis are unlikely to receive timely diagnosis and treatment. Pregnant women at high risk for syphilis may need additional social and material support to prevent a congenital syphilis case. Additional efforts are needed to reach the male partners of vulnerable females with syphilis.

      5. Public health responses during measles outbreaks in elimination settings: Strategies and challengesExternal
        Gastanaduy PA, Banerjee E, DeBolt C, Bravo-Alcantara P, Samad SA, Pastor D, Rota PA, Patel M, Crowcroft NS, Durrheim DN.
        Hum Vaccin Immunother. 2018 Jun 22:1-46.

        In late September 2016, the Americas became the first region in the world to have eliminated endemic transmission of measles virus. Several other countries have also verified measles elimination, and countries in all six World Health Organization regions have adopted measles elimination goals. The public health strategies used to respond to measles outbreaks in elimination settings are thus becoming relevant to more countries. This review highlights the strategies used to limit measles spread in elimination settings: (1) assembly of an outbreak control committee; (2) isolation of measles cases while infectious; (3) exclusion and quarantining of individuals without evidence of immunity; (4) vaccination of susceptible individuals; (5) use of immunoglobulin to prevent measles in exposed susceptible high-risk persons; (6) and maintaining laboratory proficiency for confirmation of measles. Deciding on the extent of containment efforts should be based on the expected benefit of reactive interventions, balanced against the logistical challenges in implementing them.

      6. Impact of providing pre-exposure prophylaxis for HIV at clinics for sexually transmitted infections in Baltimore City: an agent-based modelExternal
        Kasaie P, Berry SA, Shah MS, Rosenberg ES, Hoover KW, Gift TL, Chesson H, Pennington J, German D, Flynn CP, Beyrer C, Dowdy DW.
        Sex Transm Dis. 2018 Jun 25.

        BACKGROUND: Pre-exposure prophylaxis (PrEP) greatly reduces the risk of HIV acquisition, but its optimal delivery strategy remains uncertain. Clinics for sexually transmitted infections (STIs) can provide an efficient venue for PrEP delivery. METHODS: To quantify the added value of STI clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission among men who have sex with men (MSM). We simulated the impact of PrEP delivery through STI clinics compared with PrEP delivery in other community-based settings. Our primary outcome was the projected twenty-year reduction in HIV incidence among MSM. RESULTS: Assuming PrEP uptake and adherence of 60% each, evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV incidence by 16% [95% uncertainty range: 14% – 18%] over 20 years, an impact that was 1.8 [1.7-2.0] times as great as that achieved by evaluating an equal number of MSM recruited from the community. Comparing strategies where an equal number of MSM received PrEP in each strategy (i.e., evaluating more individuals for PrEP in the community-based strategy, since MSM attending STI clinics are more likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic-based strategy was 1.3 [1.3-1.4] times as great as that of community-based delivery. CONCLUSIONS: Delivering PrEP to MSM who attend STI clinics can improve efficiency and effectiveness. If high levels of adherence can be achieved in this population, STI clinics may be an important venue for PrEP implementation.

      7. Challenges in recruiting African-born, US-based participants for HIV and tuberculosis researchExternal
        Kerani R, Narita M, Lipira L, Endeshaw M, Holmes KK, Golden MR.
        J Immigr Minor Health. 2018 Jun 26.

        Research is critical for developing HIV and tuberculosis (TB) programming for U.S. African-born communities, and depends on successful recruitment of African-born people. From January 2014 to June 2016, we recruited African-born people for HIV and TB research in King County, Washington. We compared the characteristics of study participants and the underlying populations of interest, and assessed recruitment strategies. Target enrollment for the HIV study was 167 participants; 51 participants (31%) were enrolled. Target enrollment for the TB study was 218 participants; 38 (17%) were successfully recruited. Of 249 prior TB patients we attempted to contact by phone, we reached 72 (33%). Multiple recruitment strategies were employed with variable impact. Study participants differed from the underlying populations in terms of gender, country of origin and language. Inequities in research participation and in meaningful opportunities for such participation may exacerbate existing health disparities.

      8. BACKGROUND: Partner notification services (PNS) remain the backbone of syphilis control. The popularity of internet-based apps to meet sex partners among early syphilis (ES) patients may hinder the success of PNS if partners cannot be located. METHODS: We compared demographic and clinical characteristics between male ES patients indicating sex with men (MSM) and reported in North Carolina between 2013 and 2016 by reported use of an internet-based app to meet sex partners (app user). We used multivariable log-binomial regression to assess the association between app usage and ES exposure notification of >/=1 sex partner. RESULTS: Among 3,414 MSM ES patients, 58.6% were app users. App users were more frequently white (33.2% vs. 27.3%; p=0.003), younger (median: 28 vs. 30 years; p=0.0002) and less frequently HIV co-infected (54.1% vs. 58.2%; p=0.02) compared to non-app users. Overall, 94.9% of app users and 89.6% of non-app users reported >/=1 sex partner. App users reported 2.5-times more locatable and 2.7-times more unlocatable sex partners than non-app users. Similar proportions of app (23.6%) and non-app users (25.0%) reported only unlocatable partners (p=0.4). App usage was not associated with ES exposure notification of >/=1 sex partner (adjusted risk ratio: 0.99; 95% confidence interval: 0.87-1.13). CONCLUSION: We observed no difference in the proportion of locatable partners or likelihood of notifying >/=1 sex partner of exposure among MSM ES patients, by reported use of internet-based apps to meet sex partners. PNS continues to be an important mechanism to locate and assure treatment for sex partners in this population.

      9. Models of integration of HIV and noncommunicable disease care in sub-Saharan Africa: lessons learned and evidence gapsExternal
        Njuguna B, Vorkoper S, Patel P, Reid MJ, Vedanthan R, Pfaff C, Park PH, Fischer L, Laktabai J, Pastakia SD.
        Aids. 2018 Jul 1;32 Suppl 1:S33-s42.

        OBJECTIVE: To describe available models of HIV and noncommunicable disease (NCD) care integration in sub-Saharan Africa (SSA). DESIGN: Narrative review of published articles describing various models of HIV and NCD care integration in SSA. RESULTS: We identified five models of care integration across various SSA countries. These were integrated community-based screening for HIV and NCDs in the general population; screening for NCDs and NCD risk factors among HIV patients enrolled in care; integration of HIV and NCD care within clinics; differentiated care for patients with HIV and/or NCDs; and population healthcare for all. We illustrated these models with descriptive case studies highlighting the lessons learned and evidence gaps from the various models. CONCLUSION: Leveraging existing HIV infrastructure for NCD care is feasible with various approaches possible depending on available program capacity. Process and clinical outcomes for existing models of care integration are not yet described but are urgently required to further advise policy decisions on HIV/NCD care integration.

      10. Etiology and impact of coinfections in children hospitalized with community-acquired pneumoniaExternal
        Nolan VG, Arnold SR, Bramley AM, Ampofo K, Williams DJ, Grijalva CG, Self WH, Anderson EJ, Wunderink RG, Edwards KM, Pavia AT, Jain S, McCullers JA.
        J Infect Dis. 2018 Jun 20;218(2):179-188.

        Background: Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. Methods: We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics. Results: A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. Conclusions: Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.

      11. Transcriptome analysis of Neisseria gonorrhoeae during natural infection reveals differential expression of antibiotic resistance determinants between men and womenExternal
        Nudel K, McClure R, Moreau M, Briars E, Abrams AJ, Tjaden B, Su XH, Trees D, Rice PA, Massari P, Genco CA.
        mSphere. 2018 Aug 29;3(3).

        Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections and in vitro-grown N. gonorrhoeae isolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions, while 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic-resistant genotypes and in vitro phenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programed genotypically and also driven by sex-specific environments. Collectively, our results indicate that distinct N. gonorrhoeae gene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex-specific differences in expression of antibiotic resistance genes.IMPORTANCE Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high and increasing. We found that N. gonorrhoeae transcriptional responses to infection differed in genital specimens taken from men and women, particularly antibiotic resistance gene expression, which was increased in men. These sex-specific findings may provide a new approach to guide therapeutic interventions and preventive measures that are also sex specific while providing additional insight to address antimicrobial resistance of N. gonorrhoeae.

      12. Costs and cost-effectiveness of HIV/noncommunicable disease integration in Africa: from theory to practiceExternal
        Nugent R, Barnabas RV, Golovaty I, Osetinsky B, Roberts DA, Bisson C, Courtney L, Patel P, Yonga G, Watkins D.
        Aids. 2018 Jul 1;32 Suppl 1:S83-s92.

        The current article reviews economic aspects of selected HIV/noncommunicable disease (NCD) service delivery integration programs to assess the efficiency of integration in limited capacity settings. We define economies of scope and scale and their relevance to HIV/NCD integration. We summarize the results of a systematic review of cost and cost-effectiveness studies of integrated care, which identified 12 datasets (nine studies) with a wide range of findings driven by differences in research questions, study methods, and health conditions measured. All studies were done in Africa and examined screening interventions only. No studies assessed the cost of integrated, long-term disease management. Few studies estimated the cost-effectiveness of integrated screening programs. The additional cost of integrating NCD screening with HIV care platforms represented a 6-30% increase in the total costs of the programs for noncancer NCDs, with cervical cancer screening costs dependent on screening strategy. We conducted 11 key informant interviews to uncover perceptions of the economics of HIV/NCD integration. None of the informants had hard information about the economic efficiency of integration. Most expected integrated care to be more cost-effective than current practice, though a minority thought that greater specialization could be more cost-effective. In the final section of this article, we summarize research needs and propose a ‘minimum economic dataset’ for future studies. We conclude that, although integrated HIV/NCD care has many benefits, the economic justification is unproven. Better information on the cost, cost-effectiveness, and fiscal sustainability of integrated programs is needed to justify this approach in limited-resource countries.

      13. Cholera outbreak caused by drinking contaminated water from a lakeshore water-collection site, Kasese District, south-western Uganda, June-July 2015External
        Pande G, Kwesiga B, Bwire G, Kalyebi P, Riolexus A, Matovu JK, Makumbi F, Mugerwa S, Musinguzi J, Wanyenze RK, Zhu BP.
        PLoS One. 2018 ;13(6):e0198431.

        On 20 June 2015, a cholera outbreak affecting more than 30 people was reported in a fishing village, Katwe, in Kasese District, south-western Uganda. We investigated this outbreak to identify the mode of transmission and to recommend control measures. We defined a suspected case as onset of acute watery diarrhoea between 1 June and 15 July 2015 in a resident of Katwe village; a confirmed case was a suspected case with Vibrio cholerae cultured from stool. For case finding, we reviewed medical records and actively searched for cases in the community. In a case-control investigation we compared exposure histories of 32 suspected case-persons and 128 age-matched controls. We also conducted an environmental assessment on how the exposures had occurred. We found 61 suspected cases (attack rate = 4.9/1000) during this outbreak, of which eight were confirmed. The primary case-person had onset on 16 June; afterwards cases sharply increased, peaked on 19 June, and rapidly declined afterwards. After 22 June, eight scattered cases occurred. The case-control investigation showed that 97% (31/32) of cases and 62% (79/128) of controls usually collected water from inside a water-collection site “X” (ORM-H = 16; 95% CI = 2.4-107). The primary case-person who developed symptoms while fishing, reportedly came ashore in the early morning hours on 17 June, and defecated “near” water-collection site X. We concluded that this cholera outbreak was caused by drinking lake water collected from inside the lakeshore water-collection site X. At our recommendations, the village administration provided water chlorination tablets to the villagers, issued water boiling advisory to the villagers, rigorously disinfected all patients’ faeces and, three weeks later, fixed the tap-water system.

      14. Noncommunicable diseases among HIV-infected persons in low-income and middle-income countries: a systematic review and meta-analysisExternal
        Patel P, Rose CE, Collins PY, Nuche-Berenguer B, Sahasrabuddhe VV, Peprah E, Vorkoper S, Pastakia SD, Rausch D, Levitt NS.
        Aids. 2018 Jul 1;32 Suppl 1:S5-s20.

        OBJECTIVE: To appropriately identify and treat noncommunicable diseases (NCDs) among persons living with HIV (PLHIV) in low-and-middle-income countries (LMICs), it is imperative to understand the burden of NCDs among PLHIV in LMICs and the current management of the diseases. DESIGN: Systematic review and meta-analysis. METHODS: We examined peer-reviewed literature published between 1 January 2010 and 31 December 2016 to assess currently available evidence regarding HIV and four selected NCDs (cardiovascular disease, cervical cancer, depression, and diabetes) in LMICs with a focus on sub-Saharan Africa. The databases, PubMed/MEDLINE, Cochrane Review, and Scopus, were searched to identify relevant literature. For conditions with adequate data available, pooled estimates for prevalence were generated using random fixed effects models. RESULTS: Six thousand one hundred and forty-three abstracts were reviewed, 377 had potentially relevant prevalence data and 141 were included in the summary; 57 were selected for quantitative analysis. Pooled estimates for NCD prevalence were hypertension 21.2% (95% CI 16.3-27.1), hypercholesterolemia 22.2% (95% CI 14.7-32.1), elevated low-density lipoprotein 23.2% (95% CI 15.2-33.6), hypertriglyceridemia 27.2% (95% CI 20.7-34.8), low high-density lipoprotein 52.3% (95% CI 35.6-62.8), obesity 7.8% (95% CI 4.3-13.9), and depression 24.4% (95% CI 12.5-42.1). Invasive cervical cancer and diabetes prevalence were 1.3-1.7 and 1.3-18%, respectively. Few NCD-HIV integrated programs with screening and management approaches that are contextually appropriate for resource-limited settings exist. CONCLUSION: Improved data collection and surveillance of NCDs among PLHIV in LMICs are necessary to inform integrated HIV/NCD care models. Although efforts to integrate care exist, further research is needed to optimize the efficacy of these programs.

      15. Obesity, diabetes, and the risk of invasive group B Streptococcal disease in nonpregnant adults in the United StatesExternal
        Pitts SI, Maruthur NM, Langley GE, Pondo T, Shutt KA, Hollick R, Schrag SJ, Thomas A, Nichols M, Farley M, Watt JP, Miller L, Schaffner W, Holtzman C, Harrison LH.
        Open Forum Infect Dis. 2018 01 Jun;5(6):1-7.

        Background. Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. Methods. We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m<sup>2</sup>) and class III (BMI >= 40.0 kg/m<sup>2</sup>). Results. In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/ II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. Conclusions. Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.

      16. Performance of surveillance case definitions in detecting respiratory syncytial virus infection among young children hospitalized with severe respiratory illness – South Africa, 2009-2014External
        Rha B, Dahl RM, Moyes J, Binder AM, Tempia S, Walaza S, Bi D, Groome MJ, Variava E, Naby F, Kahn K, Treurnicht F, Cohen AL, Gerber SI, Madhi SA, Cohen C.
        J Pediatric Infect Dis Soc. 2018 Jun 21.

        Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRTI) in young children, but data on surveillance case definition performance in estimating burdens have been limited. Methods: We enrolled children aged <5 years hospitalized for ALRTI (or neonatal sepsis in young infants) through active prospective surveillance at 5 sentinel hospitals in South Africa and collected nasopharyngeal aspirates from them for RSV molecular diagnostic testing between 2009 and 2014. Clinical data were used to characterize RSV disease and retrospectively evaluate the performance of respiratory illness case definitions (including the World Health Organization definition for severe acute respiratory infection [SARI]) in identifying hospitalized children with laboratory-confirmed RSV according to age group (<3, 3-5, 6-11, 12-23, and 24-59 months). Results: Of 9969 hospitalized children, 2723 (27%) tested positive for RSV. Signs and symptoms in RSV-positive children varied according to age; fever was less likely to occur in children aged <3 months (57%; odds ratio [OR], 0.8 [95% CI, 0.7-0.9]) but more likely in those aged >/=12 months (82%; OR, 1.7-1.9) than RSV-negative children. The sensitivity (range, 55%-81%) and specificity (range, 27%-54%) of the SARI case definition to identify hospitalized RSV-positive children varied according to age; the lowest sensitivity was for infants aged <6 months. Using SARI as the case definition would have missed 36% of RSV-positive children aged <5 years and 49% of those aged <3 months; removing the fever requirement from the definition recovered most missed cases. Conclusion: Including fever in the SARI case definition lowers the sensitivity for RSV case detection among young children hospitalized with an ALRTI and likely underestimates its burden.

      17. BACKGROUND: Men who have sex with men (MSM) are at high risk for sexually transmitted infections (STIs). National guidelines recommend that MSM receive HIV, syphilis, gonorrhea, and chlamydia screening at least annually, and hepatitis A and B and human papillomavirus vaccinations. We investigated associations between disclosure of male-male sexual orientation/behavior and receipt of this panel of services. METHODS: Gay, bisexual and other MSM aged 18-26 years were enrolled from health clinics serving lesbian, gay, bisexual, and transgender communities in Los Angeles and Chicago during 2012-2014. Participants completed a computer-assisted self-interview regarding healthcare services, disclosure of sexual orientation/behavior, and recent HIV test results. Proportions receiving recommended care, prevalence ratios (PRs), and 95% confidence intervals (CIs) were calculated using SAS 9.4. RESULTS: Overall, 817 participants visited a provider within the past year. Of these, 525 (64.3%) had disclosed, and 749 (91.7%) felt they could disclose if important to health. In total, 548 (67.1%) received all STI screenings, 74 (9.1%) received all vaccinations. Only 105 (12.9%) received any HPV vaccination. More disclosing participants received all recommended screenings (aPR:1.4, CI:1.3-1.6) and all recommended care components (aPR:2.2, CI:1.4-4.3) than non-disclosing participants. CONCLUSIONS: Despite national recommendations, receipt of a complete panel of STI care services was low among young MSM. Vaccine uptake was lower than STI screening. However, most participants visited a healthcare provider in the past year and most disclosed, suggesting opportunities to improve services. Providers might encourage disclosure by improving sexual history-taking and education, which could increase opportunities for MSM to receive recommended care.

      18. The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006-2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child’s residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease.

      19. PURPOSE: Effectively measuring progress in delivering HIV pre-exposure prophylaxis (PrEP) requires subnational estimates of the number of adults with indications for its use that account for differences in HIV infection rates by transmission risk (risk) group and race/ethnicity. METHODS: We applied a multiplier method with 2015 Centers for Disease Control and Prevention surveillance data on proportions of HIV diagnoses by race/ethnicity and risk group and population-based estimates of risk group sizes to derive estimated numbers of adults with indications by risk group (men who have sex with men [MSM], heterosexually active adults [HET], and persons who inject drugs [PWID]) by race/ethnicity in each jurisdiction. RESULTS: An estimated 1.1 million adults had indications for PrEP use in 2015: 813,970 MSM, 258,080 HET, and 72,510 persons who inject drugs, and 500,340 blacks, 282,260 Latinos, and 303,230 whites. Among HET, 176,670 females and 81,410 males had indications. The proportions of adults with indications in each risk and race/ethnicity group varied by jurisdiction. CONCLUSIONS: Blacks comprised the highest number of adults with indications showing that increasing PrEP use in this population must be the highest priority. MSM remain a priority because of the high number with indications. These estimates can be used as denominators to assess PrEP coverage and impact on HIV incidence at subnational levels.

      20. Prevalence of pretreatment HIV drug resistance in Cameroon following a nationally representative WHO surveyExternal
        Tchouwa GF, Eymard-Duvernay S, Cournil A, Lamare N, Serrano L, Butel C, Bertagnolio S, Mpoudi-Ngole E, Raizes E, Aghokeng AF.
        J Antimicrob Chemother. 2018 Jun 19.

        Background: Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods: From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaounde, Cameroon, for drug resistance testing. HIV drug resistance mutations were identified using the Stanford algorithm. Results: Overall, from the 379 participants recruited, 321 pol sequences were successfully interpreted. Two hundred and five sequences were from patients attending urban ART clinics and 116 from patients seen at rural facilities. Nine percent of sequences (29/321) were from participants reporting previous exposure to antiretrovirals. PDR prevalence among all initiators was 10.4% (95% CI 5.4%-19.1%), with 14.2% (95% CI 6.6%-27.9%) reported in urban areas and 4.3% (95% CI 1.2%-14.3%) in rural areas. Among participants with no prior exposure to antiretrovirals, PDR prevalence was 10.4% (95% CI 4.7%-21.5%) overall, with 13.5% (95% CI 5.1%-31.5%) and 5.3% (95% CI 1.4%-17.5%) reported in urban and rural areas, respectively. Conclusions: Our findings indicate that at least 10% of patients initiating ART in Cameroon carry viruses with PDR and may be at risk of premature ART failure. The high level of NNRTI-associated resistance is of particular concern and supports introduction of drugs with a higher genetic barrier to resistance.

      21. Building on the HIV chronic care platform to address noncommunicable diseases in sub-Saharan Africa: a research agendaExternal
        Vorkoper S, Kupfer LE, Anand N, Patel P, Beecroft B, Tierney WM, Ferris R, El-Sadr WM.
        Aids. 2018 Jul 1;32 Suppl 1:S107-s113.

        OBJECTIVE: The remarkable progress made in confronting the global HIV epidemic offers a unique opportunity to address the increasing threat of noncommunicable diseases (NCDs). However, questions remain about how to enhance the HIV platforms to deliver integrated HIV and NCD care to people living with HIV (PLHIV) in sub-Saharan Africa (SSA). We aimed to develop a priority research agenda to advance this effort. METHODS: Researchers, policymakers, and implementers from the United States and SSA conducted three scoping reviews on HIV/NCD prevention and care focused on clinical, health system, and community levels. Based on the review findings and expert inputs, we conducted iterative consensus-development activities to generate a prioritized research agenda. RESULTS: Population-level data on NCD prevalence among PLHIV in SSA are sparse. The review identified NCD screening and management approaches that could be integrated into HIV programs in SSA. However, few studies focused on the effectiveness, cost, and best practices for integrated chronic care platforms, making it difficult to derive policy recommendations. To address these gaps, we propose a prioritized research agenda focused on developing evidence-based service delivery models, increasing human capacity through workforce education, generating data through informatics platforms and research, managing the medication supply chain, developing new financing and sustainability models, advancing research-informed policy, and addressing other crosscutting health system issues. CONCLUSION: Based on collaborative, interdisciplinary efforts, a research agenda was developed to provide guidance that advances efforts to adapt the current health system to deliver integrated chronic care for PLHIV and the population at large.

      22. Implementation and assessment of a model to increase HIV testing among men who have sex with men and transgender women in Thailand, 2011-2016External
        Wasantioopapokakorn M, Manopaiboon C, Phoorisri T, Sukkul A, Lertpiriyasuwat C, Ongwandee S, Langkafah F, Kritsanavarin U, Visavakum P, Jetsawang B, Nookhai S, Kitwattanachai P, Weerawattanayotin W, Losirikul M, Yenyarsun N, Jongchotchatchawal N, Martin M.
        AIDS Care. 2018 Jun 27:1-7.

        HIV testing among men who have sex with men (MSM) and transgender (TG) women remains low in Thailand. The HIV prevention program (PREV) to increase HIV testing and link those who tested HIV-positive to care provided trainings to peer educators to conduct target mapping, identify high risk MSM and TG women through outreach education and offer them rapid HIV testing. Trained hospital staff provided HIV testing and counseling with same-day results at hospitals and mobile clinics and referred HIV-positive participants for care and treatment. We used a standardized HIV pre-test counseling form to collect participant characteristics and analyzed HIV test results using Poisson regression and Wilcoxon rank sum trend tests to determine trends over time. We calculated HIV incidence using data from participants who initially tested HIV-negative and tested at least one more time during the program. Confidence intervals for HIV incidence rates were calculated using the Exact Poisson method. From September 2011 through August 2016, 5,629 participants had an HIV test; their median age was 24 years, 1,923 (34%) tested at mobile clinics, 5,609 (99.6%) received their test result, and 1,193 (21%) tested HIV positive. The number of people testing increased from 458 in 2012 to 1,832 in 2016 (p < 0.001). Participants testing at mobile clinics were younger (p < 0.001) and more likely to be testing for the first time (p < 0.001) than those tested at hospitals. Of 1,193 HIV-positive participants, 756 (63%) had CD4 testing. Among 925 participants who returned for HIV testing, HIV incidence was 6.2 per 100 person-years. Incidence was highest among people 20-24 years old (10.9 per 100 person-years). HIV testing among MSM and TG women increased during the PREV program. HIV incidence remains alarmingly high especially among young participants. There is an urgent need to expand HIV prevention services to MSM and TG women in Thailand.

    • Disaster Control and Emergency Services

      1. Setting priorities for humanitarian water, sanitation and hygiene research: A meeting reportExternal
        D’Mello-Guyett L, Yates T, Bastable A, Dahab M, Deola C, Dorea C, Dreibelbis R, Grieve T, Handzel T, Harmer A, Lantagne D, Maes P, Opryszko M, Palmer-Felgate S, Reed B, Van Den Bergh R, Porteaud D, Cumming O.
        Confl Health. 2018 ;12(1).

        Recent systematic reviews have highlighted a paucity of rigorous evidence to guide water, sanitation and hygiene (WASH) interventions in humanitarian crises. In June 2017, the Research for Health in Humanitarian Crises (R2HC) programme of Elrha, convened a meeting of representatives from international response agencies, research institutions and donor organisations active in the field of humanitarian WASH to identify research priorities, discuss challenges conducting research and to establish next steps. Topics including cholera transmission, menstrual hygiene management, and acute undernutrition were identified as research priorities. Several international response agencies have existing research programmes; however, a more cohesive and coordinated effort in the WASH sector would likely advance this field of research. This report shares the conclusions of that meeting and proposes a research agenda with the aim of strengthening humanitarian WASH policy and practice.

    • Disease Reservoirs and Vectors

      1. Surveillance for Heartland and Bourbon viruses in Eastern Kansas, June 2016External
        Savage HM, Godsey MS, Tatman J, Burkhalter KL, Hamm A, Panella NA, Ghosh A, Raghavan RK.
        J Med Entomol. 2018 Jun 27.

        In June 2016, we continued surveillance for tick-borne viruses in eastern Kansas following upon a larger surveillance program initiated in 2015 in response to a fatal human case of Bourbon virus (BRBV) (Family Orthomyxoviridae: Genus Thogotovirus). In 4 d, we collected 14,193 ticks representing four species from four sites. Amblyomma americanum (L.) (Acari: Ixodidae) accounted for nearly all ticks collected (n = 14,116, 99.5%), and the only other species identified were Amblyomma maculatum Koch (Acari: Ixodidae), Dermacentor variabilis (Say) (Acari: Ixodidae) and Ixodes scapularis Say (Acari: Ixodidae). All ticks were tested for both BRBV and Heartland virus (Family Bunyaviridae: Genus Phlebovirus) in 964 pools. Five Heartland virus positive tick pools were detected and confirmed by real-time reverse transcription PCR (rRT-PCR), while all pools tested negative for BRBV. Each Heartland positive pool was composed of 25 A. americanum nymphs with positive pools collected at three different sites in Bourbon County. A. americanum is believed to be the primary vector of both Heartland and BRBVs to humans based upon multiple detections of virus in field-collected ticks, its abundance, and its aggressive feeding behavior on mammals including humans. However, it is possible that A. americanum encounters viremic vertebrate hosts of BRBV less frequently than viremic hosts of Heartland virus, or that BRBV is less efficiently passed among ticks by co-feeding, or less efficiently passed vertically from infected female ticks to their offspring resulting in lower field infection rates.

      2. Identification and characterization of novel mosquito-borne (Kammavanpettai virus) and tick-borne (Wad Medani) reoviruses isolated in IndiaExternal
        Yadav PD, Shete AM, Nyayanit DA, Albarino CG, Jain S, Guerrero LW, Kumar S, Patil DY, Nichol ST, Mourya DT.
        J Gen Virol. 2018 Jun 25.

        In 1954, a virus named Wad Medani virus (WMV) was isolated from Hyalomma marginatum ticks from Maharashtra State, India. In 1963, another virus was isolated from Sturnia pagodarum birds in Tamil Nadu, India, and named Kammavanpettai virus (KVPTV) based on the site of its isolation. Originally these virus isolates could not be identified with conventional methods. Here we describe next-generation sequencing studies leading to the determination of their complete genome sequences, and identification of both virus isolates as orbiviruses (family Reoviridae). Sequencing data showed that KVPTV has an AT-rich genome, whereas the genome of WMV is GC-rich. The size of the KVPTV genome is 18 234 nucleotides encoding proteins ranging 238-1290 amino acids (aa) in length. Similarly, the size of the WMV genome is 16 941 nucleotides encoding proteins ranging 214-1305 amino acids in length. Phylogenetic analysis of the VP1 gene, along with the capsid genes VP5 and VP7, revealed that KVPTV is likely a novel mosquito-borne virus and WMV is a tick-borne orbivirus. This study focuses on the phylogenetic comparison of these newly identified orbiviruses with mosquito-, tick- and Culicoides-borne orbiviruses isolated in India and other countries.

    • Environmental Health

      1. Environmental assessment and blood lead levels of children in Owino Uhuru and Bangladesh settlements in KenyaExternal
        Etiang NA, Arvelo W, Galgalo T, Amwayi S, Gura Z, Kioko J, Omondi G, Patta S, Lowther SA, Brown MJ.
        J Health Pollut. 2018 ;8(18).

        Background. Lead exposure is linked to intellectual disability and anemia in children. The United States Centers for Disease Control and Prevention (CDC) recommends biomonitoring of blood lead levels (BLLs) in children with BLL >/=5 microg/dL and chelation therapy for those with BLL >/=45 microg/dL. Objectives. This study aimed to determine blood and environmental lead levels and risk factors associated with elevated BLL among children from Owino Uhuru and Bangladesh settlements in Mombasa County, Kenya. Methods. The present study is a population-based, cross-sectional study of children aged 12-59 months randomly selected from households in two neighboring settlements, Owino Uhuru, which has a lead smelter, and Bangladesh settlement (no smelter). Structured questionnaires were administered to parents and 1-3 ml venous blood drawn from each child was tested for lead using a LeadCare II portable analyzer. Environmental samples collected from half of the sampled households were tested for lead using graphite furnace atomic absorption spectroscopy. Results: We enrolled 130 children, 65 from each settlement. Fifty-nine (45%) were males and the median age was 39 months (interquartile range (IQR): 30-52 months). BLLs ranged from 1 microg/dL to 31 microg/dL, with 45 (69%) children from Owino Uhuru and 18 (28%) children from Bangladesh settlement with BLLs > 5 microg/dL. For Owino Uhuru, the geometric mean BLL in children was 7.4 microg/dL (geometric standard deviation (GSD); 1.9) compared to 3.7 microg/ dL (GSD: 1.9) in Bangladesh settlement (p < 0.05). The geometric mean lead concentration of soil samples from Owino Uhuru was 146.5 mg/Kg (GSD: 5.2) and 11.5 mg/Kg (GSD: 3.9) (p < 0.001) in Bangladesh settlement. Children who resided < 200 m from the lead smelter were more likely to have a BLL ?5 microg/dL than children residing >/=200 m from the lead smelter (adjusted odds ratio (aOR): 33.6 (95% confidence interval (CI): 7.4-153.3). Males were also more likely than females to have a BLL >/=5 microg/dL (39, 62%) compared to a BLL < 5 microg/dL [aOR: 2.4 (95% CI: 1.0-5.5)]. Conclusions. Children in Owino Uhuru had significantly higher BLLs compared with children in Bangladesh settlement. Interventions to diminish continued exposure to lead in the settlement should be undertaken. Continued monitoring of levels in children with detectable levels can evaluate whether interventions to reduce exposure are effective. Participant Consent. Obtained Ethics Approval. Scientific approval for the study was obtained from the Ministry of Health, lead poisoning technical working group. Since this investigation was considered a public health response of immediate concern, expedited ethical approval was obtained from the Kenya Medical Research Institute and further approval from the Mombasa County Department of Health Services. The investigation was considered a non-research public health response activity by the CDC. Competing Interests. The authors declare no competing financial interests.

      2. Outbreaks associated with untreated recreational water – United States, 2000-2014External
        Graciaa DS, Cope JR, Roberts VA, Cikesh BL, Kahler AM, Vigar M, Hilborn ED, Wade TJ, Backer LC, Montgomery SP, Secor WE, Hill VR, Beach MJ, Fullerton KE, Yoder JS, Hlavsa MC.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 29;67(25):701-706.

        Outbreaks associated with untreated recreational water can be caused by pathogens, toxins, or chemicals in fresh water (e.g., lakes, rivers) or marine water (e.g., ocean). During 2000-2014, public health officials from 35 states and Guam voluntarily reported 140 untreated recreational water-associated outbreaks to CDC. These outbreaks resulted in at least 4,958 cases of disease and two deaths. Among the 95 outbreaks with a confirmed infectious etiology, enteric pathogens caused 80 (84%); 21 (22%) were caused by norovirus, 19 (20%) by Escherichia coli, 14 (15%) by Shigella, and 12 (13%) by Cryptosporidium. Investigations of these 95 outbreaks identified 3,125 cases; 2,704 (87%) were caused by enteric pathogens, including 1,459 (47%) by norovirus, 362 (12%) by Shigella, 314 (10%) by Cryptosporidium, and 155 (5%) by E. coli. Avian schistosomes were identified as the cause in 345 (11%) of the 3,125 cases. The two deaths were in persons affected by a single outbreak (two cases) caused by Naegleria fowleri. Public parks (50 [36%]) and beaches (45 [32%]) were the leading settings associated with the 140 outbreaks. Overall, the majority of outbreaks started during June-August (113 [81%]); 65 (58%) started in July. Swimmers and parents of young swimmers can take steps to minimize the risk for exposure to pathogens, toxins, and chemicals in untreated recreational water by heeding posted advisories closing the beach to swimming; not swimming in discolored, smelly, foamy, or scummy water; not swimming while sick with diarrhea; and limiting water entering the nose when swimming in warm freshwater.

      3. Patient-provider discussions about strategies to limit air pollution exposuresExternal
        Mirabelli MC, Damon SA, Beavers SF, Sircar KD.
        Am J Prev Med. 2018 Jun 11.

        INTRODUCTION: Exposure to air pollution negatively affects respiratory and cardiovascular health. The objective of this study was to describe the extent to which health professionals report talking about how to limit exposure to air pollution during periods of poor air quality with their at-risk patients. METHODS: In 2015, a total of 1,751 health professionals completed an online survey and reported whether they talk with their patients about limiting their exposure to air pollution. In 2017, these data were analyzed to assess the frequency that health professionals in primary care, pediatrics, obstetrics/gynecology, and nursing reported talking about limiting air pollution exposure with patients who have respiratory or cardiovascular diseases, were aged </=18 years, were aged >/=65 years, or were pregnant women. Frequencies of positive responses were assessed across categories of provider- and practice-level characteristics. RESULTS: Overall, 714 (41%) respondents reported ever talking with their patients about limiting their exposure to air pollution. Thirty-four percent and 16% of providers specifically reported talking with their patients with respiratory or cardiovascular disease diagnoses, respectively. Percentages of health professionals who reported talking with their patients about limiting air pollution exposure were highest among respondents in pediatrics (56%) and lowest among respondents in obstetrics/gynecology (0%). CONCLUSIONS: Despite the well-described health effects of exposure to air pollution, the majority of respondents did not report talking with their patients about limiting their exposure to air pollution. These findings reveal clear opportunities to improve awareness about strategies to limit air pollution exposure among sensitive groups of patients and their health care providers.

      4. Unintentional non-fire-related (UNFR) carbon monoxide (CO) poisoning is a leading cause of poisoning in the US and a preventable cause of death. We generated national estimates of accidental CO poisoning and characterized the populations most at risk. UNFR CO poisoning cases were assessed using hospitalization and emergency department (ED) data from the Healthcare Costs and Utilization Project National Inpatient Sample and Nationwide Emergency Department Sample databases. We used hospitalization data from 2003 to 2013 and ED data from 2007 to 2013. We calculated trends using a linear regression of UNFR CO poisonings over the study period and age-adjusted rates using direct standardization and U.S. Census Bureau estimates. During 2003-2013, approximately 14,365 persons (4.1 cases/million annually) with confirmed or probable UNFR CO poisoning were admitted to hospitals and the annual rate of poisonings showed a weak downward trend (p=0.12). During 2007-2013, approximately 101,847 persons (48.3 visits/million annually) visited the ED and the annual rate of poisonings showed a significant downward trend (p</=0.01). Most UNFR CO hospital cases involved patients who were older (aged 45-64years), white, male, or living in the South or Midwest. Overall, the rate of hospitalizations did not change over the study period. Unintentional CO poisoning is preventable and these cases represent the most recent national estimates. ED visits declined over the study period, but the hospitalization rates did not change. This emphasizes the need for prevention efforts, such as education in the ED setting, increased use of CO alarms, and proper use and maintenance of fuel-powered household appliances.

    • Genetics and Genomics

      1. Evidence-based medicine and big genomic dataExternal
        Ioannidis JP, Khoury MJ.
        Hum Mol Genet. 2018 May 1;27(R1):R2-r7.

        Genomic and other related big data (Big Genomic Data, BGD for short) are ushering a new era of precision medicine. This overview discusses whether principles of evidence-based medicine hold true for BGD and how they should be operationalized in the current era. Major evidence-based medicine principles include the systematic identification, description and analysis of the validity and utility of BGD, the combination of individual clinical expertise with individual patient needs and preferences, and the focus on obtaining experimental evidence, whenever possible. BGD emphasize information of single patients with an overemphasis on N-of-1 trials to personalize treatment. However, large-scale comparative population data remain indispensable for meaningful translation of BGD personalized information. The impact of BGD on population health depends on its ability to affect large segments of the population. While several frameworks have been proposed to facilitate and standardize decision making for use of genomic tests, there are new caveats that arise from BGD that extend beyond the limitations that were applicable for more simple genetic tests. Non-evidence-based use of BGD may be harmful and result in major waste of healthcare resources. Randomized controlled trials will continue to be the strongest arbitrator for the clinical utility of genomic technologies, including BGD. Research on BGD needs to focus not only on finding robust predictive associations (clinical validity) but also more importantly on evaluating the balance of health benefits and potential harms (clinical utility), as well as implementation challenges. Appropriate features of such useful research on BGD are discussed.

    • Global Health

      1. Human rights as political determinants of health: A retrospective study of North Korean RefugeesExternal
        Cha J, Surkan PJ, Kim J, Yoon IA, Robinson C, Cardozo BL, Lee H.
        Am J Prev Med. 2018 Jun 19.

        INTRODUCTION: The gravity, scale, and nature of human rights violations are severe in North Korea. Little is known about the mental health consequences of the lifelong exposures to these violations. METHODS: In 2014-2015, a retrospective study was conducted among 383 North Korean refugees in South Korea using respondent-driven sampling to access this hidden population. This study collected information on the full range of political and economic rights violations and measured post-traumatic stress disorder, anxiety and depression symptoms, and social functioning by standard instruments. Multivariate regression analysis was performed with the adjustment of political, economic, and demographic variables in 2016-2017. RESULTS: The results indicate elevated symptoms of anxiety (60.1%, 95% CI=54.3%, 65.7%), depression (56.3%, 95% CI=50.8%, 61.9%), and post-traumatic stress disorder (22.8%, 95% CI=18.6%, 27.4%), which are significantly associated with exposures to political rights violations (ten to 19 items versus non-exposure: anxiety AOR=16.78, p<0.001, depression AOR=12.52, p<0.001, post-traumatic stress disorder AOR=16.71, p<0.05), and economic rights violations (seven to 13 items versus non-exposure: anxiety AOR=5.68, p<0.001, depression AOR=4.23, p<0.01, post-traumatic stress disorder AOR=5.85, p<0.05). The mean score of social functioning was also lower in those who were exposed to political (adjusted difference= -13.29, p<0.001) and economic rights violations (adjusted difference= -11.20, p<0.001). CONCLUSIONS: This study highlights mental health consequences of lifelong human rights violations in North Korea. Beyond the conventional approach, it suggests the need for a collaborative preventive response from global health and human rights activists to address human rights in regard to mental health determinants of the 20 million people in North Korea.

    • Healthcare Associated Infections

      1. Fatal sepsis associated with bacterial contamination of platelets – Utah and California, August 2017External
        Horth RZ, Jones JM, Kim JJ, Lopansri BK, Ilstrup SJ, Fridey J, Kelley WE, Stramer SL, Nambiar A, Ramirez-Avila L, Nichols A, Garcia W, Oakeson KF, Vlachos N, McAllister G, Hunter R, Nakashima AK, Basavaraju SV.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 29;67(25):718-722.

        During August 2017, two separate clusters of platelet transfusion-associated bacterial sepsis were reported in Utah and California. In Utah, two patients died after platelet transfusions from the same donation. Clostridium perfringens isolates from one patient’s blood, the other patient’s platelet bag, and donor skin swabs were highly related by whole genome sequencing (WGS). In California, one patient died after platelet transfusion; Klebsiella pneumoniae isolates from the patient’s blood and platelet bag residuals and a nontransfused platelet unit were matched using WGS. Investigation revealed no deviations in blood supplier or hospital procedures. Findings in this report highlight that even when following current procedures, the risk for transfusion-related infection and fatality persists, making additional interventions necessary. Clinicians need to be vigilant in monitoring for platelet-transmitted bacterial infections and report adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers and hospitals could consider additional evidence-based bacterial contamination risk mitigation strategies, including pathogen inactivation, rapid detection devices, and modified screening of bacterial culture protocols.

      2. Notes from the field: Domestically acquired Verona integron-mediated metallo-beta-lactamase-producing Enterobacteriaceae – Indiana, 2016-2017External
        Shannon DJ, Blosser S, Walters M, Kallen A, Feaster C.
        MMWR Morb Mortal Wkly Rep. 2018 Jun 29;67(25):727-728.

        [No abstract]

    • Immunity and Immunization
      1. We reported previously that the annual average mortality rate in the United States in 2008-2011 for varicella listed as the underlying cause declined 87% compared with the prevaccine period (1990-1994). Here, we update the analysis with five additional years of data. We used varicella death data from the 2012-2016 Mortality Multiple Cause-of Death records to calculate mortality rates during 2012-2016 and trends since the prevaccine period and end of 1-dose vaccination program (2005-2007). The annual average age-adjusted mortality rate for varicella as the underlying cause was 0.03 per million population during 2012-2016, a 94% reduction from prevaccine years and a 47% reduction from 2005-2007. Varicella deaths continue to decline due to the varicella vaccination program in the United States.

      2. Both immune priming and egg-adaptation in the vaccine influence antibody responses to circulating A(H1N1)pdm09 viruses following influenza vaccination in adultsExternal
        Liu F, Tzeng WP, Horner L, Kamal RP, Tatum HR, Blanchard EG, Xu X, York I, Tumpey TM, Katz JM, Lu X, Levine MZ.
        J Infect Dis. 2018 Jun 21.

        Background: Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during 2015-16 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses following vaccination. Methods: Over 300 paired adult (18-49 yrs) pre and post-vaccination sera collected in 6 seasons (2010-11 to 2015-16) were analyzed by hemagglutination inhibition assays to evaluate the antibody responses to thirteen A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify 163K- and 223R-specificity of antibodies. Results: Individual antibody profiles to A(H1N1) viruses revealed three priming patterns: USSR/77-, TW/86- or NC/99-priming. Over 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared to the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was only observed in USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts. Conclusion: Both 163K-specificity driven by immune priming and 223R-specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses following vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection.

      3. Evaluation of the influence of gastrointestinal coinfections on rotavirus vaccine effectiveness in BotswanaExternal
        Mokomane M, Tate JE, Steenhoff AP, Esona MD, Bowen MD, Lechiile K, Pernica JM, Kasvosve I, Parashar UD, Goldfarb DM.
        Pediatr Infect Dis J. 2018 Mar;37(3):e58-e62.

        BACKGROUND: Studies have demonstrated reduced rotavirus vaccine effectiveness (VE) in resource-limited settings. Enteropathogen coinfections in rotavirus cases have been hypothesized to contribute to the lower VE in such settings. We sought to determine if coinfections affect rotavirus VE in Botswana. METHODS: Between June 2013 and April 2015, children <60 months old, presenting with severe gastroenteritis at 4 hospitals as part of a national rotavirus surveillance were enrolled. Rotavirus enzyme immunoassay (EIA)-positive samples were tested with an in-house real-time polymerase chain reaction (PCR) panel that detected 9 pathogens and a commercial 15 multiplex PCR gastrointestinal pathogen panel. Coinfection was defined as detection of rotavirus plus 1 of the 5 pathogens with the highest attributable fractions for diarrhea. Vaccine status was compared between rotavirus case patients and non-rotavirus “test-negative” controls. VE was also calculated restricting cases to those with rotavirus as the only pathogen detected. RESULTS: Two hundred and forty-two children tested rotavirus EIA positive, and 368 children were negative. Of the 182 rotavirus EIA-positive samples tested with the gastrointestinal pathogen panel assay, coinfections were detected in 60 (33%). The overall adjusted 2-dose VE was 59% (95% confidence interval [CI]: 27-77) in the rotavirus coinfection group and 51% (95% CI: -14 to 79) in the rotavirus monoinfection subgroup. Using in-house multiplex PCR panel, of 213 rotavirus EIA-positive subjects, coinfections were detected in 98 samples (46%). The overall adjusted VEs for 2 doses were 48% (95% CI: -2 to 74) and 62% (95% CI: 25-80) in rotavirus monoinfection subgroup. CONCLUSIONS: We could not find evidence of an effect of enteric coinfections on the effectiveness of rotavirus vaccine.

      4. Sustained impact of rotavirus vaccine on rotavirus hospitalisations in Lusaka, Zambia, 2009-2016External
        Mpabalwani EM, Simwaka JC, Mwenda JM, Matapo B, Parashar UD, Tate JE.
        Vaccine. 2018 May 21.

        BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Lusaka in February 2012 and rolled out countrywide in November 2013 in the routine Expanded Programme on Immunisation and administered at 6 and 10weeks with no catch up dose. Reported here is the monitoring of rotavirus acute gastroenteritis hospitalisations at the University Teaching Hospital, Lusaka, Zambia as part of efforts to document the impact of rotavirus vaccine. METHODS: Children <5years hospitalised for acute gastroenteritis (AGE) from January 2009 to December 2016 were recruited into the rotavirus disease burden active surveillance and had their stools tested for rotavirus by enzyme immunoassay. We compared rotavirus-associated AGE hospitalisations of the pre-vaccine era (2009-2011) with the post-rotavirus vaccine introduction period (2013-2016). RESULTS: With the increase in RV1 coverage in Lusaka, rotavirus AGE declined significantly from 40% of diarrhoea hospitalisation in the pre-vaccine era to 29% of diarrhoea hospitalisation in the post-vaccine era (p<0.001) in children <5years. After a decreasing trend in rotavirus positivity from 2013 to 2015, positivity increased to 37% in 2016. However, the post-vaccine years (2012-2016) saw substantial decline in the number tested (median decline: 34% (range: 20-43%)) and the number of positive results (median decline: 52% (range: 30-65%). CONCLUSION: A sustained and significant decline in rotavirus AGE hospitalisations was observed in children <5years since the introduction of RV1 in Lusaka, Zambia. Despite an increase in rotavirus positivity in 2016, the total number of children enrolled and the number of rotavirus positive children remained below baseline. The reason for the increase in rotavirus positivity in 2016 is unknown but could be due to an accumulation of susceptible children and the shifting of disease to children of older age groups. This finding underscores the need for continued monitoring of rotavirus vaccine impact.

      5. Pneumococcal conjugate vaccine safety in elderly adultsExternal
        Tseng HF, Qian L, Liu IL, Mercado C, Lewin B, Tartof SY, Nelson J, Jackson LA, Daley MF, Weintraub E, Klein NP, Belongia E, Liles EG, Jacobsen SJ.
        Open Forum Infect Dis. 2018 01 Jun;5(6):1-8.

        The 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) were both recommended to adults aged >=65 years. The study examines adults >=65 years for risk of adverse events (AEs) requiring medical attention following vaccination with PCV13 as compared with vaccination with PPSV23, a long-standing vaccine with a satisfactory safety profile. Methods. The cohort study included 6 Vaccine Safety Datalink sites. The exposed person-time included follow-up time of the first PCV13 received by subjects age >=65 years from January 1 to August 15, 2015. The comparator person-time included follow-up time after the first PPSV23 received by subjects of the same age during Janaury 1 to August 15 of each year of 2011-2015. The prespecified AEs included cardiovascular events, Bell’s palsy, Guillain-Barre syndrome, syncope, erythema multiforme, thrombocytopenia, cellulitis and infection, allergic reaction, and anaphylaxis. Inverse probability of treatment weighting-adjusted Poisson regression models was used to estimate the relative risk (RR) of each AE. Results. A total of 313 136 doses of PCV13 and 232 591 doses of PPSV23 were included. The adjusted RRs comparing the incidence of AEs following PCV13 vs PPSV23 were all < 1, except for anaphylaxis, which was insignificant with an RR of 1.32 (95% confidence interval, 0.30-5.79). Only 1 patient who received PCV13 and 4 other vaccines concomitantly was confirmed by medical chart review as having experienced anaphylaxis after vaccination. Conclusions. These data do not support an increased rate of adverse events following PCV13 administration in elders compared with PPSV23 and should provide reassurance regarding continued use of PCV13.

    • Injury and Violence

      1. Healthcare professional involvement and RTP compliance in high school athletes with concussionExternal
        Haarbauer-Krupa JK, Comstock RD, Lionbarger M, Hirsch S, Kavee A, Lowe B.
        Brain Inj. 2018 Jun 28:1-8.

        OBJECTIVES: To describe concussion rates in high school athletes and involvement of healthcare professionals in concussion diagnosis, management and compliance with return to play (RTP) guidelines. METHODS: Data were analysed from injury reports in the National High School Sports-Related Injury Surveillance System between 2009/2010 and 2012/2013 to identify student athletes with concussion and determine compliance with RTP guidelines. Compliance with RTP guidelines was examined using logistic regression, adjusting for sport and injury-related variables. RESULTS: There were 5611 concussions recorded during 15 712 475 athlete exposures (AEs), a rate of 3.6 concussions per 10 000 AEs. Rates were higher during competition and among girls compared to boys in gender equitable sports. Healthcare professionals were less likely to be present at the time of concussion for girls’ sports, lower competition levels and practices. Compliance with RTP guidelines was higher for athletes with recurrent concussions, those sustained in collision sports, for athletes reporting more symptoms and when a physician made the RTP decision. CONCLUSIONS: Presence of healthcare professionals and compliance with RTP guidelines varied by sport, gender, level of play and exposure type. High school athletes with concussion are best served by assessment teams with athletic trainers and physicians working together to manage concussions and contribute to RTP decisions.

      2. Research has demonstrated the effectiveness of family-based programs for reducing adolescent risk behaviors and promoting adolescent health; however, parent engagement, specifically in terms of recruitment and retention, remains a consistent challenge. Recruitment rates for family-based prevention programs range from 3 to 35%, while, on average, 28% of caregivers drop out before program completion. Thus, engagement of parents in prevention programming is of utmost concern to ensure families and youth benefit from implementation of family-based programs. In this manuscript, two Centers for Disease Control and Prevention-funded projects share their experiences with engagement of parents in violence prevention programs. Problems related to parent engagement are reviewed, as are structural, attitudinal, and interpersonal barriers specific to recruitment and retention. Examples of successful implementation strategies identified across urban and rural sites are also analyzed and lessons learned are provided.

      3. The epidemiology of pediatric head injury treated outside of hospital emergency departmentsExternal
        Zogg CK, Haring RS, Xu L, Canner JK, AlSulaim HA, Hashmi ZG, Salim A, Engineer LD, Haider AH, Bell JM, Schneider EB.
        Epidemiology. 2018 Mar;29(2):269-279.

        BACKGROUND: Although head trauma-related deaths, hospitalizations, and emergency department visits are well characterized, few studies describe pediatric patients presenting outside of emergency departments. We compared the epidemiology and extent of healthcare-seeking pediatric (0-17 years) patients presenting in outpatient settings with those of patients seeking nonhospitalized emergency department care. METHODS: We used MarketScan Medicaid and commercial claims, 2004-2013, to identify patients managed in two outpatient settings (physician’s offices/clinics, urgent care) and the emergency department. We then examined differences in demographic and injury-specific factors, Centers for Disease Control and Prevention-defined head trauma diagnoses, the extent of and reasons for post-index visit ambulatory care use within 30/90/180 days, and annual and monthly variations in head trauma trends. Outpatient incidence rates in 2013 provided estimates of the nationwide US outpatient burden. RESULTS: A total of 1,683,097 index visits were included, representing a nationwide burden in 2013 of 844,660 outpatient cases, a number that encompassed 51% of healthcare-seeking head trauma that year and that substantially increased in magnitude from 2004 to 2013. Two-thirds (68%) were managed in outpatient settings. While demographic distributions varied with index-visit location, injury-specific factors were comparable. Seasonal spikes appeared to coincide with school sports. CONCLUSIONS: There is an urgent need to better understand the natural history of head trauma in the >800,000 pediatric patients presenting each year for outpatient care. These outpatient injuries, which are more than double the number of head trauma cases recorded in the hospital-affiliated settings, illustrate the potential importance of expanding inclusion criteria in surveillance and prevention efforts designed to address this critical issue.

    • Laboratory Sciences

      1. Sensitive and selective gas chromatography-tandem mass spectrometry method for the detection of nitrobenzene in tobacco smokeExternal
        Chapman GM, Bravo R, Stanelle RD, Watson CH, Valentin-Blasini L.
        J Chromatogr A. 2018 Jun 11.

        Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been largely excluded from prior analysis due to difficulties with quantification. Quantifying harmful compounds in cigarette smoke is useful to compare products, to examine the impact of design parameters on delivery, and to help estimate exposures. A sensitive high-throughput method has been developed for quantifying nitrobenzene in machine-generated mainstream cigarette smoke using isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in the low nanogram range, with a 418pg/cig method limit of detection. Precision estimates from two quality control cigarette products resulted in percent relative standard deviations of 11.5% and 14.9%; product variability estimates from 13 cigarette products resulted in percent relative standard deviations ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream smoke from 15 cigarette products are reported and range from 18 to 38ng/cig under the Health Canada Intense smoking regimen.

      2. A predictive 7-gene assay and prognostic protein biomarkers for non-small cell lung cancerExternal
        Guo NL, Dowlati A, Raese RA, Dong C, Chen G, Beer DG, Shaffer J, Singh S, Bokhary U, Liu L, Howington J, Hensing T, Qian Y.
        EBioMedicine. 2018 Jun;32:102-110.

        PURPOSE: This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets. PATIENTS AND METHODS: The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples. RESULTS: A 7-gene signature was identified from training cohort (n=83) with accurate patient stratification (P=0.0043) and was validated in independent patient cohorts (n=248, P<0.0001) in Kaplan-Meier analyses. In the predicted benefit group, there was a significantly better disease-specific survival in patients receiving adjuvant chemotherapy in both training (P=0.035) and validation (P=0.0049) sets. In the predicted non-benefit group, there was no survival benefit in patients receiving chemotherapy in either set. The protein expression of ZNF71 quantified with AQUA scores produced robust patient stratification in separate training (P=0.021) and validation (P=0.047) NSCLC cohorts. The protein expression of CD27 quantified with ELISA had a strong correlation with its mRNA expression in NSCLC tumors (Spearman coefficient=0.494, P<0.0088). Multiple signature genes had concordant DNA copy number variation, mRNA and protein expression in NSCLC progression. CONCLUSIONS: This study presents a predictive multi-gene assay and prognostic protein biomarkers clinically applicable for improving NSCLC treatment, with important implications in lung cancer chemotherapy and immunotherapy.

      3. Quantification of ricinine and abrine in human plasma by HPLC-MS-MS: Biomarkers of exposure to ricin and abrinExternal
        Isenberg SL, Carter MD, Miller MA, Noras AI, Mojica MA, Carlsen ST, Bulathsinghala CP, Thomas JD, Johnson RC.
        J Anal Toxicol. 2018 Jun 21.

        Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 +/- 0.003 and 0.998 +/- 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay’s time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.

      4. Per- and polyfluoroalkyl substances (PFAS), man-made chemicals with variable length carbon chains containing the perfluoroalkyl moiety (CnF2n+1-), are used in many commercial applications. Since 1999-2000, several long-chain PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have been detected at trace levels in the blood of most participants of the National Health and Nutrition Examination Survey (NHANES)-representative samples of the U.S. general population-while short-chain PFAS have not. Lower detection frequencies and concentration ranges may reflect lower exposure to short-chain PFAS than to PFOS or PFOA or that, in humans, short-chain PFAS efficiently eliminate in urine. We developed on-line solid phase extraction-HPLC-isotope dilution-MS/MS methods for the quantification in 50muL of urine or serum of 15 C3-C11 PFAS (C3 only in urine), and three fluorinated alternatives used as PFOA or PFOS replacements: GenX (ammonium salt of 2,3,3,3,-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoate, also known as HFPO-DA), ADONA (ammonium salt of 4,8-dioxa-3H-perfluorononanoate), and 9Cl-PF3ONS (9-chlorohexadecafluoro-3-oxanonane-1-sulfonate), main component of F53-B. Limit of detection for all analytes was 0.1ng/mL. To validate the method, we analyzed 50 commercial urine/serum paired samples collected in 2016 from U.S. volunteers with no known exposure to the chemicals. In serum, detection frequency and concentration patterns agreed well with those from NHANES. By contrast, except for perfluorobutanoate, we did not detect long-chain or short-chain PFAS in urine. Also, we did not detect fluorinated alternatives in either urine or serum. Together, these results suggest limited exposure to both short-chain PFAS and select fluorinated alternatives in this convenience population.

      5. Genotyping performance evaluation of commercially available HIV-1 drug resistance testExternal
        Rosemary A, Chika O, Jonathan O, Godwin I, Georgina O, Azuka O, Zaidat M, Philippe C, Oliver E, Oche A, David O, Jay S, Ibrahim D, Mukhtar A, Joshua D, Chunfu Y, Elliot R, Beth C, Phyllis K, Emmanuel I.
        PLoS One. 2018 ;13(6):e0198246.

        BACKGROUND: ATCC HIV-1 drug resistance test kit was designed to detect HIV-1 drug resistance (HIVDR) mutations in the protease and reverse transcriptase genes for all HIV-1 group M subtypes and circulating recombinant forms. The test has been validated for both plasma and dried blood spot specimen types with viral load (VL) of >/=1000 copies/ml. We performed an in-country assessment on the kit to determine the genotyping sensitivity and its accuracy in detecting HIVDR mutations using plasma samples stored under suboptimal conditions. METHODS: Among 572 samples with VL >/=1000 copies/ml that had been genotyped by ViroSeq assay, 183 were randomly selected, including 85 successful genotyped and 98 unsuccessful genotyped samples. They were tested with ATCC kits following the manufacturer’s instructions. Sequence identity and HIVDR patterns were analysed with Stanford University HIV Drug Resistance HIVdb program. RESULTS: Of the 183 samples, 127 (69.4%) were successfully genotyped by either method. While ViroSeq system genotyped 85/183 (46.5%) with median VL of 32,971 (IQR: 11,150-96,506) copies/ml, ATCC genotyped 115/183 (62.8%) samples with median VL of 23,068 (IQR: 7,397-86,086) copies/ml. Of the 98 unsuccessful genotyped samples with ViroSeq assay, 42 (42.9%) samples with lower median VL of 13,906 (IQR: 6,122-72,329) copies/ml were successfully genotyped using ATCC. Sequence identity analysis revealed that the sequences generated by both methods were >98% identical and yielded similar HIVDR profiles at individual patient level. CONCLUSION: This study confirms that ATCC kit showed greater sensitivity in genotyping plasma samples stored in suboptimal conditions experiencing frequent and prolonged power outage. Thus, it is more sensitive particularly for subtypes A and A/G HIV-1 in resource-limited settings.

      6. Candida auris is a multidrug-resistant pathogenic yeast whose recent emergence is of increasing public-health concern. C. auris can colonize multiple body sites, including patients’ skin, and survive for weeks in the healthcare environment, facilitating patient-to-patient transmission and fueling healthcare-associated outbreaks. Rapid and accurate detection of C. auris colonization is essential for timely implementation of infection control measures and prevent transmission. Currently, axilla/groin composite swabs, used to assess colonization status, are processed using a culture-based method that is sensitive and specific but requires 14 days. This delay limits the opportunity to respond and highlights the need for a faster alternative. The culture-independent T2 Magnetic Resonance (T2MR) system is a rapid diagnostic platform shown to detect target pathogens of interest from unprocessed blood samples in <5 hours. In this study, a new C. auris-specific T2 assay was evaluated for screening of the skin surveillance samples. Inclusivity and limit of detection of the T2 C. auris assay were assessed with spiked samples in a representative skin flora background. The T2 C. auris assay recognized isolates from each of the 4 known clades of C. auris and consistently detected cells at 5 CFU/mL. Finally, 89 clinical axilla/groin swab samples were processed with the T2 C. auris assay. The culture-based diagnostic assay was used as a gold standard to determine performance statistics including sensitivity (0.89) and specificity (0.98). Overall, the T2 C. auris assay performed well as a rapid diagnostic and could help expedite the detection of C. auris in patient skin swabs. This article is protected by copyright. All rights reserved.

      7. Field evaluation of onsite near real-time monitors for surface contamination by 5-fluorouracilExternal
        Smith JP, Sammons D, Robertson S, Krieg E, Snawder J.
        J Oncol Pharm Pract. 2018 Jan 1.

        Objectives In order to produce near real-time onsite results to detect surface contamination by antineoplastic drugs, the National Institute for Occupational Safety and Health developed monitors for 5-fluorouracil, which use surface wiping and lateral flow immunoassay for measurement. The monitors were tested in the laboratory to assess the sensitivity of detection on laboratory-produced contaminated surfaces. A field evaluation to assess the capability of the monitors to make measurements in healthcare workplaces was carried out in collaboration with a medical device company and the results are presented in this report. Methods The 5-fluorouracil monitor was evaluated in areas where oncology drugs were prepared and administered to patients at five different hospitals. The levels of contamination measured with the monitors were compared to levels measured with liquid chromatography-tandem mass spectrometry. Results The 5-fluorouracil values measured with the liquid chromatography-tandem mass spectrometry ranged from 0 to over 200,000 ng/100 cm(2). Measurements by the 5-fluorouracil monitors in the range 10-100 ng/100 cm(2) correlated with the liquid chromatography-tandem mass spectrometry. Receiver operating characteristic curves developed for the data indicated that a positive limit of 22 ng/100 cm(2) would give an acceptable level of false-positives while retaining most true-positive samples. If the liquid chromatography-tandem mass spectrometry measured greater than 100 ng/100 cm(2), then the monitors also measured levels greater than 100 ng/100 cm(2) for the majority of samples. Conclusion The data indicate that there are many areas in hospitals that are contaminated with 5-fluorouracil and the monitors will be useful in identifying this contamination.

      8. Development of a high-throughput assay to detect antibody inhibition of low pH induced conformational changes of influenza virus hemagglutininExternal
        Trost JF, LeMasters EH, Liu F, Carney P, Lu X, Sugawara K, Hongo S, Stevens J, Steinhauer DA, Tumpey T, Katz JM, Levine MZ, Li ZN.
        PLoS One. 2018 ;13(6):e0199683.

        Many broadly neutralizing antibodies (bnAbs) bind to conserved areas of the hemagglutinin (HA) stalk region and can inhibit the low pH induced HA conformational changes necessary for viral membrane fusion activity. We developed and evaluated a high-throughput virus-free and cell-free ELISA based low pH induced HA Conformational Change Inhibition Antibody Detection Assay (HCCIA) and a complementary proteinase susceptibility assay. Human serum samples (n = 150) were tested by HCCIA using H3 recombinant HA. Optical density (OD) ratios of mAb HC31 at pH 4.8 to pH 7.0 ranged from 0.87 to 0.09. Our results demonstrated that low pH induced HA conformational change inhibition antibodies (CCI) neutralized multiple H3 strains after removal of head-binding antibodies. The results suggest that HCCIA can be utilized to detect and characterize CCI in sera, that are potentially broadly neutralizing, and serves as a useful tool for evaluating universal vaccine candidates targeting the HA stalk.

    • Maternal and Child Health

      1. Multiple bias analysis using logistic regression: an example from the National Birth Defects Prevention StudyExternal
        Johnson CY, Howards PP, Strickland MJ, Waller DK, Flanders WD.
        Ann Epidemiol. 2018 Jun 2.

        PURPOSE: Exposure misclassification, selection bias, and confounding are important biases in epidemiologic studies, yet only confounding is routinely addressed quantitatively. We describe how to combine two previously described methods and adjust for multiple biases using logistic regression. METHODS: Weights were created from selection probabilities and predictive values for exposure classification and applied to multivariable logistic regression models in a case-control study of prepregnancy obesity (body mass index >/=30 vs. <30 kg/m(2)) and cleft lip with or without cleft palate (CL/P) using data from the National Birth Defects Prevention Study (2523 cases, 10,605 controls). RESULTS: Adjusting for confounding by race/ethnicity, prepregnancy obesity, and CL/P were weakly associated (odds ratio [OR]: 1.10; 95% confidence interval: 0.98, 1.23). After weighting the data to account for exposure misclassification, missing exposure data, selection bias, and confounding, multiple bias-adjusted ORs ranged from 0.94 to 1.03 in nonprobabilistic bias analyses and median multiple bias-adjusted ORs ranged from 0.93 to 1.02 in probabilistic analyses. CONCLUSIONS: This approach, adjusting for multiple biases using a logistic regression model, suggested that the observed association between obesity and CL/P could be due to the presence of bias.

      2. Using Medicaid data to characterize persons with intellectual and developmental disabilities in five U.S. StatesExternal
        McDermott S, Royer J, Cope T, Lindgren S, Momany E, Lee JC, McDuffie MJ, Lauer E, Kurtz S, Armour BS.
        Am J Intellect Dev Disabil. 2018 Jul;123(4):371-381.

        This project sought to identify Medicaid members with intellectual and developmental disabilities (IDD) in five states (Delaware, Iowa, Massachusetts, New York, and South Carolina) to develop a cohort for subsequent analyses of medical conditions and service utilization. We estimated that over 300,000 Medicaid members in these states had IDD. All members with diagnostic codes for IDD were identified and the three most frequent diagnoses were unspecified intellectual disability, autism or pervasive developmental disorder, and cerebral palsy. The percentage of Medicaid members with IDD ranged from 2.3% in New York to 4.2% in South Carolina. Identifying and characterizing people with IDD is a first step that could guide public health promotion efforts for this population.

    • Occupational Safety and Health

      1. A model for simulating vibration responses of grinding machine-workpiece-hand-arm systemsExternal
        Dong RG, Welcome DE, Xu X, Chen Q, Lin H, McDowell TW, Wu JZ.
        J Sound Vib. 2018 ;431:276-294.

        The objective of this study was to develop a vibration model of a grinding machine-workpiece-hand-arm system. A lumped-parameter model structure of the system was proposed, and its major parameters were determined using the mechanical impedance measured at the grinding point of a typical workpiece (golf club head) held by two hands and referenced to the vibration transmissibility spectra measured at the wrist and on the upper arm of human subjects. The model reasonably predicted the vibration transmissibility spectra measured on the club head and the driving-point response function when the grinding contact stiffness was below a certain value. This suggests that the model is acceptable not only to enhance the understanding of the system responses, but also to explore some engineering methods for controlling vibration exposures during the grinding process. The identified model parameters reveal that the major resonance of the handheld workpiece depends primarily on its mass and grinding contact stiffness. The feed force applied in the grinding process can substantially affect the grinding contact stiffness; as a result, it can significantly influence the resonance. Vibration-reducing gloves can marginally increase the workpiece resonance, but these gloves can reduce some vibration transmitted to the hand-arm system. This study also clarified an important mechanism for the prediction errors of linear human vibration models, which is useful to further improve human vibration modeling.

      2. Exposures to volatile organic compounds among healthcare workers: Modeling the effects of cleaning tasks and product useExternal
        Su FC, Friesen MC, Stefaniak AB, Henneberger PK, LeBouf RF, Stanton ML, Liang X, Humann M, Virji MA.
        Ann Work Expo Health. 2018 Jun 21.

        Objectives: Use of cleaning and disinfecting products is associated with work-related asthma among healthcare workers, but the specific levels and factors that affect exposures remain unclear. The objective of this study was to evaluate the determinants of selected volatile organic compound (VOC) exposures in healthcare settings. Methods: Personal and mobile-area air measurements (n = 143) from 100 healthcare workers at four hospitals were used to model the determinants of ethanol, acetone, 2-propanol, d-limonene, alpha-pinene, and chloroform exposures. Hierarchical cluster analysis was conducted to partition workers into groups with similar cleaning task/product-use profiles. Linear mixed-effect regression models using log-transformed VOC measurements were applied to evaluate the association of individual VOCs with clusters of task/product use, industrial hygienists’ grouping (IH) of tasks, grouping of product application, chemical ingredients of the cleaning products used, amount of product use, and ventilation. Results: Cluster analysis identified eight task/product-use clusters that were distributed across multiple occupations and hospital units, with the exception of clusters consisting of housekeepers and floor strippers/waxers. Results of the mixed-effect models showed significant associations between selected VOC exposures and several clusters, combinations of IH-generated task groups and chemical ingredients, and product application groups. The patient/personal cleaning task using products containing chlorine was associated with elevated levels of personal chloroform and alpha-pinene exposures. Tasks associated with instrument sterilizing and disinfecting were significantly associated with personal d-limonene and 2-propanol exposures. Surface and floor cleaning and stripping tasks were predominated by housekeepers and floor strippers/waxers, and use of chlorine-, alcohol-, ethanolamine-, and quaternary ammonium compounds-based products was associated with exposures to chloroform, alpha-pinene, acetone, 2-propanol, or d-limonene. Conclusions: Healthcare workers are exposed to a variety of chemicals that vary with tasks and ingredients of products used during cleaning and disinfecting. The combination of product ingredients with cleaning and disinfecting tasks were associated with specific VOCs. Exposure modules for questionnaires used in epidemiologic studies might benefit from seeking information on products used within a task context.

    • Parasitic Diseases

      1. The epidemiology of porcine Taenia solium cysticercosis in communities of the Central Highlands in VietnamExternal
        Ng-Nguyen D, Noh J, Breen K, Stevenson MA, Handali S, Traub RJ.
        Parasit Vectors. 2018 Jun 22;11(1):360.

        BACKGROUND: Taenia solium cysticercosis, recognized as a neglected tropical disease by the WHO, is distributed mostly in developing countries of Latin America, sub-Saharan Africa and Asia. Pigs and humans act as intermediate hosts, acquiring T. solium cysticerci (larval stage) in their tissue, through the ingestion of T. solium eggs shed in the faeces of humans infected with adult tapeworms. The disease has a negative impact on rural economies due to losses in productivity arising from human disease, pork carcass condemnations and loss of market access. The aim of this study was to estimate the prevalence of T. solium cysticercosis in pigs in Dak Lak Province in the Central Highlands of Vietnam and to identify household level characteristics associated with T. solium porcine cysticercosis. METHODS: This was a cross-sectional study of household pigs in three districts of Dak Lak Province. A total of 408 households in six villages in three districts were visited between June and October 2015. A questionnaire was administered to the head of each household, and within each household, serum samples were collected from three pigs. Serum samples were analyzed using the recombinant T24H antigen in enzyme-linked immunoelectrotransfer blot assay and lentil lectin purified glycoprotein in EITB assay. A Bayesian, mixed-effects logistic regression model was developed to identify management factors associated with the probability of a household having at least one cysticercosis-positive pig. RESULTS: The prevalence of porcine T. solium cysticercosis in this study was low at 0.94 [95% confidence interval (CI) 0.51-1.68] cases per 100 pigs at risk, in agreement with other studies conducted throughout Vietnam. Scavenging of food and coprophagy were associated with T. solium cysticercosis [odds ratios 1.98 (95% CrI: 0.55-4.74) and 2.57 (95% CrI: 1.22-4.66), respectively]. CONCLUSIONS: This study proves that the seroprevalence of porcine cysticercosis in Dak Lak Province was as low as that of other studies conducted throughout Vietnam. Scavenging of food and coprophagy are modifiable factors, providing the opportunity to decrease the prevalence of porcine cysticercosis further in the province.

      2. The potential consequences of parasitic infections on a person’s immune responsiveness to unrelated antigens are often conjectured upon in relationship to allergic responses and autoimmune diseases. These considerations sometimes extend to whether parasitic infection of pregnant women can influence the outcomes of responses by their offspring to the immunizations administered during national Expanded Programs of Immunization. To provide additional data to these discussions, we have enrolled 99 close-to-term pregnant women in western Kenya and determined their Schistosoma mansoni and Plasmodium falciparum infection status. At 2 years of age, when the initial immunization schedule was complete, we determined their children’s IgG antibody levels to tetanus toxoid, diphtheria toxoid, and measles nucleoprotein (N-protein) antigens using a multiplex assay. We also monitored antibody responses during the children’s first 2 years of life to P. falciparum MSP119 (PfMSP119), S. mansoni Soluble Egg Antigen (SEA), Ascaris suum hemoglobin (AsHb), and Strongyloides stercoralis (SsNIE). Mothers’ infections with either P. falciparum or S. mansoni had no impact on the level of antibody responses of their offspring or the proportion of offspring that developed protective levels of antibodies to either tetanus or diphtheria antigens at 2 years of age. However, children born of S. mansoni-positive mothers and immunized for measles at 9 months of age had significantly lower levels of anti-measles N-protein antibodies when they were 2 years old (p = 0.007) and a lower proportion of these children (62.5 vs. 90.2%, OR = 0.18, 95% CI = 0.04-0.68, p = 0.011) were considered positive for measles N-protein antibodies. Decreased levels of measles antibodies may render these children more susceptible to measles infection than children whose mothers did not have schistosomiasis. None of the children demonstrated responses to AsHb or SsNIE during the study period. Anti-SEA and anti-PfMSP119 responses suggested that 6 and 70% of the children acquired schistosomes and falciparum malaria, respectively, during the first 2 years of life.

      3. How far are we from reaching universal malaria testing of all fever cases?External
        Plucinski MM, Guilavogui T, Camara A, Ndiop M, Cisse M, Painter J, Thwing J.
        Am J Trop Med Hyg. 2018 Jun 25.

        Universal malaria diagnostic testing of all fever cases is the first step in correct malaria case management. However, monitoring adherence to universal testing is complicated by unreliable recording and reporting of the true number of fever cases. We searched the literature to obtain gold-standard estimates for the proportion of patients attending outpatient clinics in sub-Saharan Africa with malarial and non-malarial febrile illness. To correct for differences in malaria transmission, we calculated the proportion of patients with fever after excluding confirmed malaria cases. Next, we analyzed routine data from Guinea and Senegal to calculate the proportion of outpatients tested after exclusion of confirmed malaria cases from the numerator and denominator. From 12 health facility surveys in sub-Saharan Africa with gold-standard fever screening, the median proportion of febrile illness among outpatients after exclusion of confirmed malaria fevers was 57% (range: 46-80%). Analysis of routine data after exclusion of confirmed malaria cases demonstrated much lower testing proportions of 23% (Guinea) and 13% (Senegal). There was substantial spatial and temporal heterogeneity in this testing proportion, and testing in Senegal was correlated with malaria season. Given the evidence from gold-standard surveys that at least 50% of non-malaria consultations in sub-Saharan Africa are for febrile illness, it appears that a substantial proportion of patients with fever are not tested for malaria in health facilities when considering routine data. Tracking the proportion of patients tested for malaria after exclusion of the confirmed malaria cases could allow programs to make inferences about malaria testing practices using routine data.

    • Reproductive Health

      1. Live birth and multiple birth rates in US in vitro fertilization treatment using donor oocytes: a comparison of single-embryo transfer and double-embryo transferExternal
        Klenov VE, Boulet SL, Mejia RB, Kissin DM, Munch E, Mancuso A, Van Voorhis BJ.
        J Assist Reprod Genet. 2018 Jun 21.

        OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level. RESULTS: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively). CONCLUSIONS: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

    • Statistics as Topic

      1. Strategies for imputing missing covariates in accelerated failure time modelsExternal
        Qi L, Wang YF, Chen R, Siddique J, Robbins J, He Y.
        Stat Med. 2018 Jun 25.

        Missing covariates often occur in biomedical studies with survival outcomes. Multiple imputation via chained equations (MICE) is a semi-parametric and flexible approach that imputes multivariate data by a series of conditional models, one for each incomplete variable. When applying MICE, practitioners tend to specify the conditional models in a simple fashion largely dictated by the software, which could lead to suboptimal results. Practical guidelines for specifying appropriate conditional models in MICE are lacking. Motivated by a study of time to hip fractures in the Women’s Health Initiative Observational Study using accelerated failure time models, we propose and experiment with some rationales leading to appropriate MICE specifications. This strategy starts with specifying a joint model for the variables involved. We first derive the conditional distribution of each variable under the joint model, then approximate these conditional distributions to the extent which can be characterized by commonly used regression models. We propose to fit separate models to impute incomplete variables by the failure status, which is key to generating appropriate MICE specifications for survival outcomes. The proposed strategy can be conveniently implemented with all available imputation software that uses fully conditional specifications. Our simulation results show that some commonly used simple MICE specifications can produce suboptimal results, while those based on the proposed strategy appear to perform well and be robust toward model misspecifications. Hence, we warn against a mechanical use of MICE and suggest careful modeling of the conditional distributions of variables to ensure proper performance.

    • Substance Use and Abuse

      1. Use of price promotions among U.S. adults who use electronic vapor productsExternal
        Ali FR, Xu X, Tynan MA, King BA.
        Am J Prev Med. 2018 Jun 11.

        INTRODUCTION: Sales of electronic vapor products have increased in recent years. This increase in use may be related to manufacturer price promotions. This study assessed the use of price-related promotions among current electronic vapor product users. METHODS: Data from the 2015 and 2016 Summer Styles, an Internet survey of U.S. adults aged >/=18 years, were analyzed in 2017. Current electronic vapor product users (n=300) were those who reported past 30-day electronic vapor product use. Price-related promotion use was defined as reported use of coupons, rebates, discount codes, or other special price-related promotions when purchasing electronic vapor products (e.g., electronic cigarettes [e-cigarettes], electronic hookah [e-hookah], or vape pens). Associations between price-related promotion use and sex, age, race/ethnicity, educational attainment, U.S. region, cigarette smoking status, electronic vapor product use frequency, place electronic vapor products were obtained, and survey year were assessed using multivariable logistic regression. RESULTS: Among current electronic vapor product users, 15.0% reported using price-related promotions. The adjusted odds of using price-related promotions was significantly higher among respondents who obtained electronic vapor products from a gas station, grocery or drug store, or the Internet (AOR=2.65, 95% CI=1.22, 5.74) versus anywhere else (i.e., mall kiosks, vape shop, friends/family) and among those who used electronic vapor products >/=15 days in the past 30 days (AOR=2.57, 95% CI=1.18, 5.56) versus </=14 days. CONCLUSIONS: Nearly one in seven current U.S. adult electronic vapor product users reported using price promotions during 2015-2016, and variations in price promotion use existed by electronic vapor product use frequency and where electronic vapor products were obtained. Continued monitoring of the use of price-related promotions could help inform public health policy, planning, and practice.

      2. Opioids have many beneficial uses in medicine, but, taken inappropriately, they can cause life-threatening health effects. The increasing use of physician-prescribed and illicit opioids, including highly potent fentanyl and its analogs, have contributed to a significant increase in opioid-related drug overdoses in the United States, leading to a public health emergency. There have been a number of reports describing adverse health effects experienced by police officers, fire-fighter emergency medical services providers, and private sector ambulance personnel when responding to drug overdose incidents. Several sets of exposure prevention recommendations for first responders are available from government and the private sector. Understanding the scientific basis for these recommendations, increasing awareness by responders of the potential risks associated with opioid exposure during a response, and educating responders about safe work practices when exposure to opioids is suspected or confirmed are all critical prevention measures that can keep first responders safe.

      3. OBJECTIVE: To assess spatial accessibility measures to on-premise alcohol outlets at census block, census tract, county, and state levels for the United States. METHODS: Using network analysis in a geographic information system, we computed distance-based measures (Euclidean distance, driving distance, and driving time) to on-premise alcohol outlets for the entire U.S. at the census block level. We then calculated spatial access-based measures, specifically a population-weighted spatial accessibility index and population-weighted distances (Euclidean distance, driving distance, and driving time) to alcohol outlets at the census tract, county, and state levels. A multilevel model-based sensitivity analysis was conducted to evaluate the associations between different on-premise alcohol outlet accessibility measures and excessive drinking outcomes. RESULTS: The national average population-weighted driving time to the nearest 7 on-premise alcohol outlets was 5.89 min, and the average population-weighted driving distance was 2.63 miles. At the state level, population-weighted driving times ranged from 1.67 min (DC) to 15.29 min (Arizona). Population-weighted driving distances ranged from 0.67 miles (DC) to 7.91 miles (Arkansas). At the county level, population-weighted driving times and distances exhibited significant geographic variations, and averages for both measures increased by the degree of county rurality. The population-weighted spatial accessibility indexes were highly correlated to respective population-weighted distance measures. Sensitivity analysis demonstrated that population weighted accessibility measures were more sensitive to excessive drinking outcomes than were population weighted distance measures. CONCLUSIONS: These results can be used to assess the relationship between geographic access to on-premise alcohol outlets and health outcomes. This study demonstrates a flexible and robust method that can be applied or modified to quantify spatial accessibility to public resources such as healthy food stores, medical care providers, and parks and greenspaces, as well as, quantify spatial exposure to local adverse environments such as tobacco stores and fast food restaurants.

    • Veterinary Medicine

      1. Canine amoebic meningoencephalitis due to Balamuthia mandrillarisExternal
        Chien RC, Telford CR, Roy S, Ali IK, Shieh WJ, Confer AW.
        Veterinary Parasitology: Regional Studies and Reports. 2018 August;13:156-159.

        A 1-year-old Siberian Husky dog with acute-onset of seizures, recumbency, paddling, and muscular fasciculations was autopsied. A locally extensive hemorrhagic and malacic focus was noted in the right cerebral frontal cortex, and severe necrotizing and hemorrhagic, neutrophilic meningoencephalitis was diagnosed microscopically. Amoebic trophozoites and cysts were identified within the affected cerebral parenchyma and confirmed by indirect immunofluorescence assay and real-time PCR as Balamuthia mandrillaris. B. mandrillaris is found in soil and water and the infection has been reported in both immunocompromised and immunocompetent humans and rarely in the dog.

    • Zoonotic and Vectorborne Diseases

      1. Rabies exposures and pre-exposure vaccination practices among individuals with an increased risk of rabies exposure in the United StatesExternal
        Blanton JD, Colwell E, Walden CL, Davis LM, Hoang C, Legred JA, Pieracci EG, Wallace RM, Ebell MH, Fu ZF, Shwiff SA, Lee JM.
        J Am Vet Med Assoc. 2018 Jun 15;252(12):1491-1502.

        OBJECTIVE To identify knowledge and practices related to rabies vaccination and serologic monitoring among animal care workers in the United States. DESIGN Cross-sectional survey. SAMPLE 2,334 animal care workers (ie, veterinarians, veterinary technicians, animal control workers, and wildlife rehabilitators). PROCEDURES Participants were contacted through relevant professional organizations to participate in an anonymous web-based survey. The survey collected demographic and occupational information, animal handling and potential rabies exposure information, and individual rabies vaccination and serologic monitoring practices. Comparisons of animal bite and rabies exposure rates were made between occupational groups. Multiple logistic regression was used to evaluate factors associated with rabies vaccination status and adherence to serologic monitoring recommendations. RESULTS Respondents reported 0.77 animal bites/person-year or 0.10 bites/1,000 animals handled. The overall rate of postexposure prophylaxis due to an occupational rabies exposure was 1.07/100 person-years. Veterinarians reported the highest rabies vaccination rate (98.7% [367/372]), followed by animal control workers (78.5% [344/438]), wildlife rehabilitators (78.2% [122/156]), and veterinary technicians (69.3% [937/1,352]). Respondents working for employers requiring rabies vaccination and serologic monitoring were 32.16 and 6.14 times, respectively, as likely to be vaccinated or have a current serologic monitoring status as were respondents working for employers without such policies. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, given the high reported rates of animal bites and potential rabies exposures among animal care workers, improvements in rabies vaccination and serologic monitoring practices are needed.

      2. Seroprevalence and risk factors for infection with Bartonella bacilliformis in Loja province, EcuadorExternal
        Lydy SL, Lascano MS, Garcia-Perez JE, Williams-Newkirk AJ, Grijalva MJ.
        Emerg Microbes Infect. 2018 Jun 25;7(1):115.

        The seroprevalence and epidemiology of Bartonella bacilliformis infection in the Andean highlands of Ecuador is largely unknown. We conducted a sero-epidemiologic survey of 319 healthy children aged 1-15 years living in six rural, mountain communities in Loja Province, Ecuador. Blood was collected by finger stick onto filter paper and dried, and the eluted sera analyzed for antibodies to B. bacilliformis by rPap31 ELISA. Demographic, entomologic, and household variables were assessed to investigate associated risk factors for antibody seropositivity to B. bacilliformis. Seroprevalence of 28% was found among children in the study communities. Increased risk of seropositivity was associated with the presence of lumber piles near houses. Decreased risk of seropositivity was observed with the presence of animal waste and incremental 100 meter increases in elevation. Although investigation of clinical cases of Carrion’s disease was not within the scope of this study, our serology data suggest that infection of children with B. bacilliformis is prevalent in this region of Ecuador and is largely unrecognized and undiagnosed. This study highlights the need to further investigate the prevalence, pathogenesis, epidemiology, and disease impact of this pathogen in Ecuador.

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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: January 31, 2019
Content source: Centers for Disease Control and Prevention