Volume 12, Issue, 1 January 14, 2020

CDC Science Clips: Volume 12, Issue 1, January 14, 2020

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016external icon
        Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G.
        JAMA Pediatr. 2019 Dec 2:e194498.
        Importance: Individuals with prediabetes are at increased risk of developing type 2 diabetes, chronic kidney disease, and cardiovascular disease. The incidence and prevalence of type 2 diabetes in the US adolescent population have increased in the last decade. Therefore, it is important to monitor the prevalence of prediabetes and varying levels of glucose tolerance to assess the future risk of type 2 diabetes in the youngest segment of the population. Objective: To examine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased glycated hemoglobin A1c (HbA1c) levels in US adolescents (aged 12-18 years) and young adults (aged 19-34 years) without diabetes. Design, Setting, and Participants: This cross-sectional analyses of the 2005-2016 National Health and Nutrition Examination Survey assessed a population-based sample of adolescents and young adults who were not pregnant, did not have diabetes, and had measured fasting plasma glucose, 2-hour plasma glucose after a 75-g oral glucose tolerance test, and HbA1c levels. Analysis began in April 2017. Main Outcomes and Measures: Impaired fasting glucose was defined as fasting plasma glucose of 100 mg/dL to less than 126 mg/dL, IGT as 2-hour plasma glucose of 140 mg/dL to less than 200 mg/dL, and increased HbA1c level as HbA1c level between 5.7% and 6.4%. The prevalence of IFG, isolated IFG, IGT, isolated IGT, increased HbA1c level, isolated increased HbA1c level, and prediabetes (defined as having IFG, IGT, or increased HbA1c level) were estimated. Fasting insulin levels and cardiometabolic risk factors across glycemic abnormality phenotypes were also compared. Obesity was defined as having age- and sex-specific body mass index (calculated as weight in kilograms divided by height in meters squared) in the 95th percentile or higher in adolescents or 30 or higher in young adults. Results: Of 5786 individuals, 2606 (45%) were adolescents and 3180 (55%) were young adults. Of adolescents, 50.6% (95% CI, 47.6%-53.6%) were boys, and 50.6% (95% CI, 48.8%-52.4%) of young adults were men. Among adolescents, the prevalence of prediabetes was 18.0% (95% CI, 16.0%-20.1%) and among young adults was 24.0% (95% CI, 22.0%-26.1%). Impaired fasting glucose constituted the largest proportion of prediabetes, with prevalence of 11.1% (95% CI, 9.5%-13.0%) in adolescents and 15.8% (95% CI, 14.0%-17.9%) in young adults. In multivariable logistic models including age, sex, race/ethnicity, and body mass index, the predictive marginal prevalence of prediabetes was significantly higher in male than in female individuals (22.5% [95% CI, 19.5%-25.4%] vs 13.4% [95% CI, 10.8%-16.5%] in adolescents and 29.1% [95% CI, 26.4%-32.1%] vs 18.8% [95% CI, 16.5%-21.3%] in young adults). Prediabetes prevalence was significantly higher in individuals with obesity than in those with normal weight (25.7% [95% CI, 20.0%-32.4%] vs 16.4% [95% CI, 14.3%-18.7%] in adolescents and 36.9% [95% CI, 32.9%-41.1%] vs 16.6% [95% CI, 14.2%-19.4%] in young adults). Compared with persons with normal glucose tolerance, adolescents and young adults with prediabetes had significantly higher non-high-density lipoprotein cholesterol levels, systolic blood pressure, central adiposity, and lower insulin sensitivity (P < .05 for all). Conclusions and Relevance: In the United States, about 1 of 5 adolescents and 1 of 4 young adults have prediabetes. The adjusted prevalence of prediabetes is higher in male individuals and in people with obesity. Adolescents and young adults with prediabetes also present an unfavorable cardiometabolic risk profile, putting them both at increased risk of type 2 diabetes and cardiovascular diseases.

    • Communicable Diseases
      • Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA Clinical Practice Guidelineexternal icon
        Nahid P, Mase SR, Migliori GB, Sotgiu G, Bothamley GH, Brozek JL, Cattamanchi A, Cegielski JP, Chen L, Daley CL, Dalton TL, Duarte R, Fregonese F, Horsburgh CR, Ahmad Khan F, Kheir F, Lan Z, Lardizabal A, Lauzardo M, Mangan JM, Marks SM, McKenna L, Menzies D, Mitnick CD, Nilsen DM, Parvez F, Peloquin CA, Raftery A, Schaaf HS, Shah NS, Starke JR, Wilson JW, Wortham JM, Chorba T, Seaworth B.
        Am J Respir Crit Care Med. 2019 Nov 15;200(10):e93-e142.
        Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

      • Changes in HIV antiretroviral prescribing practices in the United Statesexternal icon
        Vu QM, Shouse RL, Brady K, Brooks JT, Weiser J.
        Int J STD AIDS. 2019 Dec 2.

    • Environmental Health
      • Environmental health practice challenges and research needs for U.S. health departmentsexternal icon
        Brooks BW, Gerding JA, Landeen E, Bradley E, Callahan T, Cushing S, Hailu F, Hall N, Hatch T, Jurries S, Kalis MA, Kelly KR, Laco JP, Lemin N, McInnes C, Olsen G, Stratman R, White C, Wille S, Sarisky J.
        Environ Health Perspect. 2019 Dec;127(12):125001.
        BACKGROUND: Environmental health (EH) professionals, one of the largest segments of the public health workforce, are responsible for delivery of essential environmental public health services. The challenges facing these professionals and research needs to improve EH practice are not fully understood, but 26% of EH professionals working in health departments of the United States plan to retire in 5 y, while only 6% of public health students are currently pursuing EH concentrations. OBJECTIVES: A groundbreaking initiative was recently launched to understand EH practice in health departments of the United States. This commentary article aims to identify priority EH practice challenges and related research needs for health departments. METHODS: A horizon scanning approach was conducted in which challenges facing EH professionals were provided by 1,736 respondents working at health departments who responded to a web-based survey fielded in November 2017. Thematic analyses of the responses and determining the frequency at which respondents reported specific issues and opportunities identified primary EH topic areas. These topic areas and related issues informed focus group discussions at an in-person workshop held in Anaheim, California. The purpose of the in-person workshop was to engage each of the topic areas and issues, through facilitated focus groups, leading to the formation of four to five related problem statements for each EH topic. DISCUSSION: EH professionals are strategically positioned to diagnose, intervene, and prevent public health threats. Focus group engagement resulted in 29 priority problem statements partitioned among 6 EH topic areas: a) drinking water quality, b) wastewater management, c) healthy homes, d) food safety, e) vectors and public health pests, and f) emerging issues. This commentary article identifies priority challenges and related research needs to catalyze effective delivery of essential environmental public health services for common EH program areas in health departments. An unprecedented initiative to revitalize EH practice with timely and strategic recommendations for student and professional training, nontraditional partnerships, and basic and translational research activities is recommended.

    • Epidemiology and Surveillance
      • Male mortality trends in the United States, 1900-2010: Progress, challenges, and opportunitiesexternal icon
        Jones WK, Hahn RA, Parrish RG, Teutsch SM, Chang MH.
        Public Health Rep. 2019 Dec 5:33354919893029.
        OBJECTIVES: Male mortality fell substantially during the past century, and major causes of death changed. Building on our recent analysis of female mortality trends in the United States, we examined all-cause and cause-specific mortality trends at each decade from 1900 to 2010 among US males. METHODS: We conducted a descriptive study of age-adjusted death rates (AADRs) for 11 categories of disease and injury stratified by race (white, nonwhite, and, when available, black), the excess of male mortality over female mortality ([male AADR - female AADR]/female AADR), and potential causes of persistent excess of male mortality. We used national mortality data for each decade. RESULTS: From 1900 to 2010, the all-cause AADR declined 66.4% among white males and 74.5% among nonwhite males. Five major causes of death in 1900 were pneumonia and influenza, heart disease, stroke, tuberculosis, and unintentional nonmotor vehicle injuries; in 2010, infectious conditions were replaced by cancers and chronic lower respiratory diseases. The all-cause excess of male mortality rose from 9.1% in 1900 to 65.5% in 1980 among white males and a peak of 63.7% in 1990 among nonwhite males, subsequently falling among all groups. CONCLUSION: During the last century, AADRs among males declined more slowly than among females. Although the gap diminished in recent decades, exploration of social and behavioral factors may inform interventions that could further reduce death rates among males.

    • Health Disparities
    • Healthcare Associated Infections
      • Candida auris: A review of recommendations for detection and control in healthcare settingsexternal icon
        Caceres DH, Forsberg K, Welsh RM, Sexton DJ, Lockhart SR, Jackson BR, Chiller T.
        J Fungi (Basel). 2019 Nov 28;5(4).
        Candida auris is an emerging multidrug-resistant fungal pathogen. Since first reported in 2009, C. auris has caused healthcare outbreaks around the world, often involving high mortality. Identification of C. auris has been a major challenge as many common conventional laboratory methods cannot accurately detect it. Early detection and implementation of infection control practices can prevent its spread. The aim of this review is to describe recommendations for the detection and control of C. auris in healthcare settings.

    • Immunity and Immunization
      • Human papillomavirus vaccine effectiveness against HPV infection: Evaluation of one, two, and three dosesexternal icon
        Markowitz LE, Naleway AL, Klein NP, Lewis RM, Crane B, Querec TD, Hsiao A, Aukes L, Timbol J, Weinmann S, Liu G, Steinau M, Unger ER.
        J Infect Dis. 2019 Nov 30.
        BACKGROUND: Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses. METHODS: We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses. RESULTS: Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at </=18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12). CONCLUSIONS: Among women who received their first dose at age </=18, estimated HPV vaccine effectiveness was high regardless of number of doses.

    • Laboratory Sciences
      • Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humansexternal icon
        Krewski D, Rice JM, Bird M, Milton B, Collins B, Lajoie P, Billard M, Grosse Y, Cogliano VJ, Caldwell JC, Rusyn I, Portier CJ, Melnick RL, Baan RA, Little J, Zielinski JM.
        J Toxicol Environ Health B Crit Rev. 2019 ;22(7-8):203-236.
        Since the inception of the IARC Monographs Programme in the early 1970s, this Programme has developed 119 Monograph Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the Monographs, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with sufficient evidence (82 agents) or limited evidence (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the IARC Monographs, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and gamma-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the IARC Monographs did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for sufficient evidence of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.

    • Maternal and Child Health
      • BACKGROUND: Despite WHO advocating for an integrated approach to antenatal care (ANC), testing coverage for conditions other than HIV remains low and women are referred to distant laboratories for testing. Using point-of-care tests (POCTs) at peripheral dispensaries could improve access to testing and timely treatment. However, the effect of providing additional services on nurse workload and client wait times are unknown. We use discrete-event simulation (DES) modelling to understand the effect of providing four point-of-care tests for ANC on nurse utilization and wait times for women seeking maternal and child health (MCH) services. METHODS: We collected detailed time-motion data over 20 days from one high volume dispensary in western Kenya during the 8-month implementation period (2014-2015) of the intervention. We constructed a simulation model using empirical arrival distributions, activity durations and client pathways of women seeking MCH services. We removed the intervention from the model to obtain wait times, length-of-stay and nurse utilization rates for the baseline scenario where only HIV testing was offered for ANC. Additionally, we modelled a scenario where nurse consultations were set to have minimum durations for sufficient delivery of all WHO-recommended services. RESULTS: A total of 183 women visited the dispensary for MCH services and 14 of these women received point-of-care testing (POCT). The mean difference in total waiting time was 2 min (95%CI: < 1-4 min, p = 0.026) for MCH women when integrated POCT was given, and 9 min (95%CI: 4-14 min, p < 0.001) when integrated POCT with adequate ANC consult times was given compared to the baseline scenario. Mean length-of-stay increased by 2 min (95%CI: < 1-4 min, p = 0.015) with integrated POCT and by 16 min (95%CI: 10-21 min, p < 0.001) with integrated POCT and adequate consult times compared to the baseline scenario. The two nurses' overall daily utilization in the scenario with sufficient minimum consult durations were 72 and 75%. CONCLUSION: The intervention had a modest overall impact on wait times and length-of-stay for women seeking MCH services while ensuring pregnant women received essential diagnostic testing. Nurse utilization rates fluctuated among days: nurses experienced spikes in workload on some days but were under-utilized on the majority of days. Overall, our model suggests there was sufficient time to deliver all WHO's required ANC activities and offer integrated testing for ANC first and re-visits with the current number of healthcare staff. Further investigations on improving healthcare worker, availability, performance and quality of care are needed. Delivering four point-of-care tests together for ANC at dispensary level would be a low burden strategy to improve ANC.

    • Occupational Safety and Health
      • Exposure to hazardous noise is one of the most common occupational risks, both in the U.S. and worldwide. Repeated overexposure to noise at or above 85 dBA can cause permanent hearing loss, tinnitus, and difficulty understanding speech in noise. It is also associated with cardiovascular disease, depression, balance problems, and lower income. About 22 million U.S. workers are currently exposed to hazardous occupational noise. Approximately 33% of working-age adults with a history of occupational noise exposure have audiometric evidence of noise-induced hearing damage, and 16% of noise-exposed workers have material hearing impairment. While the Mining, Construction, and Manufacturing sectors typically have the highest prevalence of noise exposure and hearing loss, there are noise-exposed workers in every sector and every sector has workers with hearing loss. Noise-induced hearing loss is preventable. Increased understanding of the biological processes underlying noise damage may lead to protective pharmacologic or genetic therapies. For now, an integrated public health approach that (1) emphasizes noise control over reliance on hearing protection, (2) illustrates the full impact of hearing loss on quality of life, and (3) challenges the cultural acceptance of loud noise can substantially reduce the impact of noise on worker health.

    • Substance Use and Abuse
      • State policies in the United States impacting drug-related convictions and their consequences in 2015external icon
        Cramer R, Hexem S, Thompson K, LaPollo AB, Chesson HW, Leichliter JS.
        Drug Sci Policy Law. 2019 ;5.
        Background: Criminal justice system involvement has been associated with health issues, including sexually transmitted disease. Both incarceration and sexually transmitted disease share associations with various social conditions, including poverty, stigma, and drug use. Methods: United States state laws (including Washington, D.C.) regarding drug possession and consequences of drug-related criminal convictions were collected and coded. Drug possession policies focused on mandatory sentences for possession of marijuana, crack cocaine and methamphetamines. Consequences of drug-related convictions included ineligibility for public programmes, ineligibility for occupational licences and whether employers may ask prospective employees about criminal history. We analysed correlations between state sexually transmitted disease rates and percentage of a state's population convicted of a felony. Results: First-time possession of marijuana results in mandatory incarceration in one state; first-time possession of crack cocaine or methamphetamines results in mandatory incarceration in 12 (23.5%) states. Many states provide enhanced punishment upon a third possession conviction. A felony drug conviction results in mandatory ineligibility for the Supplemental Nutrition Assistance Program and/or Temporary Assistance for Needy Families in 17 (33.3%) states. Nine (17.6%) states prohibit criminal history questions on job applications. Criminal convictions limit eligibility for various professional licences in all states. State chlamydia, gonorrhoea and syphilis rates were positively associated with the percentage of the state population convicted of a felony (p < 0.05). Conclusion: While associations between crime, poverty, stigma and health have been investigated, our findings could be used to investigate the relationship between the likelihood of criminal justice system interactions, their consequences and public health outcomes including sexually transmitted disease risk.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. BACKGROUND: We recently introduced a system of partial differential equations (PDEs) to model the prevalence of chronic diseases with a possibly prolonged state of asymptomatic, undiagnosed disease preceding a diagnosis. Common examples for such diseases include coronary heart disease, type 2 diabetes or cancer. Widespread application of the new method depends upon mathematical treatment of the system of PDEs. METHODS: In this article, we study the existence and the uniqueness of the solution of the system of PDEs. To demonstrate the usefulness and importance of the system, we model the age-specific prevalence of hypertension in the US 1999-2010. RESULTS: The examinations of mathematical properties provide a way to solve the systems of PDEs by the method of characteristics. In the application to hypertension, we obtain a good agreement between modeled and surveyed age-specific prevalences. CONCLUSIONS: The described system of PDEs provides a practical way to examine the epidemiology of chronic diseases with a state of undiagnosed disease preceding a diagnosis.

      2. Receipt of recommended complications and comorbidities screening in youth and young adults with type 1 diabetes: Associations with metabolic status and satisfaction with careexternal icon
        Malik FS, Stafford JM, Reboussin BA, Klingensmith GJ, Dabelea D, Lawrence JM, Mayer-Davis E, Saydah S, Corathers S, Pihoker C.
        Pediatr Diabetes. 2019 Dec 2.
        OBJECTIVES: This study sought to: 1) Assess the prevalence of diabetes complications and comorbidities screening as recommended by the American Diabetes Association (ADA) for youth and young adults (YYAs) with type 1 diabetes (T1D), 2) Examine the association of previously measured metabolic status related to diabetes complications with receipt of recommended clinical screening, and 3) Examine the association of satisfaction with diabetes care with receipt of recommended clinical screening. METHODS: The study included 2172 SEARCH for Diabetes in Youth participants with T1D (>10 years old, diabetes duration >5 years). Mean participant age was 17.7 +/- 4.3 years with a diabetes duration of 8.1 +/- 1.9 years. Linear and multinomial regression models were used to evaluate associations. RESULTS: Sixty percent of participants reported having 3 or more HbA1c measurements in the past year. In terms of diabetes complications screening, 93% reported having blood pressure measured, 81% having an eye examination, 71% having lipid levels checked, 64% having a foot exam, and 63% completing albuminuria screening in accordance with ADA recommendations. Youth known to have worse glycemic control in the past had higher odds of not meeting HbA1c screening criteria (OR 1.11, 95% CI = 1.05, 1.17); however, after adjusting for race/ethnicity, this was no longer statistically significant. Greater satisfaction with diabetes care was associated with increased odds of meeting screening criteria for most of the ADA-recommended measures. CONCLUSIONS: Efforts should be made to improve diabetes complications screening efforts for YYAs with T1D, particularly for those at higher risk for diabetes complications. This article is protected by copyright. All rights reserved.

      3. Amyotrophic lateral sclerosis (ALS) is a fatal, rare, and hard to diagnose neurological disease with unknown etiology. Objective: To understand the incidence, prevalence, and survival characteristics of ALS cases in the Atlanta metropolitan area. Methods: Neurologists in Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties provided case reports for ALS patients under their care from 1 January 2009 to 31 December 2011. Incidence and prevalence rates were calculated for 2009, 2010, and 2011 by sex, race, and ethnicity. Using data from the National Death Index, survival time was calculated for age, sex, race, ethnicity, and El Escorial criteria. Results: There were 281 unique ALS cases reported, which is approximately 104% of the expected cases. The majority of the 281 cases were white, non-Hispanic, male, and in the 50-59 age category. The overall average incidence rate for 2009 to 2011 was 1.54 per 100,000 person-years, with higher annual incidence rates for whites, males, and non-Hispanics. The prevalence rates for 2009, 2010, and 2011 were 5.05, 5.44, and 5.56 per 100,000, respectively. Median survival time was highest for the 18-39 age group, Asians, non-Hispanics, and males. Additionally, the log-rank tests for homogeneity across strata indicate a statistical significance between strata for the age category for survival time. Conclusion: The findings for Atlanta are similar to other population-based studies in the United States. Although the Atlanta metropolitan area was selected to over-represent the minority population, the strongest predictor of survival time was age at diagnosis.

    • Communicable Diseases
      1. Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV studyexternal icon
        Abreu RM, Bassit LC, Tao S, Jiang Y, Ferreira AS, Hori PC, Ganova-Raeva LM, Khudyakov Y, Schinazi RF, Carrilho FJ, Ono SK.
        Antivir Ther. 2019 Dec 4.
        BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Brazilian CHB patients cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and / or tenofovir disoproxil fumarate was studied in a reference tertiary center. Treatment adherence was evaluated by a validated questionnaire named "Assessment of Adherence to Antiviral Therapy Questionnaire" (CEAT-HBV) within three year-periods (2010/2011, 2013/2014 and 2014/2015). RESULTS: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. Two years after the first assessment, the CEAT-HBV indicated that 71% (101/143) subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. Hepatitis B virus (HBV) booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (p<0.001). CONCLUSIONS: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV DNA negative group.

      2. Spatial distribution and temporal trends of leprosy in Uganda, 2012-2016: a retrospective analysis of public health surveillance dataexternal icon
        Aceng FL, Kawuma HJ, Majwala R, Lamunu M, Ario AR, Rwabinumi FM, Harris JR, Zhu BP.
        BMC Infect Dis. 2019 Nov 29;19(1):1016.
        BACKGROUND: Leprosy is a neglected disease that poses a significant challenge to public health in Uganda. The disease is endemic in Uganda, with 40% of the districts in the country affected in 2016, when 42 out of 112 districts notified the National Tuberculosis and Leprosy Program (NTLP) of at least one case of leprosy. We determined the spatial and temporal trends of leprosy in Uganda during 2012-2016 to inform control measures. METHODS: We analyzed quarterly leprosy case-finding data, reported from districts to the Uganda National Leprosy Surveillance system (managed by NTLP) during 2012-2016. We calculated new case detection by reporting district and administrative regions of treatment during this period. New case detection was defined as new leprosy cases diagnosed by the Uganda health services divided by regional population; population estimates were based on 2014 census data. We used logistic regression analysis in Epi-Info version 7.2.0 to determine temporal trends. Population estimates were based on 2014 census data. We used QGIS software to draw choropleth maps showing leprosy case detection rates, assumed to approximate the new case detection rates, per 100,000 population. RESULTS: During 2012-2016, there was 7% annual decrease in reported leprosy cases in Uganda each year (p = 0.0001), largely driven by declines in the eastern (14%/year, p = 0.0008) and central (11%/year, p = 0.03) regions. Declines in reported cases in the western (9%/year, p = 0.12) and northern (4%/year, p = 0.16) regions were not significant. The combined new case detection rates from 2012 to 2016 for the ten most-affected districts showed that 70% were from the northern region, 20% from the eastern, 10% from the western and 10% from the central regions. CONCLUSION: There was a decreasing trend in leprosy new case detection in Uganda during 2012-2016; however, the declining trends were not consistent in all regions. The Northern region consistently identified more leprosy cases compared to the other regions. We recommend evaluation of the leprosy surveillance system to ascertain the leprosy situation.

      3. Highlights from the 2019 HIV Diagnostics Conference: optimizing testing for HIV, STIs, and hepatitis Cexternal icon
        Chavez PR, Soehnlen M, Van Der Pol B, Gaynor AM, Wesolowski LG, Owen SM.
        Sex Transm Dis. 2019 Dec 3.

      4. HIV-1 genetic diversity to estimate time of infection and infer adherence to preexposure prophylaxisexternal icon
        Council OD, Ruone S, Mock PA, Khalil G, Martin A, Curlin ME, McNicholl JM, Heneine W, Leelawiwat W, Choopanya K, Vanichseni S, Cherdtrakulkiat T, Anekvorapong R, Martin M, Garcia-Lerma JG.
        Aids. 2019 Dec 1;33(15):2299-2307.
        OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three. CONCLUSION: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.

      5. "To me, everybody is infected": Understanding narratives about HIV risk among HIV-negative black men who have sex with men in the Deep Southexternal icon
        Denson DJ, Gelaude D, Saul H, Schoua-Glusberg A, Randall LA, Kenward K, Gall E, Hickson D, Schamel J, Frew PM.
        J Homosex. 2019 Dec 3:1-20.
        For black MSM living in the Deep South, the intersection of sexuality, race, and geography impacts HIV risk substantially. Between July and September 2016, we conducted a qualitative study among HIV-negative black MSM in five southern cities in the US with elevated HIV prevalence. Analysis included assessment of interrater reliability, cluster analysis, and descriptive statistics. We enrolled 99 black MSM (mean age: 33.6; SD = 12.8; range: 17-68 years). Four overarching themes emerged: harboring fear of HIV and the internalization of HIV stigma; scrutinizing potential partners to assess riskiness and HIV status; embracing distance and isolation from those perceived as a threat to HIV status; and exhibiting self-efficacy toward HIV prevention and utilizing risk reduction strategies. Future HIV prevention efforts may benefit by balancing risk and deficit based strategies with those that emphasize resilience, address disenfranchisement via structural interventions, and assess and treat inherent trauma(s).

      6. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortiumexternal icon
        Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG.
        Clin Infect Dis. 2019 Dec 5.
        BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

      7. Gastrointestinal illnesses are the most frequently diagnosed conditions among returning U.S. travelers. Although most episodes of travelers' diarrhea do not require antibiotic therapy, fluoroquinolones (a type of quinolone antibiotic) are recommended for treatment of moderate and severe travelers' diarrhea as well as many other types of severe infection. To assess associations between quinolone susceptibility and international travel, we linked data about isolate susceptibility in NARMS to cases of enteric infections reported to FoodNet. We categorized isolates as quinolone-nonsusceptible (QNS) if they were resistant or had intermediate susceptibility to >/=1 quinolone. Among 1,726 travel-associated infections reported to FoodNet with antimicrobial susceptibility data in NARMS during 2004-2014, 56% of isolates were quinolone-nonsusceptible, of which most (904/960) were Campylobacter. International travel was associated with >10-fold increased odds of infection with quinolone-nonsusceptible bacteria. Most QNS infections were associated with travel to Latin America and the Caribbean (390/743; 52%); however, the greatest risk of QNS infection was associated with travel to Africa (120 per 1,000,000 passenger journeys). Preventing acquisition and onward transmission of antimicrobial-resistant enteric infections among travelers is critical.

      8. Vital Signs: Status of human immunodeficiency virus testing, viral suppression, and HIV preexposure prophylaxis - United States, 2013-2018external icon
        Harris NS, Johnson AS, Huang YA, Kern D, Fulton P, Smith DK, Valleroy LA, Hall HI.
        MMWR Morb Mortal Wkly Rep. 2019 Dec 6;68(48):1117-1123.
        BACKGROUND: Approximately 38,000 new human immunodeficiency virus (HIV) infections occur in the United States each year; these infections can be prevented. A proposed national initiative, Ending the HIV Epidemic: A Plan for America, incorporates three strategies (diagnose, treat, and prevent HIV infection) and seeks to leverage testing, treatment, and preexposure prophylaxis (PrEP) to reduce new HIV infections in the United States by at least 90% by 2030. Targets to reach this goal include that at least 95% of persons with HIV receive a diagnosis, 95% of persons with diagnosed HIV infection have a suppressed viral load, and 50% of those at increased risk for acquiring HIV are prescribed PrEP. Using surveillance, pharmacy, and other data, CDC determined the current status of these three initiative strategies. METHODS: CDC analyzed HIV surveillance data to estimate annual number of new HIV infections (2013-2017); estimate the percentage of infections that were diagnosed (2017); and determine the percentage of persons with diagnosed HIV infection with viral load suppression (2017). CDC analyzed surveillance, pharmacy, and other data to estimate PrEP coverage, reported as a percentage and calculated as the number of persons who were prescribed PrEP divided by the estimated number of persons with indications for PrEP. RESULTS: The number of new HIV infections remained stable from 2013 (38,500) to 2017 (37,500) (p = 0.448). In 2017, an estimated 85.8% of infections were diagnosed. Among 854,206 persons with diagnosed HIV infection in 42 jurisdictions with complete reporting of laboratory data, 62.7% had a suppressed viral load. Among an estimated 1.2 million persons with indications for use of PrEP, 18.1% had been prescribed PrEP in 2018. CONCLUSION: Accelerated efforts to diagnose, treat, and prevent HIV infection are needed to achieve the U.S. goal of at least 90% reduction in the number of new HIV infections by 2030.

      9. A national approach to pediatric sepsis surveillanceexternal icon
        Hsu HE, Abanyie F, Agus MS, Balamuth F, Brady PW, Brilli RJ, Carcillo JA, Dantes R, Epstein L, Fiore AE, Gerber JS, Gokhale RH, Joyner BL, Kissoon N, Klompas M, Lee GM, Macias CG, Puopolo KM, Sulton CD, Weiss SL, Rhee C.
        Pediatrics. 2019 Dec;144(6).
        Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of age-dependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment.

      10. Progress toward measles elimination - China, January 2013-June 2019external icon
        Ma C, Rodewald L, Hao L, Su Q, Zhang Y, Wen N, Fan C, Yang H, Luo H, Wang H, Goodson JL, Yin Z, Feng Z.
        MMWR Morb Mortal Wkly Rep. 2019 Dec 6;68(48):1112-1116.
        In 2005, the World Health Organization (WHO) Western Pacific Region countries, including China, resolved to eliminate measles by 2012 or as soon as feasible thereafter (1). As of 2018, nine* of the 37 Western Pacific Region countries or areas(dagger) had eliminated( section sign) measles. China's Measles Elimination Action Plan 2006-2012 included strengthening routine immunization; conducting measles risk assessments, followed by supplementary immunization activities (SIAs) with measles-containing vaccine (MCV) at national and subnational levels; strengthening surveillance and laboratory capacity; and investigating and responding to measles outbreaks. Most recently, progress toward measles elimination in China was described in a 2014 report documenting measles elimination efforts in China during 2008-2012 and a resurgence in 2013 (2). This report describes progress toward measles elimination in China during January 2013-June 2019.( paragraph sign) Measles incidence per million persons decreased from 20.4 in 2013 to 2.8 in 2018; reported measles-related deaths decreased from 32 in 2015 to one in 2018 and no deaths in 2019 through June. Measles elimination in China can be achieved through strengthening the immunization program's existing strategy by ensuring sufficient vaccine supply; continuing to improve laboratory-supported surveillance, outbreak investigation and response; strengthening school entry vaccination record checks; vaccinating students who do not have documentation of receipt of 2 doses of measles-rubella vaccine; and vaccinating health care professionals and other adults at risk for measles.

      11. Peer support for adolescents and young people living with HIV in sub-Saharan Africa: Emerging insights and a methodological agendaexternal icon
        Mark D, Hrapcak S, Ameyan W, Lovich R, Ronan A, Schmitz K, Hatane L.
        Curr HIV/AIDS Rep. 2019 Nov 27.
        PURPOSE: Despite clear need and disproportionate risk, adolescents, and young people living with HIV (AYPLHIV) are underserved within the HIV response. "Peer support" increasingly forms part of adolescent and youth-responsive service packages as a class of implementation strategies that can support adolescents to access, engage, and sustain treatment. This paper examines examples of peer support for AYPLHIV within sub-saharan Africa to explore the determinants of successful implementation, outcomes and scale-up, as well as policy and programmatic implications. RECENT FINDINGS: Although adolescent peer support has been observed to be widely implemented, there are few examples of detailed program descriptions describing operational logistics or outcomes around peer support interventions. Nevertheless the few examples available provide preliminary support for the potential utility of peer support to improve AYPLHIV outcomes. Implementation science research is an urgent imperative to examine applicability of peer support for this priority population. In the meantime, programs should move forward with implementation based on promising outcomes, programmatic experience, contextual understanding of challenges and gaps, and best practice examples.

      12. Multicountry analysis of spectrum of clinical manifestations of children <5 years of age hospitalized with diarrheaexternal icon
        Murray J, Soenarto SY, Mulyani NS, Wijesinghe PS, Mpabalwani EM, Simwaka JC, Matapo B, Mwenda JM, Sahakyan G, Grigoryan S, Vanyan A, Khactatryan S, Sanwogou J, Helena de Oliveira L, Rey-Benito G, Kang G, Serhan F, Tate JE, Aliabadi N, Cohen AL.
        Emerg Infect Dis. 2019 Dec;25(12):2253-2256.
        After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children <5 years of age. Our study in 33 hospitals in 7 countries found acute gastroenteritis accounted for most (84%) reported hospitalizations of children with diarrhea. Bloody and persistent diarrhea each accounted for <1%.

      13. Progress toward regional measles elimination - worldwide, 2000-2018external icon
        Patel MK, Dumolard L, Nedelec Y, Sodha SV, Steulet C, Gacic-Dobo M, Kretsinger K, McFarland J, Rota PA, Goodson JL.
        MMWR Morb Mortal Wkly Rep. 2019 Dec 6;68(48):1105-1111.
        In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to >/=90% at the national level and to >/=80% in every district, 2) reduce global annual measles incidence to less than five cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan,(dagger) with the objective of eliminating measles( section sign) in five of the six World Health Organization (WHO) regions by 2020. This report updates a previous report (2) and describes progress toward WHA milestones and regional measles elimination during 2000-2018. During 2000-2018, estimated MCV1 coverage increased globally from 72% to 86%; annual reported measles incidence decreased 66%, from 145 to 49 cases per 1 million population; and annual estimated measles deaths decreased 73%, from 535,600 to 142,300. During 2000-2018, measles vaccination averted an estimated 23.2 million deaths. However, the number of measles cases in 2018 increased 167% globally compared with 2016, and estimated global measles mortality has increased since 2017. To continue progress toward the regional measles elimination targets, resource commitments are needed to strengthen routine immunization systems, close historical immunity gaps, and improve surveillance. To achieve measles elimination, all communities and countries need coordinated efforts aiming to reach >/=95% coverage with 2 doses of measles vaccine (3).

      14. Evaluation of rapid syphilis testing using the Syphilis Health Check in Florida, 2015-2016external icon
        Richards J, Matthias J, Baker C, Wilson C, Peterman TA, Brown CP, Dutton M, Dokurugu Y.
        Fla Public Health Rev. 2019 ;16.
        The Syphilis Health Check (SHC) had low estimated specificity (91.5%) in one Florida county. We investigated use of SHC by a range of Florida publicly-funded programs between 2015 and 2016 to estimate specificity, positive predictive value (PPV), field staff acceptance, and impacts on programmatic outcomes. All reported SHC results were extracted from routinely collected program data. Field staff were surveyed about SHC's utility. Analyses investigated differences between SHC and traditional syphilis testing outcomes. Of 3,630 SHC results reported, 442 were reactive; 92 (20.8%) had prior diagnoses of syphilis; 7 (1.6%) had no further testing. Of the remaining 343; 158 (46.0%) were confirmed cases, 168 (49.0%) were considered false-positive, and 17 (5.0%) were not cases but not clearly false-positive. Estimated specificity of SHC was 95.0%. Overall, 48.5% of positives became confirmed cases (PPV). PPV varied according to prevalence of syphilis in populations tested. Staff (90%) thought SHC helped identify new cases but expressed concern regarding discordance between reactive SHC and lab-based testing. Programmatic outcomes assessment showed shorter time to treatment and increased numbers of partners tested for the SHC group; these enhanced outcomes may better mitigate the spread of syphilis compared to traditional syphilis testing alone, but more research is needed.

      15. High prevalence of HIV, HBsAg and anti-HCV positivity among people who injected drugs: results of the first bio-behavioral survey using respondent-driven sampling in two urban areas in Mozambiqueexternal icon
        Sema Baltazar C, Horth R, Boothe M, Sathane I, Young P, Chitsondzo Langa D, Condula M, Ricardo H, Dengo Baloi L, Cummings B, Schaad N, Gouveia L, Teodoro E, Raymond HF.
        BMC Infect Dis. 2019 Dec 2;19(1):1022.
        BACKGROUND: Few countries in sub-Saharan Africa know the magnitude of their HIV epidemic among people who inject drugs (PWID). This was the first study in Mozambique to measure prevalence of HIV, HBV, and HCV, and to assess demographic characteristics and risk behaviors in this key population. METHODS: We used respondent-driven sampling (RDS) to conduct a cross-sectional behavioral surveillance survey of PWID in two cities of Mozambique lasting six months. Participants were persons who had ever injected drugs without a prescription. Participants completed a behavioral questionnaire and provided blood specimens for HIV, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We performed RDS-adjusted analysis in R 3.2 using RDSAT 7.1 weights. RESULTS: We enrolled 353 PWID in Maputo and 139 in Nampula/Nacala; approximately 95% of participants were men. Disease prevalence in Maputo and Nampula/Nacala, respectively, was 50.1 and 19.9% for HIV, 32.1 and 36.4% for HBsAg positivity, and 44.6 and 7.0% for anti-HCV positivity. Additionally, 8% (Maputo) and 28.6% (Nampula/Nacala) of PWID reported having a genital sore or ulcer in the 12 months preceding the survey. Among PWID who injected drugs in the last month, 50.3% (Maputo) and 49.6% (Nampula/Nacala) shared a needle at least once that month. Condomless sex in the last 12 months was reported by 52.4% of PWID in Maputo and 29.1% in Nampula/Nacala. Among PWID, 31.6% (Maputo) and 41.0% (Nampula/Nacala) had never tested for HIV. In multivariable analysis, PWID who used heroin had 4.3 (Maputo; 95% confidence interval [CI]: 1.2, 18.2) and 2.3 (Nampula/Nacala; 95% CI: 1.2, 4.9) greater odds of having HIV. CONCLUSION: Unsafe sexual behaviors and injection practices are frequent among PWID in Mozambique, and likely contribute to the disproportionate burden of disease we found. Intensified efforts in prevention, care, and treatment specific for PWID have the potential to limit disease transmission.

      16. Use of viral load to improve survey estimates of known HIV-positive status and antiretroviral treatment coverageexternal icon
        Young PW, Zielinski-Gutierrez E, Wamicwe J, Mukui I, Kim AA, Waruru A, Zeh C, Kretzschmar ME, De Cock KM.
        Aids. 2019 Dec 2.
        OBJECTIVE: To compare alternative methods of adjusting self-reported knowledge of HIV-positive status and antiretroviral (ARV) therapy use based on undetectable viral load (UVL) and ARV detection in blood. DESIGN: Post hoc analysis of nationally representative household survey to compare alternative biomarker-based adjustments to population HIV indicators. METHODS: We reclassified HIV-positive participants aged 15-64 years in the 2012 Kenya AIDS Indicator Survey (KAIS) that were unaware of their HIV-positive status by self-report as aware and on antiretroviral treatment if either ARVs were detected or viral load was undetectable (<550 copies/ml) on dried blood spots. We compared self-report to adjustments for ARV measurement, UVL, or both. RESULTS: Treatment coverage among all HIV-positive respondents increased from 31.8% for self-report to 42.5% [95% confidence interval (CI) 37.4-47.8] based on ARV detection alone, to 42.8% (95% CI 37.9-47.8) when ARV-adjusted, 46.2% (95% CI 41.3-51.1) when UVL-adjusted and 48.8% (95% CI 43.9-53.8) when adjusted for either ARV or UVL. Awareness of positive status increased from 46.9% for self-report to 56.2% (95% CI 50.7-61.6) when ARV-adjusted, 57.5% (95% CI 51.9-63.0) when UVL-adjusted, and 59.8% (95% CI 54.2-65.1) when adjusted for either ARV or UVL. CONCLUSION: Undetectable viral load, which is routinely measured in surveys, may be a useful adjunct or alternative to ARV detection for adjusting survey estimates of knowledge of HIV status and antiretroviral treatment coverage.

      17. Correlates of HIV-infection among men who have sex with men: results from a community-based, cross-sectional study in Tianjin, Chinaexternal icon
        Yu M, Xu J, Jiang G, Li Z, Song W, Gong H, Ning T, Zheng M, Li L, Gao Y, Yang J, Fleming PJ, King EJ.
        AIDS Care. 2019 Dec;31(12):1574-1579.
        China has 747,000 confirmed HIV/AIDS cases and sexual transmission between men who have sex with men (MSM) is the most prevalent mode of transmission. Our study aims to (a) examine HIV prevalence and behavioral risk factors for HIV infection among 1900 MSM recruited from a community-based organization in Tianjin, China, and (b) describe HIV treatment outcomes for those diagnosed with HIV. We used multivariable logistic regression to identify which socio-demographics and behaviors were associated with HIV infection. The overall HIV prevalence was 3.95%. Key behavioral risk factors included: receptive sex role, older age at first sex with man, condomless anal sex, and having used 2+ drugs. Of those living with HIV, 83% were successfully enrolled in antiretroviral therapy and those enrolled were all virally suppressed after one year. These findings highlight key behavioral risk factors for HIV infection in Tianjin, China and can inform interventions to preventing further HIV transmission.

    • Disaster Control and Emergency Services
      1. In spring 2011, the Centers for Disease Control and Prevention (CDC) released Public Health Preparedness Capabilities: National Standards for State and Local Planning. The capability standards provide a framework that supports state, local, tribal, and territorial public health agency preparedness planning and response to public health threats and emergencies. In 2017, a project team at the CDC Division of State and Local Readiness incorporated input from subject matter experts, national partners, and stakeholders to update the 2011 capability standards. As a result, CDC released the updated capability standards in October 2018, which were amended in January 2019. The original structure of the 15 capability standards remained unchanged, but updates were made to capability functions, tasks, and resource elements to reflect advances in public health emergency preparedness and response practices since 2011. When the number of functions and tasks in the 2018 capability standards were compared to those in the 2011 capabilities, only 20% (3/15) of the capabilities had a decrease in function number. The majority of changes were at the task level (task numbers changed in 80%, or 12/15, capabilities) in the 2018 version. The capability standards provide public health agencies with a practical framework, informed by updated science and tools, which can guide prioritization of limited resources to strengthen public health agency emergency preparedness and response capacities.

    • Disease Reservoirs and Vectors
      1. Determining the post-elimination level of vaccination needed to prevent re-establishment of dog rabiesexternal icon
        Jeon S, Cleaton J, Meltzer MI, Kahn EB, Pieracci EG, Blanton JD, Wallace R.
        PLoS Negl Trop Dis. 2019 Dec 2;13(12):e0007869.
        BACKGROUND: Once a canine rabies-free status has been achieved, there is little guidance available on vaccination standards to maintain that status. In areas with risk of reintroduction, it may be practical to continue vaccinating portions of susceptible dogs to prevent re-establishment of canine rabies. METHODS: We used a modified version of RabiesEcon, a deterministic mathematical model, to evaluate the potential impacts and cost-effectiveness of preventing the reintroduction of canine rabies through proactive dog vaccination. We analyzed four scenarios to simulate varying risk levels involving the reintroduction of canine rabies into an area where it is no longer present. In a sensitivity analysis, we examined the influences of reintroduction frequency and intensity, the density of susceptible dog population, dog birth rate, dog life expectancy, vaccine efficacy, rate of loss of vaccine immunity, and the basic reproduction number (R0). RESULTS: To prevent the re-establishment of canine rabies, it is necessary to vaccinate 38% to 56% of free-roaming dogs that have no immunity to rabies. These coverage levels were most sensitive to adjustments in R0 followed by the vaccine efficacy and the rate of loss of vaccine immunity. Among the various preventive vaccination strategies, it was most cost-effective to continue dog vaccination at the minimum coverage required, with the average cost per human death averted ranging from $257 to $398 USD. CONCLUSIONS: Without strong surveillance systems, rabies-free countries are vulnerable to becoming endemic when incursions happen. To prevent this, it may be necessary to vaccinate at least 38% to 56% of the susceptible dog population depending on the risk of reintroduction and transmission dynamics.

      2. Molecular confirmation of Rickettsia parkeri in Amblyomma ovale Ticks, Veracruz, Mexicoexternal icon
        Sanchez-Montes S, Ballados-Gonzalez GG, Hernandez-Velasco A, Zazueta-Islas HM, Solis-Cortes M, Miranda-Ortiz H, Canseco-Mendez JC, Fernandez-Figueroa EA, Colunga-Salas P, Lopez-Perez AM, Delgado-de la Mora J, Licona-Enriquez JD, Delgado-de la Mora D, Karpathy SE, Paddock CD, Rangel-Escareno C.
        Emerg Infect Dis. 2019 Dec;25(12):2315-2317.
        We found Rickettsia parkeri in Amblyomma ovale ticks collected in Veracruz, Mexico, in 2018. We sequenced gene segments of gltA, htrA, sca0, and sca5; phylogenetic reconstruction revealed near-complete identity with R. parkeri strain Atlantic Rainforest. Enhanced surveillance is needed in Mexico to determine the public health relevance of this bacterium.

    • Environmental Health
      1. Many local health departments (LHDs) across the country coordinate with their service areas on environmental health or land reuse. The Brownfields & Reuse Opportunity Working Group (BROWN) is a multipartner land reuse stakeholder network that includes member representatives from state and local health agencies, federal agencies, environmental consultants, environmental health professionals, and academia. In 2015, BROWN provided input on five Environmental Health Resources Self Learning Modules (Epidemiology, Risk Assessment, Risk Communications, Land Reuse Sites, and Toxicology) that the Agency for Toxic Substances and Disease Registry (ATSDR) was developing. ATSDR created the educational modules as resources and self-study guides to increase LHD capacity to respond to environmental issues. Following input from BROWN members on the modules, the National Environmental Health Association independently developed a short survey to identify baseline capacity of environmental professionals, primarily LHD professionals, to address environmental health and land reuse issues. The survey results of 93 LHD personnel indicated variation in the level of education among LHD employees and how often specific environmental health and land reuse services were requested. A subset of three LHD respondents also provided input into the learning modules.

      2. Field sampling of indoor bioaerosolsexternal icon
        Cox J, Mbareche H, Lindsley WG, Duchaine C.
        Aerosol Sci Technol. 2019 ;2019.
        Because bioaerosols are related to adverse health effects in exposed humans and indoor environments represent a unique framework of exposure, concerns about indoor bioaerosols have risen over recent years. One of the major issues in indoor bioaerosol research is the lack of standardization in the methodology, from air sampling strategies and sample treatment to the analytical methods applied. The main characteristics to consider in the choice of indoor sampling methods for bioaerosols are the sampler performance, the representativeness of the sampling, and the concordance with the analytical methods to be used. The selection of bioaerosol collection methods is directly dependent on the analytical methods, which are chosen to answer specific questions raised while designing a study for exposure assessment. In this review, the authors present current practices in the analytical methods and the sampling strategies, with specificity for each type of microbe (fungi, bacteria, archaea and viruses). In addition, common problems and errors to be avoided are discussed. Based on this work, recommendations are made for future efforts towards the development of viable bioaerosol samplers, standards for bioaerosol exposure limits, and making association studies to optimize the use of the big data provided by high-throughput sequencing methods.

      3. A fresh look at stress and resilience in communities affected by environmental contaminationexternal icon
        Gerhardstein B, Tucker PG, Rayman J, Reh CM.
        J Environ Health. 2019 Nov;82(4):36-38.

      4. Choose safe places for early care and education: Building state programsexternal icon
        Wendel AM, Somers TS, Freed J, Hall E.
        J Environ Health. 2019 Oct;82(3):40-42.

    • Health Disparities
      1. New research directions on disparities in obesity and type 2 diabetesexternal icon
        Thornton PL, Kumanyika SK, Gregg EW, Araneta MR, Baskin ML, Chin MH, Crespo CJ, de Groot M, Garcia DO, Haire-Joshu D, Heisler M, Hill-Briggs F, Ladapo JA, Lindberg NM, Manson SM, Marrero DG, Peek ME, Shields AE, Tate DF, Mangione CM.
        Ann N Y Acad Sci. 2019 Dec 3.
        Obesity and type 2 diabetes disproportionately impact U.S. racial and ethnic minority communities and low-income populations. Improvements in implementing efficacious interventions to reduce the incidence of type 2 diabetes are underway (i.e., the National Diabetes Prevention Program), but challenges in effectively scaling-up successful interventions and reaching at-risk populations remain. In October 2017, the National Institutes of Health convened a workshop to understand how to (1) address socioeconomic and other environmental conditions that perpetuate disparities in the burden of obesity and type 2 diabetes; (2) design effective prevention and treatment strategies that are accessible, feasible, culturally relevant, and acceptable to diverse population groups; and (3) achieve sustainable health improvement approaches in communities with the greatest burden of these diseases. Common features of guiding frameworks to understand and address disparities and promote health equity were described. Promising research directions were identified in numerous areas, including study design, methodology, and core metrics; program implementation and scalability; the integration of medical care and social services; strategies to enhance patient empowerment; and understanding and addressing the impact of psychosocial stress on disease onset and progression in addition to factors that support resiliency and health.

    • Health Economics
      1. Cost-effectiveness of a school-based chlamydia screening program, Duval County, FLexternal icon
        Wang LY, Owusu-Edusei K, Parker JT, Wilson K.
        J Sch Nurs. 2019 Dec 1:1059840519890026.
        During the 2015-2016 school year, the Florida Department of Health in Duval County hosted Teen Health Centers (TeenHC) at five high schools of Jacksonville providing HIV/STD screening and pregnancy testing. The purpose of this study was to assess the cost-effectiveness of the TeenHC chlamydia screening program and determine at what student participation level, the program can be cost-effective. We assessed the costs and effectiveness of the chlamydia screening program compared with "no TeenHC". Cost-effectiveness was measured as cost per quality-adjusted life years (QALY) gained. At a program cost of US$61,001 and 3% participation rate, the cost/QALY gained was $124,328 in the base-case analysis and $81,014-$264,271 in 95% of the simulation trials, all greater than the frequently citied $50,000/QALY benchmark. The cost/QALY gained could be <$50,000/QALY if student participation rate was >7%. The TeenHC chlamydia screening has the potential to be cost-effective. Future program efforts should focus on improving student participation.

    • Healthcare Associated Infections

    • Immunity and Immunization
      1. Barriers to healthcare workers reporting adverse events following immunization in four regions of Ghanaexternal icon
        Gidudu JF, Shaum A, Dodoo A, Bosomprah S, Bonsu G, Amponsa-Achiano K, Darko DM, Sabblah G, Opare J, Nyaku M, Owusu-Boakye B, Oduro A, Aborigo R, Conklin L, Welaga P, Ampadu HH.
        Vaccine. 2019 Nov 29.
        Despite didactic training on adverse events following immunization (AEFI) in Ghana, the reporting ratio of AEFI was 1.56 per 100,000 surviving infants in 2015, below the minimum reporting ratio of 10. We aimed to estimate the proportion of health care workers (HCWs) reporting AEFI and to identify barriers to reporting. We conducted a cross-sectional survey of HCWs in four regions in Ghana. A simple random sample of 176 health facilities was selected and up to two HCWs were randomly selected per facility. We used the Rao-Scott Chi-squared test to compare factors associated with reporting of AEFI in the last year. We used an open-ended question to identify reasons for low reporting. One supervisor from each facility, responsible for overall reporting and management of AEFI, was also interviewed. A total of 306 HCWs from 169 facilities were interviewed. Of these, 176 (57.5%) reported they had ever encountered an AEFI. Of the 120 who had encountered an AEFI in the last year, 66 (55.0%) indicated they had reported the AEFI, and 38 (31.7%) completed a reporting form. HCWs (n=120) reported multiple barriers to reporting of AEFI; the most common barriers were fear of personal consequences (44.1%), lack of knowledge or training (25.2%), and not believing an AEFI was serious enough to report (22.2%). Discussion of AEFI during the last supervisory visit was significantly associated with reporting in the past year (OR 7.39; p<.001). Of 172 supervisors interviewed, 65 (37.8%) mentioned their facilties had ever encountered an AEFI; over 90% of facilities had reporting forms. We identified low reporting of AEFI and multiple barriers to reporting among HCWs in the four selected regions of Ghana. Discussing AEFI during supervisory visits with HCWs might improve reporting. Additionally, strategies to address fear of personal consequences as a barrier to reporting of AEFI are needed.

      2. Vaccine Oka varicella meningitis in two adolescentsexternal icon
        Harrington WE, Mato S, Burroughs L, Carpenter PA, Gershon A, Schmid DS, Englund JA.
        Pediatrics. 2019 Dec;144(6).
        The live-attenuated varicella vaccine, a routine immunization in the United States since 1995, is both safe and effective. Like wild-type varicella-zoster virus, however, vaccine Oka (vOka) varicella can establish latency and reactivate as herpes zoster, rarely leading to serious disease, particularly among immunocompromised hosts. Previous cases of reactivated vOka resulting in meningitis have been described in young children who received a single dose of varicella vaccine; less is known about vOka reactivation in older children after the 2-dose vaccine series. We present 2 adolescents with reactivated vOka meningitis, 1 immunocompetent and 1 immunocompromised, both of whom received 2 doses of varicella vaccine many years before as children. Pediatricians should be aware of the potential of vOka varicella to reactivate and cause clinically significant central nervous system disease in vaccinated children and adolescents.

      3. BACKGROUND: Vaccines administered into or too close to underlying joint structures have the potential to cause shoulder injuries. Limited data exist on the epidemiology of such events. OBJECTIVE: To describe case reports of atypical shoulder pain and dysfunction following injection of inactivated influenza vaccine (IIV). METHODS: We searched the Vaccine Adverse Event Reporting System (VAERS) database from July 2010 to June 2017 for reports of atypical shoulder pain and dysfunction following IIV. When identifying reports, we made no assumptions about true incident injury or causality with respect to vaccination. Pain had to begin <48 h after vaccination and signs and symptoms had to continue for >7 days to differentiate from self-limited local reactions. We conducted descriptive analysis. RESULTS: We identified 1220 reports that met our case definition (2.0% of all IIV reports, range 1.5%-2.5% across influenza seasons). Median age was 52 years (range 16-94) and most patients (82.6%) were female. Shoulder pain (44.1%), injected limb mobility decreased (40.8%), joint range of motion decreased (21.2%), rotator cuff syndrome (9.2%), and bursitis (9.0%) were frequently reported. In 86.6% of reports, signs and symptoms had not resolved by the time of report submission. In reports that included descriptions suggesting contributing factors (n = 266), vaccination given "too high" on the arm was cited in 81.2%. Nearly half (n = 605, 49.6%) of reports described a healthcare provider evaluation. Treatments included non-narcotic analgesics, physical therapy, and corticosteroid injection. Vaccinations were most commonly administered in a pharmacy or retail store (41.0%) or doctor's office or hospital (31.6%). CONCLUSIONS: Reports of atypical shoulder pain and dysfunction following IIV were uncommon, considering the amount of IIV use, and stable across influenza seasons. While specific etiology of cases is unknown, improperly administered vaccine, which is preventable, might be a factor. Prevention strategies include education, training, and adherence to best practices for vaccine administration.

      4. Serological response to influenza vaccination among adults hospitalized with community-acquired pneumoniaexternal icon
        Pratt CQ, Zhu Y, Grijalva CG, Wunderink RG, Mark Courtney D, Waterer G, Levine MZ, Jefferson S, Self WH, Williams DJ, Finelli L, Bramley AM, Edwards KM, Jain S, Anderson EJ.
        Influenza Other Respir Viruses. 2019 Mar;13(2):208-212.
        Ninety-five adults enrolled in the Etiology of Pneumonia in the Community study with negative admission influenza polymerase chain reaction (PCR) tests received influenza vaccination during hospitalization. Acute and convalescent influenza serology was performed. After vaccination, seropositive (>/=1:40) hemagglutination antibody titers (HAI) were achieved in 55% to influenza A(H1N1)pdm09, 58% to influenza A(H3N2), 77% to influenza B (Victoria), and 74% to influenza B (Yamagata) viruses. Sixty-six (69%) patients seroconverted (>/=4-fold HAI rise) to >/=1 strain. Failure to seroconvert was associated with diabetes, bacterial detection, baseline seropositive titers for influenza B (Yamagata), and influenza vaccination in the previous season.

      5. A community-based survey on influenza and vaccination knowledge, perceptions and practices in Peruexternal icon
        Reinders S, Romero C, Carcamo C, Tinoco Y, Valderrama M, La Rosa S, Mallma P, Neyra J, Soto G, Azziz-Baumgartner E, Garcia PJ.
        Vaccine. 2019 Nov 28.
        BACKGROUND: Although Peru provides safe and effective influenza vaccines free-of-charge, coverage among vaccine target groups like pregnant women and older adults remains low. To improve risk communication messages and vaccine uptake, we explored knowledge, perceptions and practices about influenza illness and vaccination. METHODS: A cross-sectional, community-based survey with a three-stage cluster sampling design was conducted in three cities in Peru. We included mothers of young children, pregnant women and persons >/=65 years. Participants completed a questionnaire about knowledge, perceptions and practices about influenza illness and vaccination against influenza during the past year. Generalized linear models were used to explore factors associated with vaccination in the past year. RESULTS: 624/645 (97%) mothers, 54/55 (98%) pregnant women and 622/673 (92%) older adults approached provided informed consent and were surveyed. While most mothers, pregnant women and older adults (94%, 96% and 91%, respectively) perceived influenza as a potentially serious illness, few pregnant women (13%) and older adults (34%) self-identified themselves as a target group for influenza vaccination. Only 28% of mothers, 19% pregnant women, and 27% older adults were vaccinated against influenza during the previous year. Among the participants that did not get vaccinated against influenza in the previous year, "being afraid of vaccination and its effects" was the most commonly cited barrier. Knowledge of the recommendation for annual vaccination was significantly associated with vaccination status among pregnant women (p = 0.048) and older adults (p = 0.004). CONCLUSION: Despite a government subsidized vaccine program, vaccine utilization remained low among pregnant women and older adults, who seemed typically unaware of their status as high-risk groups targeted for vaccination. Those aware of the recommendations for annual vaccination were more likely to be vaccinated. Information campaigns addressing fears and highlighting populations at risk for severe influenza illness that are targeted for vaccination might increase vaccine coverage in Peru.

      6. The use of natural language processing to identify vaccine-related anaphylaxis at five health care systems in the vaccine safety Datalinkexternal icon
        Yu W, Zheng C, Xie F, Chen W, Mercado C, Sy LS, Qian L, Glenn S, Tseng HF, Lee G, Duffy J, McNeil MM, Daley MF, Crane B, McLean HQ, Jackson LA, Jacobsen SJ.
        Pharmacoepidemiol Drug Saf. 2019 Dec 3.
        PURPOSE: The objective was to develop a natural language processing (NLP) algorithm to identify vaccine-related anaphylaxis from plain-text clinical notes, and to implement the algorithm at five health care systems in the Vaccine Safety Datalink. METHODS: The NLP algorithm was developed using an internal NLP tool and training dataset of 311 potential anaphylaxis cases from Kaiser Permanente Southern California (KPSC). We applied the algorithm to the notes of another 731 potential cases (423 from KPSC; 308 from other sites) with relevant codes (ICD-9-CM diagnosis codes for anaphylaxis, vaccine adverse reactions, and allergic reactions; Healthcare Common Procedure Coding System codes for epinephrine administration). NLP results were compared against a reference standard of chart reviewed and adjudicated cases. The algorithm was then separately applied to the notes of 6 427 359 KPSC vaccination visits (9 402 194 vaccine doses) without relevant codes. RESULTS: At KPSC, NLP identified 12 of 16 true vaccine-related cases and achieved a sensitivity of 75.0%, specificity of 98.5%, positive predictive value (PPV) of 66.7%, and negative predictive value of 99.0% when applied to notes of patients with relevant diagnosis codes. NLP did not identify the five true cases at other sites. When NLP was applied to the notes of KPSC patients without relevant codes, it captured eight additional true cases confirmed by chart review and adjudication. CONCLUSIONS: The current study demonstrated the potential to apply rule-based NLP algorithms to clinical notes to identify anaphylaxis cases. Increasing the size of training data, including clinical notes from all participating study sites in the training data, and preprocessing the clinical notes to handle special characters could improve the performance of the NLP algorithms. We recommend adding an NLP process followed by manual chart review in future vaccine safety studies to improve sensitivity and efficiency.

    • Laboratory Sciences
      1. Generalizability of clinically measured acoustic reflexes to brief soundsexternal icon
        Deiters KK, Flamme GA, Tasko SM, Murphy WJ, Greene NT, Jones HG, Ahroon WA.
        J Acoust Soc Am. 2019 Nov;146(5):3993.
        Middle ear muscle contractions (MEMC) can be elicited in response to high-level sounds, and have been used clinically as acoustic reflexes (ARs) during evaluations of auditory system integrity. The results of clinical AR evaluations do not necessarily generalize to different signal types or durations. The purpose of this study was to evaluate the likelihood of observing MEMC in response to brief sound stimuli (tones, recorded gunshots, noise) in adult participants (N = 190) exhibiting clinical ARs and excellent hearing sensitivity. Results revealed that the presence of clinical ARs was not a sufficient indication that listeners will also exhibit MEMC for brief sounds. Detection rates varied across stimulus types between approximately 20% and 80%. Probabilities of observing MEMC also differed by clinical AR magnitude and latency, and declined over the period of minutes during the course of the MEMC measurement series. These results provide no support for the inclusion of MEMC as a protective factor in damage-risk criteria for impulsive noises, and the limited predictability of whether a given individual will exhibit MEMC in response to a brief sound indicates a need to measure and control for MEMC in studies evaluating pharmaceutical interventions for hearing loss.

      2. Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates: In situ analyses of epithelial and immune cell markers in rectal mucosaexternal icon
        Gunaydin G, Edfeldt G, Garber DA, Asghar M, Noel-Romas L, Burgener A, Wahlby C, Wang L, Rohan LC, Guenthner P, Mitchell J, Matoba N, McNicholl JM, Palmer KE, Tjernlund A, Broliden K.
        Sci Rep. 2019 Dec 2;9(1):18120.
        Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin(+) cells, CD4(+) cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin(+) cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4(+) cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4(+) cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4(+) lamina propria cells (placebo: median 30%; 0.1-1% Q-GRFT: median 36-39%). The resting time between sampling points were further associated with minor changes in the total and CD4(+) rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

      3. The genus Phlebovirus is a diverse group of globally occurring viruses, including tick-, mosquito-, and sand fly-borne pathogens. Phleboviruses have historically been classified by serological methods. However, molecular methods alone have been used to identify emergent novel and related strains in recent years. This makes reconciling the classification of historically and newly characterized viruses challenging. To address this in part, we describe the characterization of the genomes of the Frijoles and Chilibre species complex phleboviruses, and three unclassified phleboviruses isolated in the Americas: Caimito, Itaporanga, and Rio Grande viruses that had previously only been described at the serological level. With the exception of Itaporanga virus, the phleboviruses sequenced in this study are phylogenetically related to the current species Frijoles phlebovirus, Bujaru phlebovirus, or the Chagres antigenic complex. Unexpectedly, molecular and phylogenetic analysis suggests Chilibre and Caimito viruses are taxonomically related to the family Peribunyaviridae. These viruses have a genomic architecture similar to peribunyaviruses and form monophyletic groups within the genus Pacuvirus. Our data highlight the importance of reconciling serological and molecular taxonomic classification. In addition, we suggest the taxonomy of Chilibre and Caimito viruses should be revised.

      4. A mosaic tetracycline resistance gene tet(S/M) detected in an MDR pneumococcal CC230 lineage that underwent capsular switching in South Africaexternal icon
        Lo SW, Gladstone RA, van Tonder AJ, Du Plessis M, Cornick JE, Hawkins PA, Madhi SA, Nzenze SA, Kandasamy R, Ravikumar KL, Elmdaghri N, Kwambana-Adams B, Almeida SC, Skoczynska A, Egorova E, Titov L, Saha SK, Paragi M, Everett DB, Antonio M, Klugman KP, Li Y, Metcalf BJ, Beall B, McGee L, Breiman RF, Bentley SD, von Gottberg A.
        J Antimicrob Chemother. 2019 Dec 2.
        OBJECTIVES: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions. METHODS: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model. RESULTS: We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of approximately 2.5. R declined to approximately 1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage. CONCLUSIONS: The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.

      5. Room acoustic modeling and auralization at an indoor firing rangeexternal icon
        Murphy WJ, Xiang N.
        J Acoust Soc Am. 2019 Nov;146(5):3868.
        Reverberation time measurements were conducted in the 21-lane indoor firing range at Wright Patterson Air Force Base. Long reverberation times resulted in poor speech transmission indices (STI) which required acoustical treatments within the range. After treatment, reverberation times were significantly reduced and STI was dramatically enhanced. Standard Sabine and Eyring models failed to accurately predict the reverberation times. A computer simulation of the range was developed to predict room acoustic conditions and auralize speech performance for perceptual evaluation in the range.

      6. Rousette bat dendritic cells overcome Marburg virus-mediated antiviral responses by upregulation of interferon-related genes while downregulating proinflammatory disease mediatorsexternal icon
        Prescott J, Guito JC, Spengler JR, Arnold CE, Schuh AJ, Amman BR, Sealy TK, Guerrero LW, Palacios GF, Sanchez-Lockhart M, Albarino CG, Towner JS.
        mSphere. 2019 Dec 4;4(6).
        Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg virus (MARV), a filovirus and the etiological agent of the highly lethal Marburg virus disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filovirus diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat's immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection.IMPORTANCE Marburg viruses (MARVs) cause severe human disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in virus replication and shedding, with asymptomatic control of the virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding disease are unknown. Because DC infection and modulation are important early events in human disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.

      7. Coxiella burnetii, the etiologic agent of Q fever, replicates in an intracellular phagolysosome with pH between 4 and 5. The impact of this low pH environment on antimicrobial treatment is not well understood. An in vitro system for testing antibiotic susceptibility of C. burnetii in axenic media was set up to evaluate the impact of pH on C. burnetii growth and survival in the presence and absence of antimicrobial agents. The data show that C. burnetii does not grow in axenic media at pH 6.0 or higher, but the organisms remain viable. At pH of 4.75, 5.25, and 5.75 moxifloxacin, doxycycline, and rifampin are effective at preventing growth of C. burnetii in axenic media, with moxifloxacin and doxycycline being bacteriostatic and rifampin having bactericidal activity. The efficacy of doxycycline and moxifloxacin improved at higher pH, whereas rifampin activity was pH independent. Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments. It had no direct bactericidal or bacteriostatic activity on C. burnetii in axenic media, suggesting that raising pH of acidic intracellular compartments is its primary mechanism of action in vivo. The data suggest that doxycycline and hydroxychloroquine are primarily independent bacteriostatic agents.

      8. Evaluation of sorbent sampling and analysis procedures for acetone in workplace air: Variations of concentration and relative humidityexternal icon
        Soo JC, Lebouf RF, Chisholm WP, Nelson J, Roberts J, Kashon ML, Lee EG, Harper M.
        Ann Work Expo Health. 2019 Dec 1.
        This study experimentally evaluates the performance of different sorbent tubes for sampling acetone vapor in workplace air. A dynamic atmosphere system produced an acetone alone and a mixture with other analytes containing ~73, 483, and 1898 microg acetone mass loading at 25, 50, and 75% relative humidity (RH) at 25 degrees C. Sorbent samples were analyzed in accordance with OSHA Method 69 (Carbosieve S-III) and NMAM 1501, modified to use Anasorb 747 sorbent. Both methods were modified to include the additional analytes. Additional extraction procedures with and without 1% dimethylformamide and anhydrous magnesium sulfate were included in the modified NMAM 1501 using Anasorb 747. Silica gel sorbent tubes analyzed according to NMAM 2027 were included. There were significant reductions in the recovery of acetone from both Anasorb 747 and Carbosieve S-III collected from air at 75% RH, relative to collection at 25 or 50% RH at very low loading compared with that of samples collected at mid to high loading. Silica gel provided a consistent recovery of acetone at all RHs and in the presence of other chemical interferences at 75% RH. The likely cause of mass dependence may arise from the humidity effect on acetone adsorption onto both beaded active carbon and carbon molecular sieve either in sampling or in analysis. The present study confirms not only previous observations but also adds to the literature showing carbonaceous sorbents are not well suited for sampling ketones at high humidity and low concentration.

      9. Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- miceexternal icon
        Welch SR, Ritter JM, McElroy AK, Harmon JR, Coleman-McCray JD, Scholte FE, Kobinger GP, Bergeron E, Zaki SR, Nichol ST, Spengler JR, Spiropoulou CF.
        PLoS Pathog. 2019 Dec 2;15(12):e1008183.
        Crimean-Congo hemorrhagic fever virus (CCHFV, order Bunyavirales, family Nairoviridae, genus Orthonairovirus) is the tick-borne etiological agent of Crimean-Congo hemorrhagic fever (CCHF) in humans. Animals are generally susceptible to CCHFV infection but refractory to disease. Small animal models are limited to interferon-deficient mice, that develop acute fatal disease following infection. Here, using a ZsGreen1- (ZsG) expressing reporter virus (CCHFV/ZsG), we examine tissue tropism and dissemination of virus in interferon-alpha/beta receptor knock-out (Ifnar-/-) mice. We demonstrate that CCHFV/ZsG retains in vivo pathogenicity comparable to wild-type virus. Interestingly, despite high levels of viral RNA in all organs assessed, 2 distribution patterns of infection were observed by both fluorescence and immunohistochemistry (IHC), corresponding to the permissiveness of organ tissues. To further investigate viral dissemination and to temporally define cellular targets of CCHFV in vivo, mice were serially euthanized at different stages of disease. Flow cytometry was used to characterize CCHFV-associated alterations in hematopoietic cell populations and to classify infected cells in the blood, lymph node, spleen, and liver. ZsG signal indicated that mononuclear phagocytic cells in the lymphatic tissues were early targets of infection; in late-stage infection, overall, the highest levels of signal were detected in the liver, and ZsG was found in both antigen-presenting and lymphocyte cell populations.

      10. SeqSero2: Rapid and improved Salmonella serotype determination using whole-genome sequencing dataexternal icon
        Zhang S, den Bakker HC, Li S, Chen J, Dinsmore BA, Lane C, Lauer AC, Fields PI, Deng X.
        Appl Environ Microbiol. 2019 Dec 1;85(23).
        SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (;, an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification.IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing.

      11. Mutations in the NA-like protein of bat influenza H18N11 virus enhance virus replication in mammalian cells, mice, and ferretsexternal icon
        Zhong G, Fan S, Hatta M, Nakatsu S, Walters KB, Lopes TJ, Wang JI, Ozawa M, Karasin A, Li Y, Tong S, Donis RO, Neumann G, Kawaoka Y.
        J Virol. 2019 Dec 4.
        To characterize bat influenza H18N11 virus, we propagated a reverse genetics-generated H18N11 virus in MDCK II cells and detected two adapting mutations in the neuraminidase (NA)-like protein (NA-F144C and NA-T342A, N2 numbering) that increased virus titers in three mammalian cell lines (i.e., Madin-Darby canine kidney, Madin-Darby canine kidney II, and human lung adenocarcinoma Calu-3 cells). In mice, wild-type H18N11 virus replicated only in the lungs of the infected animals, whereas the NA-T342A and NA-F144C/T342A mutant viruses were detected in the nasal turbinates in addition to the lungs. Bat influenza viruses have not been tested for their virulence and organ tropism in ferrets. We detected wild-type and single mutant viruses each possessing NA-F144C or NA-T342A in the nasal turbinates of one or several infected ferret(s), respectively. A mutant virus possessing both NA-F144C and T342A was isolated from both the lung and trachea, suggesting broader organ tropism compared with wild-type virus. However, none of the H18N11 viruses caused symptoms in mice or ferrets. The NA-F144C/T342A double mutation did not substantially affect virion morphology or the release of virions from cells. Collectively, our data demonstrate that propagation of bat influenza H18N11 virus in mammalian cells can result in mammalian-adapting mutations that could increase virus replicative ability and/or organ tropism; overall, however, these viruses did not replicate to high titers throughout the respiratory tract of mice and ferrets.IMPORTANCE Bats are reservoirs for several severe zoonotic pathogens. The genomes of influenza A viruses of the H17N10 and H18N11 subtypes were identified in bats, but no live virus has been isolated. The characterization of artificially generated bat influenza H18N11 virus in mammalian cell lines and animal models revealed that this virus can acquire mammalian-adapting mutations that could increase its zoonotic potential; however, the wild-type and mutant viruses did not replicate in the lungs of all infected animals.

    • Occupational Safety and Health

      1. Preparing the future workforce for safe and healthy employmentexternal icon
        Guerin RJ, Castillo D, Hendricks KJ, Howard J, Piacentino J, Okun AH.
        Am J Public Health. 2020 Jan;110(1):69-71.

      2. Work tasks as determinants of respirable and inhalable indium exposure among workers at an indium-tin oxide production and reclamation facilityexternal icon
        Hawley Blackley B, Cummings KJ, Stanton M, Stefaniak AB, Gibbs JL, Park JY, Harvey RR, Virji MA.
        Ann Work Expo Health. 2019 Dec 5.
        Increased global demand for touch screens, photovoltaics, and optoelectronics has resulted in an increase in the production of indium-tin oxide (ITO). Occupational exposure to indium compounds is associated with the development of indium lung disease. Although many previous epidemiologic investigations highlight an excess of lung abnormalities in workplaces where ITO is produced, few assessments of occupational exposure to respirable and inhalable indium are reported to date. The objective of this study was to identify the determinants of respirable and inhalable indium at an ITO production facility to target exposure interventions. In 2012 and 2014, we conducted exposure assessments at an ITO production facility and collected full-shift personal respirable (n = 159) and inhalable (n = 57) indium samples. We also observed workers and recorded information on task duration and location, materials used, and use of personal protective equipment (PPE). Tasks (n = 121) recorded in task diaries were categorized into 40 similar task groups using the Advanced REACH Tool and process-related information. Mixed-effects models were fit separately for log-transformed respirable and inhalable indium, with random effect of subject and fixed effects of task groups. Overall, respirable and inhalable indium measurements ranged from 0.1 to 796.6 microg m-3 and 1.6 to 10 585.7 microg m-3, respectively, and were highly correlated with Spearman correlation coefficient of 0.90. The final model for respirable indium explained 36.3% of total variance and identified sanding, powder transfer tasks in reclaim, powder transfer tasks in refinery, handling indium materials, and liquid transfer tasks in ITO production as tasks associated with increased respirable indium exposure. The final model for inhalable indium explained 24.6% of total variance and included powder transfer tasks in ITO production, cleaning cylinder or tile, and handling indium material tasks. Tasks identified as strong predictors of full-shift exposure to respirable and inhalable indium can guide the use of engineering, administrative, and PPE controls designed to mitigate occupational exposure to indium. Moreover, since the tasks were aligned with REACH activities, results from this study can also be used to inform REACH activity scenarios.

      3. Cumulative noise exposure model for outdoor shooting rangesexternal icon
        Wall AT, Wagner CM, Rasband RD, Gee KL, Murphy WJ.
        J Acoust Soc Am. 2019 Nov;146(5):3863.
        An impulsive noise exposure model for outdoor military shooting ranges was created. The inputs to the model included spatial interpolation of noise exposure metrics measured from a single round of fire from a small-arms ballistic weapon. Energies from this single-shot model were spatially translated and summed to simulate multiple shooters firing multiple rounds based on the equal energy hypothesis for damage risk assessment. A validation measurement was performed, and the uncertainties associated with measurement and modeling were shown to be acceptably low. This model can predict and assess total exposures and protection measures for shooters, instructors, and other range personnel.

    • Parasitic Diseases
      1. A review of the WHO malaria rapid diagnostic test product testing programme (2008-2018): performance, procurement and policyexternal icon
        Cunningham J, Jones S, Gatton ML, Barnwell JW, Cheng Q, Chiodini PL, Glenn J, Incardona S, Kosack C, Luchavez J, Menard D, Nhem S, Oyibo W, Rees-Channer RR, Gonzalez I, Bell D.
        Malar J. 2019 Dec 2;18(1):387.
        Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.

      2. Multiplex malaria antigen detection by bead-based assay and molecular confirmation by PCR shows no evidence of Pfhrp2 and Pfhrp3 deletion in Haitiexternal icon
        Herman C, Huber CS, Jones S, Steinhardt L, Plucinski MM, Lemoine JF, Chang M, Barnwell JW, Udhayakumar V, Rogier E.
        Malar J. 2019 Nov 27;18(1):380.
        BACKGROUND: The Plasmodium falciparum parasite is the only human malaria that produces the histidine-rich protein 2 and 3 (HRP2/3) antigens. Currently, HRP2/3 are widely used in malaria rapid diagnostic tests (RDTs), but several global reports have recently emerged showing genetic deletion of one or both of these antigens in parasites. Deletion of these antigens could pose a major concern for P. falciparum diagnosis in Haiti which currently uses RDTs based solely on the detection of the HRP2/3 antigens. METHODS: From September 2012 through February 2014, dried blood spots (DBS) were collected in Haiti from 9317 febrile patients presenting to 17 health facilities in 5 departments throughout the country as part of a bed net intervention study. All DBS from RDT positive persons and a random sampling of DBS from RDT negative persons were assayed for P. falciparum DNA by nested and PET-PCR (n = 2695 total). All PCR positive samples (n = 331) and a subset of PCR negative samples (n = 95) were assayed for three malaria antigens by a multiplex bead assay: pan-Plasmodium aldolase (pAldo), pan-Plasmodium lactate dehydrogenase (pLDH), and HRP2/3. Any samples positive for P. falciparum DNA, but negative for HRP2/3 antigens were tested by nested PCR for Pfhrp2 and Pfhrp3 gene deletions. RESULTS: Of 2695 DBS tested for Plasmodium DNA, 345 (12.8%) were originally found to be positive for P. falciparum DNA; 331 of these had DBS available for antigen detection. Of these, 266 (80.4%) were positive for pAldo, 221 (66.8%) positive for pLDH, and 324 (97.9%) were positive for HRP2/3 antigens. Seven samples (2.1%) positive for P. falciparum DNA were not positive for any of the three antigens by the bead assay, and were investigated for potential Pfhrp2/3 gene deletion by PCR. These samples either successfully amplified Pfhrp2/3 genes or were at an estimated parasite density too low for sufficient DNA to perform successful genotyping. CONCLUSIONS: Malaria positive samples in multiple Haitian sites were found to contain the HRP2/3 antigens, and no evidence was found of Pfhrp2/3 deletions. Malaria RDTs based on the detection of the HRP2/3 antigens remain a reliable P. falciparum diagnostic tool as Haiti works towards malaria elimination.

      3. High-throughput malaria serosurveillance using a one-step multiplex bead assayexternal icon
        Rogier E, van den Hoogen L, Herman C, Gurrala K, Joseph V, Stresman G, Presume J, Romilus I, Mondelus G, Elisme T, Ashton R, Chang M, Lemoine JF, Druetz T, Eisele TP, Existe A, Boncy J, Drakeley C, Udhayakumar V.
        Malar J. 2019 Dec 4;18(1):402.
        BACKGROUND: Serological data indicating the presence and level of antibodies against infectious disease antigens provides indicators of exposure and transmission patterns in a population. Laboratory testing for large-scale serosurveys is often hindered by time-consuming immunoassays that employ multiple tandem steps. Some nations have recently begun using malaria serosurveillance data to make inferences about the malaria exposure in their populations, and serosurveys have grown increasingly larger as more accurate estimates are desired. Presented here is a novel approach of antibody detection using bead-based immunoassay that involves incubating all assay reagents concurrently overnight. RESULTS: A serosurvey in was performed in Haiti in early 2017 with both sera (n = 712) and dried blood spots (DBS, n = 796) collected for the same participants. The Luminex((R)) multiplex bead-based assay (MBA) was used to detect total IgG against 8 malaria antigens: PfMSP1, PvMSP1, PmMSP1, PfCSP, PfAMA1, PfLSA1, PfGLURP-R0, PfHRP2. All sera and DBS samples were assayed by MBA using a standard immunoassay protocol with multiple steps, as well a protocol where sample and all reagents were incubated together overnight-termed here the OneStep assay. When compared to a standard multi-step assay, this OneStep assay amplified the assay signal for IgG detection for all 8 malaria antigens. The greatest increases in assay signal were seen at the low- and mid-range IgG titers and were indicative of an enhancement in the analyte detection, not simply an increase in the background signal of the assay. Seroprevalence estimates were generally similar for this sample Haitian population for all antigens regardless of serum or DBS sample type or assay protocol used. CONCLUSIONS: When using the MBA for IgG detection, overnight incubation for the test sample and all assay reagents greatly minimized hands-on time for laboratory staff. Enhanced IgG signal was observed with the OneStep assay for all 8 malaria antigens employed in this study, and seroprevalence estimates for this sample population were similar regardless of assay protocol used. This overnight incubation protocol has the potential to be deployed for large-scale malaria serosurveys for the high-throughput and timely collection of antibody data, particularly for malaria seroprevalence estimates.

      4. We conducted a cluster randomized trial comparing the target population and timing of mass drug administration (MDA) with praziquantel for control of schistosomiasis in villages in western Kenya with high initial prevalence (> 25%) according to a harmonized protocol developed by the Schistosomiasis Consortium for Operational Research and Evaluation. A total of 150 villages were randomized into six treatment arms (25 villages per arm), were assessed at baseline, and received two or four rounds of MDA using community-wide (CWT) or school-based (SBT) treatment over 4 years. In the fifth year, a final evaluation was conducted. The primary outcomes were prevalence and intensity of Schistosoma mansoni infections in children aged 9-12 years, each year their village received MDA. Baseline and year 5 assessments of first-year students and adults were also performed. Using Poisson and negative binomial regression with generalized estimating equations, we found similar effects of CWT and SBT MDA treatment strategies in children aged 9-12 years: significant reductions of prevalence of infection in all arms and of heavy-intensity (>/= 400 eggs/gram) infections in most arms but no significant differences between arms. Combined arms of villages that received four rounds of treatment had greater reduction than villages in arms that only received two rounds of treatment. Surprisingly, we also found benefits of SBT for first-year primary students and adults, who never received treatment in those arms. Our data support the use of annual SBT for control programs when coupled with attention to infections in younger children and occasional treatment of adults.

    • Public Health Law
      1. Exploring the development of three law-based competency models for practitionersexternal icon
        Ransom MM, Yassine B.
        J Soc Behav Health Sci. 2019 ;13(1):128-148.
        As public health promotion and protection become increasingly complex and integrated into various fields, public health law is emerging as an important tool for public health professionals. To ensure that public health professionals are effectively trained in public health law principles and theories, educators, trainers, and others who develop educational curricula should integrate public health law-related competencies into their training and workforce development efforts. This article provides three competency models developed by the Public Health Law Program at the Centers for Disease Control and Prevention: (a) the public health emergency law competency model, (b) the public health law competency model, and (c) the legal epidemiology competency model. These competency models provide a foundation upon which public health law curricula can be developed for governmental, nongovernmental, and academic public health practitioners. Such standardization of public health law curricula will ameliorate not only the training, but also selection and evaluation of public health practitioners, as well as better align public health training with national public health efforts.

    • Reproductive Health

    • Substance Use and Abuse
      1. Tobacco product use and associated factors among middle and high school students - United States, 2019external icon
        Wang TW, Gentzke AS, Creamer MR, Cullen KA, Holder-Hayes E, Sawdey MD, Anic GM, Portnoy DB, Hu S, Homa DM, Jamal A, Neff LJ.
        MMWR Surveill Summ. 2019 Nov 6;68(12):1-22.
        PROBLEM/CONDITION: Tobacco use is the leading cause of preventable disease, disability, and death in the United States. Most tobacco product use begins during adolescence. In recent years, tobacco products have evolved to include various smoked, smokeless, and electronic products. PERIOD COVERED: 2019. DESCRIPTION OF SYSTEM: The National Youth Tobacco Survey (NYTS) is an annual, cross-sectional, school-based, self-administered survey of U.S. middle school (grades 6-8) and high school (grades 9-12) students. A three-stage cluster sampling procedure is used to generate a nationally representative sample of U.S. students attending public and private schools. NYTS is the only nationally representative survey of U.S. middle and high school students that focuses exclusively on tobacco use patterns and associated factors. NYTS is designed to provide national data on tobacco product use and has been conducted periodically during 1999-2009 and annually since 2011. Data from NYTS are used to support the design, implementation, and evaluation of comprehensive tobacco use prevention and control programs and to inform tobacco regulatory activities. Since its inception in 1999 through 2018, NYTS had been conducted via paper and pencil questionnaires. In 2019, NYTS for the first time was administered in schools using electronic data collection methods. CDC's Office on Smoking and Health, in collaboration with the U.S. Food and Drug Administration's (FDA's) Center for Tobacco Products, analyzed data from the 2019 NYTS to assess tobacco product use patterns and associated factors among U.S. middle and high school students. Overall, 19,018 questionnaires were completed and weighted to represent approximately 27.0 million students. On the basis of self-reported grade level, this included 8,837 middle school questionnaires (11.9 million students) and 10,097 high school questionnaires (15.0 million students); 84 questionnaires with missing information on grade level were excluded from school-level analyses. RESULTS: In 2019, an estimated 53.3% of high school students (8.0 million) and 24.3% of middle school students (2.9 million) reported having ever tried a tobacco product. Current (past 30-day) use of a tobacco product (i.e., electronic cigarettes [e-cigarettes], cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis [small brown cigarettes wrapped in a leaf]) was reported by 31.2% of high school students (4.7 million) and 12.5% of middle school students (1.5 million). E-cigarettes were the most commonly cited tobacco product currently used by 27.5% of high school students (4.1 million) and 10.5% of middle school students (1.2 million), followed in order by cigars, cigarettes, smokeless tobacco, hookahs, and pipe tobacco. Tobacco product use also varied by sex and race/ethnicity. Among current users of each tobacco product, the prevalence of frequent tobacco product use (on >/=20 days of the preceding 30 days) ranged from 16.8% of cigar smokers to 34.1% of smokeless tobacco product users. Among current users of each individual tobacco product, e-cigarettes were the most commonly used flavored tobacco product (68.8% of current e-cigarette users). Among students who reported ever having tried e-cigarettes, the three most commonly selected reasons for use were "I was curious about them" (55.3%), "friend or family member used them" (30.8%), and "they are available in flavors, such as mint, candy, fruit, or chocolate" (22.4%). Among never users of each individual tobacco product, curiosity and susceptibility (a construct that can help to identify future tobacco product experimentation or use) was highest for e-cigarettes (39.1% and 45.0%, respectively) and cigarettes (37.0% and 45.9%, respectively). Overall, 86.3% of students who reported contact with an assessed potential source of tobacco product advertisements or promotions (going to a convenience store, supermarket, or gas station; using the Internet; watching television or streaming services or going to the movies; or reading newspapers or magazines) reported exposure to marketing for any tobacco product; 69.3% reported exposure to e-cigarette marketing and 81.7% reported exposure to marketing for cigarettes or other tobacco products. Among all students, perceiving no harm or little harm from intermittent tobacco product use (use on some days but not every day) was 28.2% for e-cigarettes, 16.4% for hookahs, 11.5% for smokeless tobacco products, and 9.5% for cigarettes. Among current users of any tobacco product, 24.7% reported experiencing cravings to use tobacco products during the past 30 days and 13.7% reported wanting to use a tobacco product within 30 minutes of waking. Moreover, 57.8% of current tobacco product users reported they were seriously thinking about quitting the use of all tobacco products and 57.5% reported they had stopped using all tobacco products for >/=1 day because they were trying to quit. INTERPRETATION: In 2019, approximately one in four youths (23.0%) had used a tobacco product during the past 30 days. By school level, this represented approximately three in 10 high school students (31.2%) and approximately one in eight middle school students (12.5%). Since 2014, e-cigarettes have been the most commonly used tobacco product among youths. Importantly, more than half of current youth tobacco product users reported seriously thinking about quitting all tobacco products in 2019. However, established factors of use and initiation, including the availability of flavors, exposure to tobacco product marketing, curiosity and susceptibility, and misperceptions about harm from tobacco product use, remained prevalent in 2019 and continue to promote tobacco product use among youths. PUBLIC HEALTH ACTION: The continued monitoring of all forms of youth tobacco product use and associated factors through surveillance efforts including NYTS is important to the development of public health policy and action at national, state, and community levels. Everyone, including public health professionals, health care providers, policymakers, educators, parents, and others who influence youths, can help protect youths from the harms of all tobacco products. In addition, the comprehensive and sustained implementation of evidence-based tobacco control strategies, combined with FDA's regulation of tobacco products, is important for reducing all forms of tobacco product use among U.S. youths.

    • Zoonotic and Vectorborne Diseases
      1. Can we make human plague history? A call to actionexternal icon
        Baril L, Valles X, Stenseth NC, Rajerison M, Ratsitorahina M, Pizarro-Cerda J, Demeure C, Belmain S, Scholz H, Girod R, Hinnebusch J, Vigan-Womas I, Bertherat E, Fontanet A, Yazadanpanah Y, Carrara G, Deuve J, D'Ortenzio E, Angulo JO, Mead P, Horby PW.
        BMJ Glob Health. 2019 ;4(6):e001984.

      2. Forecasting the 2014 West African Ebola outbreakexternal icon
        Carias C, O'Hagan JJ, Gambhir M, Kahn EB, Swerdlow DL, Meltzer MI.
        Epidemiol Rev. 2019 Nov 29.
        In 2014/15 an Ebola outbreak of unprecedented dimensions afflicted the West African countries of Liberia, Guinea, and Sierra Leone. We performed a systematic review of manuscripts that forecasted the outbreak while it was occurring, and derive implications on the ways results could be interpreted by policy-makers. We reviewed 26 manuscripts, published between 2014 and April 2015, that presented forecasts of the West African Ebola outbreak. Forecasted case counts varied widely. An important determinant of forecast accuracy for case counts was how far into the future predictions were made. Generally, those that made forecasts less than 2 months into the future tended to be more accurate than those that made forecasts more than 10 weeks into the future. The exceptions were parsimonious statistical models in which the decay of the rate of spread of the pathogen among susceptible individuals was dealt with explicitly. Regarding future outbreaks, the most important lessons for policy makers when using similar modeling results are: i) uncertainty of forecasts will be higher in the beginning of the outbreak, ii) when data are limited, forecasts produced by models designed to inform specific decisions should be used in complimentary fashion for robust decision making - for this outbreak, two statistical models produced the most reliable case counts forecasts, but did not allow to understand the impact of interventions, while several compartmental models could estimate the impact of interventions but required data that was not available; iii) timely collection of essential data is necessary for optimal model use.

      3. Zika virus IgM 25 months after symptom onset, Miami-Dade County, Florida, USAexternal icon
        Griffin I, Martin SW, Fischer M, Chambers TV, Kosoy OL, Goldberg C, Falise A, Villamil V, Ponomareva O, Gillis LD, Blackmore C, Jean R.
        Emerg Infect Dis. 2019 Dec;25(12):2264-2265.
        We assessed IgM detection in Zika patients from the 2016 outbreak in Miami-Dade County, Florida, USA. Of those with positive or equivocal IgM after 12-19 months, 87% (26/30) had IgM 6 months later. In a survival analysis, approximately 76% had IgM at 25 months. Zika virus IgM persists for years, complicating serologic diagnosis.

      4. Dengue fever and chikungunya virus infections: identification in travelers in Uganda - 2017external icon
        Kayiwa JT, Nankya AM, Ataliba I, Nassuna CA, Omara IE, Koehler JW, Dye JM, Mossel EC, Lutwama JJ.
        Trop Dis Travel Med Vaccines. 2019 ;5:21.
        Arboviruses are (re-) emerging viruses that cause significant morbidity globally. Clinical manifestations usually consist of a non-specific febrile illness that may be accompanied by rash, arthralgia and arthritis and/or with neurological or hemorrhagic syndromes. The broad range of differential diagnoses of other infectious and non-infectious etiologies presents a challenge for clinicians. While knowledge of the geographic distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the non-specific and variable clinical presentation can delay final diagnosis. This case report summarizes the laboratory-based findings of three travel-related cases of arbovirus infections in Uganda. These include a patient from Bangladesh with chikungunya virus infection and two cases of dengue fever from Ethiopia. Early detection of travel-imported cases by public health laboratories is important to reduce the risk of localized outbreaks of arboviruses such as dengue virus and chikungunya virus. Because of the global public health importance and the continued risk of (re-) emerging arbovirus infections, specific recommendations following diagnosis by clinicians should include obtaining travel histories from persons with arbovirus-compatible illness and include differential diagnoses when appropriate.

      5. Evaluating the potential misuse of the Lyme disease surveillance case definitionexternal icon
        Perea AE, Hinckley AF, Mead PS.
        Public Health Rep. 2019 Dec 4:33354919890024.

      6. Persistent Zika virus infection associated with early fetal demise: A case reportexternal icon
        Perez-Padilla J, Paz-Bailey G, Meaney-Delman D, Doyle K, Gary J, Rodriguez DM, Bhatnagar J, Perez-Rodriguez NM, Montalvo S, Alvarado L, Sharp TM.
        Open J Obstet Gynecol. 2019 May;9(5):698-706.
        Background: Infection with Zika virus (ZIKV) during pregnancy is known to cause birth defects and could also be linked to pregnancy loss. Case: A pregnant woman in Puerto Rico contracted ZIKV at 16 weeks gestation. ZIKV RNA persisted in serum from her initial test at 16 weeks through 24 weeks gestation, when fetal demise occurred, and was detected in placental tissue. Conclusion: Prolonged detection of ZIKV RNA in maternal serum was associated with ZIKV RNA detection in the placenta of a patient who experienced fetal demise. While detection of placenta ZIKV RNA does not establish that ZIKV conclusively caused the demise, these findings support emerging evidence that the placenta may serve as a reservoir for ZIKV, which may be associated with prolonged detection of ZIKV RNA in serum.

      7. Seroprevalence and risk factors possibly associated with emerging zoonotic vaccinia virus in a farming community, Colombiaexternal icon
        Styczynski A, Burgado J, Walteros D, Usme-Ciro J, Laiton K, Farias AP, Nakazawa Y, Chapman C, Davidson W, Mauldin M, Morgan C, Martinez-Ceron J, Patina E, Lopez Sepulveda LL, Torres CP, Cruz Suarez AE, Olaya GP, Riveros CE, Cepeda DY, Lopez LA, Espinosa DG, Gutierrez Lozada FA, Li Y, Satheshkumar PS, Reynolds M, Gracia-Romero M, Petersen B.
        Emerg Infect Dis. 2019 Dec;25(12).
        In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caqueta Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.

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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.

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