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Volume 10, Issue 2, January 16, 2018

CDC Science Clips: Volume 10, Issue 2, January 16, 2018

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

  1. CDC Public Health Grand Rounds
    • Communicable Diseases – Influenza
      1. Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza
        Arriola C, Garg S, Anderson EJ, Ryan PA, George A, Zansky SM, Bennett N, Reingold A, Bargsten M, Miller L, Yousey-Hindes K, Tatham L, Bohm SR, Lynfield R, Thomas A, Lindegren ML, Schaffner W, Fry AM, Chaves SS.
        Clin Infect Dis. 2017 Oct 15;65(8):1289-1297.
        Background: We investigated the effect of influenza vaccination on disease severity in adults hospitalized with laboratory-confirmed influenza during 2013-14, a season in which vaccine viruses were antigenically similar to those circulating. Methods: We analyzed data from the 2013-14 influenza season and used propensity score matching to account for the probability of vaccination within age strata (18-49, 50-64, and >/=65 years). Death, intensive care unit (ICU) admission, and hospital and ICU lengths of stay (LOS) were outcome measures for severity. Multivariable logistic regression and competing risk models were used to compare disease severity between vaccinated and unvaccinated patients, adjusting for timing of antiviral treatment and time from illness onset to hospitalization. Results: Influenza vaccination was associated with a reduction in the odds of in-hospital death among patients aged 18-49 years (adjusted odds ratios [aOR] = 0.21; 95% confidence interval [CI], 0.05 to 0.97), 50-64 years (aOR = 0.48; 95% CI, 0.24 to 0.97), and >/=65 years (aOR = 0.39; 95% CI, 0.17 to 0.66). Vaccination also reduced ICU admission among patients aged 18-49 years (aOR = 0.63; 95% CI, 0.42 to 0.93) and >/=65 years (aOR = 0.63; 95% CI, 0.48 to 0.81), and shortened ICU LOS among those 50-64 years (adjusted relative hazards [aRH] = 1.36; 95% CI, 1.06 to 1.74) and >/=65 years (aRH = 1.34; 95% CI, 1.06 to 1.73), and hospital LOS among 50-64 years (aRH = 1.13; 95% CI, 1.02 to 1.26) and >/=65 years (aRH = 1.24; 95% CI, 1.13 to 1.37). Conclusions: Influenza vaccination during 2013-14 influenza season attenuated adverse outcome among adults that were hospitalized with laboratory-confirmed influenza.

      2. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies
        Belongia EA, Simpson MD, King JP, Sundaram ME, Kelley NS, Osterholm MT, McLean HQ.
        Lancet Infect Dis. 2016 Aug;16(8):942-51.
        BACKGROUND: Influenza vaccine effectiveness (VE) can vary by type and subtype. Over the past decade, the test-negative design has emerged as a valid method for estimation of VE. In this design, VE is calculated as 100% x (1 – odds ratio) for vaccine receipt in influenza cases versus test-negative controls. We did a systematic review and meta-analysis to estimate VE by type and subtype. METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase from Jan 1, 2004, to March 31, 2015. Test-negative design studies of influenza VE were eligible if they enrolled outpatients on the basis of predefined illness criteria, reported subtype-level VE by season, used PCR to confirm influenza, and adjusted for age. We excluded studies restricted to hospitalised patients or special populations, duplicate reports, interim reports superseded by a final report, studies of live-attenuated vaccine, and studies of prepandemic seasonal vaccine against H1N1pdm09. Two reviewers independently assessed titles and abstracts to identify articles for full review. Discrepancies in inclusion and exclusion criteria and VE estimates were adjudicated by consensus. Outcomes were VE against H3N2, H1N1pdm09, H1N1 (pre-2009), and type B. We calculated pooled VE using a random-effects model. FINDINGS: We identified 3368 unduplicated publications, selected 142 for full review, and included 56 in the meta-analysis. Pooled VE was 33% (95% CI 26-39; I(2)=44.4) for H3N2, 54% (46-61; I(2)=61.3) for type B, 61% (57-65; I(2)=0.0) for H1N1pdm09, and 67% (29-85; I(2)=57.6) for H1N1; VE was 73% (61-81; I(2)=31.4) for monovalent vaccine against H1N1pdm09. VE against H3N2 for antigenically matched viruses was 33% (22-43; I(2)=56.1) and for variant viruses was 23% (2-40; I(2)=55.6). Among older adults (aged >60 years), pooled VE was 24% (-6 to 45; I(2)=17.6) for H3N2, 63% (33-79; I(2)=0.0) for type B, and 62% (36-78; I(2)=0.0) for H1N1pdm09. INTERPRETATION: Influenza vaccines provided substantial protection against H1N1pdm09, H1N1 (pre-2009), and type B, and reduced protection against H3N2. Vaccine improvements are needed to generate greater protection against H3N2 than with current vaccines. FUNDING: None.

      3. Oseltamivir shortens hospital stays of critically ill children hospitalized with seasonal influenza: a retrospective cohort study
        Coffin SE, Leckerman K, Keren R, Hall M, Localio R, Zaoutis TE.
        Pediatr Infect Dis J. 2011 Nov;30(11):962-6.
        BACKGROUND: Antiviral therapy reduces symptom duration and hospitalization risk among previously healthy and chronically ill children infected with seasonal influenza. The effect of oseltamivir on outcomes of hospitalized children is unknown. The primary objective of this study was to determine whether oseltamivir improves outcomes of critically ill children hospitalized with influenza. METHODS: We performed a retrospective cohort study of children with influenza infection admitted to a pediatric intensive care unit during 6 consecutive winter seasons (2001-2007). We used the Pediatric Health Information System database, which contains resource utilization data from 41 children’s hospitals. We matched oseltamivir-treated patients with oseltamivir-nontreated patients by the probability of oseltamivir exposure using a propensity score we derived from patient and hospital characteristics. We subsequently compared the outcomes of critically ill children treated with oseltamivir within 24 hours of admission with propensity score matched children who were not treated with oseltamivir. RESULTS: We identified 1257 children with influenza infection, 264 of whom were treated with oseltamivir within 24 hours of hospital admission. Multivariable analysis of 252 oseltamivir-treated patients and 252 propensity score-matched untreated patients demonstrated that patients treated with oseltamivir experienced an 18% reduction in total hospital days (time ratio: 0.82, P = 0.02), whereas intensive care unit stay, in-hospital mortality, and readmission rates did not differ. CONCLUSION: For critically ill children infected with seasonal influenza, treatment with oseltamivir within 24 hours of hospitalization was associated with a shorter duration of hospital stay. Additional study is needed to determine the effect of delayed initiation of oseltamivir on clinical outcomes.

      4. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials
        Dobson J, Whitley RJ, Pocock S, Monto AS.
        Lancet. 2015 May 2;385(9979):1729-1737.
        BACKGROUND: Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety. METHODS: We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes. FINDINGS: We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0.79, 95% CI 0.74-0.85; p<0.0001). The median times to alleviation were 97.5 h for oseltamivir and 122.7 h for placebo groups (difference -25.2 h, 95% CI -36.2 to -16.0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0.85) but remained highly significant (median difference -17.8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0.56, 95% CI 0.42-0.75; p=0.0001; 4.9% oseltamivir vs 8.7% placebo, risk difference -3.8%, 95% CI -5.0 to -2.2) and also fewer admittances to hospital for any cause (RR 0.37, 95% CI 0.17-0.81; p=0.013; 0.6% oseltamivir, 1.7% placebo, risk difference -1.1%, 95% CI -1.4 to -0.3). Regarding safety, oseltamivir increased the risk of nausea (RR 1.60, 95% CI 1.29-1.99; p<0.0001; 9.9% oseltamivir vs 6.2% placebo, risk difference 3.7%, 95% CI 1.8-6.1) and vomiting (RR 2.43, 95% CI 1.83-3.23; p<0.0001; 8.0% oseltamivir vs 3.3% placebo, risk difference 4.7%, 95% CI 2.7-7.3). We recorded no effect on neurological or psychiatric disorders or serious adverse events. INTERPRETATION: Our findings show that oseltamivir in adults with influenza accelerates time to clinical symptom alleviation, reduces risk of lower respiratory tract complications, and admittance to hospital, but increases the occurrence of nausea and vomiting. FUNDING: Multiparty Group for Advice on Science (MUGAS) foundation.

      5. Risk factors for mechanical ventilation in U.S. children hospitalized with seasonal influenza and 2009 pandemic influenza A*
        Eriksson CO, Graham DA, Uyeki TM, Randolph AG.
        Pediatr Crit Care Med. 2012 Nov;13(6):625-31.
        OBJECTIVE: We tested the hypothesis that the use of mechanical ventilator support in children hospitalized with influenza during the 2009 H1N1 influenza A (H1N1) pandemic was higher than would be expected in children hospitalized for seasonal influenza after adjusting for patient risk. DESIGN: Retrospective cohort study. SETTING: Forty-three U.S. pediatric hospitals. PATIENTS: Children <18 yrs old with a discharge diagnosis of influenza admitted July 2006 through March 2009 (seasonal influenza) and June through December 2009 (2009 pandemic influenza A). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 10,173 children hospitalized with seasonal influenza and 9837 with presumed 2009 pandemic influenza A. The 2009 pandemic influenza A cohort was older (median 5.0 vs. 1.9 yrs), more likely to have asthma (30% vs. 18%), and less likely to receive mechanical ventilation (7.1% [n = 701] vs. 9.2% [n = 940]). Using logistic regression, we created a multivariable model of risk factors associated with endotracheal mechanical ventilator support in the seasonal influenza cohort and used this model to predict the number of expected mechanical ventilation cases in children with presumed 2009 pandemic influenza A. Adjusted for underlying health conditions, race, age, and a co-diagnosis of bacterial pneumonia, the observed/expected rate of mechanical ventilation in the presumed 2009 pandemic influenza A cohort was 0.74 (95% confidence interval 0.68-0.79). Early hospital treatment with influenza antiviral medications was associated with decreased initiation of mechanical ventilation on hospital day >/= 3 in the seasonal influenza (odds ratio 0.66; 95% confidence interval 0.45-0.97) and 2009 pandemic influenza A (odds ratio 0.23; 95% confidence interval 0.16-0.34) periods; influenza antiviral use in the 2009 pandemic influenza A period was much higher (70% vs. 20%; p < .001). CONCLUSIONS: Although the number of children with a hospital discharge diagnosis of influenza almost tripled during the 2009 pandemic influenza A period, the risk-adjusted proportion of children receiving mechanical ventilation was lower than we would have predicted in a seasonal influenza cohort. Early hospital use of influenza antiviral medications was associated with a decrease in late-onset mechanical ventilation.

      6. Influenza vaccine effectiveness against pediatric deaths: 2010-2014
        Flannery B, Reynolds SB, Blanton L, Santibanez TA, O’Halloran A, Lu PJ, Chen J, Foppa IM, Gargiullo P, Bresee J, Singleton JA, Fry AM.
        Pediatrics. 2017 May;139(5).
        BACKGROUND AND OBJECTIVES: Surveillance for laboratory-confirmed influenza-associated pediatric deaths since 2004 has shown that most deaths occur in unvaccinated children. We assessed whether influenza vaccination reduced the risk of influenza-associated death in children and adolescents. METHODS: We conducted a case-cohort analysis comparing vaccination uptake among laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States. Case vaccination and high-risk status were determined by case investigation. Influenza vaccination coverage estimates were obtained from national survey data or a national insurance claims database. We estimated odds ratios from logistic regression comparing odds of vaccination among cases with odds of vaccination in comparison cohorts. We used Bayesian methods to compute 95% credible intervals (CIs) for vaccine effectiveness (VE), calculated as (1 – odds ratio) x 100. RESULTS: From July 2010 through June 2014, 358 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months through 17 years. Vaccination status was determined for 291 deaths; 75 (26%) received vaccine before illness onset. Average vaccination coverage in survey cohorts was 48%. Overall VE against death was 65% (95% CI, 54% to 74%). Among 153 deaths in children with underlying high-risk medical conditions, 47 (31%) were vaccinated. VE among children with high-risk conditions was 51% (95% CI, 31% to 67%), compared with 65% (95% CI, 47% to 78%) among children without high-risk conditions. CONCLUSIONS: Influenza vaccination was associated with reduced risk of laboratory-confirmed influenza-associated pediatric death. Increasing influenza vaccination could prevent influenza-associated deaths among children and adolescents.

      7. Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014-2015
        Flannery B, Zimmerman RK, Gubareva LV, Garten RJ, Chung JR, Nowalk MP, Jackson ML, Jackson LA, et al .
        J Infect Dis. 2016 Oct 1;214(7):1010-9.
        BACKGROUND: During the 2014-2015 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of the genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). METHODS: A novel pyrosequencing assay was used to determine genetic group, based on hemagglutinin (HA) gene sequences, of influenza A(H3N2) viruses from patients enrolled at US Influenza Vaccine Effectiveness Network sites. VE was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. RESULTS: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2) virus; genetic characterization of 1397 viruses showed that 1134 (81%) belonged to 1 HA genetic group (3C.2a) of antigenically drifted influenza A(H3N2) viruses. Effectiveness of 2014-2015 influenza vaccination varied by influenza A(H3N2) virus genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted influenza A(H3N2) virus group 3C.2a viruses versus 44% (95% CI, 16%-63%) against illness caused by vaccine-like influenza A(H3N2) virus group 3C.3b viruses. CONCLUSIONS: Effectiveness of 2014-2015 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in HA genes related to antigenic drift were associated with reduced VE.

      8. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study
        Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, et al .
        Lancet. 2017 Dec 13.
        BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and >/=75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country’s MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0.1 to 6.4 per 100 000 individuals for people younger than 65 years, 2.9 to 44.0 per 100 000 individuals for people aged between 65 and 74 years, and 17.9 to 223.5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4.0-8.8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2.8-16.5 per 100 000 individuals), southeast Asia (3.5-9.2 per 100 000 individuals), and among people aged 75 years or older (51.3-99.4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

      9. Influenza illness and hospitalizations averted by influenza vaccination in the United States, 2005-2011
        Kostova D, Reed C, Finelli L, Cheng PY, Gargiullo PM, Shay DK, Singleton JA, Meltzer MI, Lu PJ, Bresee JS.
        PLoS One. 2013 ;8(6):e66312.
        CONTEXT: The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits. OBJECTIVE: To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons. DESIGN: Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination). RESULTS: We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6-1.7 million) during the 2006-2007 season to a high of 5 million (CI 2.9-8.6 million) during the 2010-2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700-14,100) in 2009-2010 to a high of 40,400 (CI 20,800-73,000) in 2010-2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010-2011, reflecting the post-pandemic expansion of vaccination coverage. CONCLUSIONS: Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.

      10. [No abstract]

      11. Efficacy and safety of oseltamivir in children: Systematic review and individual patient data meta-analysis of randomized controlled trials
        Malosh RE, Martin ET, Heikkinen T, Brooks WA, Whitley RJ, Monto AS.
        Clin Infect Dis. 2017 Nov 23.
        Background: Oseltamivir has been used to treat children with influenza for nearly two decades, with treatment currently approved for infants 2 weeks of age or older, but efficacy and safety remain controversial. Newer randomized placebo controlled trials (RCT), not included in previous meta-analyses, can add to the evidence base. Methods: We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a two-stage, random effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RSMT) by treatment group. We also examined complications and safety. Results: We identified 5 trials including 2561 patients in the intent to treat (ITT) and 1598 in the intent to treat infected (ITTI) population. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference -17.6 hours 95% CI: -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours 95% CI -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group. Conclusion: Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.

      12. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data
        Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, et al .
        Lancet Respir Med. 2014 May;2(5):395-404.
        BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0.81; 95% CI 0.70-0.93; p=0.0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0.48; 95% CI 0.41-0.56; p<0.0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0.50; 95% CI 0.37-0.67; p<0.0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day’s delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1.23] [95% CI 1.18-1.28]; p<0.0001 for the increasing HR with each day’s delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

      13. Novel framework for assessing epidemiologic effects of influenza epidemics and pandemics
        Reed C, Biggerstaff M, Finelli L, Koonin LM, Beauvais D, Uzicanin A, Plummer A, Bresee J, Redd SC, Jernigan DB.
        Emerg Infect Dis. 2013 Jan;19(1):85-91.
        The effects of influenza on a population are attributable to the clinical severity of illness and the number of persons infected, which can vary greatly between seasons or pandemics. To create a systematic framework for assessing the public health effects of an emerging pandemic, we reviewed data from past influenza seasons and pandemics to characterize severity and transmissibility (based on ranges of these measures in the United States) and outlined a formal assessment of the potential effects of a novel virus. The assessment was divided into 2 periods. Because early in a pandemic, measurement of severity and transmissibility is uncertain, we used a broad dichotomous scale in the initial assessment to divide the range of historic values. In the refined assessment, as more data became available, we categorized those values more precisely. By organizing and prioritizing data collection, this approach may inform an evidence-based assessment of pandemic effects and guide decision making.

  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. Health care provider counseling for physical activity or exercise among adults with arthritis – United States, 2002 and 2014
        Hootman JM, Murphy LB, Omura JD, Brady TJ, Boring M, Barbour KE, Helmick CG.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 5;66(5152):1398-1401.
        Arthritis affects an estimated 54 million U.S. adults and, as a common comorbidity, can contribute arthritis-specific limitations or barriers to physical activity or exercise for persons with diabetes, heart disease, and obesity (1). The American College of Rheumatology’s osteoarthritis management guidelines recommend exercise as a first-line, nonpharmacologic strategy to manage arthritis symptoms (2), and a Healthy People 2020 objective is to increase health care provider counseling for physical activity or exercise among adults with arthritis.* To determine the prevalence and percentage change from 2002 to 2014 in receipt of health care provider counseling for physical activity or exercise (counseling for exercise) among adults with arthritis, CDC analyzed 2002 and 2014 National Health Interview Survey (NHIS) data. From 2002 to 2014, the age-adjusted prevalence of reporting health care provider counseling for exercise among adults with arthritis increased 17.6%, from 51.9% (95% confidence interval [CI] = 49.9%-53.8%) to 61.0% (CI = 58.6%-63.4%) (p<0.001). The age-adjusted prevalence of reporting health care provider counseling for exercise among persons with arthritis who described themselves as inactive increased 20.1%, from 47.2% (CI = 44.0%-50.4%) in 2002 to 56.7% (CI = 52.3%-61.0%) in 2014 (p = 0.001). Prevalence of counseling for exercise has increased significantly since 2002; however, approximately 40% of adults with arthritis are still not receiving counseling for exercise. Improving health care provider training and expertise in exercise counseling and incorporating prompts into electronic medical records are potential strategies to facilitate counseling for exercise that can help adults manage their arthritis and comorbid conditions.

      2. Primary care providers’ physical activity counseling and referral practices and barriers for cardiovascular disease prevention
        Omura JD, Bellissimo MP, Watson KB, Loustalot F, Fulton JE, Carlson SA.
        Prev Med. 2017 Dec 27.
        The US Preventive Services Task Force (USPSTF) recommends offering or referring adults who are overweight or obese and have additional cardiovascular disease (CVD) risk factors to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. This study determined the proportion of primary care providers (PCPs) who discussed physical activity with most of their at-risk patients and referred them to intensive behavioral counseling, and reported barriers to counseling. Our analyses used data from DocStyles 2015, a Web-based panel survey of 1251 PCPs. Overall, 58.6% of PCPs discussed physical activity with most of their at-risk patients. Among these PCPs, the prevalence of components offered ranged from 98.5% encouraging increased physical activity to 13.9% referring to intensive behavioral counseling. Overall, only 8.1% both discussed physical activity with most at-risk patients and referred to intensive behavioral counseling. Barriers related to PCPs’ attitudes and beliefs about counseling (e.g., counseling is not effective) were significantly associated with both discussing physical activity with most at-risk patients and referring them to intensive behavioral counseling (adjusted odds ratio, 1.92; 95% confidence interval, 1.15-3.20). System-level barriers (e.g., referral services not available) were not. Just over half of PCPs discussed physical activity with most of their at-risk patients, and few both discussed physical activity and referred patients to intensive behavioral counseling. Overcoming barriers related to attitudes and beliefs about physical activity counseling could help improve low levels of counseling and referrals to intensive behavioral counseling for CVD prevention.

    • Communicable Diseases
      1. The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent.

      2. The status of hepatitis B control in the African region
        Breakwell L, Tevi-Benissan C, Childs L, Mihigo R, Tohme R.
        Pan Afr Med J. 2017 ;27(Suppl 3):17.
        The World Health Organization (WHO) African Region has approximately 100 million people with chronic hepatitis B virus (HBV) infection. This review describes the status of hepatitis B control in the Region. We present hepatitis B vaccine (HepB) coverage data and from available data in the published literature, the impact of HepB vaccination on hepatitis B surface antigen (HBsAg) prevalence, a marker of chronic infection, among children, HBsAg prevalence in pregnant women, and risk of perinatal transmission. Lastly, we describe challenges with HepB birth dose (HepB-BD) introduction reported in the Region, and propose strategies to increase coverage. In 2015, regional three dose HepB coverage was 76%, and 16(34%) of 47 countries reported >/= 90% coverage. Overall, 11 countries introduced HepB-BD; only nine provide universal HepB-BD, and of these, five reported >/= 80% coverage. From non-nationally representative serosurveys among children, HBsAg prevalence was lower among children born after HepB introduction compared to those born before HepB introduction. However, some studies still found HBsAg prevalence to be above 2%. From limited surveys among pregnant women, the median HBsAg prevalence varied by country, ranging from 1.9% (Madagascar) to 16.1% (Niger); hepatitis B e antigen (HBeAg) prevalence among HBsAg-positive women ranged from 3.3% (Zimbabwe) to 28.5% (Nigeria). Studies in three countries indicated that the risk of perinatal HBV transmission was associated with HBeAg expression or high HBV DNA viral load. Major challenges for timely HepB-BD administration were poor knowledge of or lack of national HepB-BD vaccination guidelines, high prevalence of home births, and unreliable vaccine supply. Overall, substantial progress has been made in the region. However, countries need to improve HepB3 coverage and some countries might need to consider introducing the HepB-BD to help achieve the regional hepatitis B control goal of < 2% HBsAg prevalence among children < 5 years old by 2020. To facilitate HepB-BD introduction and improve timely coverage, strategies are needed to reach both facility-based and home births. Strong political commitment, clear policy recommendations and staff training on HepB-BD administration are also required. Furthermore, high quality nationally representative serosurveys among children are needed to inform decision makers about progress towards the regional control goal.

      3. Improved survival and cure rates with concurrent treatment for MDR-TB/HIV co-infection in South Africa
        Brust JC, Shah NS, Mlisana K, Moodley P, Allana S, Campbell A, Johnson BA, Master I, Mthiyane T, Lachman S, Larkan LM, Ning Y, Malik A, Smith JP, Gandhi NR.
        Clin Infect Dis. 2017 Dec 26.
        Background: The global epidemic of multidrug-resistant tuberculosis (MDR-TB) threatens gains in TB and HIV outcomes over the past two decades. Mortality in MDR-TB/HIV co-infection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR-TB/HIV co-infected patients on ART to those in patients with MDR-TB alone. Methods: This prospective, observational study enrolled culture-confirmed MDR-TB patients, with and without HIV co-infection, in South Africa between 2011-2013. Participants received standardized MDR-TB and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Results: Among 206 participants, 150 were HIV-infected, 131 (64%) were female, and the median age was 33 years (IQR 26-41). Of the 191 participants with a final MDR-TB outcome, 130 (73%) were cured or successfully completed treatment, which did not differ by HIV status (p=0.50). After two years, the median CD4 count was 386 cells/mm3 (IQR 219-510), an increase of 140 cells/mm3 from baseline (p=0.005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; p=0.34). The strongest risk factor for mortality was having a CD4 count </=100 cells/mm3 (aHR 15.6, 95%CI 4.4-55.6). Conclusions: Survival and treatment outcomes among MDR-TB/HIV individuals receiving concurrent ART were improved, approaching those of HIV-uninfected MDR-TB patients. The greatest risk of death was among HIV-infected individuals with CD4 counts </=100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR-TB and HIV.

      4. Clinical features of foodborne and wound botulism: A systematic review of the literature, 1932-2015
        Chatham-Stephens K, Fleck-Derderian S, Johnson SD, Sobel J, Rao AK, Meaney-Delman D.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S11-s16.
        Background: Botulism is a rare, potentially fatal paralytic illness caused by neurotoxins. To inform the evaluation of patients with suspected botulism, we conducted a systematic review to describe the clinical features of botulism. Methods: We searched Medline Ovid, Embase Dialog, Embase Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Global Health Ovid, Cochrane Library, Scopus, and for English language articles through May 2015. Information abstracted included demographics, signs and symptoms, laboratory results, and clinical outcome for foodborne and wound botulism patients confirmed by laboratory testing, epidemiologic link, or association with an outbreak. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42015024784). Results: We identified 402 patients from 233 articles published in English between 1932 and 2015. Most cases (n = 346 [86%]) were foodborne botulism and most (n = 263 [65%]) were associated with an outbreak. The median incubation period was 1 day, and the median time from illness onset to hospital admission was 2 days. Shortness of breath, dyspnea, or respiratory distress or failure at hospital admission was reported in 169 (42%) patients; 71 (42%) reported respiratory involvement without report of extremity weakness. Among 154 patients for whom the hospital day of intubation was reported, 134 (87%) were intubated on the first or second hospital day. Conclusions: Botulism patients can experience a range of signs and symptoms. Respiratory involvement may occur early in the illness and can occur without preceding extremity weakness. Clinicians and public health departments preparing for and responding to botulism events should use this information to guide the evaluation of suspected botulism patients.

      5. An integrated surveillance system to examine testing, services, and outcomes for sexually transmitted diseases
        Dixon BE, Tao G, Wang J, Tu W, Hoover S, Zhang Z, Batteiger TA, Arno JN.
        Stud Health Technol Inform. 2017 ;245:361-365.
        Despite laws that require reporting of sexually transmitted diseases (STDs) to governmental health agencies, integrated surveillance of STDs remains challenging. Data and information about testing are fragmented from information on treatment and outcomes. To overcome this fragmentation, data from multiple electronic systems spanning clinical and public health environments were integrated to create an STD surveillance registry. Electronic health records, disease case records, and birth registry records were linked and then stored in a de-identified, secure server for use by health officials and researchers. The registry contains nearly 6 million tests for 628,138 individuals over a 12-year period. The registry supports efforts to understand the epidemiology of STDs as well as health services and outcomes for those diagnosed with STDs. Specialized disease registries hold promise for collaboration across clinical and public health domains to improve surveillance efforts, reduce health disparities, and increase prevention efforts at the local level.

      6. Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010-2015
        Geter A, Sutton MY, Armon C, Durham MD, Palella FJ, Tedaldi E, Hart R, Buchacz K.
        PLoS One. 2018 ;13(1):e0189973.
        In the United States, women accounted for 19% of new HIV diagnoses in 2015 and were less likely to reach virologic suppression when compared to men. We assessed trends and disparities in virologic suppression among HIV-positive women to inform HIV treatment strategies. Data were from a prospective cohort of the HIV Outpatient Study and collected at nine United States HIV clinics. We included women aged >/=18 years, with >/=1 visit, who were prescribed antiretroviral therapy, and had >/=1 viral load test performed between 2010 and 2015. We defined virologic suppression as viral load <50 copies/mL and calculated adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) for virologic suppression by race/ethnicity and year of measure. Generalized estimating equations were used for multivariable analyses to assess factors associated with virologic suppression. Among 809 women (median age = 44 years), 482 (60%) were black, 177 (22%) white, 150 (19%) Hispanic/Latina. Virologic suppression was less prevalent among black women (73%) compared with Hispanic/Latina women (83%) and white women (91%). In multivariable analyses, not achieving virologic suppression was more likely among black women (aPR = 2.13; CI = 1.50-3.02) or Hispanic/Latina women (aPR = 1.66; CI = 1.08-2.56) compared with white women, and among women who attended public clinics (aPR = 1.42; CI = 1.07-1.87) compared with those who attended a private clinic. Between 2010 and 2015, virologic suppression among HIV-positive women increased from 68% to 83%, but racial/ethnic disparities persisted. Black and Hispanic/Latina women had significantly lower rates of virologic suppression than white women. Interventions targeting virologic suppression improvement among HIV-positive women of color, especially those who attend public clinics, are warranted.

      7. Pediatric botulism and use of equine botulinum antitoxin in children: A systematic review
        Griese SE, Kisselburgh HM, Bartenfeld MT, Thomas E, Rao AK, Sobel J, Dziuban EJ.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S17-s29.
        Background: Botulism manifests with cranial nerve palsies and flaccid paralysis in children and adults. Botulism must be rapidly identified and treated; however, clinical presentation and treatment outcomes of noninfant botulism in children are not well described. Methods: We searched 12 databases for peer-reviewed and non-peer-reviewed reports with primary data on botulism in children (persons <18 years of age) or botulinum antitoxin administration to children. Reports underwent title and abstract screening and full text review. For each case, patient demographic, clinical, and outcome data were abstracted. Results: Of 7065 reports identified, 184 met inclusion criteria and described 360 pediatric botulism cases (79% confirmed, 21% probable) that occurred during 1929-2015 in 34 countries. Fifty-three percent were male; age ranged from 4 months to 17 years (median, 10 years). The most commonly reported signs and symptoms were dysphagia (53%), dysarthria (39%), and generalized weakness (37%). Inpatient length of stay ranged from 1 to 425 days (median, 24 days); 14% of cases required intensive care unit admission; 25% reported mechanical ventilation. Eighty-three (23%) children died. Median interval from illness onset to death was 1 day (range, 0-260 days). Among patients who received antitoxin (n = 193), 23 (12%) reported an adverse event, including rash, fever, serum sickness, and anaphylaxis. Relative risk of death among patients treated with antitoxin compared with patients not treated with antitoxin was 0.24 (95% confidence interval, .14-.40; P < .0001). Conclusions: Dysphagia and dysarthria were the most commonly reported cranial nerve symptoms in children with botulism; generalized weakness was described more than paralysis. Children who received antitoxin had better survival; serious adverse events were rare. Most deaths occurred early in the clinical course; therefore, botulism in children should be identified and treated rapidly.

      8. Type F infant botulism: Investigation of recent clusters and overview of this exceedingly rare disease
        Halpin AL, Khouri JM, Payne JR, Nakao JH, Cronquist A, Kalas N, Mohr M, Osborne M, O’Dell S, Luquez C, Klontz KC, Sobel J, Rao AK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S92-s94.
        From 1976 to 2016, neurotoxigenic Clostridium baratii type F caused 18 (<0.5%) reported US infant botulism cases. Six cases occurred during 2012-2013; no common source was identified. Type F infant botulism mostly occurs in very young infants and typically presents more rapidly and severely than illness caused by types A and B botulinum neurotoxin.

      9. A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania
        Hercik C, Cosmas L, Mogeni OD, Wamola N, Kohi W, Omballa V, Ochieng M, Lidechi S, Bonventure J, Ochieng C, Onyango C, Fields BS, Mfinanga S, Montgomery JM.
        PLoS One. 2017 ;12(12):e0189712.
        INTRODUCTION: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment. METHODS: We conducted a year-long exploratory study of fever syndrome among patients >/= 1 year if age, presenting to clinical settings with an axillary temperature of >/=37.5 degrees C and symptomatic onset of </=5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. RESULTS: From 15 September 2014-13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) >/=15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (Ct) values for Plasmodium also identified statistically significant lower mean Ct values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4). CONCLUSIONS: This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean Ct values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.

      10. Sensitivity and specificity of suspected case definition used during West Africa Ebola epidemic
        Hsu CH, Champaloux SW, Keita S, Martel L, Bilivogui P, Knust B, McCollum AM.
        Emerg Infect Dis. 2018 Jan;24(1):9-14.
        Rapid early detection and control of Ebola virus disease (EVD) is contingent on accurate case definitions. Using an epidemic surveillance dataset from Guinea, we analyzed an EVD case definition developed by the World Health Organization (WHO) and used in Guinea. We used the surveillance dataset (March-October 2014; n = 2,847 persons) to identify patients who satisfied or did not satisfy case definition criteria. Laboratory confirmation determined cases from noncases, and we calculated sensitivity, specificity and predictive values. The sensitivity of the defintion was 68.9%, and the specificity of the definition was 49.6%. The presence of epidemiologic risk factors (i.e., recent contact with a known or suspected EVD case-patient) had the highest sensitivity (74.7%), and unexplained deaths had the highest specificity (92.8%). Results for case definition analyses were statistically significant (p<0.05 by chi(2) test). Multiple components of the EVD case definition used in Guinea contributed to improved overall sensitivity and specificity.

      11. Reducing Legionnaires’ disease in public spas
        Hunter CM, Laco J, Kunz J.
        ASHRAE Journal. 2017 ;59(12):56-58.
        Data from the Centers for Disease Control and Prevention (CDC) shows improper maintenance of public spas increases risk for Legionnaires’ disease. Legionnaires’ disease affects thousands of individuals each year and represents a significant public health burden, with a 10% case fatality rate and an estimated annual hospitalization cost burden of $433 million.1,2 CDC’s Model Aquatic Health Code (MAHC) offers critical guidance for reducing the risk of Legionnaires’ disease in public aquatic facilities.

      12. A case of localized, unilateral (cephalic) wound botulism
        Jacobs Slifka K, Harris JA, Nguyen V, Luquez C, Tiwari T, Rao AK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S95-s98.
        We describe a rare presentation of botulism originally presenting with exclusively unilateral cranial nerve deficits following a puncture wound to the face. Cephalic tetanus was initially suspected but laboratory testing confirmed botulism. Botulism caused by local diffusion of toxin from a contaminated head wound can be confused with cephalic tetanus.

      13. Evolution and virulence of influenza A virus protein PB1-F2
        Kamal RP, Alymova IV, York IA.
        Int J Mol Sci. 2017 Dec 29;19(1).
        PB1-F2 is an accessory protein of most human, avian, swine, equine, and canine influenza A viruses (IAVs). Although it is dispensable for virus replication and growth, it plays significant roles in pathogenesis by interfering with the host innate immune response, inducing death in immune and epithelial cells, altering inflammatory responses, and promoting secondary bacterial pneumonia. The effects of PB1-F2 differ between virus strains and host species. This can at least partially be explained by the presence of multiple PB1-F2 sequence variants, including premature stop codons that lead to the expression of truncated PB1-F2 proteins of different lengths and specific virulence-associated residues that enhance susceptibility to bacterial superinfection. Although there has been a tendency for human seasonal IAV to gradually reduce the number of virulence-associated residues, zoonotic IAVs contain a reservoir of PB1-F2 proteins with full length, virulence-associated sequences. Here, we review the molecular mechanisms by which PB1-F2 may affect influenza virulence, and factors associated with the evolution and selection of this protein.

      14. Background: Differences in human papillomavirus (HPV) prevalence among males and females have been reported. Using the 2013-2014 National Health and Nutrition Examination Survey, we evaluated sex differences in prevalence overall and by demographic and sexual behavior characteristics. Methods: Self-collected penile and cervicovaginal swabs from participants ages 14-59 were tested for HPV DNA. Prevalences of any HPV and high-risk (HR-)HPV were estimated for sexually experienced males and females. Overall and in models stratified by demographic characteristics and behaviors, prevalence was compared in males to females using prevalence ratios (PR). Results: Overall, males had higher prevalences than females of any HPV (PR: 1.14, 95% confidence interval [CI]: 1.03-1.27) and HR-HPV (PR: 1.24, 95% CI: 1.07-1.43). Prevalences were lower among males than females at ages 14-19 and higher at ages 40-49 and 50-59. Sex differences in models stratified by race/ethnicity, poverty, sexual behaviors, and smoking were observed. After adjusting for lifetime sex partners, most sex differences were attenuated, but males had lower prevalences at ages 14-19 and 20-24 and higher HR-HPV prevalence among non-Hispanic blacks. Conclusions: Any HPV and HR-HPV prevalences were significantly higher in males; sex differences varied by age group and race/ethnicity. Lifetime partners explained many of the differences by sex.

      15. Background.: Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. Methods.: We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on >/=1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results.: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions.: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.

      16. Estimation of undiagnosed Naegleria fowleri primary amebic meningoencephalitis, United States
        Matanock A, Mehal JM, Liu L, Blau DM, Cope JR.
        Emerg Infect Dis. 2018 Jan;24(1):162-164.
        Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.

      17. Efficacy of antitoxin therapy in treating patients with foodborne botulism: A systematic review and meta-analysis of cases, 1923-2016
        O’Horo JC, Harper EP, El Rafei A, Ali R, DeSimone DC, Sakusic A, Abu Saleh OM, Marcelin JR, Tan EM, Rao AK, Sobel J, Tosh PK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S43-s56.
        Background: Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods: We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results: We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions: Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.

      18. Characteristics and outcomes of influenza-associated encephalopathy cases among children and adults in Japan, 2010-2015
        Okuno H, Yahata Y, Tanaka-Taya K, Arai S, Satoh H, Morino S, Shimada T, Sunagawa T, Uyeki TM, Oishi K.
        Clin Infect Dis. 2017 Dec 26.
        Background: Influenza-associated encephalopathy (IAE) can result in severe neurologic disease with high mortality. Most IAE cases have been reported among children worldwide; understanding of IAE among adults is limited. Methods: Data were collected on IAE cases reported through the National Epidemiological Surveillance of Infectious Diseases database in Japan during 2010 through 2015. IAE cases were stratified by age category and analyzed using descriptive statistics to assess differences in characteristics and outcomes. Results: Among 385 reported IAE cases, median age at diagnosis was 7 years (range 0-90), and 283 (74%) were children aged <18 years. The mean seasonal incidence of IAE cases among children and adults (>/=18 years) was 2.83 and 0.19 cases per 1,000,000 population, respectively. IAE incidence did not vary by predominant influenza A virus subtype. The frequency of IAE was highest in school-aged (5-12 years) children (38%), followed by young children aged 2-4 years (21%) and adults aged 18-49 years (11%). The proportion of cases with seizures was more common in pediatric IAE cases. There were more cases with cerebrospinal fluid pleocytosis among adults than in children (p<0.01), especially among those aged 18-49 (17%) and 50-64 (19%) years. Case fatality proportion was highest in those aged 40-64 (17%) and >/=65 (20%) years. Conclusions: We identified differences in the characteristics of IAE patients between adults and children in Japan. Although IAE cases were more frequently reported among children, mortality was higher in adults. Further efforts are needed to prevent and improve survival of patients with IAE, especially in adults.

      19. HIV drug resistance in adults receiving early versus delayed antiretroviral therapy: HPTN 052
        Palumbo PJ, Fogel JM, Hudelson SE, Wilson EA, Hart S, Hovind L, Piwowar-Manning E, Wallis C, Papathanasopoulos MA, Morgado MG, Saravanan S, Tripathy S, Eron JJ, Gallant JE, Mph , McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Pilotto JH, Kumwenda J, Akelo V, Godbole SV, Santos BR, Grinsztejn B, Panchia R, Chariyalertsak S, Makhema J, Badal-Faesen S, Chen YQ, Cohen MS, Eshleman SH.
        J Acquir Immune Defic Syndr. 2017 Dec 28.
        INTRODUCTION: We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral therapy (ART) in a multi-national trial (HPTN 052, enrollment 2005-2010). In HPTN 052, 1,763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm3 (early ART arm) or <250 cells/mm3 (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015. METHODS: Virologic failure was defined as two consecutive viral loads >1,000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pre-treatment (baseline) and failure samples from participants with virologic failure. RESULTS: HIV genotyping results were obtained for 211/249 participants (128 early ART arm; 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared to delayed ART arm, p=0.06; compared to delayed ART arm with ART initiation before May 2011, p=0.032). In multivariate analysis, higher baseline viral load (p=0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared to other regimens, p=0.024) were independently associated with higher risk of new resistance at failure. CONCLUSIONS: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.

      20. A case of adult intestinal toxemia botulism during prolonged hospitalization in an allogeneic hematopoietic cell transplant recipient
        Parameswaran L, Rao A, Chastain K, Ackelsburg J, Adams E, Jackson B, Voigt LP, Chen X, Boulad F, Taur Y.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S99-s102.
        We report a laboratory-confirmed case of adult intestinal toxemia botulism in an allogeneic hematopoietic stem cell transplantation (allo-HCT) recipient. Onset of symptoms occurred within the hospitalized setting, making this case particularly unique. Botulism may have arisen because of significant intestinal disruption and compromise, and not directly from immune compromise.

      21. [No abstract]

      22. Clinical criteria to trigger suspicion for botulism: An evidence-based tool to facilitate timely recognition of suspected cases during sporadic events and outbreaks
        Rao AK, Lin NH, Griese SE, Chatham-Stephens K, Badell ML, Sobel J.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S38-s42.
        Effective treatment for botulism requires early clinical recognition. Diagnosis of botulism, including during outbreaks, can be challenging. We assessed combinations of signs and symptoms among confirmed cases and identified sensitive clinical criteria to trigger suspicion. We produced a tool that may facilitate rapid identification of sporadic and outbreak-associated cases.

      23. Clinical characteristics and ancillary test results among patients with botulism – United States, 2002-2015
        Rao AK, Lin NH, Jackson KA, Mody RK, Griffin PM.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S4-s10.
        Background: Botulism is classically described as a bilateral, symmetric, descending flaccid paralysis in an afebrile and alert patient without sensory findings. We describe the reported spectrum of clinical findings among persons >12 months of age in the United States during 2002-2015. Methods: The Centers for Disease Control and Prevention collects clinical findings reported by physicians treating suspected cases of botulism nationwide. We analyzed symptoms and signs, and neuroimaging and cerebrospinal fluid (CSF) results. A case was defined as illness compatible with botulism with laboratory confirmation or epidemiologic link to a confirmed case, and presence or absence of at least 1 sign or symptom recorded. Physicians’ differential diagnoses were evaluated. Results: Clinical information was evaluated for 332 botulism cases; data quality and completeness were variable. Most had no fever (99%), descending paralysis (93%), no mental status change (91%), at least 1 ocular weakness finding (84%), and neuroimaging without acute changes (82%). Some had paresthesias (17%), elevated CSF protein level (13%), and other features sometimes considered indicative of alternative diagnoses. Five of 71 (7%) cases with sufficient information were reported to have atypical findings (eg, at least 1 cranial nerve finding that was unilateral or ascending paralysis). Illnesses on the physician differential included Guillain-Barre syndrome (99 cases) and myasthenia gravis (76 cases) and, rarely, gastrointestinal-related illness (5 cases), multiple sclerosis (3 cases), sepsis (3 cases), and Lyme disease (2 cases). Conclusions: Our analysis illustrates that classic symptoms and signs were common among patients with botulism but that features considered atypical were reported by some physicians. Diagnosis can be challenging, as illustrated by the broad range of illnesses on physician differentials.

      24. Outbreak of botulism due to illicit prison-brewed alcohol: Public health response to a serious and recurrent problem
        Rao AK, Walters M, Hall J, Guymon C, Garden R, Sturdy P, Thurston D, Smith L, Dimond M, Vitek D, Bogdanow L, Hill M, Lin NH, Luquez C, Griffin PM.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S85-s91.
        Background: Botulism is a rare, sometimes lethal neuroparalytic illness. On 2 October 2011, an inmate at prison A developed symptoms compatible with botulism after drinking pruno, an illicit, prison-brewed alcoholic beverage. Additional illnesses were identified within several days. We conducted an investigation to determine the cause and extent of the outbreak. Methods: A case was defined as signs or symptoms of botulism in a prison A inmate with onset during 30 September-9 October 2011. Cases were identified through medical evaluations and interviews with inmates about recent pruno consumption. Laboratory testing was performed for Clostridium botulinum and botulinum neurotoxin. Ingredients, preparation, and sharing of the implicated pruno were investigated. Results: Eight prisoners developed botulism; all drank pruno made with a potato. Three received mechanical ventilation. Culture of fluid from a sock that inmates reported using to filter the implicated pruno yielded C. botulinum type A. The implicated batch may have been shared between cells during delivery of meal trays. Challenges of the investigation included identifying affected inmates, overcoming inaccuracies in histories, and determining how the illicit beverage was shared. Costs to taxpayers were nearly $500000 in hospital costs alone. Conclusions: Pruno made with potato has emerged as an important cause of botulism in the United States. This public health response illustrates the difficulties of investigating botulism in correctional facilities and lessons learned for future investigations.

      25. Understanding orthopoxvirus host range and evolution: from the enigmatic to the usual suspects
        Reynolds MG, Guagliardo SA, Nakazawa YJ, Doty JB, Mauldin MR.
        Curr Opin Virol. 2017 Dec 27;28:108-115.
        In general, orthopoxviruses can be considered as falling into one of three host-utilization categories: highly specialized, single-host; broad host range; or ‘cryptic’, the last encompassing those viruses about which very little is known. Single-host viruses tend to exploit abundant hosts that have consistent patterns of interaction. For these viruses, observed genome reduction and loss of presumptive host-range genes is thought to be a consequence of relaxed selection. In contrast, the large genome size retained among broad host range orthopoxviruses suggests these viruses may depend on multiple host species for persistence in nature. Our understanding of the ecologic requirements of orthopoxviruses is strongly influenced by geographic biases in data collection. This hinders our ability to predict potential sources for emergence of orthopoxvirus-associated infections.

      26. Background: Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods: We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles’ references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results: Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Conclusions: Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.

      27. Making the best of the evidence: Toward national clinical guidelines for botulism
        Sobel J, Rao AK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S1-s3.

        [No abstract]

      28. [No abstract]

      29. Recognition of azole-resistant aspergillosis by physicians specializing in infectious diseases, United States
        Walker TA, Lockhart SR, Beekmann SE, Polgreen PM, Santibanez S, Mody RK, Beer KD, Chiller TM, Jackson BR.
        Emerg Infect Dis. 2018 Jan;24(1).
        Infections caused by pan-azole-resistant Aspergillus fumigatus strains have emerged in Europe and recently in the United States. Physicians specializing in infectious diseases reported observing pan-azole-resistant infections and low rates of susceptibility testing, suggesting the need for wider-scale testing.

      30. Increased tuberculosis risk among immigrants arriving in California with abnormal domestic chest radiographs
        Wong J, Lowenthal P, Flood J, Watt J, Barry PM.
        Int J Tuberc Lung Dis. 2018 Jan 1;22(1):73-79.
        SETTING: Tuberculosis (TB) cases in California, USA, occur predominantly among foreign-born persons, many of whom have abnormal chest radiographs (CXRs) on overseas medical examination. These persons are recommended for follow-up TB evaluation upon arrival in the United States. OBJECTIVE: To estimate the increased TB risk associated with abnormal vs. normal domestic CXRs among individuals arriving with abnormal overseas CXRs. DESIGN: Cox regression analyses of 35 633 foreign-born persons aged >/=15 years who arrived in California during 1999-2012 with abnormal overseas CXRs and were free of imported active TB. Domestic CXRs were conducted during post-arrival evaluation. Subsequent cases through 2014 were identified from California’s TB registry. RESULTS: A total of 121 (0.3%) arrivers developed TB disease. Progression rates were respectively 63.6 (95%CI 50.8-76.4) and 25.4 (95% CI 15.7-35.2) cases/100 000 person-years among persons with abnormal and normal domestic CXRs. Relative to arrivers with normal domestic CXRs, those with abnormal domestic CXRs had an elevated disease risk during the first 4 years after immigration; this increased risk was greatest during the first year (hazard ratio 2.9, 95%CI 1.8-4.8). CONCLUSION: Among arrivers with abnormal overseas CXRs, those with abnormal CXRs upon domestic evaluation have an elevated disease risk and represent an important target group for preventive treatment.

      31. Safety and improved clinical outcomes in patients treated with new equine-derived heptavalent botulinum antitoxin
        Yu PA, Lin NH, Mahon BE, Sobel J, Yu Y, Mody RK, Gu W, Clements J, Kim HJ, Rao AK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S57-s64.
        Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods: From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results: Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (</=2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

    • Disaster Control and Emergency Services
      1. We studied departures from regulatory requirements identified on US Federal Select Agent Program (FSAP) inspections to increase transparency regarding biosafety and security risk at FSAP-regulated entities and identify areas for programmatic improvement. Regulatory departures from inspections led by Centers for Disease Control and Prevention inspectors during 2014-15 were grouped into “biosafety,” “security,” and “other” observation categories and assigned a risk level and score reflecting perceived severity. The resulting 2,267 biosafety (n = 1,153) and security (n = 1,114) observations from 296 inspections were analyzed by frequency and risk across entity and inspection characteristics. The greatest proportion of biosafety observations involved equipment and facilities (28%), and the greatest proportion of security observations involved access restrictions (33%). The greatest proportion of higher-risk observations for biosafety were containment issues and for security were inventory discrepancies. Commercial entities had the highest median cumulative risk score per inspection (17), followed by private (13), academic (10), federal government (10), and nonfederal government (8). Maximum containment (BSL-4) inspections had higher median biosafety risk per inspection (13) than other inspections (5) and lower security risk (0 vs 4). Unannounced inspections had proportionally more upper risk level observations than announced (biosafety, 21% vs 12%; security, 18% vs 7%). Possessors of select agents had higher median biosafety risk per inspection (6) than nonpossessors (4) and more upper risk level security observations (10% vs 0%). Programmatic changes to balance resources according to entity risk may strengthen FSAP oversight. Varying inspection methods by select agent possession and entity type, and conducting more unannounced inspections, may be beneficial.

      2. Preparedness planning is essential to minimizing the impact of disasters on communities and individuals. Attention to the needs of people with disabilities is vital as they have additional needs before, during and after a disaster that are specific to the disabling condition. In this Commentary, we emphasize national guidelines on disability inclusion in emergency preparedness. We examine some potential areas of planning and response that need attention as suggested by preparedness data for people with self-reported disabilities (also referred to as access and functional needs) and highlight selected resources (e.g., tools, trainings, and online webinars) to enhance whole community preparedness and disability inclusion efforts. This Commentary intends to bridge the gap between those various facets of preparedness, at all levels of government and among individuals, with the aim of ensuring that the whole community is prepared to adapt, withstand and rapidly recover from disruptions due to disasters.

      3. A calculation tool and process to pre-position pharmaceuticals for anthrax post-exposure prophylaxis
        Peksa GD, Robbins MJ, Beyer AR, Weber EK, Johnson K.
        Health Secur. 2017 Nov/Dec;15(6):569-574.
        Anthrax, caused by Bacillus anthracis, is considered a severe bioterrorism threat because of its high mortality rate. The Chicago Healthcare System Coalition for Preparedness and Response (CHSCPR) aims to pre-position antibiotic medical countermeasures (MCMs) at healthcare facilities in order to provide on-site anthrax post-exposure prophylaxis. Pharmacists proposed moving toward a new process that involved the development of a standardized calculation methodology for acquiring supply drugs. This was an interventional quality improvement project aimed at optimizing inventory, acquisition, and distribution of antibiotic MCMs for anthrax post-exposure prophylaxis at Chicago hospitals for hospital personnel, associated first responders, and their families. The primary goal of the project was to pre-position a sufficient quantity of pharmaceuticals to allow Chicago hospitals to function as closed points of dispensing (PODs) for 72 hours; a secondary goal was to provide a 96-hour supply of anthrax post-exposure prophylaxis. A total of 35 Chicago hospitals were invited to participate in this intervention study, and 30 hospitals agreed to participate. Based on our calculation tool, we initially identified 6 (20%) hospitals with adequate oral doxycycline and ciprofloxacin inventory to last 72 hours and 3 (10%) hospitals with inventory to last 96 hours as a closed POD for anthrax post-exposure prophylaxis. The necessary quantities of medication needed to establish 72 and 96 hours of anthrax post-exposure prophylaxis were calculated by the CHSCPR and negotiated with a drug wholesaler to obtain product with maximum shelf-life and discounted pricing. Acting as a group purchaser, the CHSCPR organized drop shipment of medication directly to facilities from a wholesaler. This systematically calculated, pre-deployed pharmaceutical cache enhanced availability of antibiotic MCMs for anthrax post-exposure prophylaxis in 30 Chicago hospitals, allowing them to function as closed PODs for 96 hours during an incident.

    • Disease Reservoirs and Vectors
      1. Rat infestations are common, particularly in impoverished, inner-city neighborhoods. However, there has been little research into the nature and consequences of rat exposure in these neighborhoods, particularly in Canada. In this study, we sought to characterize exposure to rats and rat-associated Leptospira interrogans and Bartonella tribocorum, as well as risk factors associated with exposure, in residents (n = 202) of the Downtown Eastside (DTES) neighborhood of Vancouver, Canada. There was no evidence of exposure to rat-associated L. interrogans but 6/202 (3.0%) of participants were exposed to B. tribocorum, which is known to be circulating among DTES rats. We also found that frequent and close rat exposure was common among DTES residents, and that this exposure was particularly associated with injection drug use and outdoor income-generating activities (e.g., drug dealing). These risk factors may be good targets for interventions geared toward effectively reducing rat exposure.

      2. Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan
        Wallace RM, Lai Y, Doty JB, Chen CC, Vora NM, Blanton JD, Chang SS, Cleaton JM, Pei KJ.
        PLoS One. 2018 ;13(1):e0189998.
        BACKGROUND: Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. METHODOLOGY/PRINCIPLE FINDINGS: As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. CONCLUSIONS/SIGNIFICANCE: Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent ‘dog to ferret-badger’ host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals’ competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be considered in future studies.

    • Environmental Health
      1. Prenatal maternal serum concentrations of per- and polyfluoroalkyl substances in association with autism spectrum disorder and intellectual disability
        Lyall K, Yau VM, Hansen R, Kharrazi M, Yoshida CK, Calafat AM, Windham G, Croen LA.
        Environ Health Perspect. 2018 Jan 2;126(1):017001.
        BACKGROUND: Emerging work has examined neurodevelopmental outcomes following prenatal exposure to per- and polyfluoroalkyl substances (PFAS), but few studies have assessed associations with autism spectrum disorder (ASD). OBJECTIVES: Our objective was to estimate associations of maternal prenatal PFAS concentrations with ASD and intellectual disability (ID) in children. METHODS: Participants were from a population-based nested case-control study of children born from 2000 to 2003 in southern California, including children diagnosed with ASD (n=553), ID without autism (n=189), and general population (GP) controls (n=433). Concentrations of eight PFAS from stored maternal sera collected at 15-19 wk gestational age were quantified and compared among study groups. We used logistic regression to obtain adjusted odds ratios for the association between prenatal PFAS concentrations (parameterized continuously and as quartiles) and ASD versus GP controls, and separately for ID versus GP controls. RESULTS: Geometric mean concentrations of most PFAS were lower in ASD and ID groups relative to GP controls. ASD was not significantly associated with prenatal concentrations of most PFAS, though significant inverse associations were found for perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) [adjusted ORs for the highest vs. lowest quartiles 0.62 (95% CI: 0.41, 0.93) and 0.64 (95% CI: 0.43, 0.97), respectively]. Results for ID were similar. CONCLUSIONS: Results from this large case-control study with prospectively collected prenatal measurements do not support the hypothesis that prenatal exposure to PFAS is positively associated with ASD or ID.

    • Food Safety
      1. The epidemiology of foodborne botulism outbreaks: A systematic review
        Fleck-Derderian S, Shankar M, Rao AK, Chatham-Stephens K, Adjei S, Sobel J, Meltzer MI, Meaney-Delman D, Pillai SK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S73-s81.
        Background: We performed a systematic review of foodborne botulism outbreaks to describe their clinical aspects and descriptive epidemiology in order to inform public health response strategies. Methods: We searched seven databases for reports of foodborne botulism outbreaks published in English from database inception to May 2015. We summarized descriptive characteristics and analyzed differences in exposure and toxin types by geographic region. We performed logistic regression to assess correlations between exposure source, implicated food, and outbreak size. Results: There were 197 outbreaks reported between 1920 and 2014. The median number of cases per outbreak was 3 (range 2-97). The majority of reported outbreaks (109; 55%) occurred in the United States. Toxin types A, B, E, and F were identified as the causative agent in 34%, 16%, 17%, and 1% of outbreaks, respectively. The median duration between exposure and symptom onset was approximately 1 day. The mean percentage of cases requiring mechanical ventilation per outbreak was 34%. Seventy percent of all outbreaks and 77% of small outbreaks (</=11 cases) originated from point source exposures, while commercial foods were significantly (odds ratio, 6.9; 95% confidence interval, 2.2-21.1) associated with large outbreaks (>/=12 cases). Conclusions: Toxin type A accounted for half of outbreaks, and these outbreaks had a higher proportion of patient ventilatory failure. Most outbreaks were due to point source exposures, while outbreaks due to commercial food were larger. For effective responses to foodborne botulism outbreaks, these findings demonstrate the need for timely outbreak investigation and hospital surge capacity.

      2. Outbreak of foodborne botulism in an immigrant community: Overcoming delayed disease recognition, ambiguous epidemiologic links, and cultural barriers to identify the cause
        Harvey RR, Cooper R, Bennett S, Richardson M, Duke D, Stoughton C, Smalligan R, Gaul L, Drenzek C, Griffin PM, Geissler A, Rao AK.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S82-s84.
        We describe a botulism outbreak involving 4 Middle Eastern men complicated by delayed diagnosis, ambiguous epidemiologic links among patients, and illness onset dates inconsistent with a point-source exposure. Homemade turshi, a fermented vegetable dish, was the likely cause. Patients ate turshi at 2 locations on different days over 1 month.

    • Genetics and Genomics
      1. Proposed outcomes measures for state public health genomic programs
        Doyle DL, Clyne M, Rodriguez JL, Cragun DL, Senier L, Hurst G, Chan K, Chambers DA.
        Genet Med. 2018 Jan 4.
        PurposeTo assess the implementation of evidence-based genomic medicine and its population-level impact on health outcomes and to promote public health genetics interventions, in 2015 the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine formed an action collaborative, the Genomics and Public Health Action Collaborative (GPHAC). This group engaged key stakeholders from public/population health agencies, along with experts in the fields of health disparities, health literacy, implementation science, medical genetics, and patient advocacy.MethodsIn this paper, we present the efforts to identify performance objectives and outcome metrics. Specific attention is placed on measures related to hereditary breast ovarian cancer (HBOC) syndrome and Lynch syndrome (LS), two conditions with existing evidence-based genomic applications that can have immediate impact on morbidity and mortality.ResultsOur assessment revealed few existing outcome measures. Therefore, using an implementation research framework, 38 outcome measures were crafted.ConclusionEvidence-based public health requires outcome metrics, yet few exist for genomics. Therefore, we have proposed performance objectives that states might use and provided examples of a few state-level activities already under way, which are designed to collect outcome measures for HBOC and LS.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.229.

      2. Phylogenetic inference of Coxiella burnetii by 16S rRNA gene sequencing
        McLaughlin HP, Cherney B, Hakovirta JR, Priestley RA, Conley A, Carter A, Hodge D, Pillai SP, Weigel LM, Kersh GJ, Sue D.
        PLoS One. 2017 ;12(12):e0189910.
        Coxiella burnetii is a human pathogen that causes the serious zoonotic disease Q fever. It is ubiquitous in the environment and due to its wide host range, long-range dispersal potential and classification as a bioterrorism agent, this microorganism is considered an HHS Select Agent. In the event of an outbreak or intentional release, laboratory strain typing methods can contribute to epidemiological investigations, law enforcement investigation and the public health response by providing critical information about the relatedness between C. burnetii isolates collected from different sources. Laboratory cultivation of C. burnetii is both time-consuming and challenging. Availability of strain collections is often limited and while several strain typing methods have been described over the years, a true gold-standard method is still elusive. Building upon epidemiological knowledge from limited, historical strain collections and typing data is essential to more accurately infer C. burnetii phylogeny. Harmonization of auspicious high-resolution laboratory typing techniques is critical to support epidemiological and law enforcement investigation. The single nucleotide polymorphism (SNP) -based genotyping approach offers simplicity, rapidity and robustness. Herein, we demonstrate SNPs identified within 16S rRNA gene sequences can differentiate C. burnetii strains. Using this method, 55 isolates were assigned to six groups based on six polymorphisms. These 16S rRNA SNP-based genotyping results were largely congruent with those obtained by analyzing restriction-endonuclease (RE)-digested DNA separated by SDS-PAGE and by the high-resolution approach based on SNPs within multispacer sequence typing (MST) loci. The SNPs identified within the 16S rRNA gene can be used as targets for the development of additional SNP-based genotyping assays for C. burnetii.

    • Health Economics
      1. Relevance of global health security to the US export economy
        Cassell CH, Bambery Z, Roy K, Meltzer MI, Ahmed Z, Payne RL, Bunnell RE.
        Health Secur. 2017 Nov/Dec;15(6):563-568.
        To reduce the health security risk and impact of outbreaks around the world, the US Centers for Disease Control and Prevention and its partners are building capabilities to prevent, detect, and contain outbreaks in 49 global health security priority countries. We examine the extent of economic vulnerability to the US export economy posed by trade disruptions in these 49 countries. Using 2015 US Department of Commerce data, we assessed the value of US exports and the number of US jobs supported by those exports. US exports to the 49 countries exceeded $308 billion and supported more than 1.6 million jobs across all US states in agriculture, manufacturing, mining, oil and gas, services, and other sectors. These exports represented 13.7% of all US export revenue worldwide and 14.3% of all US jobs supported by all US exports. The economic linkages between the United States and these global health security priority countries illustrate the importance of ensuring that countries have the public health capacities needed to control outbreaks at their source before they become pandemics.

    • Healthcare Associated Infections
      1. Notes from the field: Investigation of carbapenemase-producing carbapenem-resistant Enterobacteriaceae among patients at a community hospital – Kentucky, 2016
        Chae SR, Yaffee AQ, Weng MK, Ham DC, Daniels K, Wilburn AB, Porter KA, Flinchum AH, Boyd S, Shams A, Walters MS, Kallen A.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 5;66(5152):1410.

        [No abstract]

      2. Nipah virus contamination of hospital surfaces during outbreaks, Bangladesh, 2013-2014
        Hassan MZ, Sazzad HM, Luby SP, Sturm-Ramirez K, Bhuiyan MU, Rahman MZ, Islam MM, Stroher U, Sultana S, Kafi MA, Daszak P, Rahman M, Gurley ES.
        Emerg Infect Dis. 2018 Jan;24(1):15-21.
        Nipah virus (NiV) has been transmitted from patient to caregivers in Bangladesh presumably through oral secretions. We aimed to detect whether NiV-infected patients contaminate hospital surfaces with the virus. During December 2013-April 2014, we collected 1 swab sample from 5 surfaces near NiV-infected patients and tested surface and oral swab samples by real-time reverse transcription PCR for NiV RNA. We identified 16 Nipah patients; 12 cases were laboratory-confirmed and 4 probable. Of the 12 laboratory-confirmed cases, 10 showed NiV RNA in oral swab specimens. We obtained surface swab samples for 6 Nipah patients; 5 had evidence of NiV RNA on >1 surface: 4 patients contaminated towels, 3 bed sheets, and 1 the bed rail. Patients with NiV RNA in oral swab samples were significantly more likely than other Nipah patients to die. To reduce the risk for fomite transmission of NiV, infection control should target hospital surfaces.

    • Immunity and Immunization
      1. Impact and effectiveness of pentavalent rotavirus vaccine in children <5 years of age in Burkina Faso
        Bonkoungou IJ, Aliabadi N, Leshem E, Kam M, Nezien D, Drabo MK, Nikiema M, Ouedraogo B, Medah I, Konate S, Ouedraogo-Traore R, Sangare L, Kam L, Ye D, Ouattara M, Biey JN, Mwenda JM, Tate JE, Parashar UD.
        Vaccine. 2017 Dec 28.
        BACKGROUND: Burkina Faso was one of the first African nations to introduce pentavalent rotavirus vaccine (RV5, RotaTeq) into its national immunization program in October 2013. We describe the impact and effectiveness of rotavirus vaccine on acute gastroenteritis (AGE) hospitalizations among Burkinabe children. METHODS: Sentinel hospital-based surveillance for AGE was conducted at four hospitals during December 2013 – February 2017. Demographic, clinical, and vaccination information was collected and stool specimens were tested by EIA. Trends in rotavirus AGE hospitalizations and changes in the proportion of AGE hospitalizations due to rotavirus were examined at two sentinel sites from January 2014 – December 2016. Unconditional logistic regression models using data from all 4 surveillance sites were used to calculate vaccine effectiveness (VE, defined as 1-odds ratio) by comparing the odds of vaccination among rotavirus AGE (cases) and non-rotavirus AGE (controls) patients, controlling for age, season, hospital site and socioeconomic factors. RESULTS: The proportion of AGE hospitalizations that tested positive for rotavirus declined significantly among children <5years of age, from 36% (154/422) in 2014 to 22% (71/323, 40% reduction, p<.01) in 2015 and 20% (61/298, 44% reduction, p<.01) in 2016. Among infants, the percentage of AGE admissions due to rotavirus fell significantly from 38% (94/250) in 2014 to 21% (32/153, 44% reduction, p<.01) in 2015 and 17% (26/149, 54% reduction, p<.01) in 2016. The adjusted VE for full 3-dose series of RV5 against rotavirus hospitalization was 58% (95% [CI], 10%, 81%) in children 6-11months of age and 19% (-78%, 63%) in children >/=12months. CONCLUSION: Rotavirus hospitalizations declined after introduction of pentavalent rotavirus vaccine in children, particularly among infants. RV5 significantly protected against severe rotavirus gastroenteritis in infants, but effectiveness decreased in older children.

      2. State of equity: childhood immunization in the World Health Organization African Region
        Casey RM, Hampton LM, Anya BM, Gacic-Dobo M, Diallo MS, Wallace AS.
        Pan Afr Med J. 2017 ;27(Suppl 3):5.
        Introduction: In 2010, the Global Vaccine Action Plan called on all countries to reach and sustain 90% national coverage and 80% coverage in all districts for the third dose of diphtheria-tetanus-pertussis vaccine (DTP3) by 2015 and for all vaccines in national immunization schedules by 2020. The aims of this study are to analyze recent trends in national vaccination coverage in the World Health Organization African Region andto assess how these trends differ by country income category. Methods: We compared national vaccination coverage estimates for DTP3 and the first dose of measles-containing vaccine (MCV) obtained from the World Health Organization (WHO)/United Nations Children’s Fund (UNICEF) joint estimates of national immunization coverage for all African Region countries. Using United Nations (UN) population estimates of surviving infants and country income category for the corresponding year, we calculated population-weighted average vaccination coverage by country income category (i.e., low, lower middle, and upper middle-income) for the years 2000, 2005, 2010 and 2015. Results: DTP3 coverage in the African Region increased from 52% in 2000 to 76% in 2015,and MCV1 coverage increased from 53% to 74% during the same period, but with considerable differences among countries. Thirty-six African Region countries were low income in 2000 with an average DTP3 coverage of 50% while 26 were low income in 2015 with an average coverage of 80%. Five countries were lower middle-income in 2000 with an average DTP3 coverage of 84% while 12 were lower middle-income in 2015 with an average coverage of 69%. Five countries were upper middle-income in 2000 with an average DTP3 coverage of 73% and eight were upper middle-income in 2015 with an average coverage of 76%. Conclusion: Disparities in vaccination coverage by country persist in the African Region, with countries that were lower middle-income having the lowest coverage on average in 2015. Monitoring and addressing these disparities is essential for meeting global immunization targets.

      3. [No abstract]

      4. The WHO Tailoring Immunization Programmes (TIP) approach: Review of implementation to date
        Dube E, Leask J, Wolff B, Hickler B, Balaban V, Hosein E, Habersaat K.
        Vaccine. 2017 Dec 26.
        INTRODUCTION: The WHO Regional Office for Europe developed the Guide to tailoring immunization programmes (TIP), offering countries a process through which to diagnose barriers and motivators to vaccination in susceptible low vaccination coverage and design tailored interventions. A review of TIP implementation was conducted in the European Region. MATERIAL AND METHODS: The review was conducted during June to December 2016 by an external review committee and was based on visits in Bulgaria, Lithuania, Sweden and the United Kingdom that had conducted a TIP project; review of national and regional TIP documents and an online survey of the Member States in the WHO European Region that had not conducted a TIP project. A review committee workshop was held to formulate conclusions and recommendations. RESULTS: The review found the most commonly cited strengths of the TIP approach to be the social science research as well as the interdisciplinary approach and community engagement, enhancing the ability of programmes to “listen” and learn, to gain an understanding of community and individual perspectives. National immunization managers in the Region are generally aware that TIP exists and that there is strong demand for the type of research it addresses. Further work is needed to assist countries move towards implementable strategies based on the TIP findings, supported by an emphasis on enhanced local ownership; integrated diagnostic and intervention design; and follow-up meetings, advocacy and incentives for decision-makers to implement and invest in strategies. CONCLUSIONS: Understanding the perspectives of susceptible and low-coverage populations is crucial to improving immunization programmes. TIP provides a framework that facilitated this in four countries. In the future, the purpose of TIP should go beyond identification of susceptible groups and diagnosis of challenges and ensure a stronger focus on the design of strategies and appropriate and effective interventions to ensure long-term change.

      5. Immunization delivery in the second year of life in Ghana: the need for a multi-faceted approach
        Nyaku M, Wardle M, Eng JV, Ametewee L, Bonsu G, Larbi Opare JK, Conklin L.
        Pan Afr Med J. 2017 ;27(Suppl 3):4.
        Introduction: in 2012, pneumococcal conjugate vaccine (PCV), rotavirus vaccine and a second dose of measles-containing vaccine (MCV2) were introduced into the Expanded Program on Immunization (EPI) in Ghana. According to Ghana’s EPI schedule, PCV and rotavirus vaccine are given in the first year of life and MCV2 in the second year of life (2YL) at 18 months. Although coverage with the last doses of PCV and rotavirus vaccine reached almost 90% coverage within four years of introduction, MCV2 coverage did not rise above 70%. The World Health Organization Global Measles and Rubella Strategic Plan established a 2020 milestone to achieve at least 95% coverage with the first and second doses of measles-containing vaccine in each district and nationally. We developed a project to address challenges to delivery of immunizations and other child health services at the 18-month visit and throughout the 2YL. Methods: from March to April 2016, we conducted a cluster survey of households (HHs) with children 24-35 months of age in three regions in Ghana to assess knowledge, attitudes and beliefs among caregivers about immunization during the 2YL and to collect childhood vaccination history data using vaccination cards. Three independent samples were selected from the Northern (NR), Volta (VR), and Greater Accra (GAR) regions. A survey and direct observations were performed a ta representative sample of health facilities (HFs) providing immunization services in the same regions to further characterize barriers to immunization access, utilization and delivery in the 2YL. Results: data on a total of 464 children ages 24-35 months were collected in the HH survey: 211 in NR, 153 in VR, and 100 in GAR (response rate > 99%). First dose of measles-containing vaccine (MCV1) coverage was (NR: 87%, VR: 96%, GAR: 99%); however, MCV2 coverage was lower (NR: 60%, VR: 83%, GAR: 70%). MCV1 to MCV2 dropout was 32% in NR, 14% in VR, and 31% in GAR. Caregiver awareness of immunization against measles was 69% in NR, 75% in VR, and 68% in GAR yet less than half knew the recommended ages for receiving the vaccine, (NR: 4%, VR: 9%, GAR: 44%). Among 160 HFs participating in the survey (>50 in each region), most lacked a defaulter tracing system (NR: 94%,VR: 76%,GAR: 85%). A varying proportion of HCWs correctly indicated how to record a catch-up first dose of MCV administered to an 18-month-old child in the 12-23 month immunization register (NR: 38%, VR: 55%, GAR: 67%) and on the vaccination card (NR: 54%, VR: 53%, GAR: 76%). Although more than half of caregivers would accept text messages, (NR: 57%, VR: 78%, GAR: 96%) including reminders, related to their child’s immunizations, < 10% HFs were utilizing this practice. Conclusion: challenges encountered with the establishment of an immunization visit beyond the first year of life included knowledge gaps among caregivers, high dropout rates between MCV1 and MCV2 in all study regions, and a lack of defaulter tracing systems in most healthcare facilities providing childhood immunizations. Targeted strategies that promote behavioral, cultural, and policy changes are needed to strengthen 2YL child health service delivery and improve vaccination coverage.

      6. Introduction: Missed opportunities and barriers to vaccination limit progress toward achieving high immunization coverage and other global immunization goals. Little is known about vaccination practices contributing to missed opportunities and barriers among private healthcare providers in Africa. Methods: Service Provision Assessments (SPA) of representative samples of health facilities in four African countries (Kenya, Tanzania, Senegal, Malawi) in 2010-2015 were used to describe missed opportunities and barriers for vaccination in public, private for-profit, private not-for-profit and faith-based facilities. Data included vaccination practices, observations during sick child and antenatal visits, and exit interviews following sick child visits. Results: Data from 3,219 health facilities, 11,613 sick child visits and 8,698 antenatal visits were included. A smaller proportion of for-profit facilities offered child vaccination services (country range, 25-37%) than did public facilities (range, 90-96%). The proportion of facilities offering pentavalent vaccine (diphtheria, pertussis, tetanus, hepatitis B and Haemophilus influenza type b antigens) daily ranged 0-77% across countries and facility types. Less than 33% of for-profit facilities in any country offered measles vaccination daily. A minority of public or private providers assessed the child’s vaccination status during a sick child visit (range by country and facility type, 14-44%), or offered tetanus toxoid during antenatal visits (range, 19-51%). Very few providers discussed the importance of newborn vaccination. Conclusion: Substantial missed opportunities for, and barriers to, vaccination were identified across this representative sample of health facilities in four African countries. Strategies are needed to ensure that private and public providers implement practices to minimize barriers and missed opportunities for vaccination.

      7. Progress towards achieving and maintaining maternal and neonatal tetanus elimination in the African region
        Ridpath AD, Scobie HM, Shibeshi ME, Yakubu A, Zulu F, Raza AA, Masresha B, Tohme R.
        Pan Afr Med J. 2017 ;27(Suppl 3):24.
        Despite the availability of effective tetanus prevention strategies, as of 2016, Maternal and Neonatal Tetanus Elimination (MNTE) has not yet been achieved in 18 countries globally. In this paper, we review the status of MNTE in the World Health Organization African Region (AFR),and provide recommendations for achieving and maintaining MNTE in AFR. As of November 2016, 37 (79%) AFR countries have achieved MNTE, with 10 (21%) countries remaining. DTP3 coverage increased from 52% in 2000 to 76% in 2015. In 2015, coverage with at least 2 doses of tetanus containing vaccine (TT2+) and proportion of newborns protected at birth (PAB) were 69% and 77%, compared with 44% and 62% in 2000, respectively. Since 1999, over 79 million women of reproductive age (WRA) have been vaccinated with TT2+ through supplementary immunization activities (SIAs). Despite the progress, only 54% of births were attended by skilled birth attendants (SBAs), 5 (11%) countries provided the 3 WHO-recommended booster doses to both sexes, and about 5.5 million WRA still need to be reached with SIAs. Coverage disparities still exist between countries that have achieved MNTE and those that have not. In 2015, coverage with DTP3 and PAB were higher in MNTE countries compared with those yet to achieve MNTE: 84% vs. 68% and 86% vs. 69%, respectively. Challenges to achieving MNTE in the remaining AFR countries include weak health systems, competing priorities, insufficient funding, insecurity, and sub-optimal neonatal tetanus (NT) surveillance. To achieve and maintain MNTE in AFR, increasing SBAs and tetanus vaccination coverage, integrating tetanus vaccination with other opportunities (e.g., polio and measles campaigns, mother and child health days), and providing appropriately spaced booster doses are needed. Strengthening NT surveillance and conducting serosurveys would ensure appropriate targeting of MNTE activities and high-quality information for validating the achievement and maintenance of elimination.

      8. Innovations in adult influenza vaccination in China, 2014-2015: Leveraging a chronic disease management system in a community-based intervention
        Yi B, Zhou S, Song Y, Chen E, Lao X, Cai J, Greene CM, Feng L, Zheng J, Yu H, Dong H.
        Hum Vaccin Immunother. 2018 Jan 4:0.
        OBJECTIVES: To evaluate a community-based intervention that leveraged the non-communicable disease management system to increase seasonal influenza vaccination coverage among older adults in Ningbo, China. METHODS: From October 2014 – March 2015, we piloted the following on one street in Ningbo, China: educating community healthcare workers (C-HCWs) about influenza and vaccination; requiring C-HCWs to recommend influenza vaccination to older adults during routine chronic disease follow-up; and opening 14 additional temporary vaccination clinics. We selected a non-intervention street for comparison pre- and post-intervention vaccine coverage. In April 2016, we interviewed a random sample of unvaccinated older adults on the intervention street to ask why they remained unvaccinated. RESULTS: Pre-intervention influenza vaccine coverage among adults aged 60 years and older on both streets was 0.3%. Post-intervention, coverage among adults 60 years and older was 19% (1338/7013) on the intervention street and 0.4% (20/5500) on the non-intervention street (p<0.01). Among vaccinated older adults, 98% reported their main reason for vaccination was receiving a C-HCW’s recommendation, 90% were vaccinated at temporary vaccination clinics, and 53% paid for vaccine (10 USD) out-of-pocket. Reasons for not getting vaccinated among 150 unvaccinated adults (response rate = 75%) included: good health (39%); not trusting C-HCWs’ recommendations (24%); not knowing where to get vaccinated (17%); and not wanting to pay (9%). CONCLUSIONS: Recommending influenza vaccination within a non-communicable disease management system, combined with adding vaccination sites, increased vaccine coverage among older adults in Ningbo, China.

    • Injury and Violence
      1. Applying structural equation modeling to measure violence exposure and its impact on mental health: Malawi Violence Against Children and Young Women Survey, 2013
        Fan AZ, Liu J, Kress H, Gupta S, Shawa M, Wadonda-Kabondo N, Mercy J.
        J Interpers Violence. 2017 Nov 1:886260517741214.
        This study examines exposure to multiple forms of violence among Malawian children and youth and their association with mental health outcomes. The Malawi Violence Against Children and Young Women Survey was conducted among a nationally representative sample of males and females aged 13 to 24 years ( n = 2,162) in Malawi in 2013. The experience of sexual, physical, and emotional violence prior to age 18 and during the past 12 months and associated health outcomes were ascertained using a comprehensive interview. Latent factors of sexual violence, physical violence, and emotional violence as well as psychological distress were constructed. We examined whether the experience of violence was related to psychological distress after controlling for age and gender. Violence exposure prior to age 18 (early life) and during the past 12 months (proximal) were valid indicators for a latent factor representing overall lifetime violence exposure. Females were more likely to experience sexual violence, whereas males were more likely to experience physical violence. Experience of any type of violence decreased with age whereas experience of psychological distress increased with age. Current psychological distress was directly associated with exposure to sexual and emotional violence recently or during childhood. Exposure to multiple forms of violence during lifetime was related to two to seven folds higher odds of experiencing psychological distress compared with those who had never experienced violence. Future intervention strategies should address three forms of violence against children simultaneously in light of the associated adverse mental health outcomes.

      2. Peer influence on IPV by young adult males: Investigating the case for a social norms approach
        McKool M, Stephenson R, Winskell K, Teten Tharp A, Parrott D.
        J Interpers Violence. 2017 Aug 1:886260517725735.
        Nearly 32% of women report experiencing physical violence from an intimate partner and more than 8% report being raped by a significant other in their lifetime. Young people’s perceptions that their peers perpetrate relationship violence have been shown to increase the odds of self-reported perpetration. Yet, limited research has been conducted on this relationship as individuals begin to age out of adolescence. The present study sought to examine the link between the perception of peer perpetration of intimate partner violence (IPV) and self-reported IPV perpetration among a sample of predominately young adult (21-35 years) males. This study also explored the discordance between the perception of peer IPV behavior and self-reported perpetration. Data from 101 male peer dyads ( n = 202) were taken from a study on the effects of alcohol and bystander intervention in Atlanta, Georgia. Thirty-six percent ( n = 73) of men reported perpetrating physical IPV and 67% ( n = 135) reported perpetrating sexual IPV in the past 12 months. Nearly 35% ( n = 55) of the sample reported that none of their peers had perpetrated physical IPV, which contradicted their friend’s self-report of physical IPV perpetration. Similarly, 68% ( n = 115) of the men perceived none of their peers to have perpetrated sexual IPV, which contradicted their friend’s self-report of sexual IPV perpetration. Discordance variables were significantly associated with self-reported perpetration for both physical (chi(2) = 152.7, p < .01) and sexual (chi(2) = 164.4, p < .01) IPV. These results point to an underestimation of peer IPV perpetration among young adult males. Findings suggest a traditional social norms approach to IPV prevention, which seeks to persuade individuals that negative behaviors are less common than perceived, may not be the best approach given a significant number of men believed their friends were nonviolent when they had perpetrated violence.

      3. Physical and sexual teen dating violence victimization and sexual identity among U.S. high school students, 2015
        Olsen EO, Vivolo-Kantor A, Kann L.
        J Interpers Violence. 2017 May 1:886260517708757.
        Lesbian, gay, and bisexual (LGB) youth are at risk for many negative behaviors associated with teen dating violence victimization (TDVV). This study describes the prevalence of physical and sexual TDVV by sexual identity and quantifies the increased risk for TDVV among LGB youth compared with heterosexual youth. The participants for this study were students in Grades 9 to 12 participating in the 2015 national Youth Risk Behavior Survey (YRBS) who responded to questions ascertaining sexual identity and both physical and sexual TDVV. Data were analyzed by sexual identity, stratified by sex, and controlled for race/ethnicity and grade in school. Frequencies of physical and sexual TDVV and prevalence of TDVV from a combined TDVV measure were calculated. Associations between these behaviors and sexual identity were identified. Generally, LGB youth had greater prevalence and frequency of TDVV compared with heterosexual youth. Prevalence of TDVV within sexual identity subgroups further differed by sex. Students who were not sure of their sexual identity had the highest risk of most categories of TDVV when adjusting for sex, race/ethnicity, and grade in school. These results are the first to use a nationally representative sample to describe frequency of TDVV and to determine prevalence of a combined physical and sexual TDVV measure by sexual identity among youth. Schools, communities, and families can help prevent teen dating violence and ameliorate the potential impacts of these victimizations.

      4. Families experiencing child maltreatment or risk factors for child maltreatment often receive referrals to interventions focused on changing parenting practices. Compliance with specific parenting programs can be challenging as many of the stressors that place families at-risk may also interfere with program participation. Because families may receive limited benefit from programs they do not fully receive, it is critical to understand the relationship between parenting stress and barriers to program completion. We used structural equation modeling to examine the relationship among parenting stress, perceived barriers to program participation, and program completion in two datasets involving low-income parents. Data were collected at two time points from a sample of parents involved with child welfare services and a sample of parents considered at-risk of future involvement (total study n = 803). Direct paths from parenting stress at time 1 to barriers to participation and parenting stress at time 2, and from parenting stress at time 2 to program completion were significant. Interestingly, increased barriers to participation were related to increased parenting stress at time 2, and greater parenting stress was related to increased program completion. Results suggest that with increasing levels of parenting stress, parents have an increased likelihood of completing the program. Assessing and addressing the influence of perceived barriers and parenting stress on program participation may decrease the likelihood of treatment attrition.

    • Laboratory Sciences
      1. Mammalian pathogenesis and transmission of avian influenza A(H7N9) viruses, Tennessee, USA, 2017
        Belser JA, Brock N, Sun X, Jones J, Zanders N, Hodges E, Pulit-Penaloza JA, Wentworth D, Tumpey TM, Davis T, Maines TR.
        Emerg Infect Dis. 2018 Jan;24(1):149-152.
        Infections with low pathogenicity and highly pathogenic avian influenza A(H7N9) viruses affected poultry in 4 states in the southeastern United States in 2017. We evaluated pathogenicity and transmission of representative viruses in mouse and ferret models and examined replication kinetics in human respiratory tract cells. These viruses can cause respiratory infections in mammalian models.

      2. Standardization and validation of real time PCR assays for the diagnosis of histoplasmosis using three molecular targets in an animal model
        Lopez LF, Munoz CO, Caceres DH, Tobon AM, Loparev V, Clay O, Chiller T, Litvintseva A, Gade L, Gonzalez A, Gomez BL.
        PLoS One. 2017 ;12(12):e0190311.
        Histoplasmosis is considered one of the most important endemic and systemic mycoses worldwide. Until now few molecular techniques have been developed for its diagnosis. The aim of this study was to develop and evaluate three real time PCR (qPCR) protocols for different protein-coding genes (100-kDa, H and M antigens) using an animal model. Fresh and formalin-fixed and paraffin-embedded (FFPE) lung tissues from BALB/c mice inoculated i.n. with 2.5×106 Histoplasma capsulatum yeast or PBS were obtained at 1, 2, 3, 4, 8, 12 and 16 weeks post-infection. A collection of DNA from cultures representing different clades of H. capsulatum (30 strains) and other medically relevant pathogens (36 strains of related fungi and Mycobacterium tuberculosis) were used to analyze sensitivity and specificity. Analytical sensitivity and specificity were 100% when DNAs from the different strains were tested. The highest fungal burden occurred at first week post-infection and complete fungal clearance was observed after the third week; similar results were obtained when the presence of H. capsulatum yeast cells was demonstrated in histopathological analysis. In the first week post-infection, all fresh and FFPE lung tissues from H. capsulatum-infected animals were positive for the qPCR protocols tested except for the M antigen protocol, which gave variable results when fresh lung tissue samples were analyzed. In the second week, all qPCR protocols showed variable results for both fresh and FFPE tissues. Samples from the infected mice at the remaining times post-infection and uninfected mice (controls) were negative for all protocols. Good agreement was observed between CFUs, histopathological analysis and qPCR results for the 100-kDa and H antigen protocols. We successfully standardized and validated three qPCR assays for detecting H. capsulatum DNA in fresh and FFPE tissues, and conclude that the 100-kDa and H antigen molecular assays are promising tests for diagnosing this mycosis.

      3. The reduction of gunshot noise and auditory risk through the use of firearm suppressors and low-velocity ammunition
        Murphy WJ, Flamme GA, Campbell AR, Zechmann EL, Tasko SM, Lankford JE, Meinke DK, Finan DS, Stewart M.
        Int J Audiol. 2018 Jan 4:1-14.
        OBJECTIVE: This research assessed the reduction of peak levels, equivalent energy and sound power of firearm suppressors. DESIGN: The first study evaluated the effect of three suppressors at four microphone positions around four firearms. The second study assessed the suppressor-related reduction of sound power with a 3 m hemispherical microphone array for two firearms. RESULTS: The suppressors reduced exposures at the ear between 17 and 24 dB peak sound pressure level and reduced the 8 h equivalent A-weighted energy between 9 and 21 dB depending upon the firearm and ammunition. Noise reductions observed for the instructor’s position about a metre behind the shooter were between 20 and 28 dB peak sound pressure level and between 11 and 26 dB LAeq,8h. Firearm suppressors reduced the measured sound power levels between 2 and 23 dB. Sound power reductions were greater for the low-velocity ammunition than for the same firearms fired with high-velocity ammunition due to the effect of N-waves produced by a supersonic bullet. CONCLUSIONS: Firearm suppressors may reduce noise exposure, and the cumulative exposures of suppressed firearms can still present a significant hearing risk. Therefore, firearm users should always wear hearing protection whenever target shooting or hunting.

      4. Monoclonal antibody that recognizes diethoxyphosphotyrosine-modified proteins and peptides independent of surrounding amino acids
        Onder S, Dafferner AJ, Schopfer LM, Xiao G, Yerramalla U, Tacal O, Blake TA, Johnson RC, Lockridge O.
        Chem Res Toxicol. 2017 Dec 18;30(12):2218-2228.
        Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are irreversibly inhibited by organophosphorus pesticides through formation of a covalent bond with the active site serine. Proteins that have no active site serine, for example albumin, are covalently modified on tyrosine and lysine. Chronic illness from pesticide exposure is not explained by inhibition of AChE and BChE. Our goal was to produce a monoclonal antibody that recognizes proteins diethoxyphosphorylated on tyrosine. Diethoxyphosphate-tyrosine adducts for 13 peptides were synthesized. The diethoxyphosphorylated (OP) peptides cross-linked to four different carrier proteins were used to immunize, boost, and screen mice. Monoclonal antibodies were produced with hybridoma technology. Monoclonal antibody depY was purified and characterized by ELISA, western blotting, Biacore, and Octet technology to determine binding affinity and binding specificity. DepY recognized diethoxyphosphotyrosine independent of the amino acid sequence around the modified tyrosine and independent of the identity of the carrier protein or peptide. It had an IC50 of 3 x 10(-9) M in a competition assay with OP tubulin. Kd values measured by Biacore and OctetRED96 were 10(-8) M for OP-peptides and 1 x 10(-12) M for OP-proteins. The limit of detection measured on western blots hybridized with 0.14 mug/mL of depY was 0.025 mug of human albumin conjugated to YGGFL-OP. DepY was specific for diethoxyphosphotyrosine (chlorpyrifos oxon adduct) as it failed to recognize diethoxyphospholysine, phosphoserine, phosphotyrosine, phosphothreonine, dimethoxyphosphotyrosine (dichlorvos adduct), dimethoxyphosphoserine, monomethoxyphosphotyrosine (aged dichlorvos adduct), and cresylphosphoserine. In conclusion, a monoclonal antibody that specifically recognizes diethoxyphosphotyrosine adducts has been developed. The depY monoclonal antibody could be useful for identifying new biomarkers of OP exposure.

      5. Physical chemical properties and cell toxicity of sanding copper-treated lumber
        Sisler JD, Qi C, McKinney W, Shaffer J, Andrew M, Lee T, Thomas T, Castranova V, Mercer RR, Qian Y.
        J Occup Environ Hyg. 2018 Jan 4:0.
        To protect against decay and fungal invasion into the wood, the micronized copper, copper carbonate particles, has been applied in the wood treatment in recent years; however, there is little information on the health risk associated with sanding micronized copper- treated lumber. In this study, wood dust from the sanding of micronized copper azole -treated lumber (MCA) was compared to sanding dust from solubilized copper azole-treated wood (CA-C) and untreated yellow pine (UYP). The test found that sanding MCA released a much higher concentration of nanoparticles than sanding CA-C and UYP, and the particles between about 0.4 microm to 2 microm from sanding MCA had the highest percentage of copper. The percentage of copper in the airborne dust from sanding CA-C had a weak dependency on particle size and was lower than that from sanding MCA. Nanoparticles were seen in the MCA PM2.5 particles, while none were detected in the UYP or CA-C. Inductively coupled plasma mass spectrometry (ICP-MS) analysis found that the bulk lumber for MCA and CA-C had relatively equal copper content; however, the PM2.5 particles from sanding the MCA had a higher copper concentration when compared to the PM2.5 particles from sanding UYP or CA-C. The cellular toxicity assays show that exposure of RAW 264.7 macrophages (RAW) to MCA and CA-C wood dust suspensions did not induce cellular toxicity even at the concentration of 200 microg PM2.5 wood dust/mL. Since the copper from the treated wood dust can leach into the wood dust supernatant, the supernatants of MCA, CA-C and UYP wood dusts were subjected to the cellular toxicity assays. The data showed that at the higher concentrations of copper (>/= 5 microg/ml), both MCA and CA-C supernatants induced cellular toxicity. This study suggests that sanding MCA-treated lumber releases copper nanoparticles and both the MCA and CA-C-treated lumber can release copper, which are potentially related to the observed in vitro toxicity.

      6. CD4 lymphocyte enumeration and hemoglobin assessment aid for priority decisions: a multisite evaluation of the BD FACSPresto System
        Thakar M, Angira F, Pattanapanyasat K, Wu AH, O’Gorman M, Zeng H, Qu C, Mahajan B, Sukapirom K, Chen D, Hao Y, Gong Y, Indig MA, Graminske S, Orta D, d’Empaire N, Lu B, Omana-Zapata I, Zeh C.
        Open AIDS J. 2017 ;11:76-90.
        Background: The BD FACSPresto system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. Methods: Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur() system, and for Hb, using the Sysmex((R)) KX-21N() analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. Results: For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96-1.05 and R(2) >/=0.96; Hb slopes were >/=1.00 and R(2) >/=0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. Conclusion: The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems.

      7. Diagnosis of Chlamydia psittaci and Chlamydia pneumoniae infections has traditionally relied on serological assays. We developed a multiplex real-time PCR assay for detection of C. psittaci, C. pneumoniae and an internal control. Results of this assay demonstrated 100% concordance compared to results of previously tested human clinical specimens.

    • Maternal and Child Health
      1. Botulism during pregnancy and the postpartum period: A systematic review
        Badell ML, Rimawi BH, Rao AK, Jamieson DJ, Rasmussen S, Meaney-Delman D.
        Clin Infect Dis. 2017 Dec 27;66(suppl_1):S30-s37.
        Background: Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed. Methods: We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations. Results: Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it. Conclusions: Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation.

      2. Prevalence and trends in prepregnancy normal weight – 48 States, New York City, and District of Columbia, 2011-2015
        Deputy NP, Dub B, Sharma AJ.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 5;66(5152):1402-1407.
        Women who enter pregnancy at a weight above or below normal weight, defined as a body mass index (BMI) of 18.5-24.9 (calculated as weight in kg/height in m(2)), are more likely to experience adverse pregnancy outcomes and to have infants who experience adverse health outcomes. For example, prepregnancy underweight (BMI <18.5) increases the risk for small-for-gestational-age births, whereas prepregnancy overweight (BMI 25.0-29.9) and obesity (BMI >/=30.0) increase risks for cesarean delivery, large-for-gestational-age births, and childhood obesity (1). Given these outcomes, Healthy People 2020 includes an objective to increase the proportion of women entering pregnancy with a normal weight from 52.5% in 2007 to 57.8% by 2020.* Because recent trends in prepregnancy normal weight have not been reported, CDC examined 2011-2015 National Vital Statistics System (NVSS) natality data, which included prepregnancy BMI. In 2015, for 48 states, the District of Columbia (DC), and New York City (NYC) combined, the prevalence of prepregnancy normal weight was 45.0%; prevalence ranged from 37.7% in Mississippi to 52.2% in DC. Among 38 jurisdictions with prepregnancy BMI data during 2011-2015, normal weight prevalence declined from 47.3% to 45.1%; declines were observed in all jurisdictions but were statistically significant for 27 jurisdictions after standardizing to the 2011 national maternal age and race/ethnicity distribution. Screening women’s BMI during routine clinical care provides opportunities to promote normal weight before entering pregnancy.

    • Mining
      1. A recent seismic event was recorded by a deep longwall mine in Virginia at 3.7 ML on the local magnitude scale and 3.4 MMS by the United States Geological Survey (USGS) in 2016. Further investigations by the National Institute for Occupational Safety and Health (NIOSH) and Coronado Coal researchers have shown that this event was associated with geological features that have also been associated with other, similar seismic events in Virginia. Detailed mapping and geological exploration in the mining area has made it possible to forecast possible locations for future seismic activity. In order to use the geology as a forecaster of mining-induced seismic events and their energy potential, two primary components are needed. The first component is a long history of recorded seismic events with accurately plotted locations. The second component is a high density of geologic data within the mining area. In this case, 181 events of 1.0 ML or greater were recorded by the mine’s seismic network between January, 2009, and October, 2016. Within the mining area, 897 geophysical logs, 224 core holes, and 1031 fiberscope holes were examined by mine geologists. From this information, it was found that overburden thickness, sandstone thickness, and sandstone quality contributed greatly to seismic locations. After the data was analyzed, a pattern became apparent indicating that the majority of seismic events occurred under specific conditions. Three forecast maps were created based on geology of previous seismic locations. The forecast maps have shown an accuracy of within 74-89% when compared to the recorded 181 events that were 1.0 ML or greater when considering three major geological criteria of overburden thickness of 579.12 m or greater, 6.096-12.192 m of sandstone within 15.24 m of the Pocahontas number 3 seam, and a longwall caving height of 4.572 m or less.

      2. Geotechnical considerations for concurrent pillar recovery in close-distance multiple seams
        Zhang P, Tulu B, Sears M, Trackemas J.
        Int J Min Sci Technol. 2017 .
        Room-and-pillar mining with pillar recovery has historically been associated with more than 25% of all ground fall fatalities in underground coal mines in the United States. The risk of ground falls during pillar recovery increases in multiple-seam mining conditions. The hazards associated with pillar recovery in multiple-seam mining include roof cutters, roof falls, rib rolls, coal outbursts, and floor heave. When pillar recovery is planned in multiple seams, it is critical to properly design the mining sequence and panel layout to minimize potential seam interaction. This paper addresses geotechnical considerations for concurrent pillar recovery in two coal seams with 21 m of interburden under about 305 m of depth of cover. The study finds that, for interburden thickness of 21 m, the multiple-seam mining influence zone in the lower seam is directly under the barrier pillar within about 30 m from the gob edge of the upper seam. The peak stress in the interburden transfers down at an angle of approximately 20?away from the gob, and the entries and crosscuts in the influence zone are subjected to elevated stress during development and retreat. The study also suggests that, for full pillar recovery in close-distance multiple-seam scenarios, it is optimal to superimpose the gobs in both seams, but it is not necessary to superimpose the pillars. If the entries and/or crosscuts in the lower seam are developed outside the gob line of the upper seam, additional roof and rib support needs to be considered to account for the elevated stress in the multiple-seam influence zone.

    • Nutritional Sciences
      1. The dietary impact of introducing new retailers of fruits and vegetables into a community: results from a systematic review
        Woodruff RC, Raskind IG, Harris DM, Gazmararian JA, Kramer M, Haardorfer R, Kegler MC.
        Public Health Nutr. 2017 Dec 29:1-11.
        OBJECTIVE: To investigate the potential dietary impact of the opening of new retailers of healthy foods. DESIGN: Systematic review of the peer-reviewed research literature. SETTING: References published before November 2015 were retrieved from MEDLINE, EMBASE and Web of Science databases using keyword searches. SUBJECTS: The outcome of the review was change in fruit and vegetable consumption among adults. RESULTS: Of 3514 references retrieved, ninety-two articles were reviewed in full text, and twenty-three articles representing fifteen studies were included. Studies used post-test only (n 4), repeated cross-sectional (n 4) and repeated measures designs (n 7) to evaluate the dietary impact of supermarket (n 7), farmers’ market (n 4), produce stand (n 2) or mobile market (n 2) openings. Evidence of increased fruit and vegetable consumption was most consistent among adults who began shopping at the new retailer. Three of four repeated measures studies found modest, albeit not always statistically significant, increases in fruit and vegetable consumption (range 0.23-0.54 servings/d) at 6-12 months after baseline. Dietary change among residents of the broader community where the new retailer opened was less consistent. CONCLUSIONS: The methodological quality of studies, including research designs, sampling methods, follow-up intervals and outcome measures, ranged widely. Future research should align methodologically with previous work to facilitate meta-analytic synthesis of results. Opening a new retailer may result in modest short-term increases in fruit and vegetable consumption among adults who choose to shop there, but the potential longer-term dietary impact on customers and its impact on the broader community remain unclear.

    • Occupational Safety and Health – Mining
      1. Coal rib response during bench mining: A case study
        Sears MM, Rusnak J, Van Dyke M, Rashed G, Mohamed K, Sloan M.
        Int J Min Sci Technol. 2017 .
        In 2016, room-and-pillar mining provided nearly 40% of underground coal production in the United States. Over the past decade, rib falls have resulted in 12 fatalities, representing 28% of the ground fall fatalities in U.S. underground coal mines. Nine of these 12 fatalities (75%) have occurred in room-and-pillar mines. The objective of this research is to study the geomechanics of bench room-and-pillar mining and the associated response of high pillar ribs at overburden depths greater than 300 m. This paper provides a definition of the bench technique, the pillar response due to loading, observational data for a case history, a calibrated numerical model of the observed rib response, and application of this calibrated model to a second site.

    • Physical Activity
      1. Evaluation of Let’s Move! active schools activation grants
        Miller GF, Sliwa S, Michael S, Lee S, Burgeson C, Krautheim AM, Hatfield DP, Sharma S, Economos CD.
        Prev Med. 2017 Dec 27.
        Let’s Move! Active Schools (LMAS), now Active Schools, is a national initiative in the United States (US) that aims to engage schools to increase students’ opportunities to be physically active. This evaluation describes changes in school-level practices related to physical education (PE) and physical activity (PA) among schools that received an LMAS-partner grant from ChildObesity180 or Fuel Up to Play 60 (FUTP60). ChildObesity180 and FUTP60 asked grantee schools to complete nine common questions, between October 2013 and August 2014, before and after receiving the grants to assess progress in implementing practices for PE and PA. “Yes” responses indicated presence of PE/PA-supportive practices. For schools with complete pre and post data (n=972), frequencies of “yes” responses were calculated for each practice at pre/post. Schools receiving a FUTP60 partner grant reported statistically significant improvements from pre to post across five practices for PE and PA, and ChildObesity180 grantees reported significant increases on all practices except daily recess, which was already in place at 95% of schools at pre-survey. Schools across both grant programs reported the largest increases for promoting PA via messaging, implementing classroom PA breaks, and providing PA before and after school. Schools in both programs reported smaller, but statistically significant, increases in requiring the recommended minutes of PE. This study illustrates the feasibility of offering small grants, at a national scale, for schools to make changes that support PA throughout the day. Results suggest that schools can shift PA policies and practices over the course of a school year.

    • Reproductive Health
      1. Sexual intercourse among high school students – 29 states and United States overall, 2005-2015
        Ethier KA, Kann L, McManus T.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 5;66(5152):1393-1397.
        Early initiation of sexual activity is associated with having more sexual partners, not using condoms, sexually transmitted infection (STI), and pregnancy during adolescence (1,2). The majority of adolescents initiate sexual activity during high school, and the proportion of high school students who have ever had sexual intercourse increases by grade; black students are more likely to have ever had sexual intercourse than are white students (3). The proportion of high school students overall who had ever had sexual intercourse did not change significantly during 1995-2005 (53.1% to 46.8%) (Division of Adolescent and School Health, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, unpublished data). To assess whether changes have occurred in recent years in the proportion of high school students who have ever had sexual intercourse, CDC examined trends overall and by grade, race/ethnicity, and sex among U.S. high school students, using data from the 2005-2015 national Youth Risk Behavior Surveys (YRBSs) and data from 29 states* that conduct the YRBS and have weighted data. Nationwide, the proportion of high school students who had ever had sexual intercourse decreased significantly overall and among 9th and 10th grade students, non-Hispanic black (black) students in all grades, and Hispanic students in three grades. A similar pattern by grade was observed in nearly half the states (14), where the prevalence of ever having had sexual intercourse decreased only in 9th grade or only in 9th and 10th grades; nearly all other states saw decreases in some or all grades. The overall decrease in the prevalence of ever having had sexual intercourse during 2005-2015 is a positive change in sexual risk among adolescents (i.e., behaviors that place them at risk for human immunodeficiency virus, STI, or pregnancy) in the United States, an overall decrease that did not occur during the preceding 10 years. Further, decreases by grade and race/ethnicity represent positive changes among groups of students who have been determined in previous studies to be at higher risk for negative outcomes associated with early sexual initiation, such as greater numbers of partners, condom non-use, teen pregnancy, and STI (1-3). More work is needed to understand the reasons for these decreases and to ensure that they continue.

      2. Assisted reproductive technology with donor sperm: National trends and perinatal outcomes
        Gerkowicz SA, Crawford SB, Hipp HS, Boulet SL, Kissin DM, Kawwass JF.
        Am J Obstet Gynecol. 2017 Dec 29.
        BACKGROUND: Information regarding use of donor sperm in assisted reproductive technology, as well as subsequent treatment and perinatal outcomes, remains limited. Outcome data would aid patient counseling and clinical decision-making. OBJECTIVES: To report national trends in donor sperm utilization and live birth rates of donor sperm assisted reproductive technology cycles in the United States, and to compare assisted reproductive technology treatment and perinatal outcomes between cycles using donor and non-donor sperm. We hypothesize these outcomes to be comparable between donor and non-donor sperm cycles. STUDY DESIGN: Retrospective cohort study using data from all United States fertility centers reporting to the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology Surveillance System, accounting for approximately 98% of assisted reproductive technology cycles (definition excludes intrauterine insemination). The number and percentage of assisted reproductive technology cycles using donor sperm and rates of pregnancy, live birth, preterm birth (<37 weeks), and low birth weight (<2500g) were the primary outcomes measured. Treatments assessed include use of donor versus non-donor sperm. The trends analysis included all banking and fresh assisted reproductive technology cycles using donor and autologous oocytes performed between 1996 and 2014 (n=1,710,034). The outcomes analysis was restricted to include only fresh autologous cycles performed between 2010 and 2014 (n=437,569) in order to focus on cycles with a potential outcome and cycles reflective of current practice, thereby improving the clinical relevance. Cycles cancelled prior to retrieval were excluded. Statistical analysis included linear regression to explore polynomial trends and log-binomial regression to estimate relative risk for outcomes among cycles using donor and non-donor sperm. RESULTS: Of all banking and fresh donor and autologous oocyte assisted reproductive technology cycles performed between 1996 and 2014, 74,892 (4.4%) used donor sperm. In 2014, 7,351 assisted reproductive technology cycles using donor sperm were performed, as compared to 1,763 in 1996 (6.2% vs. 3.8% of all cycles). Among all autologous oocyte cycles performed between 2010 and 2014, the live birth rate was lower for donor sperm (27.9%) than non-donor sperm cycles (32.5%); however, after adjustment for maternal age, donor sperm use was associated with an increased likelihood of live birth (adjusted relative risk=1.06, 95% confidence interval=1.01-1.10). Per transfer, there was no significant difference in live birth rates for donor versus non-donor sperm (31.9% vs. 36.8%; adjusted relative risk =1.04, 95% confidence interval =0.998-1.09). Per singleton live birth there was no significant difference in preterm birth (11.5% vs. 11.8%; adjusted relative risk =0.98, 95% confidence interval =0.90-1.06); however, low birth weight delivery was slightly lower in donor sperm cycles (8.8% vs. 9.4%; adjusted relative risk =0.91, 95% confidence interval =0.83-0.99). CONCLUSIONS: Donor sperm use in assisted reproductive technology has increased in the United States, accounting for approximately 6% of all assisted reproductive technology cycles in 2014. Assisted reproductive technology treatment and perinatal outcomes were clinically similar in donor and non-donor sperm cycles.

      3. Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants
        Litzky JF, Boulet SL, Esfandiari N, Zhang Y, Kissin DM, Theiler RN, Marsit CJ.
        Am J Obstet Gynecol. 2017 Dec 29.
        BACKGROUND: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally-conceived infants and are more likely to be born low birthweight (<2500 grams). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported. OBJECTIVES: To compare the effect of frozen/thawed versus fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 grams) and low birthweight (<2500 grams). STUDY DESIGN: We used data from the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models. RESULTS: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142.34 gram increase in birthweight compared with infants born after fresh embryo transfer (p<0.001). An interaction between infant sex and embryo transfer type was significant (p<0.0001), with FET having a larger effect on male infants by 16 grams. The adjusted risk of a macrosomic infant was 1.70 (95%CI 1.64-1.76) times higher following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95%CI 0.48-0.56) compared to fresh embryo transfer. CONCLUSIONS: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.

      4. Drug interactions between hormonal contraceptives and antiretrovirals
        Nanda K, Stuart GS, Robinson J, Gray AL, Tepper NK, Gaffield ME.
        Aids. 2017 Apr 24;31(7):917-952.
        OBJECTIVE: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. DESIGN: Systematic review of the published literature. METHODS: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. RESULTS: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. CONCLUSION: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices.

    • Substance Use and Abuse
      1. Surgeon General’s Reports on Tobacco: A continued legacy of unbiased and rigorous synthesis of the scientific evidence
        King BA, Creamer MR, Harrell M, Kelder S, Norman L, Perry CL.
        Nicotine Tob Res. 2017 Dec 28.

        [No abstract]

      2. Protecting young children from tobacco smoke exposure: A pilot study of Project Zero Exposure
        Rosen L, Guttman N, Myers V, Brown N, Ram A, Hovell M, Breysse P, Rule A, Berkovitch M, Zucker D.
        Pediatrics. 2018 Jan;141(Suppl 1):S107-s117.
        BACKGROUND: Tobacco smoke exposure (TSE) harms children, who are often “captive smokers” in their own homes. Project Zero Exposure is a parent-oriented, theory-based intervention designed to reduce child TSE. This paper reports on findings from the pilot study, which was conducted in Israel from 2013 to 2014. METHODS: The intervention consisted of motivational interviews, child biomarker and home air quality feedback, a Web site, a video, and self-help materials. The primary outcome was child TSE as measured by hair nicotine. Secondary outcome measures were air nicotine and particulate matter, parental reports of TSE, parental smoking behavior, and TSE child protection. A single-group pre- and posttest design was used. RESULTS: Twenty-six of the 29 recruited families completed the study. The intervention was feasible to implement and acceptable to participants. Among the 17 children with reliable hair samples at baseline and follow-up, log hair nicotine dropped significantly after the intervention (P = .04), hair nicotine levels decreased in 64.7% of children, and reductions to levels of nonexposed children were observed in 35.3% of children. The number of cigarettes smoked by parents (P = .001) and parent-reported child TSE declined (P = .01). Logistical issues arose with measurement of all objective measures, including air nicotine, which did not decline; home air particulate matter; and hair nicotine. CONCLUSIONS: A program based on motivational interviewing and demonstrating TSE and contamination to parents in a concrete and easily understandable way is a promising approach to protect children from TSE. Further research is needed to enhance current methods of measurement and assess promising interventions.

    • Zoonotic and Vectorborne Diseases
      1. Postmortem findings in patient with Guillain-Barre syndrome and Zika virus infection
        Dirlikov E, Torres JV, Martines RB, Reagan-Steiner S, Perez GV, Rivera A, Major C, Matos D, Munoz-Jordan J, Shieh WJ, Zaki SR, Sharp TM.
        Emerg Infect Dis. 2018 Jan;24(1):114-117.
        Postmortem examination results of a patient with Guillain-Barre syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barre syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.

      2. Dengue fever in Burkina Faso, 2016
        Tarnagda Z, Cisse A, Bicaba BW, Diagbouga S, Sagna T, Ilboudo AK, Tialla D, Lingani M, Sondo KA, Yougbare I, Yameogo I, Sow HE, Sakande J, Sangare L, Greco R, Muscatello DJ.
        Emerg Infect Dis. 2018 Jan;24(1):170-172.
        We report 1,327 probable cases of dengue in Burkina Faso in 2016. Of 35 serum samples tested by a trioplex test, 19 were confirmed dengue virus (DENV)positive: 11 DENV-2, 6 DENV-3, 2 nontypeable, and 1 DENV-2/DENV-3 co-infection. Molecular testing should be conducted to correctly identify causative agents in this complex infectious disease landscape.

      3. Investigation of canine-mediated human rabies death, Haiti, 2015
        Tran CH, Etheart MD, Andrecy LL, Augustin PD, Kligerman M, Crowdis K, Adrien P, Dismer A, Blanton JD, Millien M, Wallace RM.
        Emerg Infect Dis. 2018 Jan;24(1):156-158.
        In Haiti, an investigation occurred after the death of a 4-year-old girl with suspected rabies. With tips provided by community members, the investigation led to the identification of 2 probable rabies-related deaths and 16 persons bitten by rabid dogs, 75% of which chose postexposure prophylaxis. Community engagement can bolster rabies control.

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