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Volume 10, Issue 3, January 23, 2018

CDC Science Clips: Volume 10, Issue 3, January 23, 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. Top Articles of the Week

    Selected weekly by a senior CDC scientist from the standard sections listed below.

    The names of CDC authors are indicated in bold text.
    • Communicable Diseases
    • Environmental Health
      • Assessment of child lead exposure in a Philadelphia community, 2014
        Dignam T, Pomales A, Werner L, Newbern EC, Hodge J, Nielsen J, Grober A, Scruton K, Young R, Kelly J, Brown MJ.
        J Public Health Manag Pract. 2018 Jan 10.
        INTRODUCTION: Several urban neighborhoods in Philadelphia, Pennsylvania, have a history of soil, household lead paint, and potential lead-emitting industry contamination. OBJECTIVES: To (1) describe blood lead levels (BLLs) in target neighborhoods, (2) identify risk factors and sources of lead exposure, (3) describe household environmental lead levels, and (4) compare results with existing data. METHODS: A simple, random, cross-sectional sampling strategy was used to enroll children 8 years or younger living in selected Philadelphia neighborhoods with a history of lead-emitting industry during July 2014. Geometric mean of child BLLs and prevalence of BLLs of 5 mug/dL or more were calculated. Linear and logistic regression analyses were used to ascertain risk factors for elevated BLLs. RESULTS: Among 104 children tested for blood lead, 13 (12.4%; 95% confidence interval [CI], 7.5-20.2) had BLLs of 5 mug/dL or more. The geometric mean BLL was 2.0 mug/dL (95% CI, 1.7-2.3 mug/dL). Higher geometric mean BLLs were significantly associated with front door entryway dust lead content, residence built prior to 1900, and a child currently or ever receiving Medicaid. Seventy-one percent of households exceeded the screening level for soil, 25% had an elevated front door floor dust lead level, 28% had an elevated child play area floor dust lead level, and 14% had an elevated interior window dust lead level. Children in households with 2 to 3 elevated environmental lead samples were more likely to have BLLs of 5 mug/dL or more. A spatial relationship between household proximity to historic lead-emitting facilities and child BLL was not identified. CONCLUSION: Entryway floor dust lead levels were strongly associated with blood lead levels in participants. Results underscore the importance to make housing lead safe by addressing all lead hazards in and around the home. Reduction of child lead exposure is crucial, and continued blood lead surveillance, testing, and inspection of homes of children with BLLs of 5 mug/dL or more to identify and control lead sources are recommended. Pediatric health care providers can be especially vigilant screening Medicaid-eligible/enrolled children and children living in very old housing.

    • Health Disparities
      • Work as an inclusive part of population health inequities research and prevention
        Ahonen EQ, Fujishiro K, Cunningham T, Flynn M.
        Am J Public Health. 2018 Jan 18:e1-e6.
        Despite its inclusion in models of social and ecological determinants of health, work has not been explored in most health inequity research in the United States. Leaving work out of public health inequities research creates a blind spot in our understanding of how inequities are created and impedes our progress toward health equity. We first describe why work is vital to our understanding of observed societal-level health inequities. Next, we outline challenges to incorporating work in the study of health inequities, including (1) the complexity of work as a concept; (2) work’s overlap with socioeconomic position, race, ethnicity, and gender; (3) the development of a parallel line of inquiry into occupational health inequities; and (4) the dearth of precise data with which to explore the relationships between work and health status. Finally, we summarize opportunities for advancing health equity and monitoring progress that could be achieved if researchers and practitioners more robustly include work in their efforts to understand and address health inequities. (Am J Public Health. Published online ahead of print January 18, 2018: e1-e6. doi:10.2105/AJPH.2017.304214).

    • Health Economics
      • The economic burden of asthma in the United States, 2008 – 2013
        Nurmagambetov T, Kuwahara R, Garbe P.
        Ann Am Thorac Soc. 2018 Jan 11.
        RATIONALE: Asthma is a chronic disease that affects quality of life, productivity at work and school, healthcare use, and can result in death. Measuring the current economic burden of asthma provides important information on the impact of asthma on society. This information can be used to make informed decisions about allocation of limited public health resources. OBJECTIVES: In this paper, we provide a comprehensive approach to estimate current prevalence, medical costs, cost of absenteeism (missed work and schooldays) and mortality attributable to asthma from a national perspective. In addition, we estimate the association of incremental medical cost of asthma with several important factors, including race/ethnicity, education, poverty, and insurance status. METHODS: The primary source of data was the 2008-2013 household component of the Medical Expenditure Panel Survey. We defined treated asthma as the presence of at least one medical or pharmaceutical encounter or claim associated with asthma. For the main analysis, we applied two-part regression models to estimate asthma-related annual per-person incremental medical costs and negative binomial models to estimate absenteeism associated with asthma. RESULTS: Out of 213,994 people in the pooled sample, 10,237 persons had treated asthma (prevalence = 4.8%). The annual per-capita incremental medical cost of asthma was $3,266 (in 2015 US dollars): $1,830 was attributable to prescription medication, $640 to office visits, $529 to hospitalizations, $176 to hospital-based outpatient visits, and $105 to emergency room visits. For certain groups, the per-person incremental medical cost of asthma differed from that of the population average, namely, $2,145 for uninsured persons and $3.581 for those living below the poverty line. During 2008-2013, asthma was responsible for $3 billion in losses from missed work and school days, $29 billion from asthma-related mortality, and $50.3 billion in medical costs. All combined, the total cost of asthma in the U.S. based on the pooled sample amounted to $81.9 billion in 2013. CONCLUSION: Asthma places a significant economic burden on the United States with a total cost of asthma, including costs incurred by absenteeism and mortality, of $81.9 billion in 2013.

    • Immunity and Immunization
      • Association of provider recommendation and offer and influenza vaccination among adults aged >/=18 years – United States
        Lu PJ, Srivastav A, Amaya A, Dever JA, Roycroft J, Kurtz MS, O’Halloran A, Williams WW.
        Vaccine. 2018 Jan 9.
        BACKGROUND: Influenza vaccination has been recommended for all persons aged >/=6months since 2010. METHODS: Data from the 2016 National Internet Flu Survey were analyzed to assess provider vaccination recommendations and early influenza vaccination during the 2016-17 season among adults aged >/=18years. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with early vaccine uptake by provider vaccination recommendation status. RESULTS: Overall, 24.0% visited a provider who both recommended and offered influenza vaccination, 9.0% visited a provider who only recommended but did not offer, 25.1% visited a provider who neither recommended nor offered, and 41.9% did not visit a doctor from July 1 through date of interview. Adults who reported that a provider both recommended and offered vaccine had significantly higher vaccination coverage (66.6%) compared with those who reported that a provider only recommended but did not offer (48.4%), those who neither received recommendation nor offer (32.0%), and those who did not visit a doctor during the vaccination period (28.8%). Results of multivariable logistic regression indicated that having received a provider recommendation, with or without an offer for vaccination, was significantly associated with higher vaccination coverage after controlling for demographic and access-to-care factors. CONCLUSIONS: Provider recommendation was significantly associated with influenza vaccination. However, overall, 67.0% of adults did not visit a doctor during the vaccination period or did visit a doctor but did not receive a provider recommendation. Evidence-based strategies such as client reminder/recall, standing orders, provider reminders, or health systems interventions in combination should be undertaken to improve provider recommendation and influenza vaccination coverage. Other factors significantly associated with a higher level of influenza vaccination included age >/=50years, being Hispanic, having a college or higher education, having a usual place for medical care, and having public health insurance.

      • Rubella vaccine – a tale of appropriate caution and remarkable success
        Zimmerman LA, Reef SE, Orenstein WA.
        JAMA Pediatr. 2018 Jan 1;172(1):95-96.

        [No abstract]

    • Laboratory Sciences
      • Detection of apparent cell-free M. tuberculosis DNA from plasma
        Click ES, Murithi W, Ouma GS, McCarthy K, Willby M, Musau S, Alexander H, Pevzner E, Posey J, Cain KP.
        Sci Rep. 2018 Jan 12;8(1):645.
        New diagnostics are needed to improve clinicians’ ability to detect tuberculosis (TB) disease in key populations such as children and persons living with HIV and to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma is a diagnostic target in new obstetric and oncologic applications, but its utility for diagnosing TB is not known. Here we show that Mycobacterium tuberculosis complex DNA can be detected in plasma of persons with sputum smear-positive TB, even in the absence of mycobacteremia. Among 40 participants with bacteriologically-confirmed smear-positive TB disease who had plasma tested by quantitative PCR (qPCR), 18/40 (45%) had a positive result on at least one triplicate reaction. Our results suggest that plasma DNA may be a useful target for improving clinicians’ ability to diagnose TB. We anticipate these findings to be the starting point for optimized methods of TB ccfDNA testing and sequence-based diagnostic applications such as molecular detection of drug resistance.

    • Maternal and Child Health
      • Preconception health indicators for public health surveillance
        Robbins CL, D’Angelo D, Zapata L, Boulet SL, Sharma AJ, Adamski A, Farfalla J, Stampfel C, Verbiest S, Kroelinger C.
        J Womens Health (Larchmt). 2018 Jan 11.
        OBJECTIVES: In response to an expressed need for more focused measurement of preconception health (PCH), we identify a condensed set of PCH indicators for state and national surveillance. METHODS: We used a systematic process to evaluate, prioritize, and select 10 PCH indicators that maternal and child health programs can use for surveillance. For each indicator, we assessed prevalence, whether it was addressed by professional recommendations, Healthy People 2020 objectives, or Centers for Disease Control and Prevention winnable battles, measurement simplicity, data completeness, and stakeholders’ input. RESULTS: Fifty PCH indicators were evaluated and prioritized. The condensed set includes indicators that rely on data from the Pregnancy Risk Assessment Monitoring System (n = 4) and the Behavioral Risk Factor Surveillance System (n = 6). The content encompasses heavy alcohol consumption, depression, diabetes, folic acid intake, hypertension, normal weight, recommended physical activity, current smoking, unwanted pregnancy, and use of contraception. CONCLUSIONS: Having a condensed set of PCH indicators can facilitate surveillance of reproductive-aged women’s health status that supports monitoring, comparisons, and benchmarking at the state and national levels.

    • Nutritional Sciences
      • Importance: Severe obesity in childhood is associated with negative health consequences. A previous study examined trends in severe obesity among preschool-aged children in low-income families during 1998 to 2010. No recent trends have been reported. Objective: To examine trends in severe obesity by age, sex, and race/ethnicity among enrollees in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) aged 2 to 4 years during 2000 to 2014. Design, Setting, and Participants: Serial cross-sectional data from 22.6 million young children enrolled in WIC from 50 states, the District of Columbia, and 5 US territories from 2000 to 2014. Data analysis was conducted from February 16, 2017, to March 9, 2017. Main Outcomes and Measures: Prevalence of severe obesity. Severe obesity was defined as a sex-specific body mass index-for-age 120% or more of the 95th percentile on the 2000 Centers for Disease Control and Prevention growth charts. Children’s weights and heights were measured. Children whose sex, weight, height, or body mass index was missing or biologically implausible were excluded. Results: The prevalence of severe obesity was 1.96% in 2014. During 2000 to 2004, the prevalence increased significantly overall from 1.80% to 2.11% (adjusted prevalence difference [APD], 0.26%) and among all the age, sex, and racial/ethnic groups except for Asian/Pacific Islander (APD, 0.05%-0.54% across groups with increases). The largest relative increase occurred in children aged 4 years (adjusted prevalence ratio [APR], 1.21) and non-Hispanic white (APR, 1.22) and American Indian/Alaska Native children (APR, 1.19). During 2004 to 2010, the prevalence decreased significantly overall (APD, -0.05%), among boys, children aged 2 and 3 years, and non-Hispanic black and Asian/Pacific Islander children (APD, -0.05% to -0.18%). During 2010 to 2014, the prevalence decreased significantly overall from 2.12% to 1.96% (APD, -0.14%) and among all demographic groups (APD, -0.04% to -0.30% across groups). The largest relative decrease occurred in children aged 2 years (APR, 0.88) and Hispanic (APR, 0.92), American Indian/Alaska Native (APR, 0.89), and Asian/Pacific Islander (APR, 0.87) children. Conclusions and Relevance: This study provides updated prevalence and trends of severe obesity among young children enrolled in WIC and reports recent modest declines in severe obesity in all subgroups. Ongoing surveillance can assess whether declines continue into the future among low-income children.

    • Public Health Leadership and Management
      • INTRODUCTION: The purpose of this study is to reconcile public health workforce supply and demand data to understand whether the expected influx of public health graduates can meet turnover events. METHODS: Four large public health workforce data sources were analyzed to establish measures of workforce demand, voluntary separations, and workforce employees likely to retire at state and local health departments. Data were collected in 2014-2016 and analyzed in 2016 and 2017. Potential workforce supply (i.e., candidates with formal public health training) was assessed by analyzing data on public health graduates. Supply and demand data were reconciled to identify potential gaps in the public health workforce. RESULTS: At the state and local level, congruent with197,000 staff are employed in health departments. This is down more than 50,000 from 2008. In total, >/=65,000 staff will leave their organizations during fiscal years 2016-2020, with </=100,000 staff leaving if all planned retirements occur by 2020. During 2000-2015, more than 223,000 people received a formal public health degree at some level. More than 25,000 students will receive a public health degree at some level in each year through 2020. CONCLUSIONS: Demands for public health staff could possibly be met by the influx of graduates from schools and programs of public health. However, substantial implications exist for transferal of institutional knowledge and ability to recruit and retain the best staff to sufficiently meet demand.

  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. Misclassification of body mass index (BMI) categories arising from self-reported weight and height can bias hazard ratios in studies of BMI and mortality. We examined the effects on hazard ratios of such misclassification using national US survey data for 1976 through 2010 that had both measured and self-reported weight and height along with mortality follow-up for 48,763 adults and a subset of 17,405 healthy never-smokers. BMI was categorized as <22.5 (low), 22.5-24.9 (referent), 25.0-29.9 (overweight), 30.0-34.9 (class I obesity), and >/=35.0 (class II-III obesity). Misreporting at higher BMI categories tended to bias hazard ratios upwards for those categories, but that effect was augmented, counterbalanced, or even reversed by misreporting in other BMI categories, in particular those that affected the reference category. For example, among healthy male never-smokers, misclassifications affecting the overweight and the reference categories changed the hazard ratio for overweight from 0.85 with measured data to 1.24 with self-reported data. Both the magnitude and direction of bias varied according to the underlying hazard ratios in measured data, showing that findings on bias from one study should not be extrapolated to a study with different underlying hazard ratios. Because of misclassification effects, self-reported weight and height cannot reliably indicate the lowest-risk BMI category.

      2. Cardiovascular autonomic neuropathy in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Cohort Study
        Jaiswal M, Divers J, Urbina EM, Dabelea D, Bell RA, Pettitt DJ, Imperatore G, Pihoker C, Dolan LM, Liese AD, Marcovina S, Linder B, Feldman EL, Pop-Busui R.
        Pediatr Diabetes. 2018 Jan 2.
        OBJECTIVE: To estimate the prevalence of and risk factors for cardiovascular autonomic neuropathy (CAN) in adolescents and young adults with type 1 and type 2 diabetes enrolled in the SEARCH for Diabetes in Youth Study. METHODS: The study included 1646 subjects with type 1 diabetes (age 18 +/- 4 years, diabetes duration 8 +/- 2 years, HbA1c 9.1 +/- 1.9%, 76% non-Hispanic Whites) and 252 with type 2 diabetes (age 22 +/- 4 years, diabetes duration 8 +/- 2 years, HbA1c 9.2 +/- 3.0%, 45% non-Hispanic Blacks). Cross-sectional and longitudinal risk factors were assessed at baseline and follow-up visits. Area under the curve (AUC) was used to assess the longitudinal glycemic exposure and cardiovascular risk factors. CAN was assessed by time and frequency domain indices of heart rate variability (HRV). CAN was defined as the presence of >/=3 of 5 abnormal HRV indices. RESULTS: The prevalence of CAN was 12% in adolescents and young adults with type 1 diabetes and 17% in those with type 2 diabetes. Poor long-term glycemic control (AUC HbA1c), high blood pressure, and elevated triglyceride levels were correlates of CAN in subjects with type 1 diabetes. In those with type 2 diabetes, CAN was associated with elevated triglycerides and increased urinary albumin excretion. CONCLUSIONS: The prevalence of CAN in this multiethnic cohort of adolescents and young adults with type 1 and type 2 diabetes are comparable to those reported in adults with diabetes. Suboptimal glycemic control and elevated triglycerides were the modifiable risk factors associated with CAN.

      3. Prior exposure to corticosterone markedly enhances and prolongs the neuroinflammatory response to systemic challenge with LPS
        Kelly KA, Michalovicz LT, Miller JV, Castranova V, Miller DB, O’Callaghan JP.
        PLoS One. 2018 ;13(1):e0190546.
        Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflammatory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to interact with and alter neuroinflammatory responses and associated behaviors. Here, we examined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a single injection (2mg/kg, s.c.) or inhalation exposure (7.5 mug/m3) of LPS or polyinosinic:polycytidylic acid (PIC; 12mg/kg, i.p.) in adult male C57BL/6J mice. CORT was given in the drinking water (200 mg/L) for 1 week or every other week for 90 days followed by LPS. Proinflammatory cytokine expression (TNFalpha, IL-6, CCL2, IL-1beta, LIF, and OSM) was measured by qPCR. The activation of the neuroinflammation downstream signaling activator, STAT3, was assessed by immunoblot of pSTAT3Tyr705. The presence of astrogliosis was assessed by immunoassay of GFAP. Acute exposure to LPS caused brain-wide neuroinflammation without producing astrogliosis; exposure to CORT for 1 week caused marked exacerbation of the LPS-induced neuroinflammation. This neuroinflammatory “priming” by CORT was so pronounced that sub-neuroinflammatory exposures by inhalation instigated neuroinflammation when paired with prior CORT exposure. This effect also was extended to another common inflammagen, PIC (a viral mimic). Furthermore, a single week of CORT exposure maintained the potential for priming for 30 days, while intermittent exposure to CORT for up to 90 days synergistically primed the LPS-induced neuroinflammatory response. These findings highlight the possibility for an isolated inflammatory event to be exacerbated by a temporally distant stressful stimulus and demonstrates the potential for recurrent stress to greatly aggravate chronic inflammatory disorders.

      4. Intercountry consensus building: Lessons from developing a chronic-conditions self-management support framework
        Mills SL, Ziabakhsh S, Brady TJ, Jayanthan J, Sargious PM.
        Health Promot Pract. 2018 Jan 1:1524839917746147.
        Self-management support initiatives that aim to improve the self-care of chronic conditions are considered a key part of a health promotion strategy for addressing the impacts of long-term illness. Given the growth of these activities and still evolving evidence base, thoughtful intercountry collaborations with subject matter experts can be an effective way to expedite building self-management support capacity, promoting the advancement of evidence, and developing effective policies and programs. The challenge is to find an effective consensus building process that promotes linkages between researchers and health promotion decisions makers across vast geographical boundaries and limited resources. This paper describes the international, multistage, face-to-face, and online process that was used for developing an international framework for self-management support by researchers, educators, health care providers, policy makers, program managers/directors, program planners, consultants, patient group representatives, and consumers in 16 countries. We reflect on key lessons from this international initiative and discuss how this type of process may be useful for other health promotion groups trying to exchange knowledge and build consensus on how to move a field of research, policy, and/or practice forward, and advance the evidence-base of practice and the relevance of research.

    • Communicable Diseases
      1. Optimizing delivery of HIV preexposure prophylaxis for women in the United States
        Aaron E, Blum C, Seidman D, Hoyt MJ, Simone J, Sullivan M, Smith DK.
        AIDS Patient Care STDS. 2018 Jan;32(1):16-23.
        Preexposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, it is underutilized among women who are at risk for acquisition of HIV. Women comprise one in five HIV diagnoses in the United States, and significant racial disparities in new HIV diagnoses persist. The rate of new HIV diagnoses among black and African American women in 2015 was 16 times greater than that of white women. These disparities highlight the importance of HIV prevention strategies for women, including the use of PrEP. PrEP is the first highly effective HIV prevention method available to women that is entirely within their control. However, because so few women who may benefit from PrEP are aware of it, few women’s healthcare providers offer PrEP to their patients, PrEP has not yet achieved its potential to reduce HIV infections in women. This article describes individual and systemic barriers for women related to the uptake of PrEP services; explains how providers can identify women at risk for HIV; reviews how to provide PrEP to women; and outlines client-centered models for HIV prevention services. Better access to culturally acceptable and affordable medical and social services may offer support to women for consistent and ongoing use of PrEP. This discussion may be used to inform HIV prevention activities for women and guide interventions to decrease racial/ethnic disparities in rates of HIV infection among US women.

      2. Multi-drug resistant non-typhoidal Salmonella associated with invasive disease in western Kenya
        Akullian A, Montgomery JM, John-Stewart G, Miller SI, Hayden HS, Radey MC, Hager KR, Verani JR, Ochieng JB, Juma J, Katieno J, Fields B, Bigogo G, Audi A, Walson J.
        PLoS Negl Trop Dis. 2018 Jan 12;12(1):e0006156.
        Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007-2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates. Multi-drug resistant strains of NTS were more commonly isolated from patients presenting with NTS bacteremia compared to NTS diarrhea. This relationship was observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P = 0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P = 0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P = 0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI (2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P = 0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia compared to diarrhea among children and adults. This association was seen in HIV-uninfected individuals infected with either S. Typhimurium or S. Enteritidis. Risk of developing bacteremia from NTS infection may be driven by virulence properties of the Salmonella pathogen.

      3. Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial
        Baxi SM, Vittinghoff E, Bacchetti P, Huang Y, Chillag K, Wiegand R, Anderson PL, Grant R, Greenblatt RM, Buchbinder S, Gandhi M, Liu AY.
        PLoS One. 2018 ;13(1):e0190118.
        CLINICAL TRIAL REGISTRATION: Clinical NCT00131677.

      4. Rapid increase in gonorrhea cases with reduced susceptibility to azithromycin in Columbus, Ohio
        Bazan JA, Williams Roberts M, Soge OO, Torrone EA, Dennison A, Ervin M, Hun S, Fields KS, Turner AN.
        Sex Transm Dis. 2018 Feb;45(2):e5-e6.

        [No abstract]

      5. Risk factors and outcomes associated with multidrug-resistant Acinetobacter baumannii upon intensive care unit admission
        Blanco N, Harris AD, Rock C, Johnson JK, Pineles L, Bonomo RA, Srinivasan A, Pettigrew MM, Thom KA.
        Antimicrob Agents Chemother. 2018 Jan;62(1).
        Multidrug-resistant (MDR) Acinetobacter baumannii, associated with broad-spectrum antibiotic use, is an important nosocomial pathogen associated with morbidity and mortality. This study aimed to investigate the prevalence of MDR A. baumannii perirectal colonization among adult patients upon admission to the intensive care unit (ICU) over a 5-year period and to identify risk factors and outcomes associated with colonization. A retrospective cohort analysis of patients admitted to the medical intensive care unit (MICU) and surgical intensive care unit (SICU) at the University of Maryland Medical Center from May 2005 to September 2009 was performed using perirectal surveillance cultures on admission. Poisson and logistic models were performed to identify associated risk factors and outcomes. Four percent of the cohort were positive for MDR A. baumannii at ICU admission. Among patients admitted to the MICU, those positive for MDR A. baumannii at admission were more likely to be older, to have received antibiotics before ICU admission, and to have shorter length of stay in the hospital prior to ICU admission. Among patients admitted to the SICU, those colonized were more likely to have at least one previous admission to our hospital. Patients positive for MDR A. baumannii at ICU admission were 15.2 times more likely to develop a subsequent positive clinical culture for A. baumannii and 1.4 times more likely to die during the current hospitalization. Risk factors associated with MDR A. baumannii colonization differ by ICU type. Colonization acts as a marker of disease severity and of risk of developing a subsequent Acinetobacter infection and of dying during hospitalization. Therefore, active surveillance could guide empirical antibiotic selection and inform infection control practices.

      6. Status of HIV epidemic control among adolescent girls and young women aged 15-24 years – seven African countries, 2015-2017
        Brown K, Williams DB, Kinchen S, Saito S, Radin E, Patel H, Low A, Delgado S, Mugurungi O, Musuka G, Tippett Barr BA, Nwankwo-Igomu EA, Ruangtragool L, Hakim AJ, Kalua T, Nyirenda R, Chipungu G, Auld A, Kim E, Payne D, Wadonda-Kabondo N, West C, Brennan E, Deutsch B, Worku A, Jonnalagadda S, Mulenga LB, Dzekedzeke K, Barradas DT, Cai H, Gupta S, Kamocha S, Riggs MA, Sachathep K, Kirungi W, Musinguzi J, Opio A, Biraro S, Bancroft E, Galbraith J, Kiyingi H, Farahani M, Hladik W, Nyangoma E, Ginindza C, Masangane Z, Mhlanga F, Mnisi Z, Munyaradzi P, Zwane A, Burke S, Kayigamba FB, Nuwagaba-Biribonwoha H, Sahabo R, Ao TT, Draghi C, Ryan C, Philip NM, Mosha F, Mulokozi A, Ntigiti P, Ramadhani AA, Somi GR, Makafu C, Mugisha V, Zelothe J, Lavilla K, Lowrance DW, Mdodo R, Gummerson E, Stupp P, Thin K, Frederix K, Davia S, Schwitters AM, McCracken SD, Duong YT, Hoos D, Parekh B, Justman JE, Voetsch AC.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):29-32.
        In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries. The national prevalence of HIV infection in adolescent girls and young women aged 15-24 years, the percentage who were aware of their status, and among those persons who were aware, the percentage who had achieved viral suppression were calculated. The target for viral suppression among all persons with HIV infection is 73% (the product of 90% x 90% x 90%). Among all seven countries, the prevalence of HIV infection among adolescent girls and young women was 3.6%; among those in this group, 46.3% reported being aware of their HIV-positive status, and 45.0% were virally suppressed. Sustained efforts by national HIV and public health programs to diagnose HIV infection in adolescent girls and young women as early as possible to ensure rapid initiation of ART should help achieve epidemic control among adolescent girls and young women.

      7. Disparities in HIV viral load suppression by race/ethnicity among men who have sex with men in the HIV Outpatient Study
        Buchacz K, Armon C, Tedaldi E, Palella FJ, Novak RM, Ward D, Hart R, Durham M, Brooks J.
        AIDS Res Hum Retroviruses. 2018 Jan 9.
        INTRODUCTION: Maximizing the rates of virologic suppression (VS) among gay, bisexual, and other men who have sex with men (MSM) is essential to limiting HIV morbidity and sexual transmission of HIV in the United States. METHODS: We analyzed data for MSM of non-Hispanic white (white), non-Hispanic black (black) or Hispanic/Latino race/ethnicity in the HIV Outpatient Study (HOPS) at nine U.S. HIV clinics. VS (HIV RNA < 50 copies/mL) was measured closest to January 1, 2015. We modeled factors associated with VS among persons prescribed ART for >/= 6 months and assessed VS for a subset of participants with behavioral interview data. RESULTS: Among 1,303 MSM studied, 24% were black and 11% were Hispanic/Latino. Fewer black than white or Hispanic/Latino MSM had any documented ART use history (92% vs. 99% and 94%, respectively), and fewer had VS (72% vs. 91% and 81%), P < 0.001. In analyses of MSM prescribed ART, which adjusted for insurance type, duration of ART use, and CD4+ cell count, blacks had lower prevalence of VS than whites (adjusted prevalence ratio [PR] 0.87, 95% confidence interval [95% CI] 0.81-0.93) and Hispanics/Latinos did not (PR 0.95, 95% CI 0.88-1.02). Among 331 MSM with interview data, 6% had no VS but reported anal sex without a condom with an HIV-uninfected or unknown HIV serostatus male partner in the past six months. DISCUSSION: In this study of HIV-infected MSM, blacks had a significantly lower prevalence of VS than white men. Optimizing HIV care and prevention among all MSM will require addressing underlying risk factors and social determinants of health that contribute to racial/ethnic disparities in HIV outcomes.

      8. HIV infection and HIV-associated behaviors among persons who inject drugs – 20 cities, United States, 2015
        Burnett JC, Broz D, Spiller MW, Wejnert C, Paz-Bailey G.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):23-28.
        In the United States, 9% of human immunodeficiency virus (HIV) infections diagnosed in 2015 were attributed to injection drug use (1). In 2015, 79% of diagnoses of HIV infection among persons who inject drugs occurred in urban areas (2). To monitor the prevalence of HIV infection and associated behaviors among persons who inject drugs, CDC’s National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing in selected metropolitan statistical areas (MSAs) (3). The prevalence of HIV infection among persons who inject drugs in 20 MSAs in 2015 was 7%. In a behavioral analysis of HIV-negative persons who inject drugs, an estimated 27% receptively shared syringes and 67% had condomless vaginal sex in the previous 12 months. During the same period, 58% had tested for HIV infection and 52% received syringes from a syringe services program. Given the increased number of persons newly injecting drugs who are at risk for HIV infection because of the recent opioid epidemic (2,4), these findings underscore the importance of continuing and expanding health services, HIV prevention programs, and community-based strategies, such as those provided by syringe services programs, for this population.

      9. Iatrogenic Creutzfeldt-Jakob disease with amyloid-beta pathology: an international study
        Cali I, Cohen ML, Hasmall yi U, Parchi P, Giaccone G, Collins SJ, Kofskey D, Wang H, McLean CA, Brandel JP, Privat N, Sazdovitch V, Duyckaerts C, Kitamoto T, Belay ED, Maddox RA, Tagliavini F, Pocchiari M, Leschek E, Appleby BS, Safar JG, Schonberger LB, Gambetti P.
        Acta Neuropathol Commun. 2018 Jan 8;6(1):5.
        The presence of pathology related to the deposition of amyloid-beta (Abeta) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases – 21 with adequate number of histopathological sections – originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP(Sc)), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP(Sc) with the exception of iCJD harboring the “MMi” phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Abeta pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients’ younger age CAA was more severe in iCJD than sCJD, while Abeta diffuse plaques, in absence of Abeta CP, populated one third of sCJD. Abeta pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Abeta phenotypes indicating that the occurrence of Abeta pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Abeta phenotype in iCJD since it is observed in nearly 90% of all iCJD with Abeta pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Abeta pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.

      10. Risk behaviors among young men who have sex with men in Bangkok: A qualitative study to understand and contextualize high HIV incidence
        Chemnasiri T, Beane CR, Varangrat A, Chaikummao S, Chitwarakorn A, Van Griensven F, Holtz TH.
        J Homosex. 2018 Jan 8.
        The Bangkok Men Who Have Sex with Men (MSM) Cohort Study has shown high HIV incidence (8-12/100 person-years) among 18-21 year-old MSM. These data led to a further study using qualitative methods among young (18-24 year old) MSM in order to understand the factors driving the HIV epidemic among YMSM. We conducted 8 focus group discussions and 10 key informant interviews among YMSM in Bangkok, Thailand. Socio-demographic and behavioral data were collected using a questionnaire. We audio-recorded, transcribed, and analyzed qualitative and questionnaire data using computer software. The categories relating to risk behavior were 1) the use of social network for seeking sexual partners and the marketing promotions of MSM entertainment venues, 2) social influence by peer and older MSM, 3) easy access to high parties and group sex, 4) easy access to club drugs, 5) conceptions related to HIV risk, and 6) sexual preferences of YMSM. Increased HIV testing, same-sex education, and YMSM-specific HIV prevention efforts are urgently needed for YMSM in Bangkok.

      11. Comparison of the outcomes of individuals with medically attended influenza A and B virus infections enrolled in 2 international cohort studies over a 6-year period: 2009-2015
        Dwyer DE, Lynfield R, Losso MH, Davey RT, Cozzi-Lepri A, Wentworth D, Uyeki TM, Gordin F, Angus B, Qvist T, Emery S, Lundgren J, Neaton JD.
        Open Forum Infect Dis. 2017 Fall;4(4):ofx212.
        Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes. Results: Of 3952 outpatients, 1290 (32.6%) had A(H1N1)pdm09 virus infection, 1857 (47.0%) had A(H3N2), and 805 (20.4%) had influenza B. Of 1398 inpatients, 641 (45.8%) had A(H1N1)pdm09, 532 (38.1%) had A(H3N2), and 225 (16.1%) had influenza B. Outpatients with A(H1N1)pdm09 were younger with fewer comorbidities and were more likely to be hospitalized during the 14-day follow-up (3.3%) than influenza B (2.2%) or A(H3N2) (0.7%; P < .0001). Hospitalized patients with A(H1N1)pdm09 (20.3%) were more likely to be enrolled from intensive care units (ICUs) than those with A(H3N2) (11.3%) or B (9.8%; P < .0001). However, 60-day follow-up of discharged inpatients showed no difference in disease progression (P = .32) or all-cause mortality (P = .30) among influenza types/subtypes. These findings were consistent after covariate adjustment, in sensitivity analyses, and for subgroups defined by age, enrollment location, and comorbidities. Conclusions: Outpatients infected with influenza A(H1N1)pdm09 or influenza B were more likely to be hospitalized than those with A(H3N2). Hospitalized patients infected with A(H1N1)pdm09 were younger and more likely to have severe disease at study entry (measured by ICU enrollment), but did not have worse 60-day outcomes.

      12. Virologic suppression and CD4+ cell count recovery after initiation of raltegravir or efavirenz-containing HIV treatment regimens
        Edwards JK, Cole SR, Hall HI, Mathews WC, Moore RD, Mugavero MJ, Eron JJ.
        Aids. 2018 Jan 14;32(2):261-266.
        OBJECTIVE: To explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care. DESIGN: Cohort study of adults enrolled in HIV care in the United States. METHODS: We compared virologic suppression and CD4 cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV. We accounted for nonrandom treatment assignment, informative censoring, and nonrandom selection from the US target population using inverse probability weights. RESULTS: Of the 2843 patients included in the study, 2476 initiated the efavirenz-containing regimen and 367 initiated the raltegravir-containing regimen. In the weighted intent-to-treat analysis, patients spent an average of 74 (95% confidence interval: 41, 106) additional days alive with a suppressed viral load on the raltegravir regimen than on the efavirenz regimen over the 2.5-year study period. CD4 cell count recovery was also superior under the raltegravir regimen. CONCLUSION: Patients receiving raltegravir spent more time alive and suppressed than patients receiving efavirenz, but the probability of viral suppression by 2.5 years after treatment was similar between groups. Optimizing the amount of time spent in a state of viral suppression is important to improve survival among people living with HIV and to reduce onward transmission.

      13. Implementing voluntary medical male circumcision using an innovative, integrated, health systems approach: experiences from 21 districts in Zimbabwe
        Feldacker C, Makunike-Chikwinya B, Holec M, Bochner AF, Stepaniak A, Nyanga R, Xaba S, Kilmarx PH, Herman-Roloff A, Tafuma T, Tshimanga M, Sidile-Chitimbire VT, Barnhart S.
        Glob Health Action. 2018 ;11(1):1414997.
        BACKGROUND: Despite increased support for voluntary medical male circumcision (VMMC) to reduce HIV incidence, current VMMC progress falls short. Slow progress in VMMC expansion may be partially attributed to emphasis on vertical (stand-alone) over more integrated implementation models that are more responsive to local needs. In 2013, the ZAZIC consortium began implementation of a 5-year, integrated VMMC program jointly with Ministry of Health and Child Care (MoHCC) in Zimbabwe. OBJECTIVE: To explore ZAZIC’s approach emphasizing existing healthcare workers and infrastructure, increasing program sustainability and resilience. METHODS: A process evaluation utilizing routine quantitative data. Interviews with key MoHCC informants illuminate program strengths and weaknesses. METHODS: A process evaluation utilizing routine quantitative data. Interviews with key MoHCC informants illuminate program strengths and weaknesses. RESULTS: In start-up and year 1 (March 2013-September, 2014), ZAZIC expanded from two to 36 static VMMC sites and conducted 46,011 VMMCs; 39,840 completed from October 2013 to September 2014. From October 2014 to September 2015, 44,868 VMMCs demonstrated 13% increased productivity. In October, 2015, ZAZIC was required by its donor to consolidate service provision from 21 to 10 districts over a 3-month period. Despite this shock, 57,282 VMMCs were completed from October 2015 to September 2016 followed by 44,414 VMMCs in only 6 months, from October 2016 to March 2017. Overall, ZAZIC performed 192,575 VMMCs from March 2013 to March, 2017. The vast majority of VMMCs were completed safely by MoHCC staff with a reported moderate and severe adverse event rate of 0.3%. CONCLUSION: The safety, flexibility, and pace of scale-up associated with the integrated VMMC model appears similar to vertical delivery with potential benefits of capacity building, sustainability and health system strengthening. These models also appear more adaptable to local contexts. Although more complicated than traditional approaches to program implementation, attention should be given to this country-led approach for its potential to spur positive health system changes, including building local ownership, capacity, and infrastructure for future public health programming.

      14. Characteristics of cases with repeated sexually transmitted infections, Massachusetts, 2014-2016
        Hsu KK, Molotnikov LE, Roosevelt KA, Elder HR, Klevens RM, DeMaria A, Aral SO.
        Clin Infect Dis. 2018 Jan 13.
        Background: Persons with prior sexually transmitted infections (STIs) are at high risk for re-infection. No recent studies have examined the frequency with which persons within a geographic area are diagnosed and reported with multiple bacterial STIs over time. Methods: We conducted a retrospective, population-based study of confirmed syphilis, gonorrhea, and chlamydial infections reported to the Massachusetts state surveillance system within a two-year period, July 28, 2014 – July 27, 2016. Results: Among the Massachusetts population 13-65 years old (4,847,510), 49,142 (1.0%) were reported with >/=1 STI; 6,999 (14.2% of those with one STI) had >/=2 STIs, accounting for 27.7% of STIs. Of cases with >/=5 STIs (high-volume repeaters), 118 (74%) were men and 42 (26%) women. Men spanned the age spectrum, were predominantly white, non-Hispanic, and 87% reported same-sex contacts. Women were younger, predominantly non-white, without known same-sex contacts. Women were re-infected with gonorrhea and chlamydia, or chlamydia alone; none had syphilis or HIV infection. All men with syphilis also had gonorrhea and/or chlamydia; 35% were diagnosed with HIV, before, during the study period, or within 10 months after. The majority (56%) of high-volume repeaters were seen at more than one care site/system. Conclusions: In Massachusetts, a large proportion of bacterial STIs are reported from a small sub-population, many of whom have been repeatedly infected and are likely to have a higher impact on STI/HIV rates. Public health can play a crucial role in reaching high-volume repeaters, whose STI history may be hidden from clinicians due to fragmented care.

      15. Diarrheagenic Escherichia coli and acute gastroenteritis in children in Davidson County, Tennessee, United States: A case-control study
        Imdad A, Foster MA, Iqbal J, Fonnesbeck C, Payne DC, Zhang C, Chappell JD, Halasa N, Gomez-Duarte OG.
        Pediatr Infect Dis J. 2018 Jan 16.
        BACKGROUND: Diarrheagenic Escherichia coli (DEC) are an important cause of acute gastroenteritis in children; however, there is limited information available on the epidemiology, phylogenetics, serotyping, and antibiotic susceptibility of DEC in children in the United States. The aim of this study was to determine the molecular epidemiology of DEC among children with and without acute gastroenteritis in Davidson County, Tennessee. METHODS: This prospective, frequency matched, case-control study recruited subjects 15 days to 17 years of age and detected DEC with polymerase chain reaction from stool samples. Additional testing was done to define phylogenetics and antibiotics resistance. RESULTS: Among 1267 participants, 857 cases and 410 controls, 5.5 % were positive for at least one subtype of DEC. Enteroaggregative E. coli (EAEC) [n=32 (45%)] was the most common subtype followed by enteropathogenic E. coli (EPEC) [n=30 (43%)], Shiga toxin-producing E. coli [n=4 (6%)], and diffusely adherent E. coli [n=4 (6%)]. No significant difference in prevalence of DEC was found between cases (5%) and controls (7%) [Odds ratio (OR): 0.66 (95 % confidence interval (CI) 0.4-1.07)] and results were similar when data were stratified by subtypes and adjusted for age, sex, race, and ethnicity. Substantial diversity was found among DEC isolates in terms of phylotypes and serotypes and a large proportion was resistant to, at least, one antibiotic. CONCLUSIONS: EAEC and EPEC were frequently found in both cases and controls in this study population. DNA-based methods for detection of these subtypes need further investigation to help differentiate between pathogenic and colonizing strains.

      16. Human immunodeficiency virus (HIV) drug resistance in african infants and young children newly diagnosed with HIV: A multicountry analysis
        Jordan MR, Penazzato M, Cournil A, Vubil A, Jani I, Hunt G, Carmona S, Maphalala G, Mthethwa N, Watera C, Kaleebu P, Musanhu CC, Mtapuri-Zinyowera S, Dzangare J, Peeters M, Yang C, Parkin N, Bertagnolio S.
        Clin Infect Dis. 2017 Nov 29;65(12):2018-2025.
        Background: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. Methods: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. Results: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. Conclusions: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

      17. Changes in the epidemiological landscape of invasive candidiasis
        Lamoth F, Lockhart SR, Berkow EL, Calandra T.
        J Antimicrob Chemother. 2018 Jan 1;73(suppl_1):i4-i13.
        The epidemiology of invasive candidiasis has evolved in recent years, warranting a review of the changes and the implications for current and future diagnosis and treatment. The overall burden of invasive candidiasis remains high, particularly in the expanding populations of patients at risk of opportunistic infection, such as the elderly or immunosuppressed. Progressive shifts from Candida albicans to non-albicans Candida spp. have been observed globally. The recent emergence of novel, multiresistant species, such as Candida auris, amplifies the call for vigilance in detection and advances in treatment. Among the current treatment options, fluconazole is still widely used throughout the world. Increased resistance to fluconazole, both acquired and naturally emerging, has been observed. Resistance to echinocandins is presently low but this may change with increased use. Improvement of diagnostic techniques and strategies, development of international surveillance networks and implementation of antifungal stewardship programmes represent major challenges for a better epidemiological control of invasive candidiasis.

      18. Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination
        Lim AG, Qureshi H, Mahmood H, Hamid S, Davies CF, Trickey A, Glass N, Saeed Q, Fraser H, Walker JG, Mukandavire C, Hickman M, Martin NK, May MT, Averhoff F, Vickerman P.
        Int J Epidemiol. 2018 Jan 3.
        Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results: With no further treatment (currently approximately 150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan’s HCV burden will increase markedly.

      19. Susceptibility of Neisseria gonorrhoeae to gentamicin – Gonococcal Isolate Surveillance Project, 2015-2016
        Mann LM, Kirkcaldy RD, Papp JR, Torrone EA.
        Sex Transm Dis. 2018 Feb;45(2):96-98.
        The gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates were determined. Seventy-three percent of isolates demonstrated an MIC range of 8 to 16 mug/mL, and 27% demonstrated an MIC of 4 mug/mL or less. Significant associations between gentamicin MIC and resistance or reduced susceptibility to other antimicrobials were found.

      20. Molecular characterisation of measles virus strains among refugees from Central African Republic in Cameroon in 2014
        Ndombo PK, Ndze VN, Mbarga FD, Anderson R, Acho A, Ebua Chia J, Njamnshi AK, Rota PA, Waku-Kouomou D.
        Epidemiol Infect. 2018 Jan 9:1-5.
        Measles is a highly infectious human viral disease caused by measles virus (MeV). An estimated 114 900 measles deaths occurred worldwide in 2014. There are currently eight clades (A-H) comprised 24 MeV genotypes. We sought to characterise MeVs among Central African Republic (CAR) refugees during the 2014 measles epidemic in Cameroon. Samples were collected from children <15 years with suspected measles infections in two refugee camps in the east region of Cameroon. Viral RNA was extracted directly from urine samples. RNA detection of MeV RNA was performed with real-time reverse transcription polymerase chain reaction (PCR) to amplify a 634 bp nucleotide fragment of the N gene. The sequence of the PCR product was obtained to determine the genotype. MeV RNA was detected in 25 out of 30 samples from suspected cases, and among the 25 positive samples, MeV sequences were obtained from 20. The MeV strains characterised were all genotype B3. The MeV strains from genotype B3 found in this outbreak were more similar to those circulating in Northern Cameroon in 2010-2011 than to MeV strains circulating in the CAR in 2011. Surveillance system should be improved to focus on refugees for early detection of and response to outbreaks.

      21. Factors contributing to measles transmission during an outbreak in Kamwenge District, Western Uganda, April to August 2015
        Nsubuga F, Bulage L, Ampeire I, Matovu JK, Kasasa S, Tanifum P, Riolexus AA, Zhu BP.
        BMC Infect Dis. 2018 Jan 8;18(1):21.
        BACKGROUND: In April 2015, Kamwenge District, western Uganda reported a measles outbreak. We investigated the outbreak to identify potential exposures that facilitated measles transmission, assess vaccine effectiveness (VE) and vaccination coverage (VC), and recommend prevention and control measures. METHODS: For this investigation, a probable case was defined as onset of fever and generalized maculopapular rash, plus >/=1 of the following symptoms: Coryza, conjunctivitis, or cough. A confirmed case was defined as a probable case plus identification of measles-specific IgM in serum. For case-finding, we reviewed patients’ medical records and conducted in-home patient examination. In a case-control study, we compared exposures of case-patients and controls matched by age and village of residence. For children aged 9 m-5y, we estimated VC using the percent of children among the controls who had been vaccinated against measles, and calculated VE using the formula, VE = 1 – ORM-H, where ORM-H was the Mantel-Haenszel odds ratio associated with having a measles vaccination history. RESULTS: We identified 213 probable cases with onset between April and August, 2015. Of 23 blood specimens collected, 78% were positive for measles-specific IgM. Measles attack rate was highest in the youngest age-group, 0-5y (13/10,000), and decreased as age increased. The epidemic curve indicated sustained propagation in the community. Of the 50 case-patients and 200 controls, 42% of case-patients and 12% of controls visited health centers during their likely exposure period (ORM-H = 6.1; 95% CI = 2.7-14). Among children aged 9 m-5y, VE was estimated at 70% (95% CI: 24-88%), and VC at 75% (95% CI: 67-83%). Excessive crowding was observed at all health centers; no patient triage-system existed. CONCLUSIONS: The spread of measles during this outbreak was facilitated by patient mixing at crowded health centers, suboptimal VE and inadequate VC. We recommended emergency immunization campaign targeting children <5y in the affected sub-counties, as well as triaging and isolation of febrile or rash patients visiting health centers.

      22. Comparative assessment of five trials of universal HIV testing and treatment in sub-Saharan Africa
        Perriat D, Balzer L, Hayes R, Lockman S, Walsh F, Ayles H, Floyd S, Havlir D, Kamya M, Lebelonyane R, Mills LA, Okello V, Petersen M, Pillay D, Sabapathy K, Wirth K, Orne-Gliemann J, Dabis F.
        J Int AIDS Soc. 2018 Jan;21(1).
        DESIGN: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials. METHODS: We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations. RESULTS: All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation. CONCLUSIONS: We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally.

      23. Kinetics of serological responses in critically ill patients hospitalized with influenza A(H1N1)pdm09 virus infection in Canada, 2009-2011
        Rolfes MA, Gross FL, Flannery B, Meyers AF, Luo M, Bastien N, Fowler RA, Katz JM, Levine MZ, Kumar A, Uyeki TM.
        J Infect Dis. 2018 Jan 12.
        Background: The kinetics of the antibody response during severe influenza are not well documented. Methods: Critically ill patients with influenza A(H1N1)pdm09 virus infection, confirmed by RT-PCR or seroconversion (>/=4-fold rise in titers), during 2009-2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed effects models and compared by patient outcome, age, and corticosteroid treatment. Results: Of 47 patients with A(H1N1)pdm09 virus infection (median age 47 years), 59% had baseline HAI and 68% had baseline neutralizing titers <40. Antibody titers rose quickly after symptom onset and, by day 14, 83% of patients had HAI and 80% had neutralizing titers >/=40. Baseline HAI titers were significantly higher in patients who died compared with patients who survived; however, the antibody kinetics were similar by patient outcome and corticosteroid treatment. Geometric mean titers over time in older patients were lower compared with younger patients. Conclusions: Critically ill patients with influenza A(H1N1)pdm09 virus infection had strong HAI and neutralizing antibody responses during their illness. Antibody kinetics differed by age but were not associated with patient outcome.

      24. Respiratory syncytial virus seasonality – United States, 2014-2017
        Rose EB, Wheatley A, Langley G, Gerber S, Haynes A.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):71-76.
        Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide (1-3). In the United States, RSV infection results in >57,000 hospitalizations and 2 million outpatient visits each year among children aged <5 years (3). Recent studies have highlighted the importance of RSV in adults as well as children (4). CDC reported RSV seasonality nationally, by U.S. Department of Health and Human Services (HHS) regions* and for the state of Florida, using a new statistical method that analyzes polymerase chain reaction (PCR) laboratory detections reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) ( Nationally, across three RSV seasons, lasting from the week ending July 5, 2014 through July 1, 2017, the median RSV onset occurred at week 41 (mid-October), and lasted 31 weeks until week 18 (early May). The median national peak occurred at week 5 (early February). Using these new methods, RSV season circulation patterns differed from those reported from previous seasons (5). Health care providers and public health officials use RSV circulation data to guide diagnostic testing and to time the administration of RSV immunoprophylaxis for populations at high risk for severe respiratory illness (6). With several vaccines and other immunoprophlyaxis products in development, estimates of RSV circulation are also important to the design of clinical trials and future vaccine effectiveness studies.

      25. Epidemiology of sapovirus infections in a birth cohort in Peru
        Sanchez GJ, Mayta H, Pajuelo MJ, Neira K, Xiaofang L, Cabrera L, Ballard SB, Crabtree JE, Kelleher D, Cama V, Bern C, Oshitani H, Gilman RH, Saito M.
        Clin Infect Dis. 2017 Dec 22.
        Background: Sapovirus is one of the primary viral causes of acute gastroenteritis, especially in settings where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Methods: Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and one non-diarrheal stools collected trimonthly from children up to two years of age (n=1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n=440), collected before and after a sapovirus positive sample. Results: The incidence of sapovirus infection in the first and second year of life was 4.3 and 11.1 per 100-child months, respectively. By two years of age, 82% of children had at least one sapovirus infection, and 64% had at least one sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from four genogroups (GI, GII, GIV and GV) were determined. Among genogroups, GI viruses were more frequently found in symptomatic infections than in asymptomatic infections (OR: 3.1 [CI: 1.3-7.4]). Fifty-nine children had serial sapovirus infections but only three had repeated infection of the same genotype. Conclusions: Sapovirus was frequently detected in children with acute gastroenteritis at the community level during the first two years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which need to be taken into account for vaccine development.

      26. Burden of invasive pneumococcal disease among children in rural Mozambique: 2001-2012
        Sigauque B, Verani JR, Massora S, Vubil D, Quinto L, Acacio S, Mandomando I, Bassat Q, Nhampossa T, Pimenta F, Sacoor C, Carvalho MD, Macete E, Alonso PL.
        PLoS One. 2018 ;13(1):e0190687.
        BACKGROUND: Invasive pneumococcal disease (IPD) is a major cause of illness and death among children worldwide. 10-valent pneumococcal conjugate vaccine (PCV10) was introduced as part of the Mozambican routine immunization program in April 2013. We characterized the IPD burden in a rural area of Mozambique before PCV introduction and estimated the potential impact of this intervention. METHODS: We conducted population-based surveillance for IPD, defined as S. pneumoniae isolated from blood or cerebrospinal fluid, among children <5 years old admitted to Manhica District Hospital, a referral hospital in a rural area with high prevalence of human immunodiciency virus infection. S. pneumoniae was identified using standard microbiologic methods and serotyped using sequential multiplex PCR or Quellung. IPD incidence was calculated among cases from a defined catchment area. RESULTS: From January 2001 through December 2012, we isolated 768 cases of IPD, 498 (65%) of which were bacteraemic pneumonia episodes. A total of 391 (51%) were from the catchment area, yielding IPD incidence rates of 479, 390 and 107 episodes per 100,000 children-years at risk among children <12, 12-23 and 24-<60 months old, respectively. The overall IPD incidence fluctuated and showed a downward trend over time. In these same age groups, in-hospital death occurred in 48 (17%), 26 (12%), and 21 (13%) of all IPD cases, respectively. Overall 90% (543/603) of IPD isolates were available for serotyping; of those, 65% were covered by PCV10 and 83% by PCV13. Among 77 hospital deaths associated with serotyped IPD, 49% and 69% were caused by isolates included in the PCV10 and PCV13, respectively. CONCLUSIONS: We describe very high rates of IPD among children in rural Mozambique that were declining before PCV introduction. Children <1 year old have the greatest incidence and case fatality; although the rates remain high among older groups as well. Most IPD episodes and many deaths among children <5 years old will likely be prevented through PCV10 introduction in Mozambique.

      27. Oseltamivir treatment of influenza in children
        Uyeki TM.
        Clin Infect Dis. 2018 Jan 5.

        [No abstract]

      28. An intervention for reducing the sexual risk of men released from jails
        Williams SP, Myles RL, Sperling CC, Carey D.
        J Correct Health Care. 2018 Jan 1:1078345817745537.
        Incarceration history can affect sexual health behaviors. A randomized controlled trial of a prevention intervention tailored for post-incarcerated men was administered in a reentry setting. Men </=45 days post release were recruited into a five-session intervention study. Participants ( N = 255) were assessed and tested for three sexually transmitted diseases (STDs) and HIV at baseline and 3 months post-intervention and followed up for 3 more months. The intervention group’s STD risks knowledge ( p < .001), partner communication about condoms ( p < .001), and condom application skills ( p < .001) improved. Although fewer men tested positive for an STD at 3 months post-intervention (10% vs. 8%) and no new HIV cases were found, the finding was not significant. A tailored risk reduction intervention for men with incarceration histories can affect sexual risk behaviors.

      29. Pneumococcal community-acquired pneumonia detected by serotype-specific urinary antigen detection assays
        Wunderink RG, Self WH, Anderson EJ, Balk R, Fakhran S, Courtney DM, Qi C, Williams DJ, Zhu Y, Whitney CG, Moore MR, Bramley A, Jain S, Edwards KM, Grijalva CG.
        Clin Infect Dis. 2018 Jan 12.
        Background: Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods: We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens. Results: Among 1736 patients with SSUAD and >/=1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of PCV13 serotype cases identified was not significantly different between the first and second July-June study periods (6.4% vs 4.0%). Conclusions: Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.

    • Disaster Control and Emergency Services
      1. Addressing children’s needs in disasters: A regional pediatric tabletop exercise
        Chung S, Gardner AH, Schonfeld DJ, Franks JL, So M, Dziuban EJ, Peacock G.
        Disaster Med Public Health Prep. 2018 Jan 15:1-5.
        OBJECTIVE: Preparing and responding to the needs of children during public health emergencies continues to be challenging. The purpose of this study was to assess the usefulness of a tabletop exercise in initiating pediatric preparedness strategies and assessing the impact of the exercise on participants’ understanding of and confidence in their roles during pediatric public health emergencies. METHODS: A tabletop exercise was developed to simulate a public health emergency scenario involving smallpox in a child, with subsequent spread to multiple states. During the exercise, participants discussed and developed communication, collaboration, and medical countermeasure strategies to enhance pediatric public health preparedness. Exercise evaluation was designed to assess participants’ knowledge gained and level of confidence surrounding pediatric public health emergencies. RESULTS: In total, 22 participants identified over 100 communication and collaboration strategies to promote pediatric public health preparedness during the exercise and found that the most beneficial aspect during the exercise was the partnership between pediatricians and public health officials. Participants’ knowledge and level of confidence surrounding a pediatric public health emergency increased after the exercise. CONCLUSION: The tabletop exercise was effective in identifying strategies to improve pediatric public health preparedness as well as enhancing participants’ knowledge and confidence surrounding a potential pediatric public health emergency. (Disaster Med Public Health Preparedness. 2018;page 1 of 5).

    • Disease Reservoirs and Vectors
      1. Divergent Cryptosporidium parvum subtype and Enterocytozoon bieneusi genotypes in dromedary camels in Algeria
        Baroudi D, Zhang H, Amer S, Khelef D, Roellig DM, Wang Y, Feng Y, Xiao L.
        Parasitol Res. 2018 Jan 6.
        Little information is available on the occurrence of the zoonotic protists Cryptosporidium spp. and none on Enterocytozoon bieneusi in camels. This preliminary study was conducted to examine the identity of Cryptosporidium subtypes and E. bieneusi genotypes in dromedary camels in Algeria. A total of 39 fecal specimens were collected from young camels. PCR-sequence analysis of the small subunit rRNA was used to detect and genotype Cryptosporidium spp. Cryptosporidium parvum present was further subtyped by sequence analysis of the 60 kDa glycoprotein gene. PCR-sequence analysis of the ribosomal internal transcribed spacer gene was used to detect and genotype E. bieneusi. Altogether, two and eight of the specimens analyzed were positive for C. parvum and E. bieneusi, respectively. The former was identified as a new subtype that is genetically related to the C. hominis If subtype family, whereas the latter was identified as two related genotypes (Macaque1 and a novel genotype) in the newly assigned E. bieneusi genotype group 8. Although they are not known hosts for C. parvum and E. bieneusi, camels are apparently infected with genetically distinct variants of these pathogens.

      2. Guidance for evaluating the safety of experimental releases of mosquitoes, emphasizing mark-release-recapture techniques
        Benedict MQ, Charlwood JD, Harrington LC, Lounibos LP, Reisen WK, Tabachnick WJ.
        Vector Borne Zoonotic Dis. 2018 Jan;18(1):39-48.
        Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, “experimental releases” means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals.

      3. Genetically engineered mosquitoes for pathogen control
        Benedict MQ, Quinlan MM.
        Vector Borne Zoonotic Dis. 2018 Jan;18(1):1.

        [No abstract]

      4. In the United States, the blacklegged tick, Ixodes scapularis, is a vector of seven human pathogens, including those causing Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate of discovery of I. scapularis-borne pathogens over the past two decades, the geographic range of the tick, and incidence and range of I. scapularis-borne disease cases, have increased. Despite knowledge of when and where humans are most at risk of exposure to infected ticks, control of I. scapularis-borne diseases remains a challenge. Human vaccines are not available, and we lack solid evidence for other prevention and control methods to reduce human disease. The way forward is discussed.

      5. Survey of parasitic bacteria in bat bugs, Colorado
        McKee CD, Osikowicz LM, Schwedhelm TR, Bai Y, Castle KT, Kosoy MY.
        J Med Entomol. 2018 Jan 10;55(1):237-241.
        Bat bugs (Cimex adjunctus Barber) (Hemiptera: Cimicidae) collected from big brown bats (Eptesicus fuscus Palisot de Beauvoir) in Colorado, United States were assessed for the presence of Bartonella, Brucella, and Yersinia spp. using molecular techniques. No evidence of Brucella or Yersinia infection was found in the 55 specimens collected; however, 4/55 (7.3%) of the specimens were positive for Bartonella DNA. Multi-locus characterization of Bartonella DNA shows that sequences in bat bugs are phylogenetically related to other Bartonella isolates and sequences from European bats.

      6. Maintaining quality of candidate strains of transgenic mosquitoes for studies in containment facilities in disease endemic countries
        Mumford JD, Leach AW, Benedict MQ, Facchinelli L, Quinlan MM.
        Vector Borne Zoonotic Dis. 2018 Jan;18(1):31-38.
        Transgenic mosquitoes are being developed as novel components of area-wide approaches to vector-borne disease control. Best practice is to develop these in phases, beginning with laboratory studies, before moving to field testing and inclusion in control programs, to ensure safety and prevent costly field testing of unsuitable strains. The process of identifying and developing good candidate strains requires maintenance of transgenic colonies over many generations in containment facilities. By working in disease endemic countries with target vector populations, laboratory strains may be developed and selected for properties that will enhance intended control efficacy in the next phase, while avoiding traits that introduce unnecessary risks. Candidate strains aiming toward field use must consistently achieve established performance criteria, throughout the process of scaling up from small study colonies to production of sufficient numbers for field testing and possible open release. Maintenance of a consistent quality can be demonstrated by a set of insect quality and insectary operating indicators, measured over time at predetermined intervals. These indicators: inform comparability of studies using various candidate strains at different times and locations; provide evidence of conformity relevant to compliance with terms of approval for regulated use; and can be used to validate some assumptions related to risk assessments covering the contained phase and for release into the environment.

      7. Studies of transgenic mosquitoes in disease-endemic countries: Preparation of containment facilities
        Quinlan MM, Mutunga JM, Diabate A, Namountougou M, Coulibaly MB, Sylla L, Kayondo J, Balyesima V, Clark L, Benedict MQ, Raymond P.
        Vector Borne Zoonotic Dis. 2018 Jan;18(1):21-30.
        Novel approaches to area-wide control of vector species offer promise as additional tools in the fight against vectored diseases. Evaluation of transgenic insect strains aimed at field population control in disease-endemic countries may involve international partnerships and should be done in a stepwise approach, starting with studies in containment facilities. The preparations of both new-build and renovated facilities are described, including working with local and national regulations regarding land use, construction, and biosafety requirements, as well as international guidance to fill any gaps in regulation. The examples given are for containment categorization at Arthropod Containment Level 2 for initial facility design, classification of wastes, and precautions during shipping. Specific lessons were derived from preparations to evaluate transgenic (non-gene drive) mosquitoes in West and East African countries. Documented procedures and the use of a non-transgenic training strain for trial shipments and culturing were used to develop competence and confidence among the African facility staff, and along the chain of custody for transport. This practical description is offered to support other research consortia or institutions preparing containment facilities and operating procedures in conditions where research on transgenic insects is at an early stage.

      8. Comparative evaluation of anopheline sampling methods in three localities in Indonesia
        St Laurent B, Sukowati S, Burton TA, Bretz D, Zio M, Firman S, Sumardi , Sudibyo H, Safitri A, Suwito , Asih PB, Kosasih S, Shinta , Hawley WA, Burkot TR, Collins FH, Syafruddin D, Lobo NF.
        Malar J. 2018 Jan 8;17(1):13.
        BACKGROUND: The effectiveness of vector control efforts can vary based on the interventions used and local mosquito behaviour and adaptability. In many settings, biting patterns of Anopheles mosquitoes can shift in response to interventions targeting indoor-biting mosquitoes, often resulting in higher proportions of mosquitoes feeding outside or at times when people are not protected. These behaviourally resistant mosquitoes have been shown to sustain residual malaria transmission and limit control efforts. Therefore, it is important to accurately sample mosquitoes to understand their behaviour. METHODS: A variety of traps were evaluated in three geographically diverse sites in malaria-endemic Indonesia to investigate local mosquito feeding behaviour and determine effective traps for surveillance. RESULTS: Eight traps were evaluated in three sites: Canti village, Lampung, Kaliharjo village, Purworejo, and Saketa village, Halmahera, Indonesia, including the gold standard human landing collection (HLC) and a variety of traps targeting host-seeking and resting mosquitoes both indoors and outdoors. Trapping, using indoor and outdoor HLC, the Ifakara tent trap C, goat and human-occupied tents, resting pots and boxes, and CDC miniature light traps was conducted for 16 nights in two sites and 8 nights in a third site, using a Latin square design. Trap efficacy varied by site, with outdoor HLC yielding the highest catch rates in Canti and Kaliharjo and a goat-baited tent trap proving most effective in Saketa. In Canti village, anthropophilic Anopheles sundaicus were caught indoors and outdoors using HLCs, peaking in the early morning. In Kaliharjo, a variety of mosquitoes were caught, mostly outdoors throughout the night. HLC was ineffective in Saketa, the only site where a goat-baited tent trap was tested. This trap was effective in catching zoophilic vectors outdoors before midnight. CONCLUSIONS: Different trapping methods were suitable for different species, likely reflecting differences in behaviour among species. The three villages, each located on a different island in the Indonesian archipelago, contained mosquito populations with unique behaviours. These data suggest that the effectiveness of specific vector monitoring and control measures may vary by location.

    • Environmental Health
      1. Incorporation of fetal and child PFOA dosimetry in the derivation of health-based toxicity values
        Kieskamp KK, Worley RR, McLanahan ED, Verner MA.
        Environ Int. 2017 Dec 23.
        BACKGROUND: Multiple agencies have developed health-based toxicity values for exposure to perfluorooctanoic acid (PFOA). Although PFOA exposure occurs in utero and through breastfeeding, current health-based toxicity values have not been derived using fetal or child dosimetry. Therefore, current values may underestimate the potential risks to fetuses and nursing infants. OBJECTIVE: Using fetal and child dosimetry, we aimed to calculate PFOA maternal human equivalent doses (HEDs), corresponding to a developmental mouse study lowest observed adverse effect level (LOAEL, 1mg/kg/day). Further, we investigated the impact of breastfeeding duration and PFOA half-life on the estimated HEDs. METHODS: First, a pharmacokinetic model of pregnancy and lactation in mice was used to estimate plasma PFOA levels in pups following a maternal exposure to 1mg PFOA/kg/day for gestational days 1-17. Four plasma PFOA concentration metrics were estimated in pups: i) average prenatal; ii) average postnatal; iii) average overall (prenatal and postnatal); and iv) maximum. Then, Monte Carlo simulations were performed using a pharmacokinetic model of pregnancy and lactation in humans to generate distributions of maternal HEDs that would result in fetal/child plasma levels equivalent to those estimated in pups using the mouse model. Median (HED50) and 1st percentile (HED01) of calculated HEDs were calculated. RESULTS: Estimated PFOA maternal HED50s ranged from 3.0×10(-4) to 1.1×10(-3)mg/kg/day and HED01s ranged from 4.7×10(-5) to 2.1×10(-4)mg/kg/day. All calculated HEDs were lower than the HED based on adult dosimetry derived by the Environmental Protection Agency (EPA) (5.3×10(-3)mg/kg/day). CONCLUSION: Our results suggest that fetal/child dosimetry should be considered when deriving health-based toxicity values for potential developmental toxicants.

    • Food Safety
      1. An integrated electrolysis – electrospray – ionization antimicrobial platform using Engineered Water Nanostructures (EWNS) for food safety applications
        Vaze N, Jiang Y, Mena L, Zhang Y, Bello D, Leonard SS, Morris AM, Eleftheriadou M, Pyrgiotakis G, Demokritou P.
        Food Control. 2018 Mar;85:151-160.
        Engineered water nanostructures (EWNS) synthesized utilizing electrospray and ionization of water, have been, recently, shown to be an effective, green, antimicrobial platform for surface and air disinfection, where reactive oxygen species (ROS), generated and encapsulated within the particles during synthesis, were found to be the main inactivation mechanism. Herein, the antimicrobial potency of the EWNS was further enhanced by integrating electrolysis, electrospray and ionization of de-ionized water in the EWNS synthesis process. Detailed physicochemical characterization of these enhanced EWNS (eEWNS) was performed using state-of-the-art analytical methods and has shown that, while both size and charge remain similar to the EWNS (mean diameter of 13 nm and charge of 13 electrons), they possess a three times higher ROS content. The increase of the ROS content as a result of the addition of the electrolysis step before electrospray and ionization led to an increased antimicrobial ability as verified by E. coli inactivation studies using stainless steel coupons. It was shown that a 45-minute exposure to eEWNS resulted in a 4-log reduction as opposed to a 1.9-log reduction when exposed to EWNS. In addition, the eEWNS were assessed for their potency to inactivate natural microbiota (total viable and yeast and mold counts), as well as, inoculated E.coli on the surface of fresh organic blackberries. The results showed a 97% (1.5-log) inactivation of the total viable count, a 99% (2-log) reduction in the yeast and mold count and a 2.5-log reduction of the inoculated E.coli after 45 minutes of exposure, without any visual changes to the fruit. This enhanced antimicrobial activity further underpins the EWNS platform as an effective, dry and chemical free approach suitable for a variety of food safety applications and could be ideal for delicate fresh produce that cannot withstand the classical, wet disinfection treatments.

    • Genetics and Genomics
      1. Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient
        Dhenni R, Karyanti MR, Putri ND, Yohan B, Yudhaputri FA, Ma’roef CN, Fadhilah A, Perkasa A, Restuadi R, Trimarsanto H, Mangunatmadja I, Ledermann JP, Rosenberg R, Powers AM, Myint KS, Sasmono RT.
        PLoS Negl Trop Dis. 2018 Jan 12;12(1):e0006198.
        Although neurological manifestations associated with dengue viruses (DENV) infection have been reported, there is very limited information on the genetic characteristics of neurotropic DENV. Here we describe the isolation and complete genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing was employed to deduce the complete genome of the neurotropic DENV-3 isolate. Based on complete genome analysis, two unique and nine uncommon amino acid changes in the protein coding region were observed in the virus. A phylogenetic tree and molecular clock analysis revealed that the neurotropic virus was a member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor with other isolates from Jakarta around 1998. This is the first report of neurotropic DENV-3 complete genome analysis, providing detailed information on the genetic characteristics of this virus.

      2. Emergence of G12 and G9 rotavirus genotypes in the Central African Republic, January 2014 to February 2016
        Moure UA, Banga-Mingo V, Gody JC, Mwenda JM, Fandema J, Waku-Kouomou D, Manengu C, Koyazegbe TD, Esona MD, Bowen MD, Gouandijka-Vasilache I.
        BMC Res Notes. 2018 Jan 5;11(1):5.
        OBJECTIVES: Rotavirus gastroenteritis is a major cause of death among children under 5 years globally. A rotavirus gastroenteritis surveillance program started in October 2011 in the Central African Republic (CAR) with the Surveillance Epidemiologique en Afrique Centrale (SURVAC) project. We present here genotyping results showing the emergence of G9 and G12 genotypes in Central African Republic. RESULTS: Among 222 children hospitalized with acute gastroenteritis who had a stool sample collected at the sentinel site, Complexe Pediatrique de Bangui (CPB), Bangui, Central African Republic, 100 (45%) were positive for rotavirus between January 2014 and February 2016. During this period the most common rotavirus strains were G1P[8] (37%), G12P[6] (27%) and G9P[8] (18%).

      3. Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected in Honduras
        Quaye O, Roy S, Rungsrisuriyachai K, Esona MD, Xu Z, Tam KI, Banegas DJ, Rey-Benito G, Bowen MD.
        Mem Inst Oswaldo Cruz. 2018 Jan;113(1):9-16.
        BACKGROUND: Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. OBJECTIVES: In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. METHODS: For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. FINDINGS: The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. MAIN CONCLUSIONS: The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions.

      4. High-quality complete and draft genome sequences for three Escherichia spp. and three Shigella spp. generated with Pacific Biosciences and Illumina Sequencing and Optical Mapping
        Schroeder MR, Juieng P, Batra D, Knipe K, Rowe LA, Sheth M, Smith P, Garcia-Toledo L, Loparev VN, Lindsey RL.
        Genome Announc. 2018 Jan 4;6(1).
        Escherichia spp., including E. albertii and E. coli, Shigella dysenteriae, and S. flexneri are causative agents of foodborne disease. We report here reference-level whole-genome sequences of E. albertii (2014C-4356), E. coli (2011C-4315 and 2012C-4431), S. dysenteriae (BU53M1), and S. flexneri (94-3007 and 71-2783).

      5. QUENTIN: reconstruction of disease transmissions from viral quasispecies genomic data
        Skums P, Zelikovsky A, Singh R, Gussler W, Dimitrova Z, Knyazev S, Mandric I, Ramachandran S, Campo D, Jha D, Bunimovich L, Costenbader E, Sexton C, O’Connor S, Xia GL, Khudyakov Y.
        Bioinformatics. 2018 Jan 1;34(1):163-170.
        Motivation: Genomic analysis has become one of the major tools for disease outbreak investigations. However, existing computational frameworks for inference of transmission history from viral genomic data often do not consider intra-host diversity of pathogens and heavily rely on additional epidemiological data, such as sampling times and exposure intervals. This impedes genomic analysis of outbreaks of highly mutable viruses associated with chronic infections, such as human immunodeficiency virus and hepatitis C virus, whose transmissions are often carried out through minor intra-host variants, while the additional epidemiological information often is either unavailable or has a limited use. Results: The proposed framework QUasispecies Evolution, Network-based Transmission INference (QUENTIN) addresses the above challenges by evolutionary analysis of intra-host viral populations sampled by deep sequencing and Bayesian inference using general properties of social networks relevant to infection dissemination. This method allows inference of transmission direction even without the supporting case-specific epidemiological information, identify transmission clusters and reconstruct transmission history. QUENTIN was validated on experimental and simulated data, and applied to investigate HCV transmission within a community of hosts with high-risk behavior. It is available at Contact: or or or Supplementary information: Supplementary data are available at Bioinformatics online.

      6. High-quality whole-genome sequences for 21 enterotoxigenic Escherichia coli strains generated with PacBio sequencing
        Smith P, Lindsey RL, Rowe LA, Batra D, Stripling D, Garcia-Toledo L, Drapeau D, Knipe K, Strockbine N.
        Genome Announc. 2018 Jan 11;6(2).
        Enterotoxigenic Escherichia coli (ETEC) is an important diarrheagenic pathogen. We report here the high-quality whole-genome sequences of 21 ETEC strains isolated from patients in the United States, international diarrheal surveillance studies, and cruise ship outbreaks.

    • Health Communication and Education
      1. Frequency of risk-related news media messages in 2016 coverage of Zika virus
        Sell TK, Watson C, Meyer D, Kronk M, Ravi S, Pechta LE, Lubell KM, Rose DA.
        Risk Anal. 2018 Jan 3.
        News media plays a large role in the information the public receives during an infectious disease outbreak, and may influence public knowledge and perceptions of risk. This study analyzed and described the content of U.S. news media coverage of Zika virus and Zika response during 2016. A random selection of 800 Zika-related news stories from 25 print and television news sources was analyzed. The study examined 24 different messages that appeared in news media articles and characterized them using theories of risk perception as messages with characteristics that could increase perception of risk (risk-elevating messages; n = 14), messages that could decrease perception of risk (risk-minimizing messages; n = 8), or messages about travel or testing guidance (n = 2). Overall, 96% of news stories in the study sample contained at least one or more risk-elevating message(s) and 61% contained risk-minimizing message(s). The frequency of many messages changed after local transmission was confirmed in Florida, and differed between sources in locations with or without local transmission in 2016. Forty percent of news stories included messages about negative potential outcomes of Zika virus infection without mentioning ways to reduce risk. Findings from this study may help inform current federal, state, and local Zika responses by offering a detailed analysis of how news media are covering the outbreak and response activities as well as identifying specific messages appearing more or less frequently than intended. Findings identifying the types of messages that require greater emphasis may also assist public health communicators in responding more effectively to future outbreaks.

    • Health Disparities
      1. Sleep duration, sleep quality, and sexual orientation: findings from the 2013-2015 National Health Interview Survey
        Galinsky AM, Ward BW, Joestl SS, Dahlhamer JM.
        Sleep Health. 2018 Feb;4(1):56-62.
        INTRODUCTION: This study identifies associations between sleep outcomes and sexual orientation net of sociodemographic and health-related characteristics, and produces estimates generalizable to the US adult population. PARTICIPANTS/METHODS: We used 2013-2015 National Health Interview Survey data (46,909 men; 56,080 women) to examine sleep duration and quality among straight, gay/lesbian, and bisexual US adults. Sleep duration was measured as meeting National Sleep Foundation age-specific recommendations for hours of sleep per day. Sleep quality was measured by 4 indicators: having trouble falling asleep, having trouble staying asleep, taking medication to help fall/stay asleep (all >/=4 times in the past week), and having woken up not feeling well rested (>/=4 days in the past week). RESULTS: In the adjusted models, there were no differences by sexual orientation in the likelihood of meeting National Sleep Foundation recommendations for sleep duration. For sleep quality, gay men were more likely to have trouble falling asleep, to use medication to help fall/stay asleep, and to wake up not feeling well rested relative to both straight and bisexual men. Gay/lesbian women were more likely to have trouble staying asleep and to use medication to help fall/stay asleep relative to straight women. Finally, bisexual women were more likely to have trouble falling and staying asleep relative to straight women. CONCLUSIONS: Sexual minority women and gay men report poorer sleep quality compared with their straight counterparts.

    • Health Economics
      1. Recommendations of the Second Panel on Cost Effectiveness in Health and Medicine: A reference, not a rule book
        Carias C, Chesson HW, Grosse SD, Li R, Meltzer MI, Miller GF, Murphy LB, Nurmagambetov TA, Pike JJ, Whitham HK.
        Am J Prev Med. 2018 Jan 12.

        [No abstract]

      2. Tuberculosis test usage and medical expenditures from outpatient insurance claims data, 2013
        Owusu-Edusei K, Winston CA, Marks SM, Langer AJ, Miramontes R.
        Tuberc Res Treat. 2017 ;2017:3816432.
        Objective: To evaluate TB test usage and associated direct medical expenditures from 2013 private insurance claims data in the United States (US). Methods: We extracted outpatient claims for TB-specific and nonspecific tests from the 2013 MarketScan(R) commercial database. We estimated average expenditures (adjusted for claim and patient characteristics) using semilog regression analyses and compared them to the Centers for Medicare and Medicaid Services (CMS) national reimbursement limits. Results: Among the TB-specific tests, 1.4% of the enrollees had at least one claim, of which the tuberculin skin test was most common (86%) and least expensive ($9). The T-SPOT(R) was the most expensive among the TB-specific tests ($106). Among nonspecific TB tests, the chest radiograph was the most used test (78%), while chest computerized tomography was the most expensive ($251). Adjusted average expenditures for the majority of tests ( approximately 74%) were above CMS limits. We estimated that total United States medical expenditures for the employer-based privately insured population for TB-specific tests were $53.0 million in 2013, of which enrollees paid 17% ($9 million). Conclusions: We found substantial differences in TB test usage and expenditures. Additionally, employer-based private insurers and enrollees paid more than CMS limits for most TB tests.

      3. Trends in health insurance and type among military veterans: United States, 2000-2016
        Zelaya CE, Nugent CN.
        Am J Public Health. 2018 Jan 18:e1-e7.
        OBJECTIVES: To describe long-term national trends in health insurance coverage among US veterans from 2000 to 2016 in the context of recent health care reform. METHODS: We used 2000 to 2016 National Health Interview Survey data on veterans aged 18 to 64 years to examine trends in insurance coverage and uninsurance by year, income, and state Medicaid expansion status. We also explored the current proportions of veterans with each type of insurance by age group. RESULTS: The percentage of veterans with private insurance decreased from 70.8% in 2000 to 56.9% in 2011, whereas between 2000 and 2016 Department of Veterans Affairs (VA) health care coverage (only) almost tripled, Medicaid (without concurrent TRICARE or private coverage) doubled, and TRICARE coverage of any type tripled. After 2011, the percentage of veterans who were uninsured decreased. In 2016, low-income veterans in Medicaid expansion states had double the Medicaid coverage (41.1%) of low-income veterans in nonexpansion states (20.1%). CONCLUSIONS: Our estimates, which are nationally representative of noninstitutionalized veterans, show marked increases in military-related coverage through TRICARE and VA health care. In 2016, only 7.2% of veterans aged 18 to 64 years and 3.7% of all veterans (aged 18 years or older) remained uninsured. (Am J Public Health. Published online ahead of print January 18, 2018: e1-e7. doi:10.2105/AJPH.2017.304212).

    • Healthcare Associated Infections
      1. A multistate investigation of health care-associated Burkholderia cepacia complex infections related to liquid docusate sodium contamination, January-October 2016
        Glowicz J, Crist M, Gould C, Moulton-Meissner H, Noble-Wang J, de Man TJ, Perry KA, Miller Z, Yang WC, Langille S, Ross J, Garcia B, Kim J, Epson E, Black S, Pacilli M, LiPuma JJ, Fagan R.
        Am J Infect Control. 2018 Jan 9.
        BACKGROUND: Outbreaks of health care-associated infections (HAIs) caused by Burkholderia cepacia complex (Bcc) have been associated with medical devices and water-based products. Water is the most common raw ingredient in nonsterile liquid drugs, and the significance of organisms recovered from microbiologic testing during manufacturing is assessed using a risk-based approach. This incident demonstrates that lapses in manufacturing practices and quality control of nonsterile liquid drugs can have serious unintended consequences. METHODS: An epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred among critically ill, hospitalized, adult and pediatric patients was performed between January 1, 2016, and October 31, 2016. RESULTS: One hundred and eight case patients with Bcc infections at a variety of body sites were identified in 12 states. Two distinct strains of Bcc were obtained from patient clinical cultures. These strains were found to be indistinguishable or closely related to 2 strains of Bcc obtained from cultures of water used in the production of liquid docusate, and product that had been released to the market by manufacturer X. CONCLUSIONS: This investigation highlights the ability of bacteria present in nonsterile, liquid drugs to cause infections or colonization among susceptible patients. Prompt reporting and thorough investigation of potentially related infections may assist public health officials in identifying and removing contaminated products from the market when lapses in manufacturing occur.

      2. Trends in incidence of long-term-care facility onset Clostridium difficile infections in 10 US geographic locations during 2011-2015
        Guh AY, Mu Y, Baggs J, Winston LG, Bamberg W, Lyons C, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Beldavs ZG, Kainer MA, Karlsson M, Gerding DN, Dumyati G.
        Am J Infect Control. 2018 Jan 9.
        During 2011-2015, the adjusted long-term-care facility onset Clostridium difficile infection incidence rate in persons aged >/=65 years decreased annually by 17.45% (95% confidence interval, 14.53%-20.43%) across 10 US sites. A concomitant decline in inpatient fluoroquinolone use and the C difficile epidemic strain NAP1/027 among persons aged >/=65 years may have contributed to the decrease in long-term-care facility-onset C difficile infection incidence rate.

      3. Accuracy of provider-selected indications for antibiotic orders
        Heil EL, Pineles L, Mathur P, Morgan DJ, Harris AD, Srinivasan A, Thom KA.
        Infect Control Hosp Epidemiol. 2018 Jan;39(1):111-113.
        Documentation of antibiotic indication provides helpful information for antimicrobial stewardship, but accuracy is not understood. Review of 396 antibiotic orders in a pediatric ICU and adult medicine step-down unit found 90% agreement between provider-selected indication and independent review. Prompts to enter antibiotic indication during order entry provide largely accurate information. Infect Control Hosp Epidemiol 2018;39:111-113.

      4. Hepatitis E virus infection in kidney transplant patients: A single-center study
        Lim MA, Int J Min Sci Technol, Cohen J, Green-Montfort T, Tejada-Strop A, Kohli J, Drobeniuc J, Patel P, Vanderveen M, Bloom RD.
        Transplantation. 2018 Jan 11.

        [No abstract]

      5. High hand contamination rates during norovirus outbreaks in long-term care facilities
        Park GW, Williamson KJ, DeBess E, Cieslak PR, Gregoricus N, De Nardo E, Fricker C, Costantini V, Vinje J.
        Infect Control Hosp Epidemiol. 2018 Jan 14:1-3.
        We examined norovirus contamination on hands of ill patients during 12 norovirus outbreaks in 12 long-term care facilities (LTCFs). The higher frequency and norovirus titers on hands of residents compared to hands of heathcare workers highlights the importance of adhering to appropriate hand hygiene practices during norovirus outbreaks in LTCFs. Infect Control Hosp Epidemiol 2018;1-3.

    • Immunity and Immunization
      1. Intestinal immune responses to type 2 oral polio vaccine (OPV) challenge in infants previously immunized with bivalent OPV and either high-dose or standard inactivated polio vaccine
        Brickley EB, Strauch CB, Wieland-Alter WF, Connor RI, Lin S, Weiner JA, Ackerman ME, Arita M, Oberste MS, Weldon WC, Saez-Llorens X, Bandyopadhyay AS, Wright PF.
        J Infect Dis. 2018 Jan 3.
        Background: The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. Methods: In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2-specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants’ intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Results: Despite mIPV2HD’s 4-fold higher type 2 polio D-antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants’ intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2-specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Conclusions: Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge. Clinical Trials Registration: NCT02111135.

      2. Modeling poliovirus transmission in Pakistan and Afghanistan to inform vaccination strategies in undervaccinated subpopulations
        Duintjer Tebbens RJ, Pallansch MA, Cochi SL, Ehrhardt DT, Farag NH, Hadler SC, Hampton LM, Martinez M, Wassilak SG, Thompson KM.
        Risk Anal. 2018 Jan 3.
        Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

      3. We examined the uptake of rotavirus vaccine and compared trends in acute gastroenteritis (AGE)-associated hospitalizations and outpatient visits among American Indian and Alaska Native (AI/AN) children aged <5 years before and after introduction of the rotavirus vaccine. The rates of AGE-associated hospitalization and outpatient visits among AI/AN children remained below prevaccine levels.

      4. Primary care physicians’ struggle with current adult pneumococcal vaccine recommendations
        Hurley LP, Allison MA, Pilishvili T, O’Leary ST, Crane LA, Brtnikova M, Beaty BL, Lindley MC, Bridges CB, Kempe A.
        J Am Board Fam Med. 2018 Jan-Feb;31(1):94-104.
        INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices recommended 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for at-risk adults >/=19; in 2014, it expanded this recommendation to adults >/=65. Primary care physicians’ practice, knowledge, attitudes, and beliefs regarding these recommendations are unknown. METHODS: Primary care physicians throughout the U.S. were surveyed by E-mail and post from December 2015 to January 2016. RESULTS: Response rate was 66% (617 of 935). Over 95% of respondents reported routinely assessing adults’ vaccination status and recommending both vaccines. A majority found the current recommendations to be clear (50% “very clear,” 38% “somewhat clear”). Twenty percent found the upfront cost of purchasing PCV13, lack of insurance coverage, inadequate reimbursement, and difficulty determining vaccination history to be “major barriers” to giving these vaccines. Knowledge of recommendations varied, with 83% identifying the PCV13 recommendation for adults >/=65 and only 21% identifying the recommended interval between PCV13 and PPSV23 in an individual <65 at increased risk. CONCLUSIONS: Almost all surveyed physicians reported recommending both pneumococcal vaccines, but a disconnect seems to exist between perceived clarity and knowledge of the recommendations. Optimal implementation of these recommendations will require addressing knowledge gaps and reported barriers.

      5. Mumps virus nucleoprotein and hemagglutinin-specific antibody response following a third dose of measles mumps rubella vaccine
        Latner DR, Parker Fiebelkorn A, McGrew M, Williams NJ, Coleman LA, McLean HQ, Rubin S, Hickman CJ.
        Open Forum Infect Dis. 2017 Fall;4(4):ofx263.
        Background: Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure. Methods: Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels. Results: There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year post-MMR3, mumps antibody declined toward baseline but remained elevated (P < .05). The correlation between PRN titers and ELISA measurements was poor (r(2) = .49), although sera with the highest amount of HN IgG also had the highest PRN titers. Conclusions: Individuals with the lowest baseline PRN titers had the largest increase in frequency of samples that became positive for HN and NP by ELISA. A third dose of MMR may benefit certain individuals with a low level of mumps virus-neutralizing antibody, especially in the context of an outbreak or other high-risk setting. Additionally, poor correlation among serologic tests does not allow effective prediction of PRN titer by ELISA.

      6. Improving the efficiency and standards of a national immunization program review: Lessons learnt from United Republic of Tanzania
        Lyimo D, Kamugisha C, Yohana E, Eshetu M, Wallace A, Ward K, Mantel C, Hennessey K.
        Pan African Medical Journal. 2017 ;28.
        A National Immunization Program Review (NIP Review) is a comprehensive external assessment of the performance of a country?s immunization programme. The number of recommended special-topic NIP assessments, such as those for vaccine introduction or vaccine management, has increased. These assessments often have substantial overlap with NIP reviews, raising concern about duplication. Innovative technical and management approaches, including integrating several assessments into one, were applied in the United Republic of Tanzania?s 2015 NIP Review. These approaches and processes were documented and a post-Review survey and group discussion. The Tanzania Review found that integrating assessments so they can be conducted at one time was feasible and efficient. There are concrete approaches for successfully managing a Review that can be shared and practiced including having a well-planned desk review and nominating topic-leads. The use of tablets for data entry has the potential to improve Review data quality and timely analysis; however, careful team training is needed. A key area to improve was to better coordinate and link findings from the national-level and field teams.

      7. A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).

      8. Background: Rotavirus is a common cause of acute gastroenteritis and has also been associated with generalized tonic-clonic afebrile seizures. Since rotavirus vaccine introduction, hospitalizations for treatment of acute gastroenteritis have decreased. We assess whether there has been an associated decrease in seizure-associated hospitalizations. Methods: We used discharge codes to abstract data on seizure hospitalizations among children <5 years old from the State Inpatient Databases of the Healthcare Cost and Utilization Project. We compared seizure hospitalization rates before and after vaccine introduction, using Poisson regression, stratifying by age and by month and year of admission. We performed a time-series analysis with negative binomial models, constructed using prevaccine data from 2000 to 2006 and controlling for admission month and year. Results: We examined 962899 seizure hospitalizations among children <5 years old during 2000-2013. Seizure rates after vaccine introduction were lower than those before vaccine introduction by 1%-8%, and rate ratios decreased over time. Time-series analyses demonstrated a decrease in the number of seizure-coded hospitalizations in 2012 and 2013, with notable decreases in children 12-17 months and 18-23 months. Conclusions: Our analysis provides evidence for a decrease in seizure hospitalizations following rotavirus vaccine introduction in the United States, with the greatest impact in age groups with a high rotavirus-associated disease burden and during rotavirus infection season.

      9. Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine
        Seagle EE, Bednarczyk RA, Hill T, Fiebelkorn AP, Hickman CJ, Icenogle JP, Belongia EA, McLean HQ.
        Vaccine. 2018 Jan 6.
        BACKGROUND: Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence. METHODS: Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6years of age were followed up to 12years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects. RESULTS: Most of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with >/=2-fold experienced a slower decline (</=7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12-15months and >15months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens. CONCLUSIONS: The rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.

      10. Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22-23 March 2017
        Teresa Aguado M, Barratt J, Beard JR, Blomberg BB, Chen WH, Hickling J, Hyde TB, Jit M, Jones R, Poland GA, Friede M, Ortiz JR.
        Vaccine. 2018 Jan 11.
        Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual’s abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide.

      11. Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals
        Widdice LE, Unger ER, Panicker G, Hoagland R, Callahan ST, Jackson LA, Berry AA, Kotloff K, Frey SE, Harrison CJ, Pahud BA, Edwards KM, Mulligan MJ, Sudman J, Bernstein DI.
        Vaccine. 2018 Jan 3.
        BACKGROUND: The originally recommended dosing schedule, 0, 2, 6months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. METHODS: This multi-site, prospective study enrolled healthy 9-17year old girls (n=1321) on the day of or within 28days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. RESULTS: Compared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants >/=15years old had no difference in post-dose 2 titers compared to <15year olds when dose 2 was substantially delayed. CONCLUSIONS: Prolonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV. (NCT00524745).

    • Informatics
      1. INTRODUCTION: Monitoring and understanding population health requires conducting health-related surveys and surveillance. The objective of our study was to assess whether data from self-administered surveys could be collected electronically from patients in urban, primary-care, safety-net clinics and subsequently linked and compared with the same patients’ electronic health records (EHRs). METHODS: Data from self-administered surveys were collected electronically from a convenience sample of 527 patients at 2 Chicago health centers from September through November, 2014. Survey data were linked to EHRs. RESULTS: A total of 251 (47.6%) patients who completed the survey consented to having their responses linked to their EHRs. Consenting participants were older, more likely to report fair or poor health, and took longer to complete the survey than those who did not consent. For 8 of 18 categorical variables, overall percentage of agreement between survey data and EHR data exceeded 80% (sex, race/ethnicity, pneumococcal vaccination, self-reported body mass index [BMI], diabetes, high blood pressure, medication for high blood pressure, and hyperlipidemia), and of these, the level of agreement was good or excellent (kappa >/=0.64) except for pneumococcal vaccination (kappa = 0.40) and hyperlipidemia (kappa = 0.47). Of 7 continuous variables, agreement was substantial for age and weight (concordance coefficients >/=0.95); however, with the exception of calculated survey BMI and EHR-BMI (concordance coefficient = 0.88), all other continuous variables had poor agreement. CONCLUSIONS: Self-administered and web-based surveys can be completed in urban, primary-care, safety-net clinics and linked to EHRs. Linking survey and EHR data can enhance public health surveillance by validating self-reported data, completing gaps in patient data, and extending sample sizes obtained through current methods. This approach will require promoting and sustaining patient involvement.

    • Injury and Violence
      1. Circumstances preceding homicide-suicides involving child victims: A qualitative analysis
        Holland KM, Brown SV, Hall JE, Logan JE.
        J Interpers Violence. 2018 Feb;33(3):379-401.
        Homicide-suicide incidents involving child victims can have a detrimental impact on survivors of the violence, family members and friends of the decedents, and other community members, but the rare occurrence of these acts makes using quantitative data to examine their associated antecedents challenging. Therefore, using qualitative data from the 2003-2011 National Violent Death Reporting System, we examined 175 cases of homicide-suicide involving child victims in an effort to better understand the complex situational factors of these events. Our findings indicate that 98% of homicide-suicides with child victims are perpetrated by adults (mostly parents) and propelled by the perpetrators’ intimate partner problems, mental health problems, and criminal/legal problems. These events are often premeditated, and plans for the violence are sometimes disclosed prior to its occurrence. Findings provide support for several theoretical perspectives, and implications for prevention are discussed.

      2. Interventions that address intimate partner violence and HIV among women: A systematic review
        Marshall KJ, Fowler DN, Walters ML, Doreson AB.
        AIDS Behav. 2018 Jan 8.
        Recognizing the high prevalence of human immunodeficiency virus (HIV)-positive women and girls who are either at risk for or suffer from intimate partner violence (IPV) and the overlapping challenges posed by both public health issues, the White House established an Interagency Federal Working Group to address the intersection of both public health issues in 2012. We conducted this systematic review in response to the Working Group’s charge to identify and describe interventions that address both IPV and HIV among women. We identified 14 studies that met our inclusion criteria, including seven studies (nine unique intervention arms) that significantly affected at least one outcome related to IPV and HIV. In this article, we examine the characteristics of these studies including core components, intervention populations, and effectiveness data. We highlight opportunities to improve the effectiveness of existing interventions, guide future research about IPV and HIV, and inform prevention programmatic delivery. This knowledge will improve the lives of populations at risk, reduce gender-related health disparities, and ultimately reduce the societal burden of both public health issues.

    • Laboratory Sciences
      1. Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris
        Berkow EL, Lockhart SR.
        Diagn Microbiol Infect Dis. 2017 Nov 7.
        CD101 is a new echinocandin with a prolonged half-life. CD101 was tested by broth microdilution against 100 isolates of the emerging yeast Candida auris. It showed activity against most isolates, including some that were resistant to other echinocandins.

      2. Quantitation of saxitoxin in human urine using immunocapture extraction and LC-MS
        Bragg WA, Garrett A, Hamelin EI, Coleman RM, Campbell K, Elliott CT, Johnson RC.
        Bioanalysis. 2018 Jan 15.
        AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method uses monoclonal antibodies coupled to magnetic beads. STX was certified reference material grade from National Research Council, Canada. Analysis was carried out using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1.00-100 ng/ml, the method is well suited to quantify STX exposures based on previously reported cases. CONCLUSION: Compared with our previously published protocols, this method has improved selectivity, a fivefold increase in sensitivity and uses only a third of the sample volume. This method can diagnose future toxin exposures and may complement the shellfish monitoring programs worldwide.

      3. EQcorrscan: Repeating and near-repeating earthquake detection and analysis in python
        Chamberlain CJ, Hopp CJ, Boese CM, Warren-Smith E, Chambers D, Chu SX, Michailos K, Townend J.
        Seismological Research Letters. 2018 ;89(1):173-181.
        EQcorrscan is an open-source Python package for the detection and analysis of repeating and near-repeating seismicity. The package provides reliable, well-Tested, system-Agnostic implementations of matched-filter and subspace detection. Detection can be carried out on machines of diverse architectures, ranging from single-board computers, workstations, and servers to supercomputers and distributed computing environments. The package has been developed in Python to provide readable and user-friendly code and is accompanied by comprehensive and continuously updated documentation and examples. Because the package is written in Python, and extensively leverages ObsPy, EQcorrscan can be run on all major operating systems and can parse most commonly used seismological data formats. In addition to the core detection routines, EQcorrscan includes functions for template creation, stacking (both linear and phase-weighted stacking), magnitude calculation (including singular value decomposition-derived relative moments), event clustering, and others. Numerically intensive routines are written in C to improve efficiency.

      4. Studies of exposure to petroleum (crude oil/fuel) often involve monitoring benzene, toluene, ethylbenzene, xylenes (BTEX), and styrene (BTEXS) because of their toxicity and gas-phase prevalence, where exposure is typically by inhalation. However, BTEXS levels in the general U.S. population are primarily from exposure to tobacco smoke, where smokers have blood levels on average up to eight times higher than nonsmokers. This work describes a method using partition theory and artificial neural network (ANN) pattern recognition to classify exposure source based on relative BTEXS and 2,5-dimethylfuran blood levels. A method using surrogate signatures to train the ANN was validated by comparing blood levels among cigarette smokers from the National Health and Nutrition Examination Survey (NHANES) with BTEXS and 2,5-dimethylfuran signatures derived from the smoke of machine-smoked cigarettes. Classification agreement for an ANN model trained with relative VOC levels was up to 99.8% for nonsmokers and 100.0% for smokers. As such, because there is limited blood level data on individuals exposed to crude oil/fuel, only surrogate signatures derived from crude oil and fuel were used for training the ANN. For the 2007-2008 NHANES data, the ANN model assigned 7 out of 1998 specimens (0.35%) and for the 2013-2014 NHANES data 12 out of 2906 specimens (0.41%) to the crude oil/fuel signature category.

      5. Infection and replication of influenza virus at the ocular surface
        Creager HM, Kumar A, Zeng H, Maines TR, Tumpey TM, Belser JA.
        J Virol. 2018 Jan 10.
        Though influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subject to aerosol inoculation. The temperature at which cells were cultured post-inoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33 degrees C relative to 37 degrees C and this effect was slightly greater for the conjunctivitis isolates than the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multi-layer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited hemagglutination of both ocular and non-ocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of non-ocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells, but that this is more likely for ocular tropic viruses as they are better able to maintain their infectivity during passage through the tear film.IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza viral tropism have yet to be fully elucidated. Here, we sought to identify factors which limit the ability of most influenza viruses to cause ocular infection. Though ocular symptoms in humans caused by avian influenza viruses tend to be relatively mild, these infections are concerning due to the potential of the ocular surface to serve as a portal of entry for viruses that go on to establish respiratory infections. Furthermore, a better understanding of the factors which influence infection and replication in this non-canonical site may point toward novel determinants of tropism in the respiratory tract.

      6. Comparative proteomics of the larval and adult stages of the model cestode parasite Mesocestoides corti
        de Lima JC, Monteiro KM, Cabrera TN, Paludo GP, Moura H, Barr JR, Zaha A, Ferreira HB.
        J Proteomics. 2018 Jan 6.
        Mesocestoides corti is a widely used model for the study of cestode biology, and its transition from the larval tetrathyridium (TT) stage to the strobilated, adult worm (ST) stage can be induced and followed in vitro. Here, a proteomic approach was used to describe and compare M. corti TT and ST protein repertories. Overall, 571 proteins were identified, 238 proteins in TT samples and 333 proteins in ST samples. Among the identified proteins, 207 proteins were shared by TTs and STs, while 157 were stage-specific, being 31 exclusive from TTs, and 126 from STs. Functional annotation revealed fundamental metabolic differences between the TT and the ST stages. TTs perform functions related mainly to basic metabolism, responsible for growth and vegetative development by asexual reproduction. STs, in contrast, perform a wider range of functions, including macromolecule biosynthetic processes, gene expression and control pathways, which may be associated to its proglottization/segmentation, sexual differentiation and more complex physiology. Furthermore, the generated results provided an extensive list of cestode proteins of interest for functional studies in M. corti. Many of these proteins are novel candidate diagnostic antigens, and/or potential targets for the development of new and more effective antihelminthic drugs. BIOLOGICAL SIGNIFICANCE: Cestodiases are parasitic diseases with serious impact on human and animal health. Efforts to develop more effective strategies for diagnosis, treatment or control of cestodiases are impaired by the still limited knowledge on many aspects of cestode biology, including the complex developmental processes that occur in the life cycles of these parasites. Mesocestoides corti is a good experimental model to study the transition from the larval to the adult stage, called strobilation, which occur in typical cestode life-cycles. The performed proteomics approach provided large-scale identification and quantification of M. corti proteins. Many stage-specific or differentially expressed proteins were detected in the larval tetrathyridium (TT) stage and in the strobilated, adult worm (ST) stage. Functional comparative analyses of the described protein repertoires shed light on function and processes associated to specific features of both stages, such as less differentiation and asexual reproduction in TTs, and proglottization/segmentation and sexual differentiation in ST. Moreover, many of the identified stage-specific proteins are useful as cestode developmental markers, and are potential targets for development of novel diagnostic methods and therapeutic drugs for cestodiases.

      7. Pulmonary exposure to carbon nanotubes (CNTs) induces fibrosing lesions in the lungs that manifest rapid-onset inflammatory and fibrotic responses, leading to chronic fibrosis in animals and health concerns in exposed humans. The mechanisms underlying CNT-induced fibrogenic effects remain undefined. Macrophages are known to play important roles in immune regulation and fibrosis development through their distinct subsets. Here we investigated macrophage polarization and activation in mouse lungs exposed to multi-walled CNTs (MWCNTs). Male C57BL/6J mice were treated with MWCNTs (XNRI MWNT-7) at 40 mug per mouse ( approximately 1.86 mg/kg body weight) by oropharyngeal aspiration. The treatment stimulated prominent acute inflammatory and fibrotic responses. Moreover, it induced pronounced enrichment and polarization of macrophages with significantly increased M1 and M2 populations in a time-dependent manner. Induction of M1 polarization was apparent on day 1 with a peak on day 3, but declined rapidly thereafter. On the other hand, the M2 polarization was induced on day 1 modestly, but was remarkably elevated on day 3 and maintained at a high level through day 7. M1 and M2 macrophages were functionally activated by MWCNTs as indicated by the expression of their distinctive functional markers, such as iNOS and ARG1, with time courses parallel to M1 and M2 polarization, respectively. Molecular analysis revealed MWCNTs boosted specific STAT and IRF signaling pathways to regulate M1 and M2 polarization in the lungs. These findings suggest a new mechanistic connection between inflammation and fibrosis induced by MWCNTs through the polarization and activation of macrophages during MWCNT-induced lung pathologic response.

      8. Structural characterization of cardiolipin-driven activation of cytochrome C into a peroxidase and membrane perturbation
        Mohammadyani D, Yanamala N, Samhan Arias AK, Kapralov AA, Stepanov G, Nuar N, Planas-Iglesias J, Sanghera N, Kagan VE, Klein-Seetharaman J.
        Biochim Biophys Acta. 2018 Jan 6.
        The interaction between CL and cytochrome c (cyt-c), results in a gain of function of peroxidase activity by cyt-c. Despite intensive research, disagreements on nature and molecular details of this interaction remain. In particular, it is still not known how the interaction triggers the onset of apoptosis. Enzymatic characterization of peroxidase activity has highlighted the need for a critical threshold concentration of CL, a finding of profound physiological relevance in vivo. Using solution NMR, fluorescence spectroscopy, and in silico modeling approaches we here confirm that full binding of cyt-c to the membrane requires a CL:cyt-c threshold ratio of 5:1. Among three binding sites, the simultaneous binding of two sites, at two opposing sides of the heme, provides a mechanism to open the heme crevice to substrates, resulting in “productive binding” in which cyt-c then sequesters CL, inducing curvature in the membrane. Membrane perturbation along with lipid peroxidation, due to interactions of heme/CL acyl chains, initiates the next step in the apoptotic pathway of making the membrane leaky. The third CL binding site while allowing interaction with the membrane, does not cluster CL or induce subsequent events, making this interaction “unproductive”.

      9. Accuracy and reproducibility of the Etest to detect drug-resistant Neisseria gonorrhoeae to contemporary treatment
        Papp JR, Rowlinson MC, O’Connor NP, Wholehan J, Razeq JH, Glennen A, Ware D, Iwen PC, Lee LV, Hagan C.
        J Med Microbiol. 2018 Jan;67(1):68-73.
        PURPOSE: Neisseria gonorrhoeae is a sexually transmitted bacterial pathogen that continues to evolve to become resistant to known antibiotics. In preparing for potential emergence, the Centers for Disease Control and Prevention recommends that clinical laboratories maintain or develop protocols to assess antibiotic susceptibly for this organism. This study examines the intra-laboratory variability of using the Etest method to provide consistent MIC values for N. gonorrhoeae and also compared the results of the Etest to known agar dilution MIC values. METHODOLOGY: Clinical N. gonorrhoeae isolates, 100 paired duplicates, were tested by eight laboratories for antibiotic susceptibility to ceftriaxone, cefixime and azithromycin using Etest strips.Results/Key findings. Overall, >80 % of the paired Etest MIC values were within one log2 dilution of the replicate. When compared to the agar dilution reference method, the cefixime Etest MIC values were consistently underreported by one dilution (seven laboratories) or two dilutions (one laboratory). The azithromycin Etest MIC values agreed 90.7 % with the agar dilution MIC values while the agreement with ceftriaxone was 90.9 %. CONCLUSION: Overall, the Etest method yielded reproducible MIC values within each laboratory with the azithromycin and ceftriaxone MIC results consistent to the reference agar dilution method while the cefixime result tended to provide a lower MIC value.

      10. Establishing Ebola virus disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening
        Raftery P, Condell O, Wasunna C, Kpaka J, Zwizwai R, Nuha M, Fallah M, Freeman M, Harris V, Miller M, Baller A, Massaquoi M, Katawera V, Saindon J, Bemah P, Hamblion E, Castle E, Williams D, Gasasira A, Nyenswah T.
        PLoS Negl Trop Dis. 2018 Jan;12(1):e0006135.
        The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region.

      11. Inactivated rotavirus vaccine by parenteral administration induces mucosal immunity in mice
        Resch TK, Wang Y, Moon SS, Joyce J, Li S, Prausnitz M, Jiang B.
        Sci Rep. 2018 Jan 12;8(1):561.
        To improve the safety and efficacy of oral rotavirus vaccines, we developed an inactivated rotavirus vaccine (IRV) for parenteral administration. Since it remains unknown whether parenteral vaccination can induce mucosal immunity, we performed a comprehensive assessment of immune responses to IRV in mice with an adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on T and B cells in spleen and mLN of vaccinated mice. MN patch IRV vaccination induced a slight Th1 phenotype while IM vaccination induced a balanced Th1/Th2 phenotype. In addition, a dose-sparing effect was seen for rotavirus-specific serum IgG and neutralizing activity for both vaccination routes. Our study is the first to show that parenterally administered IRV can induce mucosal immunity in the gut, in addition to strong serum antibody response, and is a promising candidate vaccine in achieving global immunization against rotavirus.

      12. The objective of this present study was to evaluate the performance of a portable gas chromatograph horizontal line photoionization detector (GC-PID), under various test conditions to determine if it could be used in occupational settings. A mixture of seven volatile organic compounds (VOCs) – acetone, ethylbenzene, methyl isobutyl ketone, toluene, m-xylene, p-xylene, and o-xylene – was selected because its components are commonly present in paint manufacturing industries. A full-factorial combination of four concentration levels (exposure scenarios) of VOC mixtures, three different temperatures (25 C, 30 C, and 35 C), and three relative humidities (RHs; 25%, 50%, and 75%) was conducted in a full- size controlled environmental chamber. Three repetitions were conducted for each test condition allowing for estimation of accuracy. Time-weighted average exposure data were collected using solid sorbent tubes (Anasorb 747, SKC Inc.) as the reference sampling medium. Calibration curves of Frog-4000 using the dry gases showed R(2) > 0.99 for all analytes except for toluene (R(2) = 0.97). Frog-4000 estimates within a test condition showed good consistency for the performance of repeated measurement. However, there was approximately 41-64% reduction in the analysis of polar acetone with 75% RH relative to collection at 25% RH. Although Frog-4000 results correlated well with solid sorbent tubes (r = 0.808-0.993, except for toluene) most of the combinations regardless of analyte did not meet the < 25% accuracy criterion recommended by NIOSH. The effect of chromatographic co-elution can be seen with m, p-xylene when the results are compared to the sorbent tube sampling technique with GC-flame ionization detector. The results indicated an effect of humidity on the quantification of the polar compounds that might be attributed to the pre-concentrator placed in the selected GC-PID. Further investigation may resolve the humidity effect on sorbent trap with micro GC pre-concentrator when water vapor is present. Although this instrument does not fulfill the accuracy criterion specified in the NIOSH technical report No. 2012-162, it can be used as a screening tool for range finding monitoring with dry gases calibration in the occupational setting rather than compliance monitoring.

      13. A non-human primate model for rectally transmitted syphilis
        Tansey C, Zhao C, Hopkins A, Ritter JM, Fakile YF, Pillay A, Katz SS, Pereira L, Mitchell J, Deyounks F, Kersh EN, McNicholl JM, Vishwanathan SA.
        J Infect Dis. 2017 Dec 22.
        Men, diagnosed with syphilis or other rectal sexually transmitted infections (STIs), who have sex with men (MSM) are at a higher risk for HIV acquisition, which is concerning given the large increase in recently reported syphilis cases in the United States. We have developed the first non-human primate model for rectally transmitted syphilis by exposing SHIV-infected and naive rhesus macaques to Treponema pallidum in the rectum. All animals showed mucosal lesions, systemic dissemination, and seroconversion (treponemal antibodies). This model would be valuable for studying the manifestations of and interventions for T. pallidum infection, with and without HIV coinfection.

      14. Development of a new enzyme immunoassay for improved detection of rotavirus in fecal specimens of vaccinated infants
        Wang H, Liu M, Sugata K, Wang Y, Hull J, Foytich K, Jiang B.
        J Clin Virol. 2017 Dec 26;99-100:44-49.
        BACKGROUND: Group A rotavirus is the most common cause of acute diarrhea in young children worldwide. A simple and rapid enzyme immunoassay (EIA) has been commonly used to detect rotavirus infection and evaluate rotavirus vaccines. Currently licensed commercial EIA kits have low sensitivity. A more sensitive detection of rotavirus can improve rotavirus diagnostics and vaccine efficacy studies. OBJECTIVE: A biotin-avidin based sandwich EIA was developed and compared with commercial EIA kits for improved detection of viral shedding in fecal samples from infants who received human rotavirus vaccine Rotarix in Mexico. STUDY DESIGN: A monoclonal antibody (mAb: 1D4) specific to human rotavirus group antigen VP6 was prepared and used to develop a biotin-avidin based sandwich EIA. This EIA was employed to test 128 fecal samples from vaccinated infants, in comparison with two commercial EIA kits using RT-PCR as a reference. RESULTS: A new biotin-avidin based sandwich EIA showed specific reaction to group A rotaviruses, but not to other enteric viruses. This new EIA had a detection rate of 36.7% for rotavirus antigen shedding in fecal specimens, which was two times higher (16.4%, 18.0%) than those from two commercial EIA kits. CONCLUSION: The new EIA had specificity and higher sensitivity than commercial kits. This new EIA has the potential to detect rotavirus at lower concentration in clinical specimens and thus should be further evaluated as a more sensitive kit for use in diagnostics and vaccine efficacy and effectiveness studies.

      15. Detection of Mycobacterium tuberculosis pncA mutations by the Nipro Genoscholar PZA-TB II assay compared to conventional sequencing
        Willby MJ, Wijkander M, Havumaki J, Johnson K, Werngren J, Hoffner S, Denkinger CM, Posey JE.
        Antimicrob Agents Chemother. 2018 Jan;62(1).
        Pyrazinamide (PZA) is a standard component of first-line treatment regimens for Mycobacterium tuberculosis and is included in treatment regimens for drug-resistant M. tuberculosis whenever possible. Therefore, it is imperative that susceptibility to PZA be assessed reliably prior to the initiation of therapy. Currently available growth-based PZA susceptibility tests are time-consuming, and results can be inconsistent. Molecular tests have been developed for most first-line antituberculosis drugs; however, a commercial molecular test is not yet available for rapid detection of PZA resistance. Recently, a line probe assay, the Nipro Genoscholar PZA-TB II assay, was developed for the detection of mutations within the pncA gene, including the promoter region, that are likely to lead to PZA resistance. The sensitivity and specificity of this assay were evaluated by two independent laboratories, using a combined total of 249 strains with mutations in pncA or its promoter and 21 strains with wild-type pncA Overall, the assay showed good sensitivity (93.2% [95% confidence interval, 89.3 to 95.8%]) and moderate specificity (91.2% [95% confidence interval, 77.0 to 97.0%]) for the identification of M. tuberculosis strains predicted to be resistant to PZA on the basis of the presence of mutations (excluding known PZA-susceptible mutations) in the pncA coding region or promoter. The assay shows promise for the molecular prediction of PZA resistance.

      16. Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles
        Yanamala N, Kisin ER, Gutkin DW, Shurin MR, Harper M, Shvedova AA.
        J Toxicol Environ Health A. 2018 ;81(4):60-79.
        Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

    • Maternal and Child Health
      1. Antibiotics dispensed to privately insured pregnant women with urinary tract infections – United States, 2014
        Ailes EC, Summers AD, Tran EL, Gilboa SM, Arnold KE, Meaney-Delman D, Reefhuis J.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):18-22.
        Urinary tract infections (UTIs) occur in about 8% of pregnant women, and untreated UTIs can have serious consequences, including pyelonephritis, preterm labor, low birth weight, and sepsis (1). Pregnant women are typically screened for UTIs during early pregnancy, and those with bacteriuria are treated with antibiotics (1,2). Antibiotic stewardship is critical to improving patient safety and to combating antibiotic resistance. Because of the potential risk for birth defects, including anencephaly, heart defects, and orofacial clefts, associated with use of sulfonamides and nitrofurantoin during pregnancy (3), a 2011 committee opinion from the American College of Obstetricians and Gynecologists (ACOG) recommended that sulfonamides and nitrofurantoin may be prescribed in the first trimester of pregnancy only when other antimicrobial therapies are deemed clinically inappropriate (4). To assess the effects of these recommendations, CDC analyzed the Truven Health MarketScan Commercial Database* to examine antibiotic prescriptions filled by pregnant women with UTIs. Among 482,917 pregnancies in 2014, 7.2% of women had an outpatient UTI diagnosis during the 90 days before the date of last menstrual period (LMP) or during pregnancy. Among pregnant women with UTIs, the most frequently prescribed antibiotics during the first trimester were nitrofurantoin, ciprofloxacin, cephalexin, and trimethoprim-sulfamethoxazole. Given the potential risks associated with use of some of these antibiotics in early pregnancy and the potential for unrecognized pregnancy, women’s health care providers should be familiar with the ACOG recommendations and consider the possibility of early pregnancy when treating women of reproductive age.

      2. Attention-deficit/hyperactivity disorder medication prescription claims among privately insured women aged 15-44 years – United States, 2003-2015
        Anderson KN, Ailes EC, Danielson M, Lind JN, Farr SL, Broussard CS, Tinker SC.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):66-70.
        Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects individuals across the lifespan. ADHD medication use among pregnant women is increasing (1), but consensus about the safety of ADHD medication use during pregnancy is lacking. Given that nearly half of U.S. pregnancies are unintended (2), and early pregnancy is a critical period for fetal development, examining trends in ADHD medication prescriptions among reproductive-aged women is important to quantify the population at risk for potential exposure. CDC used the Truven Health MarketScan Commercial Database* for the period 2003-2015 to estimate the percentage of women aged 15-44 years with private employer-sponsored insurance who filled prescriptions for ADHD medications each year. The percentage of reproductive-aged women who filled at least one ADHD medication prescription increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the most frequently filled medications were mixed amphetamine salts, lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to reproductive-aged women is increasingly common; additional research on ADHD medication safety during pregnancy is warranted to inform women and their health care providers about any potential risks associated with ADHD medication exposure before and during pregnancy.

      3. Vital signs: Trends and disparities in infant safe sleep practices – United States, 2009-2015
        Bombard JM, Kortsmit K, Warner L, Shapiro-Mendoza CK, Cox S, Kroelinger CD, Parks SE, Dee DL, D’Angelo DV, Smith RA, Burley K, Morrow B, Olson CK, Shulman HB, Harrison L, Cottengim C, Barfield WD.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):39-46.
        INTRODUCTION: There have been dramatic improvements in reducing infant sleep-related deaths since the 1990s, when recommendations were introduced to place infants on their backs for sleep. However, there are still approximately 3,500 sleep-related deaths among infants each year in the United States, including those from sudden infant death syndrome, accidental suffocation and strangulation in bed, and unknown causes. Unsafe sleep practices, including placing infants in a nonsupine (on side or on stomach) sleep position, bed sharing, and using soft bedding in the sleep environment (e.g., blankets, pillows, and soft objects) are modifiable risk factors for sleep-related infant deaths.

      4. Achieving appropriate gestational weight gain: The role of healthcare provider advice
        Deputy NP, Sharma AJ, Kim SY, Olson CK.
        J Womens Health (Larchmt). 2018 Jan 10.
        BACKGROUND: The Institute of Medicine (IOM) revised gestational weight gain recommendations in 2009. We examined associations between healthcare provider advice about gestational weight gain and inadequate or excessive weight gain, stratified by prepregnancy body mass index category. MATERIALS AND METHODS: We analyzed cross-sectional data from women delivering full-term (37-42 weeks of gestation), singleton infants from four states that participated in the 2010-2011 Pregnancy Risk Assessment Monitoring System (unweighted n = 7125). Women reported the weight gain range (start and end values) advised by their healthcare provider; advice was categorized as follows: starting below recommendations, starting and ending within recommendations (IOM consistent), ending above recommendations, not remembered, or not received. We examined associations between healthcare provider advice and inadequate or excessive, compared with appropriate, gestational weight gain using adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs). RESULTS: Overall, 26.3% of women reported receiving IOM-consistent healthcare provider advice; 26.0% received no advice. Compared with IOM-consistent advice, advice below recommendations was associated with higher likelihood of inadequate weight gain among underweight (aPR 2.22, CI 1.29-3.82) and normal weight women (aPR 1.57, CI 1.23-2.02); advice above recommendations was associated with higher likelihood of excessive weight gain among all but underweight women (aPR range 1.36, CI 1.08-1.72 to aPR 1.42, CI 1.19-1.71). Not remembering or not receiving advice was associated with both inadequate and excessive weight gain. CONCLUSIONS: Few women reported receiving IOM-consistent advice; not receiving IOM-consistent advice put women at-risk for weight gain outside recommendations. Strategies that raise awareness of IOM recommendations and address barriers to providing advice are needed.

      5. Uptake and predictors of early postnatal follow-up care amongst mother-baby pairs in South Africa: Results from three population-based surveys, 2010-2013
        Larsen A, Cheyip M, Aynalem G, Dinh TH, Jackson D, Ngandu N, Chirinda W, Mogashoa M, Kindra G, Lombard C, Goga A.
        J Glob Health. 2017 Dec;7(2):021001.
        Background: Achieving World Health Organization (WHO) recommendations for postnatal care (PNC) within the first few weeks of life is vital to eliminating early mother-to-child transmission of HIV (MTCT) and improving infant health. Almost half of the annual global deaths among children under five occur during the first six weeks of life. This study aims to identify uptake of three PNC visits within the first six weeks of life as recommended by WHO among South African mother-infant pairs, and factors associated with uptake. Methods: We analyzed data from three facility-based, nationally representative surveys (2010, 2011/12 and 2012/13) primarily designed to determine the effectiveness of the South African program to prevent MTCT. This analysis describes the proportion of infants achieving the WHO recommendation of at least 3 PNC visits. Interviews from 27 699 HIV-negative and HIV-positive mothers of infants aged 4-8 weeks receiving their six week immunization were included in analysis. Data were analyzed using STATA 13.0 and weighted for sample ascertainment and South African live births. We fitted a multivariable logistic regression model to estimate factors associated with early PNC uptake. Results: Over half (59.6%, 95% confidence interval (CI) = 59.0-60.3) of mother-infant pairs received the recommended three PNC visits during the first 6 weeks; uptake was 63.1% (95% CI = 61.9-64.3) amongst HIV exposed infants and 58.1% (95% CI = 57.3-58.9) amongst HIV unexposed infants. Uptake of early PNC improved significantly with each survey, but varied significantly by province. Multivariable analysis of the pooled data, controlling for survey year, demonstrated that number of antenatal visits (4+ vs <4 Adjusted odds ratio (aOR) = 1.13, 95% CI = 1.04-1.23), timing of initial antenatal visits (</=12 weeks vs >12 weeks, aOR = 1.13, 95% CI = 1.04-1.23), place of delivery (clinic vs hospital aOR = 1.5, 1.3-1.6), and infant HIV exposure (exposed vs unexposed aOR = 1.2, 95% CI = 1.1-1.2) were the key factors associated with receiving recommended PNC visits. Conclusions: Approximately 40% of neonates did not receive three or more postnatal care visits in the first 6 weeks of life from 2010-2013. To improve uptake of early PNC, early antenatal booking, more frequent antenatal care attendance, and attention to HIV negative women is needed.

      6. Disparities in preconception health indicators – Behavioral Risk Factor Surveillance System, 2013-2015, and Pregnancy Risk Assessment Monitoring System, 2013-2014
        Robbins C, Boulet SL, Morgan I, D’Angelo DV, Zapata LB, Morrow B, Sharma A, Kroelinger CD.
        MMWR Surveill Summ. 2018 Jan 19;67(1):1-16.
        PROBLEM/CONDITION: Preconception health is a broad term that encompasses the overall health of nonpregnant women during their reproductive years (defined here as aged 18-44 years). Improvement of both birth outcomes and the woman’s health occurs when preconception health is optimized. Improving preconception health before and between pregnancies is critical for reducing maternal and infant mortality and pregnancy-related complications. The National Preconception Health and Health Care Initiative’s Surveillance and Research work group suggests ten prioritized indicators that states can use to monitor programs or activities for improving the preconception health status of women of reproductive age. This report includes overall and stratified estimates for nine of these preconception health indicators. REPORTING PERIOD: 2013-2015. DESCRIPTION OF SYSTEMS: Survey data from two surveillance systems are included in this report. The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing state-based, landline and cellular telephone survey of noninstitutionalized adults in the United States aged >/=18 years that is conducted by state and territorial health departments. BRFSS is the main source of self-reported data for states on health risk behaviors, chronic health conditions, and preventive health services primarily related to chronic disease in the United States. The Pregnancy Risk Assessment Monitoring System (PRAMS) is an ongoing U.S. state- and population-based surveillance system administered collaboratively by CDC and state health departments. PRAMS is designed to monitor selected maternal behaviors, conditions, and experiences that occur before, during, and shortly after pregnancy that are self-reported by women who recently delivered a live-born infant. This report summarizes BRFSS and PRAMS data on nine of 10 prioritized preconception health indicators (i.e., depression, diabetes, hypertension, current cigarette smoking, normal weight, recommended physical activity, recent unwanted pregnancy, prepregnancy multivitamin use, and postpartum use of a most or moderately effective contraceptive method) for which the most recent data are available. BRFSS data from all 50 states and the District of Columbia were used for six preconception health indicators: depression, diabetes (excluded if occurring only during pregnancy or if limited to borderline/prediabetes conditions), hypertension (excluded if occurring only during pregnancy or if limited to borderline/prehypertension conditions), current cigarette smoking, normal weight, and recommended physical activity. PRAMS data from 30 states, the District of Columbia, and New York City were used for three preconception health indicators: recent unwanted pregnancy, prepregnancy multivitamin use, and postpartum use of a most or moderately effective contraceptive method by women or their husbands or partners (i.e., male or female sterilization, hormonal implant, intrauterine device, injectable contraceptive, oral contraceptive, hormonal patch, or vaginal ring). Heavy alcohol use during the 3 months before pregnancy also was included in the prioritized set of 10 indicators, but PRAMS data for each reporting area are not available until 2016 for that indicator. Therefore, estimates for heavy alcohol use are not included in this report. All BRFSS preconception health estimates are based on 2014-2015 data except two (hypertension and recommended physical activity are based on 2013 and 2015 data). All PRAMS preconception health estimates rely on 2013-2014 data. Prevalence estimates of indicators are reported for women aged 18-44 years overall, by age group, race-ethnicity, health insurance status, and reporting area. Chi-square tests were conducted to assess differences in indicators by age group, race/ethnicity, and insurance status. RESULTS: During 2013-2015, prevalence estimates of indicators representing risk factors were generally highest and prevalence estimates of health-promoting indicators were generally lowest among older women (35-44 years), non-Hispanic black women, uninsured women, and those residing in southern states. For example, prevalence of ever having been told by a health care provider that they had a depressive disorder was highest among women aged 35-44 years (23.1%) and lowest among women aged 18-24 years (19.2%). Prevalence of postpartum use of a most or moderately effective method of contraception was lowest among women aged 35-44 years (50.6%) and highest among younger women aged 18-24 years (64.9%). Self-reported prepregnancy multivitamin use and getting recommended levels of physical activity were lowest among non-Hispanic black women (21.6% and 42.8%, respectively) and highest among non-Hispanic white women (37.8% and 53.8%, respectively). Recent unwanted pregnancy was lowest among non-Hispanic white women and highest among non-Hispanic black women (5.0% and 11.6%, respectively). All but three indicators (diabetes, hypertension, and use of a most or moderately effective contraceptive method) varied by insurance status; for instance, prevalence of current cigarette smoking was higher among uninsured women (21.0%) compared with insured women (16.1%), and prevalence of normal weight was lower among women who were uninsured (38.6%), compared with women who were insured (46.1%). By reporting area, the range of women reporting ever having been told by a health care provider that they had diabetes was 5.0% (Alabama) to 1.9% (Utah), and women reporting ever having been told by a health care provider that they had hypertension ranged from 19.2% (Mississippi) to 7.0% (Minnesota). INTERPRETATION: Preconception health risk factors and health-promoting indicators varied by age group, race/ethnicity, insurance status, and reporting area. These disparities highlight subpopulations that might benefit most from interventions that improve preconception health. PUBLIC HEALTH ACTION: Eliminating disparities in preconception health can potentially reduce disparities in two of the leading causes of death in early and middle adulthood (i.e., heart disease and diabetes). Public health officials can use this information to provide a baseline against which to evaluate state efforts to improve preconception health.

      7. Variation in surgical management of neurogenic bowel among centers participating in National Spina Bifida Patient Registry
        Routh JC, Joseph DB, Liu T, Schechter MS, Thibadeau JK, Chad Wallis M, Ward EA, Wiener JS.
        J Pediatr Rehabil Med. 2017 Dec 11;10(3-4):303-312.
        PURPOSE: Optimal management of neurogenic bowel in patients with spina bifida (SB) remains controversial. Surgical interventions may be utilized to treat constipation and provide fecal continence, but their use may vary among SB treatment centers. METHODS: We queried the National Spina Bifida Patient Registry (NSBPR) to identify patients who underwent surgical interventions for neurogenic bowel. We abstracted demographic characteristics, SB type, functional level, concurrent bladder surgery, mobility, and NSBPR clinics to determine whether any of these factors were associated with interventions for management of neurogenic bowel. Multivariable logistic regression with adjustment for selection bias was performed. RESULTS: We identified 5,528 patients with SB enrolled in the 2009-14 NSBPR. Of these, 1,088 (19.7%) underwent procedures for neurogenic bowel, including 957 (17.3%) ACE/cecostomy tube and 155 (2.8%) ileostomy/colostomy patients. Procedures were more likely in patients who were older, white, non-ambulatory, with higher-level lesion, with myelomeningocele lesion, with private health insurance (all p< 0.001), and female (p= 0.006). On multivariable analysis, NSBPR clinic, older age (both p< 0.001), race (p= 0.002), mobility status (p= 0.011), higher lesion level (p< 0.001), private insurance (p= 0.002) and female sex (p= 0.015) were associated with increased odds of surgery. CONCLUSIONS: There is significant variation in rates of procedures to manage neurogenic bowel among NSBPR clinics. In addition to SB-related factors such as mobility status and lesion type/level, non-SB-related factors such as patient age, sex, race and treating center are also associated with the likelihood of undergoing neurogenic bowel intervention.

      8. The National Spina Bifida Patient Registry: Past, present, and future
        Thibadeau J.
        J Pediatr Rehabil Med. 2017 Dec 11;10(3-4):205-210.
        “The National Spina Bifida Patient Registry: Past, Present, and Future” was presented at the Spina Bifida World Congress, March 17, 2017, San Diego, California. This commentary provides a summary of registry activities including the reason for development, a description of the clinic participants and their patients who are participating, analytic works and publications. Two specific efforts that are related to the work of the registry, a urologic protocol to preserve renal function for newborns and young children, and a skin breakdown prevention bundle developed and implemented in registry clinics, are highlighted.

    • Mining
      1. Open-air sprays for capturing and controlling airborne float coal dust on longwall faces
        Beck TW, Seaman CE, Shahan MR, Mischler SE.
        Mining Engineering. 2018 ;70(1):42-48.
        Float dust deposits in coal mine return airways pose a risk in the event of a methane ignition. Controlling airborne dust prior to deposition in the return would make current rock dusting practices more effective and reduce the risk of coal-dust-fueled explosions. The goal of this U.S. National Institute for Occupational Safety and Health study is to determine the potential of open-Air water sprays to reduce concentrations of airborne float coal dust, smaller than 75 microm in diameter, in longwall face airstreams. This study evaluated unconfined water sprays in a featureless tunnel ventilated at a typical longwall face velocity of 3.6 m/s (700 fpm). Experiments were conducted for two nozzle orientations and two water pressures for hollow cone, full cone, flat fan, air atomizing and hydraulic atomizing spray nozzles. Gravimetric samples show that airborne float dust removal efficiencies averaged 19.6 percent for all sprays under all conditions. The results indicate that the preferred spray nozzle should be operated at high fluid pressures to produce smaller droplets and move more air. These findings agree with past respirable dust control research, providing guidance on spray selection and spray array design in ongoing efforts to control airborne float dust over the entire longwall ventilated opening.

      2. Analysis of monitored ground support and rock mass response in a longwall tailgate entry
        Esterhuizen GS, Gearhart DF, Tulu IB.
        Int J Min Sci Technol. 2017 .
        A comprehensive monitoring program was conducted to measure the rock mass displacements, support response, and stress changes at a longwall tailgate entry in West Virginia. Monitoring was initiated a few days after development of the gateroad entries and continued during passage of the longwall panels on both sides of the entry. Monitoring included overcore stress measurements of the initial stress within the rock mass, changes in cable bolt loading, standing support pressure, roof deformation, rib deformation, stress changes in the coal pillar, and changes in the full three-dimensional stress tensor within the rock mass at six locations around the monitoring site. During the passage of the first longwall, stress measurements in the rock and coal detected minor changes in loading while minor changes were detected in roof deformation. As a result of the relatively favorable stress and geological conditions, the support systems did not experience severe loading or rock deformation until the second panel approached within 10-15 m of the instrumented locations. After reaching the peak loading at about 50-75 mm of roof sag, the cable bolts started to unload, and load was transferred to the standing supports. The standing support system was able to maintain an adequate opening inby the shields to provide ventilation to the first crosscut inby the face, as designed. The results were used to calibrate modeled cable bolt response to field data, and to validate numerical modeling procedures that have been developed to evaluate entry support systems. It is concluded that the support system was more than adequate to control the roof of the tailgate up to the longwall face location. The monitoring results have provided valuable data for the development and validation of support design strategies for longwall tailgate entries.

      3. Bumps and other types of dynamic failure have been a persistent, worldwide problem in the underground coal mining industry, spanning decades. For example, in just five states in the U.S. from 1983 to 2014, there were 388 reportable bumps. Despite significant advances in mine design tools and mining practices, these events continue to occur. Many conditions have been associated with bump potential, such as the presence of stiff units in the local geology. The effect of a stiff sandstone unit on the potential for coal bumps depends on the location of the stiff unit in the stratigraphic column, the relative stiffness and strength of other structural members, and stress concentrations caused by mining. This study describes the results of a robust design to consider the impact of different lithologic risk factors impacting dynamic failure risk. Because the inherent variability of stratigraphic characteristics in sedimentary formations, such as thickness, engineering material properties, and location, is significant and the number of influential parameters in determining a parametric study is large, it is impractical to consider every simulation case by varying each parameter individually. Therefore, to save time and honor the statistical distributions of the parameters, it is necessary to develop a robust design to collect sufficient sample data and develop a statistical analysis method to draw accurate conclusions from the collected data. In this study, orthogonal arrays, which were developed using the robust design, are used to define the combination of the (a) thickness of a stiff sandstone inserted on the top and bottom of a coal seam in a massive shale mine roof and floor, (b) location of the stiff sandstone inserted on the top and bottom of the coal seam, and (c) material properties of the stiff sandstone and contacts as interfaces using the 3-dimensional numerical model, FLAC3D. After completion of the numerical experiments, statistical and multivariate analysis are performed using the calculated results from the orthogonal arrays to analyze the effect of these variables. As a consequence, the impact of each of the parameters on the potential for bumps is quantitatively classified in terms of a normalized intensity of plastic dissipated energy. By multiple regression, the intensity of plastic dissipated energy and migration of the risk from the roof to the floor via the pillars is predicted based on the value of the variables. The results demonstrate and suggest a possible capability to predict the bump potential in a given rock mass adjacent to the underground excavations and pillars. Assessing the risk of bumps is important to preventing fatalities and injuries resulting from bumps.

      4. Deep cover bleeder entry performance and support loading: A case study
        Klemetti TM, Van Dyke MA, Tulu IB.
        Int J Min Sci Technol. 2018 .
        Several questions have emerged in relation to deep cover bleeder entry performance and support loading: how well do current modeling procedures calculate the rear abutment extent and loading? Does an improved understanding of the rear abutment extent warrant a change in standing support in bleeder entries? To help answer these questions and to determine the current utilization of standing support in bleeder entries, four bleeder entries at varying distances from the startup room were instrumented, observed, and numerically modeled. This paper details observations made by NIOSH researchers in the bleeder entries of a deep cover longwall panel-specifically data collected from instrumented pumpable cribs, observations of the conditions of the entries, and numerical modeling of the bleeder entries during longwall extraction. The primary focus was on the extent and magnitude of the abutment loading experienced by the standing support. As expected, the instrumentation of the standing supports showed very little loading relative to the capacity of the standing supports-less than 23 Mg load and 2.54 cm convergence. The Flac3D program was used to evaluate these four bleeder entries using previously defined modeling and input parameter estimation procedures. The results indicated only a minor increase in load during the extraction of the longwall panel. The model showed a much greater increase in stress due to the development of the gateroad and bleeder entries, with about 80% of the increase associated with development and 20% with longwall extraction. The Flac3D model showed very good correlation between expected gateroad loading during panel extraction and that expected based on previous studies. The results of this study showed that the rear abutment stress experienced by this bleeder entry design was minimal. The farther away from the startup room, the lower the applied load and smaller the convergence in the entry if all else is held constant. Finally, the numerical modeling method used in this study was capable of replicating the expected and measured results near seam.

      5. Guest editorial – special issue on ground control in mining in 2017
        Murphy MM, Mishra B, Perry K, Lawson H.
        Int J Min Sci Technol. 2018 .

        [No abstract]

      6. User-friendly finite element design of main entries, barrier pillars, and bleeder entries
        Pariseau WG, Larson MK, Lawson HE, Tesarik DR.
        Int J Min Sci Technol. 2017 .
        This contribution describes development and application of a user-friendly finite element program, UT3PC, to address three important problems in underground coal mine design: (1) safety of main entries, (2) barrier pillar size needed for entry protection, and (3) safety of bleeder entries during the advance of an adjacent longwall panel. While the finite element method is by far the most popular engineering design tool of the digital age, widespread use by the mining community has been impeded by the relatively high cost of and the need for lengthy specialized training in numerical methods. Implementation of UT3PC overcomes these impediments in three easy steps. First, a material properties file is prepared for the considered site. Next, mesh generation is automatic through an interactive process. A third and last step is simply execution of the program. Examples using data from several western coal mines illustrate the ease of using the application for analysis of main entries, barrier pillars, and bleeder entry safety.

      7. Foam property tests to evaluate the potential for longwall shield dust control
        Reed WR, Beck TW, Zheng Y, Klima S, Driscoll J.
        Mining Engineering. 2018 ;70(1):35-41.
        Tests were conducted to determine properties of four foam agents for their potential use in longwall mining dust control. Foam has been tried in underground mining in the past for dust control and is currently being reconsidered for use in underground coal longwall operations in order to help those operations comply with the Mine Safety and Health Administration’s lower coal mine respirable dust standard of 1.5 mg/m3. Foams were generated using two different methods. One method used compressed air and water pressure to generate foam, while the other method used low-pressure air generated by a blower and water pressure using a foam generator developed by the U.S. National Institute for Occupational Safety and Health. Foam property tests, consisting of a foam expansion ratio test and a water drainage test, were conducted to classify foams. Compressed-Air-generated foams tended to have low expansion ratios, from 10 to 19, with high water drainage. Blower-Air-generated foams had higher foam expansion ratios, from 30 to 60, with lower water drainage. Foams produced within these ranges of expansion ratios are stable and potentially suitable for dust control. The test results eliminated two foam agents for future testing because they had poor expansion ratios. The remaining two foam agents seem to have properties adequate for dust control. These material property tests can be used to classify foams for their potential use in longwall mining dust control.

    • Nutritional Sciences
      1. BACKGROUND: Although there has been inconsistency in recommendations regarding the optimal time for introducing complementary foods, most experts agree that introduction should not occur before 4 months. Despite recommendations, studies suggest that 20% to 40% of US infants are introduced to foods at younger than 4 months. Previous studies focused on the introduction of solid foods and are not nationally representative. OBJECTIVE: Our aims were to provide a nationally representative estimate of the timing of introduction of complementary foods and to describe predictors of early (<4 months) introduction. DESIGN: We conducted a cross-sectional analysis of 2009-2014 National Health and Nutrition Examination Survey data. PARTICIPANTS: The study included 1,482 children aged 6 to 36 months. MAIN OUTCOME MEASURES: Timing of first introduction to complementary foods (anything other than breast milk or formula) was analyzed. STATISTICAL ANALYSES PERFORMED: Prevalence estimates of first introduction to complementary foods are presented by month. Logistic regression was used to assess characteristics associated with early (<4 months) introduction. RESULTS: In this sample, 16.3% of US infants were introduced to complementary foods at <4 months, 38.3% between 4 and <6 months, 32.5% between 6 and <7 months, and 12.9% at >/=7 months of age. In unadjusted analyses, early introduction varied by breastfeeding status; race/Hispanic origin; Special Supplemental Nutrition Program for Women, Infants, and Children participation; and maternal age. In adjusted analyses, only breastfeeding status remained significant; infants who never breastfed or stopped at <4 months were more likely (odds ratio 2.27; 95% CI 1.62 to 3.18) to be introduced to complementary foods early than infants who breastfed >/=4 months. CONCLUSIONS: Despite using a broader definition of complementary foods, this analysis found a lower prevalence of early introduction in this nationally representative sample than previous studies that included only solids. However, many young children were still introduced to complementary foods earlier than recommended. Strategies to support caregivers to adhere to infant feeding guidelines may be needed.

    • Occupational Safety and Health
      1. Exposure assessments for a cross-sectional epidemiologic study of US carbon nanotube and nanofiber workers
        Dahm MM, Schubauer-Berigan MK, Evans DE, Birch ME, Bertke S, Beard JD, Erdely A, Fernback JE, Mercer RR, Grinshpun SA.
        Int J Hyg Environ Health. 2018 Jan 11.
        BACKGROUND: Recent animal studies have suggested the potential for wide-ranging health effects resulting from exposure to carbon nanotubes and nanofibers (CNT/F). To date, no studies in the US have directly examined the relationship between occupational exposure and potential human health effects. OBJECTIVES: Our goal was to measure CNT/F exposures among US workers with representative job types, from non-exposed to highly exposed, for an epidemiologic study relating exposure to early biologic effects. METHODS: 108 participants were enrolled from 12 facilities across the US. Personal, full-shift exposures were assessed based on the mass of elemental carbon (EC) at the respirable and inhalable aerosol particle size fractions, along with quantitatively characterizing CNT/F and estimating particle size via transmission electron microscopy (TEM). Additionally, sputum and dermal samples were collected and analyzed to determine internal exposures and exposures to the hands/wrists. RESULTS: The mean exposure to EC was 1.00mug/m(3) at the respirable size fraction and 6.22mug/m(3) at the inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F structures/cm(3), generally to agglomerated materials between 2 and 10mum. Internal exposures to CNT/F via sputum analysis were confirmed in 18% of participants while approximately 70% had positive dermal exposures. CONCLUSIONS: We demonstrated the occurrence of a broad range of exposures to CNT/F within 12 facilities across the US. Analysis of collected sputum indicated internal exposures are currently occurring within the workplace. This is an important first step in determining if exposures in the workforce have any acute or lasting health effects.

      2. BACKGROUND: Police officers in the New Orleans geographic area faced a number of challenges following Hurricane Katrina. AIM: This cross-sectional study examined the effect of social support, gratitude, resilience and satisfaction with life on symptoms of depression. METHOD: A total of 86 male and 30 female police officers from Louisiana participated in this study. Ordinary least-square (OLS) regression mediation analysis was used to estimate direct and indirect effects between social support, gratitude, resilience, satisfaction with life and symptoms of depression. All models were adjusted for age, alcohol intake, military experience and an increase in the number of sick days since Hurricane Katrina. RESULTS: Mean depressive symptom scores were 9.6 +/- 9.1 for females and 10.9 +/- 9.6 for males. Mediation analyses indicates that social support and gratitude are directly associated with fewer symptoms of depression. Social support also mediated the relationships between gratitude and depression, gratitude and satisfaction with life, and satisfaction with life and depression. Similarly, resilience mediated the relationship between social support and fewer symptoms of depression. CONCLUSION: Social support, gratitude and resilience are associated with higher satisfaction with life and fewer symptoms of depression. Targeting and building these factors may improve an officer’s ability to address symptoms of depression.

      3. There is limited information on the natural history of building occupants’ health in relation to attempts to remediate moisture damage. We examined changes in respiratory and non-respiratory symptoms in 1,175 office building occupants over seven years with multiple remediation attempts. During each of four surveys, we categorized participants using a severity score: 0 = asymptomatic; 1 = mild, symptomatic in the last 12 months, but not frequently in the last 4 weeks; 2 = severe, symptomatic at least once weekly in the last 4 weeks. Building-related symptoms were defined as improving away from the building. We used random intercept models adjusted for demographics, smoking, building tenure, and microbial exposures to estimate temporal changes in the odds of building-related symptoms or severity scores independent of the effect of microbial exposures. Trend analyses of combined mild/severe symptoms showed no changes in the odds of respiratory symptoms but significant improvement in non-respiratory symptoms over time. Separate analyses showed increases in the odds of severe respiratory symptoms (odds ratio/year = 1.151.16, p-values<0.05) and severity scores (0.02/year, p-values<0.05) for wheezing and shortness of breath on exertion, due to worsening of participants in the mild symptom group. For non-respiratory symptoms, we found no changes in the odds of severe symptoms but improvement in severity scores (-0.04-0.01/year, p-values<0.05) and the odds for mild fever and chills, excessive fatigue, headache, and throat symptoms (0.65-0.79/year, p-values<0.05). Our study suggests that after the onset of respiratory and severe non-respiratory symptoms associated with dampness/mold, remediation efforts might not be effective in improving occupants’ health.

      4. BACKGROUND: Metalworking fluids (MWF) are complex mixtures with dermal and inhalation exposure. Published reports reveal excess cancer risk. METHODS: Using published findings exposure response was derived for each attributable cancer site. Aggregate excess lifetime risk was estimated by applying a lifetable calculation. RESULTS: Cancer sites contributing the most attributable cases were larynx, esophagus, brain, female breast, and uterine cervix. With constant workplace MWF exposure of 0.1 mg/m(3) over a 45 years working life, the risk of attributable cancer was 3.7% or, excluding the less certain female cancers, 3.1%. CONCLUSION: Substantial cancer risks occurred at 0.1 mg/m(3) MWF, one fourth of the current NIOSH recommended exposure limit for MWF total particulate. Because ingredients in current MWF remain from earlier formulations, it is likely that some MWF carcinogenicity persists today. Although important changes have occurred, newer agents are being continually introduced with little or no knowledge of chronic health risks.

      5. Asthma mortality among persons aged 15-64 years, by industry and occupation – United States, 1999-2016
        Patel O, Syamlal G, Wood J, Dodd KE, Mazurek JM.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):60-65.
        In 2015, an estimated 18.4 million U.S. adults had current asthma, and 3,396 adult asthma deaths were reported (1). An estimated 11%-21% of asthma deaths might be attributable to occupational exposures (2). To describe asthma mortality among persons aged 15-64 years,* CDC analyzed multiple cause-of-death datafor 1999-2016 and industry and occupation information collected from 26 states( section sign) for the years 1999, 2003, 2004, and 2007-2012. Proportionate mortality ratios (PMRs)( paragraph sign) for asthma among persons aged 15-64 years were calculated. During 1999-2016, a total of 14,296 (42.9%) asthma deaths occurred among males and 19,011 (57.1%) occurred among females. Based on an estimate that 11%-21% of asthma deaths might be related to occupational exposures, during this 18-year period, 1,573-3,002 asthma deaths in males and 2,091-3,992 deaths in females might have resulted from occupational exposures. Some of these deaths might have been averted by instituting measures to prevent potential workplace exposures. The annual age-adjusted asthma death rate** per 1 million persons aged 15-64 years declined from 13.59 in 1999 to 9.34 in 2016 (p<0.001) among females, and from 9.14 (1999) to 7.78 (2016) (p<0.05) among males. The highest significantly elevated asthma PMRs for males were for those in the food, beverage, and tobacco products manufacturing industry (1.82) and for females were for those in the social assistance industry (1.35) and those in community and social services occupations (1.46). Elevated asthma mortality among workers in certain industries and occupations underscores the importance of optimal asthma management and identification and prevention of potential workplace exposures.

      6. Frequent exertion and frequent standing at work, by industry and occupation group – United States, 2015
        Shockey TM, Luckhaupt SE, Groenewold MR, Lu ML.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):1-6.
        Repeated exposure to occupational ergonomic hazards, such as frequent exertion (repetitive bending or twisting) and frequent standing, can lead to injuries, most commonly musculoskeletal disorders (1). Work-related musculoskeletal disorders have been estimated to cost the United States approximately $2.6 billion in annual direct and indirect costs (2). A recent literature review provided evidence that prolonged standing at work also leads to adverse health outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine which industry and occupation groups currently have the highest prevalence rates of frequent exertion at work and frequent standing at work, CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement (OHS) regarding currently employed adults in the United States. By industry, the highest prevalence of both frequent exertion and frequent standing at work was among those in the agriculture, forestry, fishing, and hunting industry group (70.9%); by occupation, the highest prevalence was among those in the construction and extraction occupation group (76.9%). Large differences among industry and occupation groups were found with regard to these ergonomic hazards, suggesting a need for targeted interventions designed to reduce workplace exposure.

    • Occupational Safety and Health – Mining
      1. Effects of FAME biodiesel and HVORD on emissions from an older-technology diesel engine
        Bugarski A, Hummer J, Vanderslice S.
        Min Eng. 2017 Dec;69(12):43-49.
        The results of laboratory evaluations were used to compare the potential of two alternative, biomass-derived fuels as a control strategy to reduce the exposure of underground miners to aerosols and gases emitted by diesel-powered equipment. The effects of fatty acid methyl ester (FAME) biodiesel and hydrotreated vegetable oil renewable diesel (HVORD) on criteria aerosol and gaseous emissions from an older-technology, naturally aspirated, mechanically controlled engine equipped with a diesel oxidation catalytic converter were compared with those of widely used petroleum-derived, ultralow-sulfur diesels (ULSDs). The emissions were characterized for four selected steady-state conditions. When fueled with FAME biodiesel and HVORD, the engine emitted less aerosols by total particulate mass, total carbon mass, elemental carbon mass and total number than when it was fueled with ULSDs. Compared with ULSDs, FAME biodiesel and HVORD produced aerosols that were characterized by single modal distributions, smaller count median diameters, and lower total and peak concentrations. For the majority of test cases, FAME biodiesel and HVORD favorably affected nitric oxide (NO) and adversely affected nitrogen dioxide (NO2) generation. Therefore, the use of these alternative fuels appears to be a viable tool for the underground mining industry to address the issues related to emissions from diesel engines, and to transition toward more universal solutions provided by advanced engines with integrated exhaust aftertreatment technologies.

    • Parasitic Diseases
      1. Safety of single dose primaquine in G6PD-deficient and G6PD-normal males in Mali without malaria: an open-label, phase 1, dose-adjustment trial
        Chen I, Diawara H, Mahamar A, Sanogo K, Keita S, Kone D, Diarra K, Djimde M, Keita M, Brown J, Roh ME, Hwang J, Pett H, Murphy M, Niemi M, Greenhouse B, Bousema T, Gosling R, Dicko A.
        J Infect Dis. 2018 Jan 12.
        Background: The World Health Organization recommendation on the use of single low-dose primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. Methods: We conducted an open-label, non-randomized, dose-adjustment trial of the safety of three single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys ages 11-17 years, and 5-10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days post-treatment. Results: 51 participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n=4) were mild. The mean largest within-person percent drop in hemoglobin between day 0 and 10 was -9.7% (95% CI: -13.5, -5.90) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, -11.5% (95%CI: -16.1, -6.96) in G6PD-deficient boys aged 11-17, and -9.61% (95%CI: -7.59, -13.9) in G6PD-deficient boys aged 5-10. The lowest hemoglobin concentration at any point during the study was 92 g/L. Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well-tolerated in G6PD-d males in Mali. Trial registration: NCT02535767.

      2. Notes from the field: Baylisascaris procyonis encephalomyelitis in a toddler – King County, Washington, 2017
        Kawakami V, Casto A, Natarajan N, Snyder A, Mosser J, Bonwitt J, Kronman MP, Kay M.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):79-80.

        [No abstract]

    • Physical Activity
      1. Postexercise whole-body sweating increases during muscle metaboreceptor activation in young men
        Friesen BJ, Poirier MP, Lamarche DT, D’Souza AW, Kim JH, Notley SR, Kenny GP.
        Appl Physiol Nutr Metab. 2018 Jan 9.
        We assessed the effect of metaboreceptor activation on whole-body evaporative heat loss (WB-EHL) in twelve men (24+/-4 years) in the early-to-late-stages of a 60-min exercise recovery in the heat. Metaboreceptor activation induced by 1-min isometric-handgrip (IHG) exercise followed by 5-min forearm ischemia to trap metabolites increased WB-EHL by 25-31% and 26-34% during the ischemic period relative to IHG-Only and Control (natural recovery only) respectively throughout recovery. We show that metaboreceptor activation enhances WB-EHL in recovery.

      2. Using two disability measures to compare physical inactivity among US adults with disabilities
        McGuire DO, Watson KB, Carroll DD, Courtney-Long EA, Carlson SA.
        Prev Chronic Dis. 2018 Jan 18;15:E08.
        Prevalence of health behaviors among adults with disabilities may vary by disability measure. We used data from the 2011-2015 National Health Interview Survey to estimate prevalence of physical inactivity by disability status using 2 measures of disability: Basic Actions Difficulty questions (BADQ) and a standard 6-question measure (6Q). Disability prevalence (BADQ, 31.1%; 6Q, 17.5%) and inactivity prevalence among adults with disability (BADQ, 42.9%; 6Q, 52.5%) and without disability (BADQ, 24.3%; 6Q, 26.2%) varied by measure; however, both measures highlight inactivity disparities for adults with disability. Disability measures influence physical inactivity estimates and are important for guiding surveillance and health promotion activities for adults with disabilities.

    • Statistics as Topic
      1. Bayesian local extremum splines
        Wheeler MW, Dunson DB, Herring AH.
        Biometrika. 2017 ;104(4):939-952.
        We consider shape-restricted nonparametric regression on a closed set X CR, where it is reasonable to assume that the function has no more than H local extrema interior to X. Following a Bayesian approach we develop a nonparametric prior over a novel class of local extremum splines. This approach is shown to be consistent when modelling any continuously differentiable function within the class considered, and we use it to develop methods for testing hypotheses on the shape of the curve. Sampling algorithms are developed, and the method is applied in simulation studies and data examples where the shape of the curve is of interest.

    • Substance Use and Abuse
      1. Epidemics of opioid use and injection drug use (IDU) are associated with an increase in HIV and viral hepatitis infections and overdose deaths in the United States. Persons who inject drugs (PWID) are also at risk for serious infections caused by skin organisms introduced via IDU. We examined National Inpatient Sample hospital discharge data to determine trends in three serious infectious disease-associated conditions that primarily affect PWID in addition to HIV and viral hepatitis: infective endocarditis (IE), central nervous system (CNS) abscesses, and osteomyelitis. We found an increase in the number of primary hospitalization discharge diagnoses for IE among persons aged </=39 years from 2009 to 2013. Hospitalization rates for these diagnoses also increased over this study period for person with secondary diagnoses of hepatitis B, C, or D viruses and substance-related disorders for IE, CNS abscess and osteomyelitis. Policies that improve access to sterile injection equipment, improve education regarding IDU, and treatment for substance use disorder may help to reduce the impact of serious and often fatal infectious diseases among PWID.

      2. Current cigarette smoking among adults – United States, 2016
        Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, Neff LJ.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):53-59.
        The U.S. Surgeon General has concluded that the burden of death and disease from tobacco use in the United States is overwhelmingly caused by cigarettes and other combusted tobacco products (1). Cigarettes are the most commonly used tobacco product among U.S. adults, and about 480,000 U.S. deaths per year are caused by cigarette smoking and secondhand smoke exposure (1). To assess progress toward the Healthy People 2020 target of reducing the proportion of U.S. adults aged >/=18 years who smoke cigarettes to </=12.0% (objective TU-1.1),* CDC analyzed data from the 2016 National Health Interview Survey (NHIS). In 2016, the prevalence of current cigarette smoking among adults was 15.5%, which was a significant decline from 2005 (20.9%); however, no significant change has occurred since 2015 (15.1%). In 2016, the prevalence of cigarette smoking was higher among adults who were male, aged 25-64 years, American Indian/Alaska Native or multiracial, had a General Education Development (GED) certificate, lived below the federal poverty level, lived in the Midwest or South, were uninsured or insured through Medicaid, had a disability/limitation, were lesbian, gay, or bisexual (LGB), or had serious psychological distress. During 2005-2016, the percentage of ever smokers who quit smoking increased from 50.8% to 59.0%. Proven population-based interventions are critical to reducing the health and economic burden of smoking-related diseases among U.S. adults, particularly among subpopulations with the highest smoking prevalences (1,2).

      3. Tobacco product use among military veterans – United States, 2010-2015
        Odani S, Agaku IT, Graffunder CM, Tynan MA, Armour BS.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):7-12.
        In 2015, an estimated 18.8 million U.S. adults were military veterans (1). Although the prevalence of tobacco-attributable conditions is high among veterans (2), there is a paucity of data on use of tobacco products, other than cigarettes, in this population. To monitor tobacco product use among veterans, CDC analyzed self-reported current (i.e., past 30-day) use of five tobacco product types (cigarettes, cigars [big cigars, cigarillos, or little cigars], roll-your-own tobacco, pipes, and smokeless tobacco [chewing tobacco, snuff, dip, or snus]) from the National Survey on Drug Use and Health (NSDUH). Overall, 29.2% of veterans reported current use of any of the assessed tobacco products. Cigarettes were the most commonly used tobacco product (21.6%), followed by cigars (6.2%), smokeless tobacco (5.2%), roll-your-own tobacco (3.0%), and pipes (1.5%); 7.0% of veterans currently used two or more tobacco products. Within subgroups of veterans, current use of any of the assessed tobacco products was higher among persons aged 18-25 years (56.8%), Hispanics (34.0%), persons with less than a high school diploma (37.9%), those with annual family income <$20,000 (44.3%), living in poverty (53.7%), reporting serious psychological distress (48.2%), and with no health insurance (60.1%). By age and sex subgroups, use of any of the assessed tobacco products was significantly higher among all veteran groups than their nonveteran counterparts, except males aged >/=50 years. Expanding the reach of evidence-based tobacco control interventions among veterans could reduce tobacco use prevalence in this population.

    • Vital Statistics
      1. The WHO 2016 verbal autopsy instrument: An international standard suitable for automated analysis by InterVA, InSilicoVA, and Tariff 2.0
        Nichols EK, Byass P, Chandramohan D, Clark SJ, Flaxman AD, Jakob R, Leitao J, Maire N, Rao C, Riley I, Setel PW.
        PLoS Med. 2018 Jan;15(1):e1002486.
        BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.

    • Zoonotic and Vectorborne Diseases
      1. West Nile Virus and other nationally notifiable arboviral diseases – United States, 2016
        Burakoff A, Lehman J, Fischer M, Staples JE, Lindsey NP.
        MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):13-17.
        Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1,2). Other arboviruses, including La Crosse, Powassan, Jamestown Canyon, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2016 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, as these are primarily nondomestic viruses typically acquired through travel. Forty-seven states and the District of Columbia (DC) reported 2,240 cases of domestic arboviral disease, including 2,150 (96%) WNV disease cases. Of the WNV disease cases, 1,310 (61%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, acute flaccid paralysis), for a national incidence of 0.41 cases per 100,000 population. After WNV, the most frequently reported arboviruses were La Crosse (35 cases), Powassan (22), and Jamestown Canyon (15) viruses. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities.

      2. Background: Clinical features of Lyme disease (LD) range from localized skin lesions to serious disseminated disease. Information on risk factors for Lyme arthritis, facial palsy, carditis, and meningitis is limited but could facilitate disease recognition and elucidate pathophysiology. Methods: Patients from high-incidence states treated for LD during 2005-2014 were identified in a nationwide insurance claims database using the International Classification of Diseases, Ninth Revision code for LD (088.81), antibiotic treatment history, and clinically compatible codiagnosis codes for LD manifestations. Results: Among 88022 unique patients diagnosed with LD, 5122 (5.8%) patients with 5333 codiagnoses were identified: 2440 (2.8%) arthritis, 1853 (2.1%) facial palsy, 534 (0.6%) carditis, and 506 (0.6%) meningitis. Patients with disseminated LD had lower median age (35 vs 42 years) and higher male proportion (61% vs 50%) than nondisseminated LD. Greatest differential risks included arthritis in males aged 10-14 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 3.0-4.2), facial palsy (OR, 2.1; 95% CI, 1.6-2.7) and carditis (OR, 2.4; 95% CI, 1.6-3.6) in males aged 20-24 years, and meningitis in females aged 10-14 years (OR, 3.4; 95% CI, 2.1-5.5) compared to the 55-59 year referent age group. Males aged 15-29 years had the highest risk for complete heart block, a potentially fatal condition. Conclusions: The risk and manifestations of disseminated LD vary by age and sex. Provider education regarding at-risk populations and additional investigations into pathophysiology could enhance early case recognition and improve patient management.

      3. Ability to serologically confirm recent Zika virus infection in areas with varying past incidence of dengue virus infection in the United States and U.S. Territories in 2016
        Lindsey NP, Staples JE, Powell K, Rabe IB, Fischer M, Powers AM, Kosoy OI, Mossel EC, Munoz-Jordan JL, Beltran M, Hancock WT, Toews KE, Ellis EM, Ellis BR, Panella AJ, Basile AJ, Calvert AE, Laven J, Goodman CH, Gould CV, Martin SW, Thomas JD, Villanueva J, Mataia ML, Sciulli R, Gose R, Whelen AC, Hills SL.
        J Clin Microbiol. 2018 Jan;56(1).
        Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections.

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