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Issue 1, January 9, 2018

CDC Science Clips: Volume 10, Issue 1, January 9, 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!

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue ( The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Maternal and Child Health – Safe Sleep for Babies
      1. Importance: Sudden infant death syndrome remains the leading cause of death in infants aged 1 month to 1 year in the United States. Observations: While its exact cause is unknown, sudden infant death syndrome is believed to be multifactorial, ie, occurs in infants with underlying biological vulnerability who experience an exogenous stressor, such as prone/side sleeping or soft bedding, during a critical developmental period. Much genetic and physiologic evidence points to impaired arousal responses to hypercarbia and hypoxia, which ultimately leads to asphyxia. Known risk factors for infants include prone and side sleeping, soft bedding, bed sharing, inappropriate sleep surfaces (including sofas), exposure to tobacco smoke, and prematurity; protective factors include breastfeeding, pacifier use, room sharing, and immunizations. Conclusions and Relevance: Despite our improved understanding of the physiologic mechanisms that cause sudden infant death, the mainstay of risk reduction continues to be a safe sleep environment, as most infants who die suddenly and unexpectedly do so in unsafe sleep environments.

      2. *Safe infant sleep interventions: What is the evidence for successful behavior change?
        Moon RY, Hauck FR, Colson ER.
        Curr Pediatr Rev. 2016 ;12(1):67-75.
        Sudden infant death syndrome (SIDS) and other sleep-related infant deaths, such as accidental suffocation and strangulation in bed and ill-defined deaths, account for >4000 deaths annually in the USA. Evidence-based recommendations for reducing the risk of sleep-related deaths have been published, but some caregivers resist adoption of these recommendations. Multiple interventions to change infant sleep-related practices of parents and professionals have been implemented. In this review, we will discuss illustrative examples of safe infant sleep interventions and evidence of their effectiveness. Facilitators of and barriers to change, as well as the limitations of the data currently available for these interventions, will be considered.

      3. Factors associated with choice of infant sleep position
        Colson ER, Geller NL, Heeren T, Corwin MJ.
        Pediatrics. 2017 Sep;140(3).
        BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics recommends infants be placed supine for sleep. Our objectives in this study were to, in a nationally representative sample, examine (1) prevalence of maternal intention regarding infant sleeping position and of actual practice and (2) factors associated with their choices. METHODS: We recruited mothers from 32 US hospitals, oversampling African American and Hispanic mothers, in a nationally representative sample of mothers of infants aged 2 to 6 months. Survey questions assessed choice of usual infant sleeping position, all sleeping positions, intention for sleep position, as well as actual practice. Multivariable logistic regression analyses controlled for demographic, receipt of doctor advice, and theory of planned behavior variables (attitudes, subjective norms, and perceived control). RESULTS: Of the 3297 mothers, 77.3% reported they usually placed their infants in the supine position for sleep, but fewer than half reported that they exclusively did so. Only 43.7% of mothers reported that they both intended to and then actually placed their infants exclusively supine. African American mothers and those who did not complete high school were more likely to intend to use the prone position. Theory of planned behavior factors (attitudes, subjective norms, and perceived control) and doctor advice were associated with maternal choice. CONCLUSIONS: Not all mothers place their infants exclusively supine for sleep. Many mothers intend to place their infants supine yet often do not do so in actual practice. Factors potentially amenable to intervention including attitudes, subjective norms, and doctor advice are associated with intention and practice.

      4. Trends and factors associated with infant sleeping position: the National Infant Sleep Position Study, 1993-2007
        Colson ER, Rybin D, Smith LA, Colton T, Lister G, Corwin MJ.
        Arch Pediatr Adolesc Med. 2009 Dec;163(12):1122-8.
        OBJECTIVE: To determine trends and factors associated with choice of infant sleeping position. DESIGN: Annual nationally representative telephone surveys from 1993 through 2007. SETTING: Forty-eight contiguous states of the United States. PARTICIPANTS: Nighttime caregivers of infants born within the last 7 months; approximately 1000 interviews were given each year. Main Outcome Measure Whether infant is usually placed supine to sleep. RESULTS: For the 15-year period, supine sleep increased (P < .001) and prone sleep decreased (P < .001) for all infants, with no significant difference in trend by race. Since 2001, a plateau has been reached for all races. Factors associated with increased supine sleep between 1993 and 2007 included time, maternal race other than African American, higher maternal educational level, not living in Southern states, first-born infant, and full-term infant. The effect of these variables was reduced when variables related to maternal concerns about infant comfort, choking, and advice from physicians were taken into account. Between 2003 and 2007, there was no significant yearly increase in supine sleep. Choice of sleep position could be explained almost entirely by caregiver concern about comfort, choking, and advice. Race no longer was a significant predictor. CONCLUSIONS: Since 2001, supine sleep has reached a plateau, and there continue to be racial disparities. There have been changes in factors associated with sleep position, and maternal attitudes about issues such as comfort and choking may account for much of the racial disparity in practice. To decrease sudden infant death syndrome rates, we must ensure that public health measures reach the populations at risk and include messages that address concerns about infant comfort and choking.

      5. National and state trends in sudden unexpected infant death, United States, 1990-2015
        Erck Lambert A, Parks S, Shapiro-Mendoza C.
        Pediatrics. ;In press.

        [No abstract]

      6. Approximately 3500 infants die annually in the United States from sleep-related infant deaths, including sudden infant death syndrome (SIDS), ill-defined deaths, and accidental suffocation and strangulation in bed. After an initial decrease in the 1990s, the overall sleep-related infant death rate has not declined in more recent years. Many of the modifiable and nonmodifiable risk factors for SIDS and other sleep-related infant deaths are strikingly similar. The American Academy of Pediatrics recommends a safe sleep environment that can reduce the risk of all sleep-related infant deaths. Recommendations for a safe sleep environment include supine positioning, use of a firm sleep surface, room-sharing without bed-sharing, and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include avoidance of exposure to smoke, alcohol, and illicit drugs; breastfeeding; routine immunization; and use of a pacifier. New evidence and rationale for recommendations are presented for skin-to-skin care for newborn infants, bedside and in-bed sleepers, sleeping on couches/armchairs and in sitting devices, and use of soft bedding after 4 months of age. In addition, expanded recommendations for infant sleep location are included. The recommendations and strength of evidence for each recommendation are published in the accompanying policy statement, “SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant Sleeping Environment,” which is included in this issue.

      7. The effect of nursing quality improvement and mobile health interventions on infant sleep practices: A randomized clinical trial
        Moon RY, Hauck FR, Colson ER, Kellams AL, Geller NL, Heeren T, Kerr SM, Drake EE, Tanabe K, McClain M, Corwin MJ.
        Jama. 2017 Jul 25;318(4):351-359.
        Importance: Inadequate adherence to recommendations known to reduce the risk of sudden unexpected infant death has contributed to a slowing in the decline of these deaths. Objective: To assess the effectiveness of 2 interventions separately and combined to promote infant safe sleep practices compared with control interventions. Design, Setting, and Participants: Four-group cluster randomized clinical trial of mothers of healthy term newborns who were recruited between March 2015 and May 2016 at 16 US hospitals with more than 100 births annually. Data collection ended in October 2016. Interventions: All participants were beneficiaries of a nursing quality improvement campaign in infant safe sleep practices (intervention) or breastfeeding (control), and then received a 60-day mobile health program, in which mothers received frequent emails or text messages containing short videos with educational content about infant safe sleep practices (intervention) or breastfeeding (control) and queries about infant care practices. Main Outcomes and Measures: The primary outcome was maternal self-reported adherence to 4 infant safe sleep practices of sleep position (supine), sleep location (room sharing without bed sharing), soft bedding use (none), and pacifier use (any); data were collected by maternal survey when the infant was aged 60 to 240 days. Results: Of the 1600 mothers who were randomized to 1 of 4 groups (400 per group), 1263 completed the survey (78.9%). The mean (SD) maternal age was 28.1 years (5.8 years) and 32.8% of respondents were non-Hispanic white, 32.3% Hispanic, 27.2% non-Hispanic black, and 7.7% other race/ethnicity. The mean (SD) infant age was 11.2 weeks (4.4 weeks) and 51.2% were female. In the adjusted analyses, mothers receiving the safe sleep mobile health intervention had higher prevalence of placing their infants supine compared with mothers receiving the control mobile health intervention (89.1% vs 80.2%, respectively; adjusted risk difference, 8.9% [95% CI, 5.3%-11.7%]), room sharing without bed sharing (82.8% vs 70.4%; adjusted risk difference, 12.4% [95% CI, 9.3%-15.1%]), no soft bedding use (79.4% vs 67.6%; adjusted risk difference, 11.8% [95% CI, 8.1%-15.2%]), and any pacifier use (68.5% vs 59.8%; adjusted risk difference, 8.7% [95% CI, 3.9%-13.1%]). The independent effect of the nursing quality improvement intervention was not significant for all outcomes. Interactions between the 2 interventions were only significant for the supine sleep position. Conclusions and Relevance: Among mothers of healthy term newborns, a mobile health intervention, but not a nursing quality improvement intervention, improved adherence to infant safe sleep practices compared with control interventions. Whether widespread implementation is feasible or if it reduces sudden and unexpected infant death rates remains to be studied. Trial Registration: Identifier: NCT01713868.

      8. Racial and ethnic trends in sudden unexpected infant deaths: United States, 1995-2013
        Parks SE, Erck Lambert AB, Shapiro-Mendoza CK.
        Pediatrics. 2017 Jun;139(6).
        BACKGROUND AND OBJECTIVES: Immediately after the 1994 Back-to-Sleep campaign, sudden unexpected infant death (SUID) rates decreased dramatically, but they have remained relatively stable (93.4 per 100 000 live births) since 2000. In this study, we examined trends in SUID rates and disparities by race/ethnicity since the Back-to-Sleep campaign. METHODS: We used 1995-2013 US period-linked birth-infant death data to evaluate SUID rates per 100 000 live births by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander racial/ethnic groupings. To examine racial/ethnic disparities, we calculated rate ratios with NHWs as the referent group. Unadjusted linear regression was used to evaluate trends (P < .05) in rates and rate ratios. The distribution and rates of SUID by demographic and birth characteristics were compared for 1995-1997 and 2011-2013, and chi(2) tests were used to evaluate significance. RESULTS: From 1995 to 2013, SUID rates were consistently highest for American Indian/Alaska Natives, followed by NHBs. The rate for NHBs decreased significantly, whereas the rate for NHWs also declined, but not significantly. As a result, the disparity between NHWs and NHBs narrowed slightly. The SUID rates for Hispanics and Asian/Pacific Islanders were lower than the rates for NHWs and showed a significant decrease, resulting in an increase in their advantage over NHWs. CONCLUSIONS: Each racial/ethnic group showed a unique trend in SUID rates since the Back-to-Sleep campaign. When implementing risk-reduction strategies, it is important to consider these trends in targeting populations for prevention and developing culturally appropriate approaches for racial/ethnic communities.

      9. The Sudden Unexpected Infant Death Case Registry: a method to improve surveillance
        Shapiro-Mendoza CK, Camperlengo LT, Kim SY, Covington T.
        Pediatrics. 2012 Feb;129(2):e486-93.
        This article describes a multistate population-based surveillance system for monitoring sudden unexpected infant deaths (SUIDs) known as the SUID Case Registry pilot program. The pilot program represents collaboration between the Centers for Disease Control and Prevention and the National Center for Child Death Review (NCCDR), which is funded by the Health Resources and Services Administration. The SUID Case Registry builds on existing child death review system activities and protocols. The objectives of the SUID Case Registry are to collect accurate and consistent population-based data about the circumstances and events associated with SUID cases, to improve the completeness and quality of SUID case investigations, and to use a decision-making algorithm with standardized definitions to categorize SUID cases. States who participate in the pilot program commit to review all SUID cases in their state by using their multidisciplinary state and local child death review teams. These teams request and review data from death scene investigators, medical examiners and coroners, law enforcement, social services, pediatric and obstetric providers, and public health per usual, but as part of the pilot program, supplement their SUID case reviews by discussing additional medical, environmental, and behavioral factors, and entering this data using the NCCDR Web-based Case Reporting System. This new surveillance system aims to improve knowledge of factors surrounding SUID events and improve investigation practices. The surveillance system will allow researchers and program planners to create prevention strategies and interventions, ultimately reducing SUIDs and injury-related infant deaths.

      10. Trends in infant bedding use: National Infant Sleep Position study, 1993-2010
        Shapiro-Mendoza CK, Colson ER, Willinger M, Rybin DV, Camperlengo L, Corwin MJ.
        Pediatrics. 2015 Jan;135(1):10-7.
        BACKGROUND: Use of potentially hazardous bedding, as defined by the American Academy of Pediatrics (eg, pillows, quilts, comforters, loose bedding), is a modifiable risk factor for sudden infant death syndrome and unintentional sleep-related suffocation. The proportion of US infants sleeping with these types of bedding is unknown. METHODS: To investigate the US prevalence of and trends in bedding use, we analyzed 1993-2010 data from the National Infant Sleep Position study. Infants reported as being usually placed to sleep with blankets, quilts, pillows, and other similar materials under or covering them in the last 2 weeks were classified as bedding users. Logistic regression was used to describe characteristics associated with bedding use. RESULTS: From 1993 to 2010, bedding use declined but remained a widespread practice (moving average of 85.9% in 1993-1995 to 54.7% in 2008-2010). Prevalence was highest for infants of teen-aged mothers (83.5%) and lowest for infants born at term (55.6%). Bedding use was also frequently reported among infants sleeping in adult beds, on their sides, and on a shared surface. The rate of decline in bedding use was markedly less from 2001-2010 compared with 1993-2000. For 2007 to 2010, the strongest predictors (adjusted odds ratio: >/=1.5) of bedding use were young maternal age, non-white race and ethnicity, and not being college educated. CONCLUSIONS: Bedding use for infant sleep remains common despite recommendations against this practice. Understanding trends in bedding use is important for tailoring safe sleep interventions.

  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. County-level contextual factors associated with diabetes incidence in the United States
        Cunningham SA, Patel SA, Beckles GL, Geiss LS, Mehta N, Xie H, Imperatore G.
        Ann Epidemiol. 2017 Nov 23.
        PURPOSE: Health and administrative systems are facing spatial clustering in chronic diseases such as diabetes. This study explores how geographic distribution of diabetes in the United States is associated with socioeconomic and built environment characteristics and health-relevant policies. METHODS: We compiled nationally representative county-level data from multiple data sources. We standardized characteristics to a mean = 0 and a SD = 1 and modeled county-level age-adjusted diagnosed diabetes incidence in 2013 using 2-level hierarchical linear regression. RESULTS: Incidence of age-standardized diagnosed diabetes in 2013 varied across U.S. counties (n = 3109), ranging from 310 to 2190 new cases/100,000, with an average of 856.4/100,000. Socioeconomic and health-related characteristics explained approximately 42% of the variation in diabetes incidence across counties. After accounting for other characteristics, counties with higher unemployment, higher poverty, and longer commutes had higher incidence rates than counties with lower levels. Counties with more exercise opportunities, access to healthy food, and primary care physicians had fewer diabetes cases. CONCLUSIONS: Features of the socioeconomic and built environment were associated with diabetes incidence; identifying the salient modifiable features of counties can inform targeted policies to reduce diabetes incidence.

      2. [No abstract]

      3. A spatial analysis of amyotrophic lateral sclerosis (ALS) cases in the United States and their proximity to multidisciplinary ALS clinics, 2013
        Horton DK, Graham S, Punjani R, Wilt G, Kaye W, Maginnis K, Webb L, Richman J, Bedlack R, Tessaro E, Mehta P.
        Amyotroph Lateral Scler Frontotemporal Degener. 2017 Dec 20:1-8.
        BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that typically results in death within 2-5 years of initial symptom onset. Multidisciplinary ALS clinics (MDCs) have been established to provide specialty care to people living with the disease. OBJECTIVE: To estimate the proximity of ALS prevalence cases to the nearest MDC in the US to help evaluate one aspect of access to care. METHODS: Using 2013 prevalence data from the National ALS Registry, cases were geocoded by city using geographic information system (GIS) software, along with the locations of all MDCs in operation during 2013. Case-to-MDC proximity was calculated and analyzed by sex, race, and age group. RESULTS: During 2013, there were 72 MDCs in operation in 30 different states. A total of 15,633 ALS cases were geocoded and were distributed throughout all 50 states. Of these, 62.6% were male, 77.9% were white, and 76.2% were 50-79 years old. For overall case-to-MDC proximity, nearly half (44.9%) of all geocoded cases in the US lived >50 miles from an MDC, including approximately a quarter who lived >100 miles from an MDC. There was a statistically significant difference between distance to MDC by race and age group. CONCLUSIONS: The high percentage of those living more than 50 miles from the nearest specialized clinic underscores one of the many challenges of ALS. Having better access to care, whether at MDCs or through other modalities, is likely key to increasing survivability and obtaining appropriate end-of-life treatment and support for people with ALS.

      4. VKORC1-1639A allele influences warfarin maintenance dosage among blacks receiving warfarin anticoagulation: a retrospective cohort study
        Mili FD, Allen T, Wadell PW, Hooper WC, Staercke C, Bean CJ, Lally C, Austin H, Wenger NK.
        Future Cardiol. 2018 Jan;14(1):15-26.
        AIM: The study objectives were to investigate the association between selected CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or thrombotic risk, and to estimate mean daily maintenance dose of warfarin and international normalized ratio measurements among Blacks receiving warfarin anticoagulation. METHODS: We conducted a retrospective cohort study among 230 Black adults receiving warfarin for a minimum of three consecutive months with a confirmed date of first dosage. RESULTS: A lower mean daily maintenance dosage of warfarin was required to maintain an international normalized ratio measurement within the therapeutic range among Blacks with the VKORC1-1639G>A variant alleles ([G/A vs G/G, p = 0.02], [A/A vs G/A, p = 0.008] and [A/A vs G/G, p = 0.001]). CONCLUSION: Data indicated that VKORC1-1639A variant allele influenced warfarin daily maintenance dosage among our small, likely admixed Black patient population.

      5. Assessment of the sustainability capacity of a coordinated approach to chronic disease prevention
        Moreland-Russell S, Combs T, Polk L, Dexter S.
        J Public Health Manag Pract. 2017 Dec 7.
        OBJECTIVE: This article outlines some factors that influenced the sustainability capacity of a coordinated approach to chronic disease prevention in state and territory health departments. DESIGN: This study involved a cross-sectional design and mixed-methods approach. Quantitative data were collected using the Program Sustainability Assessment Tool (PSAT), a 40-item multiple-choice instrument that assesses 8 domains of sustainability capacity (environmental support, funding stability, partnerships, organizational capacity, program evaluation, program adaptation, communications, and strategic planning). Qualitative data were collected via phone interviews. PARTICIPANTS: The PSAT was administered to staff and stakeholders from public health departments in 50 US states, District of Columbia, and Puerto Rico, who were involved in the implementation of coordinated chronic disease programs. Phone interviews were conducted with program coordinators in each state. MAIN OUTCOME MEASURE(S): Sustainability score patterns and state-level categorical results, as well as strengths and opportunities for improvement across the 8 program sustainability domains, were explored. RESULTS: On average, programs reported the strongest sustainability capacity in the domains of program adaptation, environmental support, and organizational capacity, while funding stability, strategic planning, and communications yielded lowest scores, indicating weakest capacity. Scores varied the most by state in environmental support and strategic planning. CONCLUSION: The PSAT results highlight the process through which states approached the sustainability of coordinated chronic disease initiatives. This process included an initial focus on program evaluation and partnerships with transfer of priority to long-term strategic planning, communications, and funding stability to further establish coordinated chronic disease efforts. Qualitative interviews provided further context to PSAT results, indicating that leadership, communications, partnerships, funding stability, and policy change were perceived as keys to success of the transition. Integrating these findings into future efforts may help those in transition establish greater sustainability capacity. The PSAT results and interviews provide insight into the capacity for sustainability for programs transitioning from traditional siloed programs to coordinated chronic disease programs.

      6. Prevalence of obesity among adults, by household income and education – United States, 2011-2014
        Ogden CL, Fakhouri TH, Carroll MD, Hales CM, Fryar CD, Li X, Freedman DS.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 22;66(50):1369-1373.
        Studies have suggested that obesity prevalence varies by income and educational level, although patterns might differ between high-income and low-income countries (1-3). Previous analyses of U.S. data have shown that the prevalence of obesity varied by income and education, but results were not consistent by sex and race/Hispanic origin (4). Using data from the National Health and Nutrition Examination Survey (NHANES), CDC analyzed obesity prevalence among adults (aged >/=20 years) by three levels of household income, based on percentage (</=130%, >130% to </=350%, and >350%) of the federal poverty level (FPL) and individual education level (high school graduate or less, some college, and college graduate). During 2011-2014, the age-adjusted prevalence of obesity among adults was lower in the highest income group (31.2%) than the other groups (40.8% [>130% to </=350%] and 39.0% [</=130%]). The age-adjusted prevalence of obesity among college graduates was lower (27.8%) than among those with some college (40.6%) and those who were high school graduates or less (40.0%). The patterns were not consistent across all sex and racial/Hispanic origin subgroups. Continued progress is needed to achieve the Healthy People 2020 targets of reducing age-adjusted obesity prevalence to <30.5% and reducing disparities.

      7. BMI trajectories in youth and adulthood
        Ogden CL, Freedman DS, Hales CM.
        Pediatrics. 2017 Dec 19.

        [No abstract]

      8. Mammography use among women aged 18-39 years in the United States
        Qin J, White MC, Sabatino SA, Febo-Vazquez I.
        Breast Cancer Res Treat. 2017 Dec 20.
        PURPOSE: Recommendations for breast cancer screening using mammography target asymptomatic women aged >/= 40 years who are not at increased risk for breast cancer. Evidence is not available to demonstrate benefits of screening with mammography at younger ages, and little is known about mammography use among younger women. This study described mammography use among women aged 18-39 years. METHODS: We analyzed data from the 2011-2015 National Survey of Family Growth, an in-person survey of a nationally representative sample of the U.S. household population. We estimated the prevalence of ever receiving a mammogram and examined reasons for the first mammograms among women aged 18-39 years without personal cancer history (n = 8324). We classified the first mammogram as a screening examination if it was performed either as part of a routine exam or because of family history of cancer. RESULTS: Among women aged 18-39 years, 14.3% (95% CI 13.2-15.4) reported ever having a mammogram. Prevalence of mammography use was highest among women aged 35-39 years (31.0%, 95% CI 27.8-34.5), and was higher among non-Hispanic black women than in other race/ethnicity groups. Women with a family history of breast cancer reported a higher prevalence of mammography use than women without this family history. For both women with and without a family history of breast cancer, about half of all first mammograms were performed for screening reasons. CONCLUSIONS: Among U.S. women aged 18-39 years with no personal cancer history, one in seven reported having received a mammogram. Women with no family history of breast cancer were as likely as those with a family history to initiate breast cancer screening with mammography before age 40. Our findings provide evidence that supports further research to examine factors that prompt young women to receive screening mammograms.

      9. The distribution of epilepsy types varies by age, etiology, provider diagnostic capabilities, and assessment criteria. No recent US study has examined the distribution of epilepsy types in a large, population-based sample of people with epilepsy. We used MarketScan data from January 1, 2010 through September 30, 2015, to estimate the proportion of epilepsy types among all (N=370,570) individuals diagnosed with epilepsy. We identified cases of epilepsy as individuals with at least one International Classification of Disease, 9th version (ICD-9) diagnostic code of 345.X and the use of at least one antiseizure drug described in the 2015 MarketScan Redbook. Unspecified epilepsy was more common (36.8%) than focal-localized epilepsy (24.6%), generalized convulsive epilepsy (23.8%), generalized nonconvulsive epilepsy (8.9%), other forms of epilepsy (5.2%), infantile spasm (0.3%), and epilepsia partialis continua (0.3%). The high proportion of epilepsy classified as unspecified might be lowered by improved training in epilepsy diagnosis and coding.

      10. Global Coalition for the Fight Against Heart Disease and Stroke: A global coalition for WHF Second Global Summit on Circulatory Health
        Wood D, Asma S, Bettcher D, Wei Chieh JT, Greenland R, Italianer F, Krug E, McGuire H, Wong-Rieger D, Eisele JL, Mwangi J, Markbreiter J, Canham L, White A.
        Glob Heart. 2017 Dec 13.

        [No abstract]

      11. PURPOSE: This study assessed the associations between sociodemographic and behavioral characteristics and sugar-sweetened beverage (SSB) intake among US adults with diabetes or prediabetes. DESIGN: Quantitative, cross-sectional study. SETTING: The 2013 Behavioral Risk Factor Surveillance System. PARTICIPANTS: A total of 13 268 adults with diabetes and 9330 adults with prediabetes (median response rate: 46.8%). MEASURES: The outcome measure was SSB intake (0, >0 to <1, and >/=1 time/day). The exposure measures were sociodemographic and behavioral characteristics. ANALYSIS: Both crude and age-adjusted prevalences were calculated. Multinomial logistic regressions were used to estimate the adjusted prevalence ratio (PR) for SSB intake by participants’ characteristics. RESULTS: In 2013, 22.0% adults with diabetes and 38.2% adults with prediabetes consumed SSBs >/=1 time/day. Among adults with diabetes, adjusted PR for consuming SSBs >/=1 time/day was significantly greater for those who had shorter duration of diabetes (</=5 years: PR = 1.47; 6-10 years: PR = 1.33 vs >/=11 years), less frequently self-checking blood sugar (>/=0 to <1 time/day: PR = 1.69; >/=1 to <3 times/day: PR = 1.43 vs >/=3 times/day), and no self-management of diabetes course taken (PR = 1.25 vs yes). Among adults with prediabetes, testing blood sugar </=3 years was not associated with consuming SSBs >/=1 time/day. CONCLUSION: Daily SSB intake was associated with various characteristics among adults with diabetes or prediabetes. The findings can inform efforts to decrease SSB intake among high-risk populations.

    • Communicable Diseases
      1. A systems-based assessment of the PrePex device adverse events active surveillance system in Zimbabwe
        Adamson PC, Tafuma TA, Davis SM, Xaba S, Herman-Roloff A.
        PLoS One. 2017 ;12(12):e0190055.
        BACKGROUND: Voluntary Medical Male Circumcision (VMMC) is an effective method for HIV prevention and the World Health Organization (WHO) has recommended its expansion in 14 African countries with a high prevalence of HIV and low prevalence of male circumcision. The WHO has recently pre-qualified the PrePex device, a non-surgical male circumcision device, which reduces procedure time, can increase acceptability of VMMC, and can expand the set of potential provider cadres. The PrePex device was introduced in Zimbabwe as a way to scale-up VMMC services in the country. With the rapid scale-up of the PrePex device, as well as other similar devices, a strong surveillance system to detect adverse events (AE) is needed to monitor the safety profile of these devices. We performed a systems-based evaluation of the PrePex device AE active surveillance system in Zimbabwe. METHODS: The evaluation was based on the Centers for Disease Control and Prevention’s Updated Guidelines for Evaluating Public Health Surveillance Systems. We adapted these guidelines to fit our local context. The evaluation incorporated the review of the standard operating procedures and surveillance system documents. Additionally, structured, in-person interviews were performed with key stakeholders who were users of the surveillance system at various levels. These key stakeholders were from the Ministry of Health, implementing partners, and health facilities in Harare. RESULTS: Clients were requested to return to the facility for follow-up on days 7, 14 and 49 after placement of the device. In the event of a severe AE, a standard report was generated by the health facility and relayed to the Ministry of Health Child and Care and donor agencies through predefined channels within 24 hours of diagnosis. Clinic staff reported difficulties with the amount of documentation required to follow up with clients and to report AEs. The surveillance system’s acceptability among users interviewed was high, and users were motivated to identify all possible AEs related to this device. The surveillance system was purely paper-based and both duplicate and discrepant reporting forms between sites were identified. CONCLUSION: The PrePex AE active surveillance system was well accepted among participants in the health system. However, the amount of documentation which was required to follow-up with patients was a major barrier within the system, and might lead to decreased timeliness and quality of reporting. A passive surveillance system supported by electronic reporting would improve acceptance of the program.

      2. Higher-than-expected prevalence of non-tuberculous mycobacteria in HIV setting in Botswana: Implications for diagnostic algorithms using Xpert MTB/RIF assay
        Agizew T, Basotli J, Alexander H, Boyd R, Letsibogo G, Auld A, Nyirenda S, Tedla Z, Mathoma A, Mathebula U, Pals S, Date A, Finlay A.
        PLoS One. 2017 ;12(12):e0189981.
        BACKGROUND: Non-tuberculous mycobacteria (NTM) can cause pulmonary infection and disease especially among people living with HIV (PLHIV). PLHIV with NTM disease may clinically present with one of the four symptoms consistent with tuberculosis (TB). We describe the prevalence of NTM and Mycobacterium tuberculosis complex (MTBC) isolated among PLHIV who presented for HIV care and treatment. METHODS: All PLHIV patients presenting for HIV care and treatment services at 22 clinical sites in Botswana were offered screening for TB and were recruited. Patients who had >/=1 TB symptom were asked to submit sputa for Xpert MTB/RIF and culture. Culture growth was identified as NTM and MTBC using the SD-Bioline TB Ag MPT64 Kit and Ziehl Neelsen microscopy. NTM and MTBC isolates underwent species identification by the Hain GenoType CM and AS line probe assays. RESULTS: Among 16, 259 PLHIV enrolled 3068 screened positive for at least one TB symptom. Of these, 1940 submitted >/=1 sputum specimen, 427 (22%) patients had >/=1 positive-culture result identified phenotypically for mycobacterial growth. Of these 247 and 180 patients were identified as having isolates were NTM and MTBC, respectively. Of the 247 patients identified with isolates containing NTM; 19 were later excluded as not having NTM based on additional genotypic testing. Among the remaining 408 patients 228 (56%, 95% confidence interval, 46-66%) with NTM. M. intracellulare was the most common isolated (47.8%). Other NTMs commonly associated with pulmonary disease included M. malmoense (3.9%), M. avium (2.2%), M. abscessus (0.9%) and M. kansasii (0.4%). After excluding NTM isolates that were non-speciated and M. gordonae 154 (67.5%) of the NTM isolates were potential pathogens. CONCLUSIONS: In the setting of HIV care and treatment, over-half (56%) of a positive sputum culture among PLHIV with TB symptoms was NTM. Though we were not able to distinguish in our study NTM disease and colonization, the study suggests culture and species identification for PLHIV presenting with TB symptoms remains important to facilitate NTM diagnosis and hasten time to appropriate treatment.

      3. Cancer burden attributable to cigarette smoking among HIV-infected people in North America
        Altekruse SF, Shiels MS, Modur SP, Land SR, Crothers KA, Kitahata MM, Thorne JE, Mathews WC, Fernandez-Santos DM, Mayor AM, Gill JM, Horberg MA, Brooks JT, Moore RD, Silverberg MJ, Althoff KN, Engels EA.
        Aids. 2017 Dec 12.
        OBJECTIVE: With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes. DESIGN: Observational cohort of HIV-infected participants with 270,136 person-years of follow-up in the North American AIDS Cohort Collaboration on Research and Design consortium. Among 52,441 participants; 2306 were diagnosed with cancer during 2000-2015. MAIN OUTCOME MEASURES: Estimated hazard ratios (HR) and population-attributable fractions (PAF) associated with ever cigarette smoking for all cancers combined, smoking-related cancers, and cancers that were not attributed to smoking. RESULTS: People with cancer were more frequently ever smokers (79%) compared to people without cancer (73%). Adjusting for demographic and clinical factors, cigarette smoking was associated with increased risk of cancer overall (HR = 1.33 [95% confidence interval: 1.18-1.49]); smoking-related cancers (HR = 2.31 [1.80-2.98]), lung cancer (HR = 17.80 [5.60-56.63]); but not non-smoking-related cancers (HR = 1.12 [0.98-1.28]). Adjusted PAFs associated with ever cigarette smoking were as follows: all cancers combined, PAF = 19% [95% confidence interval: 13%-25%]; smoking-related cancers, PAF = 50% [39%-59%]; lung cancer, PAF = 94% [82%-98%]; and non-smoking-related cancers, PAF = 9% [1%-16%]. CONCLUSIONS: Among HIV-infected persons, approximately one fifth of all incident cancer, including half of smoking-related cancer, and 94% of lung cancer diagnoses could potentially be prevented by eliminating cigarette smoking. Cigarette smoking could contribute to some cancers that were classified as non-smoking-related cancers in this report. Enhanced smoking cessation efforts targeted to HIV-infected individuals are needed.

      4. Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing
        Arauz AB, Caceres DH, Santiago E, Armstrong P, Arosemena S, Ramos C, Espinosa-Bode A, Borace J, Hayer L, Cedeno I, Jackson BR, Sosa N, Berkow EL, Lockhart SR, Rodriguez-French A, Chiller T.
        Mycoses. 2018 Jan;61(1):44-47.
        Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

      5. Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies
        Arikawa S, Rollins N, Jourdain G, Humphrey J, Kourtis AP, Hoffman I, Essex M, Farley T, Coovadia HM, Gray G, Kuhn L, Shapiro R, Leroy V, Bollinger RC, Onyango-Makumbi C, Lockman S, Marquez C, Doherty T, Dabis F, Mandelbrot L, Le Coeur S, Rolland M, Joly P, Newell ML, Becquet R.
        Clin Infect Dis. 2017 Dec 21.
        Background: Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package “frailtypack” estimate the relative contribution of risk factors to overall mortality in HEU children. Results: Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion: Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates.

      6. Benefit of the shorter multidrug-resistant tuberculosis treatment regimen in California and modified eligibility criteria
        Barry PM, Lowenthal P, True L, Henry L, Schack G, Wendorf K, Flood J, Shah N.
        Am J Respir Crit Care Med. 2017 Dec 1;196(11):1488-1489.

        [No abstract]

      7. Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control?
        Bernstein K, Bowen VB, Kim CR, Counotte MJ, Kirkcaldy RD, Kara E, Bolan G, Low N, Broutet N.
        PLoS Med. 2017 Dec;14(12):e1002474.
        How do we spot the next sexually transmitted infection? Kyle Bernstein and colleagues look for lessons from past discovery.

      8. Multiple injections per injection episode: High-risk injection practice among people who injected pills during the 2015 HIV outbreak in Indiana
        Broz D, Zibbell J, Foote C, Roseberry JC, Patel MR, Conrad C, Chapman E, Peters PJ, Needle R, McAlister C, Duwve JM.
        Int J Drug Policy. 2017 Dec 23;52:97-101.
        BACKGROUND: Misuse of prescription opioid analgesics (POA) has increased dramatically in the US, particularly in non-urban areas. We examined injection practices among persons who inject POA in a rural area that experienced a large HIV outbreak in 2015. METHODS: Between August-September 2015, 25 persons who injected drugs within the past 12 months were recruited in Scott County, Indiana for a qualitative study. Data from in-depth, semi-structured interviews were analyzed. RESULTS: All 25 participants were non-Hispanic white and the median age was 33 years (range: 19-57). All had ever injected extended-release oxymorphone (Opana((R)) ER) and most (n=20) described preparing Opana((R)) ER for multiple injections per injection episode (MIPIE). MIPIE comprised 2-4 injections during an injection episode resulting from needing >1mL water to prepare Opana((R)) ER solution using 1mL syringes and the frequent use of “rinse shots.” MIPIE occurred up to 10 times/day (totaling 35 injections/day), often in the context of sharing drug and injection equipment. CONCLUSIONS: We describe a high-risk injection practice that may have contributed to the rapid spread of HIV in this community. Efforts to prevent bloodborne infections among people who inject POA need to assess for MIPIE so that provision of sterile injection equipment and safer injection education addresses the MIPIE risk environment.

      9. Healthcare provider perspectives on managing sexually transmitted infections in HIV care settings in Kenya: A qualitative thematic analysis
        Chesang K, Hornston S, Muhenje O, Saliku T, Mirjahangir J, Viitanen A, Musyoki H, Awuor C, Githuka G, Bock N.
        PLoS Med. 2017 Dec;14(12):e1002480.
        BACKGROUND: The burden of sexually transmitted infections (STIs) has been increasing in Kenya, as is the case elsewhere in sub-Saharan Africa, while measures for control and prevention are weak. The objectives of this study were to (1) describe healthcare provider (HCP) knowledge and practices, (2) explore HCP attitudes and beliefs, (3) identify structural and environmental factors affecting STI management, and (4) seek recommendations to improve the STI program in Kenya. METHODS AND FINDINGS: Using individual in-depth interviews (IDIs), data were obtained from 87 HCPs working in 21 high-volume comprehensive HIV care centers (CCCs) in 7 of Kenya’s 8 regions. Transcript coding was performed through an inductive and iterative process, and the data were analyzed using NVivo 10.0. Overall, HCPs were knowledgeable about STIs, saw STIs as a priority, reported high STI co-infection amongst people living with HIV (PLHIV), and believed STIs in PLHIV facilitate HIV transmission. Most used the syndromic approach for STI management. Condoms and counseling were available in most of the clinics. HCPs believed that having an STI increased stigma in the community, that there was STI antimicrobial drug resistance, and that STIs were not prioritized by the authorities. HCPs had positive attitudes toward managing STIs, but were uncomfortable discussing sexual issues with patients in general, and profoundly for anal sex. The main barriers to the management of STIs reported were low commitment by higher levels of management, few recent STI-focused trainings, high stigma and low community participation, and STI drug stock-outs. Solutions recommended by HCPs included formulation of new STI policies that would increase access, availability, and quality of STI services; integrated STI/HIV management; improved STI training; increased supervision; standardized reporting; and community involvement in STI prevention. The key limitations of our study were that (1) participant experience and how much of their workload was devoted to managing STIs was not considered, (2) some responses may have been subject to recall and social desirability bias, and (3) patients or clients of STI services were not interviewed, and therefore their inputs were not obtained. While considering these limitations, the number and variety of facilities sampled, the mix of staff cadres interviewed, the use of a standardized instrument, and the consistency of responses add strength to our findings. CONCLUSIONS: This study showed that HCPs understood the challenges of, and solutions for, improving the management of STIs in Kenya. Commitment by higher management, training in the management of STIs, measures for reducing stigma, and introducing new policies of STI management should be considered by health authorities in Kenya.

      10. An outbreak of Escherichia coli O157:H7 infections following a dairy education school field trip in Washington state, 2015
        Curran KG, Heiman Marshall KE, Singh T, Doobovsky Z, Hensley J, Melius B, Whitlock L, Stevenson L, Leinbach J, Oltean H, Glover WA, Kunesh T, Lindquist S, Williams I, Nichols M.
        Epidemiol Infect. 2017 Dec 22:1-11.
        On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20-24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case-control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case-control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02-0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.

      11. “Oh, I’m not alone”: Experiences of HIV-positive men who have sex with men in a health navigation program to promote timely linkage to care in Guatemala City
        Davis DA, Aguilar JM, Arandi CG, Northbrook S, Loya-Montiel MI, Morales-Miranda S, Barrington C.
        AIDS Educ Prev. 2017 Dec;29(6):554-566.
        Men who have sex with men (MSM) are disproportionately affected by HIV in Guatemala and may benefit from health navigation programs designed to support timely linkage to HIV care. We conducted qualitative in-depth interviews with MSM (n = 19) linked to care within days of their diagnosis with the support of a health navigator. We used narrative analysis and systematic coding to identify themes related to HIV diagnosis and experiences with navigators. Participants experienced strong feelings of fear upon receiving a positive HIV test result. This fear led to social isolation and limited reliance on family and friend networks for support. Health navigators developed strong relationships with participants by providing the emotional support they were lacking and supporting them to overcome their fear and other structural barriers to HIV care, including stigma. Findings support the important role of navigation for MSM in Guatemala and could be transferable to other settings in Latin America.

      12. National burden of hospitalized and non-hospitalized influenza-associated severe acute respiratory illness in Kenya, 2012-2014
        Dawa JA, Chaves SS, Nyawanda B, Njuguna HN, Makokha C, Otieno NA, Anzala O, Widdowson MA, Emukule GO.
        Influenza Other Respir Viruses. 2017 Dec 15.
        BACKGROUND: Influenza-associated respiratory illness was substantial during the emergence of the 2009 influenza pandemic. Estimates of influenza burden in the post-pandemic period are unavailable to guide Kenyan vaccine policy. OBJECTIVES: To update estimates of hospitalized and non-hospitalized influenza-associated severe acute respiratory illness (SARI) during a post-pandemic period (2012-2014) and describe the incidence of disease by narrow age categories. METHODS: We used data from Siaya County Referral Hospital to estimate age-specific base rates of SARI. We extrapolated these base rates to other regions within the country by adjusting for regional risk factors for acute respiratory illness (ARI), regional healthcare utilization for acute respiratory illness, and the proportion of influenza-positive SARI cases in each region, so as to obtain region-specific rates. RESULTS: The mean annual rate of hospitalized influenza-associated SARI among all ages was 21 (95% CI 19-23) per 100 000 persons. Rates of non-hospitalized influenza-associated SARI were approximately 4 times higher at 82 (95% CI 74-90) per 100 000 persons. Mean annual rates of influenza-associated SARI were highest in children <2 years of age with annual hospitalization rates of 147 (95% CI of 134-160) per 100 000 persons and non-hospitalization rates of 469 (95% CI 426-517) per 100 000 persons. For the period 2012-2014, there were between 8153 and 9751 cases of hospitalized influenza-associated SARI and 31 785-38 546 cases of non-hospitalized influenza-associated SARI per year. CONCLUSIONS: The highest burden of disease was observed among children <2 years of age. This highlights the need for strategies to prevent influenza infections in this age group.

      13. Sustained reduction in Chlamydia infections following a school-based screening: Detroit, 2010-2015
        Dunville R, Peterson A, Liddon N, Roach M, Coleman K, Dittus P.
        Am J Public Health. 2017 Dec 21:e1-e3.
        We describe school-based screening events in four Detroit, Michigan public high schools. To examine trends, we analyzed Chlamydia trachomatis data from 2010 to 2015. Prevalence of C. trachomatis decreased significantly (P < .01): from 10.24% to 6.27%. Future school-based screening events may bring about similar results if the program is instituted in a high-prevalence area and can achieve high student participation. (Am J Public Health. Published online ahead of print December 21, 2017: e1-e3. doi:10.2105/AJPH.2017.304163).

      14. Prevalence and predictors of late presentation for HIV care in South Africa
        Fomundam HN, Tesfay AR, Mushipe SA, Mosina MB, Boshielo CT, Nyambi HT, Larsen A, Cheyip M, Getahun A, Pillay Y.
        S Afr Med J. 2017 Nov 27;107(12):1058-1064.
        BACKGROUND: Many people living with HIV in South Africa (SA) are not aware of their seropositive status and are diagnosed late during the course of HIV infection. These individuals do not obtain the full benefit from available HIV care and treatment services. OBJECTIVES: To describe the prevalence of late presentation for HIV care among newly diagnosed HIV-positive individuals and evaluate sociodemographic variables associated with late presentation for HIV care in three high-burden districts of SA. METHODS: We used data abstracted from records of 8 138 newly diagnosed HIV-positive individuals in 35 clinics between 1 June 2014 and 31 March 2015 to determine the prevalence of late presentation among newly diagnosed HIV-positive individuals in selected high-prevalence health districts. Individuals were categorised as ‘moderately late’, ‘very late’ or ‘extremely late’ presenters based on specified criteria. Descriptive analysis was performed to measure the prevalence of late presentation, and multivariate regression analysis was conducted to identify variables independently associated with extremely late presentation. RESULTS: Overall, 79% of the newly diagnosed cases presented for HIV care late in the course of HIV infection (CD4+ count </=500 cells/microL and/or AIDS-defining illness in World Health Organization (WHO) stage III/IV), 19% presented moderately late (CD4+ count 351 – 500 cells/microL and WHO clinical stage I or II), 27% presented very late (CD4+ count 201 – 350 cells/microL or WHO clinical stage III), and 33% presented extremely late (CD4+ count </=200 cells/microL and/or WHO clinical stage IV) for HIV care. Multivariate regression analysis indicated that males, non-pregnant women, individuals aged &gt;30 years, and those accessing care in facilities located in townships and inner cities were more likely to present late for HIV care. CONCLUSIONS: The majority of newly diagnosed HIV-positive individuals in the three high-burden districts (Gert Sibande, uThukela and City of Johannesburg) presented for HIV care late in the course of HIV infection. Interventions that encourage early presentation for HIV care should be prioritised in SA and should target males, non-pregnant women, individuals aged &gt;30 years and those accessing care in facilities located in inner cities and urban townships.

      15. Targeting human immunodeficiency virus pre-exposure prophylaxis to adolescent sexual minority males in higher prevalence areas of the United States: A modeling study
        Goodreau SM, Hamilton DT, Jenness SM, Sullivan PS, Valencia RK, Wang LY, Dunville RL, Barrios LC, Rosenberg ES.
        J Adolesc Health. 2017 Dec 13.
        PURPOSE: Pre-exposure prophylaxis (PrEP) is an effective and safe intervention to prevent human immunodeficiency virus (HIV) transmission in men who have sex with men; current Centers for Disease Control and Prevention guidelines indicate its use among high-risk adults. Adolescent sexual minority males (ASMM) also have significant HIV risk, but implementation strategies are likely to differ for this population. We aimed to estimate impact and efficiency of PrEP for ASMM in higher prevalence US settings, using a variety of implementation strategies and assumptions about coverage, adherence, and background prevalence. METHODS: We develop a stochastic, dynamic, network-based model, parametrized using numerous ASMM behavioral and clinical data sources. We simulate 10 years with and without PrEP, comparing percent of incident infections averted (impact) and number of person-years on PrEP per infection averted (efficiency). RESULTS: Our main scenario (PrEP for 16- to 18-year-old ASMM, initiating PrEP 6 months after first anal intercourse, 40% coverage, adherence profiles from the ATN 113 trial; 2.9% background HIV prevalence among ASMM) prevents 27.8% of infections, with 38 person-years on PrEP per infection averted. Expanding implementation to cover younger ages or earlier initiation has small effects on impact and efficiency. Targeting highest risk ASMM increases efficiency, but requires querying sexual histories. Across levels examined, coverage and adherence do not have major impacts on efficiency, whereas background prevalence does. CONCLUSIONS: PrEP can have a large impact on HIV incidence among ASMM in the United States, especially in settings with high prevalence. However, willingness of, and support for, providers will be central to achieving the coverage needed to make this a success.

      16. Geographic variability in diagnosis and antibiotic prescribing for acute respiratory tract infections
        Hersh AL, Shapiro DJ, Pavia AT, Fleming-Dutra KE, Hicks LA.
        Infect Dis Ther. 2017 Dec 22.
        INTRODUCTION: Antibiotic prescribing rates vary substantially across regions in the USA. Whether these differences are driven primarily by a greater tendency to treat certain infections (i.e., overtreatment) in certain regions or differences in the tendency to diagnose certain infections (i.e., overdiagnosis) is poorly understood. METHODS: We examined data from 2012 to 2013 using the National Ambulatory Medical Care Survey, which is a nationally representative sample of visits to office-based physicians. For each of nine geographic regions, we examined the relationship between the visit rate/1000 population for respiratory diagnoses for which antibiotics were prescribed to the visit rate/1000 population for selected respiratory diagnoses where antibiotic therapy may be warranted. RESULTS: The visit rate for all respiratory conditions resulting in an antibiotic prescription was lowest (109/1000 population) in the Pacific Region and highest (176/1000, 95% CI 138-213) in the East South Central Region. The diagnosis rate for selected respiratory conditions where antibiotic therapy may be warranted was also lowest (119/1000, 95% CI 91-147) in the Pacific Region and highest (189/1000, 95% CI 153-225) in the East South Central Region. CONCLUSION: Antibiotic prescribing rates for respiratory conditions vary by region and are strongly associated with the rate with which selected respiratory conditions are diagnosed.

      17. Heavy precipitation as a risk factor for shigellosis among homeless persons during an outbreak – Oregon, 2015-2016
        Hines JZ, Jagger MA, Jeanne TL, West N, Winquist A, Robinson BF, Leman RF, Hedberg K.
        J Infect. 2017 Dec 4.
        OBJECTIVES: Shigella species are the third most common cause of bacterial gastroenteritis in the United States. During a Shigella sonnei outbreak in Oregon from July 2015 through June 2016, Shigella cases spread among homeless persons with onset of the wettest rainy season on record. METHODS: We conducted time series analyses using Poisson regression to determine if a temporal association between precipitation and shigellosis incidence existed. Models were stratified by housing status. RESULTS: Among 105 infections identified, 45 (43%) occurred in homeless persons. With increasing precipitation, cases increased among homeless persons (relative risk [RR] = 1.36 per inch of precipitation; 95% confidence interval [CI] = 1.17-1.59), but not among housed persons (RR = 1.04; 95% CI 0.86-1.25). CONCLUSIONS: Heavy precipitation likely contributed to shigellosis transmission among homeless persons during this outbreak. When heavy precipitation is forecast, organizations working with homeless persons could consider taking proactive measures to mitigate spread of enteric infections.

      18. High prevalence of HIV drug resistance among newly diagnosed infants aged <18 months: Results from a nationwide surveillance in Nigeria
        Inzaule SC, Osi SJ, Akinbiyi G, Emeka A, Khamofu H, Mpazanje R, Ilesanmi O, Ndembi N, Odafe S, Sigaloff KC, Rinke de Wit TF, Akanmu S.
        J Acquir Immune Defic Syndr. 2018 Jan 1;77(1):e1-e7.
        BACKGROUND: WHO recommends protease-inhibitor-based first-line regimen in infants because of risk of drug resistance from failed prophylaxis used in prevention of mother-to-child transmission (PMTCT). However, cost and logistics impede implementation in sub-Saharan Africa, and >75% of children still receive nonnucleoside reverse transcriptase inhibitor-based regimen (NNRTI) used in PMTCT. METHODS: We assessed the national pretreatment drug resistance prevalence of HIV-infected children aged <18 months in Nigeria, using WHO-recommended HIV drug resistance surveillance protocol. We used remnant dried blood spots collected between June 2014 and July 2015 from 15 early infant diagnosis facilities spread across all the 6 geopolitical regions of Nigeria. Sampling was through a probability proportional-to-size approach. HIV drug resistance was determined by population-based sequencing. RESULTS: Overall, in 48% of infants (205 of 430) drug resistance mutations (DRM) were detected, conferring resistance to predominantly NNRTIs (45%). NRTI and multiclass NRTI/NNRTI resistance were present at 22% and 20%, respectively, while resistance to protease inhibitors was at 2%. Among 204 infants with exposure to drugs for PMTCT, 57% had DRMs, conferring NNRTI resistance in 54% and multiclass NRTI/NNRTI resistance in 29%. DRMs were also detected in 34% of 132 PMTCT unexposed infants. CONCLUSION: A high frequency of PDR, mainly NNRTI-associated, was observed in a nationwide surveillance among newly diagnosed HIV-infected children in Nigeria. PDR prevalence was equally high in PMTCT-unexposed infants. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected young children regardless of PMTCT history and underscore the need to accelerate implementation of the newly disseminated guideline in Nigeria.

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

      20. Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons
        Jackson ML, Phillips CH, Benoit J, Jackson LA, Gaglani M, Murthy K, McLean HQ, Belongia EA, Malosh R, Zimmerman R, Flannery B.
        Vaccine. 2017 Dec 14.
        BACKGROUND: In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. METHODS: We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. RESULTS: Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6months to 9years (33 to 70 per 1000) and lowest in adults aged 18-49years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14). DISCUSSION: Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.

      21. National survey of Ebola-related knowledge, attitudes and practices before the outbreak peak in Sierra Leone: August 2014
        Jalloh MF, Sengeh P, Monasch R, Jalloh MB, DeLuca N, Dyson M, Golfa S, Sakurai Y, Conteh L, Sesay S, Brown V, Li W, Mermin J, Bunnell R.
        BMJ Glob Health. 2017 ;2(4):e000285.
        Background: The 2014-2015 Ebola epidemic in West Africa was the largest ever to occur. In the early phases, little was known about public knowledge, attitudes and practices (KAP) relating to Ebola virus disease (Ebola). Data were needed to develop evidence-driven strategies to address gaps in knowledge and practice. Methods: In August 2014, we conducted interviews with 1413 randomly selected respondents from 9 out of 14 districts in Sierra Leone using multistage cluster sampling. Where suitable, Ebola-related KAP questions were adapted from other internationally validated questionnaires related to infectious diseases. Results: All respondents were aware of Ebola. When asked unprompted, 60% of respondents could correctly cite fever, diarrhoea and vomiting as signs/symptoms of Ebola. A majority of respondents knew that avoiding infected blood and bodily fluids (87%) and contact with an infected corpse (85%) could prevent Ebola. However, there were also widespread misconceptions such as the belief that Ebola can be prevented by washing with salt and hot water (41%). Almost everyone interviewed (95%) expressed at least one discriminatory attitude towards Ebola survivors. Unprompted, self-reported actions taken to avoid Ebola infection included handwashing with soap (66%) and avoiding physical contact with patients with suspected Ebola (40%). Conclusion: Three months into the 2014 Ebola outbreak in Sierra Leone, our findings suggest there was high awareness of the disease but misconceptions and discriminatory attitudes toward survivors remained common. These findings directly informed the development of a national social mobilisation strategy and demonstrated the importance of KAP assessment early in an epidemic.

      22. Unhealthy environments, unhealthy consequences: Experienced homonegativity and HIV infection risk among young men who have sex with men
        Jeffries WL, Gelaude DJ, Torrone EA, Gasiorowicz M, Oster AM, Spikes PS, McCree DH, Bertolli J.
        Glob Public Health. 2017 Jan;12(1):116-129.
        Unfavourable social environments can negatively affect the health of gay, bisexual, and other men who have sex with men (MSM). We described how experienced homonegativity – negative perceptions and treatment that MSM encounter due to their sexual orientations – can increase HIV vulnerability among young MSM. Participants (n = 44) were young MSM diagnosed with HIV infection during January 2006-June 2009. All participants completed questionnaires that assessed experienced homonegativity and related factors (e.g. internalised homonegativity). We focus this analysis on qualitative interviews in which a subset of participants (n = 28) described factors that they perceived to have placed them at risk for HIV infection. Inductive content analysis identified themes within qualitative interviews, and we determined the prevalence of homonegativity and related factors using questionnaires. In qualitative interviews, participants reported that young MSM commonly experienced homonegativity. They described how homonegativity generated internalised homonegativity, HIV stigma, silence around homosexuality, and forced housing displacement. These factors could promote HIV risk. Homonegative experiences were more common among young Black (vs. non-Black) MSM who completed questionnaires. Results illustrate multiple pathways through which experienced homonegativity may increase HIV vulnerability among young MSM. Interventions that target homonegativity might help to reduce the burden of HIV within this population.

      23. Sexual minority youth (SMY) experience elevated rates of adverse sexual health outcomes. Although risk factors driving these outcomes are well studied, less attention has been paid to protective factors that potentially promote health and/or reduce negative effects of risk. Many factors within interpersonal relationships have been identified as protective for the sexual health of adolescents generally. We sought to systematically map the current evidence base of relationship-level protective factors specifically for the sexual health of SMY through a systematic mapping of peer-reviewed observational research. Articles examining at least one association between a relationship-level protective factor and a sexual health outcome in a sample or subsample of SMY were eligible for inclusion. A total of 36 articles reporting findings from 27 data sources met inclusion criteria. Included articles examined characteristics of relationships with peers, parents, romantic/sexual partners, and medical providers. Peer norms about safer sex and behaviorally specific communication with regular romantic/sexual partners were repeatedly protective in cross-sectional analyses, suggesting that these factors may be promising intervention targets. Generally, we found some limits to this literature: few types of relationship-level factors were tested, most articles focused on young sexual minority men, and the bulk of the data was cross-sectional. Future work should expand the types of relationship-level factors investigated, strengthen the measurement of relationship-level factors, include young sexual minority women in samples, and use longitudinal designs. Doing so will move the field toward development of empirically sound interventions for SMY that promote protective factors and improve sexual health.

      24. Prevalence, magnitude, and correlates of HIV-1 genital shedding in women on antiretroviral therapy
        King CC, Ellington SR, Davis NL, Coombs RW, Pyra M, Hong T, Mugo N, Patel RC, Lingappa JR, Baeten JM, Kourtis AP.
        J Infect Dis. 2017 Dec 12.
        Background: Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods: We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results: Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion: In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission.

      25. Regional epidemiology of methicillin-resistant Staphylococcus aureus among adult intensive care unit patients following state-mandated active surveillance
        Lin MY, Hayden MK, Lyles RD, Lolans K, Fogg LF, Kallen AJ, Weber SG, Weinstein RA, Trick WE.
        Clin Infect Dis. 2017 Dec 7.
        Background: In 2007, Illinois became the first state in the United States to mandate active surveillance of methicillin-resistant Staphylococcus aureus (MRSA). The Illinois law applies to intensive care unit (ICU) patients; contact precautions are required for patients found to be MRSA-colonized. However, the effectiveness of a legislated “search and isolate” approach to reduce MRSA burden among critically ill patients is uncertain. We evaluated whether the prevalence of MRSA colonization declined in the 5 years after the start of mandatory active surveillance. Methods: All hospitals with an ICU having >/=10 beds in Chicago, Illinois, USA were eligible to participate in single-day serial point prevalence surveys. We assessed MRSA colonization among adult ICU patients present at time of survey using nasal and inguinal swab cultures. The primary outcome was region-wide MRSA colonization prevalence over time. Results: All 25 eligible hospitals (51 ICUs) participated in serial point prevalence surveys over 8 survey periods (2008 – 2013). A total of 3909 adult ICU patients participated in the point prevalence surveys, with 432 (11.1%) found to be colonized with MRSA (95% confidence interval [CI] 10.1% to 12.0%). The MRSA colonization prevalence among patients was unchanged during the study period; year-over-year relative risk for MRSA colonization was 0.97, 95% CI 0.89 to 1.05, P=0.48). Conclusions: MRSA colonization prevalence among critically ill adult patients did not decline during the time period following legislatively mandated MRSA active surveillance. Our findings highlight the limits of legislated MRSA active surveillance as a strategy to reduce MRSA colonization burden among ICU patients.

      26. Thinking beyond the common Candida species: need for species-level identification of Candida due to the emergence of multidrug-resistant Candida auris
        Lockhart SR, Jackson BR, Vallabhaneni S, Ostrosky-Zeichner L, Pappas PG, Chiller T.
        J Clin Microbiol. 2017 Dec;55(12):3324-3327.
        Candida species are one of the leading causes of nosocomial infections. Because much of the treatment for Candida infections is empirical, some institutions do not identify Candida to species level. With the worldwide emergence of the multidrug-resistant species Candida auris, identification of Candida to species level has new clinical relevance. Species should be identified for invasive candidiasis isolates, and species-level identification can be considered for selected noninvasive isolates to improve detection of C. auris.

      27. Rhinovirus viremia in patients hospitalized with community-acquired pneumonia
        Lu X, Schneider E, Jain S, Bramley AM, Hymas W, Stockmann C, Ampofo K, Arnold SR, Williams DJ, Self WH, Patel A, Chappell JD, Grijalva CG, Anderson EJ, Wunderink RG, McCullers JA, Edwards KM, Pavia AT, Erdman DD.
        J Infect Dis. 2017 Nov 27;216(9):1104-1111.
        Background: Rhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RVs from the upper respiratory tract can be prolonged, complicating etiologic association in persons with severe lower respiratory tract infections. Little is known about RV viremia and its value as a diagnostic indicator in persons hospitalized with community-acquired pneumonia (CAP). Methods: Sera from RV-positive children and adults hospitalized with CAP were tested for RV by real-time reverse-transcription polymerase chain reaction. Rhinovirus species and type were determined by partial genome sequencing. Results: Overall, 57 of 570 (10%) RV-positive patients were viremic, and all were children aged <10 years (n = 57/375; 15.2%). Although RV-A was the most common RV species detected from respiratory specimens (48.8%), almost all viremias were RV-C (98.2%). Viremic patients had fewer codetected pathogens and were more likely to have chest retractions, wheezing, and a history of underlying asthma/reactive airway disease than patients without viremia. Conclusions: More than 1 out of 7 RV-infected children aged <10 years hospitalized with CAP were viremic. In contrast with other RV species, RV-C infections were highly associated with viremia and were usually the only respiratory pathogen identified, suggesting that RV-C viremia may be an important diagnostic indicator in pediatric pneumonia.

      28. Assessing stakeholder perceptions of the acceptability and feasibility of national scale-up for a dual HIV/syphilis rapid diagnostic test in Malawi
        Maddox BL, Wright SS, Namadingo H, Bowen VB, Chipungu GA, Kamb ML.
        Sex Transm Infect. 2017 Dec;93(S4):S59-s64.
        OBJECTIVES: The WHO recommends pregnant women receive both HIV and syphilis testing at their first antenatal care visit, as untreated maternal infections can lead to severe, adverse pregnancy outcomes. One strategy for increasing testing for both HIV and syphilis is the use of point-of-care (rapid) diagnostic tests that are simple, proven effective and inexpensive. In Malawi, pregnant women routinely receive HIV testing, but only 10% are tested for syphilis at their first antenatal care visit. This evaluation explores stakeholder perceptions of a novel, dual HIV/syphilis rapid diagnostic test and potential barriers to national scale-up of the dual test in Malawi. METHODS: During June and July 2015, we conducted 15 semistructured interviews with 25 healthcare workers, laboratorians, Ministry of Health leaders and partner agency representatives working in prevention of mother-to-child transmission in Malawi. We asked stakeholders about the importance of a dual rapid diagnostic test, concerns using and procuring the dual test and recommendations for national expansion. RESULTS: Stakeholders viewed the test favourably, citing the importance of a dual rapid test in preventing missed opportunities for syphilis diagnosis and treatment, improving infant outcomes and increasing syphilis testing coverage. Primary technical concerns were about the additional procedural steps needed to perform the test, the possibility that testers may not adhere to required waiting times before interpreting results and difficulty reading and interpreting test results. Stakeholders thought national scale-up would require demonstration of cost-savings, uniform coordination, revisions to testing guidelines and algorithms, training of testers and a reliable supply chain. CONCLUSIONS: Stakeholders largely support implementation of a dual HIV/syphilis rapid diagnostic test as a feasible alternative to current antenatal testing. Scale-up will require addressing perceived barriers; negotiating changes to existing algorithms and guidelines; and Ministry of Health approval and funding to support training of staff and procurement of supplies.

      29. The unwelcome houseguest: secondary household transmission of norovirus
        Marsh ZA, Grytdal SP, Beggs JC, Leshem E, Gastanaduy PA, Rha B, Nyaku M, Lopman BA, Hall AJ.
        Epidemiol Infect. 2017 Dec 12:1-9.
        Norovirus is the leading cause of acute gastroenteritis in the USA. Although secondary household transmission of norovirus is frequently reported in outbreaks, little is known about specific risk factors for susceptibility and infectiousness in the household. Three norovirus outbreaks were investigated and data were collected on individuals exposed in the primary outbreak setting and their household members. Potential individual- and household-level risk factors for susceptibility and infectiousness were assessed using univariate and multivariate generalised linear mixed models. In the univariate models, the secondary attack rate (SAR) was significantly higher when living in a household with two or more primary cases (incidence rate ratio (IRR) = 2.1; 95% confidence interval (CI) 1.37-3.29), more than one primary case with vomiting (IRR = 1.9; CI 1.11-3.37), and at least one primary case with diarrhoea (IRR = 3.0; CI 1.46-6.01). After controlling for other risk factors in the multivariate models, the SAR was significantly higher among those living in a household with two or more primary cases (adjusted IRR = 2.0; CI 1.17-3.47) and at least one primary case with diarrhoea (adjusted IRR = 2.8; CI 1.35-5.93). These findings underscore the importance of maintaining proper hygiene and isolating ill household members to prevent norovirus transmission in the household.

      30. Implication of first-line antiretroviral therapy choice on second-line options
        Meloni ST, Onwuamah CK, Agbaji O, Chaplin B, Olaleye DO, Audu R, Samuels J, Ezechi O, Imade G, Musa AZ, Odaibo G, Okpokwu J, Rawizza H, Mu’azu MA, Dalhatu I, Ahmed M, Okonkwo P, Raizes E, Ujah IA, Yang C, Idigbe EO, Kanki PJ.
        Open Forum Infect Dis. 2017 Fall;4(4):ofx233.
        Background: Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. Methods: Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University’s HIVdb program. Results: Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0-6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. Conclusions: In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

      31. Encephalitis in US children
        Messacar K, Fischer M, Dominguez SR, Tyler KL, Abzug MJ.
        Infect Dis Clin North Am. 2017 Dec 7.
        Encephalitis is an uncommon but severe disease characterized by neurologic dysfunction with central nervous system inflammation. Children with encephalitis should receive supportive care and empiric therapies for common and treatable causes while prioritizing diagnostic evaluation for common, treatable, and high-risk conditions. Even with an extensive diagnostic workup, an infectious cause is identified in less than half of cases, suggesting a role for postinfectious or noninfectious processes.

      32. Lessons from the domestic Ebola response: Improving health care system resilience to high consequence infectious diseases
        Meyer D, Kirk Sell T, Schoch-Spana M, Shearer MP, Chandler H, Thomas E, Rose DA, Carbone EG, Toner E.
        Am J Infect Control. 2017 Dec 15.
        BACKGROUND: The domestic response to the West Africa Ebola virus disease (EVD) epidemic from 2014-2016 provides a unique opportunity to distill lessons learned about health sector planning and operations from those individuals directly involved. This research project aimed to identify and integrate these lessons into an actionable checklist that can improve health sector resilience to future high-consequence infectious disease (HCID) events. METHODS: Interviews (N = 73) were completed with individuals involved in the domestic EVD response in 4 cities (Atlanta, Dallas, New York, and Omaha), and included individuals who worked in academia, emergency management, government, health care, law, media, and public health during the response. Interviews were transcribed and analyzed qualitatively. Two focus groups were then conducted to expand on themes identified in the interviews. Using these themes, an evidence-informed checklist was developed and vetted for completeness and feasibility by an expert advisory group. RESULTS: Salient themes identified included health care facility issues-specifically identifying assessment and treatment hospitals, isolation and treatment unit layout, waste management, community relations, patient identification, patient isolation, limitations on treatment, laboratories, and research considerations-and health care workforce issues-specifically psychosocial impact, unit staffing, staff training, and proper personal protective equipment. CONCLUSIONS: The experiences of those involved in the domestic Ebola response provide critical lessons that can help strengthen resilience of health care systems and improve future responses to HCID events.

      33. Using reduced inoculum densities of Mycobacterium tuberculosis in MGIT Pyrazinamide Susceptibility Testing to prevent false-resistant results and improve accuracy: A multicenter evaluation
        Morlock GP, Tyrrell FC, Baynham D, Escuyer VE, Green N, Kim Y, Longley-Olson PA, Parrish N, Pennington C, Tan D, Austin B, Posey JE.
        Tuberc Res Treat. 2017 ;2017:3748163.
        The primary platform used for pyrazinamide (PZA) susceptibility testing of Mycobacterium tuberculosis is the MGIT culture system (Becton Dickinson). Since false-resistant results have been associated with the use of this system, we conducted a multicenter evaluation to determine the effect of using a reduced cell density inoculum on the rate of false resistance. Two reduced inoculum densities were compared with that prescribed by the manufacturer (designated as “BD” method). The reduced inoculum methods (designated as “A” and “C”) were identical to the manufacturer’s protocol in all aspects with the exception of the cell density of the inoculum. Twenty genetically and phenotypically characterized M. tuberculosis isolates were tested in duplicate by ten independent laboratories using the three inoculum methods. False-resistant results declined from 21.1% using the standard “BD” method to 5.7% using the intermediate (“A”) inoculum and further declined to 2.8% using the most dilute (“C”) inoculum method. The percentages of the resistant results that were false-resistant declined from 55.2% for the “BD” test to 28.8% and 16.0% for the “A” and “C” tests, respectively. These results represent compelling evidence that the occurrence of false-resistant MGIT PZA susceptibility test results can be mitigated through the use of reduced inoculum densities.

      34. Notes from the field: Tuberculosis control activities after Hurricane Harvey – Texas, 2017
        Morris S, Miner M, Rodriguez T, Stancil R, Wiltz-Beckham D, Chorba T.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1362-1363.

        [No abstract]

      35. The etiology of genital ulcer disease and coinfections with Chlamydia trachomatis and Neisseria gonorrhoeae in Zimbabwe: Results from the Zimbabwe STI Etiology Study
        Mungati M, Machiha A, Mugurungi O, Tshimanga M, Kilmarx PH, Nyakura J, Shambira G, Kupara V, Lewis DA, Gonese E, Tippett Barr BA, Handsfield HH, Rietmeijer CA.
        Sex Transm Dis. 2018 Jan;45(1):61-68.
        BACKGROUND: In many countries, sexually transmitted infections (STIs) are treated syndromically. Thus, patients diagnosed as having genital ulcer disease (GUD) in Zimbabwe receive a combination of antimicrobials to treat syphilis, chancroid, lymphogranuloma venereum (LGV), and genital herpes. Periodic studies are necessary to assess the current etiology of GUD and assure the appropriateness of current treatment guidelines. MATERIALS AND METHODS: We selected 6 geographically diverse clinics in Zimbabwe serving high numbers of STI cases to enroll men and women with STI syndromes, including GUD. Sexually transmitted infection history and risk behavioral data were collected by questionnaire and uploaded to a Web-based database. Ulcer specimens were obtained for testing using a validated multiplex polymerase chain reaction (M-PCR) assay for Treponema pallidum (TP; primary syphilis), Haemophilus ducreyi (chancroid), LGV-associated strains of Chlamydia trachomatis, and herpes simplex virus (HSV) types 1 and 2. Blood samples were collected for testing with HIV, treponemal, and nontreponemal serologic assays. RESULTS: Among 200 GUD patients, 77 (38.5%) were positive for HSV, 32 (16%) were positive for TP, and 2 (1%) were positive for LGV-associated strains of C trachomatis. No H ducreyi infections were detected. No organism was found in 98 (49.5%) of participants. The overall HIV positivity rate was 52.2% for all GUD patients, with higher rates among women compared with men (59.8% vs 45.2%, P < 0.05) and among patients with HSV (68.6% vs 41.8%, P < 0.0001). Among patients with GUD, 54 (27.3%) had gonorrhea and/or chlamydia infection. However, in this latter group, 66.7% of women and 70.0% of men did not have abnormal vaginal or urethral discharge on examination. CONCLUSIONS: Herpes simplex virus is the most common cause of GUD in our survey, followed by T. pallidum. No cases of chancroid were detected. The association of HIV infections with HSV suggests high risk for cotransmission; however, some HSV ulcerations may be due to HSV reactivation among immunocompromised patients. The overall prevalence of gonorrhea and chlamydia was high among patients with GUD and most of them did not meet the criteria for concomitant syndromic management covering these infections.

      36. The optimal age for screening adolescents and young adults without identified risk factors for HIV
        Neilan AM, Dunville R, Ocfemia MC, Salomon JA, Francke JA, Bulteel AJ, Wang LY, Hsu KK, DiNenno EA, Walensky RP, Parker RA, Freedberg KA, Ciaranello AL.
        J Adolesc Health. 2018 Jan;62(1):22-28.
        PURPOSE: To assess the optimal age at which a one-time HIV screen should begin for adolescents and young adults (AYA) in the U.S. without identified HIV risk factors, incorporating clinical impact, costs, and cost-effectiveness. METHODS: We simulated HIV-uninfected 12-year-olds in the U.S. without identified risk factors who faced age-specific risks of HIV infection (.6-71.3/100,000PY). We modeled a one-time screen ($36) at age 15, 18, 21, 25, or 30, each in addition to current U.S. screening practices (30% screened by age 24). Outcomes included retention in care, virologic suppression, life expectancy, lifetime costs, and incremental cost-effectiveness ratios in $/year-of-life saved (YLS) from the health-care system perspective. In sensitivity analyses, we varied HIV incidence, screening and linkage rates, and costs. RESULTS: All one-time screens detected a small proportion of lifetime infections (.1%-10.3%). Compared with current U.S. screening practices, a screen at age 25 led to the most favorable care continuum outcomes at age 25: proportion diagnosed (77% vs. 51%), linked to care (71% vs. 51%), retained in care (68% vs. 44%), and virologically suppressed (49% vs. 32%). Compared with the next most effective screen, a screen at age 25 provided the greatest clinical benefit, and was cost-effective ($96,000/YLS) by U.S. standards (<$100,000/YLS). CONCLUSIONS: For U.S. AYA without identified risk factors, a one-time routine HIV screen at age 25, after the peak of incidence, would optimize clinical outcomes and be cost-effective compared with current U.S. screening practices. Focusing screening on AYA ages 18 or younger is a less efficient use of a one-time screen among AYA than screening at a later age.

      37. Large outbreak of Neisseria meningitidis serogroup C – Nigeria, December 2016-June 2017
        Nnadi C, Oladejo J, Yennan S, Ogunleye A, Agbai C, Bakare L, Abdulaziz M, Mohammed A, Stephens M, Sumaili K, Ronveaux O, Maguire H, Karch D, Dalhat M, Antonio M, Bita A, Okudo I, Nguku P, Novak R, Bolu O, Shuaib F, Ihekweazu C.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1352-1356.
        On February 16, 2017, the Ministry of Health in Zamfara State, in northwestern Nigeria, notified the Nigeria Centre for Disease Control (NCDC) of an increased number of suspected cerebrospinal meningitis (meningitis) cases reported from four local government areas (LGAs). Meningitis cases were subsequently also reported from Katsina, Kebbi, Niger, and Sokoto states, all of which share borders with Zamfara State, and from Yobe State in northeastern Nigeria. On April 3, 2017, NCDC activated an Emergency Operations Center (EOC) to coordinate rapid development and implementation of a national meningitis emergency outbreak response plan. After the outbreak was reported, surveillance activities for meningitis cases were enhanced, including retrospective searches for previously unreported cases, implementation of intensified new case finding, and strengthened laboratory confirmation. A total of 14,518 suspected meningitis cases were reported for the period December 13, 2016-June 15, 2017. Among 1,339 cases with laboratory testing, 433 (32%) were positive for bacterial pathogens, including 358 (82.7%) confirmed cases of Neisseria meningitidis serogroup C. In response, approximately 2.1 million persons aged 2-29 years were vaccinated with meningococcal serogroup C-containing vaccines in Katsina, Sokoto, Yobe, and Zamfara states during April-May 2017. The outbreak was declared over on June 15, 2017, after high-quality surveillance yielded no evidence of outbreak-linked cases for 2 consecutive weeks. Routine high-quality surveillance, including a strong laboratory system to test specimens from persons with suspected meningitis, is critical to rapidly detect and confirm future outbreaks and inform decisions regarding response vaccination.

      38. The etiology and impact of co-infections in children hospitalized with community-acquired pneumonia
        Nolan VG, Arnold SR, Bramley AM, Ampofo K, Williams DJ, Grijalva CG, Self WH, Anderson EJ, Wunderink RG, Edwards KM, Pavia AT, Jain S, McCullers JA.
        J Infect Dis. 2017 Dec 8.
        Background: Recognition that co-infections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. Methods: We analyzed data from 2219 children hospitalized with CAP and compared demographics, clinical characteristics, and outcomes between groups with viruses alone, bacteria alone, or co-infections. We also assessed the frequency of selected pairings of co-detected pathogens and their clinical characteristics. Results: 576 (26%) of the children studied had a co-infection. Children with only virus detection were younger and more likely to be black and have co-morbidities such as asthma compared to those with bacteria alone. Children with virus-bacteria co-infections had a higher frequency of leukocytosis, consolidation on chest X-ray, increased length of stay, and more frequent parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation when compared to viruses alone. Virus-virus co-infections were generally comparable to single virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. Conclusions: Co-infections occurred in 26% of children hospitalized for CAP. Children with bacterial infections, alone or complicated by a virus, have worse outcomes than children infected with a virus alone.

      39. Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews
        Nurse-Findlay S, Taylor MM, Savage M, Mello MB, Saliyou S, Lavayen M, Seghers F, Campbell ML, Birgirimana F, Ouedraogo L, Newman Owiredu M, Kidula N, Pyne-Mercier L.
        PLoS Med. 2017 Dec;14(12):e1002473.
        BACKGROUND: Benzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing to these shortages. METHODS AND FINDINGS: Country-level data about BPG shortages were collected using 3 survey approaches. First, a survey designed by the WHO Department of Reproductive Health and Research was distributed to 41 countries and territories in the Americas and 41 more in Africa. Second, WHO conducted an email survey of 28 US Centers for Disease Control and Prevention country directors. An additional 13 countries were in contact with WHO for related congenital syphilis prevention activities and also reported on BPG shortages. Third, the Clinton Health Access Initiative (CHAI) collected data from 14 countries (where it has active operations) to understand the extent of stock-outs, in-country purchasing, usage behavior, and breadth of available purchasing options to identify stock-outs worldwide. CHAI also conducted in-person interviews in the same 14 countries to understand the extent of stock-outs, in-country purchasing and usage behavior, and available purchasing options. CHAI also completed a desk review of 10 additional high-income countries, which were also included. BPG shortages were attributable to shortfalls in supply, demand, and procurement in the countries assessed. This assessment should not be considered globally representative as countries not surveyed may also have experienced BPG shortages. Country contacts may not have been aware of BPG shortages when surveyed or may have underreported medication substitutions due to desirability bias. Funding for the purchase of BPG by countries was not evaluated. In all, 114 countries and territories were approached to provide information on BPG shortages occurring during 2014-2016. Of unique countries and territories, 95 (83%) responded or had information evaluable from public records. Of these 95 countries and territories, 39 (41%) reported a BPG shortage, and 56 (59%) reported no BPG shortage; 10 (12%) countries with and without BPG shortages reported use of antibiotic alternatives to BPG for treatment of maternal syphilis. Market exits, inflexible production cycles, and minimum order quantities affect BPG supply. On the demand side, inaccurate forecasts and sole sourcing lead to under-procurement. Clinicians may also incorrectly prescribe BPG substitutes due to misperceptions of quality or of the likelihood of adverse outcomes. CONCLUSIONS: Targets for improvement include drug forecasting and procurement, and addressing provider reluctance to use BPG. Opportunities to improve global supply, demand, and use of BPG should be prioritized alongside congenital syphilis elimination efforts.

      40. Notes from the field: Use of asynchronous video directly observed therapy for treatment of tuberculosis and latent tuberculosis infection in a long-term-care facility – Puerto Rico, 2016-2017
        Olano-Soler H, Thomas D, Joglar O, Rios K, Torres-Rodriguez M, Duran-Guzman G, Chorba T.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 22;66(50):1386-1387.

        [No abstract]

      41. Reduction of injection-related risk behaviors following emergency implementation of a syringe services program during an HIV outbreak
        Patel MR, Foote C, Duwve J, Chapman E, Combs B, Fry A, Hall P, Roseberry J, Brooks JT, Broz D.
        J Acquir Immune Defic Syndr. 2017 Dec 15.
        OBJECTIVE: To describe injection-related HIV risk behaviors pre- and post-implementation of an emergency syringe services program (SSP) in Scott County, Indiana, following an HIV outbreak among persons who inject drugs (PWID). DESIGN: Mixed methods retrospective pre-post intervention analysis. METHODS: We analyzed routine SSP program data collected at first and most recent visit among clients with >/=2 visits, >/=7 days apart from April 4 to August 30, 2015 to quantify changes in injection-related risk behaviors. We also analyzed qualitative data collected from 56 PWID recruited in Scott County to understand factors contributing to these behaviors. RESULTS: SSP clients included in our analysis (n=148, 62% of all SSP clients) reported significant (p <0.001) reductions over a median 10 weeks (range 1-23) in syringe sharing to inject (18% to 2%) and divide drugs (19% to 4%), sharing other injection equipment (e.g., cookers) (24% to 5%), and number of uses of the same syringe (2 [IQR: 1-4] to 1 [IQR: 1-1]). Qualitative study participants described access to sterile syringes and safer injection education through the SSP, as explanatory factors for these reductions. Injection frequency findings were mixed, but overall suggested no change. The number of syringes returned by SSP clients increased from 0 at first visit to median 57. All qualitative study participants reported using sharps containers provided by the SSP. CONCLUSIONS: Analyses of an SSP program and in-depth qualitative interview data showed rapid reduction of injection-related HIV risk behaviors among PWID post-SSP implementation. Sterile syringe access as part of comprehensive HIV prevention is an important tool to control and prevent HIV outbreaks.

      42. Expansion of viral load testing and the potential impact on HIV drug resistance
        Raizes E, Hader S, Birx D.
        J Infect Dis. 2017 Dec 1;216(suppl_9):S805-s807.
        The US President’s Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation.

      43. Adolescent access to care and risk of early mother-to-child HIV transmission
        Ramraj T, Jackson D, Dinh TH, Olorunju S, Lombard C, Sherman G, Puren A, Ramokolo V, Noveve N, Singh Y, Magasana V, Bhardwaj S, Cheyip M, Mogashoa M, Pillay Y, Goga AE.
        J Adolesc Health. 2017 Dec 19.
        PURPOSE: Adolescent females aged 15-19 account for 62% of new HIV infections and give birth to 16 million infants annually. We quantify the risk of early mother-to-child transmission (MTCT) of HIV among adolescents enrolled in nationally representative MTCT surveillance studies in South Africa. METHODS: Data from 4,814 adolescent (</=19 years) and 25,453 adult (>/=20 years) mothers and their infants aged 4-8 weeks were analyzed. These data were gathered during three nationally representative, cross-sectional, facility-based surveys, conducted in 2010, 2011-2012, and 2012-2013. All infants were tested for HIV antibody (enzyme immunoassay), to determine HIV exposure. Enzyme immunoassay-positive infants or those born to self-reported HIV-positive mothers were tested for HIV infection (total nucleic acid polymerase chain reaction). Maternal HIV positivity was inferred from infant HIV antibody positivity. All analyses were weighted for sample realization and population live births. RESULTS: Adolescent mothers, compared with adult mothers, have almost three times less planned pregnancies 14.4% (95% confidence interval [CI]: 12.5-16.5) versus 43.9% (95% CI: 42.0-45.9) in 2010 and 15.2% (95% CI: 13.0-17.9) versus 42.8% (95% CI: 40.9-44.6) in 2012-2013 (p < .0001), less prevention of MTCT uptake (odds ratio [OR] in favor of adult mothers = 3.36, 95% CI: 2.95-3.83), and higher early MTCT (adjusted OR = 3.0, 95% CI: 1.1-8.0), respectively. Gestational age at first antenatal care booking was the only significant predictor of early MTCT among adolescents. CONCLUSIONS: Interventions that appeal to adolescents and initiate sexual and reproductive health care early should be tested in low- and middle-income settings to reduce differential service uptake and infant outcomes between adolescent and adult mothers.

      44. PURPOSE: With HIV and sexually transmitted disease (STD) rates disproportionately high among adolescent sexual minority males (ASMM), it is important to understand how school-based sexual health education may relate to sexual risk-related behavior among this population. This analysis explores reported HIV/AIDS- and condom-related education and sexual risk-related behaviors among ASMM and their adolescent non-sexual-minority male (non-ASMM) peers. METHODS: Students (n = 11,681) from seven Florida high schools completed paper-and-pencil questionnaires. A matched analytic sample of ASMM and non-ASMM students was created by using propensity score-matching techniques (n = 572). Logistic regressions controlling for individual and school characteristics examined reporting having been taught about AIDS or HIV in school, having been taught in school about using condoms, condom use at last sex, HIV/STD testing, and associations between these variables. RESULTS: Compared with matched non-ASMM peers, ASMM students were less likely to report having been taught about AIDS or HIV in school (odds ratio [OR] = 0.58, P = 0.04) and having used a condom at last sex (OR = 0.39, P < 0.01), but were more likely to report having been tested for HIV or STDs (OR = 1.88, P = 0.02). There were no significant differences for reporting having been taught in school about using condoms. Among non-ASMM, reporting having been taught in school about using condoms was associated with a greater likelihood of condom use at last sex (OR = 4.78, P < 0.01); this was not seen for ASMM. CONCLUSIONS: Differential reports of receiving HIV/AIDS education and differential associations between condom-related education and condom use in ASMM and non-ASMM suggest that sexual health education in schools may not be resonating with ASMM and non-ASMM in the same way.

      45. The etiology of male urethral discharge in Zimbabwe: Results from the Zimbabwe STI Etiology Study
        Rietmeijer CA, Mungati M, Machiha A, Mugurungi O, Kupara V, Rodgers L, Kilmarx PH, Roloff AH, Gonese E, Tippett-Barr BA, Shambira G, Lewis DA, Handsfield HH, Tshimanga M.
        Sex Transm Dis. 2018 Jan;45(1):56-60.
        INTRODUCTION: Sexually transmitted infections (STIs) are managed syndromically in most developing countries. In Zimbabwe, men presenting with urethral discharge are treated with a single intramuscular dose of kanamycin or ceftriaxone in combination with a week’s course of oral doxycycline. This study was designed to assess the current etiology of urethral discharge and other STIs to inform current syndromic management regimens. METHODS: We conducted a study among 200 men with urethral discharge presenting at 6 regionally diverse STI clinics in Zimbabwe. Urethral specimens were tested by multiplex polymerase chain reaction testing for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. In addition, serologic testing for syphilis and HIV was performed. RESULTS: Among the 200 studied men, one or more pathogens were identified in 163 (81.5%) men, including N. gonorrhoeae in 147 (73.5%), C. trachomatis in 45 (22.5%), T. vaginalis in 8 (4.0%), and M. genitalium in 7 (3.5%). Among all men, 121 (60%) had a single infection, 40 (20%) had dual infections, and 2 (1%) had 3 infections. Among the 45 men with C. trachomatis, 36 (80%) were coinfected with N. gonorrhoeae. Overall, 156 (78%) men had either N. gonorrhoeae or C. trachomatis identified. Of 151 men who consented to HIV testing, 43 (28.5%) tested positive. There were no differences in HIV status by study site or by urethral pathogen detected. CONCLUSIONS: Among men presenting at Zimbabwe STI clinics with urethral discharge, N. gonorrhoeae and C. trachomatis are the most commonly associated pathogens. Current syndromic management guidelines seem to be adequate for the treatment for symptomatic men, but future guidelines must be informed by ongoing monitoring of gonococcal resistance.

      46. BACKGROUND: Primary HPV testing (without the Pap test) has recently been recommended as a cervical cancer screening option in the United States. U.S. women’s awareness and acceptance of primary HPV testing were evaluated. METHODS: Data from a 2015 web-based survey of U.S. adults was examined. Analyses were limited to women who were >/=18years old, had not undergone a hysterectomy, had not been diagnosed with cervical cancer, and would accept cervical cancer screening (N=1309). Logistic regression was used to identify predictors of acceptance of primary HPV testing every 3years. RESULTS: Primary HPV testing every 3years was the least accepted cervical cancer screening option (13.5%), and annual Pap testing was the most accepted (41.2%). Most women (65.2%) reported that they were unsure how the HPV test is administered. HPV-vaccinated women were more likely to accept primary HPV testing every 3years than unvaccinated women (Adj OR=1.80, 95% CI=1.22-2.63, p=0.003). And, women who had participated in HPV testing at any interval were more likely to accept primary HPV testing every 3years than those who did not have regular HPV tests or were unsure how often they had HPV tests (Adj OR=1.74, 95% CI=1.20-2.52, p=0.003). CONCLUSIONS: Acceptance of primary HPV testing among U.S. women was low and associated with variables which may be indicative of general HPV awareness. Widespread adoption of primary HPV testing may require increasing women’s familiarity with the HPV test and screening guidelines.

      47. Rates and risk factors associated with hospitalization for pneumonia with ICU admission among adults
        Storms AD, Chen J, Jackson LA, Nordin JD, Naleway AL, Glanz JM, Jacobsen SJ, Weintraub ES, Klein NP, Gargiullo PM, Fry AM.
        BMC Pulm Med. 2017 Dec 16;17(1):208.
        BACKGROUND: Pneumonia poses a significant burden to the U.S. health-care system. However, there are few data focusing on severe pneumonia, particularly cases of pneumonia associated with specialized care in intensive care units (ICU). METHODS: We used administrative and electronic medical record data from six integrated health care systems to estimate rates of pneumonia hospitalizations with ICU admissions among adults during 2006 through 2010. Pneumonia hospitalization was defined as either a primary discharge diagnosis of pneumonia or a primary discharge diagnosis of sepsis or respiratory failure with a secondary diagnosis of pneumonia in administrative data. ICU admissions were collected from internal electronic medical records from each system. Comorbidities were identified by ICD-9-CM codes coded during the current pneumonia hospitalization, as well as during medical visits that occurred during the year prior to the date of admission. RESULTS: We identified 119,537 adult hospitalizations meeting our definition for pneumonia. Approximately 19% of adult pneumonia hospitalizations had an ICU admission. The rate of pneumonia hospitalizations requiring ICU admission during the study period was 76 per 100,000 population/year; rates increased for each age-group with the highest rates among adults aged >/=85 years. Having a co-morbidity approximately doubled the risk of ICU admission in all age-groups. CONCLUSIONS: Our study indicates a significant burden of pneumonia hospitalizations with an ICU admission among adults in our cohort during 2006 through 2010, especially older age-groups and persons with underlying medical conditions. These findings reinforce current strategies aimed to prevent pneumonia among adults.

      48. In a Perspective, Amitabh Suthar and Till Barnighausen discuss progress made so far in reducing HIV-related mortality in South Africa and keys towards further population mortality reductions going forward.

      49. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis
        Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N.
        Lancet Infect Dis. 2017 Dec 21.
        BACKGROUND: The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. METHODS: We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. FINDINGS: We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium’s total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. INTERPRETATION: Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori. FUNDING: World Health Organization.

      50. Influenza B virus infection and Stevens-Johnson syndrome
        Tamez RL, Tan WV, O’Malley JT, Broder KR, Garzon MC, LaRussa P, Lauren CT.
        Pediatr Dermatol. 2017 Dec 28.
        A 2-year-old boy with influenza B infection and rapidly worsening targetoid skin lesions with mucosal involvement was diagnosed with Stevens-Johnson syndrome (SJS) and treated with oseltamivir and intravenous immunoglobulin, with resolution of illness. Subsequent quadrivalent inactivated influenza vaccine was well tolerated. This case highlights the rarity of SJS in the setting of influenza B infection and addresses the safety of administering subsequent influenza vaccines to such individuals.

      51. Revisiting strategies to eliminate mother-to-child transmission of syphilis
        Taylor M, Gliddon H, Nurse-Findlay S, Laverty M, Broutet N, Pyne-Mercier L, Liljestrand J.
        Lancet Glob Health. 2018 Jan;6(1):e26-e28.

        [No abstract]

      52. The national burden of influenza-associated severe acute respiratory illness hospitalization in Zambia, 2011-2014
        Theo A, Tempia S, Cohen AL, Simusika P, Chentulo E, Chikamukwa CM, Monze M.
        Influenza Other Respir Viruses. 2017 Dec 15.
        BACKGROUND: Estimates of influenza-associated hospitalization are limited in low- and middle-income countries, especially in Africa. OBJECTIVE: To estimate the national number of influenza-associated severe acute respiratory illness (SARI) hospitalization in Zambia. METHODS: We conducted active prospective hospital-based surveillance for SARI at the University Teaching Hospital (UTH) situated in Lusaka Province during 2011-2014. Upper respiratory tract samples were tested for influenza virus using a reverse transcriptase polymerase chain reaction assay. We estimated age-specific rates of influenza-associated SARI hospitalizations for the UTH using census and secondary data on respiratory hospitalizations following estimation approaches recommended by the World Health Organization. We used the UTH hospitalization rates as a proxy for Lusaka Province. These rates were adjusted for each of the remaining 9 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. Rates were expressed per 100,000 population. RESULTS: SARI cases accounted for 77.1% (13 389/17 354) of respiratory admissions at the UTH; 82.7% (11 859/14 344) and 50.8% (1530/3010) among individuals aged <5 and >/=5 years, respectively. Among SARI cases tested, the influenza virus detection rate was 5.5% (152/2734), 4.8% (48/998), and 6.0% (104/1736) among individuals aged <5 and >/=5 years, respectively. The mean annual national number of influenza-associated SARI hospitalizations was 6181 (95% CI: 4321-8041-rate: 43.9; 95% CI: 30.7-57.1); 4669 (95% CI: 3287-6051-rate: 187.7; 95% CI: 132.1-243.3) among children aged <5 years; and 1512 (95% CI: 1037-1987-rate: 13.1; 95% CI: 9.0-17.2) among individuals aged >/=5 years. CONCLUSIONS: The burden of influenza-associated SARI hospitalizations was substantial and was highest among children aged <5 years.

      53. Safety and efficacy of the PrePex device in HIV-positive men: A single-arm study in Zimbabwe
        Tshimanga M, Makunike-Chikwinya B, Mangwiro T, Tapiwa Gundidza P, Chatikobo P, Murenje V, Herman-Roloff A, Kilmarx PH, Holec M, Gwinji G, Mugurungi O, Murwira M, Xaba S, Barnhart S, Feldacker C.
        PLoS One. 2017 ;12(12):e0189146.
        METHODS: We aimed to determine if the adverse event (AE) rate was non-inferior to an AE rate of 2%, a rate considered the global standard of MC safety. Study procedures, AE definitions, and study staff were unchanged from previous PrePex Zimbabwe trials. After PrePex placement and removal, weekly visits assessed wound healing. Men returned on Day 90. Safety was defined as occurrence of moderate and serious clinical AEs. Efficacy was defined as ability to reach the endpoint of complete circumcision. RESULTS: Among 400 healthy, HIV-positive, consenting adults, median age was 40 years (IQR: 34, 46); 79.5% in WHO stage 2; median CD4 was 336.5c/mul (IQR: 232, 459); 337 (85%) on anti-retroviral therapy. Among 385 (96%) observed completely healed, median days to complete healing was 42 (IQR: 35-49). There was no association between time to healing and CD4 (p = 0.66). Four study-related severe AEs and no moderate AEs were reported: severe/moderate AE rate of 1.0% (95% CI: 0.27% to 2.5). This was non-inferior to 2% AEs (p = 0.0003). All AEs were device displacements resulting in surgical MC and, subsequently, complete healing. CONCLUSION: Male circumcision among healthy, HIV-positive men using PrePex is safe and effective. Reducing the barrier of HIV testing while improving counseling for safer sex practices among all MC clients could increase MC uptake and avert more HIV infections.

      54. Effects of reaching national goals on HIV incidence, by race and ethnicity, in the United States
        Uzun Jacobson E, Hicks KA, Tucker EL, Farnham PG, Sansom SL.
        J Public Health Manag Pract. 2017 Dec 27.
        CONTEXT: Human immunodeficiency virus (HIV) incidence and prevalence in the United States are characterized by significant disparities by race/ethnicity. National HIV care goals, such as boosting to 90% the proportion of persons whose HIV is diagnosed and increasing to 80% the proportion of persons living with diagnosed HIV who are virally suppressed, will likely reduce HIV incidence, but their effects on HIV-related disparities are uncertain. OBJECTIVE: We sought to understand by race/ethnicity how current HIV care varies, the level of effort required to achieve national HIV care goals, and the effects of reaching those goals on HIV incidence and disparities. DESIGN: Using a dynamic model of HIV transmission, we identified 2016 progress along the HIV care continuum among blacks, Hispanics, and whites/others compared with national 2020 goals. We examined disparities over time. SETTING: United States. PARTICIPANTS: Beginning in 2006, our dynamic compartmental model simulated the sexually active US population 13 to 64 years of age, which was stratified into 195 subpopulations by transmission group, sex, race/ethnicity, age, male circumcision status, and HIV risk level. MAIN OUTCOME MEASURE: We compared HIV cumulative incidence from 2016 to 2020 when goals were reached compared with base case assumptions about progression along the HIV care continuum. RESULTS: The 2016 proportion of persons with diagnosed HIV who were on treatment and virally suppressed was 50% among blacks, 56% among Hispanics, and 61% among whites/others, compared with a national goal of 80%. When diagnosis, linkage, and viral suppression goals were reached in 2020, cumulative HIV incidence fell by 32% (uncertainty range: 18%-37%) for blacks, 25% (22%-31%) for Hispanics, and 25% (21%-28%) for whites/others. Disparity measures changed little. CONCLUSIONS: Achieving national HIV care goals will require different levels of effort by race/ethnicity but likely will result in substantial declines in cumulative HIV incidence. HIV-related disparities in incidence and prevalence may be difficult to resolve.

      55. Diagnostic importance of hyphae on heart valve tissue in Histoplasma endocarditis and treatment with isavuconazole
        Wiley Z, Woodworth MH, Jacob JT, Lockhart SR, Rouphael NG, Gullett JC, Guarner J, Workowski K.
        Open Forum Infect Dis. 2017 Fall;4(4):ofx241.
        A patient who never resided in an endemic area for dimorphic fungi was diagnosed with Histoplasma capsulatum endocarditis. His diagnosis was suggested by yeast and hyphae on cardiac valve tissue pathology. Isavuconazole was an optimal therapeutic option due to renal dysfunction and anticoagulation with warfarin for mechanical valve replacement.

      56. Using social media as a tool to predict syphilis
        Young SD, Mercer N, Weiss RE, Torrone EA, Aral SO.
        Prev Med. 2017 Dec 23.
        Syphilis rates have been rapidly rising in the United States. New technologies, such as social media, might be used to anticipate and prevent the spread of disease. Because social media data collection is easy and inexpensive, integration of social media data into syphilis surveillance may be a cost-effective surveillance strategy, especially in low-resource regions. People are increasingly using social media to discuss health-related issues, such as sexual risk behaviors, allowing social media to be a potential tool for public health and medical research. This study mined Twitter data to assess whether social media could be used to predict syphilis cases in 2013 based on 2012 data. We collected 2012 and 2013 county-level primary and secondary (P&S) and early latent syphilis cases reported to the Center for Disease Control and Prevention, along with >8500 geolocated tweets in the United States that were filtered to include sexual risk-related keywords, including colloquial terms for intercourse. We assessed the relationship between syphilis-related tweets and actual case reports by county, controlling for socioeconomic indicators and prior year syphilis cases. We found a significant positive relationship between tweets and cases of P&S and early latent syphilis. This study shows that social media may be an additional tool to enhance syphilis prediction and surveillance.

      57. Increases in acute hepatitis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014
        Zibbell JE, Asher AK, Patel RC, Kupronis B, Iqbal K, Ward JW, Holtzman D.
        Am J Public Health. 2017 Dec 21:e1-e7.
        OBJECTIVES: To compare US trends in rates of injection drug use (IDU), specifically opioid injection, with national trends in the incidence of acute HCV infection to assess whether these events correlated over time. METHODS: We calculated the annual incidence rate and demographic and risk characteristics of reported cases of acute HCV infection using surveillance data from 2004 to 2014 and the annual percentage of admissions to substance use disorder treatment facilities reporting IDU for the same time period by type of drug injected and demographic characteristics. We then tested for trends. RESULTS: The annual incidence rate of acute HCV infection increased more than 2-fold (from 0.3 to 0.7 cases/100 000) from 2004 to 2014, with significant increases among select demographic subgroups. Admissions for substance use disorder attributed to injection of heroin and prescription opioid analgesics increased significantly, with an almost 4-fold increase in prescription opioid analgesic injection. Significant increases in opioid injection mirrored those for reported cases of acute HCV infection among demographic subgroups. CONCLUSIONS: These findings strongly suggest that the national increase in acute HCV infection is related to the country’s opioid epidemic and associated increases in IDU. (Am J Public Health. Published online ahead of print December 21, 2017: e1-e7. doi:10.2105/AJPH.2017.304132).

    • Disaster Control and Emergency Services
      1. BACKGROUND: Mass casualty incidents may increase patient volume suddenly and dramatically, requiring hospitals to expeditiously manage bed inventories to release acute care beds for disaster victims. Electronic patient tracking systems combined with unit walk-throughs can identify patients for rapid discharge. The New York City (NYC) Department of Health and Mental Hygiene’s 2013 Rapid Patient Discharge Assessment (RPDA) aimed to determine the maximum number of beds NYC hospitals could make available through rapid patient discharge and to characterize discharge barriers. METHODS: Unit representatives identified discharge candidates within normal operations in round 1 and additional discharge candidates during a disaster scenario in round 2. Descriptive statistics were performed. RESULTS: Fifty-five NYC hospitals participated in the RPDA exercise; 45 provided discharge candidate counts in both rounds. Representatives identified 4225 patients through the RPDA: among these, 1138 (26.9%) were already confirmed for discharge; 1854 (43.9%) were round 1 discharge candidates; and 1233 (29.2%) were round 2 discharge candidates. These 4225 patients represented 21.4% of total bed capacity. Frequently reported barriers included missing prescriptions for aftercare or discharge orders. CONCLUSION: The NYC hospitals could implement rapid patient discharge to clear one-fifth of occupied inpatient beds for disaster victims, given they address barriers affecting patients’ safe and efficient discharge.

      2. Notes from the field: Monitoring out-of-state patients during a hurricane response using syndromic surveillance – Tennessee, 2017
        Wiedeman C, Shaffner J, Squires K, Leegon J, Murphree R, Petersen PE.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1364-1365.

        [No abstract]

    • Disease Reservoirs and Vectors
      1. Comparison of zoonotic bacterial agents in fleas collected from small mammals or host-seeking fleas from a Ugandan region where plague is endemic
        Bai Y, Osikowicz LM, Kosoy MY, Eisen RJ, Atiku LA, Mpanga JT, Boegler KA, Enscore RE, Gage KL.
        mSphere. 2017 Nov-Dec;2(6).
        Fleas (n = 407) were collected from small mammals trapped inside huts and surroundings of homesteads in five villages within the Arua and Zombo districts of Uganda. The most common flea species were Dinopsyllus lypusus (26%) and Xenopsylla cheopis (50%). Off-host fleas (n = 225) were collected inside huts by using Kilonzo flea traps. The majority of the off-host fleas were Ctenocephalides felis (80%). All fleas were examined for the presence of Bartonella spp., Rickettsia spp., and Yersinia spp. Bartonella DNA was detected in 91 fleas, with an overall prevalence of 14%. Bartonella prevalence was significantly higher in rodent or shrew fleas than in off-host fleas (22% versus 1%). The majority of Bartonella-positive fleas were of the species D. lypusus (61%), X. cheopis (20%), and Ctenophthalmus calceatus (14%). Sequencing analysis identified 12 Bartonella genetic variants, 9 of which belonged to the zoonotic pathogen B. elizabethae species complex. Rickettsia DNA was detected in 143 fleas, giving an overall prevalence of 23%, with a significantly higher prevalence in off-host fleas than in rodent or shrew fleas (56% versus 4%). The majority (88%) of Rickettsia-positive fleas were C. felis and were collected from Kilonzo traps, while a small portion (10%) were X. cheopis collected from rodents. Sequencing analysis identified six Rickettsia genogroups that belonged either to zoonotic R. felis or to the closely related “Candidatus Ricksettia asemboensis” and “Candidatus Ricksettia sengalensis.” Yersinia DNA was not detected in the fleas tested. These observations suggested that fleas in northwestern Uganda commonly carry the zoonotic agents B. elizabethae and R. felis and potentially play an important role in transmitting these infections to humans. IMPORTANCE Fleas play critical roles in transmitting some infections among animals and from animals to humans. Detection of pathogens in fleas is important to determine human risks for flea-borne diseases and can help guide diagnosis and treatment. Our findings of high prevalence rates of B. elizabethae and R. felis in fleas in the Arua and Zombo districts of Uganda implicate these agents as potential causative agents of undiagnosed febrile illnesses in this area.

      2. A molecular algorithm to detect and differentiate human pathogens infecting Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae)
        Graham CB, Maes SE, Hojgaard A, Fleshman AC, Sheldon SW, Eisen RJ.
        Ticks Tick Borne Dis. 2017 Dec 10.
        The incidence and geographic range of tick-borne illness associated with Ixodes scapularis and Ixodes pacificus have dramatically increased in recent decades. Anaplasmosis, babesiosis, and Borrelia spirochete infections, including Lyme borreliosis, account for tens of thousands of reported cases of tick-borne disease every year. Assays that reliably detect pathogens in ticks allow investigators and public health agencies to estimate the geographic distribution of human pathogens, assess geographic variation in their prevalence, and evaluate the effectiveness of prevention strategies. As investigators continue to describe new species within the Borrelia burgdorferi sensu lato complex and to recognize some Ixodes-borne Borrelia species as human pathogens, assays are needed to detect and differentiate these species. Here we describe an algorithm to detect and differentiate pathogens in unfed I. scapularis and I. pacificus nymphs including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi sensu stricto, Borrelia mayonii, and Borrelia miyamotoi. The algorithm comprises 5 TaqMan real-time polymerase chain reaction assays and 3 sequencing protocols. It employs multiple targets for each pathogen to optimize specificity, a gene target for I. scapularis and I. pacificus to verify tick-derived DNA quality, and a pan-Borrelia target to detect Borrelia species that may emerge as human disease agents in the future. We assess the algorithm’s sensitivity, specificity, and performance on field-collected ticks.

    • Drug Safety
      1. Primary care provider perceptions and practices regarding dosing units for oral liquid medications
        Lovegrove MC, Sapiano MR, Paul IM, Yin HS, Wilkins TL, Budnitz DS.
        Acad Pediatr. 2017 Dec 18.
        INTRODUCTION: To prevent errors, healthcare professional and safety organizations recommend using milliliters (mL) alone for oral liquid medication dosing instructions and devices. In 2018, for federal incentives under the Quality Payment Program, one requirement is for Electronic Health Records (EHRs) to automatically use mL alone whenever oral liquid medications are prescribed. Current perceptions and practices of primary care providers (PCPs) regarding dosing units for oral liquid medications were assessed. METHODS: Pediatricians, family practitioners, nurse practitioners, and internists participating in the 2015 DocStyles web-based survey were asked about their perceptions and practices regarding dosing units for oral liquid medications. RESULTS: Three-fifths of PCPs (59.0%) reported that using mL alone is safest for dosing oral liquid medications; however, nearly three-quarters (72.0%) thought that patients/caregivers prefer instructions that include spoon-based units. Within each specialty, fewer PCPs reported they would prescribe using mL alone than reported that using mL alone is safest (P<.0001 for all). Among PCPs who think mL-only dosing is safest, those who perceived patients/caregivers prefer spoon-based units were less likely to prescribe using mL alone (odds ratio: 0.45, 95% CI: 0.34-0.59). Pediatricians were more likely than other PCPs to report that it is safest to use mL alone (80.8% vs 54.7%) and that they would use mL alone when prescribing (56.8% vs 30.9%) (P<.0001 for both). CONCLUSIONS: Because fewer than two-thirds of pediatricians and one-third of other PCPs would use mL alone in dosing instructions, additional education to encourage prescribing and communicating with patients/caregivers using mL alone may be needed.

      2. Outpatient macrolide antibiotic prescribing in the United States, 2008-2011
        Sanchez GV, Shapiro DJ, Hersh AL, Hicks LA, Fleming-Dutra KE.
        Open Forum Infect Dis. 2017 Fall;4(4):ofx220.
        National Ambulatory Medical Care Survey data were used to assess outpatient macrolide prescribing and selection. Conditions for which macrolides are firstline therapy represented 5% of macrolide prescribing. Family practitioners selected macrolides for children more frequently than pediatricians. Macrolides are an important antibiotic stewardship target.

    • Environmental Health
      1. Polychlorinated biphenyls, indicators of thyroid function and thyroid autoantibodies in the Anniston Community Health Survey I (ACHS-I)
        Benson K, Yang E, Dutton N, Sjodin A, Rosenbaum PF, Pavuk M.
        Chemosphere. 2017 Dec 9;195:156-165.
        In this study, we examined associations between serum concentrations of 35 polychlorinated biphenyl (PCB) congeners, pesticides, and indicators of thyroid function in participants of the Anniston Community Health Survey (ACHS). Study subjects lived in the vicinity of a former PCB production facility and had PCB concentrations 2 to 3 times higher than similar age and race groups from the general population. We investigated associations among serum levels of thyroid hormones (thyroxin [T4], free thyroxin [fT4], triiodothyronine [T3], thyroid stimulation hormone [TSH]) and auto-antibodies (thyroglobulin antibody [TgAb] or thyroperoxidase antibody [TPOAb]) and combined indicators of thyroid function with the sum of PCBs, varying PCB groups, individual PCB congeners, and 8 pesticides. Logistic and linear regression models were adjusted for log10 transformed total lipids, age, sex, ethnicity, BMI, smoking, and family history of thyroid disease. We also performed analyses stratified by ethnicity and sex. Linear regression showed inverse associations between TT3 and thyroid-like PCBs (sum of PCBs 28, 52, 74, 101, 105, and 118; p = .0004), two pesticides (hexachlorobenzene, and pp’-DDE), and individual congeners (PCBs 74, 105). Null associations were observed between PCBs, pesticides, TSH, TT4, and fT4. Logistic regression analyses did not provide support for TT3 findings and found no association with other thyroid hormones, antibodies, or combined indicator of thyroid function. These results suggest there is little evidence that these chemicals have any major clinical effect on thyroid function in this highly PCB exposed population.

      2. Distribution of Legionella and bacterial community composition among regionally diverse US cooling towers
        Llewellyn AC, Lucas CE, Roberts SE, Brown EW, Nayak BS, Raphael BH, Winchell JM.
        PLoS One. 2017 ;12(12):e0189937.
        Cooling towers (CTs) are a leading source of outbreaks of Legionnaires’ disease (LD), a severe form of pneumonia caused by inhalation of aerosols containing Legionella bacteria. Accordingly, proper maintenance of CTs is vital for the prevention of LD. The aim of this study was to determine the distribution of Legionella in a subset of regionally diverse US CTs and characterize the associated microbial communities. Between July and September of 2016, we obtained aliquots from water samples collected for routine Legionella testing from 196 CTs located in eight of the nine continental US climate regions. After screening for Legionella by PCR, positive samples were cultured and the resulting Legionella isolates were further characterized. Overall, 84% (164) were PCR-positive, including samples from every region studied. Of the PCR-positive samples, Legionella spp were isolated from 47% (78), L. pneumophila was isolated from 32% (53), and L. pneumophila serogroup 1 (Lp1) was isolated from 24% (40). Overall, 144 unique Legionella isolates were identified; 53% (76) of these were Legionella pneumophila. Of the 76 L. pneumophila isolates, 51% (39) were Lp1. Legionella were isolated from CTs in seven of the eight US regions examined. 16S rRNA amplicon sequencing was used to compare the bacterial communities of CT waters with and without detectable Legionella as well as the microbiomes of waters from different climate regions. Interestingly, the microbial communities were homogenous across climate regions. When a subset of seven CTs sampled in April and July were compared, there was no association with changes in corresponding CT microbiomes over time in the samples that became culture-positive for Legionella. Legionella species and Lp1 were detected frequently among the samples examined in this first large-scale study of Legionella in US CTs. Our findings highlight that, under the right conditions, there is the potential for CT-related LD outbreaks to occur throughout the US.

      3. Urinary concentrations of polycyclic aromatic hydrocarbon metabolites in mate drinkers in Rio Grande do Sul, Brazil
        Lopes AB, Metzdorf M, Metzdorf L, Ramalho MP, Kavalco C, Etemadi A, Pritchett NR, Murphy G, Calafat AM, Abnet CC, Dawsey SM, Fagundes RB.
        Cancer Epidemiol Biomarkers Prev. 2017 Dec 20.
        BACKGROUND: Consumption of mate, an infusion of the herb Ilex paraguariensis (yerba mate), is associated with increased risk of esophageal squamous cell carcinoma (ESCC), but the carcinogenic mechanism is unclear. Commercial brands of yerba mate contain high levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are acquired during the traditional drying process. The purpose of this study was to characterize exposure to PAHs in mate drinkers over a wide range of mate consumption. METHODS: We recruited 244 adults who answered a questionnaire and collected a fasting spot urine specimen. We quantified urinary concentrations of seven PAH metabolites, and assessed associations between self-reported recent mate consumption and urinary PAH metabolites by multivariate regression. RESULTS: Recent mate consumption showed a significant dose-response association with 6 of 7 PAH metabolites in unadjusted models (p-for-trend <0.05). After adjustment for creatinine and potential confounders, concentrations of 2-naphthol, 1-hydroxyphenanthrene, and the sum of 2- and 3-hydroxyphenanthrene remained significantly associated with recent mate intake. The sum of the urinary concentrations of the phenanthrene metabolites was similar or higher among mate drinkers who did not smoke than among smokers who did not drink mate. CONCLUSIONS: Urinary concentrations of PAH metabolites were significantly associated with self-reported amount of recent mate intake, and drinking mate increased urinary concentrations of some PAH metabolites as much as smoking cigarettes. IMPACT: Drinking mate is a source of exposure to potentially carcinogenic PAHs, consistent with the hypothesis that the PAH content of mate may contribute to the increased risk of ESCC in mate drinkers.

      4. Background -Most U.S. studies of mortality and air pollution have been conducted on largely non-Hispanic white study populations. However, many health and mortality outcomes differ by race and ethnicity, and non-Hispanic white persons experience lower air pollution exposures than those who are non-Hispanic black or Hispanic. This study examines whether associations between air pollution and heart disease mortality differ by race/ethnicity. Methods -We used data from the 1997-2009 National Health Interview Survey linked to mortality records through December 2011 and annual estimates of fine particulate matter (PM2.5) by Census tract. Proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between PM2.5 (per 10 mug/m(3)) and heart disease mortality using the full sample and the sample adults, which have information on additional health variables. Interaction terms were used to examine differences in the PM2.5-mortality association by race/ethnicity. Results -Overall, 65,936 of the full sample died during follow-up and 22,152 died from heart disease. After adjustment for several factors, we found a significant positive association between PM2.5 and heart disease mortality (HR 1.16 95% CI 1.08-1.25). This association was similar in sample adults with adjustment for smoking and body mass index (HR 1.18 95% CI 1.06-1.31). Interaction terms for non-Hispanic black and Hispanic groups compared to the non-Hispanic white group were not statistically significant. Conclusions -Using a nationally representative sample, the association between PM2.5 and heart disease mortality was elevated and similar to previous estimates. Associations for non-Hispanic black and Hispanic adults were not statistically significantly different from that for non-Hispanic white adults.

      5. Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study
        Sack C, Vedal S, Sheppard L, Raghu G, Barr RG, Podolanczuk A, Doney B, Hoffman EA, Gassett A, Hinckley-Stukovsky K, Williams K, Kawut S, Lederer DJ, Kaufman JD.
        Eur Respir J. 2017 Dec;50(6).
        We studied whether ambient air pollution is associated with interstitial lung abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and quantitative measurements of subclinical interstitial lung disease (ILD) on computed tomography (CT).We performed analyses of community-based dwellers enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used cohort-specific spatio-temporal models to estimate ambient pollution (fine particulate matter (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2) and ozone (O3)) at each home. A total of 5495 participants underwent serial assessment of HAAs by cardiac CT; 2671 participants were assessed for ILAs using full lung CT at the 10-year follow-up. We used multivariable logistic regression and linear mixed models adjusted for age, sex, ethnicity, education, tobacco use, scanner technology and study site.The odds of ILAs increased 1.77-fold per 40 ppb increment in NOx (95% CI 1.06 to 2.95, p = 0.03). There was an overall trend towards an association between higher exposure to NOx and greater progression of HAAs (0.45% annual increase in HAAs per 40 ppb increment in NOx; 95% CI -0.02 to 0.92, p = 0.06). Associations of ambient fine particulate matter (PM2.5), NOx and NO2 concentrations with progression of HAAs varied by race/ethnicity (p = 0.002, 0.007, 0.04, respectively, for interaction) and were strongest among non-Hispanic white people.We conclude that ambient air pollution exposures were associated with subclinical ILD.

      6. The biomonitoring of Great Lakes Populations Program
        Wattigney WA, Li Z, Ragin-Wilson A.
        J Environ Health. 2017 Apr;79(8):42-44.

        [No abstract]

      7. Lessons learned from the Environmental Public Health Tracking Sub-County Data Pilot Project
        Werner AK, Strosnider H, Kassinger C, Shin M.
        J Public Health Manag Pract. 2017 Dec 7.
        OBJECTIVE: Small area data are key to better understanding the complex relationships between environmental health, health outcomes, and risk factors at a local level. In 2014, the Centers for Disease Control and Prevention’s National Environmental Public Health Tracking Program (Tracking Program) conducted the Sub-County Data Pilot Project with grantees to consider integration of sub-county data into the National Environmental Public Health Tracking Network (Tracking Network). DESIGN: The Tracking Program and grantees developed sub-county-level data for several data sets during this pilot project, working to standardize processes for submitting data and creating required geographies. Grantees documented challenges they encountered during the pilot project and documented decisions. RESULTS: This article covers the challenges revealed during the project. It includes insights into geocoding, aggregation, population estimates, and data stability and provides recommendations for moving forward. CONCLUSION: National standards for generating, analyzing, and sharing sub-county data should be established to build a system of sub-county data that allow for comparison of outcomes, geographies, and time. Increasing the availability and accessibility of small area data will not only enhance the Tracking Network’s capabilities but also contribute to an improved understanding of environmental health and informed decision making at a local level.

      8. Prenatal and childhood perfluoroalkyl substances exposures and children’s reading skills at ages 5 and 8years
        Zhang H, Yolton K, Webster GM, Ye X, Calafat AM, Dietrich KN, Xu Y, Xie C, Braun JM, Lanphear BP, Chen A.
        Environ Int. 2017 Dec 11;111:224-231.
        BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may impact children’s neurodevelopment. OBJECTIVE: To examine the association of prenatal and early childhood serum PFAS concentrations with children’s reading skills at ages 5 and 8years. METHODS: We used data from 167 mother-child pairs recruited during pregnancy (2003-2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16+/-3weeks of gestation and childhood sera at ages 3 and 8years. We assessed children’s reading skills using Woodcock-Johnson Tests of Achievement III at age 5years and Wide Range Achievement Test-4 at age 8years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. RESULTS: Median serum PFASs concentrations were PFOS>PFOA>PFHxS>PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children’s reading scores at ages 5 and 8years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children’s scores in Reading Composite (beta: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (beta: 4.2, 95% CI: 0.5, 8.0) at age 8years; b) 3-year PFOA was positively associated with higher children’s scores in Brief Reading (beta: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (beta: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (beta: 5.9, 95% CI: 1.5, 10.2) at age 5years; c) 8-year PFOA was positively associated with higher children’s Word Reading scores (beta: 5.8, 95% CI: 0.8, 10.7) at age 8years. Prenatal PFOS and PFNA were positively associated with children’s reading abilities at age 5years, but not at age 8years; 3-year PFOS and PFNA were positively associated with reading scores at age 5years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. CONCLUSION: Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children’s reading skills at ages 5 and 8years, but no association was found between serum PFHxS and reading skills.

    • Epidemiology and Surveillance
      1. An assessment of information exchange practices, challenges, and opportunities to support US disease surveillance in 3 states
        Garcia MC, Garrett NY, Singletary V, Brown S, Hennessy-Burt T, Haney G, Link K, Tripp J, Mac Kenzie WR, Yoon P.
        J Public Health Manag Pract. 2017 Dec 7.
        BACKGROUND: State and local public health agencies collect and use surveillance data to identify outbreaks, track cases, investigate causes, and implement measures to protect the public-s health through various surveillance systems and data exchange practices. PURPOSE: The purpose of this assessment was to better understand current practices at state and local public health agencies for collecting, managing, processing, reporting, and exchanging notifiable disease surveillance information. METHODS: Over an 18-month period (January 2014-June 2015), we evaluated the process of data exchange between surveillance systems, reporting burdens, and challenges within 3 states (California, Idaho, and Massachusetts) that were using 3 different reporting systems. RESULTS: All 3 states use a combination of paper-based and electronic information systems for managing and exchanging data on reportable conditions within the state. The flow of data from local jurisdictions to the state health departments varies considerably. When state and local information systems are not interoperable, manual duplicative data entry and other work-arounds are often required. The results of the assessment show the complexity of disease reporting at the state and local levels and the multiple systems, processes, and resources engaged in preparing, processing, and transmitting data that limit interoperability and decrease efficiency. CONCLUSIONS: Through this structured assessment, the Centers for Disease Control and Prevention (CDC) has a better understanding of the complexities for surveillance of using commercial off-the-shelf data systems (California and Massachusetts), and CDC-developed National Electronic Disease Surveillance System Base System. More efficient data exchange and use of data will help facilitate interoperability between National Notifiable Diseases Surveillance Systems.

      2. Risk factors for hematemesis in Hoima and Buliisa districts, Western Uganda, September-October 2015
        Kabwama SN, Mafigiri R, Balinandi S, Kagirita A, Riolexus AA, Zhu BP.
        Pan African Medical Journal. 2017 08 Nov;28(215).
        Introduction: On 17 September 2015, Buliisa District Health Office reported multiple deaths due to haemorrhage to the Uganda Ministry of Health. We conducted an investigation to verify the existence of an outbreak and to identify the disease nature, mode of transmission and risk factors. Methods: We defined a suspected case as onset of hematemesis between 1 June 2015 and 15 October 2015 in a resident of Hoima, Buliisa or neighbouring districts. We identified cases by reviewing medical records and actively searching in the community. We interviewed case-patients and health-care workers and performed descriptive epidemiology to generate hypotheses on possible exposures. In a case-control study we compared exposures between 21 cases and 81 controls, matched by age (+/- 10 years), sex and village of residence. We collected 22 biological specimens from 19 case-patients to test for Viral Haemorrhagic Fevers (VHF). We analysed the data using the Mantel-Haenszel method to account for the matched study design. Results: We identified 56 cases with onset from June to October (attack rate 15/100,000 in Buliisa District and 5.2/100,000 in Hoima District). The age-specific attack rate was highest in persons aged 31-60 years (15/100,000 in Hoima and 47/100,000 in Buliisa); no persons below 15 years of age had the illness. In the case-control study, 42% (5/12) of cases vs. 0.0% (0/77) of controls had liver disease (ORM-H = ; 95%CI = 3.7-); 71% (10/14) of cases vs. 35% (28/81) of controls had ulcer disease (ORM-H = 13; 95% CI = 1.6-98); 27% (3/11) of cases vs. 14% (11/81) of controls used indomethacin prior to disease onset (ORM-H= 6.0; 95% CI = 1.0-36). None of the blood samples were positive for any of the VHFs. Conclusion: This reported cluster of hematemesis illness was due to predisposing conditions and use of Non- Steroidal Anti-inflammatory Drugs (NSAID). Health education should be conducted on the danger of NSAIDs misuse, especially in persons with pre-disposing conditions.

      3. CDC Grand Rounds: National Amyotrophic Lateral Sclerosis (ALS) Registry impact, challenges, and future directions
        Mehta P, Horton DK, Kasarskis EJ, Tessaro E, Eisenberg MS, Laird S, Iskander J.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 22;66(50):1379-1382.
        Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2-5 years of diagnosis, though survival time varies depending on disease progression. For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy metals, pesticides) and occupational history.

      4. Collection of data on race, ethnicity, language, and nativity by US Public Health Surveillance and Monitoring Systems: Gaps and opportunities
        Rodriguez-Lainz A, McDonald M, Fonseca-Ford M, Penman-Aguilar A, Waterman SH, Truman BI, Cetron MS, Richards CL.
        Public Health Rep. 2017 Jan 1:33354917745503.
        OBJECTIVE: Despite increasing diversity in the US population, substantial gaps in collecting data on race, ethnicity, primary language, and nativity indicators persist in public health surveillance and monitoring systems. In addition, few systems provide questionnaires in foreign languages for inclusion of non-English speakers. We assessed (1) the extent of data collected on race, ethnicity, primary language, and nativity indicators (ie, place of birth, immigration status, and years in the United States) and (2) the use of data-collection instruments in non-English languages among Centers for Disease Control and Prevention (CDC)-supported public health surveillance and monitoring systems in the United States. METHODS: We identified CDC-supported surveillance and health monitoring systems in place from 2010 through 2013 by searching CDC websites and other federal websites. For each system, we assessed its website, documentation, and publications for evidence of the variables of interest and use of data-collection instruments in non-English languages. We requested missing information from CDC program officials, as needed. RESULTS: Of 125 data systems, 100 (80%) collected data on race and ethnicity, 2 more collected data on ethnicity but not race, 26 (21%) collected data on racial/ethnic subcategories, 40 (32%) collected data on place of birth, 21 (17%) collected data on years in the United States, 14 (11%) collected data on immigration status, 13 (10%) collected data on primary language, and 29 (23%) used non-English data-collection instruments. Population-based surveys and disease registries more often collected data on detailed variables than did case-based, administrative, and multiple-source systems. CONCLUSIONS: More complete and accurate data on race, ethnicity, primary language, and nativity can improve the quality, representativeness, and usefulness of public health surveillance and monitoring systems to plan and evaluate targeted public health interventions to eliminate health disparities.

    • Food Safety
      1. Features of illnesses caused by five species of Campylobacter, Foodborne Diseases Active Surveillance Network (FoodNet) – 2010-2015
        Patrick ME, Henao OL, Robinson T, Geissler AL, Cronquist A, Hanna S, Hurd S, Medalla F, Pruckler J, Mahon BE.
        Epidemiol Infect. 2017 Dec 14:1-10.
        The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1.4), Asian (OR = 2.3), or Black (OR = 1.7), and more likely to live in an urban area (OR = 1.2), report international travel (OR = 1.5), and have infection in autumn or winter (OR = 1.2). Campylobacter upsaliensis patients were more likely female (OR = 1.6), Hispanic (OR = 1.6), have a blood isolate (OR = 2.8), and have an infection in autumn or winter (OR = 1.7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2.9) and have an infection in autumn or winter (OR = 1.7). Campylobacter fetus patients were more likely male (OR = 3.1), hospitalized (OR = 3.5), and have a blood isolate (OR = 44.1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12.5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.

    • Genetics and Genomics
      1. Transmissibility of intra-host hepatitis C virus variants
        Campo DS, Zhang J, Ramachandran S, Khudyakov Y.
        BMC Genomics. 2017 Dec 6;18(Suppl 10):881.
        BACKGROUND: Intra-host hepatitis C virus (HCV) populations are genetically heterogeneous and organized in subpopulations. With the exception of blood transfusions, transmission of HCV occurs via a small number of genetic variants, the effect of which is frequently described as a bottleneck. Stochasticity of transmission associated with the bottleneck is usually used to explain genetic differences among HCV populations identified in the source and recipient cases, which may be further exacerbated by intra-host HCV evolution and differential biological capacity of HCV variants to successfully establish a population in a new host. RESULTS: Transmissibility was formulated as a property that can be measured from experimental Ultra-Deep Sequencing (UDS) data. The UDS data were obtained from one large hepatitis C outbreak involving an epidemiologically defined source and 18 recipient cases. k-Step networks of HCV variants were constructed and used to identify a potential association between transmissibility and network centrality of individual HCV variants from the source. An additional dataset obtained from nine other HCV outbreaks with known directionality of transmission was used for validation. Transmissibility was not found to be dependent on high frequency of variants in the source, supporting the earlier observations of transmission of minority variants. Among all tested measures of centrality, the highest correlation of transmissibility was found with Hamming centrality (r = 0.720; p = 1.57 E-71). Correlation between genetic distances and differences in transmissibility among HCV variants from the source was found to be 0.3276 (Mantel Test, p = 9.99 E-5), indicating association between genetic proximity and transmissibility. A strong correlation ranging from 0.565-0.947 was observed between Hamming centrality and transmissibility in 7 of the 9 additional transmission clusters (p < 0.05). CONCLUSIONS: Transmission is not an exclusively stochastic process. Transmissibility, as formally measured in this study, is associated with certain biological properties that also define location of variants in the genetic space occupied by the HCV strain from the source. The measure may also be applicable to other highly heterogeneous viruses. Besides improving accuracy of outbreak investigations, this finding helps with the understanding of molecular mechanisms contributing to establishment of chronic HCV infection.

      2. Inference of genetic relatedness between viral quasispecies from sequencing data
        Glebova O, Knyazev S, Melnyk A, Artyomenko A, Khudyakov Y, Zelikovsky A, Skums P.
        BMC Genomics. 2017 Dec 6;18(Suppl 10):918.
        BACKGROUND: RNA viruses such as HCV and HIV mutate at extremely high rates, and as a result, they exist in infected hosts as populations of genetically related variants. Recent advances in sequencing technologies make possible to identify such populations at great depth. In particular, these technologies provide new opportunities for inference of relatedness between viral samples, identification of transmission clusters and sources of infection, which are crucial tasks for viral outbreaks investigations. RESULTS: We present (i) an evolutionary simulation algorithm Viral Outbreak InferenCE (VOICE) inferring genetic relatedness, (ii) an algorithm MinDistB detecting possible transmission using minimal distances between intra-host viral populations and sizes of their relative borders, and (iii) a non-parametric recursive clustering algorithm Relatedness Depth (ReD) analyzing clusters’ structure to infer possible transmissions and their directions. All proposed algorithms were validated using real sequencing data from HCV outbreaks. CONCLUSIONS: All algorithms are applicable to the analysis of outbreaks of highly heterogeneous RNA viruses. Our experimental validation shows that they can successfully identify genetic relatedness between viral populations, as well as infer transmission clusters and outbreak sources.

      3. Population genetic characterization of Cyclospora cayetanensis from discrete geographical regions
        Guo Y, Li N, Ortega Y, Zhang L, Roellig DM, Feng Y, Xiao L.
        Exp Parasitol. 2017 Dec 20.
        Cyclospora cayetanensis is an emerging pathogen that is endemic in developing countries and responsible for many large foodborne cyclosporiasis outbreaks in North America since 1990s. Because of the lack of typing targets, the genetic diversity and population genetics of C. cayetanensis have not been investigated. In this study, we undertook a population genetic analysis of multilocus sequence typing data we recently collected from 64 C. cayetanensis specimens. Despite the extensive genetic heterogeneity in the overall C. cayetanensis population, there were significant intra- and inter-genic linkage disequilibria (LD). A disappearance of LD was observed when only multilocus genotypes were included in the population genetic analysis, indicative of an epidemic nature of C. cayetanensis. Geographical segregation-associated sub-structuring was observed between specimens from China and those from Peru and the United States. The two subpopulations had reduced LD, indicating the likely occurrence of genetic exchange among isolates in endemic areas. Further analyses of specimens from other geographical regions are necessary to fully understand the population genetics of C. cayetanensis.

      4. An assessment of different genomic approaches for inferring phylogeny of Listeria monocytogenes
        Henri C, Leekitcharoenphon P, Carleton HA, Radomski N, Kaas RS, Mariet JF, Felten A, Aarestrup FM, Gerner Smidt P, Roussel S, Guillier L, Mistou MY, Hendriksen RS.
        Front Microbiol. 2017 ;8:2351.
        Background/objectives: Whole genome sequencing (WGS) has proven to be a powerful subtyping tool for foodborne pathogenic bacteria like L. monocytogenes. The interests of genome-scale analysis for national surveillance, outbreak detection or source tracking has been largely documented. The genomic data however can be exploited with many different bioinformatics methods like single nucleotide polymorphism (SNP), core-genome multi locus sequence typing (cgMLST), whole-genome multi locus sequence typing (wgMLST) or multi locus predicted protein sequence typing (MLPPST) on either core-genome (cgMLPPST) or pan-genome (wgMLPPST). Currently, there are little comparisons studies of these different analytical approaches. Our objective was to assess and compare different genomic methods that can be implemented in order to cluster isolates of L. monocytogenes. Methods: The clustering methods were evaluated on a collection of 207 L. monocytogenes genomes of food origin representative of the genetic diversity of the Anses collection. The trees were then compared using robust statistical analyses. Results: The backward comparability between conventional typing methods and genomic methods revealed a near-perfect concordance. The importance of selecting a proper reference when calling SNPs was highlighted, although distances between strains remained identical. The analysis also revealed that the topology of the phylogenetic trees between wgMLST and cgMLST were remarkably similar. The comparison between SNP and cgMLST or SNP and wgMLST approaches showed that the topologies of phylogenic trees were statistically similar with an almost equivalent clustering. Conclusion: Our study revealed high concordance between wgMLST, cgMLST, and SNP approaches which are all suitable for typing of L. monocytogenes. The comparable clustering is an important observation considering that the two approaches have been variously implemented among reference laboratories.

      5. From public health genomics to precision public health: a 20-year journey
        Khoury MJ, Bowen MS, Clyne M, Dotson WD, Gwinn ML, Green RF, Kolor K, Rodriguez JL, Wulf A, Yu W.
        Genet Med. 2017 Dec 14.
        In this paper, we review the evolution of the field of public health genomics in the United States in the past two decades. Public health genomics focuses on effective and responsible translation of genomic science into population health benefits. We discuss the relationship of the field to the core public health functions and essential services, review its evidentiary foundation, and provide examples of current US public health priorities and applications. We cite examples of publications to illustrate how Genetics in Medicine reflected the evolution of the field. We also reflect on how public-health genomics is contributing to the emergence of “precision public health” with near-term opportunities offered by the US Precision Medicine (AllofUs) Initiative.GENETICS in MEDICINE advance online publication, 14 December 2017; doi:10.1038/gim.2017.211.

      6. BACKGROUND: Identification of acute or recent hepatitis C virus (HCV) infections is important for detecting outbreaks and devising timely public health interventions for interruption of transmission. Epidemiological investigations and chemistry-based laboratory tests are 2 main approaches that are available for identification of acute HCV infection. However, owing to complexity, both approaches are not efficient. Here, we describe a new sequence alignment-free method to discriminate between recent (R) and chronic (C) HCV infection using next-generation sequencing (NGS) data derived from the HCV hypervariable region 1 (HVR1). RESULTS: Using dinucleotide auto correlation (DAC), we identified physical-chemical (PhyChem) features of HVR1 variants. Significant (p < 9.58 x 10(-4)) differences in the means and frequency distributions of PhyChem features were found between HVR1 variants sampled from patients with recent vs chronic (R/C) infection. Moreover, the R-associated variants were found to occupy distinct and discrete PhyChem spaces. A radial basis function neural network classifier trained on the PhyChem features of intra-host HVR1 variants accurately classified R/C-HVR1 variants (classification accuracy (CA) = 94.85%; area under the ROC curve, AUROC = 0.979), in 10-fold cross-validation). The classifier was accurate in assigning individual HVR1 variants to R/C-classes in the testing set (CA = 84.15%; AUROC = 0.912) and in detection of infection duration (R/C-class) in patients (CA = 88.45%). Statistical tests and evaluation of the classifier on randomly-labeled datasets indicate that classifiers’ CA is robust (p < 0.001) and unlikely due to random correlations (CA = 59.04% and AUROC = 0.50). CONCLUSIONS: The PhyChem features of intra-host HVR1 variants are strongly associated with the duration of HCV infection. Application of the PhyChem biomarkers to models for detection of the R/C-state of HCV infection in patients offers a new opportunity for detection of outbreaks and for molecular surveillance. The method will be available at to the authenticated users of Global Hepatitis Outbreak and Surveillance Technology (GHOST) for further testing and validation.

      7. Antigenic characterization of a novel recombinant GII.P16-GII.4 Sydney norovirus strain with minor sequence variation leading to antibody escape
        Lindesmith LC, Brewer-Jensen PD, Mallory ML, Debbink K, Swann EW, Vinje J, Baric RS.
        J Infect Dis. 2017 Dec 22.
        Background: Human noroviruses are the leading cause of acute gastroenteritis. Strains of the GII.4 genotype cause pandemic waves associated with viral evolution and subsequent antigenic drift and ligand binding modulation. In November 2015, a novel GII.4 Sydney recombinant variant (GII.P16-GII.4 Sydney) emerged and replaced GII.Pe-GII.4 Sydney as the predominant cause of acute gastroenteritis in the 2016-2017 season in the United States. Methods: Virus-like particles of GII.4 2012 and GII.4 2015 were compared for ligand binding and antibody reactivity using a surrogate neutralization assay. Results: Residue changes in the capsid between GII.4 2012 and GII.4 2015 decreased potency of human polyclonal sera and monoclonal antibodies. Change in epitope A resulted in complete loss of reactivity of a class of blockade antibodies and reduction of a second class. Epitope D changes modulated monoclonal antibody potency and ligand binding patterns. Conclusions: Substitutions in blockade antibody epitopes between GII.4 2012 and GII.4 2015 impacted antigenicity and ligand binding properties. Although the impact of polymerases on fitness remains uncertain, antigenic variation resulting in decreased potency of antibodies to epitope A coupled with altered ligand binding, likely contributed significantly to the spread of GII.4 2015 and replacement of GII.4 2012 as the predominant norovirus outbreak strain.

      8. GHOST: global hepatitis outbreak and surveillance technology
        Longmire AG, Sims S, Rytsareva I, Campo DS, Skums P, Dimitrova Z, Ramachandran S, Medrzycki M, Thai H, Ganova-Raeva L, Lin Y, Punkova LT, Sue A, Mirabito M, Wang S, Tracy R, Bolet V, Sukalac T, Lynberg C, Khudyakov Y.
        BMC Genomics. 2017 Dec 6;18(Suppl 10):916.
        BACKGROUND: Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections associated with unsafe injection practices, drug diversion, and other exposures to blood are difficult to detect and investigate. Effective HCV outbreak investigation requires comprehensive surveillance and robust case investigation. We previously developed and validated a methodology for the rapid and cost-effective identification of HCV transmission clusters. Global Hepatitis Outbreak and Surveillance Technology (GHOST) is a cloud-based system enabling users, regardless of computational expertise, to analyze and visualize transmission clusters in an independent, accurate and reproducible way. RESULTS: We present and explore performance of several GHOST implemented algorithms using next-generation sequencing data experimentally obtained from hypervariable region 1 of genetically related and unrelated HCV strains. GHOST processes data from an entire MiSeq run in approximately 3 h. A panel of seven specimens was used for preparation of six repeats of MiSeq libraries. Testing sequence data from these libraries by GHOST showed a consistent transmission linkage detection, testifying to high reproducibility of the system. Lack of linkage among genetically unrelated HCV strains and constant detection of genetic linkage between HCV strains from known transmission pairs and from follow-up specimens at different levels of MiSeq-read sampling indicate high specificity and sensitivity of GHOST in accurate detection of HCV transmission. CONCLUSIONS: GHOST enables automatic extraction of timely and relevant public health information suitable for guiding effective intervention measures. It is designed as a virtual diagnostic system intended for use in molecular surveillance and outbreak investigations rather than in research. The system produces accurate and reproducible information on HCV transmission clusters for all users, irrespective of their level of bioinformatics expertise. Improvement in molecular detection capacity will contribute to increasing the rate of transmission detection, thus providing opportunity for rapid, accurate and effective response to outbreaks of hepatitis C. Although GHOST was originally developed for hepatitis C surveillance, its modular structure is readily applicable to other infectious diseases. Worldwide availability of GHOST for the detection of HCV transmissions will foster deeper involvement of public health researchers and practitioners in hepatitis C outbreak investigation.

      9. Multiplex reverse transcription-PCR for simultaneous surveillance of influenza A and B viruses
        Zhou B, Deng YM, Barnes JR, Sessions OM, Chou TW, Wilson M, Stark TJ, Volk M, Spirason N, Halpin RA, Kamaraj US, Ding T, Stockwell TB, Salvatore M, Ghedin E, Barr IG, Wentworth DE.
        J Clin Microbiol. 2017 Dec;55(12):3492-3501.
        Influenza A and B viruses are the causative agents of annual influenza epidemics that can be severe, and influenza A viruses intermittently cause pandemics. Sequence information from influenza virus genomes is instrumental in determining mechanisms underpinning antigenic evolution and antiviral resistance. However, due to sequence diversity and the dynamics of influenza virus evolution, rapid and high-throughput sequencing of influenza viruses remains a challenge. We developed a single-reaction influenza A/B virus (FluA/B) multiplex reverse transcription-PCR (RT-PCR) method that amplifies the most critical genomic segments (hemagglutinin [HA], neuraminidase [NA], and matrix [M]) of seasonal influenza A and B viruses for next-generation sequencing, regardless of viral type, subtype, or lineage. Herein, we demonstrate that the strategy is highly sensitive and robust. The strategy was validated on thousands of seasonal influenza A and B virus-positive specimens using multiple next-generation sequencing platforms.

    • Global Health
      1. Impact of enhanced health interventions for United States-bound refugees: Evaluating best practices in migration health
        Mitchell T, Lee D, Weinberg M, Phares C, James N, Amornpaisarnloet K, Aumpipat L, Cooley G, Davies A, Tin Shwe VD, Gajdadziev V, Gorbacheva O, Khwan-Niam C, Klosovsky A, Madilokkowit W, Martin D, Htun Myint NZ, Yen Nguyen TN, Nutman TB, O’Connell EM, Ortega L, Prayadsab S, Srimanee C, Supakunatom W, Vesessmith V, Stauffer WM.
        Am J Trop Med Hyg. 2017 Dec 18.
        With an unprecedented number of displaced persons worldwide, strategies for improving the health of migrating populations are critical. United States-bound refugees undergo a required overseas medical examination to identify inadmissible conditions (e.g., tuberculosis) 2-6 months before resettlement, but it is limited in scope and may miss important, preventable infectious, chronic, or nutritional causes of morbidity. We sought to evaluate the feasibility and health impact of diagnosis and management of such conditions before travel. We offered voluntary testing for intestinal parasites, anemia, and hepatitis B virus infection, to U.S.-bound refugees from three Thailand-Burma border camps. Treatment and preventive measures (e.g., anemia and parasite treatment, vaccination) were initiated before resettlement. United States refugee health partners received overseas results and provided post-arrival medical examination findings. During July 9, 2012 to November 29, 2013, 2,004 refugees aged 0.5-89 years enrolled. Among 463 participants screened for seven intestinal parasites overseas and after arrival, helminthic infections decreased from 67% to 12%. Among 118 with positive Strongyloides-specific antibody responses, the median fluorescent intensity decreased by an average of 81% after treatment. The prevalence of moderate-to-severe anemia (hemoglobin < 10 g/dL) was halved from 14% at baseline to 7% at departure (McNemar P = 0.001). All 191 (10%) hepatitis B-infected participants received counseling and evaluation; uninfected participants were offered vaccination. This evaluation demonstrates that targeted screening, treatment, and prevention services can be conducted during the migration process to improve the health of refugees before resettlement. With more than 250 million migrants globally, this model may offer insights into healthier migration strategies.

    • Health Disparities
      1. Racial disparities in sepsis-related in-hospital mortality: Using a broad case capture method and multivariate controls for clinical and hospital variables, 2004-2013
        Jones JM, Fingar KR, Miller MA, Coffey R, Barrett M, Flottemesch T, Heslin KC, Gray DT, Moy E.
        Crit Care Med. 2017 Dec;45(12):e1209-e1217.
        OBJECTIVES: As sepsis hospitalizations have increased, in-hospital sepsis deaths have declined. However, reported rates may remain higher among racial/ethnic minorities. Most previous studies have adjusted primarily for age and sex. The effect of other patient and hospital characteristics on disparities in sepsis mortality is not yet well-known. Furthermore, coding practices in claims data may influence findings. The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004-2013 trends in risk-adjusted in-hospital sepsis mortality rates by race/ethnicity to inform efforts to reduce disparities in sepsis deaths. DESIGN: Retrospective, repeated cross-sectional study. SETTING: Acute care hospitals in the Healthcare Cost and Utilization Project State Inpatient Databases for 18 states with consistent race/ethnicity reporting. PATIENTS: Patients diagnosed with septicemia, sepsis, organ dysfunction plus infection, severe sepsis, or septic shock. MEASUREMENTS AND MAIN RESULTS: In-hospital sepsis mortality rates adjusted for patient and hospital factors by race/ethnicity were calculated. From 2004 to 2013, sepsis hospitalizations for all racial/ethnic groups increased, and mortality rates decreased by 5-7% annually. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white (92.0 per 1,000 sepsis hospitalizations), black (94.0), and Hispanic (93.5) patients but remained elevated for Asian/Pacific Islander (106.4) and “other” (104.7; p < 0.001) racial/ethnic patients. CONCLUSIONS: Our results indicate that hospital characteristics contribute to higher rates of sepsis mortality for blacks and Hispanics. These findings underscore the importance of ensuring that improved sepsis identification and management is implemented across all hospitals, especially those serving diverse populations.

    • Health Economics
      1. BACKGROUND: The purpose of this article was to describe methods that sexually transmitted disease (STD) programs can use to estimate the potential effects of changes in their budgets in terms of disease burden and direct medical costs. METHODS: We proposed 2 distinct approaches to estimate the potential effect of changes in funding on subsequent STD burden, one based on an analysis of state-level STD prevention funding and gonorrhea case rates and one based on analyses of the effect of Disease Intervention Specialist (DIS) activities on gonorrhea case rates. We also illustrated how programs can estimate the impact of budget changes on intermediate outcomes, such as partner services. Finally, we provided an example of the application of these methods for a hypothetical state STD prevention program. RESULTS: The methods we proposed can provide general approximations of how a change in STD prevention funding might affect the level of STD prevention services provided, STD incidence rates, and the direct medical cost burden of STDs. In applying these methods to a hypothetical state, a reduction in annual funding of US $200,000 was estimated to lead to subsequent increases in STDs of 1.6% to 3.6%. Over 10 years, the reduction in funding totaled US $2.0 million, whereas the cumulative, additional direct medical costs of the increase in STDs totaled US $3.7 to US $8.4 million. CONCLUSIONS: The methods we proposed, though subject to important limitations, can allow STD prevention personnel to calculate evidence-based estimates of the effects of changes in their budget.

      2. Trends in health insurance coverage of Title X Family Planning Program clients, 2005-2015
        Decker EJ, Ahrens KA, Fowler CI, Carter M, Gavin L, Moskosky S.
        J Womens Health (Larchmt). 2017 Dec 13.
        BACKGROUND: The federal Title X Family Planning Program supports the delivery of family planning services and related preventive care to 4 million individuals annually in the United States. The implementation of the 2010 Affordable Care Act’s (ACA’s) Medicaid expansion and provisions expanding access to health insurance, which took effect in January 2014, resulted in higher rates of health insurance coverage in the U.S. population; the ACA’s impact on individuals served by the Title X program has not yet been evaluated. METHODS: Using administrative data we examined changes in health insurance coverage among Title X clinic patients during 2005-2015. RESULTS: We found that the percentage of clients without health insurance decreased from 60% in 2005 to 48% in 2015, with the greatest annual decrease occurring between 2013 and 2014 (63% to 54%). Meanwhile, between 2005 and 2015, the percentage of clients with Medicaid or other public health insurance increased from 20% to 35% and the percentage of clients with private health insurance increased from 8% to 15%. CONCLUSIONS: Although clients attending Title X clinics remained uninsured at substantially higher rates compared with the national average, the increase in clients with health insurance coverage aligns with the implementation of ACA-related provisions to expand access to affordable health insurance.

      3. Purpose: That psychopathy imposes substantial societal costs and economic burden is axiomatic, but monetization studies have overlooked cost estimates of the disorder. The paper aims to discuss these issues. Design/methodology/approach: Drawing on a near census of institutionalized delinquents from Missouri, the current study devised new crime cost measures for self-reported offending. Findings: Youth imposed $30 million in total costs annually in large part due to extensive involvement in robbery, theft, and assault. The most criminally active youth imposed costs in excess of $700 million. Psychopathy features were differentially correlated with crime costs. APSD-SR callous-unemotional traits, mPPI-SF Blame Externalization, mPPI-SF Machiavellian Egocentricity, and mPPI-SF Social Potency were significantly associated with between four and five crime costs. Psychopathic traits associated with ruthless self-interest, callousness, and expectations to control and dominate others manifest in diverse ways including serious violence and repeated property crime. Other features such as mPPI-SF Impulsive Nonconformity, mPPI-SF Stress Immunity, mPPI-SF Coldheartedness, mPPI-SF Carefree Nonplanfulness, mPPI-SF Fearlessness, APSD-SR Impulsivity, and APSD-SR Narcissism had limited associations with crime costs. Originality/value: To the authors’ knowledge, this is the first monetization study to quantify the effects of assorted psychopathy features on crime costs.

      4. Cost analysis of the implementation of portable handwashing and drinking water stations in rural Kenyan health facilities
        Freedman M, Bennett SD, Rainey R, Otieno R, Quick R.
        J Water Sanit Hyg Dev. 2017 ;7(4):659-664.
        Many health care facilities (HCFs) in developing countries lack adequate infrastructure for handwashing and drinking water, increasing the risk of healthcare-associated infections. Attaining permanent, 24-hour/day piped water access – the long-term goal – is time-consuming and expensive. To address this problem in the short- to medium-term, low-cost portable handwashing water stations (HWSs) and drinking water stations (DWSs) were installed in rural Kenyan HCFs in 2011. Access to HWSs with soap and DWSs with safe water was ascertained at baseline and 1-year follow-up. Cost data were obtained from the program budget and beneficiary data (number of health workers, households, and individuals within HCF catchment areas) from the Ministry of Health. A cost analysis was adjusted for incremental gains from baseline to follow-up in access to improved handwashing and safe DWSs. The cost of improved access to handwashing with soap was $1,527/ HCF, $217/health worker, and $0.17/individual, and to safe drinking water was $720/HCF, $103/ health worker, and $0.08/individual. The favorable cost of this intervention per beneficiary justifies its use for rapid improvement of handwashing and drinking water access in HCFs during planning and construction of permanent infrastructure.

      5. Cost analysis of Prevention Research Centers: Instrument development
        Rabarison KM, Marcelin RA, Bish CL, Chandra G, Massoudi MS, Greenlund KJ.
        J Public Health Manag Pract. 2017 Dec 7.
        The 2014-2019 Prevention Research Centers (PRC) Program Funding Opportunity Announcement stated that “all applicants will be expected to collaborate with CDC to collect data to be able to perform cost analysis.” For the first time in the 30-year history of the PRC Program, a cost indicator was included in the PRC Program Evaluation and a cost analysis (CA) instrument developed. The PRC-CA instrument systematically collects data on the cost of the PRC core research project to eventually answer the CDC PRC Program Evaluation question: “To what extent do investments in PRCs support the scalability, sustainability, and effectiveness of the outcomes resulting from community-engaged efforts to improve public health?” The objective of this article is to briefly describe the development of the PRC-CA instrument. Data obtained from the PRC-CA instrument can be used to generate cost summaries to inform decision making within the PRC Program and each individual PRC.

      6. BACKGROUND: This paper concerns public health crises today-the problem of opioid prescription access and related abuse. Inspired by Case and Deaton’s seminal work on increasing mortality among white Americans with lower education, this paper explores the relationship between opioid prescribing and local economic factors. OBJECTIVE: We examined the association between county-level socioeconomic factors (median household income, unemployment rate, Gini index) and opioid prescribing. SUBJECTS: We used the complete 2014 Medicare enrollment and part D drug prescription data from the Center for Medicare and Medicaid Services to study opioid prescriptions of disabled Medicare beneficiaries without record of cancer treatment, palliative care, or end-of-life care. MEASURES AND RESEARCH DESIGN: We summarized the demographic and geographic variation, and investigated how the local economic environment, measured by county median household income, unemployment rate, Gini index, and urban-rural classification correlated with various measures of individual opioid prescriptions. Measures included number of filled opioid prescriptions, total days’ supply, average morphine milligram equivalent (MME)/day, and annual total MME dosage. To assess the robustness of the results, we controlled for individual and other county characteristics, used multiple estimation methods including linear least squares, logistic regression, and Tobit regression. RESULTS AND CONCLUSIONS: Lower county median household income, higher unemployment rates, and less income inequality were consistently associated with more and higher MME opioid prescriptions among disabled Medicare beneficiaries. Geographically, we found that the urban-rural divide was not gradual and that beneficiaries in large central metro counties were less likely to have an opioid prescription than those living in other areas.

    • Healthcare Associated Infections
      1. Pathogen distribution and antimicrobial resistance among pediatric healthcare-associated infections reported to the National Healthcare Safety Network, 2011-2014
        Lake JG, Weiner LM, Milstone AM, Saiman L, Magill SS, See I.
        Infect Control Hosp Epidemiol. 2017 Dec 18:1-11.
        OBJECTIVE To describe pathogen distribution and antimicrobial resistance patterns for healthcare-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) from pediatric locations during 2011-2014. METHODS Device-associated infection data were analyzed for central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP), and surgical site infection (SSI). Pooled mean percentage resistance was calculated for a variety of pathogen-antimicrobial resistance pattern combinations and was stratified by location for device-associated infections (neonatal intensive care units [NICUs], pediatric intensive care units [PICUs], pediatric oncology and pediatric wards) and by surgery type for SSIs. RESULTS From 2011 to 2014, 1,003 hospitals reported 20,390 pediatric HAIs and 22,323 associated pathogens to the NHSN. Among all HAIs, the following pathogens accounted for more than 60% of those reported: Staphylococcus aureus (17%), coagulase-negative staphylococci (17%), Escherichia coli (11%), Klebsiella pneumoniae and/or oxytoca (9%), and Enterococcus faecalis (8%). Among device-associated infections, resistance was generally lower in NICUs than in other locations. For several pathogens, resistance was greater in pediatric wards than in PICUs. The proportion of organisms resistant to carbapenems was low overall but reached approximately 20% for Pseudomonas aeruginosa from CLABSIs and CAUTIs in some locations. Among SSIs, antimicrobial resistance patterns were similar across surgical procedure types for most pathogens. CONCLUSION This report is the first pediatric-specific description of antimicrobial resistance data reported to the NHSN. Reporting of pediatric-specific HAIs and antimicrobial resistance data will help identify priority targets for infection control and antimicrobial stewardship activities in facilities that provide care for children. Infect Control Hosp Epidemiol 2017;1-11.

    • Immunity and Immunization
      1. Demonstration of the use of remote temperature monitoring devices in vaccine refrigerators in Haiti
        Cavallaro KF, Francois J, Jacques R, Mentor D, Yalcouye I, Wilkins K, Mueller N, Turner R, Wallace A, Tohme RA.
        Public Health Rep. 2017 Jan 1:33354917742119.
        After the 2010 earthquake, Haiti committed to introducing 4 new antigens into its routine immunization schedule, which required improving its cold chain (ie, temperature-controlled supply chain) and increasing vaccine storage capacity by installing new refrigerators. We tested the feasibility of using remote temperature monitoring devices (RTMDs) in Haiti in a sample of vaccine refrigerators fueled by solar panels, propane gas, or electricity. We analyzed data from 16 RTMDs monitoring 24 refrigerators in 15 sites from March through August 2014. Although 5 of the 16 RTMDs exhibited intermittent data gaps, we identified typical temperature patterns consistent with refrigerator door opening and closing, propane depletion, thermostat insufficiency, and overstocking. Actual start-up, annual maintenance, and annual electricity costs for using RTMDs were $686, $179, and $9 per refrigerator, respectively. In Haiti, RTMD use was feasible. RTMDs could be prioritized for use with existing refrigerators with high volumes of vaccines and new refrigerators to certify their functionality before use. Vaccine vial monitors could provide additional useful information about cumulative heat exposure and possible vaccine denaturation.

      2. An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial
        DeZure AD, Coates EE, Hu Z, Yamshchikov GV, Zephir KL, Enama ME, Plummer SH, Gordon IJ, Kaltovich F, Andrews S, McDermott A, Crank MC, Koup RA, Schwartz RM, Bailer RT, Sun X, Mascola JR, Tumpey TM, Graham BS, Ledgerwood JE.
        NPJ Vaccines. 2017 ;2:15.
        A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential. We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost. We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks. Group 1 received H7 DNA vaccine prime and H7N9 monovalent inactivated vaccine boost. Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost. Group 3 received H7N9 monovalent inactivated vaccine in a homologous prime-boost regimen. Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations. All injections were well tolerated with no serious adverse events. 2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer >/=1:40 compared with 11% of Group 3. Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects. Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11). A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone.

      3. An updated influenza A(H3N2) vaccine generates limited antibody responses to previously encountered antigens in children
        Florek NW, Campos LM, Braun KM, McLean HQ, King JP, Flannery B, Belongia EA, Friedrich TC.
        Vaccine. 2017 Dec 14.
        BACKGROUND: Influenza vaccination may provide a “back-boost” to antibodies against previously encountered strains. If the back-boost effect is common, this could allow more aggressive vaccine updates, as emerging variants would be expected to both elicit de-novo responses and boost pre-existing responses against recently circulating strains. Here we used the emergence of an antigenically novel A(H3N2) strain to determine whether an antigenically updated vaccine boosted antibodies against historical strains. METHODS: We performed hemagglutination-inhibition (HI) assays on pre- and post-vaccination sera from 124 children 5-17years old who received 2015-2016 inactivated influenza vaccine, containing an antigenically updated A(H3N2) strain. We evaluated the mean fold increase in HI titer against both the 2015-2016 vaccine strain and representative strains from two prior antigenic clusters. Factors associated with post-vaccination titers against historical strains were evaluated using linear regression, adjusting for baseline titer. RESULTS: Geometric mean titers against each antigen examined increased significantly after vaccination (P<.0001). Mean fold increase was 3.29 against the vaccine strain and 1.22-1.46 against historical strains. Response to vaccine strain was associated with increased post-vaccination titers against historical strains. CONCLUSIONS: A vaccine containing an antigenically novel A(H3N2) strain modestly boosted antibody responses against historical influenza strains in children.

      4. BACKGROUND: The pneumococcal conjugate vaccine (PCV) was introduced in 2001. Widespread PCV use nearly eradicated pneumococcal colonization by vaccine serotypes. Since 2008, however, colonization by PCV-serotype 19F has increased in Alaska residents. We describe the epidemiology of re-emerging serotype 19F colonization. METHODS: We conducted annual cross-sectional colonization surveys from 2008 to 2013. We recruited children aged <5years at 2 urban clinics and participants of all ages from Region-A (2 villages), Region-B (4 villages), and Region-C (2 villages). We interviewed participants and reviewed their medical records to obtain demographic information and determine PCV status. We obtained nasopharyngeal swab specimens from participants to identify pneumococci and to determine the pneumococcal serotype, antimicrobial resistance, and multilocus sequence type. We used the Cochran-Armitage test to assess for significant trends in colonization across time periods. RESULTS: Among participants aged <5years, pneumococcal serotype 19F colonization remained unchanged from 2008-2009 (0.7%) to 2012-2013 (0.5%; P-value [P]=.54). Serotype 19F colonization increased from 2008-2009 to 2012-2013 among participants aged 5-11years (0.3% to 3.2%; P<.01), participants 12-17years (0.0% to 2.0%; P<.01), and participants aged >/=18years (0.1% to 0.5%; P<.01). During 2012-2013, 85 (93%) of 91 pneumococcal serotype 19F isolates were identified among participants from Region B; the majority of serotype 19F isolates belonged to an antimicrobial nonsusceptibility pattern corresponding to a novel multilocus sequence type 9074. CONCLUSIONS: PCV continues to protect against serotype 19F colonization in vaccinated children aged <5years. The direct PCV impact on serotype 19F colonization in persons aged 5-11years and indirect impact in persons aged >/=12years is waning, possibly because of a newly introduced genotype in Region-B.

      5. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015
        Haber P, Moro PL, Ng C, Lewis PW, Hibbs B, Schillie SF, Nelson NP, Li R, Stewart B, Cano MV.
        Vaccine. 2017 Dec 11.
        INTRODUCTION: Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. METHODS: We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 – December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. RESULTS: VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2years of age; 2588 (13%) in persons 2-18years and 5867 (29%) in persons >18years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1month, were nervous system disorders (15) among children aged 1-23months; infections and infestation (8) among persons age 2-18years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18years. Most common vaccination error following single antigen HepB was incorrect product storage. CONCLUSIONS: Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations.

      6. BACKGROUND: Vaccines should be stored and handled according to manufacturer specifications. Inadequate cold chain management can affect potency; but, limited data exist on adverse events (AE) following administration of vaccines kept outside of recommended temperatures. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) involving vaccines inappropriately stored outside of recommended temperatures and/or exposed to temperatures outside of manufacturer specifications for inappropriate amounts of time. METHODS: We searched the VAERS database (analytic period 2008-2012) for reports describing vaccines kept outside of recommended temperatures. We analyzed reports by vaccine type, length outside of recommended temperature and type of temperature excursion, AE following receipt of potentially compromised vaccine, and reasons for cold chain breakdown. RESULTS: We identified 476 reports of vaccines kept outside of recommended temperatures; 77% described cluster incidents involving multiple patients. The most commonly reported vaccines were quadrivalent human papillomavirus (n=146, 30%), 23-valent pneumococcal polysaccharide (n=51, 11%), and measles, mumps, and rubella (n=45, 9%). Length of time vaccines were kept outside of recommended temperatures ranged from 15mins to 6months (median 51h). Most (n=458, 96%) reports involved patients who were administered potentially compromised vaccines; AE were reported in 32 (7%), with local reactions (n=21) most frequent. Two reports described multiple patients contracting diseases they were vaccinated against, indicating possible influenza vaccine failure. Lack of vigilance, inadequate training, and equipment failure were reasons cited for cold chain management breakdowns. CONCLUSIONS: Our review does not indicate any substantial direct health risk from administration of vaccines kept outside of recommended temperatures. However, there are potential costs and risks, including vaccine wastage, possible decreased protection, and patient and parent inconvenience related to revaccination. Maintaining high vigilance, proper staff training, regular equipment maintenance, and having adequate auxiliary power are important components of comprehensive vaccine cold chain management.

      7. Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis-Burkina Faso, 2014-2015
        Kambire D, Soeters HM, Ouedraogo-Traore R, Medah I, Sangare L, Yameogo I, Sawadogo G, Ouedraogo AS, Ouangraoua S, McGee L, Srinivasan V, Ake F, Congo-Ouedraogo M, Ba AK, Whitney CG, Novak RT, Van Beneden C.
        J Infect. 2017 Dec 15.
        OBJECTIVES: We evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso. METHODS: Nationwide surveillance gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination, and strains serotyped using PCR. We compared incidence (cases per 100,000) in the early post-PCV13 period (2014 and 2015) to average pre-PCV13 incidence (2011-2013). RESULTS: In 2015, age-specific pneumococcal meningitis incidences were 87 (<1 year), 24 (1-4 years), 65 (5-14 years), and 26 (>/=15 years). Compared to 2011-2013, PCV13-serotype incidence among all ages decreased by 32% (95%CI: 23%-39%), with significant decreases among children aged <1 year (76%; 95%CI: 64%-84%) and 1-4 years (58%, 95%CI: 40%-71%). Among all ages, incidence of PCV13 serotypes besides serotype 1 decreased (68%; 95%CI: 59%-75%), but serotype 1 incidence did not. Incidence of non-PCV13 serotypes also decreased (47%; 95%CI: 29%-60%). Among children aged <1 year, serotypes 12F/12A/12B/44/46 (17%), 1 (12%), and 5 (10%) predominated. CONCLUSIONS: Following PCV13 introduction, PCV13-serotype meningitis incidence in young children significantly decreased. PCV13 impact on serotype 1 and disease in older children and adults requires continued monitoring.

      8. Maternal influenza vaccine strategies in Kenya: Which approach would have the greatest impact on disease burden in pregnant women and young infants?
        McMorrow ML, Emukule GO, Obor D, Nyawanda B, Otieno NA, Makokha C, Mott JA, Bresee JS, Reed C.
        PLoS One. 2017 ;12(12):e0189623.
        BACKGROUND: Recent influenza surveillance data from Africa suggest an important burden of influenza-associated morbidity and mortality. In tropical countries where influenza virus transmission may not be confined to a single season alternative strategies for vaccine distribution via antenatal care (ANC) or semiannual campaigns should be considered. METHODS: Using data on monthly influenza disease burden in women of child-bearing age and infants aged 0-5 months in Kenya from 2010-2014, we estimated the number of outcomes (illnesses, medical visits, hospitalizations, and deaths) that occurred and that may have been averted through influenza vaccination of pregnant women using: 1) a year-round immunization strategy through ANC, 2) annual vaccination campaigns, and 3) semiannual vaccination campaigns. RESULTS: During 2010-2014, influenza resulted in an estimated 279,047 illnesses, 36,276 medical visits, 1612 hospitalizations and 243 deaths in pregnant women and 157,053 illnesses, 65,177 medical visits, 4197 hospitalizations, and 755 deaths in infants aged 0-5 months in Kenya. Depending on the mode of distribution and the vaccine coverage achieved, 12.8-31.4% of influenza-associated disease in pregnant women and 11.6-22.1% in infants aged 0-5 months might have been prevented through maternal influenza immunization. In this model, point estimates for influenza-associated disease averted through maternal vaccination delivered year-round in ANC or semiannually in campaigns were higher than vaccination delivered in a single annual campaign, but confidence intervals overlapped. CONCLUSIONS: Vaccinating pregnant women against influenza can reduce the burden of influenza-associated illness, hospitalization and death in both pregnant women and their young infants. Alternative immunization strategies may avert more influenza-associated disease in countries where influenza virus transmission occurs throughout the year.

      9. Meningococcal carriage following a vaccination campaign with MenB-4C and MenB-FHbp in response to a university serogroup B meningococcal disease outbreak – Oregon, 2015-2016
        McNamara LA, Thomas JD, MacNeil J, Chang HY, Day M, Fisher E, Martin S, Poissant T, Schmink SE, Steward-Clark E, Jenkins LT, Wang X, Acosta A.
        J Infect Dis. 2017 Nov 27;216(9):1130-1140.
        Background: Limited data exist on the impact of the serogroup B meningococcal (MenB) vaccines MenB-FHbp and MenB-4C on meningococcal carriage and herd protection. We therefore assessed meningococcal carriage following a MenB vaccination campaign in response to a university serogroup B meningococcal disease outbreak in 2015. Methods: A convenience sample of students recommended for vaccination provided oropharyngeal swab specimens and completed questionnaires during 4 carriage surveys over 11 months. Isolates were tested by real-time polymerase chain reaction analysis, slide agglutination, and whole-genome sequencing. Vaccination history was verified via university records and the state immunization registry. Results: A total of 4225 oropharyngeal swab specimens from 3802 unique participants were analyzed. Total meningococcal and genotypically serogroup B carriage prevalence among sampled students were stable, at 11%-17% and 1.2%-2.4% during each round, respectively; no participants carried the outbreak strain. Neither 1-3 doses of MenB-FHbp nor 1-2 doses of MenB-4C was associated with decreased total or serogroup B carriage prevalence. Conclusions: While few participants completed the full MenB vaccination series, limiting analytic power, these data suggest that MenB-FHbp and MenB-4C do not have a large, rapid impact on meningococcal carriage and are unlikely to provide herd protection in the context of an outbreak response.

      10. Immunization practices of U.S. obstetrician/gynecologists for pregnant patients
        O’Leary ST, Riley LE, Lindley MC, Allison MA, Crane LA, Hurley LP, Beaty BL, Brtnikova M, Collins M, Albert AP, Fisher AK, Jiles AJ, Kempe A.
        Am J Prev Med. 2017 Dec 12.
        INTRODUCTION: U.S. obstetrician/gynecologists play a critical role as vaccinators of pregnant women. However, little is known about their current immunization practices. Thus, study objectives were to determine (1) practices related to assessment of vaccination status and vaccine delivery for pregnant patients; (2) barriers to stocking and administering vaccines; and (3) factors associated with administering both influenza and tetanus, diphtheria, and acellular pertussis (Tdap) vaccines. METHODS: An e-mail and mail survey among a national sample of obstetrician/gynecologists conducted July-October 2015 (analysis August 2016-August 2017). RESULTS: The response rate was 73.2% (353/482). Among obstetrician/gynecologists caring for pregnant women (n=324), vaccination status was most commonly assessed for influenza (97%), Tdap (92%), and measles, mumps, and rubella vaccines (88%). Vaccines most commonly administered included influenza (85%) and Tdap (76%). Few respondents reported administering other vaccines to pregnant patients. More physicians reported using standing orders for influenza (66%) than Tdap (39%). Other evidence-based strategies for increasing vaccine uptake were less frequently used (electronic decision support, 42%; immunization information system to record [13%] or assess vaccination status [11%]; reminder/recall, 7%). Barriers most commonly reported were provider financial barriers, yet provider attitudinal barriers were rare. Providers who administered both influenza and Tdap vaccines were more likely to be female, perceive fewer financial and practice barriers, less likely to be in private practice, and perceive more patient barriers. CONCLUSIONS: Although most obstetrician/gynecologists administer some vaccines to pregnant women, the focus remains on influenza and Tdap. Financial barriers and infrequent use of evidence-based strategies for increasing vaccination uptake may be hindering delivery of a broader complement of adult vaccines in obstetrician/gynecologist offices.

      11. Report on eighth WHO meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses: Chicago, USA, 23-24 August 2016
        Ortiz JR, Hickling J, Jones R, Donabedian A, Engelhardt OG, Katz JM, Madhi SA, Neuzil KM, Rimmelzwaan GF, Southern J, Spiro DJ, Hombach J.
        Vaccine. 2017 Dec 5.
        In August 2016, the World Health Organization (WHO) convened the “Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses” to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines, and to identify areas where WHO can promote the development of such vaccines. Participants included approximately 120 representatives of academia, the vaccine industry, research and development funders, and regulatory and public health agencies. They reviewed the draft WHO preferred product characteristics (PPCs) of vaccines that could address prioritized unmet public health needs and discussed the challenges facing the development of such vaccines, especially for low- and middle-income countries (LMIC). They defined the data desired by public-health decision makers globally and explored how to support the progression of promising candidates into late-stage clinical trials and for all countries. This report highlights the major discussions of the meeting.

      12. OBJECTIVE: To quantify vaccinations administered outside minimum and maximum recommended ages and to determine attendant costs of revaccination by analyzing immunization information system (IIS) records. STUDY DESIGN: We analyzed deidentified records of doses administered during 2014 to persons aged <18 years within 6 IIS sentinel sites (10% of the US population). We quantified doses administered outside of recommended ages according to the Advisory Committee on Immunization Practices childhood immunization schedule and prescribing information in package inserts, and calculated revaccination costs. To minimize misreporting bias, we analyzed publicly funded doses for which reported lot numbers and vaccine types were consistent. RESULTS: Among 3 394 047 doses with maximum age recommendations, 9755 (0.3%) were given after the maximum age. One type of maximum age violation required revaccination: 1344 (0.7%) of 194 934 doses of the 0.25-mL prefilled syringe formulation of quadrivalent inactivated influenza vaccine (Fluzone Quadrivalent, Sanofi Pasteur, Swiftwater, PA) were administered at age >/=36 months (revaccination cost, $111 964). We identified a total of 7 529 165 childhood, adolescent, and lifespan doses with minimum age recommendations, 9542 of which (0.1%) were administered before the minimum age. The most common among these violations were quadrivalent injectable influenza vaccines (3835, or 0.7% of 526 110 doses administered before age 36 months) and Kinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium; DTaP-IPV) (2509, or 1.2% of 208 218 doses administered before age 48 months). The cost of revaccination for minimum age violations (where recommended) was $179 179. CONCLUSION: Administration of vaccines outside recommended minimum and maximum ages is rare, reflecting a general adherence to recommendations. Error rates were higher for several vaccines, some requiring revaccination. Vaccine schedule complexity and confusion among similar products might contribute to errors. Minimization of errors reduces wastage, excess cost, and inconvenience for parents and patients.

      13. INTRODUCTION: Oral rotavirus vaccines are less effective when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Identifying the specific factors in developing countries that decrease and/or compromise the protection that rotavirus vaccines offer, could lead to a path for designing new strategies for the vaccines’ improvement. Areas covered: We accessed PubMed to identify rotavirus vaccine performance studies (i.e., efficacy, effectiveness and immunogenicity) and correlated performance with several risk factors. Here, we review the factors that might contribute to the low vaccine efficacy, including passive transfer of maternal rotavirus antibodies, rotavirus seasonality, oral polio vaccine (OPV) administered concurrently, microbiome composition and concomitant enteric pathogens, malnutrition, environmental enteropathy, HIV, and histo blood group antigens. Expert commentary: We highlight several clear risk factors for rotavirus vaccine failure, such as the inhibitory effect of rotavirus IgG antibodies passively transferred to the infants, and co-administration with OPV. In addition, we highlight the ambiguous and sometimes conflicting nature of the current data, which reflects the complex and interconnected nature of the aspects involved.

      14. Background: Persons with HIV infection are at increased risk for hepatitis B virus infection. In 2016, the World Health Organization resolved to eliminate hepatitis B as a public health threat by 2030. Objective: To estimate the prevalence of hepatitis B vaccination among U.S. patients receiving medical care for HIV infection (“HIV patients”). Design: Nationally representative cross-sectional survey. Setting: United States. Participants: 18 089 adults receiving HIV medical care who participated in the Medical Monitoring Project during 2009 to 2012. Measurements: Primary outcomes were prevalence of 1) no documentation of hepatitis B vaccination or laboratory evidence of immunity or infection (candidates to initiate vaccination), and 2) initiation of vaccination among candidates, defined as documentation of at least 1 vaccine dose in a 1-year surveillance period during which patients received ongoing HIV medical care. Results: At the beginning of the surveillance period, 44.2% (95% CI, 42.2% to 46.2%) of U.S. HIV patients were candidates to initiate vaccination. By the end of the surveillance period, 9.6% (CI, 8.4% to 10.8%) of candidates were vaccinated, 7.5% (CI, 6.4% to 8.6%) had no documented vaccination but had documented infection or immunity, and 82.9% (CI, 81.1% to 84.7%) remained candidates. Among patients at facilities funded by the Ryan White HIV/AIDS Program (RWHAP), 12.5% (CI, 11.1% to 13.9%) were vaccinated during the surveillance period versus 3.7% (CI, 2.6% to 4.7%) at facilities not funded by RWHAP. At the end of surveillance, 36.7% (CI, 34.4% to 38.9%) of HIV patients were candidates to initiate vaccination. Limitation: The study was not designed to describe vaccine series completion or actual prevalence of immunity. Conclusion: More than one third of U.S. HIV patients had missed opportunities to initiate hepatitis B vaccination. Meeting goals for hepatitis B elimination will require increased vaccination of HIV patients in all practice settings, particularly at facilities not funded by RWHAP. Primary Funding Source: Centers for Disease Control and Prevention.

    • Informatics
      1. Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSante in Haiti
        deRiel E, Puttkammer N, Hyppolite N, Diallo J, Wagner S, Honore JG, Balan JG, Celestin N, Valles JS, Duval N, Thimothe G, Boncy J, Coq NR, Barnhart S.
        Health Policy Plan. 2017 Dec 14.
        Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSante, Haiti’s national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSante EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings.

    • Injury and Violence
      1. Executive function and dangerous driving behaviors in young drivers
        Hayashi Y, Foreman AM, Friedel JE, Wirth O.
        Transp Res Part F Traffic Psychol Behav. 2018 ;52:51-61.
        The purpose of the present study was to investigate the behavioral and cognitive processes underlying dangerous driving behaviors. We used a survey to assess levels of executive function in college students. The sample consisted of 59 males and 77 females and their age ranged from 18 to 24. We stratified the students into two groups based on executive function scores and compared the extent to which each group engaged in four dangerous driving behaviors (texting while driving, driving without a seat belt, driving while intoxicated, and speeding) as well as how often they experienced three negative driving outcomes (crashes, pulled over, and ticketed). We also investigated how these driving behaviors and outcomes are correlated with subcategories of executive function. The results show that students with a low level of executive function were more likely to engage in dangerous driving behaviors and more likely to experience negative driving outcomes. The results also show that texting while driving, driving while intoxicated, and speeding were most strongly correlated with the executive function subcategory of Impulse Control, whereas driving without a seat belt was most strongly correlated with the executive function subcategory of Strategic Planning. These results suggest that different behavioral or cognitive processes are involved in different dangerous driving behaviors and different interventions may be needed to target each underlying process.

      2. Assessing the public health impact of using poison center data for public health surveillance
        Wang A, Law R, Lyons R, Choudhary E, Wolkin A, Schier J.
        Clin Toxicol (Phila). 2017 Dec 13:1-7.
        CONTEXT: The National Poison Data System (NPDS) is a database and surveillance system for US poison centers (PCs) call data. The Centers for Disease Control and Prevention (CDC) and American Association of Poison Control Centers (AAPCC) use NPDS to identify incidents of potential public health significance. State health departments are notified by CDC of incidents identified by NPDS to be of potential public health significance. Our objective was to describe the public health impact of CDC’s notifications and the use of NPDS data for surveillance. METHODS: We described how NPDS data informed three public health responses: the Deepwater Horizon incident, national exposures to laundry detergent pods, and national exposures to e-cigarettes. Additionally, we extracted survey results of state epidemiologists regarding NPDS incident notification follow-up from 1 January 2015 to 31 December 2016 to assess current public health application of NPDS data using Epi Info 7.2 and analyzed data using SAS 9.3. We assessed whether state health departments were aware of incidents before notification, what actions were taken, and whether CDC notifications contributed to actions. DISCUSSION: NPDS data provided evidence for industry changes to improve laundry detergent pod containers safety and highlighted the need to regulate e-cigarette sale and manufacturing. NPDS data were used to improve situational awareness during the 2010 Deepwater Horizon oil spill. Of 59 health departments and PCs who responded to CDC notifications about anomalies (response rate = 49.2%), 27 (46%) reported no previous awareness of the incident, and 20 (34%) said that notifications contributed to public health action. CONCLUSIONS: Monitoring NPDS data for anomalies can identify emerging public health threats and provide evidence-based science to support public health action and policy changes.

    • Laboratory Sciences
      1. Prediction of WBGT-based clothing adjustment values from evaporative resistance
        Bernard TE, Ashley CD, Garzon XP, Kim JH, Coca A.
        Ind Health. 2017 Dec 7;55(6):549-554.
        Wet bulb globe temperature (WBGT) index is used by many professionals in combination with metabolic rate and clothing adjustments to assess whether a heat stress exposure is sustainable. The progressive heat stress protocol is a systematic method to prescribe a clothing adjustment value (CAV) from human wear trials, and it also provides an estimate of apparent total evaporative resistance (Re,T,a). It is clear that there is a direct relationship between the two descriptors of clothing thermal effects with diminishing increases in CAV at high Re,T,a. There were data to suggest an interaction of CAV and Re,T,a with relative humidity at high evaporative resistance. Because human trials are expensive, manikin data can reduce the cost by considering the static total evaporative resistance (Re,T,s). In fact, as the static evaporative resistance increases, the CAV increases in a similar fashion as Re,T,a. While the results look promising that Re,T,s can predict CAV, some validation remains, especially for high evaporative resistance. The data only supports air velocities near 0.5 m/s.

      2. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
        Bowden JA, Heckert A, Ulmer CZ, Jones CM, Koelmel JP, Abdullah L, Ahonen L, Alnouti Y, Armando AM, Asara JM, Bamba T, Barr JR, Bergquist J, Borchers CH, Brandsma J, Breitkopf SB, Cajka T, Cazenave-Gassiot A, Checa A, Cinel MA, Colas RA, Cremers S, Dennis EA, Evans JE, Fauland A, Fiehn O, Gardner MS, Garrett TJ, Gotlinger KH, Han J, Huang Y, Neo AH, Hyotylainen T, Izumi Y, Jiang H, Jiang H, Jiang J, Kachman M, Kiyonami R, Klavins K, Klose C, Kofeler HC, Kolmert J, Koal T, Koster G, Kuklenyik Z, et al .
        J Lipid Res. 2017 Dec;58(12):2275-2288.
        As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

      3. Evaluation of a Cryptococcal antigen Lateral Flow Assay in serum and cerebrospinal fluid for rapid diagnosis of cryptococcosis in Colombia
        Caceres DH, Zuluaga A, Tabares AM, Chiller T, Gonzalez A, Gomez BL.
        Rev Inst Med Trop Sao Paulo. 2017 Dec 21;59:e76.
        A Lateral Flow Assay to detect cryptococcal antigen (CrAg(R) LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg(R) LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS(R)) and CrAg(R) LFA was observed. CrAg(R) LFA showed higher analytical sensitivity for detecting low concentrations of cryptococcal antigen.

      4. Galactosylation of the secondary cell wall polysaccharide of Bacillus anthracis and its contribution to anthrax pathogenesis
        Chateau A, Lunderberg JM, Oh SY, Abshire T, Friedlander A, Quinn CP, Missiakas DM, Schneewind O.
        J Bacteriol. 2017 Dec 11.
        Bacillus anthracis, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is essential for bacterial growth and cell division. B. anthracis SCWP is comprised of trisaccharide repeats, [–>4)-beta-ManNAc-(1–>4)-beta-GlcNAc-(1–>6)-alpha-GlcNAc-(1–>], where alpha-GlcNAc is substituted with alpha-Gal and beta-Gal at O3 and O4, respectively, and beta-GlcNAc is substituted with alpha-Gal at O3. The genes whose products promote the galactosylation of B. anthracis SCWP are not yet known. We show here that expression of galE1, encoding a UDP-glucose 4-epimerase necessary for the synthesis of UDP-galactose, is required for B. anthracis SCWP galactosylation. The galE1 mutant assembles S-layer and S-layer associated proteins, which associate with ketal-pyruvylated SCWP via their S-layer homology domains in a manner similar to wild-type B. anthracis, but displays a defect in gamma-phage murein hydrolase binding to SCWP. Further, deletion of galE1 diminishes capsulation of B. anthracis with poly-D-gamma-glutamic acid (PDGA) and causes a reduction in bacterial virulence. These data suggest that SCWP galactosylation is required for the physiologic assembly of the B. anthracis cell wall envelope and for the pathogenesis of anthrax disease.IMPORTANCE Unlike virulent Bacillus anthracis isolates, B. anthracis CDC684 synthesizes secondary cell wall polysaccharide (SCWP) trisaccharide repeats without galactosyl modification, exhibits diminished growth in vitro in broth cultures and is severely attenuated in an animal model of anthrax. To examine whether SCWP galactosylation is a requirement for anthrax disease, we generated B. anthracis 34F2 and Ames variants lacking UDP-glucose 4-epimerase by mutating the genes galE1 and galE2 We identified galE1 as necessary for SCWP galactosylation. Deletion of galE1 decreased B. anthracis vegetative form poly-D-gamma-glutamic acid (PDGA) capsulation and increased the bacterial inoculum required to produce lethal disease in mice, indicating that SCWP galactosylation is indeed a determinant of anthrax disease.

      5. Phylogeny and antimicrobial resistance in Neisseria gonorrhoeae isolates from Rio de Janeiro, Brazil
        Costa-Lourenco AP, Abrams AJ, Dos Santos KT, Argentino IC, Coelho-Souza T, Canine MC, Ferreira AL, Moreira BM, Fracalanzza SE, Trees DL, Bonelli RR.
        Infect Genet Evol. 2017 Dec 7.

        [No abstract]

      6. Validated MALDI-TOF-MS method for anthrax lethal factor provides early diagnosis and evaluation of therapeutics
        Gallegos-Candela M, Boyer AE, Woolfitt AR, Brumlow J, Lins RC, Quinn CP, Hoffmaster AR, Meister G, Barr JR.
        Anal Biochem. 2017 Dec 7.
        Anthrax lethal factor (LF) is a zinc-dependent endoprotease and a critical virulence factor for Bacillus anthracis, the causative agent of anthrax. The mass spectrometry (MS) method for total-LF quantification includes three steps; 1) LF specific antibody capture/concentration, 2) LF-specific hydrolysis of a peptide substrate, and 3) detection and quantification of LF-cleaved peptides by isotope-dilution MALDI-TOF/MS. Recombinant LF spiked plasma was used for calibration and quality control (QC) materials. Specificity was 100% from analysis of serum and plasma from 383 non-infected humans, 31 rabbits, and 24 rhesus macaques. Sensitivity was 100% from 32 human clinical anthrax cases including infections by inhalation, ingestion, cutaneous and injection exposures and experimental infections for 29 rabbits and 24 rhesus macaques with inhalation anthrax. Robustness evaluation included sample storage, serum and plasma, antimicrobial and antitoxin effects and long-term performance. Data from 100 independent runs gave detection limits 0.01 ng/mL (111 amol/mL) for the 4-h method and 0.0027 ng/mL (30 amol/mL) for an alternate 20-h method. QC precision ranged from 7.7 to 14.8% coefficient of variation and accuracy from 0.2 to 9.8% error. The validated LF MS method provides sensitive quantification of anthrax total-LF using a robust high throughput platform for early diagnosis and evaluation of therapeutics during an anthrax emergency.

      7. Neutralizing antibodies against hemagglutinin (HA) of influenza viruses are considered the main immune mechanism that correlates with protection for influenza infections. Microneutralization (MN) assays are often used to measure neutralizing antibody responses in human sera after influenza vaccination or infection. Madine Darby Canine Kidney (MDCK) cells are the commonly used cell substrate for MN assays. However, currently circulating 3C.2a and 3C.3a A(H3N2) influenza viruses have acquired altered receptor binding specificity. The MDCK-SIAT1 cell line with increased alpha-2,6 sialic galactose moieties on the surface has proven to provide improved infectivity and more faithful replications than conventional MDCK cells for these contemporary A(H3N2) viruses. Here, we describe a MN assay using MDCK-SIAT1 cells that has been optimized to quantify neutralizing antibody titers to these contemporary A(H3N2) viruses. In this protocol, heat inactivated sera containing neutralizing antibodies are first serially diluted, then incubated with 100 TCID50/well of influenza A(H3N2) viruses to allow antibodies in the sera to bind to the viruses. MDCK-SIAT1 cells are then added to the virus-antibody mixture, and incubated for 18 – 20 h at 37 degrees C, 5% CO2 to allow A(H3N2) viruses to infect MDCK-SIAT1 cells. After overnight incubation, plates are fixed and the amount of virus in each well is quantified by an enzyme-linked immunosorbent assay (ELISA) using anti-influenza A nucleoprotein (NP) monoclonal antibodies. Neutralizing antibody titer is defined as the reciprocal of the highest serum dilution that provides >/=50% inhibition of virus infectivity. 2017 Journal of Visualized Experiments.

      8. A combined syndromic approach to examine viral, bacterial, and parasitic agents among febrile patients: A pilot study in Kilombero, Tanzania
        Hercik C, Cosmas L, Mogeni OD, Wamola N, Kohi W, Houpt E, Liu J, Ochieng C, Onyango C, Fields B, Mfinanga S, Montgomery JM.
        Am J Trop Med Hyg. 2017 Dec 26.
        The use of fever syndromic surveillance in sub-Saharan Africa is an effective approach to determine the prevalence of both malarial and nonmalarial infectious agents. We collected both blood and naso/oro-pharyngeal (NP/OP) swabs from consecutive consenting patients >/= 1 year of age, with an axillary temperature >/= 37.5 degrees C, and symptom onset of </= 5 days. Specimens were analyzed using both acute febrile illness (AFI) and respiratory TaqMan array cards (TAC) for multiagent detection of 56 different bloodstream and respiratory agents. In addition, we collected epidemiologic data to further characterize our patient population. We enrolled 205 febrile patients, including 70 children (1 < 15 years of age; 34%) and 135 adults (>/= 15 years of age; 66%). AFI TAC and respiratory TAC were performed on 191 whole blood specimens and 115 NP/OP specimens, respectively. We detected nucleic acid for Plasmodium (57%), Leptospira (2%), and dengue virus (1%) among blood specimens. In addition, we detected 17 different respiratory agents, most notably, Haemophilus influenzae (64%), Streptococcus pneumonia (56%), Moraxella catarrhalis (39%), and respiratory syncytial virus (11%) among NP/OP specimens. Overall median cycle threshold was measured at 26.5. This study provides a proof-of-concept for the use of a multiagent diagnostic approach for exploratory research on febrile illness and underscores the utility of quantitative molecular diagnostics in complex epidemiologic settings of sub-Saharan Africa.

      9. Molecular pathogenesis of Chlamydia disease complications: Epithelial-mesenchymal transition and fibrosis
        Igietseme JU, Omosun Y, Nagy T, Stuchlik O, Reed MS, He Q, Partin J, Joseph K, Ellerson D, George Z, Goldstein J, Eko FO, Bandea C, Pohl J, Black CM.
        Infect Immun. 2018 Jan;86(1).
        The reproductive system complications of genital chlamydial infection include fallopian tube fibrosis and tubal factor infertility. However, the molecular pathogenesis of these complications remains poorly understood. The induction of pathogenic epithelial-mesenchymal transition (EMT) through microRNA (miRNA) dysregulation was recently proposed as the pathogenic basis of chlamydial complications. Focusing on fibrogenesis, we investigated the hypothesis that chlamydia-induced fibrosis is caused by EMT-driven generation of myofibroblasts, the effector cells of fibrosis that produce excessive extracellular matrix (ECM) proteins. The results revealed that the targets of a major category of altered miRNAs during chlamydial infection are key components of the pathophysiological process of fibrogenesis; these target molecules include collagen types I, III, and IV, transforming growth factor beta (TGF-beta), TGF-beta receptor 1 (TGF-betaR1), connective tissue growth factor (CTGF), E-cadherin, SRY-box 7 (SOX7), and NFAT (nuclear factor of activated T cells) kinase dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1a (Dyrk1a). Chlamydial induction of EMT resulted in the generation of alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts that produced ECM proteins, including collagen types I and III and fibronectin. Furthermore, the inhibition of EMT prevented the generation of myofibroblasts and production of ECM proteins during chlamydial infection. These findings may provide useful avenues for targeting EMT or specific components of the EMT pathways as a therapeutic intervention strategy to prevent chlamydia-related complications.

      10. Pair housing of vervets/African green monkeys for biomedical research
        Jorgensen MJ, Lambert KR, Breaux SD, Baker KC, Snively BM, Weed JL.
        Am J Primatol. 2017 Jan;79(1):1-10.
        Vervets, also known as African green monkeys, are a nonhuman primate species widely used in biomedical research. However, there are currently few references available describing techniques and rates of success for pair-housing this species. We present data from four cohorts of vervets from three different facilities: (i) the Wake Forest Vervet Research Colony (VRC; n = 72 female pairs, n= 52 male pairs), (ii) the University of Louisiana at Lafayette-New Iberia Research Center (UL-NIRC; n = 57 female pairs, n = 54 male pairs), (iii) the Tulane National Primate Research Center (TNRPC; n = 18 male pairs), and (iv) a cohort of imported males (n = 18 pairs) at Wake Forest. Compatibility was measured at 14, 30, and 60 days following introduction. Success rates for pair-housing at 14 days ranged from 96% to 98% for females and 96% to 100% for males at the VRC and UL-NIRC but were lower in the smaller imported male cohorts (TNPRC: 50%; WF: 28%). Among the UL-NIRC cohort and VRC male cohort, most of the pair separations after 14 days were due to reasons unrelated to social incompatibility. In contrast, a large proportion of TNPRC and imported male pairs successful at 14 days required separation within 60 days due to incompatibility. Multiple logistic regressions were performed using cohort, mean age of pair and weight difference between pair-mates as potential predictors of compatibility at 14 days. All three predicted the 14-day outcome in males but not females. A separate analysis in the VRC cohort found no evidence that prior familiarity in a group setting influenced outcomes. Variations in success rates across cohorts may have been influenced by introduction methodology. Behavioral differences between vervets and macaques, coupled with our findings, lead us to theorize that the gradual introduction techniques commonly implemented to pair house macaques may not be beneficial or suitable for this species. Am. J. Primatol. 79:e22501, 2017. (c) 2015 Wiley Periodicals, Inc.

      11. The influence of exposure duration on chemical toxicity has important implications for risk assessment. Although a default 10-fold extrapolation factor is commonly applied when the toxicological dataset includes a subchronic (90-day) study but lacks studies of chronic duration, little consensus has been reached on an appropriate extrapolation factor to apply when the dataset includes a 28-day study but lacks studies of longer durations. The goal of the present assessment was to identify a 28-day to 90-day extrapolation factor by analyzing distributions of ratios of No-Observed-Adverse-Effect Levels (NOAELs) and Benchmark Doses (BMDs) derived from 28-day and 90-day studies. The results of this analysis suggest that a default 10-fold extrapolation factor in chemical risk assessment applications is sufficient to account for the uncertainty associated with evaluating human health risk based on results from a 28-day study in the absence of results from a 90-day study. This analysis adds significantly to the growing body of literature interpreting the influence of exposure duration on chemical toxicity that will likewise facilitate discussions on the future state of testing requirements in the international regulatory community.

      12. Acoustic reflexes are common but not pervasive: evidence using a diagnostic middle ear analyser
        McGregor KD, Flamme GA, Tasko SM, Deiters KK, Ahroon WA, Themann CL, Murphy WJ.
        Int J Audiol. 2017 Dec 19:1-9.
        OBJECTIVE: The objective of this study is to determine whether acoustic reflexes are pervasive (i.e. known with 95% confidence to be observed in at least 95% of people) by examining the frequency of occurrence using a friction-fit diagnostic middle ear analyser. DESIGN: Adult participants with very good hearing sensitivity underwent audiometric and middle ear testing. Acoustic reflexes were tested ipsilaterally and contralaterally in both ears across a range of elicitor frequencies. Reflex elicitors were 700 ms tones presented at maximum level of 100 dB HL. Two automated methods were used to detect the presence of an acoustic reflex. STUDY SAMPLE: A group of 285 adult volunteers with normal hearing. RESULTS: There were no conditions in which the proportion of participants exhibiting acoustic reflexes was high enough to be deemed pervasive. Ipsilateral reflexes were more likely to be observed than contralateral reflexes and reflexes were more common at 0.5 and 1 kHz elicitor frequencies as compared with 2 and 4 kHz elicitor frequencies. CONCLUSIONS: Acoustic reflexes are common among individuals with good hearing. However, acoustic reflexes are not pervasive and should not be included in damage risk criteria and health hazard assessments for impulsive noise.

      13. Immunohistochemistry and electrophysiological findings in swine abattoir workers with immune-mediated polyradiculoneuropathy
        Muley SA, Holzbauer S, Clark B, Sejvar J, Lynfield R, Parry G, DeVries AS.
        J Neurol Sci. 2018 ;385:34-38.
        Importance: Workers exposed to aerosolized brain in a swine-processing plant developed immune-mediated polyradiculoneuropathy (IP) possibly triggered by an immune response. Objective Immunohistochemistry results were correlated with electrophysiological variables to examine the immunopathogenesis of this disorder. Design/setting Laboratory studies used normal nerve tissue that was exposed to sera from 12 IP patients; 10 exposed controls; and 10 unexposed controls. Clinical and electrophysiological data from IP patients were obtained from medical record reviews. Main outcome measures Analysis included electromyography results of IP patients and nerve conduction studies examining CMAP amplitude, distal motor latency, motor conduction velocity, F-wave latency, sensory nerve action potential amplitude, and sensory nerve conduction velocity. Case and control results were compared relative to distance from exposure. Results Electrodiagnostic findings revealed prolongation of the distal and f-wave latencies suggestive of demyelination at the level of the nerve root and distal nerve terminals. Immunohistochemical results identified an antibody to the peripheral nerve, with staining at the level of the axolemma. Thus, IP may be a primary axonopathy with secondary paranodal demyelination causing the conduction changes. Staining of the distal and proximal portions of the nerve appears consistent with easier access through the blood-nerve barrier. Conclusions and relevance IP is an immune-mediated neuropathy related to antibodies to an axon-based antigen on peripheral nerves. Secondary paranodal demyelination is likely. Further studies to identify the primary axonal antigenic target would be useful.

      14. Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges
        Pfeiffer CM, Looker AC.
        Am J Clin Nutr. 2017 Dec;106(Suppl 6):1606s-1614s.
        Biochemical assessment of iron status relies on serum-based indicators, such as serum ferritin (SF), transferrin saturation, and soluble transferrin receptor (sTfR), as well as erythrocyte protoporphyrin. These indicators present challenges for clinical practice and national nutrition surveys, and often iron status interpretation is based on the combination of several indicators. The diagnosis of iron deficiency (ID) through SF concentration, the most commonly used indicator, is complicated by concomitant inflammation. sTfR concentration is an indicator of functional ID that is not an acute-phase reactant, but challenges in its interpretation arise because of the lack of assay standardization, common reference ranges, and common cutoffs. It is unclear which indicators are best suited to assess excess iron status. The value of hepcidin, non-transferrin-bound iron, and reticulocyte indexes is being explored in research settings. Serum-based indicators are generally measured on fully automated clinical analyzers available in most hospitals. Although international reference materials have been available for years, the standardization of immunoassays is complicated by the heterogeneity of antibodies used and the absence of physicochemical reference methods to establish “true” concentrations. From 1988 to 2006, the assessment of iron status in NHANES was based on the multi-indicator ferritin model. However, the model did not indicate the severity of ID and produced categorical estimates. More recently, iron status assessment in NHANES has used the total body iron stores (TBI) model, in which the log ratio of sTfR to SF is assessed. Together, sTfR and SF concentrations cover the full range of iron status. The TBI model better predicts the absence of bone marrow iron than SF concentration alone, and TBI can be analyzed as a continuous variable. Additional consideration of methodologies, interpretation of indicators, and analytic standardization is important for further improvements in iron status assessment.

      15. Diagnosis of hepatitis C virus (HCV) infection is based on testing for antibodies to HCV (anti-HCV), hepatitis C core antigen (HCV cAg) and HCV RNA. To ensure quality control (QC) and quality assurance (QA), proficiency panels are provided by reference laboratories and various international organizations, requiring costly dry ice shipments to maintain specimen integrity. Alternative methods of specimen preservation and transport can save on shipping and handling and help in improving diagnostics by facilitating QA/QC of various laboratories especially in resource limited countries. Plasma samples positive for anti-HCV and HCV RNA were either dried using dried tube specimens (DTS) method or lyophilization for varying durations of time and temperature. Preservation of samples using DTS method resulted in loss of anti-HCV reactivity for low-positive samples and did not generate enough volume for HCV RNA testing. Lyophilized samples tested positive for anti-HCV even after storage at 4 degrees C and 25 degrees C for 12 weeks. Further, HCV RNA was detectable in 5 of 5 (100%) samples over the course of 12 week storage at 4, 25, 37 and 45 degrees C. In conclusion, lyophilization of specimens maintains integrity of plasma samples for testing for markers of HCV infection and can be a potent mode of sharing proficiency samples without incurring huge shipping costs and avoids challenges with dry ice shipments between donor and recipient laboratories.

      16. Streptococcus azizii sp. nov., isolated from naive weanling mice
        Shewmaker PL, Whitney AM, Gulvik CA, Lipman NS.
        Int J Syst Evol Microbiol. 2017 Oct 12.
        Three isolates of a previously reported novel catalase-negative, Gram-stain-positive, coccoid, alpha-haemolytic, Streptococcus species that were associated with meningoencephalitis in naive weanling mice were further evaluated to confirm their taxonomic status and to determine additional phenotypic and molecular characteristics. Comparative 16S rRNA gene sequence analysis showed nearly identical intra-species sequence similarity (>/=99.9 %), and revealed the closest phylogenetically related species, Streptococcus acidominimus and Streptococcus cuniculi, with 97.0 and 97.5 % sequence similarity, respectively. The rpoB, sodA and recN genes were identical for the three isolates and were 87.6, 85.7 and 82.5 % similar to S. acidominimus and 89.7, 86.2 and 80.7 % similar to S. cuniculi, respectively. In silico DNA-DNA hybridization analyses of mouse isolate 12-5202(T) against S. acidominimus CCUG 27296(T) and S. cuniculi CCUG 65085(T) produced estimated values of 26.4 and 25.7 % relatedness, and the calculated average nucleotide identity values were 81.9 and 81.7, respectively. These data confirm the taxonomic status of 12-5202(T) as a distinct Streptococcus species, and we formally propose the type strain, Streptococcusazizii 12-5202(T) (=CCUG 69378(T)=DSM 103678(T)). The genome of Streptococcus azizii sp. nov. 12-5202(T) contains 2062 total genes with a size of 2.34 Mbp, and an average G+C content of 42.76 mol%.

      17. Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats
        Shoeb M, Joseph P, Kodali V, Mustafa G, Farris BY, Umbright C, Roberts JR, Erdely A, Antonini JM.
        Sci Rep. 2017 Dec 11;7(1):17284.
        Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m(3) of silica x 6 h/d x 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

      18. The use of a shared services model for mycobacteriology testing: Lessons learned
        Stafford C, Atkinson-Dunn R, Buss SN, Dalton T, Gibson D, Johnston S, King E, Grace Lin SY, Mitchell KK, Murtaugh WA, Sease H, Southern TR, Tans-Kersten JL, Travanty EA, Triplett LR, Wroblewski K, Starks AM.
        Public Health Rep. 2017 Jan 1:33354917743498.
        OBJECTIVES: Public health laboratories (PHLs) provide essential services in the diagnosis and surveillance of diseases of public health concern, such as tuberculosis. Maintaining access to high-quality laboratory testing is critical to continued disease detection and decline of tuberculosis cases in the United States. We investigated the practical experience of sharing tuberculosis testing services between PHLs through the Shared Services Project. METHODS: The Shared Services Project was a 9-month-long project funded through the Association of Public Health Laboratories and the Centers for Disease Control and Prevention during 2012-2013 as a one-time funding opportunity to consortiums of PHLs that proposed collaborative approaches to sharing tuberculosis laboratory services. Submitting PHLs maintained testing while simultaneously sending specimens to reference laboratories to compare turnaround times. RESULTS: During the 9-month project period, 107 Mycobacterium tuberculosis complex submissions for growth-based drug susceptibility testing and molecular detection of drug resistance testing occurred among the 3 consortiums. The median transit time for all submissions was 1.0 day. Overall, median drug susceptibility testing turnaround time (date of receipt in submitting laboratory to result) for parallel testing performed in house by submitting laboratories was 31.0 days; it was 43.0 days for reference laboratories. The median turnaround time for molecular detection of drug resistance results was 1.0 day (mean = 2.8; range, 0-14) from specimen receipt at the reference laboratories. CONCLUSIONS: The shared services model holds promise for specialized tuberculosis testing. Sharing of services requires a balance among quality, timeliness, efficiency, communication, and fiscal costs.

      19. Surfaceome analysis protocol for the identification of novel Bordetella pertussis antigens
        Williamson YM, Whitmon J, West-Deadwyler R, Moura H, Woolfitt AR, Rees J, Schieltz DM, Barr JR.
        Methods Mol Biol. 2018 ;1722:3-20.
        The bacterial surfaceome, comprising outer membrane-sorted and/or associated (i.e., cell transporters), cell surface-exposed (i.e., adhesins) and extracellularly secreted proteins (i.e., toxins), has been characterized in bacterial pathogens, such as Bordetella pertussis (Bp) to provide information for use in development of diagnostic and prevention strategies. This protein subset has clinical significance, as these bacterial proteins are often associated with attachment to host cells, microbial pathogenesis and antibody-mediated immunity. Here we describe classical surface membrane protein enrichment techniques, followed by proteomic methodologies, such as gel-free protein separation and antibody-affinity capture technologies in combination with nano-liquid chromatography mass spectrometry, for the identification and characterization of Bp surfaceome proteins.

    • Maternal and Child Health
      1. Implementing CDC’s Level of Care Assessment Tool (LOCATe): A National Collaboration to Improve Maternal and Child Health
        Catalano A, Bennett A, Busacker A, Carr A, Goodman D, Kroelinger C, Okoroh E, Brantley M, Barfield W.
        J Womens Health (Larchmt). 2017 Dec;26(12):1265-1269.
        Perinatal regionalization, or risk-appropriate care, is an approach that classifies facilities based on capabilities to ensure women and infants receive care at a facility that aligns with their risk. The CDC designed the Levels of Care Assessment Tool (LOCATe) to assist jurisdictions working in risk-appropriate care in assessing a facility’s level of maternal and neonatal care aligned with the most current American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine (ACOG/SMFM) and American Academy of Pediatrics (AAP) guidelines. LOCATe produces standardized assessments for each hospital that participates and facilitates conversations among stakeholders in risk-appropriate care. This article describes how public health departments implement and use LOCATe in their jurisdictions.

      2. Improving the quality of child anthropometry: Manual anthropometry in the Body Imaging for Nutritional Assessment Study (BINA)
        Conkle J, Ramakrishnan U, Flores-Ayala R, Suchdev PS, Martorell R.
        PLoS One. 2017 ;12(12):e0189332.
        Anthropometric data collected in clinics and surveys are often inaccurate and unreliable due to measurement error. The Body Imaging for Nutritional Assessment Study (BINA) evaluated the ability of 3D imaging to correctly measure stature, head circumference (HC) and arm circumference (MUAC) for children under five years of age. This paper describes the protocol for and the quality of manual anthropometric measurements in BINA, a study conducted in 2016-17 in Atlanta, USA. Quality was evaluated by examining digit preference, biological plausibility of z-scores, z-score standard deviations, and reliability. We calculated z-scores and analyzed plausibility based on the 2006 WHO Child Growth Standards (CGS). For reliability, we calculated intra- and inter-observer Technical Error of Measurement (TEM) and Intraclass Correlation Coefficient (ICC). We found low digit preference; 99.6% of z-scores were biologically plausible, with z-score standard deviations ranging from 0.92 to 1.07. Total TEM was 0.40 for stature, 0.28 for HC, and 0.25 for MUAC in centimeters. ICC ranged from 0.99 to 1.00. The quality of manual measurements in BINA was high and similar to that of the anthropometric data used to develop the WHO CGS. We attributed high quality to vigorous training, motivated and competent field staff, reduction of non-measurement error through the use of technology, and reduction of measurement error through adequate monitoring and supervision. Our anthropometry measurement protocol, which builds on and improves upon the protocol used for the WHO CGS, can be used to improve anthropometric data quality. The discussion illustrates the need to standardize anthropometric data quality assessment, and we conclude that BINA can provide a valuable evaluation of 3D imaging for child anthropometry because there is comparison to gold-standard, manual measurements.

      3. Using a quality improvement approach to improve maternal and neonatal care in North Kivu, Democratic Republic of Congo
        Hynes M, Meehan K, Meyers J, Mashukano Maneno L, Hulland E.
        Reprod Health Matters. 2017 Dec 12:1-11.
        Providing quality health care services in humanitarian settings is challenging due to population displacement, lack of qualified staff and supervisory oversight, and disruption of supply chains. This study explored whether a participatory quality improvement (QI) intervention could be used in a protracted conflict setting to improve facility-based maternal and newborn care. A longitudinal quasi-experimental design was used to examine delivery of maternal and newborn care components at 12 health facilities in eastern Democratic Republic of Congo. Study facilities were split into two groups, with both groups receiving an initial “standard” intervention of clinical training. The “enhanced” intervention group then applied a QI methodology, which involved QI teams in each facility, supported by coaches, testing small changes to improve care. This paper presents findings on two of the study outcomes: delivery of active management of the third stage of labour (AMTSL) and essential newborn care (ENC). We measured AMTSL and ENC through exit interviews with post-partum women and matched partographs at baseline and endline over a 9-month period. Using generalised equation estimation models, the enhanced intervention group showed a greater rate of change than the control group for AMTSL (aOR 3.47, 95% CI: 1.17-10.23) and ENC (OR: 49.62, 95% CI: 2.79-888.28), and achieved 100% ENC completion at endline. This is one of the first studies where this QI methodology has been used in a protracted conflict setting. A method where health staff take ownership of improving care is of even greater value in a humanitarian context where external resources and support are scarce.

      4. Using theory-based messages to motivate U.S. pregnant women to prevent cytomegalovirus infection: results from formative research
        Levis DM, Hillard CL, Price SM, Reed-Gross E, Bonilla E, Amin M, Stowell JD, Clark R, Johnson D, Mask K, Carpentieri C, Cannon MJ.
        BMC Womens Health. 2017 Dec 14;17(1):131.
        BACKGROUND: An estimated 1 in 150 infants is born each year with congenital cytomegalovirus (CMV); nearly 1 in 750 suffers permanent disabilities. Congenital CMV is the result of a pregnant woman becoming infected with CMV. Educating pregnant women about CMV is currently the best approach to prevention. Limited research is available on how to effectively communicate with women about CMV. We conducted formative research on fear appeals theory-based messages about CMV and prevention with U.S. women. Fear appeal theories suggest that message recipients will take action if they feel fear. METHODS: First, we conducted in-depth interviews (N = 32) with women who had young children who tested positive for CMV. Second, we conducted eight focus groups (N = 70) in two phases and two cities (Phase 2: Atlanta, GA; Phase 3: San Diego, CA) with pregnant women and non-pregnant women who had young children. Few participants knew about CMV before the focus groups. Participants reviewed and gave feedback on messages created around fear appeals theory-based communication concepts. The following concepts were tested in one or more of the three phases of research: CMV is severe, CMV is common, CMV is preventable, CMV preventive strategies are similar to other behavior changes women make during pregnancy, CMV preventive strategies can be incorporated in moderation to reduce exposure, and CMV is severe but preventable. RESULTS: Participants recommended communicating that CMV is common by using prevalence ratios (e.g., 1 in 150) or comparing CMV to other well-known disabilities. To convey the severity of CMV, participants preferred stories about CMV along with prevention strategies. Participants also welcomed prevention strategies when it included a message about risk reduction. In general, participants said messages were motivating, even if they felt that it could be difficult to make certain behavior changes. CONCLUSIONS: Findings from this research can contribute to future efforts to educate pregnant women about CMV, especially regarding use of fear appeals-based messages. Pregnant women may face certain challenges to practicing prevention strategies but, overall, are motivated make changes to increase their chances of having a healthy baby.

      5. Monitoring and surveillance for multiple micronutrient supplements in pregnancy
        Mei Z, Jefferds ME, Namaste S, Suchdev PS, Flores-Ayala RC.
        Matern Child Nutr. 2017 Dec 22.
        The World Health Organization (WHO) recommends iron-folic acid (IFA) supplementation during pregnancy to improve maternal and infant health outcomes. Multiple micronutrient (MMN) supplementation in pregnancy has been implemented in select countries and emerging evidence suggests that MMN supplementation in pregnancy may provide additional benefits compared to IFA alone. In 2015, WHO, the United Nations Children’s Fund (UNICEF), and the Micronutrient Initiative held a “Technical Consultation on MMN supplements in pregnancy: implementation considerations for successful incorporation into existing programmemes,” which included a call for indicators needed for monitoring, evaluation, and surveillance of MMN supplementation programmes. Currently, global surveillance and monitoring data show that overall IFA supplementation programmes suffer from low coverage and intake adherence, despite inclusion in national policies. Common barriers that limit the effectiveness of IFA-which also apply to MMN programmes-include weak supply chains, low access to antenatal care services, low-quality behaviour change interventions to support and motivate women, and weak or non-existent monitoring systems used for programme improvement. The causes of these barriers in a given country need careful review to resolve them. As countries heighten their focus on supplementation during pregnancy, or if they decide to initiate or transition into MMN supplementation, a priority is to identify key monitoring indicators to address these issues and support effective programmes. National and global monitoring and surveillance data on IFA supplementation during pregnancy are primarily derived from cross-sectional surveys and, on a more routine basis, through health and logistics management information systems. Indicators for IFA supplementation exist; however, the new indicators for MMN supplementation need to be incorporated. We reviewed practice-based evidence, guided by the WHO/Centers for Disease Control and Prevention logic model for vitamin and mineral interventions in public health programmes, and used existing manuals, published literature, country reports, and the opinion of experts, to identify monitoring, evaluation, and surveillance indicators for MMN supplementation programmes. We also considered cross-cutting indicators that could be used across programme settings, as well as those specific to common delivery models, such as antenatal care services. We then described mechanisms for collecting these data, including integration within existing government monitoring systems, as well as other existing or proposed systems. Monitoring data needs at all stages of the programme lifecycle were considered, as well as the feasibility and cost of data collection. We also propose revisions to global-, national-, and subnational-surveillance indicators based on these reviews.

      6. Trends in special education eligibility among children with autism spectrum disorder, 2002-2010
        Rubenstein E, Daniels J, Schieve LA, Christensen DL, Van Naarden Braun K, Rice CE, Bakian AV, Durkin MS, Rosenberg SA, Kirby RS, Lee LC.
        Public Health Rep. 2017 Jan 1:33354917739582.
        OBJECTIVE: Although data on publicly available special education are informative and offer a glimpse of trends in autism spectrum disorder (ASD) and use of educational services, using these data for population-based public health monitoring has drawbacks. Our objective was to evaluate trends in special education eligibility among 8-year-old children with ASD identified in the Autism and Developmental Disabilities Monitoring Network. METHODS: We used data from 5 Autism and Developmental Disabilities Monitoring Network sites (Arizona, Colorado, Georgia, Maryland, and North Carolina) during 4 surveillance years (2002, 2006, 2008, and 2010) and compared trends in 12 categories of special education eligibility by sex and race/ethnicity. We used multivariable linear risk regressions to evaluate how the proportion of children with a given eligibility changed over time. RESULTS: Of 6010 children with ASD, more than 36% did not receive an autism eligibility in special education in each surveillance year. From surveillance year 2002 to surveillance year 2010, autism eligibility increased by 3.6 percentage points ( P = .09), and intellectual disability eligibility decreased by 4.6 percentage points ( P < .001). A greater proportion of boys than girls had an autism eligibility in 2002 (56.3% vs 48.8%). Compared with other racial/ethnic groups, Hispanic children had the largest increase in proportion with autism eligibility from 2002 to 2010 (15.4%, P = .005) and the largest decrease in proportion with intellectual disability (-14.3%, P = .004). CONCLUSION: Although most children with ASD had autism eligibility, many received special education services under other categories, and racial/ethnic disparities persisted. To monitor trends in ASD prevalence, public health officials need access to comprehensive data collected systematically, not just special education eligibility.

      7. “You have to take action”: changing knowledge and attitudes towards newborn care practices during crisis in South Sudan
        Sami S, Kerber K, Tomczyk B, Amsalu R, Jackson D, Scudder E, Dimiti A, Meyers J, Kenneth K, Kenyi S, Kennedy CE, Ackom K, Mullany LC.
        Reprod Health Matters. 2017 Dec 13:1-15.
        Highest rates of neonatal mortality occur in countries that have recently experienced conflict. International Medical Corps implemented a package of newborn interventions in June 2016, based on the Newborn health in humanitarian settings: field guide, targeting community- and facility-based health workers in displaced person camps in South Sudan. We describe health workers’ knowledge and attitudes toward newborn health interventions, before and after receiving clinical training and supplies, and recommend dissemination strategies for improved uptake of newborn guidelines during crises. A mixed methods approach was utilised, including pre-post knowledge tests and in-depth interviews. Study participants were community- and facility-based health workers in two internally displaced person camps located in Juba and Malakal and two refugee camps in Maban from March to October 2016. Mean knowledge scores for newborn care practices and danger signs increased among 72 community health workers (pre-training: 5.8 [SD: 2.3] vs. post-training: 9.6 [SD: 2.1]) and 25 facility-based health workers (pre-training: 14.2 [SD: 2.7] vs. post-training: 17.4 [SD: 2.8]). Knowledge and attitudes toward key essential practices, such as the use of partograph to assess labour progress, early initiation of breastfeeding, skin-to-skin care and weighing the baby, improved among skilled birth attendants. Despite challenges in conflict-affected settings, conducting training has the potential to increase health workers’ knowledge on neonatal health post-training. The humanitarian community should reinforce this knowledge with key actions to shift cultural norms that expand the care provided to women and their newborns in these contexts.

      8. OBJECTIVE: To determine current status, areas for improvement and effect of conflict on infant and young child feeding (IYCF) practices among internally displaced persons (IDP) in eastern Ukraine. DESIGN: Cross-sectional household survey, June 2015. SETTING: Kharkiv, Dnipropetrovsk and Zaporizhia oblasts (Ukrainian administrative divisions) bordering conflict area in Ukraine. SUBJECTS: Randomly selected IDP households with children aged <2 years registered with local non-governmental organizations. Questions based on the WHO IYCF assessment questionnaire were asked for 477 children. Mid-upper arm circumference was measured in 411 children aged 6-23 months. RESULTS: Exclusive breast-feeding prevalence for infants aged <6 months was 25.8 (95 % CI 15.8, 38.0) %. Percentage of mothers continuing breast-feeding when their child was aged 1 and 2 years was 53.5 (95 % CI 43.2, 63.6) % and 20.6 (95 % CI 11.5, 32.7) %, respectively. Bottle-feeding was common for children aged <2 years (68.1 %; 95 % CI 63.7, 72.3 %). Almost all infants aged 6-8 months received solid foods (98.6 %; 95 % CI 88.5, 99.9 %). Mothers who discontinued breast-feeding before their infant was 6 months old more often listed stress related to conflict as their primary reason for discontinuation (45.7 %) compared with mothers who discontinued breast-feeding when their child was aged 6-23 months (14.3 %; P<0.0001). CONCLUSIONS: To mitigate the effects of conflict and improve child health, humanitarian action is needed focused on helping mothers cope with stress related to conflict and displacement while supporting women to adhere to recommended IYCF practices if possible and providing appropriate support to women when adherence is not feasible.

      9. Building U.S. capacity to review and prevent maternal deaths
        Zaharatos J, St Pierre A, Cornell A, Pasalic E, Goodman D.
        J Womens Health (Larchmt). 2017 Dec 14.
        In the United States, the risk of death during and up to a year after pregnancy from pregnancy-related causes increased from approximately 10 deaths per 100,000 live births in the early 1990s to 17 deaths per 100,000 live births in 2013. While vital statistics-based surveillance systems are useful for monitoring trends and disparities, state and local maternal mortality review committees (MMRCs) are best positioned to both comprehensively assess deaths to women during pregnancy and the year after the end of pregnancy, and identify opportunities for prevention. Although the number of committees that exist has increased over the last several years, both newly formed and long-established committees struggle to achieve and sustain progress toward reviewing and preventing deaths. We describe the key elements of a MMRC; review a logic model that represents the general inputs, activities, and outcomes of a fully functional MMRC; and describe Building U.S. Capacity to Review and Prevent Maternal Deaths, a recent multisector initiative working to remove barriers to fully functional MMRCs. Increased standardization of review committee processes allows for better data to understand the multiple factors that contribute to maternal deaths and facilitates the collaboration that is necessary to eliminate preventable maternal deaths in the United States.

    • Mining
      1. Chemical properties of coal largely determine coal handling, processing, beneficiation methods, and design of coal-fired power plants. Furthermore, these properties impact coal strength, coal blending during mining, as well as coal’s gas content, which is important for mining safety. In order for these processes and quantitative predictions to be successful, safer, and economically feasible, it is important to determine and map chemical properties of coals accurately in order to infer these properties prior to mining. Ultimate analysis quantifies principal chemical elements in coal. These elements are C, H, N, S, O, and, depending on the basis, ash, and/or moisture. The basis for the data is determined by the condition of the sample at the time of analysis, with an “as-received” basis being the closest to sampling conditions and thus to the in-situ conditions of the coal. The parts determined or calculated as the result of ultimate analyses are compositions, reported in weight percent, and pose the challenges of statistical analyses of compositional data. The treatment of parts using proper compositional methods may be even more important in mapping them, as most mapping methods carry uncertainty due to partial sampling as well. In this work, we map the ultimate analyses parts of the Springfield coal from an Indiana section of the Illinois basin, USA, using sequential Gaussian simulation of isometric log-ratio transformed compositions. We compare the results with those of direct simulations of compositional parts. We also compare the implications of these approaches in calculating other properties using correlations to identify the differences and consequences. Although the study here is for coal, the methods described in the paper are applicable to any situation involving compositional data and its mapping.

      2. Analysis of global and local stress changes in a longwall gateroad
        Tulu IB, Esterhuizen GS, Gearhart D, Klemetti TM, Mohamed KM, Su DW.
        Int J Min Sci Technol. 2017 .
        A numerical-model-based approach was recently developed for estimating the changes in both the horizontal and vertical loading conditions induced by an approaching longwall face. In this approach, a systematic procedure is used to estimate the model’s inputs. Shearing along the bedding planes is modeled with ubiquitous joint elements and interface elements. Coal is modeled with a newly developed coal mass model. The response of the gob is calibrated with back analysis of subsidence data and the results of previously published laboratory tests on rock fragments. The model results were verified with the subsidence and stress data recently collected from a longwall mine in the eastern United States.

    • Nutritional Sciences
      1. Iron status of toddlers, nonpregnant females, and pregnant females in the United States
        Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z.
        Am J Clin Nutr. 2017 Dec;106(Suppl 6):1640s-1646s.
        Background: Total-body iron stores (TBI), which are calculated from serum ferritin and soluble transferrin receptor concentrations, can be used to assess the iron status of populations in the United States.Objective: This analysis, developed to support workshop discussions, describes the distribution of TBI and the prevalence of iron deficiency (ID) and ID anemia (IDA) among toddlers, nonpregnant females, and pregnant females.Design: We analyzed data from NHANES; toddlers aged 12-23 mo (NHANES 2003-2010), nonpregnant females aged 15-49 y (NHANES 2007-2010), and pregnant females aged 12-49 y (NHANES 1999-2010). We used SAS survey procedures to plot distributions of TBI and produce prevalence estimates of ID and IDA for each target population. All analyses were weighted to account for the complex survey design.Results: According to these data, ID prevalences (+/- SEs) were 15.1% +/- 1.7%, 10.4% +/- 0.5%, and 16.3% +/- 1.3% in toddlers, nonpregnant females, and pregnant females, respectively. ID prevalence in pregnant females increased significantly with each trimester (5.3% +/- 1.5%, 12.7% +/- 2.3%, and 27.5% +/- 3.5% in the first, second, and third trimesters, respectively). Racial disparities in the prevalence of ID among both nonpregnant and pregnant females exist, with Mexican American and non-Hispanic black females at greater risk of ID than non-Hispanic white females. IDA prevalence was 5.0% +/- 0.4% and 2.6% +/- 0.7% in nonpregnant and pregnant females, respectively.Conclusions: Available nationally representative data suggest that ID and IDA remain a concern in the United States. Estimates of iron-replete status cannot be made at this time in the absence of established cutoffs for iron repletion based on TBI. The study was registered at as NCT03274726.

      2. INTRODUCTION: Information on dietary intake, including sugar-sweetened beverages (SSBs), for adults with disabilities is limited. Such information can inform interventions to prevent chronic disease and promote health among adults with disabilities. The objective of this study was to describe the associations between SSB consumption and disability among adults. METHODS: We examined data on adults aged 18 years or older in 23 states and the District of Columbia who participated in the 2013 Behavioral Risk Factor Surveillance System (n = 150,760). Participants who reported a limitation in any activity caused by physical, mental, or emotional problems or who reported use of special equipment were considered to have a disability (n = 41,199). Participants were classified as daily SSB consumers (>/=1 time/d) and non-daily SSB consumers (<1 time/d). Multivariable logistic regression was used to examine associations between daily SSB intake and disability after controlling for sociodemographic characteristics. An interaction effect between disability and obesity status was tested to consider obesity status as a potential effect modifier. RESULTS: The prevalence of drinking SSBs at least once daily was significantly higher among adults with disabilities (30.3%) than among adults without disabilities (28.6%) (P = .01). After controlling for sociodemographic characteristics, among nonobese adults, the odds of daily SSB intake were significantly higher among adults with disabilities than among adults without disabilities (adjusted odds ratio = 1.27, P < .001). Among obese adults, daily SSB intake was not associated with disability status (adjusted odds ratio = 0.97; P = .58). CONCLUSION: Our findings highlight the need for increased awareness of SSB consumption among adults with disabilities.

      3. Assessment of iron status in settings of inflammation: challenges and potential approaches
        Suchdev PS, Williams AM, Mei Z, Flores-Ayala R, Pasricha SR, Rogers LM, Namaste SM.
        Am J Clin Nutr. 2017 Dec;106(Suppl 6):1626s-1633s.
        The determination of iron status is challenging when concomitant infection and inflammation are present because of confounding effects of the acute-phase response on the interpretation of most iron indicators. This review summarizes the effects of inflammation on indicators of iron status and assesses the impact of a regression analysis to adjust for inflammation on estimates of iron deficiency (ID) in low- and high-infection-burden settings. We overviewed cross-sectional data from 16 surveys for preschool children (PSC) (n = 29,765) and from 10 surveys for nonpregnant women of reproductive age (WRA) (n = 25,731) from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Effects of C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) concentrations on estimates of ID according to serum ferritin (SF) (used generically to include plasma ferritin), soluble transferrin receptor (sTfR), and total body iron (TBI) were summarized in relation to infection burden (in the United States compared with other countries) and population group (PSC compared with WRA). Effects of the concentrations of CRP and AGP on SF, sTfR, and TBI were generally linear, especially in PSC. Overall, regression correction changed the estimated prevalence of ID in PSC by a median of +25 percentage points (pps) when SF concentrations were used, by -15 pps when sTfR concentrations were used, and by +14 pps when TBI was used; the estimated prevalence of ID in WRA changed by a median of +8 pps when SF concentrations were used, by -10 pps when sTfR concentrations were used, and by +3 pps when TBI was used. In the United States, inflammation correction was done only for CRP concentrations because AGP concentrations were not measured; regression correction for CRP concentrations increased the estimated prevalence of ID when SF concentrations were used by 3 pps in PSC and by 7 pps in WRA. The correction of iron-status indicators for inflammation with the use of regression correction appears to substantially change estimates of ID prevalence in low- and high-infection-burden countries. More research is needed to determine the validity of inflammation-corrected estimates, their dependence on the etiology of inflammation, and their applicability to individual iron-status assessment in clinical settings.

      4. Youth access to school salad bars in the United States – 2011 to 2014
        VanFrank BK, Onufrak S, Harris DM.
        Am J Health Promot. 2018 Jan;32(1):84-88.
        PURPOSE: To examine differences in students’ access to school salad bars across sociodemographic groups and changes in availability over time. DESIGN: Nonexperimental. SETTING: Nationally representative 2011 and 2014 YouthStyles surveys. PARTICIPANTS: A total of 833 (2011) and 994 (2014) US youth aged 12 to 17 years. MEASURES: Youth-reported availability of school salad bars. ANALYSIS: Multivariable logistic regression models were used to assess differences in school salad bar availability by sociodemographics and changes in availability from 2011 to 2014. RESULTS: Youth-reported salad bar availability differed by age in 2011 and race/ethnicity in 2014, but not by sex, income, metropolitan residence, or region in either year. Salad bars were reported by 62% of youth in 2011 and 67% in 2014; the increase was not statistically significant ( P = .07). Significant increases from 2011 to 2014 were noted among youth aged 12 to 14 years (56%-69%; P < .01), youth of non-Hispanic other races (60%-85%; P < .01), and youth in the Midwest (58%-72%; P = .01). CONCLUSION: These results suggest that youth-reported access to school salad bars does not differ significantly across most sociodemographic groups. Although overall salad bar availability did not increase significantly from 2011 to 2014, some increases were observed among subgroups. Continued efforts to promote school salad bars through initiatives such as Let’s Move Salad Bars to Schools could help increase access for the nearly one-third of US youth reporting no access.

    • Occupational Safety and Health
      1. [No abstract]

      2. Position statement: Reducing fatigue associated with sleep deficiency and work hours in nurses
        Caruso CC, Baldwin CM, Berger A, Chasens ER, Landis C, Redeker NS, Scott LD, Trinkoff A.
        Nurs Outlook. 2017 Nov – Dec;65(6):766-768.

        [No abstract]

      3. Mental Health in the Workplace: A Call to Action proceedings from the Mental Health in the Workplace: Public Health Summit
        Goetzel RZ, Roemer EC, Holingue C, Fallin MD, McCleary K, Eaton W, Agnew J, Azocar F, Ballard D, Bartlett J, Braga M, Conway H, Crighton KA, Frank R, Jinnett K, Keller-Greene D, Rauch SM, Safeer R, Saporito D, Schill A, Shern D, Strecher V, Wald P, Wang P, Mattingly CR.
        J Occup Environ Med. 2017 Dec 26.
        OBJECTIVE: To declare a call to action to improve mental health in the workplace. METHODS: We convened a public health summit and assembled an Advisory Council consisting of experts in the field of occupational health and safety, workplace wellness, and public policy to offer recommendations for action steps to improve health and well-being of workers. RESULTS: The Advisory Council narrowed the list of ideas to four priority projects. CONCLUSIONS: The recommendations for action include developing a Mental Health in the Workplace 1) “How to” Guide, 2) Scorecard, 3) Recognition Program, and 4) Executive Training.

      4. Association between blood pressure and retinal vessel diameters among police officers in the US northeast
        Gu JK, Charles LE, Klein R, Grady LM, Ma CC, Baughman P, Violanti JM, Andrew ME.
        J Occup Environ Med. 2017 Dec 8.
        OBJECTIVE: To examine relationships of blood pressure with central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) among 242 police officers. METHODS: Computerized retinal images of each eye were taken. Mean values of CRAE and CRVE were compared across hypertension status categories using ANOVA and ANCOVA. Associations of mean arterial blood pressure (MABP) with CRAE and CRVE were obtained using regression models. RESULTS: CRAE were significantly narrower in officers with uncontrolled hypertension (142.8 +/- 2.7 mum), compared to those with controlled hypertension (153.6 +/- 2.7 mum, p = 0.0013) and those with no hypertension (156.4 +/- 1.0 mum, p </= 0.0001) after covariate adjustment. CRAE decreased by 3.43 mum for each 5 mmHG increase in MABP (p </= 0.0001). CONCLUSION: Uncontrolled hypertension was significantly associated with narrower retinal arterioles. No association was observed with retinal venules.

      5. Serum YKL-40 in workers at an indium-tin oxide production facility
        Harvey RR, Hawley BM, Virji MA, Cummings KJ.
        Respirology. 2017 Dec 15.

        [No abstract]

      6. Surgical smoke control with local exhaust ventilation: Experimental study
        Lee T, Soo JC, LeBouf RF, Burns D, Schwegler-Berry D, Kashon M, Bowers J, Harper M.
        J Occup Environ Hyg. 2017 Dec 28:0.
        This experimental study aimed to evaluate airborne particulates and volatile organic compounds (VOCs) from surgical smoke when a local exhaust ventilation (LEV) system is in place. Surgical smoke was generated from human tissue in an unoccupied operating room using an electrocautery surgical device for 15 minutes with three different test settings; 1) without LEV control, 2) control with a wall irrigation suction unit with an in-line ultra-low penetration air filter and 3) control with a smoke evacuation system. Flow rate of LEVs was approximately 35 L/min and suction was maintained within 5 cm of electrocautery interaction site. A total of 6 experiments were conducted. Particle number and mass concentrations were measured using direct reading instruments including a condensation particle counter (CPC), a light-scattering laser photometer (DustTrak DRX), a scanning mobility particle sizer (SMPS), an aerodynamic particle sizer (APS) and a viable particle counter. Selected VOCs were collected using evacuated canisters using grab, personal and area sampling techniques. The largest average particle and VOCs concentrations were found in the absence of LEV control followed by LEV controls. Average ratios of LEV controls to without LEV control ranged 0.24-0.33 (CPC), 0.28-0.39 (SMPS), 0.14-0.31 (DustTrak DRX), 0.26-0.55 (APS). Ethanol and isopropyl alcohol were dominant in the canister samples. Acetaldehyde, acetone, acetonitrile, benzene, hexane, styrene and toluene were detected but at lower concentrations (<500 mug/m(3)) and concentrations of the VOCs were much less than the National Institute for Occupational Safety and Health recommended exposure limit values. Utilization of the LEVs for surgical smoke control can significantly reduce but not completely eliminate airborne particles and VOCs.

    • Parasitic Diseases
      1. Toxoplasma gondii Infection in the United States, 2011-2014
        Jones JL, Kruszon-Moran D, Elder S, Rivera HN, Press C, Montoya JG, McQuillan GM.
        Am J Trop Med Hyg. 2017 Dec 18.
        Toxoplasma gondii can cause severe neurologic and ocular disease when transmitted congenitally and in immunosuppressed persons. Sera collected in the National Health and Nutrition Examination Survey 2011 through 2014 in 13,507 persons >/= 6 years old were tested for T. gondii immunoglobulin (Ig) G and IgM antibodies, and in those both IgG and IgM antibody positive, for IgG avidity. Overall, 11.14% (95% confidence limits [CL] 9.88%, 12.51%) were seropositive for T. gondii IgG antibody (age-adjusted seroprevalence 10.42% [95% CL 9.19%, 11.76%]); in women aged 15-44 years, the age-adjusted T. gondii IgG seroprevalence was 7.50% (95% CL 6.00%, 9.25%). In multivariable analysis, risk for IgG seropositivity increased with age and was higher in males; persons living below the poverty level; persons with </= a high school education compared with those with > a high school education; and non-Hispanic black, Mexican American, and foreign born non-Hispanic white persons compared with U.S.-born non-Hispanic white persons. Overall, 1.16% (95% CL 0.94%, 1.42%) were T. gondii IgM antibody positive and 0.71%, (95% CL 0.54%, 0.92%) were both IgM and IgG antibody positive. In multivariable analysis, the significant risk factors for being both IgM and IgG positive were age, crowding, and non-U.S. birth origin compared with U.S.-born persons. Among those positive for both IgM and IgG antibody, almost all had high avidity (all women aged 15-44 years had high avidity). Toxoplasma gondii antibody prevalence remains relatively low in the United States, although it is higher in non-U.S.-born persons, males, and some minority and socioeconomically disadvantaged groups.

      2. Post-treatment HRP2 clearance in patients with uncomplicated Plasmodium falciparum malaria
        Plucinski MM, Dimbu PR, Fortes F, Abdulla S, Ahmed S, Gutman J, Kachur SP, Badiane A, Ndiaye D, Talundzic E, Lucchi N, Aidoo M, Udhayakumar V, Halsey E, Rogier E.
        J Infect Dis. 2017 Dec 6.
        Background: Response to antimalarial treatment is assessed using serial microscopy. New techniques for accurate measurement of the Plasmodium falciparum histidine rich protein 2 (HRP2) antigen have made monitoring antigen concentration over time a potential alternative for assessing treatment response. Methods: Post-treatment HRP2 concentration was measured in longitudinal samples from 537 participants with P. falciparum malaria from efficacy trials in Angola, Tanzania, and Senegal. The HRP2 half-life was estimated using a first-order kinetics clearance model. The association between HRP2 concentration three days post-treatment and recrudescence of infection was assessed. Results: Despite substantial variation in HRP2 concentration at baseline, HRP2 concentration in patients consistently showed a first-order exponential decline. The median half-life of HRP2 was estimated to be 4.5 days (interquartile range: 3.3-6.6) in Angola, 4.7 days (4.0-5.9) in Tanzania, and 3.0 days (2.1-4.5) in Senegal. The day 3 HRP2 concentration was predictive of eventual recrudescence, with an area under the receiver operating characteristic curve of 0.86 (95% confidence interval: 0.73-0.99). Conclusions: Consistent HRP2 clearance dynamics following successful antimalarial treatment imply a common underlying biological clearance mechanism. Patients that ultimately failed treatment did not exhibit this same pattern of clearance, even in the absence of other indications of inadequate response to treatment.

      3. Abbreviated atovaquone-proguanil prophylaxis regimens in travellers after leaving malaria-endemic areas: A systematic review
        Savelkoel J, Binnendijk KH, Spijker R, van Vugt M, Tan K, Hanscheid T, Schlagenhauf P, Grobusch MP.
        Travel Med Infect Dis. 2017 Dec 11.
        BACKGROUND: We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after return as per currently recommended post-travel schedule. METHODS: PubMed and Embase databases were searched to identify relevant studies. This PROSPERO-registered systematic review followed PRISMA guidelines. The search strategy included terms or synonyms relevant to AP combined with terms to identify articles relating to prophylactic use of AP and inhibitory and half-life properties of AP. Studies considered for inclusion were: randomized controlled trials, cohort studies, quasi-experimental studies, open-label trials, patient-control studies, cross-sectional studies; as well as case-series and non-clinical studies. Data on study design, characteristics of participants, interventions, and outcomes were extracted. Primary outcomes considered relevant were prophylactic efficacy and prolonged inhibitory activity and half-life properties of AP. RESULTS: The initial search identified 1,482 publications, of which 40 were selected based on screening. Following full text review, 32 studies were included and categorized into two groups, namely studies in support of the current post-travel regimen (with a total of 2,866 subjects) and studies in support of an alternative regimen (with a total of 533 subjects). CONCLUSION: There is limited direct and indirect evidence to suggest that an abbreviated post-travel regimen for AP may be effective. Proguanil, however, has a short half-life and is essential for the synergistic effect of the combination. Stopping AP early may result in mono-prophylaxis with atovaquone and possibly select for atovaquone-resistant parasites. Furthermore, the quality of the studies in support of the current post-travel regimen outweighs the quality of the studies in support of an alternative short, post-travel regimen, and the total sample size of the studies to support stopping AP early comprises a small percentage of the total sample size of the studies performed to establish the efficacy of the current AP regimen. Additional research is required – especially from studies evaluating impact on malaria parasitaemia and clinical illness and conducted among travellers in high malaria risk settings – before an abbreviated regimen can be recommended in current practice. PROSPERO REGISTRATION NUMBER: CRD42017055244.

      4. Antibody profiling by proteome microarray with multiplex isotype detection reveals overlap between human and Aotus nancymaae controlled malaria infections
        Taghavian O, Jain A, Joyner CJ, Ketchum S, Nakajima R, Jasinskas A, Liang L, Fong R, King C, Greenhouse B, Murphy M, Bailey J, Galinski MR, Barnwell JW, Plowe CV, Davies DH, Felgner PL.
        Proteomics. 2017 Dec 19.
        The development of vaccines against malaria and serodiagnostic tests for detecting recent exposure requires tools for antigen discovery and suitable animal models. The protein microarray is a high-throughput, sample sparing technique, with applications in infectious disease research, clinical diagnostics, epidemiology, and vaccine development. We recently demonstrated Qdot((R)) -based indirect immunofluorescence together with portable optical imager ArrayCAM((R)) using single isotype detection could replicate data using the conventional laser confocal scanner system. We developed a multiplexing protocol for simultaneous detection of IgG, IgA and IgM and compared samples from a controlled human malaria infection model with those from controlled malaria infections of Aotus nancymaae, a widely-used non-human primate model of human malaria. IgG profiles showed the highest concordance in number of reactive antigens; thus, of the 139 antigens recognized by human IgG antibody, 111 were also recognized by Aotus monkeys. Interestingly, IgA profiles were largely non-overlapping. Finally, on the path toward wider deployment of the portable platform, we show excellent correlations between array data obtained in 5 independent laboratories around the U.S. using the multiplexing protocol (R(2) : 0.60-0.92). This study supports the use of this platform for wider deployment, particularly in endemic areas where such a tool will have the greatest impact on global human health. This article is protected by copyright. All rights reserved.

    • Physical Activity
      1. Environmental supports for physical activity, National Health Interview Survey-2015
        Whitfield GP, Carlson SA, Ussery EN, Watson KB, Adams MA, James P, Brownson RC, Berrigan D, Fulton JE.
        Am J Prev Med. 2017 Dec 12.
        INTRODUCTION: The Guide to Community Preventive Services recommends combined built environment approaches to increase physical activity, including new or enhanced transportation infrastructure (e.g., sidewalks) and land use and environmental design interventions (e.g., close proximity of local destinations). The aim of this brief report is to provide nationally representative estimates of two types of built environment supports for physical activity: near-home walkable infrastructure and destinations, from the 2015 National Health Interview Survey. METHODS: Adults (n=30,453) reported the near-home presence of walkable transportation infrastructure (roads, sidewalks, paths, or trails where you can walk; and whether most streets have sidewalks) and four walkable destination types (shops, stores, or markets; bus or transit stops; movies, libraries, or churches; and places that help you relax, clear your mind, and reduce stress). The prevalence of each, and the count of destination types, was calculated (in 2017) and stratified by demographic characteristics. RESULTS: Overall, 85.1% reported roads, sidewalks, paths, or trails on which to walk, and 62.6% reported sidewalks on most streets. Among destinations, 71.8% reported walkable places to relax; followed by shops (58.0%); transit stops (53.2%); and movies, libraries, or churches (47.5%). For most design elements, prevalence was similar among adults aged 18-24 and 25-34 years, but decreased with age >35 years. Adults in the South reported a lower prevalence of all elements compared with those in other Census regions. CONCLUSIONS: Many U.S. adults report walkable built environment elements near their home; future efforts might target areas with many older adult residents or those living in the South.

    • Reproductive Health
      1. Access to long-acting reversible contraception among US publicly-funded health centers
        Bornstein M, Carter M, Zapata L, Gavin L, Moskosky S.
        Contraception. 2017 Dec 15.
        OBJECTIVES: Access to a full range of contraceptive methods, including long-acting reversible contraception (LARC), is central to providing quality family planning services. We describe health center-related factors associated with LARC availability, including staff training in LARC insertion/removal and approaches to offering LARC, whether onsite or through referral. STUDY DESIGN: We analyzed nationally representative survey data collected during 2013-2014 from administrators of publicly funded U.S. health centers that offered family planning. The response rate was 49.3% (n=1615). In addition to descriptive statistics, we used multivariable logistic regression to identify health center characteristics associated with offering both IUDs and implants onsite. RESULTS: Two-thirds (64%) of health centers had staff trained in all three LARC types (hormonal IUD, copper IUD, implant); 21% had no staff trained in any of those contraceptive methods. Half of health centers (52%) offered IUDs (any type) and implants onsite. After onsite provision, informal referral arrangements were the most common way LARC methods were offered. In adjusted analyses, Planned Parenthood (AOR=9.49) and hospital-based (AOR=2.35) health centers had increased odds of offering IUDs (any type) and implants onsite, compared to health departments, as did Title X-funded (AOR=1.55) compared to non-Title X-funded health centers and centers serving a larger volume of family planning clients. Centers serving mostly rural areas compared to those serving urbans areas had lower odds (AOR 0.60) of offering IUD (any type) and implants. CONCLUSIONS: Variation in LARC access remains among publicly funded health centers. In particular, health departments and rural health centers have relatively low LARC provision. IMPLICATIONS: For more women to be offered a full range of contraceptive methods, additional efforts should be made to increase availability of LARC in publicly-funded health centers, such as addressing provider training gaps, improving referrals mechanisms, and other efforts to strengthen the health care system.

      2. In April 2014, CDC published “Providing Quality Family Planning Services: Recommendations of CDC and the U.S. Office of Population Affairs” (QFP), which describes the scope of services that should be offered in a family planning visit and how to provide those services (e.g., periodicity of screening, which persons are in need of services, etc.) (1). The sections in QFP include the following: Determining the Client’s Need for Services; Contraceptive Services; Pregnancy Testing and Counseling; Clients Who Want to Become Pregnant; Basic Infertility Services; Preconception Health Services; Sexually Transmitted Disease Services; and Related Preventive Health Services. In addition, the QFP includes an appendix entitled Screening Services for Which Evidence Does Not Support Screening.

      3. Contraceptive use at last intercourse among reproductive-aged women with disabilities: an analysis of population-based data from seven states
        Haynes RM, Boulet SL, Fox MH, Carroll DD, Courtney-Long E, Warner L.
        Contraception. 2017 Dec 15.
        OBJECTIVE: To assess patterns of contraceptive use at last intercourse among women with physical or cognitive disabilities compared to women without disabilities. STUDY DESIGN: We analyzed responses to 12 reproductive health questions added by seven states to their 2013 Behavioral Risk Factor Surveillance System questionnaire. Using responses from female respondents 18-50years of age, we performed multinomial regression to calculate estimates of contraceptive use among women at risk for unintended pregnancy by disability status and type, adjusted for age, race/ethnicity, marital status, education, health insurance status, and parity. RESULTS: Women with disabilities had similar rates of sexual activity as women without disabilities (90.0% vs. 90.6%, p=.76). Of 5995 reproductive-aged women at risk for unintended pregnancy, 1025 (17.1%) reported one or more disabilities. Contraceptive use at last intercourse was reported by 744 (70.1%) of women with disabilities compared with 3805 (74.3%) of those without disabilities (p=.22). Among women using contraception, women with disabilities used male or female permanent contraception more often than women without disabilities (333 [29.6%] versus 1337 [23.1%], p<.05). Moderately effective contraceptive (injection, oral contraceptive, patch, or ring) use occurred less frequently among women with cognitive (13.1%, n=89) or independent living (13.9%, n=40) disabilities compared to women without disabilities (22.2%, n=946, p<.05). CONCLUSIONS: The overall prevalence of sexual activity and contraceptive use was similar for women with and without physical or cognitive disabilities. Method use at last intercourse varied based on presence and type of disability, especially for use of permanent contraception. IMPLICATIONS: Although women with disabilities were sexually active and used contraception at similar rates as women without disabilities, contraception use varied by disability type, suggesting the importance of this factor in reproductive health decision-making among patients and providers, and the value of further research to identify reasons why this occurs.

      4. ‘We do not know’: a qualitative study exploring boys perceptions of menstruation in India
        Mason L, Sivakami M, Thakur H, Kakade N, Beauman A, Alexander KT, van Eijke AM, Laserson KF, Thakkar MB, Phillips-Howard PA.
        Reprod Health. 2017 Dec 8;14(1):174.
        BACKGROUND: In low-middle income countries and other areas of poverty, menstrual hygiene management (MHM) can be problematic for women and girls. Issues include lack of knowledge about menstruation and MHM, and stigma around menstruation, also access to affordable and absorbent materials; privacy to change; adequate washing, cleaning and drying facilities; as well as appropriate and accessible disposal facilities. In order to effect change and tackle these issues, particularly in patriarchal societies, males may need to become advocates for MHM alongside women. However, little is known about their knowledge and attitudes towards menstruation, which may need addressing before they can assist in acting as advocates for change. The present study was undertaken to explore knowledge and attitudes about menstruation among adolescent boys across India, in order to gauge their potential to support their ‘sisters’. METHODS: The study was undertaken across three states in India, chosen a priori to represent the cultural and socio-economic diversity. Qualitative data using focus group discussions with 85 boys aged 13-17 years, from 8 schools, was gathered. Data were analysed using thematic analysis. RESULTS: The results were organised into three main themes, reflecting the key research questions: boys’ knowledge of menstruation, source of knowledge, and attitudes towards menstruation and menstruating girls. Knowledge comprised three aspects; biological function which were generally poorly understood; cultural rites which were recognized by all; and girls’ behaviour and demeanour, which were noted to be withdrawn. Some boys learnt about puberty and menstruation as part of the curriculum but had concerns this was not in-depth, or was missed out altogether. Most gathered knowledge from informal sources, from overhearing conversations or observing cultural rituals. Few boys openly displayed a negative attitude, although a minority voiced the idea that menstruation is a ‘disease’. Boys were mostly sympathetic to their menstruating sisters and wanted to support them. CONCLUSIONS: These findings provide some optimism that males can become advocates in moving forward the MHM agenda. The reasons for this are twofold: boys were keen for knowledge about menstruation, searching information out despite societal norms being for them to remain ignorant, they were also largely sympathetic to their menstruating sisters and fellow classmates and understanding of the issues surrounding the need for good MHM.

      5. Discordance between self-reported contraceptive use and detection of exogenous hormones among Malawian women enrolling in a randomized clinical trial
        Nwaohiri AN, Tang JH, Stanczyk F, Chinula L, Hurst S, Davis NL, Tegha G, Haddad L, Kourtis AP.
        Contraception. 2017 Dec 13.
        OBJECTIVE: To assess the extent of concordance between self-reported contraceptive use and the presence of contraceptive progestins in serum. STUDY DESIGN: We evaluated self-reported contraceptive use by using radioimmunoassay to examine baseline serum levels of medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) among 97 Malawian women enrolling in a contraceptive trial. RESULTS: Twelve percent (12/97) of study participants who reported no hormonal contraceptive use in the previous 6months had either MPA or LNG detected in their serum. CONCLUSIONS: The observed discordance between self-report and detection of exogenous hormones in serum indicates that caution is warranted when drawing conclusions based on self-reported contraceptive use.

      6. Teen pregnancy in rural western Kenya: a public health issue
        Omoro T, Gray SC, Otieno G, Mbeda C, Phillips-Howard PA, Hayes T, Otieno F, Gust DA.
        Int J Adolesc Youth. 2017 :1-10.
        Rates of teenage pregnancy remain high in sub-Saharan Africa. The KEMRI Health and Demographic Surveillance System provided the sampling frame for a survey. Analysis focused on 1,952 girls aged 13-19?years. Over a third (37.2%; n=727) were sexually active and 23.3% (n=454) had ever been pregnant. Adjusted odds of reporting a history of pregnancy were greater for older compared to younger teens, teens who were ever married or cohabiting compared to those who were single, teens with a primary education or less compared to those with a higher level of education, and teens who experienced partner violence in the last 12 months. Three-quarters of teens pregnant in the last 12 months did not want to get pregnant (n=190); only 64.2% (n=122) answered yes to using any family planning method. Teen pregnancy and its consequences are serious public health issues. Higher education levels are a crucial component to address the problem.

    • Substance Use and Abuse
      1. Evaluation of a federally funded mass media campaign and smoking cessation in pregnant women: a population-based study in three states
        England L, Tong VT, Rockhill K, Hsia J, McAfee T, Patel D, Rupp K, Conrey EJ, Valdivieso C, Davis KC.
        BMJ Open. 2017 Dec 19;7(12):e016826.
        OBJECTIVES: In 2012, theCenters for Disease Control and Prevention initiated a national anti-smoking campaign, Tips from Former Smokers (Tips). As a result of the campaign, quit attempts among smokers increased in the general population by 3.7 percentage points. In the current study, we assessed the effects of Tips on smoking cessation in pregnant women. METHODS: We used 2009-2013 certificates of live births in three US states: Indiana, Kentucky and Ohio. Smoking cessation by the third trimester of pregnancy was examined among women who smoked in the 3 months prepregnancy. Campaign exposure was defined as overlap between the airing of Tips 2012 (March 19-June 10) and the prepregnancy and pregnancy periods. Women who delivered before Tips 2012 were not exposed. Adjusted logistic regression was used to determine whether exposure to Tips was independently associated with smoking cessation. RESULTS: Cessation rates were stable during 2009-2011 but increased at the time Tips 2012 aired and remained elevated. Overall, 32.9% of unexposed and 34.7% of exposed smokers quit by the third trimester (p<0.001). Exposure to Tips 2012 was associated with increased cessation (adjusted OR: 1.07, 95% CI 1.05 to 1.10). CONCLUSIONS: Exposure to a national anti-smoking campaign for a general audience was associated with smoking cessation in pregnant women.

      2. State laws regarding indoor public use, retail sales, and prices of electronic cigarettes – U.S. States, Guam, Puerto Rico, and U.S. Virgin Islands, September 30, 2017
        Marynak K, Kenemer B, King BA, Tynan MA, MacNeil A, Reimels E.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1341-1346.
        Electronic cigarettes (e-cigarettes) are the most frequently used tobacco product among U.S. youths, and past 30-day e-cigarette use is more prevalent among high school students than among adults (1,2). E-cigarettes typically deliver nicotine, and the U.S. Surgeon General has concluded that nicotine exposure during adolescence can cause addiction and can harm the developing adolescent brain (2). Through authority granted by the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration (FDA) prohibits e-cigarette sales to minors, free samples, and vending machine sales, except in adult-only facilities (3). States, localities, territories, and tribes maintain broad authority to adopt additional or more stringent requirements regarding tobacco product use, sales, marketing, and other topics (2,4). To understand the current e-cigarette policy landscape in the United States, CDC assessed state and territorial laws that 1) prohibit e-cigarette use and conventional tobacco smoking indoors in restaurants, bars, and worksites; 2) require a retail license to sell e-cigarettes; 3) prohibit e-cigarette self-service displays (e.g., requirement that products be kept behind the counter or in a locked box); 4) establish 21 years as the minimum age of purchase for all tobacco products, including e-cigarettes (tobacco-21); and 5) apply an excise tax to e-cigarettes. As of September 30, 2017, eight states, the District of Columbia (DC), and Puerto Rico prohibited indoor e-cigarette use and smoking in indoor areas of restaurants, bars, and worksites; 16 states, DC, and the U.S. Virgin Islands required a retail license to sell e-cigarettes; 26 states prohibited e-cigarette self-service displays; five states, DC, and Guam had tobacco-21 laws; and eight states, DC, Puerto Rico, and the U.S. Virgin Islands taxed e-cigarettes. Sixteen states had none of the assessed laws. A comprehensive approach that combines state-level strategies to reduce youths’ initiation of e-cigarettes and population exposure to e-cigarette aerosol, coupled with federal regulation, could help reduce health risks posed by e-cigarettes among youths (2,5).

      3. Prevalence and disparities in tobacco product use among American Indians/Alaska Natives – United States, 2010-2015
        Odani S, Armour BS, Graffunder CM, Garrett BE, Agaku IT.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 22;66(50):1374-1378.
        An overarching goal of Healthy People 2020 is to achieve health equity, eliminate disparities, and improve health among all groups.* Although significant progress has been made in reducing overall commercial tobacco product use,(dagger) disparities persist, with American Indians or Alaska Natives (AI/ANs) having one of the highest prevalences of cigarette smoking among all racial/ethnic groups (1,2). Variations in cigarette smoking among AI/ANs have been documented by sex and geographic location (3), but not by other sociodemographic characteristics. Furthermore, few data exist on use of tobacco products other than cigarettes among AI/ANs (4). CDC analyzed self-reported current (past 30-day) use of five tobacco product types among AI/AN adults from the 2010-2015 National Survey on Drug Use and Health (NSDUH); results were compared with six other racial/ethnic groups (Hispanic; non-Hispanic white [white]; non-Hispanic black [black]; non-Hispanic Native Hawaiian or other Pacific Islander [NHOPI]; non-Hispanic Asian [Asian]; and non-Hispanic multirace [multirace]). Prevalence of current tobacco product use was significantly higher among AI/ANs than among non-AI/ANs combined for any tobacco product, cigarettes, roll-your-own tobacco, pipes, and smokeless tobacco. Among AI/ANs, prevalence of current use of any tobacco product was higher among males, persons aged 18-25 years, those with less than a high school diploma, those with annual family income <$20,000, those who lived below the federal poverty level, and those who were never married. Addressing the social determinants of health and providing evidence-based, population-level, and culturally appropriate tobacco control interventions could help reduce tobacco product use and eliminate disparities in tobacco product use among AI/ANs.

      4. Cigarette design features: Effects on emission levels, user perception, and behavior
        Talhout R, Richter PA, Stepanov I, Watson CV, Watson CH.
        Tob Regul Sci. 2018 Jan;4(1):592-604.
        Objectives: This paper describes the effects of non-tobacco, physical cigarette design features on smoke emissions, product appeal, and smoking behaviors – 3 factors that determine smoker’s exposure and related health risks. Methods: We reviewed available evidence for the impact of filter ventilation, new filter types, and cigarettes dimensions on toxic emissions, smoker’s perceptions, and behavior. For evidence sources we used scientific literature and websites providing product characteristics and marketing information. Results: Whereas filter ventilation results in lower machine-generated emissions, it also leads to perceptions of lighter taste and relative safety in smokers who can unwittingly employ more intense smoking behavior to obtain the desired amount of nicotine and sensory appeal. Filter additives that modify smoke emissions can also modify sensory cues, resulting in changes in smoking behavior. Flavor capsules increase the cigarette’s appeal and novelty, and lead to misperceptions of reduced harm. Slim cigarettes have lower yields of some smoke emissions, but smoking behavior can be more intense than with standard cigarettes. Conclusions: Physical design features significantly impact machine-measured emission yields in cigarette smoke, product appeal, smoking behaviors, and exposures in smokers. The influence of current and emerging design features is important in understanding the effectiveness of regulatory actions to reduce smoking-related harm.

      5. Screening for alcohol misuse: Practices among U.S. primary care providers, DocStyles 2016
        Tan CH, Hungerford DW, Denny CH, McKnight-Eily LR.
        Am J Prev Med. 2017 Dec 6.
        INTRODUCTION: Excessive alcohol use is associated with car crashes, violence, and multiple disease conditions, including fetal alcohol spectrum disorders. The U.S. Preventive Services Task Force (USPSTF) recommends that primary care providers screen all adults and conduct brief counseling interventions with those who misuse alcohol. The USPSTF prefers use of three screening tools that measure alcohol consumption (Alcohol Use Disorders Identification Test, Alcohol Use Disorders Identification Test-Consumption, and National Institute on Alcohol Abuse and Alcoholism Single Question) because these tools detect the full spectrum of alcohol misuse in adults. This study estimated the prevalence of primary care provider screening practices for alcohol misuse and examined factors associated with using a USPSTF-preferred screening tool. METHODS: In 2016, a cross-sectional analysis was conducted on self-reported 2016 DocStyles data to estimate the prevalence of different screening tools used by 1,506 primary care providers-family practitioners, internists, obstetrician/gynecologists, and nurse practitioners. Adjusted prevalence ratios were calculated using logistic regression to examine the association between provider attributes and use of USPSTF-preferred screening tools. RESULTS: In this study, 96% of providers reported screening patients for alcohol misuse. Among those that screened, 38% used a USPSTF-preferred screening tool. Provider specialty, awareness of USPSTF guidelines, and mode of administering screening tool were associated with using a preferred screening tool. CONCLUSIONS: Although most primary care providers reported screening for alcohol misuse, about two thirds did not use a tool capable of detecting the full spectrum of alcohol misuse. Using suitable screening tools will better identify patients who misuse alcohol and increase the opportunity for appropriate intervention, ultimately helping to reduce the burden from the many conditions associated with excessive alcohol consumption.

      6. Sales trends in price-discounted cigarettes, large cigars, little cigars, and cigarillos – United States, 2011-2016
        Wang TW, Falvey K, Gammon DG, Loomis BR, Kuiper NM, Rogers T, King BA.
        Nicotine Tob Res. 2017 Dec 15.
        Introduction: Tobacco manufacturers continue to implement a range of pricing strategies to increase the affordability and consumption of tobacco products. To demonstrate the extent of retail- and brand-level price discounts at the point of sale, this study assessed national sales trends in price-discounted cigarettes, large cigars, little cigars, and cigarillos. Methods: Retail scanner data for tobacco product sales were obtained for convenience stores (C-store) and all-other-outlets-combined (AOC) from September 25, 2011, to January 9, 2016. The proportion of price-discounted sales, average nondiscounted unit price, and average discounted unit price were examined by product category and brand. JoinPoint regression was used to assess average monthly percentage change. Results: Overall, price-discounted sales accounted for 11.3% of cigarette, 3.4% of large cigar, 4.1% of little cigar, and 3.9% of cigarillo sales. The average difference between nondiscounted and discounted prices was 25.5% (C-store) and 36.7% (AOC) for cigarettes; 11.0% (C-store) and 11.2% (AOC) for large cigars; 19.2% (C-store) and 9.6% (AOC) for little cigars; and 5.3% (C-store) and 14.7% (AOC) for cigarillos. Furthermore, price-discounted sales of top-selling tobacco brands comprised up to 36% of cigarette, 7.4% of large cigar, 7.7% of little cigar, and 4.2% of cigarillo unit sales. Conclusions: These findings highlight the use of price discounts by tobacco manufacturers to reduce the cost of cigarettes, large cigars, little cigars, and cigarillos to consumers. These sales patterns underscore the importance of sustained efforts to implement evidence-based strategies to increase prices and reduce availability and consumption of combustible tobacco in the United States. Implications: This study highlights the prevalence and provides a baseline of price-discounted cigarettes, large cigars, little cigars, and cigarillos. Surveillance of tobacco sales data, including state-level trends and additional product types, is critical for informing approaches to reduce tobacco consumption. These approaches include countering tobacco product price-discounting practices and raising and maintaining a high sales price for all tobacco products. The implementation of evidence-based population-level interventions, together with local, state, and federal regulation of tobacco products, could prevent tobacco initiation, increase tobacco cessation, and reduce overall tobacco use among US youth and adults.

    • Zoonotic and Vectorborne Diseases
      1. Advances in serodiagnostic testing for Lyme disease are at hand
        Branda JA, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder J, Steere AC, Witkowski J, Wong SJ, Schutzer SE.
        Clin Infect Dis. 2017 Dec 7.
        The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination. Nevertheless, 2-tiered testing with immunoblotting remains the benchmark for evaluation of new methods or approaches. Next-generation serologic assays, prepared with recombinant proteins or synthetic peptides, and alternative testing protocols, can now overcome or circumvent many of these past drawbacks. This article describes next-generation serodiagnostic testing for Lyme disease, focusing on methods that are currently available or near-at-hand.

      2. Risk factors for human brucellosis in northern Tanzania
        Cash-Goldwasser S, Maze MJ, Rubach MP, Biggs HM, Stoddard RA, Sharples KJ, Halliday JE, Cleaveland S, Shand MC, Mmbaga BT, Muiruri C, Saganda W, Lwezaula BF, Kazwala RR, Maro VP, Crump JA.
        Am J Trop Med Hyg. 2017 Dec 11.
        Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4-6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a >/= 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer >/= 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed.

      3. Modes of transmission of Zika virus
        Gregory CJ, Oduyebo T, Brault AC, Brooks JT, Chung KW, Hills S, Kuehnert MJ, Mead P, Meaney-Delman D, Rabe I, Staples E, Petersen LR.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S875-s883.
        For >60 years, Zika virus (ZIKV) has been recognized as an arthropod-borne virus with Aedes species mosquitoes as the primary vector. However in the past 10 years, multiple alternative routes of ZIKV transmission have been identified. We review the available data on vector and non-vector-borne modes of transmission and interventions undertaken, to date, to reduce the risk of human infection through these routes. Although much has been learned during the outbreak in the Americas on the underlying mechanisms and pathogenesis of non-vector-borne ZIKV infections, significant gaps remain in our understanding of the relative incidence of, and risk from, these modes compared to mosquito transmission. Additional research is urgently needed on the risk, pathogenesis, and effectiveness of measures to mitigate non-vector-borne ZIKV transmission.

      4. Epidemiology of Zika virus infection
        Hills SL, Fischer M, Petersen LR.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S868-s874.
        Long known to be endemic in Africa and Southeast Asia and a rare cause of acute febrile illness, Zika virus (ZIKAV) arose from obscurity when an Asian genotype ZIKAV caused an outbreak of mild febrile illness in 2007 in Yap State, Federated States of Micronesia. Subsequent viral spread in the Pacific led to a large outbreak in French Polynesia commencing in 2013. After its recognition in the Americas through March 2017, the Pan American Health Organization has received reports of >750000 suspected and laboratory-confirmed cases of autochthonous ZIKAV transmission. Outbreaks in most countries in the Americas peaked in early to mid-2016. Increased surveillance in several Southeast Asian counties has led to increased case recognition, including an outbreak in Singapore, and the first reports of birth defects linked to ZIKAV in the region. As of April 2017, the World Health Organization reported 84 countries or territories with current or previous ZIKAV transmission.

      5. Quantifying Zika: Advancing the epidemiology of Zika with quantitative models
        Keegan LT, Lessler J, Johansson MA.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S884-s890.
        When Zika virus (ZIKV) emerged in the Americas, little was known about its biology, pathogenesis, and transmission potential, and the scope of the epidemic was largely hidden, owing to generally mild infections and no established surveillance systems. Surges in congenital defects and Guillain-Barre syndrome alerted the world to the danger of ZIKV. In the context of limited data, quantitative models were critical in reducing uncertainties and guiding the global ZIKV response. Here, we review some of the models used to assess the risk of ZIKV-associated severe outcomes, the potential speed and size of ZIKV epidemics, and the geographic distribution of ZIKV risk. These models provide important insights and highlight significant unresolved questions related to ZIKV and other emerging pathogens.

      6. Investigating the sexual transmission of Zika virus
        Kim CR, Counotte M, Bernstein K, Deal C, Mayaud P, Low N, Broutet N.
        Lancet Glob Health. 2018 Jan;6(1):e24-e25.

        [No abstract]

      7. Surveillance for and discovery of Borrelia species in US patients suspected of tickborne illness
        Kingry LC, Anacker M, Pritt B, Bjork J, Respicio-Kingry L, Liu G, Sheldon S, Boxrud D, Strain A, Oatman S, Berry J, Sloan L, Mead P, Neitzel D, Kugeler KJ, Petersen JM.
        Clin Infect Dis. 2017 Dec 20.
        Background: Tick-transmitted Borrelia species fall into two heterogeneous bacterial complexes comprised of multiple species, the relapsing fever (RF) group and the Borrelia burgdorferi sensu lato group, which are the causative agents of Lyme borreliosis (LB), the most common tickborne disease in the northern hemisphere. Geographic expansion of human LB in the United States and discovery of emerging Borrelia pathogens underscores the importance of surveillance for disease causing Borrelia. Methods: De-identified clinical specimens, submitted by providers throughout the United States, for patients suspected of LB, anaplasmosis, ehrlichiosis, or babesiosis, were screened using a Borrelia genus level TaqMan PCR. Borrelia species and sequence types (STs) were characterized by multi-locus sequence typing (MLST) utilizing next generation sequencing. Results: Among the 7,292 tested specimens tested, five different Borrelia species were identified: two causing LB, B. burgdorferi (n=25) and B. mayonii (n=9), and three RF borreliae, B. hermsii (n=1), B. miyamotoi (n=8), and CandidatusB. johnsonii (n=1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi positive specimens, with new STs identified primarily among synovial fluids. Conclusion: These results demonstrate broad PCR screening followed by MLST is a powerful surveillance tool for uncovering the spectrum of Borrelia species causing human disease, improving understanding of their geographic distribution, and investigating the correlation between B. burgdorferi STs and joint involvement. Detection of CandidatusB. johnsonii in a patient with suspected tickborne disease suggests this species may be a previously undetected cause of illness in humans with exposure to bat ticks.

      8. [No abstract]

      9. Diagnosis of Zika virus infections: Challenges and opportunities
        Munoz-Jordan JL.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S951-s956.
        Accurate diagnosis of Zika virus (ZIKV) infections has become a pressing need for the effective prevention and control of the epidemic. The findings that ZIKV infections are associated with birth defects and neurologic disease, and that the virus can be sexually transmitted, accentuate the need for accurate diagnostic testing for different applications new to the arbovirus field. Antibody response to related flaviviruses has long been known to be cross-reactive, and antibody detection of ZIKV is nonspecific in populations previously exposed to any of the four dengue viruses or West Nile virus, or vaccinated against yellow fever virus. Therefore, the diagnosis of ZIKV infections has increasingly depended on detection by nucleic acid tests. During the recent epidemic, tests authorized for emergency use have been utilized by public health laboratories and the commercial sector, but a more dependable and responsive diagnostic testing has yet to be developed.

      10. Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE
        Paden CR, Yusof M, Al Hammadi ZM, Queen K, Tao Y, Eltahir YM, Elsayed EA, Marzoug BA, Bensalah OK, Khalafalla AI, Al Mulla M, Elkheir KA, Issa ZB, Pradeep K, Elsaleh FN, Imambaccus H, Sasse J, Weber S, Shi M, Zhang J, Li Y, Pham H, Kim L, Hall AJ, Gerber SI, Al Hosani FI, Tong S, Al Muhairi SS.
        Zoonoses Public Health. 2017 Dec 13.
        Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, there have been a number of clusters of human-to-human transmission. These cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS-CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS-CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS-CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus-positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.

      11. Vaccine and therapeutic options to control Chikungunya virus
        Powers AM.
        Clin Microbiol Rev. 2018 Jan;31(1).
        Beginning in 2004, chikungunya virus (CHIKV) went from an endemic pathogen limited to Africa and Asia that caused periodic outbreaks to a global pathogen. Given that outbreaks caused by CHIKV have continued and expanded, serious consideration must be given to identifying potential options for vaccines and therapeutics. Currently, there are no licensed products in this realm, and control relies completely on the use of personal protective measures and integrated vector control, which are only minimally effective. Therefore, it is prudent to urgently examine further possibilities for control. Vaccines have been shown to be highly effective against vector-borne diseases. However, as CHIKV is known to rapidly spread and generate high attack rates, therapeutics would also be highly valuable. Several candidates are currently being developed; this review describes the multiple options under consideration for future development and assesses their relative advantages and disadvantages.

      12. Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX) patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations-including complications and sequelae-as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data-and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth-suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications), ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies.

      13. Health and development at age 19-24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak – Brazil, 2017
        Satterfield-Nash A, Kotzky K, Allen J, Bertolli J, Moore CA, Pereira IO, Pessoa A, Melo F, Santelli A, Boyle CA, Peacock G.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1347-1351.
        In November 2015, the Brazilian Ministry of Health (MOH) declared the Zika virus outbreak a public health emergency after an increase in microcephaly cases was reported in the northeast region of the country (1). During 2015-2016, 15 states in Brazil with laboratory-confirmed Zika virus transmission reported an increase in birth prevalence of microcephaly (2.8 cases per 10,000 live births), significantly exceeding prevalence in four states without confirmed transmission (0.6 per 10,000) (2). Although children with microcephaly and laboratory evidence of Zika virus infection have been described in early infancy (3), their subsequent health and development have not been well characterized, constraining planning for the care and support of these children and their families. The Brazilian MOH, the State Health Secretariat of Paraiba, and CDC collaborated on a follow-up investigation of the health and development of children in northeastern Brazil who were reported to national surveillance with microcephaly at birth. Nineteen children with microcephaly at birth and laboratory evidence of Zika virus infection were assessed through clinical evaluations, caregiver interviews, and review of medical records. At follow-up (ages 19-24 months), most of these children had severe motor impairment, seizure disorders, hearing and vision abnormalities, and sleep difficulties. Children with microcephaly and laboratory evidence of Zika virus infection have severe functional limitations and will require specialized care from clinicians and caregivers as they age.

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