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CDC Science Clips: Volume 10, Issue 40, October 23, 2018

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

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

      2. 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.

      3. 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.

      4. National and state trends in sudden unexpected infant death: 1990-2015
        Erck Lambert AB, Parks SE, Shapiro-Mendoza CK.
        Pediatrics. 2018 Feb 12.
        BACKGROUND: Sharp declines in sudden unexpected infant death (SUID) in the 1990s and a diagnostic shift from sudden infant death syndrome (SIDS) to unknown cause and accidental suffocation and strangulation in bed (ASSB) in 1999-2001 have been documented. We examined trends in SUID and SIDS, unknown cause, and ASSB from 1990 to 2015 and compared state-specific SUID rates to identify significant trends that may be used to inform SUID prevention efforts. METHODS: We used data from US mortality files to evaluate national and state-specific SUID rates (deaths per 100 000 live births) for 1990-2015. SUID included infants with an underlying cause of death, SIDS, unknown cause, or ASSB. To examine overall US rates for SUID and SUID subtypes, we calculated the percent change by fitting Poisson regression models. We report state differences in SUID and compared state-specific rates from 2000-2002 to 2013-2015 by calculating the percent change. RESULTS: SUID rates declined from 154.6 per 100 000 live births in 1990 to 92.4 in 2015, declining 44.6% from 1990 to 1998 and 7% from 1999 to 2015. From 1999 to 2015, SIDS rates decreased 35.8%, ASSB rates increased 183.8%, and there was no significant change in unknown cause rates. SUID trends among states varied widely from 41.5 to 184.3 in 2000-2002 and from 33.2 to 202.2 in 2013-2015. CONCLUSIONS: Reductions in SUID rates since 1999 have been minimal, and wide variations in state-specific rates remain. States with significant declines in SUID rates might have SUID risk-reduction programs that could serve as models for other states.

      5. Medicolegal death investigation of sudden unexpected infant deaths
        Mitchell RA, DiAngelo C, Morgan D.
        Pediatr Ann. 2017 Aug 1;46(8):e297-e302.
        This review article describes the role of the medicolegal death investigator and medical examiner or coroner (MEC) in the investigations of a sudden unexpected infant death (SUID) beginning with an introduction into the case types that should be investigated and how infant deaths fit into that legal framework. The article also provides an overview of the history of the Centers for Disease Control and Prevention SUID investigation guidelines and process. The article concludes with a description of how the MEC correlates the scene investigation with autopsy findings, as well as the role of the MEC in cause of death determinations. There is also a brief discussion on how infant mortality data are captured and subsequently used to decrease infant mortality. [Pediatr Ann. 2017;46(8):e297-e302.].

      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. 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.

      8. 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.

      9. 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.

      10. Classification system for the Sudden Unexpected Infant Death Case Registry and its application
        Shapiro-Mendoza CK, Camperlengo L, Ludvigsen R, Cottengim C, Anderson RN, Andrew T, Covington T, Hauck FR, Kemp J, MacDorman M.
        Pediatrics. 2014 Jul;134(1):e210-9.
        Sudden unexpected infant deaths (SUID) accounted for 1 in 3 postneonatal deaths in 2010. Sudden infant death syndrome and accidental sleep-related suffocation are among the most frequently reported types of SUID. The causes of these SUID usually are not obvious before a medico-legal investigation and may remain unexplained even after investigation. Lack of consistent investigation practices and an autopsy marker make it difficult to distinguish sudden infant death syndrome from other SUID. Standardized categories might assist in differentiating SUID subtypes and allow for more accurate monitoring of the magnitude of SUID, as well as an enhanced ability to characterize the highest risk groups. To capture information about the extent to which cases are thoroughly investigated and how factors like unsafe sleep may contribute to deaths, CDC created a multistate SUID Case Registry in 2009. As part of the registry, the Centers for Disease Control and Prevention developed a classification system that recognizes the uncertainty about how suffocation or asphyxiation may contribute to death and that accounts for unknown and incomplete information about the death scene and autopsy. This report describes the classification system, including its definitions and decision-making algorithm, and applies the system to 436 US SUID cases that occurred in 2011 and were reported to the registry. These categories, although not replacing official cause-of-death determinations, allow local and state programs to track SUID subtypes, creating a valuable tool to identify gaps in investigation and inform SUID reduction strategies.

      11. 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.

      12. Variations in cause-of-death determination for sudden unexpected infant deaths
        Shapiro-Mendoza CK, Parks SE, Brustrom J, Andrew T, Camperlengo L, Fudenberg J, Payn B, Rhoda D.
        Pediatrics. 2017 Jul;140(1).
        OBJECTIVES: To quantify and describe variation in cause-of-death certification of sudden unexpected infant deaths (SUIDs) among US medical examiners and coroners. METHODS: From January to November 2014, we conducted a nationally representative survey of US medical examiners and coroners who certify infant deaths. Two-stage unequal probability sampling with replacement was used. Medical examiners and coroners were asked to classify SUIDs based on hypothetical scenarios and to describe the evidence considered and investigative procedures used for cause-of-death determination. Frequencies and weighted percentages were calculated. RESULTS: Of the 801 surveys mailed, 60% were returned, and 377 were deemed eligible and complete. Medical examiners and coroners classification of infant deaths varied by scenario. For 3 scenarios portraying potential airway obstruction and negative autopsy findings, 61% to 69% classified the death as suffocation/asphyxia. In the last scenario, which portrayed a healthy infant in a safe sleep environment with negative autopsy findings, medical examiners and coroners classified the death as sudden infant death syndrome (38%) and SUID (30%). Reliance on investigative procedures to determine cause varied, but 94% indicated using death scene investigations, 88% full autopsy, 85% toxicology analyses, and 82% medical history review. CONCLUSIONS: US medical examiners and coroners apply variable practices to classify and investigate SUID, and thus, they certify the same deaths differently. This variability influences surveillance and research, impacts true understanding of infant mortality causes, and inhibits our ability to accurately monitor and ultimately prevent future deaths. Findings may inform future strategies for promoting standardized practices for SUID classification.

  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. Kids nowadays hear better than we did: Declining prevalence of hearing loss in US youth, 1966-2010
        Hoffman HJ, Dobie RA, Losonczy KG, Themann CL, Flamme GA.
        Laryngoscope. 2018 Oct 5.
        OBJECTIVES/HYPOTHESIS: To investigate factors associated with hearing impairment (HI) in adolescent youths during the period 1966-2010. STUDY DESIGN: Cross-sectional analyses of US sociodemographic, health, and audiometric data spanning 5 decades. METHODS: Subjects were youths aged 12 to 17 years who participated in the National Health Examination Survey (NHES Cycle 3, 1966-1970; n = 6,768) and youths aged 12 to 19 years in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994; n = 3,057) and NHANES (2005-2010; n = 4,374). HI prevalence was defined by pure-tone average (PTA) >/= 20 dB HL for speech frequencies (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz). Multivariable logistic models were used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall speech-frequency HI prevalence was 10.6% (95% CI: 9.7%-11.6%) in NHES, 3.9% (95% CI: 2.8%-5.5%) in NHANES III, and 4.5% (95% CI: 3.7%-5.4%) in NHANES 2005 to 2010. The corresponding high-frequency HI prevalences were 32.8% (95% CI: 30.8%-34.9%), 7.3% (95% CI: 5.9%-9.0%), and 7.9% (95% CI: 6.8%-9.2%). After adjusting for sociodemographic factors, overall high-frequency HI was increased twofold for males and cigarette smoking. Other significant risk factors in NHANES 2005 to 2010 included very low birth weight, history of ear infections/otitis media, ear tubes, fair/poor general health, and firearms use. CONCLUSIONS: HI declined considerably between 1966 to 1970 and 1988 to 1994, with no additional decline between 1988 to 1994 and 2005 to 2010. Otitis media history was a significant HI risk factor each period, whereas very low birth weight emerged as an important risk factor after survival chances improved. Reductions in smoking, job-related noise, and firearms use may partially explain the reduction in high-frequency HI. Loud music exposure may have increased, but does not account for HI differences. LEVEL OF EVIDENCE: NA.

      2. Introduction: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that often goes undiagnosed, particularly in its early stages. Objective: To examine sociodemographic, general health, and COPD specific factors, including severity of lung obstruction, that are associated with healthcare provider-diagnosed COPD among U.S. adults. Methods: NHANES cross-sectional data collected from 2007-2012 on adults aged 40-79 years (n=10,219) were analyzed. The primary outcome was self-reported COPD diagnosis with predictive factors analyzed via chi-square and logistic regression analyses. Results: During 2007-2012, 5.2% of US adults aged 40-79 reported being diagnosed with COPD. Among those diagnosed, 50.8% reported fair or poor health, 47.1% were currently smoking cigarettes, 49.1% were taking prescription respiratory medication, 36.4% had moderate or worse lung obstruction, and nearly 90% had one or more respiratory symptoms. Logistic regression revealed positive associations between receiving a COPD diagnosis and the following: being white (AOR: 3.08, 95% CI: 1.82-5.20); being aged 60-79 years (AOR: 1.65, 95% CI: 1.07-2.53); reporting fair/poor health (AOR: 2.91, CI: 1.55-5.46); having 4-9 (AOR: 3.5, CI: 1.3-9.4) or 10 or more healthcare visits in prior year (AOR: 5.06, CI: 1.62-15.77); being a former (AOR: 1.75, CI: 1.2-2.5) or current smoker (AOR: 1.70, CI: 1.17-2.48); having more severe lung obstruction (AOR: 4.90, CI: 3.28-7.32); having 3 or more respiratory symptoms (AOR: 22.07, CI: 12.03-40.49). Conclusions: Multiple factors are associated with self-reported COPD diagnosis with number of reported respiratory symptoms having the strongest association. After controlling for other factors, having mild lung obstruction was not associated with being diagnosed.

      3. One hypothesized explanation for the recent slowing of declines in heart disease death rates is the generational shift in the timing and accumulation of risk factors. However, directly testing this hypothesis requires historical age-group-specific risk factor data that do not exist. Using national death records, we compared spatiotemporal patterns of heart disease death rates by age group, time period, and birth cohort to provide insight into possible drivers of trends. To do this, we calculated county-level percent change for five time periods (1973-1980, 1980-1990, 1990-2000, 2000-2010, 2010-2015) for four age groups (35-44, 45-54, 55-64, 65-74), resulting in eight birth cohorts for each decade from the 1900s through the 1970s. From 1973 through 1990, few counties experienced increased heart disease death rates. In 1990-2000, 49.0% of counties for ages 35-44 were increasing, while all other age groups continued to decrease. In 2000-2010, heart disease death rates for ages 45-54 increased in 30.4% of counties. In 2010-2015, all four age groups showed widespread increasing county-level heart disease death rates. Likewise, birth cohorts from the 1900s through the 1930s experienced consistently decreasing heart disease death rates in almost all counties. Similarly, with the exception of 2010-2015, most counties experienced decreases for the 1940s birth cohort. For birth cohorts in the 1950s, 1960s, and 1970s, increases were common and geographically widespread for all age groups and calendar years. This analysis revealed variation in trends across age groups and across counties. However, trends in heart disease death rates tended to be generally decreasing and increasing for early and late birth cohorts, respectively. These findings are consistent with the hypothesis that recent increases in heart disease mortality stem from the beginnings of the obesity and diabetes epidemics. However, the common geographic patterns within the earliest and latest time periods support the importance of place-based macro-level factors.

    • Communicable Diseases
      1. HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013
        Arimide DA, Abebe A, Kebede Y, Adugna F, Tilahun T, Kassa D, Assefa Y, Balcha TT, Bjorkman P, Medstrand P.
        PLoS One. 2018 ;13(10):e0205446.
        BACKGROUND: The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C’-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country. METHODS: A cross-sectional survey was conducted among young antiretroviral therapy (ART)-naive individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011-2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST. RESULT: Four of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C’-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate. CONCLUSION: TDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C’-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.

      2. Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP): An overview and lessons learned
        Barkume C, Date K, Saha SK, Qamar FN, Sur D, Andrews JR, Luby SP, Khan MI, Freeman A, Yousafzai MT, Garrett D.
        J Infect Dis. 2018 Oct 10.
        Objective: The objective of Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP), a multiphase surveillance study characterizing the burden of disease in South Asia, was to inform data collection for prospective surveillance and to capture clinical aspects of disease. Methods: Through a retrospective record review conducted at hospitals in Bangladesh, India, Nepal, and Pakistan, we examined laboratory and clinical records to assess the culture positivity rate for Salmonella Typhi and Salmonella Paratyphi, age and sex distribution, and antimicrobial susceptability in each country. Results: Of all blood cultures performed in Bangladesh, India, Nepal, and Pakistan, 1.5%, 0.43%, 2%, and 1.49%, respectively, were positive for S. Typhi and 0.24%, 0.1%, 0.5%, and 0.67%, respectively, were positive for S. Paratyphi. A higher proportion of laboratory-confirmed infections in Bangladesh and Pakistan were aged </=5 years, while India and Nepal had a higher proportion of participants aged 15-25 years. In all countries, the sex of the majority of participants was male. The majority of isolates in all countries were resistant to fluoroquinolones, with a high proportion also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Discussion: Enteric fever remains endemic in South Asia. Data generated by this study can help inform strategies for implementation and evaluation of prevention and control measures.

      3. [No abstract]

      4. Hepatitis C care cascade among persons born 1945-1965: 3 medical centers
        Brady JE, Vellozzi C, Hariri S, Kruger DL, Nerenz DR, Brown KA, Federman AD, Krauskopf K, Kil N, Massoud OI, Wise JM, Seay TA, Smith BD, Yartel AK, Rein DB.
        Am J Manag Care. 2018 Sep;24(9):421-427.
        OBJECTIVES: Effective screening, diagnosis, and treatment are needed to reduce chronic hepatitis C virus (HCV) infection-associated morbidity and mortality. In order to successfully increase HCV treatment, it is necessary to identify and understand gaps in linkage of antibody-positive patients with newly identified HCV to subsequent HCV RNA testing, clinical evaluation, and treatment. STUDY DESIGN: To estimate attainment of HCV care cascade steps among antibody-positive patients with newly identified HCV, we conducted chart reviews of patients with a new positive HCV antibody test at 3 academic medical centers participating in the Birth-Cohort Evaluation to Advance Screening and Testing of Hepatitis C (BEST-C) study. METHODS: We tracked receipt of RNA testing, clinical evaluation, treatment initiation, and treatment completion among individuals born between 1945 and 1965 who were newly diagnosed as HCV antibody-positive between December 2012 and October 2015 at 3 BEST-C centers, predominantly from the participating medical centers’ primary care practices and emergency departments. RESULTS: Of the 130 HCV-seropositive individuals identified, 118 (91%) had an RNA or genotype test, 75 (58%) were RNA-positive, 73 (56%) were linked to care, 22 (17% overall; 29% among RNA-positive) started treatment, and 21 (16%; 28% among RNA-positive) completed treatment. CONCLUSIONS: This analysis showed that although linkage to care was largely successful in the target birth cohort, the largest gap in the HCV care cascade was seen in initiating treatment. Greater emphasis on linking patients to clinical evaluation and treatment is necessary in order to achieve the public health benefits promised by birth-cohort testing.

      5. Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey
        Chow NA, Gade L, Tsay SV, Forsberg K, Greenko JA, Southwick KL, Barrett PM, Kerins JL, Lockhart SR, Chiller TM, Litvintseva AP.
        Lancet Infect Dis. 2018 Oct 4.
        BACKGROUND: Transmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA. METHODS: In this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs). FINDINGS: From May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0-12). INTERPRETATION: Isolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission. FUNDING: US Centers for Disease Control and Prevention.

      6. A new era for treatment of drug-resistant tuberculosis
        Gandhi NR, Brust JC, Shah NS.
        Eur Respir J. 2018 Oct;52(4).

        [No abstract]

      7. Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014
        Gounder PP, Koch A, Provo G, Lovlie A, Ederth JL, Axelsson M, Archibald CP, Hanley B, Mullen A, Matheson M, Allison D, Trykker H, Hennessy TW, Kuusi M, Chulanov V, McMahon BJ.
        Euro Surveill. 2018 Oct;23(40).
        We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.

      8. Modeling undetected live poliovirus circulation after apparent interruption of transmission: Pakistan and Afghanistan
        Kalkowska DA, Duintjer Tebbens RJ, Pallansch MA, Thompson KM.
        Risk Anal. 2018 Oct 8.
        Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country-specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine-derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die-out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high-quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decrease, the risks of undetected circulation increase and significantly delay the global polio endgame.

      9. Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial
        Kissinger P, Muzny CA, Mena LA, Lillis RA, Schwebke JR, Beauchamps L, Taylor SN, Schmidt N, Myers L, Augostini P, Secor WE, Bradic M, Carlton JM, Martin DH.
        Lancet Infect Dis. 2018 Oct 5.
        BACKGROUND: Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide, and is associated with serious reproductive morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose metronidazole is the first-line treatment for trichomoniasis. However, bacterial vaginosis can alter treatment efficacy in HIV-infected women, and single-dose metronidazole treatment might not always clear infection. We compared single-dose metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV-uninfected, non-pregnant women and tested whether efficacy was modified by bacterial vaginosis. METHODS: In this multicentre, open-label, randomised controlled trial, participants were recruited at three sexual health clinics in the USA. We included women positive for Trichomonas vaginalis infection according to clinical screening. Participants were randomly assigned (1:1) to receive either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of metronidazole twice daily for 7 days (7-day-dose group). The randomisation was done by blocks of four or six for each site. Patients and investigators were aware of treatment assignment. The primary outcome was T vaginalis infection by intention to treat, at test-of-cure 4 weeks after completion of treatment. The analysis of the primary outcome per nucleic acid amplification test or culture was also stratified by bacterial vaginosis status. This trial is registered with, number NCT01018095, and with the US Food and Drug Administration, number IND118276, and is closed to accrual. FINDINGS: Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028 patients assessed for eligibility, 623 women were randomly assigned to treatment groups (311 women in the single-dose group and 312 women in the 7-day-dose group; intention-to-treat population). Although planned enrolment had been 1664 women, the study was stopped early because of funding limitations. Patients in the 7-day-dose group were less likely to be T vaginalis positive at test-of-cure than those in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0.55, 95% CI 0.34-0.70; p<0.0001). Bacterial vaginosis status had no significant effect on relative risk (p=0.17). Self-reported adherence was 96% in the 7-day-dose group and 99% in the single-dose group. Side-effects were similar by group; the most common side-effect was nausea (124 [23%]), followed by headache (38 [7%]) and vomiting (19 [4%]). INTERPRETATION: The 7-day-dose metronidazole should be the preferred treatment for trichomoniasis among women. FUNDING: National Institutes of Health.

      10. Ultra-long-acting removable drug delivery system for HIV treatment and prevention
        Kovarova M, Benhabbour SR, Massud I, Spagnuolo RA, Skinner B, Baker CE, Sykes C, Mollan KR, Kashuba AD, Garcia-Lerma JG, Mumper RJ, Garcia JV.
        Nat Commun. 2018 Oct 8;9(1):4156.
        Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications.

      11. We used US national survey data to examine sexual behavior by pregnancy status and found that, overall, pregnant women did not differ from non-pregnant women in penile-anal sex and associated condom use. Compared to non-pregnant women, pregnant women had lower or similar reports of other sexual behaviors.

      12. Differences in characteristics and clinical outcomes among Hispanic/Latino men and women receiving HIV medical care – United States, 2013-2014
        Luna-Gierke RE, Shouse RL, Luo Q, Frazier E, Chen G, Beer L.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 12;67(40):1109-1114.
        The prevalence of diagnosed human immunodeficiency virus (HIV) infection among Hispanics/Latinos in the United States is approximately twice that of non-Hispanic whites (1). Barriers to, and experiences with, medical care have been found to vary by sex (2). Describing characteristics of Hispanics/Latinos in care by sex can help identify disparities and inform delivery of tailored services to this underserved population. Data from the 2013 and 2014 cycles of the Medical Monitoring Project (MMP) were analyzed to describe demographic, behavioral, and clinical characteristics among Hispanics/Latinos by sex. MMP is an annual cross-sectional, nationally representative surveillance system that, during 2013-2014, collected information about behaviors, medical care, and clinical outcomes among adults receiving outpatient HIV care. Hispanic/Latina women were significantly more likely than were men to live in poverty (78% versus 54%), report not speaking English well (38% versus 21%), and receive interpreter (27% versus 16%), transportation (35% versus 21%), and meal (44% versus 26%) services. There were no significant differences between Hispanic/Latino women and men in prescription of antiretroviral therapy (ART) (95% versus 96%) or sustained viral suppression (68% versus 73%). Although women faced greater socioeconomic and language-related challenges, the clinical outcomes among Hispanic/Latina women were similar to those among men, perhaps reflecting their higher use of ancillary services. Levels of viral suppression for Hispanics/Latinos are lower than those found among non-Hispanic whites (3) and lower than the national prevention goal of at least 80% of persons with diagnosed HIV infection. Providers should be cognizant of the challenges faced by Hispanics/Latinos with HIV infection in care and provide referrals to needed ancillary services.

      13. Non-granulomatous cerebellar infection by Acanthamoeba spp. in an immunocompetent host
        Modica S, Miracco C, Cusi MG, Tordini G, Muzii VF, Iacoangeli F, Nocentini C, Ali IK, Roy S, Cerase A, Zanelli G, De Luca A, Montagnani F.
        Infection. 2018 Oct 4.
        Acanthamoeba spp. is a free-living amoeba, frequently involved in keratitis by contact lens in immunocompetent hosts. Anecdotal reports associate Acanthamoeba spp. as a cause of severe granulomatous encephalitis in immunocompromised and, less frequently, in immunocompetent subjects. Data regarding clinical and therapeutic management are scanty and no defined therapeutic guidelines are available. We describe an unusual case of non-granulomatous Acanthamoeba cerebellitis in an immunocompetent adult male, with abrupt onset of neurological impairment, subtle hemorrhagic infarction at magnetic resonance imaging, and initial suspicion of cerebellar neoplasm. Histopathological findings of excised cerebellar mass revealed the presence of necrosis and inflammation with structure resembling amoebic trophozoites, but without granulomas. Polymerase chain reaction from cerebellar tissue was positive for Acanthamoeba T4 genotype. Due to gastrointestinal intolerance to miltefosine, the patient was treated with long-term course of fluconazole and trimethoprim/sulphamethoxazole, obtaining complete clinical and neuroradiological resolution.

      14. Effects of a brief video intervention on treatment initiation and adherence among patients attending human immunodeficiency virus treatment clinics
        Neumann MS, Plant A, Margolis AD, Borkowf CB, Malotte CK, Rietmeijer CA, Flores SA, O’Donnell L, Robilotto S, Myint UA, Montoya JA, Javanbakht M, Klausner JD.
        PLoS One. 2018 ;13(10):e0204599.
        BACKGROUND: Persons with human immunodeficiency virus (HIV) who get and keep a suppressed viral load are unlikely to transmit HIV. Simple, practical interventions to help achieve HIV viral suppression that are easy and inexpensive to administer in clinical settings are needed. We evaluated whether a brief video containing HIV-related health messages targeted to all patients in the waiting room improved treatment initiation, medication adherence, and retention in care. METHODS AND FINDINGS: In a quasi-experimental trial all patients (N = 2,023) attending two HIV clinics from June 2016 to March 2017 were exposed to a theory-based, 29-minute video depicting persons overcoming barriers to starting treatment, taking medication as prescribed, and keeping medical appointments. New prescriptions at index visit, HIV viral load test results, and dates of return visits were collected through review of medical records for all patients during the 10 months that the video was shown. Those data were compared with the same variables collected for all patients (N = 1,979) visiting the clinics during the prior 10 months (August 2015 to May 2016). Among patients exposed to the video, there was an overall 10.4 percentage point increase in patients prescribed treatment (60.3% to 70.7%, p< 0.01). Additionally, there was an overall 6.0 percentage point improvement in viral suppression (56.7% to 62.7%, p< 0.01), however mixed results between sites was observed. There was not a significant change in rates of return visits (77.5% to 78.8%). A study limitation is that, due to the lack of randomization, the findings may be subject to bias and secular trends. CONCLUSIONS: Showing a brief treatment-focused video in HIV clinic waiting rooms can be effective at improving treatment initiation and may help patients achieve viral suppression. This feasible, low resource-reliant video intervention may be appropriate for adoption by other clinics treating persons with HIV. TRIAL REGISTRATION: (NCT03508310).

      15. Using strategic information for action: lessons from the HIV/AIDS response in Vietnam
        Son VH, Abdul-Quader A, Suthar AB.
        BMJ Glob Health. 2018 ;3(5):e000793.

        [No abstract]

      16. A retrospective review of hospital-based data on enteric fever in India, 2014-2015
        Sur D, Barkume C, Mukhopadhyay B, Date K, Ganguly NK, Garrett D.
        J Infect Dis. 2018 Oct 11.
        Background: Enteric fever remains a threat to many countries with minimal access to clean water and poor sanitation infrastructure. As part of a multisite surveillance study, we conducted a retrospective review of records in 5 hospitals across India to gather evidence on the burden of enteric fever. Methods: We examined hospital records (laboratory and surgical registers) from 5 hospitals across India for laboratory-confirmed Salmonella Typhi or Salmonella Paratyphi cases and intestinal perforations from 2014-2015. Clinical data were obtained where available. For laboratory-confirmed infections, we compared differences in disease burden, age, sex, clinical presentation, and antimicrobial resistance. Results: Of 267536 blood cultures, 1418 (0.53%) were positive for S. Typhi or S. Paratyphi. Clinical data were available for 429 cases (72%); a higher proportion of participants with S. Typhi infection were hospitalized, compared with those with S. Paratyphi infection (44% vs 35%). We observed resistance to quinolones among 82% of isolates, with cases of cephalosporin resistance (1%) and macrolide resistance (9%) detected. Of 94 participants with intestinal perforations, 16 (17%) had a provisional, final, or laboratory-confirmed diagnosis of enteric fever. Discussion: Data show a moderate burden of enteric fever in India. Enteric fever data should be systematically collected to facilitate evidence-based decision-making by countries for typhoid conjugate vaccines.

      17. [No abstract]

      18. Estimating recent HIV incidence among young men who have sex with men: Reinvigorating, validating and implementing Osmond’s algorithm for behavioral imputation
        van Griensven F, Mock PA, Benjarattanaporn P, Premsri N, Thienkrua W, Sabin K, Varangrat A, Zhao J, Chitwarakorn A, Hladik W.
        PLoS One. 2018 ;13(10):e0204793.
        HIV incidence information is essential for epidemic monitoring and evaluating preventive interventions. However, reliable HIV incidence data is difficult to obtain, especially among marginalized populations, such as young men who have sex with men (YMSM). Here we evaluate the reliability of an alternative HIV incidence assessment method, behavioral imputation, as compared to serologically estimated HIV incidence. Recent HIV incidence among YMSM (aged 18 to 21 and 18 to 24 years) enrolled in a cohort study in Bangkok from 2006 to 2014 was estimated using two mid-point methods for seroconversion: 1) between age of first anal intercourse and first HIV-positive test (without previous HIV-negative test) (behavioral imputation) and 2) between the date of last negative and first positive HIV test (serological estimation). Serologically estimated HIV incidence was taken as the “gold standard” to evaluate between-method agreement. At baseline, 314 YMSM age 18 to 21 years accumulated 674 person-years (PY) of follow-up since first anal intercourse. Considering that 50 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.4 per 100 PY. Of the remaining 264 HIV-negative men, 54 seroconverted for HIV infection during the study, accumulating 724 PY of follow-up and a serologically estimated HIV incidence of 7.5 per 100 PY. At baseline, 712 YMSM age 18 to 24 years (including 18 to 21-year-old men analyzed above) accumulated 2143 PY of follow-up since first anal intercourse. Considering that 151 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.0 per 100 PY. Of the remaining 561 HIV-negative men, 125 seroconverted for HIV infection during the study, accumulating 1700 PY of follow-up and a serologically estimated HIV incidence of 7.4 per 100 PY. Behavioral imputation and serological estimation are in good agreement when estimating recent HIV incidence in YMSM.

    • Disaster Control and Emergency Services
      1. Emergency preparedness training for hospital nursing staff, New York City, 2012-2016
        Jacobs-Wingo JL, Schlegelmilch J, Berliner M, Airall-Simon G, Lang W.
        J Nurs Scholarsh. 2018 Sep 17.
        PURPOSE: Many nurses are trained inadequately in emergency preparedness (EP), preventing them from effectively executing response roles during disasters, such as chemical, biological, radiological, nuclear, and explosive (CBRNE) events. Nurses also indicate lacking confidence in their abilities to perform EP activities. The purpose of this article is to describe the phased development of, and delivery strategies for, a CBRNE curriculum to enhance EP among nursing professionals. The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) and the National Center for Disaster Preparedness at Columbia University’s Earth Institute led the initiative. METHODS: Curriculum development included four phases. In Phases I and II, nursing staff at 20 participating NYC hospitals conducted 7,177 surveys and participated in 20 focus groups to identify training gaps in EP. In Phase III, investigators developed and later refined the CBRNE curriculum based on gaps identified. In Phase IV, 22 nurse educators (representing 7 of the original 20 participating hospitals) completed train-the-trainer sessions. Of these nurse educators, three were evaluated on their ability to train other nurses using the curriculum, which investigators finalized. FINDINGS: The CBRNE curriculum included six modules, a just-in-time training, and an online annual refresher course that addressed EP gaps identified in surveys and focus groups. Among the 11 nurses who were trained by three nurse educators during a pilot training, participant knowledge of CBRNE events and response roles increased from an average of 54% (range 45%-75%) on the pre-test to 89% (range 80%-90%) on the posttest. CONCLUSIONS: By participating in nursing CBRNE training, nurses increased their knowledge of and preparedness to respond to disasters. The train-the-trainer curriculum is easily adaptable to meet the needs of other healthcare settings. CLINICAL RELEVANCE: The CBRNE curriculum can be used to train nurses to better prepare for and more effectively respond to disasters.

    • Disease Reservoirs and Vectors
      1. Bat rabies in Washington State: Temporal-spatial trends and risk factors for zoonotic transmission (2000-2017)
        Bonwitt J, Oltean H, Lang M, Kelly RM, Goldoft M.
        PLoS One. 2018 ;13(10):e0205069.
        BACKGROUND: Rabies is a zoonotic viral disease that can affect all mammals. In the United States, the majority of human rabies cases are caused by bats, which are the only known reservoirs for rabies virus (RABV) in Washington State. We sought to characterize bat RABV epidemiology in Washington among bats submitted by the public for RABV testing. METHODS: We examined temporal and spatial trends in RABV positivity (% positive) for taxonomically identified bats submitted to diagnostic laboratories during 2006-2017. For a subset of Myotis species, we evaluated sensitivity and predictive value positive (PPV) of morphological identification keys, using mitochondrial markers (cytochrome b) as a reference. For bats tested during 2000-2016, we analyzed RABV positivity by circumstances of encounters with humans, cats, and dogs. RESULTS: During 2006-2017, RABV positivity for all bat species was 6.0% (176/2,928). Among species with >/=100 submissions, RABV positivity was 2.0%-11.7% and highest among big brown bats (Eptesicus fuscus). An increasing trend in annual positivity was significant only for big brown bats (P = 0.02), and was circumstantially linked to a geographic cluster. Sensitivity and PPV of morphological identification keys was high for M. evotis but varied for M. lucifugus, M. californicus, M. yumanensis, and M. septentrionalis. A positive RABV result was significantly associated with nonsynanthropic species, abnormal behavior, abnormal hiding, injury, biting, found in a body of water, found alive, found outdoors, and caught by a dog. CONCLUSION: Monitoring passive RABV surveillance trends enables public health authorities to perform more accurate risk assessments. Differences in temporal and spatial trends in RABV positivity by bat species indicate the importance of collecting taxonomic data, although morphological identification can be unreliable for certain Myotis species. Current public health practices for RABV exposures should be maintained as RABV infection in bats can never be excluded without diagnostic testing.

    • Drug Safety
      1. Trends in antifungal use in US hospitals, 2006-12
        Vallabhaneni S, Baggs J, Tsay S, Srinivasan AR, Jernigan JA, Jackson BR.
        J Antimicrob Chemother. 2018 Oct 1;73(10):2867-2875.
        Background: Although trends in antibiotic use have been characterized, less is known about antifungal use. Data on antifungal use are important for understanding practice patterns, assessing emergence of antifungal resistance and developing antifungal stewardship programmes. We estimated national trends in inpatient antifungal use in the USA. Methods: Using billing data for antifungals from the Truven Health MarketScan(R) Hospital Drug Database during 2006-12, we estimated the proportion of discharges at which antifungals were given and days of therapy (DOT)/1000 patient days (PDs) by antifungal drug type, year, patient and facility characteristics. We created national estimates using weights generated from Centers for Medicare and Medicaid Services data and assessed trends over time. Results: Overall, 2.7% of all inpatients and 7.7% of those in ICUs received antifungals. The estimated DOT/1000 PDs for any antifungal was 35.0 for all inpatients and 73.7 for ICU patients. Azoles accounted for 80% of all antifungal use (28.5/1000 PDs), followed by echinocandins (5.0/1000 PDs). By multivariable trend analysis, DOT/1000 PDs for azoles (-21%) and polyenes (-47%) decreased between 2006 and 2012, whereas echinocandins increased 11% during 2006-10 and declined after 2011. Unspecified septicaemia, HIV and antineoplastic therapy were among the top primary diagnosis codes for patients who received antifungals. Conclusions: Antifungals were most frequently used in ICU settings and fluconazole accounted for a large, but declining, proportion of antifungal use. Antifungal stewardship efforts may have the most impact if focused in ICUs, among certain patient groups (e.g. HIV and malignancy) and on stopping empirical antifungal therapy for unspecified sepsis when not indicated.

    • Environmental Health
      1. BACKGROUND: Personal care product chemicals may be contributing to risk for asthma and other atopic illnesses. The existing literature is conflicting, and many studies do not control for multiple chemical exposures. METHODS: We quantified concentrations of three phthalate metabolites, three parabens, and four other phenols in urine collected twice during pregnancy from 392 women. We measured T helper 1 (Th1) and T helper 2 (Th2) cells in their children’s blood at ages two, five, and seven, and assessed probable asthma, aeroallergies, eczema, and lung function at age seven. We conducted linear and logistic regressions, controlling for additional biomarkers measured in this population as selected by Bayesian Model Averaging. RESULTS: The majority of comparisons showed null associations. Mono-n-butyl phthalate (MnBP) was associated with higher Th2% (RR: 10.40, 95% CI: 3.37, 17.92), and methyl paraben was associated with lower Th1% (RR: -3.35, 95% CI: -6.58, -0.02) and Th2% at borderline significance (RR: -4.45, 95% CI: -8.77, 0.08). Monoethyl phthalate was associated with lower forced expiratory flow from 25 to 75% of forced vital capacity (FEF25-75%) (RR: -3.22L/s, 95% CI: -6.02, -0.34). Propyl paraben (OR: 0.86, 95% CI: 0.74, 0.99) was associated with decreased odds of probable asthma. CONCLUSIONS: While some biomarkers, particularly those from low molecular weight phthalates, were associated with an atopic cytokine profile and poorer lung function, no biomarkers were associated with a corresponding increase in atopic disease.

      2. Prenatal exposure to organochlorine pesticides and early childhood communication development in British girls
        Jeddy Z, Kordas K, Allen K, Taylor EV, Northstone K, Dana Flanders W, Namulanda G, Sjodin A, Hartman TJ.
        Neurotoxicology. 2018 Oct 4.
        BACKGROUND: The developing brain is susceptible to exposure to neurodevelopmental toxicants such as pesticides. AIMS: We explored associations of prenatal serum concentrations of hexachlorobenzene (HCB), beta-Hexachlorocyclohexane (beta-HCH), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p’-DDE) and 2,2-Bis(4-chlorophenyl-1,1,1-trichloroethane (p,p’-DDT) with maternal-reported measures of verbal and non-verbal communication in young girls. STUDY DESIGN AND METHODS: We studied a sample of 400 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) using multivariable linear regression models adjusting for parity, Home Observation Measurement of the Environment (HOME) score, maternal age and education status, and maternal tobacco use during the first trimester of pregnancy. EXPOSURE AND OUTCOME MEASURES: Maternal serum samples (collected at median 15 wks. gestation [IQR 10, 28]) were assessed for selected organochlorine pesticide levels. Communication was assessed at 15 and 38 months, using adapted versions of the MacArthur Bates Communicative Development Inventories for Infants and Toddlers (MCDI). RESULTS: At 15 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had vocabulary comprehension and production scores approximately 16% (p = 0.007) lower than girls born to mothers with concentrations in the lowest tertile. This association varied by maternal parity in that the evidence was stronger for daughters of nulliparous mothers. At 38 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had mean adjusted intelligibility scores that were 3% (p = 0.03) lower than those born to mothers with concentrations in the lowest tertile; however, results did not vary significantly by parity. Maternal concentrations of beta-HCH and p,p’-DDE were not significantly associated with MCDI scores at 15 or 36 months. p,p’-DDT had an inconsistent pattern of association; a significant positive association was observed between p,p’-DDT with verbal comprehension scores at 15 months; however, at 38 months a significant inverse association was observed for p,p’-DDT with communicative scores. This inverse association for p,p’-DDT among older girls tended to be stronger among daughters of mothers who had lower depression scores. CONCLUSIONS: Organochlorine pesticide exposure in utero may affect communication development.

      3. Role of body composition and physical activity on permethrin urinary biomarker concentrations while wearing treated military uniforms
        Proctor SP, Scarpaci MM, Maule AL, Heaton KJ, Taylor K, Haven CC, Rood J, Ospina M, Calafat AM.
        Toxicol Lett. 2018 Oct 4.
        Wearing of permethrin treated clothing is becoming more prevalent in military and outdoor occupational and recreational settings, as a personal protection measure against vector borne diseases transmitted through arthropods (e.g., malaria, Lyme disease). The goal of the study was to prospectively examine permethrin exposure among new U.S. Army recruits who had just been issued permethrin-treated uniforms over a 10-week military training period and whether individual body composition (percent body fat, %BF) and physical workload (total energy expenditure, TEE) influenced the exposure. Exposure was assessed by quantification in urine of three permethrin metabolites, 3-phenoxybenzoic acid (3-PBA), and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid. Although there was individual variability, urinary concentrations and estimated dose levels decreased over the 10-week period. Mixed models demonstrated that 10% higher %BF was significantly associated with 4.42% higher 3-PBA concentrations and a 10% higher daily TEE was significantly associated with a 10.57% higher 3-PBA concentrations. Additional factors influencing exposure included sex, number of uniform launderings, and wear- time (hours per previous day).

    • Food Safety
      1. New product, old problem(s): multistate outbreak of Salmonella Paratyphi B variant L(+) tartrate(+) infections linked to raw sprouted nut butters, October 2015
        Heiman Marshall KE, Booth H, Harrang J, Lamba K, Folley A, Ching-Lee M, Hannapel E, Greene V, Classon A, Whitlock L, Shade L, Viazis S, Nguyen T, Neil KP.
        Epidemiol Infect. 2018 Oct 8:1-6.
        A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July-22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.

    • Health Communication and Education
      1. An interrupted time series evaluation of the Testing Makes Us Stronger HIV campaign for black gay and bisexual men in the United States
        Boudewyns V, Paquin RS, Uhrig JD, Badal H, August E, Stryker JE.
        J Health Commun. 2018 Oct 11:1-9.
        Black gay, bisexual, and other men who have sex with men (BMSM) are the subpopulation most disproportionately affected by HIV in the United States. Testing Makes Us Stronger (TMUS), a communication campaign designed to increase HIV testing rates among BMSM ages 18 to 44, was implemented in the United States from December 2011 through September 2015. We used interrupted time series analysis (ITSA) to compare pre- and post-campaign trends in monthly HIV testing events among the priority audience in six of the implementation cities from January 2011 through December 2014. In the 11 months prior to the launch of TMUS, HIV testing events among BMSM in the six campaign implementation cities decreased by nearly 35 tests per month (p = .021). After the introduction of TMUS, the number of HIV testing events among BMSM in the same cities increased by more than 6 tests per month (p = .002). ITSA represents a quasi-experimental technique for investigating campaign effects beyond underlying time trends when serial outcome data are available. Future evaluations can be further strengthened by incorporating a comparison group to account for the effects of history and maturation on pre- and post-campaign trends.

      2. Purpose: To identify methods used by local health departments (LHDs) for reaching providers and the public with information about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Methods: During 2009-2012, we conducted LHD outreach in three stages: 1) materials needs assessment with LHDs in 18 states-85% of 90 targeted LHDs; 2) dissemination to LHDs in 15 states-distributed 67,850 copies of ME/CFS printed materials to 121 LHDs; and 3) follow-up calls with LHDs 6 months after dissemination – 75% of 118 LHDs. The follow-up interview included 18 questions about ME/CFS material use, perception, and knowledge. Results: Ninety-three percent of LHDs had no ME/CFS program or materials. ME/CFS was not rated a public health priority, yet 90% were interested in receiving ME/CFS materials. Of 89 LHDs completing the follow-up interview, 50% were in rural areas, 74% had heard about ME/CFS, and 80% had used the CDC-provided ME/CFS materials. LHDs incorporated these ME/CFS materials into existing programs and dissemination formats (e.g. kiosks and printed materials were preferred). Past use of provided materials did not impact LHDs’ plan to use materials in the future. Regardless of prior ME/CFS awareness, LHDs rated ME/CFS as an important health issue. Conclusions: This paper highlights criteria to consider when developing outreach methods for LHDs including materials and dissemination. We learned materials should be concise and easily transportable to facilitate use in the community. Materials and outreach methods might require tailoring to LHDs as competing health priorities was the most common reason given by LHDs for not using ME/CFS materials.

    • Health Economics
      1. The crowding-out effect of tobacco expenditure on household spending patterns in Bangladesh
        Husain MJ, Datta BK, Virk-Baker MK, Parascandola M, Khondker BH.
        PLoS One. 2018 ;13(10):e0205120.
        BACKGROUND: Tobacco consumption constitutes a sizable portion of household consumption expenditure, which can lead to reduced expenditures on other basic commodities. This is known as the crowding-out effect. This study analyzes the crowding-out effect of tobacco consumption in Bangladesh, and the research findings have relevance for strengthening the tobacco control for improving health and well-being. METHODS: We analyzed data from the Bangladesh Household Income and Expenditure Survey 2010 to examine the differences in consumption expenditure pattern between tobacco user and non-user households. We further categorize tobacco user households in three mutually exclusive groups of smoking-only, smokeless-only, and dual (both smoking and smokeless); and investigated the crowding-out effects for these subgroups. We compared the mean expenditure shares of different types of households, and then estimated the conditional Engel curves for various expenditure categories using Seemingly Unrelated Regression (SUR) method. Crowding-out was considered to have occurred if estimated coefficient of the tobacco use indicator was negative and statistically significant. RESULTS: We find that tobacco user households on average allocated less in clothing, housing, education, energy, and transportation and communication compared to tobacco non-user households. The SUR estimates also confirmed crowding-out in these consumption categories. Mean expenditure share of food and medical expenditure of tobacco user households, however, are greater than those of tobacco non-user households. Albeit similar patterns observed for different tobacco user households, there were differences in magnitudes depending on the type of tobacco-use, rural-urban locations and economic status. CONCLUSION: Policy measures that reduce tobacco use could reduce displacement of commodities by households with tobacco users, including those commodities that can contribute to human capital investments.

      2. Cost of public health response and outbreak control with a third dose of measles-mumps-rubella vaccine during a university mumps outbreak – Iowa, 2015-2016
        Marin M, Kitzmann TL, James L, Quinlisk P, Aldous WK, Zhang J, Cardemil CV, Galeazzi C, Patel M, Ortega-Sanchez IR.
        Open Forum Infect Dis. 2018 Oct;5(10):ofy199.
        Background: The United States is experiencing mumps outbreaks in settings with high 2-dose measles-mumps-rubella (MMR) vaccine coverage, mainly universities. The economic impact of mumps outbreaks on public health systems is largely unknown. During a 2015-2016 mumps outbreak at the University of Iowa, we estimated the cost of public health response that included a third dose of MMR vaccine. Methods: Data on activities performed, personnel hours spent, MMR vaccine doses administered, miles traveled, hourly earnings, and unitary costs were collected using a customized data tool. These data were then used to calculate associated costs. Results: Approximately 6300 hours of personnel time were required from state and local public health institutions and the university, including for vaccination and laboratory work. Among activities demanding time were case/contact investigation (36%), response planning/coordination (20%), and specimen testing and report preparation (13% each). A total of 4736 MMR doses were administered and 1920 miles traveled. The total cost was >$649 000, roughly equally distributed between standard outbreak control activities and third-dose MMR vaccination (55% and 45%, respectively). Conclusions: Public health response to the mumps outbreak at the University of Iowa required important amounts of personnel time and other resources. Associated costs were sizable enough to affect other public health activities.

      3. Billing and volunteers substantially reduced school-located influenza vaccination costs, 2 Oregon counties, 2010-2011
        Patel SA, Groom HC, Cho BH, Martin K, Moore R.
        J Public Health Manag Pract. 2018 Nov/Dec;24(6):558-566.
        BACKGROUND AND OBJECTIVES: After the 2009 pandemic influenza seasons, the financial sustainability of school-located vaccination (SLV) clinics drew much attention. This study estimated and compared the labor costs of SLV clinics and reimbursements for influenza vaccinations for students attending 5 schools in 2 Oregon counties during 2010-2011. DESIGN/SETTING: Using a biweekly, Web-based survey, staff and volunteers prospectively tracked the time they spent on SLV clinic planning, implementation, and billing. They also tracked claims submitted and reimbursements by payment source. MAIN OUTCOME MEASURE: We report labor hours and associated costs for implementing school-based vaccination clinics; number of claims submitted and the reimbursement rate; and total and net costs. RESULTS: In county A, 260 doses were administered at a total cost of $5009 and received $3620 in payment. For county B, 165 doses were administered at a cost of $5598 and received $3807 in payments. With billing, the net cost per dose decreased from $19.74 to $8.57 and $38.08 to $16.17, for county A and county B, respectively. CONCLUSIONS: Reimbursements reduced cost per dose by 48% across SLV clinics across both Oregon counties. Local health departments can bill local health insurers to offset costs for implementing school-based vaccination clinics. Efforts to set up billing processes require dedicated billing staff who can effectively manage claims submission processes with multiple health insurers.

      4. The economic burden of child maltreatment in the United States, 2015
        Peterson C, Florence C, Klevens J.
        Child Abuse Negl. 2018 Oct 8;86:178-183.
        Child maltreatment incurs a high lifetime cost per victim and creates a substantial US population economic burden. This study aimed to use the most recent data and recommended methods to update previous (2008) estimates of 1) the per-victim lifetime cost, and 2) the annual US population economic burden of child maltreatment. Three ways to update the previous estimates were identified: 1) apply value per statistical life methodology to value child maltreatment mortality, 2) apply monetized quality-adjusted life years methodology to value child maltreatment morbidity, and 3) apply updated estimates of the exposed population. As with the previous estimates, the updated estimates used the societal cost perspective and lifetime horizon, but also accounted for victim and community intangible costs. Updated methods increased the estimated nonfatal child maltreatment per-victim lifetime cost from $210,012 (2010 USD) to $830,928 (2015 USD) and increased the fatal per-victim cost from $1.3 to $16.6 million. The estimated US population economic burden of child maltreatment based on 2015 substantiated incident cases (482,000 nonfatal and 1670 fatal victims) was $428 billion, representing lifetime costs incurred annually. Using estimated incidence of investigated annual incident cases (2,368,000 nonfatal and 1670 fatal victims), the estimated economic burden was $2 trillion. Accounting for victim and community intangible costs increased the estimated cost of child maltreatment considerably compared to previous estimates. The economic burden of child maltreatment is substantial and might off-set the cost of evidence-based interventions that reduce child maltreatment incidence.

      5. Economic costs attributable to diabetes in each U.S. state
        Shrestha SS, Honeycutt AA, Yang W, Zhang P, Khavjou OA, Poehler DC, Neuwahl SJ, Hoerger TJ.
        Diabetes Care. 2018 Oct 10.
        OBJECTIVE: To estimate direct medical and indirect costs attributable to diabetes in each U.S. state in total and per person with diabetes. RESEARCH DESIGN AND METHODS: We used an attributable fraction approach to estimate direct medical costs using data from the 2013 State Health Expenditure Accounts, 2013 Behavioral Risk Factor Surveillance System, and the Centers for Medicare & Medicaid Services’ 2013-2014 Minimum Data Set. We used a human capital approach to estimate indirect costs measured by lost productivity from morbidity (absenteeism, presenteeism, lost household productivity, and inability to work) and premature mortality, using the 2008-2013 National Health Interview Survey, 2013 daily housework value data, 2013 mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research, and mean wages from the 2014 Bureau of Labor Statistics. Costs were adjusted to 2017 U.S. dollars. RESULTS: The estimated median state economic cost was $5.9 billion, ranging from $694 million to $55.5 billion, in total and $18,248, ranging from $15,418 to $30,915, per person with diabetes. The corresponding estimates for direct medical costs were $2.8 billion (range: $0.3-22.9) and $8,544 (range: $6,591-12,953) and for indirect costs were $3.0 billion (range: $0.4-32.6) and $9,672 (range: $7,133-17,962). In general, the estimated state median indirect costs resulting from morbidity were larger than costs from mortality both in total and per person with diabetes. CONCLUSIONS: Economic costs attributable to diabetes were large and varied widely across states. Our comprehensive state-specific estimates provide essential information needed by state policy makers to monitor the economic burden of the disease and to better plan and evaluate interventions for preventing type 2 diabetes and managing diabetes in their states.

    • Healthcare Associated Infections
      1. Notes from the Field: Large cluster of Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Pseudomonas aeruginosa isolates colonizing residents at a skilled nursing facility – Chicago, Illinois, November 2016-March 2018
        Clegg WJ, Pacilli M, Kemble SK, Kerins JL, Hassaballa A, Kallen AJ, Walters MS, Halpin AL, Stanton RA, Boyd S, Gable P, Daniels J, Lin MY, Hayden MK, Lolans K, Burdsall DP, Lavin MA, Black SR.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 12;67(40):1130-1131.

        [No abstract]

    • Immunity and Immunization
      1. Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians’ perspectives in the endgame plan for polio eradication
        Galal NM, Meshaal S, ElHawary R, Nasr E, Bassiouni L, Ashghar H, Farag NH, Mach O, Burns C, Iber J, Chen Q, ElMarsafy A.
        BMC Res Notes. 2018 Oct 11;11(1):717.
        OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described. RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.

      2. Association between third-trimester Tdap immunization and neonatal pertussis antibody concentration
        Healy CM, Rench MA, Swaim LS, Smith EO, Sangi-Haghpeykar H, Mathis MH, Martin MD, Baker CJ.
        Jama. 2018 Oct 9;320(14):1464-1470.
        Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

      3. Vaccination coverage among children aged 19-35 months – United States, 2017
        Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 12;67(40):1123-1128.
        The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination by age 24 months against 14 potentially serious illnesses (1). CDC used data from the 2017 National Immunization Survey-Child (NIS-Child) to assess vaccination coverage at national, state, territorial, and selected local levels among children aged 19-35 months in the United States. Coverage remained high and stable overall, exceeding 90% for >/=3 doses of poliovirus vaccine, >/=1 dose of measles, mumps, and rubella vaccine (MMR), >/=3 doses of hepatitis B vaccine (HepB), and >/=1 dose of varicella vaccine. Although the proportion of children who received no vaccine doses by age 24 months was low, this proportion increased gradually from 0.9% for children born in 2011 to 1.3% for children born in 2015. Coverage was lower for most vaccines among uninsured children and those insured by Medicaid, compared with those having private health insurance, and for children living outside of metropolitan statistical areas* (MSAs), compared with those living in MSA principal cities. These disparities could be reduced with greater awareness and use of the Vaccines for Children(dagger) (VFC) program, eliminating missed opportunities to vaccinate children during visits to health care providers, and minimizing interruptions in health insurance coverage.

      4. Primary care physicians’ experience with zoster vaccine live (ZVL) and awareness and attitudes regarding the new recombinant zoster vaccine (RZV)
        Hurley LP, Allison MA, Dooling KL, O’Leary ST, Crane LA, Brtnikova M, Beaty BL, Allen JA, Guo A, Lindley MC, Kempe A.
        Vaccine. 2018 .
        Background: The Advisory Committee on Immunization Practices (ACIP) has routinely recommended zoster vaccine live (ZVL) for adults >=60 since 2008; only 33% of eligible adults received it by 2016. A recombinant zoster vaccine (RZV) was licensed in 2017 and ACIP recommended in January 2018. Our objectives were to assess among primary care physicians (1) practices and attitudes regarding ZVL and (2) awareness of RZV. Methods: We administered an Internet and mail survey from July to September 2016 to national networks of 953 primary care physicians. Results: Response rate was 65% (603/923). Ninety-three % of physicians recommended ZVL to adults >=60, but fewer recommended it to adults >=60 with a prior history of zoster (88%), adults > 85 (62%) and adults >=60 on low-dose methotrexate (42%). Several physicians recommended ZVL in ways that are not recommended by ACIP including to adults 50-59 (50%), adults >=60 with HIV (33%), and adults >=60 on high dose prednisone (>=20 mg/day) (27%). Nineteen percent of physicians stocked and administered ZVL and did not refer patients elsewhere for vaccination, 37% did not stock and only referred patients to receive it, and 44% both stocked/administered and referred elsewhere. Twenty-three % (n = 115) of physicians who had ever administered ZVL in the office (n = 490) had stopped, citing primarily financial issues (90%). Only 5% were ‘very aware’ of RZV. Conclusions: Physicians report not recommending ZVL to certain ACIP-recommended groups, but report recommending it to some groups for which the vaccine should be avoided. Implementation of recommendations for RZV will need to consider financial barriers and the complex patchwork of office-based and pharmacy delivery ZVL has encountered.

      5. Disparities in Tdap vaccination and vaccine information needs among pregnant women in the United States
        Kriss JL, Albert AP, Carter VM, Jiles AJ, Liang JL, Mullen J, Rodriguez L, Howards PP, Orenstein WA, Omer SB, Fisher A.
        Matern Child Health J. 2018 Oct 4.
        Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women’s decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June-July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women’s decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36-45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43-60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20-4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.

      6. Vaccination coverage for selected vaccines and exemption rates among children in kindergarten – United States, 2017-18 School Year
        Mellerson JL, Maxwell CB, Knighton CL, Kriss JL, Seither R, Black CL.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 12;67(40):1115-1122.
        State and local school vaccination requirements exist to ensure that students are protected from vaccine-preventable diseases (1). This report summarizes vaccination coverage and exemption estimates collected by state and local immunization programs* for children in kindergarten (kindergartners) in 49 states and the District of Columbia (DC) and kindergartners provisionally enrolled (attending school without complete vaccination or exemption while completing a catch-up vaccination schedule) or in a grace period (a set interval during which a student may be enrolled and attend school without proof of complete vaccination or exemption) for 28 states. Median vaccination coverage(dagger) was 95.1% for the state-required number of doses of diphtheria and tetanus toxoids, and acellular pertussis vaccine (DTaP); 94.3% for 2 doses of measles, mumps, and rubella vaccine (MMR); and 93.8% for 2 doses of varicella vaccine. The median percentage of kindergartners with an exemption from at least one vaccine( section sign) was 2.2%, and the median percentage provisionally enrolled or attending school during a grace period was 1.8%. Vaccination coverage among kindergartners remained high; however, schools can improve coverage by following up with students who are provisionally enrolled, in a grace period, or lacking complete documentation of required vaccinations.

      7. Influenza vaccination coverage among US-Mexico land border crossers: 2009 H1N1 pandemic and 2011-2012 influenza season
        Rodriguez-Lainz A, DeSisto C, Waterman S, Wiedemann MS, Moore CW, Williams WW, Moser K.
        Travel Med Infect Dis. 2018 Oct 5.
        BACKGROUND: The high volume of US-Mexico land border crossings can facilitate international dissemination of influenza viruses. METHODS: We surveyed adult pedestrians crossing into the United States at two international land ports of entry to assess vaccination coverage during the 2009H1N1 influenza pandemic and 2011-2012 influenza season. RESULTS: Of 559 participants in 2010, 23.4% reported receipt of the 2009H1N1 vaccine. Of 1423 participants in 2012, 33.7% received the 2011-2012 influenza vaccine. Both years, those crossing the border >/=8 times per month had lower vaccination coverage than those crossing less frequently. US-border residents had lower H1N1 coverage than those in other locations. Vaccination coverage was higher for persons age >/=65 years and, in 2010 only, those with less than high school education. Although most participants believed it is important to get vaccinated, only half believed the influenza vaccine was safe and effective. The main reasons for not receiving the influenza vaccine were beliefs of low risk of disease, time constraints, and concerns about vaccine safety (in 2010) or efficacy (in 2012). CONCLUSIONS: International land border crossers are a large and unique category of travelers that require targeted binational strategies for influenza vaccination and education.

      8. Influenza vaccine effectiveness in preventing influenza-associated hospitalizations during pregnancy: A multi-country retrospective test negative design study, 2010-2016
        Thompson MG, Kwong JC, Regan AK, Katz MA, Drews SJ, Azziz-Baumgartner E, Klein NP, Chung H, Effler PV, Feldman BS, Simmonds K, Wyant BE, Dawood FS, Jackson ML, Fell DB, Levy A, Barda N, Svenson LW, Fink RV, Ball SW, Naleway A.
        Clin Infect Dis. 2018 Oct 11.
        Background: To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results: Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy. Conclusion: Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs.

    • Informatics
      1. The information imperative for public health: A call to action to become informatics-savvy
        Brand B, LaVenture M, Lipshutz JA, Stephens WF, Baker EL.
        J Public Health Manag Pract. 2018 Nov/Dec;24(6):586-589.

        [No abstract]

    • Injury and Violence
      1. INTRODUCTION/BACKGROUND: Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease thought to be caused by repeated head impacts and associated with deficits in cognition. Despite research and media attention, there is little science-based information available for the public. Also unclear is what the public and particularly parents of youth athletes know about CTE. The U.S. Centers for Disease Control and Prevention (CDC) surveyed parents of young athletes to fill this gap. METHODS: CDC analysed 12 CTE-related questions that appeared in Porter Novelli Public Service’s 2017 SummerStyles opinion survey. Analyses focused on 674 parents of children who play in a youth sports programme. RESULTS: Half of parents had at least one child who plays contact sports. About one-third of respondents reported being somewhat or very familiar with CTE. Most parents (81.7%) have not received educational materials on CTE from a school or sports programme. Healthcare providers were the preferred source of information about CTE (70%), followed by sports coaches (54%). DISCUSSION/CONCLUSION: This analysis identified information needs related to CTE among parents of young athletes. These findings can be used by health educators to tailor educational materials to meet information needs. Educational materials that emphasize potential prevention strategies and symptom onset may be beneficial.

      2. Patient presentations in outpatient settings: Epidemiology of adult head trauma treated outside of hospital emergency departments
        Zogg CK, Haring RS, Xu L, Canner JK, Ottesen TD, Salim A, Haider AH, Schneider EB.
        Epidemiology. 2018 Nov;29(6):885-894.
        BACKGROUND: While deaths, hospitalizations, and emergency department visits for head trauma are well understood, little is known about presentations in outpatient settings. Our objective was to examine the epidemiology and extent of healthcare-seeking adult (18-64 years) head trauma patients presenting in outpatient settings compared with patients receiving nonhospitalized emergency department care. METHODS: We used 2004-2013 MarketScan Medicaid/commercial claims to identify head trauma patients managed in outpatient settings (primary care provider, urgent care) and the emergency department. We examined differences in demographic and injury-specific factors, Centers for Disease Control and Prevention-defined head trauma diagnoses, and extent of and reasons for postindex visit ambulatory care use within 30/90/180 days by index visit location, as well as annual and monthly variations in head trauma trends. We used outpatient incidence rates to estimate the US nationwide outpatient burden. RESULTS: A total of 1.19 million index outpatient visits were included (emergency department: 348,659). Nationwide, they represented a weighted annual burden of 1.16 million index outpatient cases. These encompassed 46% of all known healthcare-seeking head trauma in 2013 (outpatient/emergency department/inpatient/fatalities) and increased in magnitude (+31%) from 2004 to 2013. One fourth (27%) of office/clinic visits led to diagnosis with concussion on index presentation (urgent care: 32%). Distributions of demographic factors varied with index visit location while injury-specific factors were largely comparable. Subsequent visits reflected high demand for follow-up treatment, increased concussive diagnoses, and sequelae-associated care. CONCLUSIONS: Adult outpatient presentations of head trauma remain poorly understood. The results of this study demonstrate the extensive magnitude of their occurrence and close association with need for follow-up care.

    • Laboratory Sciences
      1. Effective regulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been linked to numerous health outcomes. Within-person variation in diurnal measures of HPA-axis regulation assessed over days, months, and years can range between 50-73% of total variation. In this study of 59 youth (ages 8-13), we quantified the stability of the cortisol awakening response (CAR), the diurnal slope, and tonic cortisol concentrations at waking and bedtime across 8 days (2 sets of 4 consecutive days separated by 3 weeks), 3 weeks, and 3 years. We then compared the stability of these indices across three key developmental factors: age, pubertal status, and sex. Youth provided 4 saliva samples per day (waking, 30 min post-waking, before dinner, and before bedtime) for 4 consecutive days during the 3rd week of an ongoing 8-week daily diary study. Youth repeated this same sampling procedure 3 weeks and 3 years later. Using multi-level modeling, we computed the amount of variance in diurnal HPA-axis regulation that was accounted for by nesting an individual’s diurnal cortisol indices within days, weeks, or years. Across days, diurnal slope was the most stable index, whereas waking cortisol and CAR were the least stable. All indices except bedtime cortisol were similarly stable when measured across weeks, and all indices were uniformly stable when measured across 3 years. Boys, younger participants, and youth earlier in their pubertal development at study enrollment exhibited greater HPA-axis stability overall compared with females and older, more physically mature participants. We conclude that important within- and between-subjects questions can be answered about health and human development by studying HPA-axis regulation, and selection of the index of interest should be determined in part by its psychometric characteristics. To this end, we propose a decision tree to guide study design for research in pediatric samples by longitudinal timeframe and sample characteristics.

      2. BACKGROUND: Reference measurement procedures (RMP) have rigorous accuracy specifications. For total 25-hydroxyvitamin D, 25(OH)D, bias </=1.7% and CV </=5% are recommended. These quality specifications are impractical for minor analytes, such as 25(OH)D2. Furthermore, documentation on RMP quality performance specifications for the individual 25(OH)D metabolites and their daily application are missing. METHODS: To assess accuracy, we used zeta-scores. Daily, 5-10 specimens (duplicate) and 3 reference materials (singleton or duplicate) were measured for 25(OH)D3 and 25(OH)D2 using JCTLM-accepted LC-MS/MS RMPs. Protocols were repeated on 3-4 occasions to generate campaign results. We used separate zeta-score acceptability criteria for daily (</=|2|) and campaign (</=|1|) evaluations. Allowable imprecision was determined experimentally. RESULTS: Across 7 campaigns, unacceptable daily zeta-scores required repeating 2 runs for 25(OH)D3 and 5 runs for 25(OH)D2. Hence, the zeta-scores of acceptable reference material results indicated high accuracy. The allowable imprecision for the RMPs was </=5% (daily) and</=3% (campaign) for 25(OH)D3 and</=7% (daily) and</=4% (campaign) for 25(OH)D2, respectively. CONCLUSIONS: Using zeta-scores and experimentally derived imprecision, we developed a straightforward approach to assess the acceptability of individual 25(OH)D reference measurements, providing also much-needed practical accuracy specifications for 25(OH)D2.

      3. Risk assessment of fifth-wave H7N9 influenza A viruses in mammalian models
        Sun X, Belser JA, Pappas C, Pulit-Penaloza JA, Brock N, Zeng H, Creager HM, Le S, Wilson M, Lewis A, Stark TJ, Shieh WJ, Barnes J, Tumpey TM, Maines TR.
        J Virol. 2018 Oct 10.
        The fifth-wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth-wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and HA cleavability. Here, several low pathogenic avian influenza (LPAI) and HPAI H7N9 human isolates from the fifth epidemic wave were assessed for their pathogenicity and transmissibility in mammalian models, as well as their ability to replicate in human airway epithelial cells. We found that a LPAI virus exhibited a similar capacity to replicate and cause disease in two animal species as viruses from previous waves. In contrast, HPAI H7N9 viruses possessed enhanced virulence, causing greater lethargy and mortality, with an extended tropism for brain tissues in both ferret and mouse models. These HPAI viruses also showed signs of adaptation to mammalian hosts by acquiring the ability to fuse at a lower pH threshold compared with other H7N9 viruses. All of the fifth-wave H7N9 viruses were able to transmit among cohoused ferrets, but exhibited a limited capacity to transmit by respiratory droplets and deep sequencing analysis revealed that the H7N9 viruses sampled after transmission showed a reduced amount of minor variants. Taken together, we conclude that the fifth-wave HPAI H7N9 viruses have gained the ability to cause enhanced disease in mammalian models, and with further adaptation may acquire the ability to cause an H7N9 pandemic.ImportanceThe potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increased number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses were evaluated for their ability to infect, cause disease, and transmit in small animal models. The ability of HPAI H7N9 viruses to cause more severe disease and to replicate in brain tissues in animal models as well as their ability to fuse at a lower pH threshold compared to LPAI H7N9 viruses suggest that the fifth-wave H7N9 viruses have evolved to acquire novel traits with the potential to pose a higher risk to humans. Although the fifth-wave H7N9 viruses have not yet gained the ability to transmit efficiently by air, continuous surveillance and risk assessment remain essential parts of our pandemic preparedness efforts.

      4. “Only a life lived for others is worth living”: Redox signaling by oxygenated phospholipids in cell fate decisions
        Tyurina YY, Shrivastava I, Tyurin VA, Mao G, Dar HH, Watkins S, Epperly M, Bahar I, Shvedova AA, Pitt B, Wenzel SE, Mallampalli RK, Sadovsky Y, Gabrilovich D, Greenberger JS, Bayir H, Kagan VE.
        Antioxid Redox Signal. 2018 Nov 1;29(13):1333-1358.
        SIGNIFICANCE: Oxygenated polyunsaturated lipids are known to play multi-functional roles as essential signals coordinating metabolism and physiology. Among them are well-studied eicosanoids and docosanoids that are generated via phospholipase A2 hydrolysis of membrane phospholipids and subsequent oxygenation of free polyunsaturated fatty acids (PUFA) by cyclooxygenases and lipoxygenases. Recent Advances: There is an emerging understanding that oxygenated PUFA-phospholipids also represent a rich signaling language with yet-to-be-deciphered details of the execution machinery-oxygenating enzymes, regulators, and receptors. Both free and esterified oxygenated PUFA signals are generated in cells, and their cross-talk and inter-conversion through the de-acylation/re-acylation reactions is not sufficiently explored. CRITICAL ISSUES: Here, we review recent data related to oxygenated phospholipids as important damage signals that trigger programmed cell death pathways to eliminate irreparably injured cells and preserve the health of multicellular environments. We discuss the mechanisms underlying the trans-membrane redistribution and generation of oxygenated cardiolipins in mitochondria by cytochrome c as pro-apoptotic signals. We also consider the role of oxygenated phosphatidylethanolamines as proximate pro-ferroptotic signals. FUTURE DIRECTIONS: We highlight the importance of sequential processes of phospholipid oxygenation and signaling in disease contexts as opportunities to use their regulatory mechanisms for the identification of new therapeutic targets.

    • Maternal and Child Health
      1. Prevalence thresholds for wasting, overweight and stunting in children under 5 years
        de Onis M, Borghi E, Arimond M, Webb P, Croft T, Saha K, De-Regil LM, Thuita F, Heidkamp R, Krasevec J, Hayashi C, Flores-Ayala R.
        Public Health Nutr. 2018 Oct 9:1-5.
        OBJECTIVE: Prevalence ranges to classify levels of wasting and stunting have been used since the 1990s for global monitoring of malnutrition. Recent developments prompted a re-examination of existing ranges and development of new ones for childhood overweight. The present paper reports from the WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring. DESIGN: Thresholds were developed in relation to sd of the normative WHO Child Growth Standards. The international definition of ‘normal’ (2 sd below/above the WHO standards median) defines the first threshold, which includes 2.3 % of the area under the normalized distribution. Multipliers of this ‘very low’ level (rounded to 2.5 %) set the basis to establish subsequent thresholds. Country groupings using the thresholds were produced using the most recent set of national surveys. SETTING: One hundred and thirty-four countries. SUBJECTS: Children under 5 years. RESULTS: For wasting and overweight, thresholds are: ‘very low’ ( approximately 6 times 2.5 %). For stunting, thresholds are: ‘very low’ ( approximately 12 times 2.5 %). CONCLUSIONS: The proposed thresholds minimize changes and keep coherence across anthropometric indicators. They can be used for descriptive purposes to map countries according to severity levels; by donors and global actors to identify priority countries for action; and by governments to trigger action and target programmes aimed at achieving ‘low’ or ‘very low’ levels. Harmonized terminology will help avoid confusion and promote appropriate interventions.

    • Nutritional Sciences
      1. Background: 24-h urine collections are the suggested method to measure daily urinary potassium excretion (uK) but are costly and burdensome to implement. Objective: This study tested how well existing equations with the use of spot urine samples can estimate 24-h uK and if accuracy varies by timing of spot urine collection, age, race, or sex. Design: This cross-sectional study used data from 407 participants aged 18-39 y from the Washington, DC area in 2011 and 554 participants aged 45-79 y from Chicago in 2013. Spot urine samples were collected in individual containers for 24 h, and 1 for each timed period (morning, afternoon, evening, and overnight) was selected. For each selected timed spot urine, 24-h uK was predicted through the use of published equations. Difference (bias) between predicted and measured 24-h uK was calculated for each timed period and within age, race, and sex subgroups. Individual-level differences were assessed through the use of Bland-Altman plots and correlation tests. Results: For all equations, regardless of the timing of spot urine, mean bias was usually significantly different than 0. No one prediction equation was unbiased across all sex, race, and age subgroups. With the use of the Kawasaki and Tanaka equations, 24-h uK was overestimated at low levels and underestimated at high levels, whereas observed differential bias with the Mage equation was in the opposite direction. Depending on prediction equation and timing of urine sample, 61-75% of individual 24-h uKs were misclassified among 500-mg incremental categories from <1500 to ?3000 mg. Correlations between predicted and measured 24-h uK were poor to moderate (0.19-0.71). Conclusion: Because predicted 24-h uK accuracy varies by timing of spot urine collection, published prediction equations, and within age-race-sex subgroups, study results making use of predicted 24-h uK in association with health outcomes should be interpreted with caution. It is possible that a more accurate prediction equation can be developed leading to different results.

    • Occupational Safety and Health
      1. Lower extremity kinematics of cross-slope roof walking
        Breloff SP, Wade C, Waddell DE.
        Applied Ergonomics. 2019 ;75:134-142.
        Working conditions of residential roofers expose them to a unique sloped environment. The purpose of this study is to determine in what way traversing across a sloped/roof surface alters lower extremity kinematics of the upslope and downslope legs compared to level walking. College aged males negotiated across a pitched (26 degrees) roof segment during which lower extremity three-dimensional kinematics were calculated. One foot was higher on the slope and one was lower for the duration of cross slope walking. Overall, cross-slope walking on a 26 degree roof significantly altered 77% of the measured lower extremity variables compared to level self-selected pace walking. The data suggest that roof pitch incite significant differences in crossslope walking of the kinematics in the lower extremity between the upslope and down slope limbs when compared to level surface walking. These alterations could temporarily alter proprioception which may in turn lead to increased falls and musculoskeletal injury, though further study is needed.

    • Occupational Safety and Health – Mining
      1. Laboratory testing of a shuttle car canopy air curtain for respirable coal mine dust control
        Reed WR, Zheng Y, Yekich M, Ross G, Salem A.
        Int J Coal Sci Technol. 2018 Sep;10:1007.
        Canopy air curtain (CAC) technology has been developed by the National Institute for Occupational Safety and Health (NIOSH) for use on continuous miners and subsequently roof bolting machines in underground coal mines to protect operators of these machines from overexposure to respirable coal mine dust. The next logical progression is to develop a CAC for shuttle cars to protect operators from the same overexposures. NIOSH awarded a contract to Marshall University and J.H. Fletcher to develop the shuttle car CAC. NIOSH conducted laboratory testing to determine the dust control efficiency of the shuttle car CAC. Testing was conducted on two different cab configurations: a center drive similar to that on a Joy 10SC32AA cab model and an end drive similar to that on a Joy 10SC32AB cab model. Three different ventilation velocities were tested-0.61, 2.0, 4.3 m/s (120, 400, and 850 fpm). The lowest, 0.61 m/s (120 fpm), represented the ventilation velocity encountered during loading by the continuous miner, while the 4.3 m/s (850 fpm) velocity represented ventilation velocity airflow over the shuttle car while tramming against ventilation airflow. Test results showed an average of the dust control efficiencies ranging from 74 to 83% for 0.61 m/s (120 fpm), 39%-43% for 2.0 m/s (400 fpm), and 6%-16% for 4.3 m/s (850 fpm). Incorporating an airflow spoiler to the shuttle car CAC design and placing the CAC so that it is located 22.86 cm (9 in.) forward of the operator improved the dust control efficiency to 51%-55% for 4.3 m/s (850 fpm) with minimal impact on dust control efficiencies for lower ventilation velocities. These laboratory tests demonstrate that the newly developed shuttle car CAC has the potential to successfully protect shuttle car operators from coal mine respirable dust overexposures.

    • Parasitic Diseases
      1. Assessing whether universal coverage with insecticide-treated nets has been achieved: is the right indicator being used?
        Koenker H, Arnold F, Ba F, Cisse M, Diouf L, Eckert E, Erskine M, Florey L, Fotheringham M, Gerberg L, Lengeler C, Lynch M, Mnzava A, Nasr S, Ndiop M, Poyer S, Renshaw M, Shargie E, Taylor C, Thwing J, Van Hulle S, Ye Y, Yukich J, Kilian A.
        Malar J. 2018 Oct 11;17(1):355.
        BACKGROUND/METHODS: Insecticide-treated nets (ITNs) are the primary tool for malaria vector control in sub-Saharan Africa, and have been responsible for an estimated two-thirds of the reduction in the global burden of malaria in recent years. While the ultimate goal is high levels of ITN use to confer protection against infected mosquitoes, it is widely accepted that ITN use must be understood in the context of ITN availability. However, despite nearly a decade of universal coverage campaigns, no country has achieved a measured level of 80% of households owning 1 ITN for 2 people in a national survey. Eighty-six public datasets from 33 countries in sub-Saharan Africa (2005-2017) were used to explore the causes of failure to achieve universal coverage at the household level, understand the relationships between the various ITN indicators, and further define their respective programmatic utility. RESULTS: The proportion of households owning 1 ITN for 2 people did not exceed 60% at the national level in any survey, except in Uganda’s 2014 Malaria Indicator Survey (MIS). At 80% population ITN access, the expected proportion of households with 1 ITN for 2 people is only 60% (p = 0.003 R(2) = 0.92), because individuals in households with some but not enough ITNs are captured as having access, but the household does not qualify as having 1 ITN for 2 people. Among households with 7-9 people, mean population ITN access was 41.0% (95% CI 36.5-45.6), whereas only 6.2% (95% CI 4.0-8.3) of these same households owned at least 1 ITN for 2 people. On average, 60% of the individual protection measured by the population access indicator is obscured when focus is put on the household “universal coverage” indicator. The practice of limiting households to a maximum number of ITNs in mass campaigns severely restricts the ability of large households to obtain enough ITNs for their entire family. CONCLUSIONS: The two household-level indicators-one representing minimal coverage, the other only ‘universal’ coverage-provide an incomplete and potentially misleading picture of personal protection and the success of an ITN distribution programme. Under current ITN distribution strategies, the global malaria community cannot expect countries to reach 80% of households owning 1 ITN for 2 people at a national level. When programmes assess the success of ITN distribution activities, population access to ITNs should be considered as the better indicator of “universal coverage,” because it is based on people as the unit of analysis.

    • Public Health Leadership and Management
      1. Advancing the science of healthcare service delivery: The NHLBI Corporate Healthcare Leaders’ Panel
        Sampson UK, McGlynn EA, Perlin JB, Frisse ME, Arnold SB, Benz EJ, Brennan T, Briss P, Beeuwkes Buntin MJ, Khosla S, King RG, Kuntz R, Leider H, Ling SM, Macrae J, Murray R, Thrailkill E, Wager C, Witchey D, Jacobson HR.
        Glob Heart. 2018 Oct 6.
        There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation. In this context, the National Heart, Lung, and Blood Institute convened a panel made up of leaders of corporate health care entities, including academic health centers, and government agency representatives to inform contemporary strategic partnerships with health care companies. This article provides insights from the meeting on how to execute a transformative innovation research agenda that will foster improvements in health care service delivery by leveraging the translation of biomedical research evidence in real-world settings.

    • Reproductive Health
      1. Report of the Office of Population Affairs’ expert work group meeting on short birth spacing and adverse pregnancy outcomes: Methodological quality of existing studies and future directions for research
        Ahrens KA, Hutcheon JA, Ananth CV, Basso O, Briss PA, Ferre CD, Frederiksen BN, Harper S, Hernandez-Diaz S, Hirai AH, Kirby RS, Klebanoff MA, Lindberg L, Mumford SL, Nelson HD, Platt RW, Rossen LM, Stuebe AM, Thoma ME, Vladutiu CJ, Moskosky S.
        Paediatr Perinat Epidemiol. 2018 Oct 9.
        BACKGROUND: The World Health Organization (WHO) recommends that women wait at least 24 months after a livebirth before attempting a subsequent pregnancy to reduce the risk of adverse maternal, perinatal, and infant health outcomes. However, the applicability of the WHO recommendations for women in the United States is unclear, as breast feeding, nutrition, maternal age at first birth, and total fertility rate differs substantially between the United States and the low- and middle-resource countries upon which most of the evidence is based. METHODS: To inform guideline development for birth spacing specific to women in the United States, the Office of Population Affairs (OPA) convened an expert work group meeting in Washington, DC, on 14-15 September 2017 among reproductive, perinatal, paediatric, social, and public health epidemiologists; obstetrician-gynaecologists; biostatisticians; and experts in evidence synthesis related to women’s health. RESULTS: Presentations and discussion topics included the methodological quality of existing studies, evaluation of the evidence for causal effects of short interpregnancy intervals on adverse perinatal and maternal health outcomes, good practices for future research, and identification of research gaps and priorities for future work. CONCLUSIONS: This report provides an overview of the presentations, discussions, and conclusions from the expert work group meeting.

      2. Quality of maternal height and weight data from the Revised Birth Certificate and Pregnancy Risk Assessment Monitoring System
        Deputy NP, Sharma AJ, Bombard JM, Lash TL, Schieve LA, Ramakrishnan U, Stein AD, Nyland-Funke M, Mullachery P, Lee E.
        Epidemiology. 2018 Oct 1.
        BACKGROUND: The 2003 revision of the US Standard Certificate of Live Birth (birth certificate) and Pregnancy Risk Assessment Monitoring System (PRAMS) are important for maternal weight research and surveillance. We examined quality of pre-pregnancy body mass index (BMI), gestational weight gain, and component variables from these sources. METHODS: Data are from a PRAMS data quality improvement study among a subset of New York City and Vermont respondents in 2009. We calculated mean differences comparing pre-pregnancy BMI data from the birth certificate and PRAMS (n=734), and gestational weight gain data from the birth certificate (n=678) to the medical record, considered the gold standard. We compared BMI categories (underweight, normal weight, overweight, obese) and gestational weight gain categories (below, within, above recommendations), classified by different sources, using percent agreement and the simple kappa statistic. RESULTS: For most maternal weight variables, mean differences between the birth certificate or PRAMS compared to the medical record were less than 1 kg. Compared to the medical record, the birth certificate classified similar proportions into pre-pregnancy BMI categories (agreement=89%, kappa=0.83); PRAMS slightly underestimated overweight and obesity (agreement=84%, kappa=0.73). Compared to the medical record, the birth certificate overestimated gestational weight gain below recommendations and underestimated weight gain within recommendations (agreement=81%, kappa=0.69). Agreement varied by maternal and pregnancy-related characteristics. CONCLUSIONS: Classification of pre-pregnancy BMI and gestational weight gain from the birth certificate or PRAMS were mostly similar to the medical record but varied by maternal and pregnancy-related characteristics. Efforts to understand how misclassification influences epidemiologic associations are needed.

    • Zoonotic and Vectorborne Diseases
      1. Infectious MERS-CoV isolated from a mildly ill patient, Saudi Arabia
        Al-Abdely HM, Midgley CM, Alkhamis AM, Abedi GR, Tamin A, Binder AM, Alanazi K, Lu X, Abdalla O, Sakthivel SK, Mohammed M, Queen K, Algarni HS, Li Y, Trivedi S, Algwizani A, Alhakeem RF, Thornburg NJ, Tong S, Ghazal SS, Erdman DD, Assiri AM, Gerber SI, Watson JT.
        Open Forum Infect Dis. 2018 Jun;5(6):ofy111.
        Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset.

      2. Notes from the field: Exported case of sin nombre hantavirus pulmonary syndrome – Israel, 2017
        Kofman A, Rahav G, Yazzie D, Shorty H, Yaglom HD, Peterson D, Peek-Bullock M, Choi MJ, Wieder-Finesod A, Klena JD, Venkat H, Chiang CF, Knust B, Gaither M, Maurer M, Hoeschele DR, Nichol ST.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 12;67(40):1129.

        [No abstract]

      3. Cross-border transmission of Ebola virus as the cause of a resurgent outbreak in Liberia in April 2016
        Mate SE, Wiley MR, Ladner JT, Dokubo EK, Fakoli L, Fallah M, Nyenswah TG, DiClaro JW, Deboer JT, Williams DE, Bolay F, Palacios G.
        Clin Infect Dis. 2018 Sep 14;67(7):1147-1149.

        [No abstract]

      4. Multihospital outbreak of a Middle East Respiratory syndrome coronavirus deletion variant, Jordan: A molecular, serologic, and epidemiologic investigation
        Payne DC, Biggs HM, Al-Abdallat MM, Alqasrawi S, Lu X, Abedi GR, Haddadin A, Iblan I, Alsanouri T, Al Nsour M, Sheikh Ali S, Rha B, Trivedi SU, Rasheed MA, Tamin A, Lamers MM, Haagmans BL, Erdman DD, Thornburg NJ, Gerber SI.
        Open Forum Infect Dis. 2018 May;5(5):ofy095.
        Background: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. Methods: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. Results: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. Conclusions: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.

      5. Screening for Zika virus RNA in sera of suspected cases: a retrospective cross-sectional study
        Sacchetto L, Zauli DA, Costa GB, Guagliardo SA, Alvim LB, Marinho FL, Abrahao JS, Trindade GS, Kroon EG, Mateo EC, Drumond BP.
        Virol J. 2018 Oct 11;15(1):155.
        BACKGROUND: Zika virus (ZIKV) became a global human health concern owing to its rapid spread worldwide and its association with congenital and neurological disorders. The current epidemiological profile of arboviruses in Brazil is characterized by widespread co-circulation of Dengue virus, Chikungunya virus, and ZIKV throughout the country. These viruses cause acute diseases frequently with overlapping symptoms, which could result in an inaccurate diagnosis based solely on clinical and epidemiological grounds. Here we conducted a screening for ZIKV RNA in serum samples from patients across Brazil with suspected ZIKV infection. METHODS: Using RT-qPCR, we investigated ZIKV RNA in 3001 serum samples. Samples were passively acquired through a private laboratory network, between December 2015 and August 2016, from 27 Brazilian Federative Units. We performed descriptive statistics on demographic variables including sex, age, and geographic location. RESULTS: ZIKV was detected in 11.4% (95%CI = 10.3-12.6%) of the sera. ZIKV RNA was detected in sera collected throughout the country, but during the analyzed period, RNA was more frequently detected in samples from the Southeast, Midwest, and North regions (3.9 to 5.8 times higher) when compared to the Northeast and South regions. CONCLUSIONS: These data reinforce the importance of laboratory diagnosis, surveillance systems, and further epidemiological studies to understand the dynamics of outbreaks and diseases associated with ZIKV and other arboviruses.

      6. Individual and spatial risk of dengue virus infection in Puerto Maldonado, Peru
        Salmon-Mulanovich G, Blazes DL, Guezala VM, Rios Z, Espinoza A, Guevara C, Lescano AG, Montgomery JM, Bausch DG, Pan WK.
        Am J Trop Med Hyg. 2018 Oct 8.
        Dengue virus (DENV) affects more than 100 countries worldwide. Dengue virus infection has been increasing in the southern Peruvian Amazon city of Puerto Maldonado since 2000. We designed this study to describe the prevalence of past DENV infection and to evaluate risk factors. In 2012, we conducted a cross-sectional serosurvey and administered a knowledge, attitudes, and practices (KAP) questionnaire to members of randomly selected households. Sera were screened for antibodies to DENV by ELISA and confirmed by plaque reduction neutralization test. We created indices for KAP (KAPi). We used SaTScan to detect clustering and created a multivariate model introducing the distance of households to potential vector and infection sources. A total of 505 participants from 307 households provided a blood sample and completed a questionnaire. Fifty-four percent of participants (95% CI: 49.6; 58.5) had neutralizing antibodies to DENV. Higher values of KAPi were positively associated with having DENV antibodies in the multivariate analysis (odds ratio [ORII]: 1.6, 95% CI: 0.6, 2.4; ORIII: 2.7, 95% CI: 1.3, 5.5; and ORIV: 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of having been exposed to DENV than younger people (OR20-30: 0.5, 95% CI: 0.2, 0.8; OR31-45: 0.5, 95% CI: 0.3, 0.9; and OR>45: 0.6, 95% CI: 0.3, 1.3). Multivariate data analysis from the 270 households with location information showed male gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We conclude that risk of DENV infection in Puerto Maldonado is related to gender, age of the population, and location.

      7. Direct diagnostic tests for Lyme disease
        Schutzer SE, 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 JL, Steere AC, Witkowski J, Wong SJ, Branda JA.
        Clin Infect Dis. 2018 Oct 11.
        Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.

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