Volume 10, Issue 15, May 1, 2018

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CDC Science Clips: Volume 10, Issue 15, May 1, 2018

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

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

The report consists of these components:

  1. CDC Vital Signs
    • Zoonotic and Vectorborne Diseases

      1. *Diagnosis and management of tickborne Rickettsial diseases: Rocky Mountain Spotted Fever and other spotted fever group Rickettsioses, Ehrlichioses, and Anaplasmosis – United StatesExternal
        Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, Folk SM, Kato CY, Lash RR, Levin ML, Massung RF, Nadelman RB, Nicholson WL, Paddock CD, Pritt BS, Traeger MS.
        MMWR Recomm Rep. 2016 May 13;65(2):1-44.

        Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

      2. *Changing paradigms for tick-borne diseases in the AmericasExternal
        Paddock C, Lane R, Staples J, Labruna M.
        In: Mack A, editor. Global health impacts of vector-borne diseases: workshop summary. 2016 ;National Academies Press:pp. 221-257.

        Ticks transmit a greater diversity of viral, bacterial, and protozoan diseases than any other arthropod vector on earth. Through 2014, at least 27 ecologically and epidemiologically distinct tickborne diseases were identified in the Western Hemisphere; remarkably, nearly half of these were discovered during the last 20 years. Against this background of expanding pathogen recognition are also unprecedented surges in the incidence of several tick-borne infections throughout the Americas.

      3. Expanding range of Amblyomma americanum and simultaneous changes in the epidemiology of spotted fever group Rickettsiosis in the United StatesExternal
        Dahlgren FS, Paddock CD, Springer YP, Eisen RJ, Behravesh CB.
        Am J Trop Med Hyg. 2016 Jan;94(1):35-42.

        Spotted fever group (SFG) Rickettsia species are etiologic agents of a wide range of human infections from asymptomatic or mild infections to severe, life-threatening disease. In the United States, recent passive surveillance for SFG rickettsiosis shows an increased incidence and decreased severity of reported cases. The reasons for this are not well understood; however, we hypothesize that less pathogenic rickettsiae are causing more human infections, while the incidence of disease caused by more pathogenic rickettsiae, particularly Rickettsia rickettsii, is relatively stable. During the same period, the range of Amblyomma americanum has expanded. Amblyomma americanum is frequently infected with “Candidatus Rickettsia amblyommii”, a SFG Rickettsia of unknown pathogenicity. We tested our hypothesis by modeling incidence rates from 1993 to 2013, hospitalization rates from 1981 to 2013, and case fatality rates from 1981 to 2013 regressed against the presence of A. americanum, the decade of onset of symptoms, and the county of residence. Our results support the hypothesis, and we show that the expanding range of A. americanum is associated with changes in epidemiology reported through passive surveillance. We believe epidemiological and acarological data collected on individual cases from enhanced surveillance may further elucidate the reasons for the changing epidemiology of SFG rickettsiosis.

      4. Tick-borne zoonoses in the United States: Persistent and emerging threats to human healthExternal
        Eisen RJ, Kugeler KJ, Eisen L, Beard CB, Paddock CD.
        Ilar j. 2017 Dec 15;58(3):319-335.

        In the United States, ticks transmit the greatest diversity of arthropod-borne pathogens and are responsible for the most cases of all vector-borne diseases. In recent decades, the number of reported cases of notifiable tick-borne diseases has steadily increased, geographic distributions of many ticks and tick-borne diseases have expanded, and new tick-borne disease agents have been recognized. In this review, we (1) describe the known disease agents associated with the most commonly human-biting ixodid ticks, (2) review the natural histories of these ticks and their associated pathogens, (3) highlight spatial and temporal changes in vector tick distributions and tick-borne disease occurrence in recent decades, and (4) identify knowledge gaps and barriers to more effective prevention of tick-borne diseases. We describe 12 major tick-borne diseases caused by 15 distinct disease agents that are transmitted by the 8 most commonly human-biting ixodid ticks in the United States. Notably, 40% of these pathogens were described within the last two decades. Our assessment highlights the importance of animal studies to elucidate how tick-borne pathogens are maintained in nature, as well as advances in molecular detection of pathogens which has led to the discovery of several new tick-borne disease agents.

      5. DengueExternal
        Guzman MG, Harris E.
        Lancet. 2015 Jan 31;385(9966):453-65.

        Dengue viruses have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue disease, hyperendemicity of multiple dengue virus serotypes in many tropical countries, and autochthonous transmission in Europe and the USA. Today, dengue is regarded as the most prevalent and rapidly spreading mosquito-borne viral disease of human beings. Importantly, the past decade has also seen an upsurge in research on dengue virology, pathogenesis, and immunology and in development of antivirals, vaccines, and new vector-control strategies that can positively impact dengue control and prevention.

      6. Epidemiology of Zika virus infectionExternal
        Hills SL, Fischer M, Petersen LR.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S868-s874.

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

      7. Recent advances in dengue: Relevance to Puerto RicoExternal
        Noyd DH, Sharp TM.
        P R Health Sci J. 2015 Jun;34(2):65-70.

        Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012-2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals’ ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico.

      8. West Nile virus: review of the literatureExternal
        Petersen LR, Brault AC, Nasci RS.
        Jama. 2013 Jul 17;310(3):308-15.

        IMPORTANCE: Since its introduction in North America in 1999, West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States. OBJECTIVE: To review the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus, with an emphasis on North America. EVIDENCE REVIEW: PubMed electronic database was searched through February 5, 2013. United States national surveillance data were gathered from the Centers for Disease Control and Prevention. FINDINGS: West Nile virus is now endemic throughout the contiguous United States, with 16,196 human neuroinvasive disease cases and 1549 deaths reported since 1999. More than 780,000 illnesses have likely occurred. To date, incidence is highest in the Midwest from mid-July to early September. West Nile fever develops in approximately 25% of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1% but carries a fatality rate of approximately 10%. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs. Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible. CONCLUSIONS AND RELEVANCE: In North America, West Nile virus has and will remain a formidable clinical and public health problem for years to come.

      9. A decade of arboviral activity – Lessons learned from the trenchesExternal
        Powers AM, Waterman SH.
        PLoS Negl Trop Dis. 2017 Apr;11(4):e0005421.

        [No abstract]

      10. Detecting the emergence of novel, zoonotic viruses pathogenic to humansExternal
        Rosenberg R.
        Cell Mol Life Sci. 2015 Mar;72(6):1115-25.

        RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2-3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations.

  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. Public awareness of health-related risks from uncontrolled hypertensionExternal
        Ahuja R, Ayala C, Tong X, Wall HK, Fang J.
        Prev Chronic Dis. 2018 Apr 5;15:E40.

        Uncontrolled hypertension, a common disorder, is associated with increased long-term risk of several serious conditions. Awareness of the health risks of uncontrolled hypertension is not well understood. We used data from a nationwide panel survey to assess the awareness of risk associated with uncontrolled hypertension, stratified by cardiovascular disease risk factors. Awareness of increased risk from uncontrolled hypertension was high for some outcomes (heart attack, heart failure, stroke), and low for others (kidney disease, dementia). Several disparities in awareness were found. Complementary clinical and public health interventions could be instituted to increase awareness and target people who are high risk.

      2. In the United States, adolescent and young adult (AYA) patients with cancer have the lowest clinical trial participation rate of all age groups and slower progress in survival improvement than younger patients. Ominously, AYA clinical trial participation has been steadily decreasing since 2010, except in 15-19 year olds and AYAs with acute lymphoblastic leukemia. In order to reverse the accrual trend, multiple changes are necessary, including convincing community oncologists to pursue clinical trials on behalf of their AYA patients and to have the new National Community Oncology Research Program and National Clinical Trials Network lead a coordinated effort to increase accrual.

      3. Operationalizing surveillance of chronic disease self-management and self-management supportExternal
        Brady TJ, Sacks JJ, Terrillion AJ, Colligan EM.
        Prev Chronic Dis. 2018 Apr 5;15:E39.

        Sixty percent of US adults have at least one chronic condition, and more than 40% have multiple conditions. Self-management (SM) by the individual, along with self-management support (SMS) by others, are nonpharmacological interventions with few side effects that are critical to optimal chronic disease control. Ruiz and colleagues laid the conceptual groundwork for surveillance of SM/SMS at 5 socio-ecological levels (individual, health system, community, policy, and media). We extend that work by proposing operationalized indicators at each socio-ecologic level and suggest that the indicators be embedded in existing surveillance systems at national, state, and local levels. Without a robust measurement system at the population level, we will not know how far we have to go or how far we have come in making SM and SMS a reality. The data can also be used to facilitate planning and service delivery strategies, monitor temporal changes, and stimulate SM/SMS-related research.

      4. OBJECTIVE: The object of this study was to explore the use of complementary health approaches among U.S. adults with a cancer diagnosis in the past 5 years and distinguish use for general wellness from use specifically for treatment. METHODS: Using data from the 2002, 2007, and 2012 National Health Interview Survey, the study included 1359 persons with a cancer diagnosis of selected cancers in the past 5 years. Participants were asked about their use of complementary health approaches for general reasons and cancer treatment in the past 12 months. Responses were aggregated into the use of any complementary approach as well as examined by mode of practice. RESULTS: Overall, 35.3% of persons with a cancer diagnosis used complementary health approaches in the past 12 months. These persons were more likely to have used a biologically based approach (22.8%) compared with other approaches. Persons with breast cancer were significantly more likely to use any complementary health approach (43.6%) compared with those with other recently diagnosed cancers. Few persons with a cancer history (2.3%) used complementary approaches specifically for cancer treatment. However, prevalence of use for treatment varied by cancer type (0.4%-6.8%). CONCLUSIONS: This study highlights differences in the use of various types of complementary health approaches for different reasons among persons with recent diagnoses of some of the most commonly diagnosed cancers in the United States.

      5. Racial disparities in the incidence of primary chronic cutaneous lupus erythematosus in the southeastern United States: The Georgia Lupus RegistryExternal
        Drenkard C, Parker S, Aspey LD, Gordon C, Helmick CG, Bao G, Lim SS.
        Arthritis Care Res (Hoboken). 2018 Apr 18.

        OBJECTIVE: Relative to SLE, epidemiologic studies on chronic cutaneous lupus erythematosus (CCLE) are rare and limited to populations without racial diversity. We sought to provide minimum estimates of the incidence of primary CCLE (CCLE in absence of SLE) in a predominantly white and black population in the Southestern United States. METHODS: The Georgia Lupus Registry used multiple sources for case finding, including dermatology and rheumatology practices, multispecialty healthcare facilities, and dermatopathology reports. Cases with a clinical or clinical-histological diagnosis of CCLE were classified as definite. Cases ascertained exclusively from dermatopathology reports were categorized as probable. Age-standardized incidence rates stratified by sex and race were calculated for discoid lupus erythematosus (DLE) in particular and for CCLE in general. RESULTS: The overall age-adjusted estimates for combined (definite and probable) CCLE were 3.9/100,000 person-years (95% CI: 3.4,4.5). The overall age-adjusted incidence of definite and combined DLE were 2.9 (95% CI: 2.4,3.4) and 3.7 (95% CI: 3.2,4.3) per 100,000 person-years, respectively. With capture-recapture methods, the age-adjusted incidence of definite DLE increased to 4.0 (95% CI: 3.2,4.3). Black-to-white and female-to-male incidence ratios were 5.4 and 3.1 for definite DLE. CONCLUSION: Our findings underscore striking racial disparities in the susceptibility for primary CCLE, with black people experiencing between three and five-fold increased incidence of CCLE in general and DLE in particular, compared to white people. Gender differences were consistent with those reported previously, with a three times higher risk of DLE in females compared to males. This article is protected by copyright. All rights reserved.

      6. Asthma morbidity, comorbidities, and modifiable factors among older adultsExternal
        Hsu J, Chen J, Mirabelli MC.
        J Allergy Clin Immunol Pract. 2018 Jan – Feb;6(1):236-243.e7.

        BACKGROUND: Asthma morbidity is increased among older adults, especially older adult women. Interventions to improve asthma control in this population are not well described. OBJECTIVE: The objective of this study was to identify risk factors (including modifiable factors) associated with asthma-related hospitalizations and emergency department or urgent care center visits (ED/UCV) among older adults. A secondary objective was to investigate sex differences in variables relevant to asthma control. METHODS: Data were obtained from 14,076 older adults >/=65 years with active asthma participating in the 2006-2010 Behavioral Risk Factor Surveillance System Asthma Call-back Survey (a random-digit dialed survey) in 40 US states, the District of Columbia, and Puerto Rico, representative of >2.6 million persons. Weighted, adjusted logistic regression was conducted. RESULTS: One or more asthma-related hospitalizations in the past year were reported by 5.7% (95% confidence interval [95% CI] = 5.0% to 6.4%) of participants; 10.6% (95% CI = 9.7% to 11.5%) reported >/=1 asthma-related ED/UCV. Compared with older adults without asthma-related hospitalizations, adjusted odds were higher among those with >/=1 asthma-related hospitalization for chronic obstructive pulmonary disease (COPD), coronary artery disease, depression, cockroaches or mold in the home, and cost barriers to asthma-related health care or medication. All these factors, except for cockroaches, were associated with asthma-related ED/UCV. Compared with males, adjusted odds were higher among females for COPD, depression, obesity, and cost barriers to asthma-related health care or medication. CONCLUSIONS: Among older adults, asthma-related hospitalizations and ED/UCV were associated with clinical comorbidities, mold in the home, and financial barriers to asthma-related health care. Interventions addressing modifiable factors could reduce asthma morbidity among older adults.

      7. [No abstract]

      8. Reducing the risk of Alzheimer’s disease and maintaining brain health in an aging societyExternal
        Kelley M, Ulin B, McGuire LC.
        Public Health Rep. 2018 Jan 1:33354918763599.

        [No abstract]

      9. Impact of sociodemographic characteristics on underemployment in a longitudinal, nationally representative study of cancer survivors: Evidence for the importance of gender and marital statusExternal
        Kent EE, Davidoff A, de Moor JS, McNeel TS, Virgo KS, Coughlan D, Han X, Ekwueme DU, Guy GP, Banegas MP, Alfano CM, Dowling EC, Yabroff KR.
        J Psychosoc Oncol. 2018 Apr 10:1-17.

        BACKGROUND: We examined the longitudinal association between sociodemographic factors and an expanded definition of underemployment among those with and without cancer history in the United States. METHODS: Medical Expenditure Panel Survey data (2007-2013) were used in multivariable regression analyses to compare employment status between baseline and two-year follow-up among adults aged 25-62 years at baseline (n = 1,614 with and n = 39,324 without cancer). Underemployment was defined as becoming/staying unemployed, changing from full to part-time, or reducing part-time work significantly. Interaction effects between cancer history/time since diagnosis and predictors known to be associated with employment patterns, including age, gender/marital status, education, and health insurance status at baseline were modeled. RESULTS: Approximately 25% of cancer survivors and 21% of individuals without cancer reported underemployment at follow-up (p = 0.002). Multivariable analyses indicated that those with a cancer history report underemployment more frequently (24.7%) than those without cancer (21.4%, p = 0.002) with underemployment rates increasing with time since cancer diagnosis. A significant interaction between gender/marital status and cancer history and underemployment was found (p = 0.0004). There were no other significant interactions. Married female survivors diagnosed >10 years ago reported underemployment most commonly (38.7%), and married men without cancer reported underemployment most infrequently (14.0%). A wider absolute difference in underemployment reports for married versus unmarried women as compared to married versus unmarried men was evident, with the widest difference apparent for unmarried versus married women diagnosed >10 years ago (18.1% vs. 38.7%). CONCLUSION: Cancer survivors are more likely to experience underemployment than those without cancer. Longer time since cancer diagnosis and gender/marital status are critical factors in predicting those at greatest risk of underemployment. The impact of cancer on work should be systematically studied across sociodemographic groups and recognized as a component of comprehensive survivorship care.

      10. Circumstances of suicide among individuals with a history of cancerExternal
        Massetti GM, Holland KM, Jack SP, Ragan KR, Lunsford NB.
        Psychooncology. 2018 Apr 6.

        OBJECTIVE: Cancer can trigger psychological distress, which may be associated with risk of suicide. We explored precipitating circumstances of suicides among decedents with and without a history of cancer. METHODS: Coroner or medical examiner and law enforcement narratives of adult suicides were coded from 17 participating states in Centers for Disease Control and Prevention’s National Violent Death Reporting System during 2004 to 2013. Bivariate and multivariate analyses examined associations between cancer history and factors that precipitated suicide. RESULTS: Of 90 581 suicides, 4182 decedents (4.6%) had a history of cancer. Significantly more decedents with a history of cancer (versus without) were male, non-Hispanic white, married, veterans, and aged 55 or older (P < .001). Decedents with a history of cancer were more likely to die of suicide by firearm and less likely to die of suicide by suffocation compared to poisoning. In matched case analyses controlling for demographic and recent circumstances, fewer decedents with a history of cancer had mental health problems, history of suicide attempts, alcohol use problems, intimate partner problems, financial problems, job problems, and recent crisis. CONCLUSIONS: Findings highlight the potential to identify high-risk populations for suicide prevention in clinical practice.

      11. Performance of the 2015 US Preventive Services Task Force Screening Criteria for Prediabetes and Undiagnosed DiabetesExternal
        O’Brien MJ, Bullard KM, Zhang Y, Gregg EW, Carnethon MR, Kandula NR, Ackermann RT.
        J Gen Intern Med. 2018 Apr 12.

        BACKGROUND: In 2015, The US Preventive Services Task Force (USPSTF) recommended screening for prediabetes and undiagnosed diabetes (collectively called dysglycemia) among adults aged 40-70 years with overweight or obesity. The recommendation suggests that clinicians consider screening earlier in people who have other diabetes risk factors. OBJECTIVE: To compare the performance of limited and expanded screening criteria recommended by the USPSTF for detecting dysglycemia among US adults. DESIGN: Cross-sectional analysis of survey and laboratory data collected from nationally representative samples of the civilian, noninstitutionalized US adult population. PARTICIPANTS: A total of 3643 adults without diagnosed diabetes who underwent measurement of hemoglobin A1c (A1c), fasting plasma glucose (FPG), and 2-h plasma glucose (2-h PG). MAIN MEASURES: Screening eligibility according to the limited criteria was based on age 40 to 70 years old and overweight/obesity. Screening eligibility according to the expanded criteria was determined by meeting the limited criteria or having >/= 1 of the following risk factors: family history of diabetes, history of gestational diabetes or polycystic ovarian syndrome, and non-white race/ethnicity. Dysglycemia was defined by A1c >/= 5.7%, FPG >/= 100 mg/dL, and/or 2-h PG >/= 140 mg/dL. KEY RESULTS: Among the US adult population without diagnosed diabetes, 49.7% had dysglycemia. Screening based on the limited criteria demonstrated a sensitivity of 47.3% (95% CI, 44.7-50.0%) and specificity of 71.4% (95% CI, 67.3-75.2%). The expanded criteria yielded higher sensitivity [76.8% (95% CI, 73.5-79.8%)] and lower specificity [33.8% (95% CI, 30.1-37.7%)]. Point estimates for the sensitivity of the limited criteria were lower in all minority groups and significantly different for Asians compared to non-Hispanic whites [29.9% (95% CI, 23.4-37.2%) vs. 49.8% (95% CI, 45.9-53.7%); P < .001]. CONCLUSIONS: Diabetes screening that follows the limited USPSTF criteria will identify approximately half of US adults with dysglycemia. Screening other high-risk subgroups defined in the USPSTF recommendation would improve detection of dysglycemia and may reduce associated racial/ethnic disparities.

      12. Objective This study assessed Health-related Quality of Life (HRQoL) and related risk factors among adults with asthma in the United States. Using the 2015 Behavioral Risk Factor Surveillance System (BRFSS), we examined the association between four domains of impaired HRQoL and selected explanatory factors. Methods A BRFSS sample of 39 321 adults with asthma was used in this study. We examined the association between fair/poor health, >/=14 mentally unhealthy days, >/=14 physically unhealthy days, and >/=14 days of activity limitation and selected explanatory variables (sex, race/ethnicity, age, annual household income, healthcare coverage, physical activity, smoking status, Body Mass Index (BMI), having a coexisting disease, and being diagnosed with depression) using multivariable logistic regression models. Results Income, physical activity status, smoking status, coexisting diseases, and depression were strongly associated with all HRQoL domains. Blacks had significantly less >/=14 physically unhealthy days (23.4%; aPR = 0.82 [95% CI: 0.72, 0.92]) and >/=14 days of activity limitation (18.3%; aPR = 0.81 [0.70, 0.94]) and Hispanics had significantly more fair/poor health (38.4%; aPR = 1.31 [1.18, 1.45]) than whites. Underweight and obese had significantly more fair/poor health, and underweight significantly more >/=14 physically unhealthy days, compared with normal weight. Adults aged 55 years or older had significantly less >/=14 mentally unhealthy days than adults 18-24 years. Conclusions Multiple factors were associated with impaired HRQoL. Providing strategies to address potential risk factors such as low income, physically inactive, smoker, and obese or underweight should be considered to improve HRQoL among adults with asthma.

      13. Inpatient glucose values: Determining the nondiabetic range and use in identifying patients at high risk for diabetesExternal
        Rhee MK, Safo SE, Jackson SL, Xue W, Olson DE, Long Q, Barb D, Haw JS, Tomolo AM, Phillips LS.
        Am J Med. 2018 Apr;131(4):443.e11-443.e24.

        BACKGROUND: Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high-risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. METHODS: We retrospectively examined 462,421 patients in the US Department of Veterans Affairs healthcare system, hospitalized on medical/surgical services in 2000-2010, for >/=3 days, with >/=2 inpatient random plasma glucose (RPG) measurements. All had continuity of care: >/=1 primary care visit and >/=1 glucose measurement within 2 years before hospitalization and yearly for >/=3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. RESULTS: Patients had a mean age of 65.0 years, body mass index of 29.9 kg/m(2), and were 96% male, 71% white, and 18% black. Pre-existing diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% were diagnosed 5 years after discharge, and 51.3% were never diagnosed (NonDM). The NonDM group had the lowest mean hospital RPG value (112 mg/dL [6.2 mmol/L]). Having at least 2 RPG values >140 mg/dL (>7.8 mmol/L), the 95th percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes within 3 years after discharge. CONCLUSIONS: Screening for diabetes could be considered in patients with at least 2 hospital glucose values at/above the 95th percentile of the nondiabetic range (141 mg/dL [7.8 mmol/L]).

      14. Active epilepsy and seizure control in adults – United States, 2013 and 2015External
        Tian N, Boring M, Kobau R, Zack MM, Croft JB.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):437-442.

        Approximately 3 million American adults reported active epilepsy* in 2015 (1). Active epilepsy, especially when seizures are uncontrolled, poses substantial burdens because of somatic, neurologic, and mental health comorbidity; cognitive and physical dysfunction; side effects of antiseizure medications; higher injury and mortality rates; poorer quality of life; and increased financial cost (2). Thus, prompt diagnosis and seizure control (i.e., seizure-free in the 12 months preceding the survey) confers numerous clinical and social advantages to persons with active epilepsy. To obtain recent and reliable estimates of active epilepsy and seizure control status in the U.S. population, CDC analyzed aggregated data from the 2013 and the 2015 National Health Interview Surveys (NHISs). Overall, an annual estimated 2.6 million (1.1%) U.S. adults self-reported having active epilepsy, 67% of whom had seen a neurologist or an epilepsy specialist in the past year, and 90% of whom reported taking epilepsy medication. Among those taking epilepsy medication, only 44% reported having their seizures controlled. A higher prevalence of active epilepsy and poorer seizure control were associated with low family income, unemployment, and being divorced, separated, or widowed. Use of epilepsy medication was higher among adults who saw an epilepsy specialist in the past year than among those who did not. Health care and public health should ensure that adults with uncontrolled seizures have appropriate care and self-management support in order to promote seizure control, improve health and social outcomes, and reduce health care costs.

      15. Global Coalition for the Fight Against Heart Disease and Stroke: A Global Coalition for WHF Second Global Summit on Circulatory HealthExternal
        Wood D, Asma S, Bettcher D, Wei Chieh JT, Greenland R, Italianer F, Krug E, McGuire H, Wong-Rieger D, Eisele JL, Mwangi J, Markbreiter J, Canham L, White A.
        Glob Heart. 2018 Mar;13(1):37-44.

        [No abstract]

    • Communicable Diseases
      1. BACKGROUND: Social distancing is one of the community mitigation measures that may be recommended during influenza pandemics. Social distancing can reduce virus transmission by increasing physical distance or reducing frequency of congregation in socially dense community settings, such as schools or workplaces. We conducted a systematic review to assess the evidence that social distancing in non-healthcare workplaces reduces or slows influenza transmission. METHODS: Electronic searches were conducted using MEDLINE, Embase, Scopus, Cochrane Library, PsycINFO, CINAHL, NIOSHTIC-2, and EconLit to identify studies published in English from January 1, 2000, through May 3, 2017. Data extraction was done by two reviewers independently. A narrative synthesis was performed. RESULTS: Fifteen studies, representing 12 modeling and three epidemiological, met the eligibility criteria. The epidemiological studies showed that social distancing was associated with a reduction in influenza-like illness and seroconversion to 2009 influenza A (H1N1). However, the overall risk of bias in the epidemiological studies was serious. The modeling studies estimated that workplace social distancing measures alone produced a median reduction of 23% in the cumulative influenza attack rate in the general population. It also delayed and reduced the peak influenza attack rate. The reduction in the cumulative attack rate was more pronounced when workplace social distancing was combined with other nonpharmaceutical or pharmaceutical interventions. However, the effectiveness was estimated to decline with higher basic reproduction number values, delayed triggering of workplace social distancing, or lower compliance. CONCLUSIONS: Modeling studies support social distancing in non-healthcare workplaces, but there is a paucity of well-designed epidemiological studies. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO registration # CRD42017065310.

      2. HIV incidence in western Kenya during scale-up of antiretroviral therapy and voluntary medical male circumcision: a population-based cohort analysisExternal
        Borgdorff MW, Kwaro D, Obor D, Otieno G, Kamire V, Odongo F, Owuor P, Muthusi J, Mills LA, Joseph R, Schmitz ME, Young PW, Zielinski-Gutierrez E, De Cock KM.
        Lancet HIV. 2018 Apr 9.

        BACKGROUND: In Kenya, coverage of antiretroviral therapy (ART) among people with HIV infection has increased from 7% in 2006, to 57% in 2016; and, in western Kenya, coverage of voluntary medical male circumcision (VMMC) increased from 45% in 2008, to 72% in 2014. We investigated trends in HIV prevalence and incidence in a high burden area in western Kenya in 2011-16. METHODS: In 2011, 2012, and 2016, population-based surveys were done via a health and demographic surveillance system and home-based counselling and testing in Gem, Siaya County, Kenya, including 28 688, 17 021, and 16 772 individuals aged 15-64 years. Data on demographic variables, self-reported HIV status, and risk factors were collected. Rapid HIV testing was offered to survey participants. Participants were tracked between surveys by use of health and demographic surveillance system identification numbers. HIV prevalence was calculated as a proportion, and HIV incidence was expressed as number of new infections per 1000 person-years of follow-up. FINDINGS: HIV prevalence was stable in participants aged 15-64 years: 15% (4300/28 532) in 2011, 12% (2051/16 875) in 2012, and 15% (2312/15 626) in 2016. Crude prevalences in participants aged 15-34 years were 11% (1893/17 197) in 2011, 10% (1015/10 118) in 2012, and 9% (848/9125) in 2016; adjusted for age and sex these prevalences were 11%, 9%, and 8%. 12 606 (41%) of the 30 520 non-HIV-infected individuals enrolled were seen again in at least one more survey round, and were included in the analysis of HIV incidence. HIV incidence was 11.1 (95% CI 9.1-13.1) per 1000 person-years from 2011 to 2012, and 5.7 (4.6-6.9) per 1000 person-years from 2012 to 2016. INTERPRETATION: With increasing coverage of ART and VMMC, HIV incidence declined substantially in Siaya County between 2011 and 2016. VMMC, but not ART, was suggested to have a direct protective effect, presumably because ART tended to be given to individuals with advanced HIV infection. HIV incidence is still high and not close to the elimination target of one per 1000 person-years. The effect of further scale-up of ART and VMMC needs to be monitored. FUNDING: Data were collected under Cooperative Agreements with the US Centers for Disease Control and Prevention, with funding from the President’s Emergency Fund for AIDS Relief.

      3. HIV and viral hepatitis coinfection analysis using surveillance data from 15 US states and two citiesExternal
        Bosh KA, Coyle JR, Hansen V, Kim EM, Speers S, Comer M, Maddox LM, Khuwaja S, Zhou W, Jatta A, Mayer R, Brantley AD, Muriithi NW, Bhattacharjee R, Flynn C, Bouton L, John B, Keusch J, Barber CA, Sweet K, Ramaswamy C, Westheimer EF, VanderBusch L, Nishimura A, Vu A, Hoffman-Arriaga L, Rowlinson E, Carter AO, Yerkes LE, Li W, Reuer JR, Stockman LJ, Tang T, Brooks JT, Teshale EH, Hall HI.
        Epidemiol Infect. 2018 Apr 11:1-11.

        Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

      4. Improved survival and cure rates with concurrent treatment for multidrug-resistant tuberculosis-human immunodeficiency virus coinfection in South AfricaExternal
        Brust JC, Shah NS, Mlisana K, Moodley P, Allana S, Campbell A, Johnson BA, Master I, Mthiyane T, Lachman S, Larkan LM, Ning Y, Malik A, Smith JP, Gandhi NR.
        Clin Infect Dis. 2018 Apr 3;66(8):1246-1253.

        Background: Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone. Methods: This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Results: Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count </=100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6). Conclusions: Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts </=100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

      5. Barriers and facilitators for clinical care engagement among HIV-positive African American and Latino men who have sex with menExternal
        Carey JW, Carnes N, Schoua-Glusberg A, Kenward K, Gelaude D, Denson D, Gall E, Randall LA, Frew PM.
        AIDS Patient Care STDS. 2018 Apr 18.

        Achieving optimal health among people living with HIV (PLWH) requires linkage to clinical care upon diagnosis, followed by ongoing engagement in HIV clinical care. A disproportionate number of black/African American and Hispanic/Latino men who have sex with men (MSM) living with HIV do not, however, achieve ongoing care. We conducted semistructured interviews in 2014 with 84 urban black/African American and Hispanic/Latino MSM living with HIV to understand their barriers and facilitators to engagement. We classified men as care-engaged or not at the time of the interview, and conducted content analysis of the interview transcripts to identify barriers and facilitators to engagement. Respondent mean age was 42.4 years (range, 20-59). Over half (59.5%, n = 50) were black/African American. Slightly more than a third (38.1%, n = 32) reported not being continuously care-engaged since diagnosis, and 17.9% (n = 15) delayed entry, although they have subsequently entered and remained in care. Sustained engagement began with overcoming denial after diagnosis and having treatment plans, as well as having conveniently located care facilities. Engagement also was facilitated by services tailored to meet multiple patient needs, effective patient-provider communication, and providers who show empathy and respect for their patients. Respondents were less likely to be care-engaged when these factors were absent. It can be difficult for racial and ethnic minority MSM living with HIV to begin and sustain care engagement. To optimize care engagement, our findings underscore the value of (1) convenient multipurpose HIV care facilities that meet patient needs; (2) excellent provider-patient communication that reinforces respect, trust, and HIV treatment literacy; and (3) assisting PLWH to create personalized treatment plans and overcome possible challenges such as diagnosis denial.

      6. The impact of school water, sanitation, and hygiene improvements on infectious disease using serum antibody detectionExternal
        Chard AN, Trinies V, Moss DM, Chang HH, Doumbia S, Lammie PJ, Freeman MC.
        PLoS Negl Trop Dis. 2018 Apr 16;12(4):e0006418.

        BACKGROUND: Evidence from recent studies assessing the impact of school water, sanitation and hygiene (WASH) interventions on child health has been mixed. Self-reports of disease are subject to bias, and few WASH impact evaluations employ objective health measures to assess reductions in disease and exposure to pathogens. We utilized antibody responses from dried blood spots (DBS) to measure the impact of a school WASH intervention on infectious disease among pupils in Mali. METHODOLOGY/PRINCIPAL FINDINGS: We randomly selected 21 beneficiary primary schools and their 21 matched comparison schools participating in a matched-control trial of a comprehensive school-based WASH intervention in Mali. DBS were collected from 20 randomly selected pupils in each school (n = 807). We analyzed eluted IgG from the DBS using a Luminex multiplex bead assay to 28 antigens from 17 different pathogens. Factor analysis identified three distinct latent variables representing vector-transmitted disease (driven primarily by dengue), food/water-transmitted enteric disease (driven primarily by Escherichia coli and Vibrio cholerae), and person-to-person transmitted enteric disease (driven primarily by norovirus). Data were analyzed using a linear latent variable model. Antibody evidence of food/water-transmitted enteric disease (change in latent variable mean (beta) = -0.24; 95% CI: -0.53, -0.13) and person-to-person transmitted enteric disease (beta = -0.17; 95% CI: -0.42, -0.04) was lower among pupils attending beneficiary schools. There was no difference in antibody evidence of vector-transmitted disease (beta = 0.11; 95% CI: -0.05, 0.33). CONCLUSIONS/SIGNIFICANCE: Evidence of enteric disease was lower among pupils attending schools benefitting from school WASH improvements than students attending comparison schools. These findings support results from the parent study, which also found reduced incidence of self-reported diarrhea among pupils of beneficiary schools. DBS collection was feasible in this resource-poor field setting and provided objective evidence of disease at a low cost per antigen analyzed, making it an effective measurement tool for the WASH field. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT01787058).

      7. An illustration of the potential health and economic benefits of combating antibiotic-resistant gonorrheaExternal
        Chesson HW, Kirkcaldy RD, Gift TL, Owusu-Edusei K, Weinstock HS.
        Sex Transm Dis. 2018 Apr;45(4):250-253.

        Preventing the emergence of ceftriaxone-resistant Neisseria gonorrhoeae can potentially avert hundreds of millions of dollars in direct medical costs of gonorrhea and gonorrhea-attributable HIV infections. In the illustrative scenario we examined, emerging ceftriaxone resistance could lead to 1.2 million additional N. gonorrhoeae infections within 10 years, costing $378.2 million.

      8. Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and sheddingExternal
        Davis BM, Foxman B, Monto AS, Baric RS, Martin ET, Uzicanin A, Rainey JJ, Aiello AE.
        Influenza Other Respir Viruses. 2018 Apr 16.

        BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the four most common human coronaviruses (HCoV) -229E, HKU1, NL63 and OC43 are poorly described OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1-3 samples (n=250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI) (cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT-PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested and 4.8% (12/250) were positive for two or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (p=0.04, and p=0.01, respectively), while runny nose increased over the same period (p=0.02). HCoV-NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3-month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV-associated illness and were similar to symptoms from influenza and rhinovirus. This article is protected by copyright. All rights reserved.

      9. Notes from the Field: Surveillance for Candida auris – Colombia, September 2016-May 2017External
        Escandon P, Caceres DH, Espinosa-Bode A, Rivera S, Armstrong P, Vallabhaneni S, Berkow EL, Lockhart SR, Chiller T, Jackson BR, Duarte C.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):459-460.

        [No abstract]

      10. Monitoring progress towards the first UNAIDS target: understanding the impact of people living with HIV who re-test during HIV-testing campaigns in rural MozambiqueExternal
        Fuente-Soro L, Lopez-Varela E, Augusto O, Sacoor C, Nhacolo A, Honwana N, Karajeanes E, Vaz P, Naniche D.
        J Int AIDS Soc. 2018 Apr;21(4):e25095.

        INTRODUCTION: Awareness of HIV-infection goes beyond diagnosis, and encompasses understanding, acceptance, disclosure and initiation of the HIV-care. We aimed to characterize the HIV-positive population that underwent repeat HIV-testing without disclosing their serostatus and the impact on estimates of the first UNAIDS 90 target. METHODS: This analysis was nested in a prospective cohort established in southern Mozambique which conducted three HIV-testing modalities: voluntary counselling and testing (VCT), provider-initiated counselling and testing (PICT) and home-based testing (HBT). Participants were given the opportunity to self-report their status to lay counsellors and HIV-positive diagnoses were verified for previous enrolment in care. This study included 1955 individuals diagnosed with HIV through VCT/PICT and 11,746 participants of a HBT campaign. Those who did not report their serostatus prior to testing, and were found to have a previous HIV-diagnosis, were defined as non-disclosures. Venue-stratified descriptive analyses were performed and factors associated with non-disclosure were estimated through log-binomial regression. RESULTS: In the first round of 2500 adults randomized for HBT, 1725 were eligible for testing and 18.7% self-reported their HIV-positivity. Of those tested with a positive result, 38.9% were found to be non-disclosures. Similar prevalence of non-disclosures was found in clinical-testing modalities, 29.4% (95% CI 26.7 to 32.3) for PICT strategy and 13.0% (95% CI 10.9 to 15.3) for VCT. Prior history of missed visits (adjusted prevalence ratio (APR) 4.2, 95% CI 2.6 to 6.8), younger age (APR 2.5, 95% CI 1.4 to 4.4) and no prior history of treatment ((APR) 1.4, 95% CI 1.0 to 2.1) were significantly associated with non-disclosure as compared to patients who self-reported. When considering non-disclosures as people living with HIV (PLWHIV) aware of their HIV-status, the proportion of PLWHIV aware increased from 78.3% (95% CI 74.2 to 81.6) to 86.8% (95% CI 83.4 to 89.6). CONCLUSION: More than one-third of individuals testing HIV-positive did not disclose their previous positive HIV-diagnosis to counsellors. This proportion varied according to testing modality and age. In the absence of an efficient and non-anonymous tracking system for HIV-testers, repeat testing of non-disclosures leads to wasted resources and may distort programmatic indicators. Developing interventions that ensure appropriate psychosocial support are needed to encourage this population to disclose their status and optimize scarce resources.

      11. Gaps up to 9 months between HIV primary care visits do not worsen viral loadExternal
        Gardner LI, Marks G, Patel U, Cachay E, Wilson TE, Stirratt M, Rodriguez A, Sullivan M, Keruly JC, Giordano TP.
        AIDS Patient Care STDS. 2018 Apr;32(4):157-164.

        Current guidelines specify that visit intervals with viral monitoring should not exceed 6 months for HIV patients. Yet, gaps in care exceeding 6 months are common. In an observational cohort using US patients, we examined the association between gap length and changes in viral load status and sought to determine the length of the gap at which significant increases in viral load occur. We identified patients with gaps in care greater than 6 months from 6399 patients from six US HIV clinics. Gap strata were >6 to <7, 7 to <8, 8 to <9, 9 to <12, and >/=12 months, with viral load measurements matched to the opening and closing dates for the gaps. We examined visit gap lengths in association with two viral load measurements: continuous (log10 viral load at gap opening and closing) and dichotomous (whether patients initially suppressed but lost viral suppression by close of the care gap). Viral load increases were nonsignificant or modest when gap length was <9 months, corresponding to 10% or fewer patients who lost viral suppression. For gaps >/=12 months, there was a significant increase in viral load as well as a much larger loss of viral suppression (in 23% of patients). Detrimental effects on viral load after a care gap were greater in young patients, black patients, and those without private health insurance. On average, shorter gaps in care were not detrimental to patient viral load status. HIV primary care visit intervals of 6 to 9 months for select patients may be appropriate.

      12. Surveillance to track progress toward polio eradication – worldwide, 2016-2017External
        Gardner TJ, Diop OM, Jorba J, Chavan S, Ahmed J, Anand A.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 13;67(14):418-423.

        Global efforts to eradicate polio began in 1988, and four of the six World Health Organization (WHO) regions currently have achieved poliofree certification. Within the remaining two regions with endemic poliomyelitis (African and Eastern Mediterranean), Afghanistan, Nigeria, and Pakistan have never interrupted transmission of wild poliovirus (WPV). The primary means of detecting poliovirus transmission is surveillance for acute flaccid paralysis (AFP) among children aged <15 years, combined with collection and testing of stool specimens for detection of WPV and vaccine-derived polioviruses (VDPVs)* in WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN) (1,2). AFP surveillance is supplemented by environmental surveillance for polioviruses in sewage from selected locations. Genomic sequencing of isolated polioviruses enables the mapping of transmission by time and place, assessment of potential gaps in surveillance, and identification of the emergence of VDPVs (3). This report presents poliovirus surveillance data from 2016-2017, with particular focus on six countries in the Eastern Mediterranean Region (EMR) and 20 countries in the African Region (AFR) that reported WPV or circulating VDPVs (cVDPVs) during 2011-2017. Included in the 20 AFR countries are the three most affected by the 2014-2015 Ebola virus disease (Ebola) outbreak (Guinea, Liberia, and Sierra Leone), even though only one (Guinea) reported WPV or cVDPVs during the surveillance period. During 2017, a total of 14 (70%) of the 20 AFR countries and five (83%) of the six EMR countries met both surveillance quality indicators at the national level; however, provincial-level variation was seen. Surveillance strengthening activities are needed in specific countries of these regions to provide evidence supporting ultimate certification of the interruption of poliovirus circulation.

      13. Impact of public health responses during a measles outbreak in an Amish community in Ohio: modelling the dynamics of transmissionExternal
        Gastanaduy PA, Funk S, Paul P, Tatham L, Fisher N, Budd J, Fowler B, de Fijter S, DiOrio M, Wallace GS, Grenfell B.
        Am J Epidemiol. 2018 Apr 7.

        We quantified measles transmissibility during a measles outbreak in Ohio in 2014 to evaluate the impact of public health responses. Case incidence and the serial interval (time between symptom onset in primary and secondary cases) were used to assess trends in the effective reproduction number R (average number of secondary cases generated per case). A mathematical model was parameterized by early R values to determine outbreak size and duration if containment measures had not been initiated, and the impact of vaccination. As containment started, we found a fourfold decline in R (~4 to 1) over 2 weeks, and maintenance of R < 1 as control measures continued. Under a conservative scenario, the model estimated 8,472 cases (90% confidence interval [CI]: 8,447, 8,489) over 195 days (90% CI: 179, 223) without control efforts, and 715 cases (90% CI: 103, 1,338) over 128 days (90% CI: 117, 139) when including vaccination; 7,757 fewer cases (90% CI: 7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to vaccination. Vaccination may not account entirely for transmission reductions, suggesting changes in community behavior (social distancing) and other control efforts (isolation, quarantining) are important. Our findings highlight the benefits of measles outbreak response and of understanding behavior change dynamics.

      14. Substantial resources are invested in human immunodeficiency virus biobehavioral surveys using respondent-driven sampling for measuring progress towards the UNAIDS 90-90-90 goals and to obtain other essential data on key populations. Survey data are used to meet country needs as well those of development partners, whose data needs may sometimes diverge. Surveys using differing eligibility criteria impede comparisons across surveys. With scant literature and guidelines on how to approach eligibility criteria, diverse criteria are used within and across countries. We conducted a review of peer-reviewed human immunodeficiency virus respondent-driven sampling biobehavioral survey literature published through December 2013. We describe eligibility criteria of 137 articles representing 214 surveys. Reporting on age, risk behavior, and reference period of risk behavior was nearly universal; however, reporting on gender, geography, and language was less common. Multiple definitions were used for each criterion, making comparisons challenging. We provide a framework for how to approach defining eligibility to improve consistency and comparability across surveys.

      15. Background: Progressively decreasing susceptibility of Neisseria gonorrhoeae to the antibiotics recommended for treatment has raised concerns about the public health threat of antibiotic resistant gonorrhea. This is not a new process and the organism has reliably developed resistance to all modern antibiotics used for treatment since the dawn of the antibiotic era. The history of changing recommendations for gonorrhea therapy however is complex and has been influenced by diagnostic test methods and surveillance. Understanding the impact of these influences may provide insights into current approaches to address this re-emerging public health challenge. Data Sources: We reviewed available literature on gonococcal susceptibility to therapeutic agents since the 1930s, changing methods for gonorrhea diagnosis, and public health recommendations for gonorrhea treatment. The literature review was supplemented by qualitative interviews with senior investigators who helped to shape gonorrhea management strategies over the past 50 years. Data Syntheses: The process of development of antimicrobial resistance to the antibiotics widely used for treatment appears to be an inexorable process. Many currently voiced concerns are similar to those raised in the past. The public health threat of increasing antimicrobial resistance by N. gonorrhoeae has been amplified as a result of a smaller pipeline introducing new drugs for gonorrhea treatment. Improved methods for gonorrhea diagnosis have also repeatedly influenced appreciation of the burden of disease caused by N. gonorrhoeae. U.S. Public Health Service leadership has also shaped and improved the management of this important public health problem.

      16. To ensure the health and safety of persons taking antiretroviral medication as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection, Centers for Disease Control and Prevention guidelines recommend initial and follow-up laboratory testing. We assessed the rates of recommended testing, using a commercial insurance claims database. Before taking PrEP, 45% of users were tested for HIV, 55% for syphilis, 43% for chlamydia/gonorrhea, and 38% for hepatitis B, and 31% had their creatinine level measured. By 6 months after PrEP initiation, 38% were tested for HIV, 49% for syphilis, and 39% for chlamydia/gonorrhea, and 37% had their creatinine level measured. Although laboratory testing was less frequent than recommended, testing rates increased over the study period.

      17. Determinants of HIV incidence disparities among young and older men who have sex with men in the United StatesExternal
        Jeffries WL, Greene KM, Paz-Bailey G, McCree DH, Scales L, Dunville R, Whitmore S.
        AIDS Behav. 2018 Apr 9.

        This study sought to determine why young men who have sex with men (MSM) have higher HIV incidence rates than older MSM in the United States. We developed hypotheses that may explain this disparity. Data came from peer-reviewed studies published during 1996-2016. We compared young and older MSM with respect to behavioral, clinical, psychosocial, and structural factors that promote HIV vulnerability. Compared with older MSM, young MSM were more likely to have HIV-discordant condomless receptive intercourse. Young MSM also were more likely to have “any” sexually transmitted infection and gonorrhea. Among HIV-positive MSM, young MSM were less likely to be virally suppressed, use antiretroviral therapy, and be aware of their infection. Moreover, young MSM were more likely than older MSM to experience depression, polysubstance use, low income, decreased health care access, and early ages of sexual expression. These factors likely converge to exacerbate age-associated HIV incidence disparities among MSM.

      18. Antigenic characterization of a novel recombinant GII.P16-GII.4 Sydney norovirus strain with minor sequence variation leading to antibody escapeExternal
        Lindesmith LC, Brewer-Jensen PD, Mallory ML, Debbink K, Swann EW, Vinje J, Baric RS.
        J Infect Dis. 2018 Mar 13;217(7):1145-1152.

        Background: Human noroviruses are the leading cause of acute gastroenteritis. Strains of the GII.4 genotype cause pandemic waves associated with viral evolution and subsequent antigenic drift and ligand-binding modulation. In November 2015, a novel GII.4 Sydney recombinant variant (GII.P16-GII.4 Sydney) emerged and replaced GII.Pe-GII.4 Sydney as the predominant cause of acute gastroenteritis in the 2016-2017 season in the United States. Methods: Virus-like particles of GII.4 2012 and GII.4 2015 were compared for ligand binding and antibody reactivity, using a surrogate neutralization assay. Results: Residue changes in the capsid between GII.4 2012 and GII.4 2015 decreased the potency of human polyclonal sera and monoclonal antibodies. A change in epitope A resulted in the complete loss of reactivity of a class of blockade antibodies and reduced levels of a second antibody class. Epitope D changes modulated monoclonal antibody potency and ligand-binding patterns. Conclusions: Substitutions in blockade antibody epitopes between GII.4 2012 and GII.4 2015 influenced antigenicity and ligand-binding properties. Although the impact of polymerases on fitness remains uncertain, antigenic variation resulting in decreased potency of antibodies to epitope A, coupled with altered ligand binding, likely contributed significantly to the spread of GII.4 2015 and its replacement of GII.4 2012 as the predominant norovirus outbreak strain.

      19. Current epidemiology and trends in meningococcal disease – United States, 1996-2015External
        MacNeil JR, Blain AE, Wang X, Cohn AC.
        Clin Infect Dis. 2018 Apr 3;66(8):1276-1281.

        Background: In 2005, meningococcal conjugate vaccine (MenACWY) was recommended for routine use among adolescents aged 11-18 years. This report describes the epidemiologic features of meningococcal disease and trends in meningococcal disease incidence following MenACWY introduction in the United States. Methods: Incidence rates and case-fatality ratios by age group and serogroup during 2006-2015 were calculated using data from the National Notifiable Diseases Surveillance System (NNDSS); changes in incidence during this time were evaluated. Additionally, 20-year trends (1996-2015) in age- and race-standardized incidence were examined using data from Active Bacterial Core surveillance (ABCs). Results: During the years 2006-2015, 7924 cases of meningococcal disease were reported to NNDSS, resulting in an average annual incidence of 0.26 cases per 100000 population; 14.9% of cases were fatal. Among cases with serogroup information, 2290 (35.8%) were serogroup B, 1827 (28.5%) were serogroup Y, 1457 (22.8%) were serogroup C, 436 (6.8%) were serogroup W, and 392 (6.1%) were other serogroups. The incidence of serogroups A, C, W, and Y combined declined 76% among persons aged 11-20 years from 2006-2010 to 2011-2015 (P < .0001). From 1996 through 2015, the incidence of meningococcal disease declined among all age groups and predominant serogroups. Conclusions: Declines in meningococcal disease incidence in the United States have been observed among all age groups and predominant serogroups (B, C, and Y). Reductions in the incidence of meningococcal disease due to serogroups A, C, W, and Y among adolescents suggest an impact of the MenACWY vaccine program in this age group.

      20. A couple-based HIV prevention intervention for Latino men who have sex with men: study protocol for a randomized controlled trialExternal
        Martinez O, Isabel Fernandez M, Wu E, Carballo-Dieguez A, Prado G, Davey A, Levine E, Mattera B, Lopez N, Valentin O, Murray A, Sutton M.
        Trials. 2018 Apr 5;19(1):218.

        BACKGROUND: Latino men who have sex with men (MSM) experienced a 13% increase in HIV diagnoses from 2010 to 2014, more than any other racial/ethnic subgroup of MSM in the United States. If current HIV diagnoses rates persist, about one in four Latino MSM in the United States will be diagnosed with HIV during their lifetime. Although some efficacious HIV prevention interventions for Latino MSM exist, none have focused on couples. This paper describes the protocol of a randomized controlled trial (RCT) to test the preliminary efficacy of a couple-based HIV prevention intervention that is culturally tailored for Latino men and their same-sex partners. METHODS: The RCT will determine the preliminary efficacy of Connecting Latinos en Pareja (CLP) to increase the proportion of anal sex acts that are HIV protected (i.e., anal sex acts in which condoms, pre-exposure prophylaxis (PrEP), treatment as prevention (TasP), or a combination thereof, are used to reduce risk of HIV transmission). CLP builds upon previous couple-based interventions with white and black MSM by incorporating biomedical prevention techniques, such as PrEP and TasP, implementing a framework responsive to the couple’s serostatus, and addressing the socio-cultural factors that influence HIV risk among Latino MSM. We also include input from community stakeholders, members of the target population, and a community advisory board as part of intervention development. Assessments will be conducted at baseline, and 3- and 6-months post-intervention to examine the intervention effects on outcomes (HIV-protected sex acts), and factors potentially mediating or moderating intervention effects. DISCUSSION: This paper describes an innovative RCT that incorporates multiple HIV prevention techniques for Latino MSM in couples, regardless of serostatus. The ongoing involvement of community stakeholders, members of the target population, and a community advisory board is emphasized, and plans for widespread dissemination and application of findings into practice are discussed. TRIAL REGISTRATION: Trial registration: NCT03048838 . Registered on 3 February 2017.

      21. Cross-border transmission of Ebola virus was the cause of a resurgent outbreak in Liberia in April 2016External
        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 Apr 5.

        [No abstract]

      22. Progression from latent infection to active disease in dynamic tuberculosis transmission models: a systematic review of the validity of modelling assumptionsExternal
        Menzies NA, Wolf E, Connors D, Bellerose M, Sbarra AN, Cohen T, Hill AN, Yaesoubi R, Galer K, White PJ, Abubakar I, Salomon JA.
        Lancet Infect Dis. 2018 Apr 10.

        Mathematical modelling is commonly used to evaluate infectious disease control policy and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history and, if these assumptions are not valid, the results of these studies can be biased. We did a systematic review of published tuberculosis transmission models to assess the validity of assumptions about progression to active disease after initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (Jan 1, 1962) to Aug 31, 2017. We identified 312 studies that met inclusion criteria. Predicted tuberculosis incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial proportion of modelled results were inconsistent with empirical evidence: for 10-year cumulative incidence, 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of tuberculosis natural history. Greater attention to reproducing known features of epidemiology would strengthen future tuberculosis modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity.

      23. Background: The first Ebola virus disease (EVD) case in the United States (US) was confirmed September 30, 2014 in a man 45 years old. This event created considerable media attention and there was fear of an EVD outbreak in the US. Methods: This study examined whether emergency department (ED) visits changed in metropolitan Dallas-Fort Worth–, Texas (DFW) after this EVD case was confirmed. Using Texas Health Services Region 2/3 syndromic surveillance data and focusing on DFW, interrupted time series analyses were conducted using segmented regression models with autoregressive errors for overall ED visits and rates of several chief complaints, including fever with gastrointestinal distress (FGI). Date of fatal case confirmation was the “event.” Results: Results indicated the event was highly significant for ED visits overall (P<0.05) and for the rate of FGI visits (P<0.0001). An immediate increase in total ED visits of 1,023 visits per day (95% CI: 797.0, 1,252.8) was observed, equivalent to 11.8% (95% CI: 9.2%, 14.4%) increase ED visits overall. Visits and the rate of FGI visits in DFW increased significantly immediately after confirmation of the EVD case and remained elevated for several months even adjusting for seasonality both within symptom specific chief complaints as well as overall. Conclusions: These results have implications for ED surge capacity as well as for public health messaging in the wake of a public health emergency.

      24. Outbreak of invasive infections from subtype emm26.3 group A streptococcus among homeless adults – Anchorage, Alaska, 2016-2017External
        Mosites E, Frick A, Gounder P, Castrodale L, Li Y, Rudolph K, Hurlburt D, Lecy KD, Zulz T, Adebanjo T, Onukwube J, Beall B, Van Beneden CA, Hennessy T, McLaughlin J, Bruce MG.
        Clin Infect Dis. 2018 Mar 19;66(7):1068-1074.

        Background: In 2016, we detected an outbreak of group A Streptococcus (GAS) invasive infections among the estimated 1000 persons experiencing homelessness (PEH) in Anchorage, Alaska. We characterized the outbreak and implemented a mass antibiotic intervention at homeless service facilities. Methods: We identified cases through the Alaska GAS laboratory-based surveillance system. We conducted emm typing, antimicrobial susceptibility testing, and whole-genome sequencing on all invasive isolates and compared medical record data of patients infected with emm26.3 and other emm types. In February 2017, we offered PEH at 6 facilities in Anchorage a single dose of 1 g of azithromycin. We collected oropharyngeal and nonintact skin swabs on a subset of participants concurrent with the intervention and 4 weeks afterward. Results: From July 2016 through April 2017, we detected 42 invasive emm26.3 cases in Anchorage, 35 of which were in PEH. The emm26.3 isolates differed on average by only 2 single-nucleotide polymorphisms. Compared to other emm types, infection with emm26.3 was associated with cellulitis (odds ratio [OR], 2.5; P = .04) and necrotizing fasciitis (OR, 4.4; P = .02). We dispensed antibiotics to 391 PEH. Colonization with emm26.3 decreased from 4% of 277 at baseline to 1% of 287 at follow-up (P = .05). Invasive GAS incidence decreased from 1.5 cases per 1000 PEH/week in the 6 weeks prior to the intervention to 0.2 cases per 1000 PEH/week in the 6 weeks after (P = .01). Conclusions: In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic administration was temporally associated with reduced invasive disease cases and colonization prevalence.

      25. Giardia and Cryptosporidium antibody prevalence and correlates of exposure among Alaska residents, 2007-2008External
        Mosites E, Miernyk K, Priest JW, Bruden D, Hurlburt D, Parkinson A, Klejka J, Hennessy T, Bruce MG.
        Epidemiol Infect. 2018 Apr 10:1-7.

        Giardia duodenalis and Cryptosporidium spp. are common intestinal protozoa that can cause diarrhoeal disease. Although cases of infection with Giardia and Cryptosporidium have been reported in Alaska, the seroprevalence and correlates of exposure to these parasites have not been characterised. We conducted a seroprevalence survey among 887 residents of Alaska, including sport hunters, wildlife biologists, subsistence bird hunters and their families and non-exposed persons. We tested serum using a multiplex bead assay to evaluate antibodies to the Giardia duodenalis variant-specific surface protein conserved structural regions and to the Cryptosporidium parvum 17- and 27-kDa antigens. Approximately one third of participants in each group had evidence of exposure to Cryptosporidium. Prevalence of Giardia antibody was highest among subsistence hunters and their families (30%), among whom positivity was associated with lack of community access to in-home running water (adjusted prevalence ratio [aPR] 1.15, 95% confidence interval (CI) 1.02-1.28) or collecting rain, ice, or snow to use as drinking water (aPR 1.09, 95% CI 1.01-1.18). Improving in-home water access for entire communities could decrease the risk of exposure to Giardia.

      26. Epidemiology of otitis media with otorrhea among Bangladeshi children: Baseline study for future assessment of pneumococcal conjugate vaccine impactExternal
        Naziat H, Saha S, Islam M, Saha S, Uddin MJ, Hussain M, Luby SP, Darmstadt GL, Whitney CG, Gessner BD, Saha SK.
        Pediatr Infect Dis J. 2018 Apr 9.

        BACKGROUND: Otitis media (OM) poses a high disease burden on Bangladeshi children but little is known about its etiologies. We conducted a surveillance study in the largest pediatric hospital to characterize pathogens responsible for OM. METHODS: In the out-patient ear-nose-throat department of Dhaka Shishu Hospital, which serves 0 -18 years old children, we collected ear swabs from OM children with otorrhea from April 2014 through March 2015. We cultured all specimens for bacterial pathogens and assessed serotype and antimicrobial susceptibility of Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hi) isolates. RESULTS: We recorded 1,111 OM episodes; 88% (981/1,111) involved otorrhea and we collected samples from 91% (891/981) of these children. Fifty-one percent (452/891) were culture-positive (contaminants excluded), with Hi (21%, 187/891) and Spn (18%, 164/891) most commonly detected. Overall, 45 distinct single and mixed pathogens were revealed. Dominant pneumococcal serotypes were 19A, 19F, 3, and 14; 98% of Hi isolates were non-typeable. PCV10 and PCV10 + 6A serotypes accounted for 8% and 9% of all OM and 46% and 49% of pneumococcus-positive cases respectively and were more likely to be non-susceptible to at least one antibiotic (erythromycin and/or cotrimoxazole) than non-vaccine serotypes (91% vs 77%). Staphylococcus aureus (9%, 83/891) and Pseudomonas aeruginosa (4%, 38/891) were also found. CONCLUSIONS: Non-typeable Hi (NTHi) and Spn are predominant causes of OM in Bangladesh. PCV10, introduced in March 2015, is likely to reduce pneumococcal and overall OM burden. Data collected post-PCV10 will provide comprehensive insight into the effects of this vaccine on these pathogens.

      27. High HIV-1 RNA among newly diagnosed people in BotswanaExternal
        Novitsky V, Prague M, Moyo S, Gaolathe T, Mmalane M, Yankinda EK, Chakalisa U, Lebelonyane R, Khan N, Powis KM, Widenfelt E, Gaseitsiwe S, Dryden-Peterson SL, Holme MP, De Gruttola V, Bachanas P, Makhema J, Lockman S, Essex M.
        AIDS Res Hum Retroviruses. 2018 Mar;34(3):300-306.

        HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to determine whether HIV-1 RNA level was associated with prior knowledge of HIV status among treatment-naive HIV-infected individuals in Botswana, a country with high rates of antiretroviral treatment (ART) coverage. This information may be helpful in targeting HIV diagnosis and treatment efforts in similar high HIV prevalence settings in a population-based survey. HIV-infected individuals were identified during a household survey performed in 30 communities across Botswana. ART-naive persons with detectable HIV-1 RNA (>400 copies/mL) were divided into two groups, newly diagnosed and individuals tested in the past who knew about their HIV infection at the time of household visit, but had not taken ART. Levels of HIV-1 RNA were compared between groups, overall and by age and gender. Among 815 HIV-infected ART-naive persons with detectable virus, newly diagnosed individuals had higher levels of HIV-1 RNA (n = 490, median HIV-1 RNA 4.35, interquartile range (IQR) 3.79-4.91 log10 copies/mL) than those who knew about their HIV-positive status (n = 325, median HIV-1 RNA 4.10, IQR 3.55-4.68 log10 copies/mL; p values <.001, but p value = .011 after adjusting for age and gender). A nonsignificant trend for higher HIV-1 RNA was found among newly diagnosed men 30 years of age or older (median HIV-1 RNA 4.58, IQR 4.07-5.02 log10 copies/mL vs. 4.17, 3.61-4.71 log10 copies/mL). Newly diagnosed individuals have elevated levels of HIV-1 RNA. This study highlights the need for early diagnosis and treatment of HIV infection for purposes of HIV epidemic control, even in a setting with high ART coverage.

      28. Trust, fear, stigma and disruptions: community perceptions and experiences during periods of low but ongoing transmission of Ebola virus disease in Sierra Leone, 2015External
        Nuriddin A, Jalloh MF, Meyer E, Bunnell R, Bio FA, Jalloh MB, Sengeh P, Hageman KM, Carroll DD, Conteh L, Morgan O.
        BMJ Glob Health. 2018 ;3(2):e000410.

        Social mobilisation and risk communication were essential to the 2014-2015 West African Ebola response. By March 2015, >8500 Ebola cases and 3370 Ebola deaths were confirmed in Sierra Leone. Response efforts were focused on ‘getting to zero and staying at zero’. A critical component of this plan was to deepen and sustain community engagement. Several national quantitative studies conducted during this time revealed Ebola knowledge, personal prevention practices and traditional burial procedures improved as the outbreak waned, but healthcare system challenges were also noted. Few qualitative studies have examined these combined factors, along with survivor stigma during periods of ongoing transmission. To obtain an in-depth understanding of people’s perceptions, attitudes and behaviours associated with Ebola transmission risks, 27 focus groups were conducted between April and May 2015 with adult Sierra Leonean community members on: trust in the healthcare system, interactions with Ebola survivors, impact of Ebola on lives and livelihood, and barriers and facilitators to ending the outbreak. Participants perceived that as healthcare practices and facilities improved, so did community trust. Resource management remained a noted concern. Perceptions of survivors ranged from sympathy and empathy to fear and stigmatisation. Barriers included persistent denial of ongoing Ebola transmission, secret burials and movement across porous borders. Facilitators included personal protective actions, consistent messaging and the inclusion of women and survivors in the response. Understanding community experiences during the devastating Ebola epidemic provides practical lessons for engaging similar communities in risk communication and social mobilisation during future outbreaks and public health emergencies.

      29. Risk factors for oral HPV infection among young men who have sex with men – 2 cities, United States, 2012-2014External
        Oliver SE, Gorbach P, Gratzer B, Steinau M, Collins T, Parrish A, Kerndt PR, Crosby R, Unger ER, Markowitz LE, Meites E.
        Sex Transm Dis. 2018 Apr 5.

        BACKGROUND: Men who have sex with men (MSM) are at risk for cancers attributable to human papillomavirus (HPV), including oropharyngeal cancer. HPV vaccination is recommended for U.S. MSM through age 26 years. Oral HPV infection is associated with oropharyngeal cancer. We determined oral HPV prevalence and risk factors among young MSM. METHODS: The Young Men’s HPV study enrolled MSM aged 18-26 years from clinics in Chicago and Los Angeles during 2012-2014. Participants self-reported demographics, sexual behaviors, vaccination and HIV status. Self-collected oral rinse specimens were tested for HPV DNA (37 types) by L1-consensus PCR. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for risk factors associated with oral HPV among participants not previously vaccinated. RESULTS: Oral HPV was detected in 87/922 (9.4%); 9-valent vaccine (9vHPV) types were detected in 37/922 (4.0%). Among HIV-positive participants, 17/88 (19.3%) had oral HPV detected. Oral HPV was more prevalent among those reporting first sex at age </=18 years (aPR:2.44; CI:1.16-5.12); HIV infection (aPR:1.99; CI:1.14-3.48); >5 sex partners within the past month (aPR:1.93; CI:1.13-3.31); performing oral sex on >5 partners within the last 3 months (aPR:1.87; CI:1.12-3.13); and having >5 male sex partners within the last 3 months (aPR:1.76; CI: 1.08-2.87). Only 454/922 (49.2%) were aware HPV can cause oropharyngeal cancers. CONCLUSIONS: Many oral HPV infections were with types targeted by vaccination. Oral HPV infections were significantly associated with HIV and sexual behaviors. Fewer than half of participants were aware HPV could cause oropharyngeal cancer.

      30. Molecular epidemiology and the transformation of HIV preventionExternal
        Oster AM, France AM, Mermin J.
        Jama. 2018 Apr 9.

        [No abstract]

      31. Care cascade for targeted tuberculosis testing and linkage to care in homeless populations in the United States: a meta-analysisExternal
        Parriott A, Malekinejad M, Miller AP, Marks SM, Horvath H, Kahn JG.
        BMC Public Health. 2018 Apr 12;18(1):485.

        BACKGROUND: Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. METHODS: We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. RESULTS: We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. CONCLUSIONS: Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of treatment, and costs of testing and treatment.

      32. Using National Ambulatory Medical Care Survey (NAMCS) data during 2006-2015, we estimated the proportions of young women tested for chlamydia who were symptomatic (urogenital symptoms) or asymptomatic in physician offices. Among women tested for chlamydia, the proportions of women with and without urogenital symptoms were 31.6% and 59.2%, respectively.

      33. Background: Neonatal herpes is a rare, devastating consequence of herpes simplex virus type 1 (HSV-1) or 2 (HSV-2) infection during pregnancy. The risk of neonatal infection is higher among pregnant women seronegative for HSV-1 or HSV-2 who acquire their first HSV infection near delivery. Methods: We estimated HSV-1 and HSV-2 seroprevalence among pregnant women aged 20-39 years in 1999-2014, assessed HSV seroprevalence changes between 1999-2006 and 2007-2014, and compared HSV seroprevalence between pregnant women and sexually active, non-pregnant women aged 20-39 years in 2007-2014 using National Health and Nutrition Examination Survey data. Results: Among pregnant women in 1999-2014, HSV-1 seroprevalence was 59.3%, HSV-2 seroprevalence was 21.1%, and HSV seronegativity was 30.6%. Between 1999-2006 and 2007-2014, HSV-1 and HSV-2 seroprevalence among pregnant women remained stable. However, among pregnant women with </=3 sex partners (approximately 40% of all pregnant women), seronegativity for both HSV-1 and HSV-2 increased from 35.6% to 51.4% (P<.05). In 2007-2014, non-pregnant women who were 1) unmarried, 2) living below poverty level, or 3) had >/=4 sex partners were more likely than pregnant women to be seronegative for both HSV-1 and HSV-2 (P<.05). Conclusions: HSV-1 and HSV-2 seroprevalence among U.S. pregnant women remained stable between 1999-2014. However, pregnant women with fewer sex partners were increasingly seronegative for both HSV-1 and HSV-2, indicating an increasing proportion of pregnant women who are vulnerable to primary HSV acquisition in pregnancy which confers an increased risk of transmitting HSV to their neonates.

      34. Field investigation with real-time virus genetic characterisation support of a cluster of Ebola virus disease cases in Dubreka, Guinea, April to June 2015External
        Pini A, Zomahoun D, Duraffour S, Derrough T, Charles M, Quick J, Loman N, Cowley L, Leno M, Ouedraogo N, Thiam O, Hernandez-Romieu A, Iko A, Keita H, Konate D, Soumah AA, Bouchouar E, Ileka-Priouzeau S, Keita S, Diallo B, Cisse F, Jansa J, Carroll M, Gunther S, Severi E, Formenty P.
        Euro Surveill. 2018 Mar;23(12).

        On 11 May 2015, the Dubreka prefecture, Guinea, reported nine laboratory-confirmed cases of Ebola virus disease (EVD). None could be epidemiologically linked to cases previously reported in the prefecture. We describe the epidemiological and molecular investigations of this event. We used the Dubreka EVD registers and the Ebola treatment centre’s (ETC) records to characterise chains of transmission. Real-time field Ebola virus sequencing was employed to support epidemiological results. An epidemiological cluster of 32 cases was found, of which 27 were laboratory confirmed, 24 were isolated and 20 died. Real-time viral sequencing on 12 cases demonstrated SL3 lineage viruses with sequences differing by one to three nt inside a single phylogenetic cluster. For isolated cases, the average time between symptom onset and ETC referral was 2.8 days (interquartile range (IQR): 1-4). The average time between sample collection and molecular results’ availability was 3 days (IQR: 2-5). In an area with scarce resources, the genetic characterisation supported the outbreak investigations in real time, linking cases where epidemiological investigation was limited and reassuring that the responsible strain was already circulating in Guinea. We recommend coupling thorough epidemiological and genomic investigations to control EVD clusters.

      35. Invasive Haemophilus influenzae serotype A infection in children: Clinical description of an emerging pathogen – Alaska, 2002-2014External
        Plumb ID, Lecy KD, Singleton R, Engel MC, Hirschfeld M, Keck JW, Klejka J, Rudolph KM, Hennessy TW, Bruce MG.
        Pediatr Infect Dis J. 2018 Apr;37(4):298-303.

        BACKGROUND: Invasive infections from Haemophilus influenzae serotype a (Hia) have been reported with increasing frequency, especially among indigenous populations. However, there are limited population-based studies of clinical severity. We studied invasive Hia infections in Alaska to determine clinical characteristics, mortality and sequelae. METHODS: We defined an invasive Hia infection as the first detection of Hia from a usually sterile site in a child <10 years of age from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases Surveillance System and reviewed medical charts up to 2 years after reported illness. RESULTS: We identified invasive Hia infections in 36 children, 28 (78%) <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without documented underlying illness. Overlapping clinical presentations included meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%); and bone, joint or soft tissue infections in 10 children (22%). In 4 other children, no source of invasive infection was identified. Intensive care was provided for 11 children (31%); 12 children (33%) required surgical intervention. One year after infection, 4 children (11%) had died from Hia, and 5 children (14%) had ongoing neurologic sequelae. CONCLUSIONS: Invasive Hia infections in Alaska occurred predominantly in Alaska Native infants in rural communities. Although one-third of children had preexisting conditions, most cases occurred without known comorbidity. Clinical syndromes were frequently severe. One year after infection, 1 in 4 children had either died or had neurologic sequelae. An effective vaccine would prevent significant morbidity and mortality in affected populations.

      36. Burden and epidemiology of influenza- and respiratory syncytial virus-associated severe acute respiratory illness hospitalization in Madagascar, 2011-2016External
        Rabarison JH, Tempia S, Harimanana A, Guillebaud J, Razanajatovo NH, Ratsitorahina M, Heraud JM.
        Influenza Other Respir Viruses. 2018 Apr 6.

        BACKGROUND: Influenza and respiratory syncytial virus (RSV) infections are responsible for substantial global morbidity and mortality in young children and elderly individuals. Estimates of the burden of influenza- and RSV-associated hospitalization are limited in Africa. METHODS: We conducted hospital-based surveillance for laboratory-confirmed influenza- and RSV-associated severe acute respiratory illness (SARI) at one hospital and a retrospective review of SARI hospitalizations in five hospitals situated in Antananarivo during 2011-2016. We estimated age-specific rates (per 100,000 population) of influenza- and RSV-associated SARI hospitalizations for the Antananarivo region and then extrapolated these rates to the national level. RESULTS: Overall the mean annual national number of influenza-associated SARI hospitalizations for all age groups was 6,609 (rate: 30.0); 4,468 (rate: 127.6) and 2,141 (rate: 11.6) among individuals aged <5 and >/=5 was respectively. For these same age groups, the mean annual number of RSV-associated SARI hospitalizations was 11,768 (rate: 53.4), 11,299 (rate: 322.7) and 469 (rate: 2.5), respectively. CONCLUSION: The burden of influenza- and RSV-associated SARI hospitalization was high among children aged <5 years. These first estimates for Madagascar will enable government to make informed evidence-based decisions when allocating scarce resources and planning intervention strategies to limit the impact and spread of these viruses. This article is protected by copyright. All rights reserved.

      37. Background: Influenza-associated hospitalizations result in high morbidity and mortality. We sought to determine if early empiric anti-influenza therapy improves outcomes of hospitalized patients with influenza-associated lower respiratory tract infections (I-LRTIs). Methods: This was a randomized, unblinded, trial of adult patients hospitalized with I-LRTIs in Kentucky during 2009-2012. Patients were randomized to group A (standard of care) or group B (standard of care plus oseltamivir as early as possible but within 24 hours of enrollment). The primary outcome was development of clinical failure (composite variable including failure to reach clinical improvement within 7 days, transfer to intensive care 24 hours after admission, or rehospitalization or death within 30 days). Intent-to-treat (ITT) (all LRTI) and per-protocol (PP) (I-LRTI) analyses were done. Results: A total of 1107 patients were enrolled and included in the ITT analysis, 556 in group A and 551 in group B. The median time from symptom onset to hospital admission was 5 days (interquartile range, 5) for both groups; oseltamivir was initiated median day 6 in group B. There was no difference in the development of clinical failure (group A, 25%, and group B, 24%; P = .561). In the PP analysis, 11 of 45 (24%) patients in group A and 4 of 29 (14%) patients in group B had clinical failure (P = .414). Conclusions: Initiation of oseltamivir more than 5 days after illness onset did not reduce clinical failures among hospitalized patients with I- LRTIs. However, we did not enroll our projected sample size of I-LRTI. Clinical Trials Registration: NCT01248715.

      38. Household transmission of Ebola Virus: risks and preventive factors, Freetown, Sierra Leone, 2015External
        Reichler MR, Bangura J, Bruden D, Keimbe C, Duffy N, Thomas H, Knust B, Farmar I, Nichols E, Jambai A, Morgan O, Hennessy T.
        J Infect Dis. 2018 Apr 6.

        BACKGROUND: Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks. METHODS: We enrolled all confirmed persons with Ebola who were the first case in a household from December 2014-April 2015 in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing. RESULTS: We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%) contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk factors for transmission included index case death in the household, Ebola symptoms but no reported fever, age <20 years, more days with wet symptoms; and providing care to the index case (P<0.01 for each). Protective factors included avoiding the index case after illness onset and a piped household drinking water source (P<0.01 for each). CONCLUSIONS: To reduce Ebola transmission, communities should rapidly identify and follow-up all household contacts; isolate those with Ebola symptoms, including those without reported fever; and consider closer monitoring of contacts who provided care to a case. Households could consider efforts to minimize risk by designating one care provider for ill persons with all others avoiding the suspected case.

      39. Guidance about integration of comprehensive hepatitis C virus (HCV)-related services in sexually transmitted disease (STD) clinics is limited. We evaluated a federally funded HCV testing and linkage-to-care program at an STD clinic in Durham County, North Carolina. During December 10, 2012, to March 31, 2015, the program tested 733 patients for HCV who reported 1 or more HCV risk factor; 81 (11%) were HCV-infected (ie, HCV antibody-positive and HCV ribonucleic acid-positive). Fifty-one infected patients (63%) were linked to care. We concluded that essential program resources include reflex HCV ribonucleic acid testing; a dedicated bridge counselor to provide test results, health education, and linkage-to-care assistance; and referral relationships for local HCV management and treatment.

      40. Patient-level outcomes and virologic suppression rates in HIV-infected patients receiving antiretroviral therapy in RwandaExternal
        Riedel DJ, Stafford KA, Memiah P, Coker M, Baribwira C, Sebeza J, Karorero E, Nsanzimana S, Morales F, Redfield RR.
        Int J STD AIDS. 2018 Jan 1:956462418761695.

        The Rwanda national HIV program has been successful at scaling up antiretroviral therapy (ART) to achieve universal access. The AIDSRelief Model of Care focuses on four key principles: (1) earlier initiation of ART; (2) use of durable, highly-potent, and sequence-friendly first-line ART regimens; (3) early detection of treatment failure; and (4) provision of community-based care and support to ensure optimal adherence and follow up/engagement in care. We conducted a retrospective cohort study of randomly-selected HIV-infected patients at AIDSRelief-supported sites using a stratified, random sample of 583 adults (>15 years) who initiated ART from 30 June 2008 to 1 February 2010. At ART initiation, the median patient age was 38 years, and 67% were female. The baseline median CD4+ cell count was 309 cells/mm(3). Overall virologic suppression was 91%. Married/ever married status (adjusted prevalence odds ratio [aPOR] 3.75, 95% confidence interval [CI] 1.30-10.78) and self-reported adherence >/=95% in the past month (aPOR 2.76, 95% CI 1.00-7.62) were significantly associated with viral suppression in the multivariable model. Excellent virologic outcomes were achieved in Rwandan AIDSRelief sites utilizing the AIDSRelief Model of Care during the scale-up of ART in the country.

      41. Kinetics of serological responses in critically ill patients hospitalized with 2009 pandemic influenza A(H1N1) virus infection in Canada, 2009-2011External
        Rolfes MA, Gross FL, Flannery B, Meyers AF, Luo M, Bastien N, Fowler RA, Katz JM, Levine MZ, Kumar A, Uyeki TM.
        J Infect Dis. 2018 Mar 13;217(7):1078-1088.

        Background: The kinetics of the antibody response during severe influenza are not well documented. Methods: Critically ill patients infected with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), confirmed by reverse-transcription polymerase chain reaction analysis or seroconversion (defined as a >/=4-fold rise in titers), during 2009-2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed-effects models and compared by patient outcome, age, and corticosteroid treatment. Results: Of 47 patients with A(H1N1)pdm09 virus infection (median age, 47 years), 59% had baseline HAI titers of <40, and 68% had baseline neutralizing titers of <40. Antibody titers rose quickly after symptom onset, and, by day 14, 83% of patients had HAI titers of >/=40, and 80% had neutralizing titers >/=40. Baseline HAI titers were significantly higher in patients who died compared with patients who survived; however, the antibody kinetics were similar by patient outcome and corticosteroid treatment. Geometric mean titers over time in older patients were lower than those in younger patients. Conclusions: Critically ill patients with influenza A(H1N1)pdm09 virus infection had strong HAI and neutralizing antibody responses during their illness. Antibody kinetics differed by age but were not associated with patient outcome.

      42. Improving estimation of HIV viral suppression in the United States: A method to adjust HIV surveillance estimates from the medical monitoring project using cohort dataExternal
        Rosenberg ES, Bradley H, Buchacz K, McKenney J, Paz-Bailey G, Prejean J, Brooks JT, Shouse L, Sullivan PS.
        Am J Epidemiol. 2018 Apr 4.

        CDC has estimated HIV viral suppression (VS) using two data sources. The National HIV Surveillance System estimate (50% of HIV-diagnosed persons in 2012) is derived from viral load reporting from a subset of jurisdictions that vary yearly. The Medical Monitoring Project (MMP) estimate (42% in 2012) is based on a sample of persons receiving HIV care during the first 4 months of each year. We developed the Cohort-adjustment Method to reconstruct VS estimates, accounting for persons receiving care later in the year. Using the HIV Outpatient Study cohort, we assessed timing of care receipt, demographics, and VS at last test (<200 vs. >/=200 copies/mL), standardizing MMP to HIV Outpatient Study data using multivariable regression models and yielding adjusted VS estimates. We estimated 52% (95% CI: 48, 56) of HIV-diagnosed persons achieved VS in 2012. Differences from previously published estimate were due to: 1) 23% underestimation of persons receiving HIV care and 2) lower VS rates among persons receiving care outside versus inside the 4-month MMP sampling period (79% vs. 88%). This methodology yielded VS estimates closer to the National HIV Surveillance System estimate than previously published. Use of more, geographically diverse cohort data may enable assessment of temporal trends.

      43. Human immunodeficiency virus-1 drug resistance patterns among adult patients failing second-line protease inhibitor-containing regimens in Namibia, 2010-2015External
        Sawadogo S, Shiningavamwe A, Roscoe C, Baughman AL, Negussie T, Mutandi G, Yang C, Hamunime N, Agolory S.
        Open Forum Infectious Diseases. 2018 01 Feb;5(2).

        Three hundred sixty-six adult patients in Namibia with second- line virologic failures were evaluated for human immunodeficiency virus drug-resistant (HIVDR) mutations. Less than half (41.5%) harbored =1 HIVDR mutations to standardized second-line antiretroviral therapy (ART) regimen. Optimizing adherence, viral load monitoring, and genotyping are critical to prevent emergence of resistance, as well as unnecessary switching to costly third-line ART regimens.

      44. Hospitalisations due to bacterial gastroenteritis: A comparison of surveillance and hospital discharge dataExternal
        Scallan E, Griffin PM, McLean HQ, Mahon BE.
        Epidemiol Infect. 2018 Apr 15:1-7.

        Studies estimating the human health impact of the foodborne disease often include estimates of the number of gastroenteritis hospitalisations. The aims of this study were to examine the degree to which hospital discharge data underreport hospitalisations due to bacterial gastroenteritis and to estimate the frequency of stool sample submission among patients presenting with gastroenteritis. Using linked laboratory and hospital discharge data from a healthcare organisation and its affiliated hospital, we examined the International Classification of Disease (ICD-9-CM) diagnosis codes assigned to hospitalised adults with culture-confirmed Campylobacter, Salmonella, or Escherichia coli O157 infections and determined the frequency of stool sample submission. Among 138 hospitalised patients with culture-confirmed infections, 43% of Campylobacter patients, 56% of Salmonella patients and 35% of E. coli O157 patients had that pathogen-specific code listed on the discharge record. Among patients without their infection listed as a diagnosis, 65% were assigned a nonspecific gastroenteritis code. Submitting a specimen for culture 3 days before discharge was significantly associated with having the pathogen-specific diagnosis listed. Of 6181 patients assigned a nonspecific gastroenteritis code, 69% had submitted a stool sample for bacterial culture. This study can be used to understand differences and adjust for the underreporting and underdiagnosed of Campylobacter, Salmonella and E. coli O157 in hospital discharge and surveillance data, respectively.

      45. Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study: reverse transcription-polymerase chain reaction and cataract surgery outcomes of Ebola survivors in Sierra LeoneExternal
        Shantha JG, Mattia JG, Goba A, Barnes KG, Ebrahim FK, Kraft CS, Hayek BR, Hartnett JN, Shaffer JG, Schieffelin JS, Sandi JD, Momoh M, Jalloh S, Grant DS, Dierberg K, Chang J, Mishra S, Chan AK, Fowler R, O’Dempsey T, Kaluma E, Hendricks T, Reiners R, Reiners M, Gess LA, O. Neill K, Kamara S, Wurie A, Mansaray M, Acharya NR, Liu WJ, Bavari S, Palacios G, Teshome M, Crozier I, Farmer PE, Uyeki TM, Bausch DG, Garry RF, Vandy MJ, Yeh S.
        EBioMedicine. 2018 Apr;30:217-224.

        BACKGROUND: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. METHODS: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). FINDINGS: We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0years (IQR 17-35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P<0.001). INTERPRETATION: EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.

      46. Influenza antiviral prescribing for outpatients with an acute respiratory illness and at high risk for influenza-associated complications during 5 influenza seasons – United States, 2011-2016External
        Stewart RJ, Flannery B, Chung JR, Gaglani M, Reis M, Zimmerman RK, Nowalk MP, Jackson L, Jackson ML, Monto AS, Martin ET, Belongia EA, McLean HQ, Fry AM, Havers FP.
        Clin Infect Dis. 2018 Mar 19;66(7):1035-1041.

        Background: Influenza causes millions of illnesses annually; certain groups are at higher risk for complications. Early antiviral treatment can reduce the risk of complications and is recommended for outpatients at increased risk. We describe antiviral prescribing among high-risk outpatients for 5 influenza seasons and explore factors that may influence prescribing. Methods: We analyzed antiviral prescription and clinical data for high-risk outpatients aged >/=6 months with an acute respiratory illness (ARI) and enrolled in the US Influenza Vaccine Effectiveness Network during the 2011-2012 through 2015-2016 influenza seasons. We obtained clinical information from interviews and electronic medical records and tested all enrollees for influenza with real-time reverse-transcription polymerase chain reaction (rRT-PCR). We calculated the number of patients with ARI that must be treated to treat 1 patient with influenza. Results: Among high-risk outpatients with ARI who presented to care within 2 days of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication, including 472 of 1292 (37%) of those with rRT-PCR-confirmed influenza. Forty percent of high-risk outpatients with influenza presented to care early. Earlier presentation was associated with antiviral treatment (odds ratio [OR], 4.1; 95% confidence interval [CI], 3.5-4.8), as was fever (OR, 3.2; 95% CI, 2.7-3.8), although 25% of high-risk outpatients with influenza were afebrile. Empiric treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with influenza. Conclusions: Influenza antiviral medications were infrequently prescribed for high-risk outpatients with ARI who would benefit most. Efforts to increase appropriate antiviral prescribing are needed to reduce influenza-associated complications.

      47. Testing for Coccidioidomycosis among community-acquired pneumonia patients, southern California, USAExternal
        Tartof SY, Benedict K, Xie F, Rieg GK, Yu KC, Contreras R, Truong J, Fong K, Tseng HF, Jacobsen SJ, Mody RK.
        Emerg Infect Dis. 2018 Apr;24(4):779-781.

        We conducted a cohort study to identify characteristics associated with testing for, and testing positive for, coccidioidomycosis among patients with community-acquired pneumonia in southern California, USA. Limited and delayed testing probably leads to underdiagnosis among non-Hispanic black, Filipino, or Hispanic patients and among high-risk groups, including persons in whom antimicrobial drug therapy has failed.

      48. Detection of influenza C viruses among outpatients and patients hospitalized for severe acute respiratory infection, Minnesota, 2013-2016External
        Thielen BK, Friedlander H, Bistodeau S, Shu B, Lynch B, Martin K, Bye E, Como-Sabetti K, Boxrud D, Strain AK, Chaves SS, Steffens A, Fowlkes AL, Lindstrom S, Lynfield R.
        Clin Infect Dis. 2018 Mar 19;66(7):1092-1098.

        Background: Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. Methods: Four outpatient clinics and 3 hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) from May 2013 through December 2016. Specimens were tested using multitarget nucleic acid amplification for 19-22 respiratory pathogens, including influenza C. Results: Influenza C virus was detected among 59 of 10 202 (0.58%) hospitalized severe ARI cases and 11 of 2282 (0.48%) outpatients. Most detections occurred from December to March, 73% during the 2014-2015 season. Influenza C detections occurred among patients of all ages, with rates being similar between inpatients and outpatients. The highest rate of detection occurred among children aged 6-24 months (1.2%). Among hospitalized cases, 7 required intensive care. Medical comorbidities were reported in 58% of hospitalized cases and all who required intensive care. At least 1 other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (20%). The hemagglutinin-esterase-fusion gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. Conclusions: We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children but occurred in all ages. Some cases that were positive for influenza C, particularly those with comorbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.

      49. To assess trends in Neisseria gonorrhoeae among gay, bisexual, and other men who have sex with men (MSM), we reviewed existing and published gonorrhea surveillance data in the United States. Data identified in this review include the following: national gonorrhea case report data and data from 3 other surveillance programs, the Gonococcal Isolate Surveillance Project (GISP), the STD Surveillance Network (SSuN), and National HIV Behavioral Surveillance.Rates of reported cases of gonorrhea among men increased 54.8% in 2006 to 2015 compared with a 2.6% increase among women. Since 2012, the rate of reported gonorrhea cases among men surpassed the rate among women; the male-to-female case rate ratio increased from 0.97 in 2012 to 1.31 in 2015. The proportion of gonococcal urethral isolates collected in the Gonococcal Isolate Surveillance Project that were collected from MSM increased from 21.5% to 38.1% in 2006 to 2015. In 2009 to 2015, the percent of MSM who tested positive for rectal and oropharyngeal gonorrhea in sexually transmitted disease (STD) clinics increased by 73.4% and 12.6%, respectively. Estimated rates of gonorrhea among MSM increased by 151% in 2010 to 2015 in jurisdictions participating in the STD Surveillance Network. Data from the National HIV Behavioral Surveillance demonstrate that testing for gonorrhea among MSM increased by 23.1% between 2011 and 2014.Together, surveillance data suggest a disproportionate burden of gonorrhea among MSM in the United States and suggest increases in both screening and disease in recent years. Because each data source has inherent limitations and biases, examining these data from different systems together strengthens this conclusion.

      50. Multimorbidity among persons living with human immunodeficiency virus in the United StatesExternal
        Wong C, Gange SJ, Moore RD, Justice AC, Buchacz K, Abraham AG, Rebeiro PF, Koethe JR, Martin JN, Horberg MA, Boyd CM, Kitahata MM, Crane HM, Gebo KA, Gill MJ, Silverberg MJ, Palella FJ, Patel P, Samji H, Thorne J, Rabkin CS, Mayor A, Althoff KN.
        Clin Infect Dis. 2018 Apr 3;66(8):1230-1238.

        Background: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. Methods: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy-exposed PLWH receiving clinical care (ie, >/=1 CD4 count) in the United States during 2000-2009. Multimorbidity was irreversible, defined as having >/=2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non-AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. Results: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34-46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (Ptrend < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77-.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01-1.34). Hypertension and hypercholesterolemia most commonly co-occurred. Conclusions: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

      51. Persistent pandemic lineages of uropathogenic Escherichia coli in a college community from 1999 to 2017External
        Yamaji R, Rubin J, Thys E, Friedman CR, Riley LW.
        J Clin Microbiol. 2018 Apr;56(4).

        The incidence of drug-resistant community-acquired urinary tract infections (CA-UTI) continues to increase worldwide. In 1999 to 2000, a single lineage of uropathogenic Escherichia coli (UPEC) sequence type 69 (ST69) caused 51% of trimethoprim-sulfamethoxazole-resistant UTI in a Northern California university community. We compared the clonal distributions of UPEC and its impact on antimicrobial resistance prevalence in the same community during two periods separated by 17 years. We analyzed E. coli isolates from urine samples from patients with symptoms of UTI who visited a health service between September 2016 and May 2017 and compared them to UPEC isolates collected similarly between October 1999 and March 2000. Isolates were tested for antimicrobial drug susceptibility and genotyped by multilocus sequence typing. In 1999 to 2000, strains belonging to ST95, ST127, ST73, ST69, ST131, and ST10 caused 125 (56%) of 225 UTI cases, while the same STs caused 148 (64%) of 233 UTI cases in 2016 to 2017. The frequencies of ampicillin resistance and ciprofloxacin resistance rose from 24.4% to 41.6% (P < 0.001) and from 0.9% to 5.1% (P < 0.003), respectively. The six STs accounted for 78.6% and 72.7% of these increases, respectively. Prevalence of drug-resistant UTI in this community appears to be largely influenced by a small set of dominant UPEC STs circulating in the same community 17 years apart. Further research to determine the origin and reasons for persistence of these dominant genotypes is necessary to combat antimicrobial-resistant CA-UTI.

      52. Assessing prevalence of missed laboratory-confirmed sexually transmitted infections among women in Kingston, Jamaica: results from a secondary analysis of the Sino-Implant clinical trialExternal
        Zia Y, Wiener J, Snead MC, Papp J, Phillips C, Flowers L, Medley-Singh N, Costenbader EC, Hylton-Kong T, Kourtis AP.
        BMJ Open. 2018 Apr 13;8(4):e019913.

        OBJECTIVES: To assess potentially missed sexually transmitted infections (STIs), we compared clinically diagnosed STIs to laboratory-confirmed diagnoses of gonorrhoea (GC), chlamydia (CT) and trichomonas (Tvag). DESIGN: Secondary analysis of a randomised controlled trial. SETTING: We used data and specimens previously collected for the Sino-Implant Study in Kingston, Jamaica. PARTICIPANTS: The Sino-Implant Study randomised 414 women to receive a levonorgestrel implant at either baseline or 3 months post-enrolment to evaluate unprotected sex after implant initiation. This analysis used 254 available vaginal swab samples. OUTCOME MEASURES: Clinically diagnosed STIs were determined from medical records by assessing clinical impressions and prescriptions. Laboratory-confirmed STIs included GC, CT and Tvag tested by Aptima Combo 2 for CT/GC and Aptima Tvag assays (Hologic, San Diego, California, USA). Log-binomial regression models fit with generalised estimating equations were used to estimate associations of clinically diagnosed STIs with laboratory-confirmed diagnoses and demographic and behavioural characteristics. RESULTS: Overall, 195 (76.8%) women had laboratory-confirmed STI (CT, GC or Tvag) while only 65 (25.6%) women had clinically diagnosed cervicitis and/or vaginitis during the study period. Clinical diagnosis missed 79.7% of laboratory-confirmed STIs: 85% of GC (n=17/20), 78.8% of CT (n=141/179) and 80.0% of Tvag (n=180/225). Hormonal contraceptive use in the month prior to the study visit was significantly associated with clinical diagnosis at any time point (prevalence ratio (PR): 1.65, 95% CI 1.07 to 2.54). As age increased, clinically missed infections significantly decreased (PR: 0.98 per year increase, 95% CI 0.97 to 1.00). CONCLUSIONS: The prevalence of laboratory-confirmed STIs was much higher than what was captured by clinical diagnosis. GC, CT and Tvag were not accurately detected without lab confirmation. Missed diagnoses decreased with older age. Increased laboratory capacity and refinement of the syndromic approach are needed to protect the health of sexually active Jamaican women. TRIAL REGISTRATION NUMBER: NCT01684358.

    • Disaster Control and Emergency Services

      1. Phosphine exposure among emergency responders – Amarillo, Texas, January 2017External
        Hall EM, Patel K, Victory KR, Calvert GM, Nogueira LM, Bojes HK.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 6;67(13):387-389.

        Phosphine is a highly toxic gas that forms when aluminum phosphide, a restricted-use pesticide* typically used in agricultural settings, reacts with water. Acute exposure can lead to a wide range of respiratory, cardiovascular, and gastrointestinal symptoms, and can be fatal (1). On January 2, 2017, the Texas Department of State Health Services (DSHS) was notified by the Texas Panhandle Poison Center of an acute phosphine exposure incident in Amarillo, Texas. DSHS investigated potential occupational phosphine exposures among the 51 on-scene emergency responders; 40 (78.4%) did not use respiratory protection during response operations. Fifteen (37.5%) of these 40 responders received medical care for symptoms or as a precaution after the incident, and seven (17.5%) reported new or worsening symptoms consistent with phosphine exposure within 24 hours of the incident. Emergency response organizations should ensure that appropriate personal protective equipment (PPE) is used during all incidents when an unknown hazardous substance is suspected. Additional evaluation is needed to identify targeted interventions that increase emergency responder PPE use during this type of incident.

      2. Acute malnutrition and anemia among Rohingya children in Kutupalong Camp, BangladeshExternal
        Leidman E, Humphreys A, Greene Cramer B, Toroitich-Van Mil L, Wilkinson C, Narayan A, Bilukha O.
        Jama. 2018 Apr 10;319(14):1505-1506.

        [No abstract]

      3. A space time analysis evaluating the impact of Hurricane Sandy on HIV testing ratesExternal
        Wilt GE, Adams EE, Thomas E, Ekperi L, LeBlanc TT, Dunn I, Molinari NA, Carbone EG.
        Int J Disaster Risk Reduct. 2018 ;28:839-844.

        Spatial proximity to infrastructural damage from natural disasters may pose a threat to established HIV testing services and contribute to delays in knowledge of one’s disease status. Physical vulnerabilities such as spatial proximity to a level 4 FEMA impact zone, are defined in this study as natural and infrastructural barriers that can impede access to care. We analyzed the storm effects and community characteristics that contributed to the changes in HIV testing rates post Hurricane Sandy. Univariate and bivariate Moran’s I tests were conducted to test for spatial autocorrelation. Combined spatial lag and error models accounted for lagged effects and alternatives in error distribution. Bivariate local Moran’s I identified many significant clusters of more extreme negative relative change in HIV testing rates in areas with high FEMA impact ranks. Spatial lag and error models highlighted a significant relationship between CBSAs closer to a level 4 FEMA impact zone and the increased effect of Hurricane Sandy on HIV testing. Additionally, as the number of habitable buildings increased, there was significantly less change in HIV testing rates. Physical vulnerability had a significant effect on HIV testing rates. However all findings became less significant over time, highlighting the recovery process. Factors including: increased communication concerning preventative measures prior to the disaster, a prompt response to mitigate infrastructural damage and resumption of HIV testing services, are essential at the government and community levels to mitigate infection risk.

    • Disease Reservoirs and Vectors

      1. Chlamydia psittaci in feral rosy-faced lovebirds (Agapornis roseicollis) and other backyard birds in Maricopa County, Arizona, USAExternal
        Dusek RJ, Justice-Allen A, Bodenstein B, Knowles S, Grear DA, Adams L, Levy C, Yaglom HD, Shearn-Bochsler VI, Ciembor PG, Gregory CR, Pesti D, Ritchie BW.
        J Wildl Dis. 2018 Apr;54(2):248-260.

        In 2013, a mortality event of nonnative, feral Rosy-faced Lovebirds ( Agapornis roseicollis) in residential backyards in Maricopa County, Arizona, US was attributed to infection with Chlamydia psittaci. In June 2014, additional mortality occurred in the same region. Accordingly, in August 2014 we sampled live lovebirds and sympatric bird species visiting backyard bird feeders to determine the prevalence of DNA and the seroprevalence of antibodies to C. psittaci using real-time PCR-based testing and elementary body agglutination, respectively. Chlamydia psittaci DNA was present in conjunctival-choanal or cloacal swabs in 93% (43/46) of lovebirds and 10% (14/142) of sympatric birds. Antibodies to C. psittaci were detected in 76% (31/41) of lovebirds and 7% (7/102) of sympatric birds. Among the sympatric birds, Rock Doves ( Columba livia) had the highest prevalence of C. psittaci DNA (75%; 6/8) and seroprevalence (25%; 2/8). Psittacine circovirus 1 DNA was also identified, using real-time PCR-based testing, from the same swab samples in 69% (11/16) of species sampled, with a prevalence of 80% (37/46) in lovebirds and 27% (38/142) in sympatric species. The presence of either Rosy-faced Lovebirds or Rock Doves at residential bird feeders may be cause for concern for epizootic and zoonotic transmission of C. psittaci in this region.

      2. An acarological risk model predicting the density and distribution of host-seeking Ixodes scapularis nymphs in MinnesotaExternal
        Johnson TL, Boegler KA, Clark RJ, Delorey MJ, Bjork JK, Dorr FM, Schiffman EK, Neitzel DF, Monaghan AJ, Eisen RJ.
        Am J Trop Med Hyg. 2018 Apr 9.

        Ixodes scapularis is the vector of at least seven human pathogens in Minnesota, two of which are known to cause Lyme disease (Borrelia burgdorferi sensu stricto and Borrelia mayonii). In Minnesota, the statewide incidence of Lyme disease and other I. scapularis-borne diseases and the geographic extent over which cases have been reported have both increased substantially over the last two decades. These changes correspond with an expanding distribution of I. scapularis over a similar time frame. Because the risk of exposure to I. scapularis-borne pathogens is likely related to the number of ticks encountered, we developed an acarological risk model predicting the density of host-seeking I. scapularis nymphs (DON) in Minnesota. The model was informed by sampling 81 sites located in 42 counties in Minnesota. Two main foci were predicted by the model to support elevated densities of host-seeking I. scapularis nymphs, which included the seven-county Minneapolis-St. Paul metropolitan area and counties in northern Minnesota, including Lake of the Woods and Koochiching counties. There was substantial heterogeneity observed in predicted DON across the state at the county scale; however, counties classified as high risk for I. scapularis-borne diseases and counties with known established populations of I. scapularis had the highest proportion of the county predicted as suitable for host-seeking nymphs (>/= 0.13 nymphs/100 m(2)). The model provides insight into areas of potential I. scapularis population expansion and identifies focal areas of predicted suitable habitat within counties where the incidence of I. scapularis-borne diseases has been historically low.

      3. Introduction and establishment of raccoon rabies on islands: Jekyll Island, Georgia, USA as a case studyExternal
        Ortiz S, Hernandez SM, Yabsley MJ, Becker TI, Carswell B, Moore Y, Fenton H, Bahnson CS, Niedringhaus K, Elsmo E, Orciari L, Yager P, Stedman NL, Nelson SE, Norton TM.
        J Wildl Dis. 2018 Apr;54(2):329-334.

        The introduction of rabies virus (RABV) to barrier islands, which are often popular tourist destinations with resource-rich habitats and connectivity and proximity to the mainland, is especially concerning because it can easily become endemic due to factors like dense rabies-vector populations (e.g., raccoons [ Procyon lotor]), high inter- and intraspecies contact rates, and anthropogenic activities such as supplemental feeding of feral cats ( Felis catus). In January 2013, a neurologic raccoon found on the Jekyll Island (JI), Georgia, US causeway tested positive for rabies. Mortality investigations of 29 raccoons have been conducted between December 2012-May 2017. The two most common diagnoses were RABV ( n=11) and canine distemper virus (CDV; n=8). Parvoviral enteritis was diagnosed in four raccoons but no coinfections were diagnosed. There was no apparent seasonality for rabies cases, but all CDV cases occurred in spring-fall. Most (64%) rabies submissions came from residential or recreational use areas located near feral cat feeding stations. Jekyll Island is a popular destination where tourists engage in numerous outdoor activities which facilitate human-wildlife interactions. Concerns regarding public and animal health highlight the importance of rabies surveillance, prevention, and control on islands. This is the first report of rabies on JI and emphasizes the importance of disease investigations because the assumption that neurologic raccoons have CDV, an endemic pathogen, can miss the establishment of novel pathogens such as RABV.

      4. West Nile virus (WNV) is a mosquito-borne flavivirus that is phylogenetically separated into distinct lineages. Lineage 1 (L1) and lineage 2 (L2) encompass all WNV isolates associated with human and veterinary disease cases. Although L1 WNV is globally distributed, including North America, L2 WNV only recently emerged out of sub-Saharan Africa into Europe and Russia. The spread of L2 WNV throughout and beyond Europe depends, in part, on availability of competent vectors. The vector competence of mosquitoes within the Culex genus for WNV is well established for L1 WNV but less extensively studied for L2 WNV. Assessing the vector competence of North American Culex mosquitoes for L2 WNV will be critical for predicting the potential for L2 WNV emergence in North America. We address the vector competence of North American Culex pipiens and Culex quinquefasciatus for L2 WNV. Both mosquito species were highly competent for each of the L2 WNV strains assessed, but variation in infection, dissemination, and transmission was observed. An L2 WNV strain (NS10) isolated during the Greek outbreak in 2010 exhibited a reduced capacity to infect Cx. pipiens compared with other L2 WNV strains. In addition, a South African L2 WNV strain (SA89) displayed a significantly shorter extrinsic incubation period in Cx. quinquefasciatus compared with other L2 WNV strains. These results demonstrate that North American Culex mosquito species are competent vectors of African and European L2 WNV and that emergence of L2 WNV is unlikely to be hindered by poor competence of North American vectors.

      5. Viral diversity of house mice in New York CityExternal
        Williams SH, Che X, Garcia JA, Klena JD, Lee B, Muller D, Ulrich W, Corrigan RM, Nichol S, Jain K, Lipkin WI.
        MBio. 2018 Apr 17;9(2).

        The microbiome of wild Mus musculus (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera. A representative screen of 15 viruses by PCR confirmed the presence of 13 of these viruses in liver. We identified an uneven distribution of diversity, with several viruses being associated with specific locations. Higher mouse weight was associated with an increase in the number of viruses detected per mouse, after adjusting for site, sex, and length. We found neither genetic footprints to known human viral pathogens nor antibodies to lymphocytic choriomeningitis virus.IMPORTANCE Mice carry a wide range of infectious agents with zoonotic potential. Their proximity to humans in the built environment is therefore a concern for public health. Laboratory mice are also the most common experimental model for investigating the pathobiology of infectious diseases. In this survey of mice trapped in multiple locations within New York City over a period of 1 year, we found a diverse collection of viruses that includes some previously not associated with house mice and others that appear to be novel. Although we found no known human pathogens, our findings provide insights into viral ecology and may yield models that have utility for clinical microbiology.

      6. New York City house mice (Mus musculus) as potential reservoirs for pathogenic bacteria and antimicrobial resistance determinantsExternal
        Williams SH, Che X, Paulick A, Guo C, Lee B, Muller D, Uhlemann AC, Lowy FD, Corrigan RM, Lipkin WI.
        MBio. 2018 Apr 17;9(2).

        House mice (Mus musculus) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella, Salmonella, Clostridium difficile, and diarrheagenic Escherichia coli Furthermore, genes mediating antimicrobial resistance to fluoroquinolones (qnrB) and beta-lactam drugs (blaSHV and blaACT/MIR) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment.IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes.

    • Drug Safety

      1. Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approachExternal
        Pulcini C, Binda F, Lamkang AS, Trett A, Charani E, Goff DA, Harbarth S, Hinrichsen SL, Levy-Hara G, Mendelson M, Nathwani D, Gunturu R, Singh S, Srinivasan A, Thamlikitkul V, Thursky K, Vlieghe E, Wertheim H, Zeng M, Gandra S, Laxminarayan R.
        Clin Microbiol Infect. 2018 Apr 2.

        OBJECTIVES: With increasing interest in hospital antimicrobial stewardship (AMS) programmes globally, there is a strong demand for core elements of AMS to be clearly defined based on principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals, regardless of resource availability, worldwide. METHODS: A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could be relevant globally. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS: The literature review identified 7 core elements and their related 29 checklist items from 48 references. Fifteen experts from 12 countries in 6 continents participated in the consensus procedure. Ultimately, all 7 core elements were retained, as well as 28 of the initial checklist items plus 1 that was newly suggested, all with >/=80% agreement; 20 elements and items were rephrased. CONCLUSIONS: This consensus on core elements for hospital AMS programmes is relevant to both high and low-to-middle income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.

      2. Vital Signs: Containment of novel multidrug-resistant organisms and resistance mechanisms – United States, 2006-2017External
        Woodworth KR, Walters MS, Weiner LM, Edwards J, Brown AC, Huang JY, Malik S, Slayton RB, Paul P, Capers C, Kainer MA, Wilde N, Shugart A, Mahon G, Kallen AJ, Patel J, McDonald LC, Srinivasan A, Craig M, Cardo DM.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 6;67(13):396-401.

        BACKGROUND: Approaches to controlling emerging antibiotic resistance in health care settings have evolved over time. When resistance to broad-spectrum antimicrobials mediated by extended-spectrum beta-lactamases (ESBLs) arose in the 1980s, targeted interventions to slow spread were not widely promoted. However, when Enterobacteriaceae with carbapenemases that confer resistance to carbapenem antibiotics emerged, directed control efforts were recommended. These distinct approaches could have resulted in differences in spread of these two pathogens. CDC evaluated these possible changes along with initial findings of an enhanced antibiotic resistance detection and control strategy that builds on interventions developed to control carbapenem resistance. METHODS: Infection data from the National Healthcare Safety Network from 2006-2015 were analyzed to calculate changes in the annual proportion of selected pathogens that were nonsusceptible to extended-spectrum cephalosporins (ESBL phenotype) or resistant to carbapenems (carbapenem-resistant Enterobacteriaceae [CRE]). Testing results for CRE and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are also reported. RESULTS: The percentage of ESBL phenotype Enterobacteriaceae decreased by 2% per year (risk ratio [RR] = 0.98, p<0.001); by comparison, the CRE percentage decreased by 15% per year (RR = 0.85, p<0.01). From January to September 2017, carbapenemase testing was performed for 4,442 CRE and 1,334 CRPA isolates; 32% and 1.9%, respectively, were carbapenemase producers. In response, 1,489 screening tests were performed to identify asymptomatic carriers; 171 (11%) were positive. CONCLUSIONS: The proportion of Enterobacteriaceae infections that were CRE remained lower and decreased more over time than the proportion that were ESBL phenotype. This difference might be explained by the more directed control efforts implemented to slow transmission of CRE than those applied for ESBL-producing strains. Increased detection and aggressive early response to emerging antibiotic resistance threats have the potential to slow further spread.

    • Environmental Health

      1. Determinants of prenatal exposure to polybrominated diphenyl ethers (PBDEs) among urban, minority infants born between 1998 and 2006External
        Cowell WJ, Sjodin A, Jones R, Wang Y, Wang S, Herbstman JB.
        Environ Pollut. 2018 Feb;233:774-781.

        Polybrominated diphenyl ethers (PBDEs) are environmentally persistent chemicals that structurally resemble legacy pollutants, such as polychlorinated biphenyls (PCBs). PBDEs were added to consumer products for over 30 years, before being phased out due to evidence of toxicity. We examined temporal changes in prenatal exposure to PBDEs, as well as other sources of variation. We measured PBDEs in umbilical cord plasma from 327 minority infants born in New York City between 1998 and 2006. We used linear regression to examine changes in concentrations over time and in relation to lifestyle characteristics collected during pregnancy. We detected BDE-47 in 80% of samples with a geometric mean concentration of 14.1 ng/g lipid. Ethnicity was the major determinant of PBDE exposure; African American infants had 58% higher geometric mean cord plasma concentrations of BDE-47 (p < 0.01) compared to Dominican infants. Notably, African American mothers were more likely to be born in the United States, which itself was associated with 40% (p < 0.01) higher concentrations. We observed small decreases in PBDE concentrations by date of birth and no difference before and after their phase-out in 2004. Final multivariable models explained 8-12% of variability in PBDE concentrations depending on the congener. Our finding that prenatal exposure to PBDEs decreased only modestly between 1998 and 2006 is consistent with the persistent properties of PBDEs and their ongoing release from existing consumer products.

      2. Temporal trends and developmental patterns of plasma polybrominated diphenyl ether concentrations over a 15-year period between 1998 and 2013External
        Cowell WJ, Sjodin A, Jones R, Wang Y, Wang S, Herbstman JB.
        J Expo Sci Environ Epidemiol. 2018 Apr 4.

        Polybrominated diphenyl ethers (PBDEs) were used extensively as flame retardants in furniture containing polyurethane foam until they were phased out of use, beginning in 2004. We examined temporal changes in plasma PBDE concentrations from 1998 to 2013 and characterized patterns of exposure over the early lifecourse among 334 children (903 samples) between birth and 9 years. We examined time trends by regressing PBDE concentration on year of sample collection in age-adjusted models and characterized developmental trajectories using latent class growth analysis (LCGA). Controlling for age, BDE-47 concentrations decreased 5% (95% confidence interval (CI): -9, -2) per year between 1998 and 2013. When considering only postnatal samples, this reduction strengthened to 13% (95% CI: -19, -9). Findings for BDE-99, 100 and 153 were similar, except that BDE-153 decreased to a lesser extent when both prenatal and postnatal samples were considered (-2%, 95% CI: -7, 0). These findings suggest that, on average, pentaBDE body burdens have decreased since the 2004 phase-out of these chemicals. When examining developmental period, PBDE concentrations peaked during toddler years for the majority of children, however, our observation of several unique trajectories suggests that a single measure may not accurately reflect exposure to PBDEs throughout early life.

      3. BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California. METHODS: Urinary concentrations of ten PAH metabolites and cotinine were quantified in 431 girls age 6-8 years at baseline. Characteristics obtained from parental interview, physical exam, and linked traffic data were examined as predictors of PAH metabolite concentrations using multivariable linear regression. A subset of girls (n = 100) had repeat measures of PAH metabolites in the second and fourth years of the study. We calculated the intraclass correlation coefficient (ICC), Spearman correlation coefficients, and how well the quartile ranking by a single measurement represented the four-year average PAH biomarker concentration. RESULTS: Eight PAH metabolites were detected in >/= 95% of the girls. The most consistent predictors of PAH biomarker concentrations were cotinine concentration, grilled food consumption, and region of residence, with some variation by demographics and season. After adjustment, select PAH metabolite concentrations were higher for Hispanic and Asian girls, and lower among black girls; 2-naphthol concentrations were higher in girls from lower income households. Other than 1-naphthol, there was modest reproducibility over time (ICCs between 0.18 and 0.49) and the concentration from a single spot sample was able to reliably rank exposure into quartiles consistent with the multi-year average. CONCLUSIONS: These results confirm diet and environmental tobacco smoke exposure as the main sources of PAHs. Controlling for these sources, differences in concentrations still existed by race for specific PAH metabolites and by income for 2-naphthol. The modest temporal variability implies adequate exposure assignment using concentrations from a single sample to define a multi-year exposure timeframe for epidemiologic exposure-response studies.

      4. Assessment of behavioral health concerns in the community affected by the Flint Water Crisis – Michigan (USA) 2016External
        Fortenberry GZ, Reynolds P, Burrer SL, Johnson-Lawrence V, Wang A, Schnall A, Pullins P, Kieszak S, Bayleyegn T, Wolkin A.
        Prehosp Disaster Med. 2018 Apr 19:1-10.

        OBJECTIVES: The Flint Community Resilience Group (Flint, Michigan USA) and the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) assessed behavioral health concerns among community members to determine the impact of lead contamination of the Flint, Michigan water supply. METHODS: A Community Assessment for Public Health Emergency Response (CASPER) was conducted from May 17 through May 19, 2016 using a multi-stage cluster sampling design to select households and individuals to interview. RESULTS: One-half of households felt overlooked by decision makers. The majority of households self-reported that at least one member experienced more behavioral health concerns than usual. The prevalence of negative quality of life indicators and financial concerns in Flint was higher than previously reported in the Michigan 2012 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) survey. CONCLUSIONS: The following can be considered to guide recovery efforts in Flint: identifying additional resources for behavioral health interventions and conducting follow-up behavioral health assessments to evaluate changes in behavioral health concerns over time; considering the impact of household economic factors when implementing behavioral health interventions; and ensuring community involvement and engagement in recovery efforts to ease community stress and anxiety. FortenberryGZ, ReynoldsP, BurrerSL, Johnson-LawrenceV, WangA, SchnallA, PullinsP, KieszakS, BayleyegnT, WolkinA. Assessment of behavioral health concerns in the community affected by the Flint water crisis – Michigan (USA) 2016.

      5. Incorporation of fetal and child PFOA dosimetry in the derivation of health-based toxicity valuesExternal
        Kieskamp KK, Worley RR, McLanahan ED, Verner MA.
        Environ Int. 2018 Feb;111:260-267.

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

      6. Assessment of community awareness and practices concerning indoor air pollutants – Madison County, Alabama, June 2017External
        Siza C, Morrison M, Harris S, Hatch T, Tyler M.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):447-450.

        The Alabama Department of Public Health (ADPH) conducts an annual community assessment to evaluate household preparedness and local public health concerns. In June 2017, ADPH conducted a Community Assessment for Public Health Emergency Response (CASPER), focusing on indoor air pollutants in seven neighborhoods in Madison County, Alabama, where a large percentage of homes were built before 1980. Local health partners had concerns about indoor air quality and environmental risks such as radon; however, limited information was available regarding community awareness, prevention, and mitigation measures related to potential exposures. Weighted response frequencies were calculated from assessment responses. Among 192 household interview respondents, 78.4% were aware of potential indoor lead exposures, but only 12.6% of respondents living in houses built before 1978 reported that the house had been tested for lead. Similarly, respondents in 70.2% of households had heard of radon; however, only 7.3% of houses had been tested for radon. Smoking was reported by residents of 45.7% of households; among those, 48.4% reported that smoking occurred inside the house. Identified gaps in exposure prevention and mitigation, including low lead and radon testing rates and a high prevalence of indoor smoking, were shared with the local health department, and recommendations for timely interventions and policy guidance (e.g., targeted education campaigns and smoking cessation programs) were presented. Results of this CASPER demonstrated its usefulness and efficiency in gathering community-level data to help guide public health policies and timely interventions.

      7. The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has thus far occurred for only a few environmental chemicals. In order to encourage decision-makers to embrace the critical role of PBPK modeling in risk assessment, several important challenges require immediate attention from the modeling community. The objective of this contemporary review is to highlight 3 of these challenges, including: (1) difficulties in recruiting peer reviewers with appropriate modeling expertise and experience; (2) lack of confidence in PBPK models for which no tissue/plasma concentration data exist for model evaluation; and (3) lack of transferability across modeling platforms. Several recommendations for addressing these 3 issues are provided to initiate dialog among members of the PBPK modeling community, as these issues must be overcome for the field of PBPK modeling to advance and for PBPK models to be more routinely applied in support of public health decision-making.

      8. Use of lead-glazed ceramic ware and lead-based folk remedies in a rural community of Baja California, MexicoExternal
        Welton M, Rodriguez-Lainz A, Loza O, Brodine S, Fraga M.
        Glob Health Promot. 2018 Mar;25(1):6-14.

        BACKGROUND: Lead exposure from lead-glazed ceramics (LGCs) and traditional folk remedies have been identified as significant sources of elevated blood lead levels in Mexico and the United States. This study took place from 2005 to 2012 in a rural community in Baja California, Mexico. OBJECTIVES: 1) Investigate the knowledge, attitudes, and practices related to lead and lead exposures from LGCs and two lead-based folk remedies ( azarcon and greta); and 2) evaluate a pilot intervention to provide alternative lead-safe cookware. METHODS: A baseline household survey was conducted in 2005, followed by the pilot intervention in 2006, and follow-up surveys in 2007 and 2012. For the pilot intervention, families who reported using LGCs were given lead-safe alternative cookware to try and its acceptance was evaluated in the following year. RESULTS: The community was mostly of indigenous background from Oaxaca and a high proportion of households had young children. In 2006, all participants using traditional ceramic ware at the time ( n = 48) accepted lead-safe alternative cookware to try, and 97% reported that they were willing to exchange traditional ceramic ware for lead-safe alternatives. The use of ceramic cookware decreased from over 90% during respondents’ childhood household use in Oaxaca to 47% in 2006 among households in Baja California, and further reduced to 16.8% in 2012. While empacho, a folk illness, was widely recognized as an intestinal disorder, there was almost universal unfamiliarity with the use and knowledge of azarcon and greta for its treatment. CONCLUSION: This pilot evaluation provides evidence 1) for an effective and innovative strategy to reduce lead exposure from LGCs and 2) of the feasibility of substituting lead-free alternative cookware for traditional ceramic ware in a rural indigenous community, when delivered in a culturally appropriate manner with health education. This strategy could complement other approaches to reduce exposure to lead from LGCs.

      9. Respirable uranyl-vanadate containing particulate matter derived from a legacy uranium mine site exhibits potentiated cardiopulmonary toxicityExternal
        Zychowski KE, Kodali V, Harmon M, Tyler C, Sanchez B, Ordonez Suarez Y, Herbert G, Wheeler A, Avasarala S, Cerrato JM, Kunda NK, Muttil P, Shuey C, Brearley A, Ali AM, Lin Y, Shoeb M, Erdely A, Campen MJ.
        Toxicol Sci. 2018 Apr 5.

        Background: Exposure to windblown particulate matter (PM) arising from legacy uranium (U) mine sites in the Navajo Nation may pose a human health hazard due to their potentially high metal content, including U and vanadium (V). Objective: To assess the toxic impact of PM derived from Claim 28 (a priority U mine) compared to background PM, and consider the putative role of metal species U and V. Methods: Two representative sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were obtained, characterized in terms of chemistry and morphology, and fractioned to the respirable (</=10mum) fraction. Mice were dosed with either PM sample, uranyl acetate or vanadyl sulfate via aspiration (100microg), with assessments of pulmonary and vascular toxicity 24h later. PM samples were also examined for in vitro effects on cytotoxicity, oxidative stress, phagocytosis, and inflammasome induction. Results: Claim 28 PM10 was highly enriched with U and V and exhibited a unique nanoparticle ultrastructure compared to background PM10. Claim 28 PM10 exhibited enhanced pulmonary and vascular toxicity relative to background PM10. Both U and V exhibited complementary pulmonary inflammatory potential, with U driving a classical inflammatory cytokine profile (elevated IL-1beta, TNFalpha, KC/GRO) while V preferentially induced a different cytokine pattern (elevated IL-5, IL-6, IL-10). Claim 28 PM10 was more potent than background PM10 in terms of in vitro cytotoxicity, impairment of phagocytosis, and oxidative stress responses. Conclusions: Resuspended PM10 derived from U mine waste exhibit greater cardiopulmonary toxicity than background dusts. Rigorous exposure assessment is needed to gauge the regional health risks imparted by these unremediated sites.

    • Epidemiology and Surveillance

      1. [No abstract]

    • Food Safety

      1. Report of erm(B)+ Campylobacter jejuni in the United StatesExternal
        Chen JC, Tagg KA, Joung YJ, Bennett C, Watkins LF, Eikmeier D, Folster JP.
        Antimicrob Agents Chemother. 2018 Apr 9.

        Campylobacter is a leading cause of foodborne illness in the United States, causing an estimated 1.3 million illnesses annually.

      2. Intensified sampling in response to a Salmonella Heidelberg outbreak associated with multiple establishments within a single poultry corporationExternal
        Green A, Defibaugh-Chavez S, Douris A, Vetter D, Atkinson R, Kissler B, Khroustalev A, Robertson K, Sharma Y, Becker K, Dessai U, Antoine N, Allen L, Holt K, Gieraltowski L, Wise M, Schwensohn C.
        Foodborne Pathog Dis. 2018 Mar;15(3):153-160.

        On June 28, 2013, the Food Safety and Inspection Service (FSIS) was notified by the Centers for Disease Control and Prevention (CDC) of an investigation of a multistate cluster of illnesses of Salmonella enterica serovar Heidelberg. Since case-patients in the cluster reported consumption of a variety of chicken products, FSIS used a simple likelihood-based approach using traceback information to focus on intensified sampling efforts. This article describes the multiphased product sampling approach taken by FSIS when epidemiologic evidence implicated chicken products from multiple establishments operating under one corporation. The objectives of sampling were to (1) assess process control of chicken slaughter and further processing and (2) determine whether outbreak strains were present in products from these implicated establishments. As part of the sample collection process, data collected by FSIS personnel to characterize product included category (whole chicken and type of chicken parts), brand, organic or conventional product, injection with salt solutions or flavorings, and whether product was skinless or skin-on. From the period September 9, 2013, through October 31, 2014, 3164 samples were taken as part of this effort. Salmonella percent positive declined from 19.7% to 5.3% during this timeframe as a result of regulatory and company efforts. The results of intensified sampling for this outbreak investigation informed an FSIS regulatory response and corrective actions taken by the implicated establishments. The company noted that a multihurdle approach to reduce Salmonella in products was taken, including on-farm efforts such as environmental testing, depopulation of affected flocks, disinfection of affected houses, vaccination, and use of various interventions within the establishments over the course of several months.

      3. A foodborne disease outbreak investigation experience in a college in Lusaka, Zambia, 2017External
        Kapaya F, Mwansa FD, Sakubita P, Gama A, Langa N, Chewe O, Mutale L, Nanzaluka F, Gershom C, Chola M, Kapata N, Sinyange N, Chibuye S, Yard E.
        Pan African Medical Journal. 2018 ;29.

        Introduction: On 19 March 2017, an outbreak of unknown etiology was reported among students at a college in Lusaka, Zambia. We investigated to confirm the outbreak, identify exposures, determine the aetiological agent, and implement preventive measures. Methods: We conducted an unmatched case-control study. Cases and controls were selected conveniently. A suspected case was diarrhea or abdominal pains in any student at College A and Controls were asymptomatic students at College A during 18-23 March. We interviewed cases and controls about exposures to suspected food and water and collected saved food samples and swabs from food-handlers’ hands and kitchen surfaces for culture. We analyzed data using Epi-info v 7.2 (Atlanta, Georgia). Results: We identified 59 suspected case-patients. Predominant symptoms were diarrhea (n = 51.83%) and abdominal pains (n = 44.75%). The outbreak started on 18 March, peaked on 19, and concluded on 20 March. We interviewed 30 case-patients and 71 controls. Exposures associated with increased odds of illness included eating food served at dinner on Saturday (18 March) in school cafeteria (OR = 5.8, 95% CI = 2.0-16.7); specifically, eating beans at Saturday dinner (OR = 21.6, 95% CI = 4.5-104) and drinking water supplied at school (OR = 8.8, 95% CI = 1.45-53.6). Samples from all food-handlers (n = 13) yielded Staphylococcus aureus and all food samples (n = 3) yielded Escherichia coli, Staphylococcus aureus and fecal coliforms. Conclusion: The results suggest a foodborne outbreak caused by consumption of contaminated food served at dinner on 18 March at College A. We educated the food handlers and school management about the importance of disinfection of preparation surfaces, supervision of food handling and handwashing practices.

      4. Retail deli slicer inspection practices: An EHS-Net studyExternal
        Lipcsei LE, Brown LG, Hoover ER, Faw BV, Hedeen N, Matis B, Nicholas D, Ripley D.
        J Food Prot. 2018 May;81(5):799-805.

        The Centers for Disease Control and Prevention (CDC) estimates that 3,000 people die in the United States each year from foodborne illness, and Listeria monocytogenes causes the third highest number of deaths. Risk assessment data indicate that L. monocytogenes contamination of particularly delicatessen meats sliced at retail is a significant contributor to human listeriosis. Mechanical deli slicers are a major source of L. monocytogenes cross-contamination and growth. In an attempt to prevent pathogen cross-contamination and growth, the U.S. Food and Drug Administration (FDA) created guidance to promote good slicer cleaning and inspection practices. The CDC’s Environmental Health Specialists Network conducted a study to learn more about retail deli practices concerning these prevention strategies. The present article includes data from this study on the frequency with which retail delis met the FDA recommendation that slicers should be inspected each time they are properly cleaned (defined as disassembling, cleaning, and sanitizing the slicer every 4 h). Data from food worker interviews in 197 randomly selected delis indicate that only 26.9% of workers ( n = 53) cleaned and inspected their slicers at this frequency. Chain delis and delis that serve more than 300 customers on their busiest day were more likely to have properly cleaned and inspected slicers. Data also were collected on the frequency with which delis met the FDA Food Code provision that slicers should be undamaged. Data from observations of 685 slicers in 298 delis indicate that only 37.9% of delis ( n = 113) had slicers that were undamaged. Chain delis and delis that provide worker training were more likely to have slicers with no damage. To improve slicer practices, food safety programs and the retail food industry may wish to focus on worker training and to focus interventions on independent and smaller delis, given that these delis were less likely to properly inspect their slicers and to have undamaged slicers.

      5. Protracted outbreak of Salmonella Newport infections linked to ground beef: Possible role of dairy cows – 21 states, 2016-2017External
        Marshall KE, Tewell M, Tecle S, Leeper M, Sinatra J, Kissler B, Fung A, Brown K, Wagner D, Trees E, Hise KB, Chaturvedi V, Schlater LK, Morningstar-Shaw BR, Whitlock L, Holt K, Becker K, Nichols M, Williams IT, Jhung M, Wise ME, Gieraltowski L.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):443-446.

        In January 2017, CDC identified a cluster of Salmonella enterica serotype Newport infections with isolates sharing an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern, JJPX01.0010 (pattern 10), through PulseNet, the national molecular subtyping network for foodborne disease surveillance. This report summarizes the investigation by CDC, state and local health and agriculture departments, and the U.S. Department of Agriculture’s Food Safety and Inspection Service (USDA-FSIS) and discusses the possible role of dairy cows as a reservoir for strains of Salmonella that persistently cause human illness. This investigation combined epidemiologic and whole genome sequencing (WGS) data to link the outbreak to contaminated ground beef; dairy cows were hypothesized to be the ultimate source of Salmonella contamination.

    • Genetics and Genomics

      1. Discovery of genetic variants of the kinases that activate tenofovir among individuals in the United States, Thailand, and South Africa: HPTN067External
        Figueroa DB, Tillotson J, Li M, Piwowar-Manning E, Hendrix CW, Holtz TH, Bokoch K, Bekker LG, van Griensven F, Mannheimer S, Hughes JP, Grant RM, Bumpus NN.
        PLoS One. 2018 ;13(4):e0195764.

        Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two phosphorylation steps to form a competitive inhibitor of HIV reverse transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA isolated from dried blood spots collected from 505 participants from Bangkok, Thailand; Cape Town, South Africa; and New York City, USA were examined for variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals (3.7% frequency) carried variants in at least one kinase that would result in a decrease or loss of enzymatic activity. To functionally test these predictions, AK2 and AK2 variants were expressed in and purified from E. coli, followed by investigation of their activities towards tenofovir. Interestingly, we found that purified AK2 had the ability to phosphorylate tenofovir-monophosphate to tenofovir-diphosphate in addition to phosphorylating tenofovir to tenofovir-monophosphate. Further, four of the six AK2 variants predicted to result in a loss or decrease of enzyme function exhibited a >/=30% decrease in activity towards tenofovir in our in vitro assays. Of note, an AK2 K28R variant resulted in a 72% and 81% decrease in the formation of tenofovir-monophosphate and tenofovir-diphosphate, respectively. These data suggest that there are naturally occurring genetic variants that could potentially impact TFV activation.

      2. Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

      3. High-quality whole-genome sequences for 59 historical Shigella strains generated with PacBio sequencingExternal
        Kim J, Lindsey RL, Garcia-Toledo L, Loparev VN, Rowe LA, Batra D, Juieng P, Stoneburg D, Martin H, Knipe K, Smith P, Strockbine N.
        Genome Announc. 2018 Apr 12;6(15).

        Shigella spp. are enteric pathogens that cause shigellosis. We report here the high-quality whole-genome sequences of 59 historical Shigella strains that represent the four species and a variety of serotypes.

      4. Phenotypic and genotypic characterization of Enterobacteriaceae producing oxacillinase-48-like carbapenemases, United StatesExternal
        Lutgring JD, Zhu W, de Man TJ, Avillan JJ, Anderson KF, Lonsway DR, Rowe LA, Batra D, Rasheed JK, Limbago BM.
        Emerg Infect Dis. 2018 Apr;24(4):700-709.

        Oxacillinase (OXA)-48-like carbapenemases remain relatively uncommon in the United States. We performed phenotypic and genotypic characterization of 30 Enterobacteriaceae producing OXA-48-like carbapenemases that were recovered from patients during 2010-2014. Isolates were collected from 12 states and not associated with outbreaks, although we could not exclude limited local transmission. The alleles beta-lactamase OXA-181 (blaOXA-181) (43%), blaOXA-232 (33%), and blaOXA-48 (23%) were found. All isolates were resistant to ertapenem and showed positive results for the ertapenem and meropenem modified Hodge test and the modified carbapenem inactivation method; 73% showed a positive result for the Carba Nordmann-Poirel test. Whole-genome sequencing identified extended-spectrum beta-lactamase genes in 93% of isolates. In all blaOXA-232 isolates, the gene was on a ColKP3 plasmid. A total of 12 of 13 isolates harboring blaOXA-181 contained the insertion sequence DeltaISEcp1. In all isolates with blaOXA-48, the gene was located on a TN1999 transposon; these isolates also carried IncL/M plasmids.

      5. Communication of cancer-related genetic and genomic information: A landscape analysis of reviewsExternal
        Peterson EB, Chou WS, Gaysynsky A, Krakow M, Elrick A, Khoury MJ, Kaphingst KA.
        Transl Behav Med. 2018 Jan 29;8(1):59-70.

        Cancer-related genetic and genomic testing (CGT) is changing cancer care by personalizing care options, leading to an era of precision medicine. Advances in and increased use of CGT add complexity to clinical communication. This landscape analysis assessed published reviews of communication issues related to CGT and discusses implications for practice and behavioral research. A comprehensive electronic literature search was conducted of peer-reviewed literature reviews on studies related to CGT communication published between January 2010 and January 2017, resulting in a final sample of 24 reviews. Reviews were categorized, with overlaps, into four domains across the genetic testing communication continuum. Reviews on CGT-related knowledge, attitudes, and perceptions (n = 8) found that despite substantial public interest, their knowledge and awareness remains low. Providers also reported insufficient knowledge and overall caution, particularly regarding direct-to-consumer (DTC) genetic testing. Reviews of decision-making about CGT and test uptake (n = 8) identified individual, interpersonal, and systems-level barriers to uptake. Reviews of patient-provider CGT communication (n = 8) revealed limited communication and little empirical research on outcomes of communication or efforts at improving clinical and family communication. There were mixed findings in reviews (n = 15) on the psychological and behavioral impact of CGT, and DTC testing particularly had little effect on behaviors. Taken together, there is very little extant research in CGT in minority and underserved communities. In order for scientific advances in CGT to translate into equitable, patient-centered care, behavioral research, including health literacy and communication, plays critical roles.

    • Global Health
      1. Non-communicable diseases (NCDs) are the leading causes of death worldwide, with higher rates of premature mortality in low- and middle-income countries (LMICs). This places a high economic burden on these countries, which usually have limited capacity to address this public health problem. We developed a guided self-assessment tool for describing national capacity for NCD prevention and control. The purpose of this tool was to assist countries in identifying key opportunities and gaps in NCD capacity. It was piloted in three countries between 2012 and 2013: Mozambique, Colombia, and the Dominican Republic. The tool includes details about NCD burden; health system infrastructure and primary care services; workforce capacity; surveillance; planning, policy, and program management; and partnerships. In the three pilot countries, the tool helped to identify differences in capacity needs pertaining to staff, training, and surveillance, but similarities were also found related to NCD challenges and opportunities. The NCD tool increased our understanding of needs and critical capacity elements for addressing NCDs in the three pilot countries. This tool can be used by other LMICs to map their efforts toward addressing NCD goals and defining priorities.

    • Health Behavior and Risk
      1. BACKGROUND: To determine daily flossing prevalence among adults 30+ years in the United States, by demographic and risk factors for periodontal disease, including current tobacco use and diabetes. METHODS: Data from the 2011-2014 National Health and Nutrition Examination Survey were analyzed for 8,356 adults. Flossing prevalence was estimated. Logistic regression analysis examined the association between daily flossing and demographic and risk factors for periodontal diseases. RESULTS: Daily flossing among adults was 31.6% (standard error [SE] = 0.8). There were significant differences among the categories of flossing according to age, sex, race-Hispanic origin, poverty status, education, current tobacco use, and diabetes status. In adjusted analyses, current tobacco users (OR: 0.82; 95% CI 0.68, 0.99) had lower odds of daily flossing than non-tobacco users; there was no significant difference between adults with and without diabetes (OR 0.75; 95% CI 0.52, 1.08). CONCLUSION: Approximately one third of US adults reported that they floss daily. Daily flossing was higher among women, those with higher income, and non-Hispanic Asian and Hispanic adults, but lower among current tobacco users. This article is protected by copyright. All rights reserved.

      2. LET’s CONNECT community mentorship program for youths with peer social problems: Preliminary findings from a randomized effectiveness trialExternal
        King CA, Gipson PY, Arango A, Foster CE, Clark M, Ghaziuddin N, Stone D.
        J Community Psychol. 2018 .

        This study examined the effectiveness of LET’s CONNECT (LC), a community mentorship program for youths who report peer social problems, which is based on a positive youth development framework. Participants were 218 youths (66.5% girls), aged 12 to 15 years, who were recruited from an urban medical emergency department and screened positive for bullying victimization, bullying perpetration, and/or low social connectedness. Youths were randomized to LC (n = 106) or the control condition (n = 112). Six-month outcomes were assessed with self-report measures of youth social connectedness, community connectedness, thwarted belongingness, depression, self-esteem, and suicidal ideation. LC was associated with a significant increase in only one of these outcomes, social connectedness (effect size = 0.4). It was associated consistently with trend-level positive changes for thwarted belongingness (decreased), depression (decreased), community connectedness, and self-esteem (effect sizes = 0.2). There was no effect on suicidal ideation (effect size = 0.0), and although not a primary outcome, eight youths in the LC condition and seven youths in the control condition engaged in suicidal behavior between baseline and follow-up. Although LC effect sizes are consistent with those from previous studies of community mentorship, there were multiple challenges to LC implementation that affected dosage and intervention fidelity, and that may account for the lack of stronger positive effects.

    • Health Disparities

      1. Unequal interactions: Examining the role of patient-centered care in reducing inequitable diffusion of a medical innovation, the human papillomavirus (HPV) vaccineExternal
        Fenton AT, Elliott MN, Schwebel DC, Berkowitz Z, Liddon NC, Tortolero SR, Cuccaro PM, Davies SL, Schuster MA.
        Soc Sci Med. 2018 Mar;200:238-248.

        RATIONALE: Studies of inequities in diffusion of medical innovations rarely consider the role of patient-centered care. OBJECTIVE: We used uptake of the human papillomavirus (HPV) vaccine shortly after its licensing to explore the role of patient-centered care. METHODS: Using a longitudinal multi-site survey of US parents and adolescents, we assessed whether patient-centered care ratings might shape racial/ethnic and socioeconomic gaps at two decision points in the HPV vaccination process: (1) Whether a medical provider recommends the vaccine and (2) whether a parent decides to vaccinate. RESULTS: We did not find evidence that the association of patient-centeredness with vaccination varies by parent education. In contrast, parent ratings of providers’ patient-centeredness were significantly associated with racial/ethnic disparities in parents’ reports of receiving a HPV vaccine recommendation from a provider: Among parents who rate patient-centered care as low, white parents’ odds of receiving such a recommendation are 2.6 times higher than black parents’ odds, but the racial/ethnic gap nearly disappears when parents report high patient-centeredness. Moderated mediation analyses suggest that patient-centeredness is a major contributor underlying vaccination uptake disparities: Among parents who report low patient-centeredness, white parents’ odds of vaccinating their child are 8.1 times higher than black parents’ odds, while both groups are equally likely to vaccinate when patient-centeredness is high. CONCLUSION: The results indicate that patient-centered care, which has been a relatively understudied factor in the unequal diffusion of medical innovations, deserves more attention. Efforts to raise HPV vaccination rates should explore why certain patient groups may be less likely to receive recommendations and should support providers to consistently inform all patient groups about vaccination.

    • Health Economics
      1. OBJECTIVES: Infants born to mothers who are hepatitis B surface antigen (HBsAg) positive are at risk for perinatal hepatitis B infection. As prevention, these infants receive a series of 3 or 4 doses of hepatitis B vaccine starting at birth and postvaccination serologic testing. Infants with antibody levels <10 mIU/mL are considered vaccine nonresponders and should be revaccinated. The objective of this cost analysis was to assess a single-dose revaccination strategy among infant nonresponders. METHODS: We used a decision analytic tree to compare the costs of a single-dose revaccination strategy with the costs of a 3-dose revaccination strategy. The analysis consisted of 3 epidemiologic scenarios that varied levels of previous protection among infants indicated for revaccination. We assumed health outcomes in each strategy were the same, and we evaluated costs from the societal perspective using 2016 US dollars. We conducted sensitivity analyses on key variables, including the minimum required efficacy of a single revaccination dose. RESULTS: In all analyses, the single-dose revaccination strategy was a lower-cost option than the 3-dose revaccination strategy. Under the assumption that all revaccination visits were previously unscheduled, single-dose revaccination reduced the cost per infant by $119.81 to $155.72 (depending on the scenario). Across all scenarios, the most conservative estimate for the threshold efficacy (the minimum efficacy required to result in a lower-cost option) value of single-dose revaccination was 67%. CONCLUSIONS: For infants who were born to HBsAg-positive mothers and who were not responding to the initial vaccine series, a single-dose revaccination strategy, compared with a 3-dose revaccination strategy, reduced costs across several scenarios. These results helped inform the Advisory Committee on Immunization Practices’ vote in February 2017 to recommend single-dose revaccination.

      2. Annual wellness visit (AWV) was introduced for Medicare patients in 2011 to help patients stay healthy. The object of this study is to assess whether AWV have an impact on the use of other preventive services in the eligible population. Medicare claims for the full sample of beneficiaries who were continuously enrolled in fee-for-service Medicare in 2013 and 2014 were analyzed. The association between AWV and three other preventive services (depression screening [DPS], influenza virus vaccine [IVV], and sexually transmitted infection screening [STI]) were assessed. In addition, the utilization pattern of these three preventative services at AWV visit by the calendar month when beneficiaries had an AWV service was also assessed. Of 28 million eligible Medicare beneficiaries, 16.0% had AWV in 2014. The patients who had AWV had a significantly higher percentage of three preventive services than those who had no AWV: 63.8% vs. 41.6% in IVV, 4.9% vs. 0.5% in DPS, and 2.3% vs. 1.8% in STI. The percentages of beneficiaries who received IVV during an AWV visit varied significantly by calendar month: from < 0.1% in June to 36.8% in October. AWV is associated with increased use of other preventive services. In addition, the association is significantly affected by type of other preventive services that may be highly related with seasonal factors.

    • Healthcare Associated Infections

      1. Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the Organ Transplant Infection Prevention and Detection Study: A multi-year, multicenter prospective cohort studyExternal
        Avery RK, Silveira FP, Benedict K, Cleveland AA, Kauffman CA, Schuster MG, Dubberke ER, Husain S, Paterson DL, Chiller T, Pappas P.
        Transpl Infect Dis. 2018 Mar 7:e12877.

        BACKGROUND: Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these 2 groups. METHODS: Patients were followed up for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. RESULTS: The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (P = .0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9%) of HCT recipients with CMV infection, respectively (P = .087). Median time to CMV infection was longer in the lung transplant group (236 vs 40 days, P < .0001), likely reflecting the effects of prophylaxis vs preemptive therapy. Total IgG levels of < 350 mg/dL in lung recipients and graft vs host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (P = .008), although duration of viremia was not significantly different between the 2 groups. CMV infection was not associated with reduced overall survival in either group. CONCLUSIONS: Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era.

      2. Risk of subsequent sepsis within 90 days after a hospital stay by type of antibiotic exposureExternal
        Baggs J, Jernigan JA, Halpin AL, Epstein L, Hatfield KM, McDonald LC.
        Clin Infect Dis. 2018 Mar 19;66(7):1004-1012.

        Background: We examined the risk of sepsis within 90 days after discharge from a previous hospital stay by type of antibiotic received during the previous stay. Methods: We retrospectively identified a cohort of hospitalized patients from the Truven Health MarketScan Hospital Drug Database. We examined the association between the use of certain antibiotics during the initial hospital stay, determined a priori, and the risk of postdischarge sepsis controlling for potential confounding factors in a multivariable logistic regression model. Our primary exposure was receipt of antibiotics more strongly associated with clinically important microbiome disruption. Our primary outcome was a hospital stay within 90 days of the index stay that included an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis of severe sepsis (ICD-9-CM code 995.92) or septic shock (785.52). Results: Among 516 hospitals, we randomly selected a single stay for eligible patients. In 0.17% of these patients, severe sepsis/septic shock developed within 90 days after discharge. The risk of sepsis associated with exposure to our high-risk antibiotics was 65% higher than in those without antibiotic exposure. Conclusions: Our study identified an increased risk of sepsis within 90 days of discharge among patients with exposure to high-risk antibiotics or increased quantities of antibiotics during hospitalization. Given that a significant proportion of inpatient antimicrobial use may be unnecessary, this study builds on previous evidence suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, Clostridium difficile infection, and other adverse effects, but may also reduce unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

      3. Carbapenemase-producing organisms: A global scourgeExternal
        Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, Westblade LF.
        Clin Infect Dis. 2018 Apr 3;66(8):1290-1297.

        The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid-based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control.

      4. Carbapenem-nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012-2015External
        Bulens SN, Yi SH, Walters MS, Jacob JT, Bower C, Reno J, Wilson L, Vaeth E, Bamberg W, Janelle SJ, Lynfield R, Vagnone PS, Shaw K, Kainer M, Muleta D, Mounsey J, Dumyati G, Concannon C, Beldavs Z, Cassidy PM, Phipps EC, Kenslow N, Hancock EB, Kallen AJ.
        Emerg Infect Dis. 2018 Apr;24(4):727-734.

        In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

      5. Genome sequence of a multidrug-resistant Candida haemulonii isolate from a patient with chronic leg ulcers in IsraelExternal
        Chow NA, Gade L, Batra D, Rowe LA, Juieng P, Ben-Ami R, Loparev VN, Litvintseva AP.
        Genome Announc. 2018 Apr 12;6(15).

        Candida haemulonii is an emerging multidrug-resistant yeast that can cause invasive candidiasis. Here, we report the first genome sequence of C. haemulonii (isolate B11899) generated using PacBio sequencing technology. The estimated genome size was 13.3 Mb, with a GC content of 45.19%.

      6. Racial disparities in invasive methicillin-resistant Staphylococcus aureus infections, 2005-2014External
        Gualandi N, Mu Y, Bamberg WM, Dumyati G, Harrison LH, Lesher L, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, McDonald M, See I.
        Clin Infect Dis. 2018 Apr 5.

        Background: Despite substantial attention to the individual topics, little is known about the relationship between racial disparities and antimicrobial-resistant and/or healthcare-associated infection trends, such as infections due to methicillin-resistant Staphylococcus aureus (MRSA). Methods: We analyzed CDC’s Emerging Infections Program 2005-2014 surveillance data (9 U.S. states) to determine whether reductions in invasive MRSA incidence (isolated from normally sterile body sites) affected racial disparities in rates. Case classification included hospital-onset (HO, culture >3 days after admission), healthcare-associated community onset (HACO, culture </=3 days after admission and dialysis, hospitalization, surgery, or long term care residence within 1 year prior), or community-associated (CA, all others). Negative binomial regression models evaluated adjusted rate ratio (aRR) of MRSA in black patients (versus in white patients) controlling for age, sex, and temporal trends. Results: From 2005-2014, invasive HO and HACO (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO (aRR: 3.20; 95% confidence interval [CI]: 2.35-4.35), HACO (aRR: 3.84; 95% CI: 2.94-5.01), and CA (aRR: 2.78; 95% CI: 2.30-3.37) MRSA. Limiting the analysis to chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA rates among blacks (aRR: 1.83: 95% CI: 1.72-1.96) even though invasive MRSA rates among dialysis patients decreased during 2005-2014. These racial differences did not change over time. Conclusions: Previous reductions in healthcare-associated MRSA infections have not affected racial disparities in MRSA rates. Improved understanding of the underlying causes of these differences is needed to develop effective prevention interventions that reduce racial disparities in MRSA infections.

    • Immunity and Immunization

      1. Factors associated with the pricing of childhood vaccines in the U.S. public sectorExternal
        Chen W, Messonnier M, Zhou F.
        Health Econ. 2018 Feb;27(2):252-265.

        Vaccine purchase cost has grown substantially over the last few decades. A closer look at vaccine prices reveals that not all vaccines shared the same increasing pattern. Various factors, such as vaccine attributes, competition, and supply shortages, could relate to price changes. In this study, we examined whether a variety of factors influenced the prices of noninfluenza childhood vaccines purchased in the public sector from 1996 to 2014. The association differed among price-capped vaccines and combination vaccines. There was an increasing time trend in real prices for non-price-capped vaccines, which was mostly offset by the effect of market longevity. The effect of competition in lowering prices was more pronounced among non-price-capped vaccines when manufacturer and vaccine component fixed effects were excluded. Supply shortage, manufacturer name change, and number of vaccine doses in series showed no effect. The results may help policy makers better understand price behaviors and make more informed decisions in vaccine planning and financing.

      2. BACKGROUND: Oral polio vaccine (OPV) containing attenuated serotype 2 polioviruses was globally withdrawn in 2016, and bivalent OPV (bOPV) containing attenuated serotype 1 and 3 polioviruses needs to be withdrawn after the certification of eradication of all wild polioviruses to eliminate future risks from vaccine-derived polioviruses (VDPVs). To minimize risks from VDPVs, the planning and implementation of bOPV withdrawal should build on the experience with withdrawing OPV containing serotype 2 polioviruses while taking into account similarities and differences between the three poliovirus serotypes. METHODS: We explored the risks from (i) a failure to synchronize OPV cessation and (ii) unauthorized post-cessation OPV use for serotypes 1 and 3 in the context of globally-coordinated future bOPV cessation and compared the results to similar analyses for serotype 2 OPV cessation. RESULTS: While the risks associated with a failure to synchronize cessation and unauthorized post-cessation OPV use appear to be substantially lower for serotype 3 polioviruses than for serotype 2 polioviruses, the risks for serotype 1 appear similar to those for serotype 2. Increasing population immunity to serotype 1 and 3 poliovirus transmission using pre-cessation bOPV supplemental immunization activities and inactivated poliovirus vaccine in routine immunization reduces the risks of circulating VDPVs associated with non-synchronized cessation or unauthorized OPV use. CONCLUSIONS: The Global Polio Eradication Initiative should synchronize global bOPV cessation during a similar window of time as occurred for the global cessation of OPV containing serotype 2 polioviruses and should rigorously verify the absence of bOPV in immunization systems after its cessation.

      3. Human papillomavirus vaccine effectiveness against incident genital warts among female health-plan enrollees, United StatesExternal
        Hariri S, Schuler MS, Naleway AL, Daley MF, Weinmann S, Crane B, Newcomer SR, Tolsma D, Markowitz LE.
        Am J Epidemiol. 2018 Feb 1;187(2):298-305.

        We examined the effectiveness of human papillomavirus vaccination by dose number and spacing against incident genital warts in a cohort of 64,517 female health-plan enrollees in the United States during 2006-2012. Eligible recipients were classified into groups by regimen: 0, 1, 2 (<6 months apart), 2 (>/=6 months apart), or 3 doses. They were followed until a genital wart diagnosis, loss to follow-up, or the end of study. Propensity score weights were used to balance baseline differences across groups. To account for latent genital warts before vaccination, we applied 6- and 12-month buffer periods from last and first vaccine dose, respectively. Incidence rates and hazard ratios were calculated using Poisson regression and Cox models. The propensity score-weighted incidence rate per 100,000 person-years was 762 among unvaccinated participants. Using 6- and 12-month buffer periods, respectively, incidence rates were 641 and 257 for 1 dose, 760 and 577 for the 2-dose (<6-month interval) regimen, 313 and 194 for the 2-dose (>/=6-month interval) regimen, and 199 and 162 among 3-dose vaccinees; vaccine effectiveness was 68% and 76% for the 2-dose (>/=6-month interval) regimen and 77% and 80% in 3-dose vaccinees compared with unvaccinated participants. Vaccine effectiveness was not significant among vaccinees receiving 1-dose and 2-dose (<6-month interval) regimens compared with unvaccinated participants. Our findings contribute to a better understanding of the real-world effectiveness of HPV vaccination.

      4. Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland TanzaniaExternal
        Jani B, Hokororo A, McHomvu J, Cortese MM, Kamugisha C, Mujuni D, Kallovya D, Parashar UD, Mwenda JM, Lyimo D, Materu A, Omari KF, Waziri M, Laswai T, Juma H, Mlay J, Dogani J, Stephen E, Seugendo M, Nkumbi U, Lyakurwa A, Matojo A, Bendera E, Senyota J, Msingwa V, Fungo Y, Michael F, Mpamba A, Chambo A, Cholobi H, Lyamuya F, Chami I, McHome E, Mshana AM, Mushi E, Mariki U, Chard R, Tuju D, Ambokile N, Lukwale F, Kyessi F, Khamis A, Michael I, Macha D, Saguti A.
        Vaccine. 2018 Apr 11.

        BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Tanzania in January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10weeks. We used the sentinel hospital rotavirus surveillance system to examine the rotavirus detection rate before and after vaccine introduction and estimate vaccine effectiveness. METHODS: Before vaccine introduction, rotavirus surveillance was established at two mainland hospitals; children admitted for acute diarrhea were eligible for enrollment and stools were tested for rotavirus antigen. We compared the rotavirus positivity rate in the pre-vaccine period (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post-introduction years, 2014-2015. In 2013, surveillance was established at 9 additional hospitals. We examined rotavirus positivity among infants at these sites for 2014-2015. We obtained vaccine records and calculated vaccine effectiveness at 3 sites using case-test-negative control design. RESULTS: At Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre-vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22-0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18% (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were similar among children <5years. At the new sites, the median site rotavirus positivity rate among infants was 26% in 2014 (range 19-44%) and 18% in 2015 (range 16-33%). The effectiveness of >/=1 RV1 dose against rotavirus hospitalization among children 5-23months was 53% (95% CI: -14, 81), and 66% (95% CI: 9-87) against hospitalization with intravenous rehydration. Following introduction, peak rotavirus activity occurred later in the year and appeared more concentrated in time. CONCLUSION: Rotavirus surveillance data from Tanzania indicate that the rotavirus positivity rate among children hospitalized with diarrhea that were enrolled was substantially reduced after vaccine introduction. Low positivity rates among infants were detected at hospitals across the country. Overall, the data support that rotavirus vaccine has been successfully introduced and is effective in Tanzanian children.

      5. BACKGROUND: Human papillomavirus (HPV) vaccination has been routinely recommended at age 11-12years in the United States for females since 2006 and males since 2011. Coverage can be estimated using self/parent-reported HPV vaccination collected in the National Health and Nutrition Examination Survey (NHANES) for a wider age range than other national surveys. We assessed vaccination coverage in 2015-2016, temporal trends by age, and the validity of self/parent-reported vaccination status. METHODS: Participants aged 9-59years completed an interview collecting demographic and vaccination information. Weighted coverage was estimated for two-year NHANES cycles by age group for 2007-2008 to 2015-2016 for females (N=14318) and 2011-2012 to 2015-2016 for males (N=7847). Temporal trends in coverage were assessed from 2007-2008 to 2011-2012 for females and from 2011-2012 to 2015-2016 for both sexes. Sensitivity and specificity of self/parent-reported vaccination were assessed using provider-verified vaccination records from a pilot study in 14-29year-olds. RESULTS: In 2015-2016, >/=1 dose coverage among females was highest in 14-19 (54.7%) and 20-24 (56.0%) year-olds and lower in successively older age groups. Among males, >/=1 dose coverage was highest in 14-19year-olds (39.5%) and lower at older ages. Coverage was similar in 9-13year-old females and males. Between 2007-2008 and 2011-2012, there were increases among females younger than 30years. Between 2011-2012 and 2015-2016, there were increases among female age groups including 20-39year-olds; male coverage increased among ages 9-13, 14-19, and 20-24years. Self/parent-reported receipt of >/=1 dose had a sensitivity and specificity of 87.0% and 83.3%. Performance was lower for 3 doses. CONCLUSIONS: While overall HPV vaccination coverage remains low, it is higher in females than males, except in 9-13year-olds. There have been increases in coverage among many age groups, but coverage has stalled in younger females. Adequate validity was demonstrated for self/parent-reported vaccination of >/=1 dose, but not 3 doses, in a pilot study.

      6. Incidence and epidemiology of intussusception among children under 2 years of age in Chenzhou and Kaifeng, China, 2009-2013External
        Liu N, Yen C, Huang T, Cui P, Tate JE, Jiang B, Parashar UD, Duan ZJ.
        Vaccine. 2018 Feb 10.

        INTRODUCTION: In China, rotavirus is the leading cause of diarrhea hospitalizations among children aged <5years. A locally manufactured rotavirus vaccine is available for private market use, but little is known about its coverage. Given the impending availability of newer rotavirus vaccines, we evaluated intussusception rates among children aged <2years to better understand intussusception epidemiology for future vaccine safety monitoring. METHODS: We conducted a retrospective review at 4 hospitals in Chenzhou City of Hunan Province and Kaifeng City of Henan Province. We identified intussusception cases admitted during 2009-2013 by reviewing medical records with the ICD-10 discharge code for intussusception and extracting demographic and clinical information from the electronic clinical record systems. RESULTS: During 2009-2013, 1715 intussusception hospitalizations among 1,487,215 children aged <2years occurred in both cities. The average annual intussusception hospitalization incidence was 112.9 per 100,000 children aged <2years (181.8 per 100,000 children <1year; 56 per 100,000 children 1 to <2years). Intussusception incidence was low among infants aged <3months and peaked at age 6-8months. No clear seasonality was observed. Ultrasound was used to diagnose 95.9% of cases. Enema reduction was performed in 80% cases; 25% of cases in Chenzhou and 16% in Kaifeng required surgical intervention. No deaths were reported. The median time between symptom onset and admission was 1day. CONCLUSIONS: This study provides information on intussusception incidence and epidemiology in two cities of China during 2009-2013. Monitoring intussusception rates in this population will be important in the post-rotavirus vaccine era.

      7. Trends in diarrhea hospitalizations among infants at three hospitals in Tanzania before and after rotavirus vaccine introductionExternal
        Lyamuya F, Michael F, Jani B, Fungo Y, Chambo A, Chami I, Bulali R, Mpamba A, Cholobi H, Kallovya D, Kamugisha C, Mwenda JM, Cortese MM.
        Vaccine. 2018 Apr 11.

        BACKGROUND: The Tanzania Ministry of Health introduced monovalent human rotavirus vaccine in January 2013, to be administered at ages 6 and 10weeks. Data suggest there was high vaccine uptake. We used hospital ward registers from 3 hospitals to examine trends in diarrhea hospitalizations among infants before and after vaccine introduction. METHODS: Ward registers from Dodoma Regional Referral Hospital (Central Tanzania), and two hospitals in Mbeya (Southwest area), Mbeya Zonal Referral Hospital and Mbalizi Hospital, were used to tally admissions for diarrhea among children by age group, month and year. Rotavirus surveillance had started at these hospitals in early 2013; the proportion of infants enrolled and rotavirus-EIA positive were examined by month to determine peak periods of rotavirus disease post-vaccine introduction. RESULTS: Registers were available for 2-4 prevaccine years and 2-3 post introduction years. At Dodoma Regional Referral Hospital, compared with the mean of 2011 and 2012, diarrhea hospitalizations among infants were 26% lower in 2015 and 58% lower in 2016. The diarrhea peak shifted later in the year first by 1 and then by 2-3 months from prevaccine. At the Mbeya hospitals, the number of diarrhea admissions in prevaccine period varied substantially by year. At Mbeya Referral Hospital, diarrhea hospitalizations among infants were lower by 25-37% in 2014 and 11-26% in 2015, while at Mbalizi Hospital, these hospitalizations were 4% lower in 2014 and 14% higher in 2015. Rotavirus testing data demonstrated a lowering of the prevaccine peak, a shift in timing of the peak months and indicated that other diarrheal peaks in post-introduction years were not due to rotavirus. CONCLUSIONS: In this ecological evaluation, total diarrhea hospitalizations among infants were lower (>/=25% lower in >/=1year) following introduction in 2 of 3 hospitals. There are challenges in using ward registers to ascertain possible impact of rotavirus vaccine introduction on trends in hospitalizations for treatment of all diarrheal illness.

      8. Hepatitis A vaccine immune response 22 years after vaccinationExternal
        Mosites E, Gounder P, Snowball M, Morris J, Spradling P, Nelson N, Bulkow L, Bruce M, McMahon B.
        J Med Virol. 2018 Apr 12.

        In the United States, the incidence of hepatitis A virus (HAV) infection has been reduced through universal childhood vaccination. However, the duration of immunogenicity for the hepatitis A vaccine is not known. We report on the 22 year follow-up time point of a cohort of Alaska children who were randomized to three different vaccine schedules: A) 0,1,2 months; B) 0,1,6 months; and C) 0,1,12 months. Among 46 participant available for follow-up, 40 (87%) maintained protective levels of anti-hepatitis A antibody. These results indicate that a supplemental booster dose is not yet necessary at or before the 22-year time point. This article is protected by copyright. All rights reserved.

      9. Distribution of rotavirus genotypes associated with acute diarrhoea in Zimbabwean children less than five years old before and after rotavirus vaccine introductionExternal
        Mukaratirwa A, Berejena C, Nziramasanga P, Ticklay I, Gonah A, Nathoo K, Manangazira P, Mangwanya D, Marembo J, Mwenda JM, Weldegebriel G, Seheri M, Tate JE, Yen C, Parashar U, Mujuru H.
        Vaccine. 2018 Apr 5.

        BACKGROUND: Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. METHODS: Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. RESULTS: During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). CONCLUSION: The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction.

      10. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel AdjuvantExternal
        Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):455-458.

        Hepatitis B (HepB) vaccination is the primary means of preventing infections and complications caused by hepatitis B virus (HBV). On February 21, 2018, the Advisory Committee on Immunization Practices (ACIP) recommended Heplisav-B (HepB-CpG), a yeast-derived vaccine prepared with a novel adjuvant, administered as a 2-dose series (0, 1 month) for use in persons aged >/=18 years. The ACIP Hepatitis Vaccines Work Group conducted a systematic review of the evidence, including data from four randomized controlled trials assessing prevention of HBV infection and six randomized controlled trials assessing adverse events in adults. Seroprotective antibody to hepatitis B surface antigen (anti-HBs) levels were achieved in 90.0%-100.0% of subjects receiving HepB-CpG (Dynavax Technologies Corporation), compared with 70.5%-90.2% of subjects receiving Engerix-B (GlaxoSmithKline Biologicals). The benefits of protection with 2 doses administered over 1 month make HepB-CpG an important option for prevention of HBV.

      11. Review of mathematical models of HSV-2 vaccination: Implications for vaccine developmentExternal
        Spicknall IH, Looker KJ, Gottlieb SL, Chesson HW, Schiffer JT, Elmes J, Boily MC.
        Vaccine. 2018 Apr 3.

        Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study’s model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts. Only eight modelling studies have assessed the potential public health impact of HSV-2 vaccination, with the majority focusing on impact of prophylactic vaccines. The studies showed that even an imperfect prophylactic HSV-2 vaccine could have an important public health impact on HSV-2 incidence, and could also impact HIV indirectly in high HIV prevalence settings. Therapeutic vaccines also may provide public health benefits, though they have been explored less extensively. However, there was substantial variation in predicted population-level impact for both types of vaccine, reflecting differences in assumptions between model scenarios. Importantly, many models did not account for heterogeneity in infection rates such as by age, sex and sexual activity. Future modelling work to inform decisions on HSV vaccine development and implementation should consider cost-effectiveness, account for additional HSV-2 sequelae such as neonatal transmission, and model greater heterogeneity in infection rates between individuals, more realistic vaccine deployment, and more thorough sensitivity and uncertainty analyses.

      12. Evaluation of intussusception after monovalent rotavirus vaccination in AfricaExternal
        Tate JE, Mwenda JM, Armah G, Jani B, Omore R, Ademe A, Mujuru H, Mpabalwani E, Ngwira B, Cortese MM, Mihigo R, Glover-Addy H, Mbaga M, Osawa F, Tadesse A, Mbuwayesango B, Simwaka J, Cunliffe N, Lopman BA, Weldegebriel G, Ansong D, Msuya D, Ogwel B, Karengera T, Manangazira P, Bvulani B, Yen C, Zawaira FR, Narh CT, Mboma L, Saula P, Teshager F, Getachew H, Moeti RM, Eweronu-Laryea C, Parashar UD.
        N Engl J Med. 2018 Apr 19;378(16):1521-1528.

        BACKGROUND: Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. METHODS: Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. RESULTS: Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. CONCLUSIONS: The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).

    • Informatics

      1. The impact of routine data quality assessments on electronic medical record data quality in KenyaExternal
        Muthee V, Bochner AF, Osterman A, Liku N, Akhwale W, Kwach J, Prachi M, Wamicwe J, Odhiambo J, Onyango F, Puttkammer N.
        PLoS One. 2018 ;13(4):e0195362.

        BACKGROUND: Routine Data Quality Assessments (RDQAs) were developed to measure and improve facility-level electronic medical record (EMR) data quality. We assessed if RDQAs were associated with improvements in data quality in KenyaEMR, an HIV care and treatment EMR used at 341 facilities in Kenya. METHODS: RDQAs assess data quality by comparing information recorded in paper records to KenyaEMR. RDQAs are conducted during a one-day site visit, where approximately 100 records are randomly selected and 24 data elements are reviewed to assess data completeness and concordance. Results are immediately provided to facility staff and action plans are developed for data quality improvement. For facilities that had received more than one RDQA (baseline and follow-up), we used generalized estimating equation models to determine if data completeness or concordance improved from the baseline to the follow-up RDQAs. RESULTS: 27 facilities received two RDQAs and were included in the analysis, with 2369 and 2355 records reviewed from baseline and follow-up RDQAs, respectively. The frequency of missing data in KenyaEMR declined from the baseline (31% missing) to the follow-up (13% missing) RDQAs. After adjusting for facility characteristics, records from follow-up RDQAs had 0.43-times the risk (95% CI: 0.32-0.58) of having at least one missing value among nine required data elements compared to records from baseline RDQAs. Using a scale with one point awarded for each of 20 data elements with concordant values in paper records and KenyaEMR, we found that data concordance improved from baseline (11.9/20) to follow-up (13.6/20) RDQAs, with the mean concordance score increasing by 1.79 (95% CI: 0.25-3.33). CONCLUSIONS: This manuscript demonstrates that RDQAs can be implemented on a large scale and used to identify EMR data quality problems. RDQAs were associated with meaningful improvements in data quality and could be adapted for implementation in other settings.

    • Injury and Violence

      1. Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific dataExternal
        Devries K, Knight L, Petzold M, Merrill KG, Maxwell L, Williams A, Cappa C, Chan KL, Garcia-Moreno C, Hollis N, Kress H, Peterman A, Walsh SD, Kishor S, Guedes A, Bott S, Butron Riveros BC, Watts C, Abrahams N.
        BMJ Paediatr Open. 2018 ;2(1):e000180.

        Objective: The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally. Design: We used random effects meta-regression to estimate prevalence. Estimates were adjusted for relevant quality covariates, variation in definitions of violence and weighted by region-specific, age-specific and sex-specific population data to ensure estimates reflect country population structures. Data sources: Secondary data from 600 population or school-based representative datasets and 43 publications obtained via systematic literature review, representing 13 830 estimates from 171 countries. Eligibility criteria for selecting studies: Estimates for recent violence against children aged 0-19 were included. Results: The most common perpetrators of physical and emotional violence for both boys and girls across a range of ages are household members, with prevalence often surpassing 50%, followed by student peers. Children reported experiencing more emotional than physical violence from both household members and students. The most common perpetrators of sexual violence against girls aged 15-19 years are intimate partners; however, few data on other perpetrators of sexual violence against children are systematically collected internationally. Few age-specific and sex-specific data are available on violence perpetration by schoolteachers; however, existing data indicate high prevalence of physical violence from teachers towards students. Data from other authority figures, strangers, siblings and other adults are limited, as are data on neglect of children. Conclusions: Without further investment in data generation on violence exposure from multiple perpetrators for boys and girls of all ages, progress towards Sustainable Development Goals 4, 5 and 16 may be slow. Despite data gaps, evidence shows violence from household members, peers in school and for girls, from intimate partners, should be prioritised for prevention. Trial registration number: PROSPERO 2015: CRD42015024315.

      2. Bullying is often ongoing during middle- and high-school. However, limited research has examined how cumulative experiences of victimization, perpetration, and bystander behavior impact adolescent behavioral and mental health and academic achievement outcomes at the end of high school. The current study used a sample of over 8000 middle- and high-school students (51% female; mean age 12.5 years) from the Rural Adaptation Project in North Carolina to investigate how cumulative experiences as a bullying victim and perpetrator over 5 years, and cumulative experiences of bystander behavior over 2 years impacted students’ aggression, internalizing symptoms, academic achievement, self-esteem, and future optimism. Following multiple imputation, analysis included a Structural Equation Model with excellent model fit. Findings indicate that cumulative bullying victimization was positively associated with aggression and internalizing symptoms, and negatively associated with self-esteem and future optimism. Cumulative bullying perpetration was positively associated with aggression and negatively associated with future optimism. Cumulative negative bystander behavior was positively associated with aggression and internalizing symptoms and negatively associated with academic achievement and future optimism. Cumulative prosocial bystander behavior was positively associated with internalizing symptoms, academic achievement, self-esteem, and future optimism. This integrative model brings together bullying dynamics to provide a comprehensive picture of implications for adolescent behavioral and mental health and academic achievement.

      3. Introduction: As more states legalize medical/recreational marijuana use, it is important to determine if state motor-vehicle surveillance systems can effectively monitor and track driving under the influence (DUI) of marijuana. This study assessed Colorado’s Department of Revenue motor-vehicle crash data system, Electronic Accident Reporting System (EARS), to monitor non-fatal crashes involving driving under the influence (DUI) of marijuana. Methods: Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to assess EARS’ usefulness, flexibility, timeliness, simplicity, acceptability, and data quality. We assessed system components, interviewed key stakeholders, and analyzed completeness of Colorado statewide 2014 motor-vehicle crash records. Results: EARS contains timely and complete data, but does not effectively monitor non-fatal motor-vehicle crashes related to DUI of marijuana. Information on biological sample type collected from drivers and toxicology results were not recorded into EARS; however, EARS is a flexible system that can incorporate new data without increasing surveillance system burden. Conclusions: States, including Colorado, could consider standardization of drug testing and mandatory reporting policies for drivers involved in motor-vehicle crashes and proactively address the narrow window of time for sample collection to improve DUI of marijuana surveillance. Practical applications: The evaluation of state motor-vehicle crash systems’ ability to capture crashes involving drug impaired driving (DUID) is a critical first step for identifying frequency and risk factors for crashes related to DUID.

      4. Suicidal ideation and attempts among students in grades 8, 10, and 12 – Utah, 2015External
        Zwald ML, Annor FB, Wilkinson A, Friedrichs M, Fondario A, Dunn AC, Nakashima A, Gilbert LK, Ivey-Stephenson A.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):451-454.

        Suicidal thoughts and behaviors among youths are important public health concerns in Utah, where the suicide rate among youths consistently exceeds the national rate and has been increasing for nearly a decade (1). In March 2017, CDC was invited to assist the Utah Department of Health (UDOH) with an investigation to characterize the epidemiology of fatal and nonfatal suicidal behaviors and identify risk and protective factors associated with these behaviors, among youths aged 10-17 years. This report presents findings related to nonfatal suicidal behaviors among Utah youths. To examine the prevalence of suicidal ideation and attempts among Utah youths and evaluate risk and protective factors, data from the 2015 Utah Prevention Needs Assessment survey were analyzed. Among 27,329 respondents in grades 8, 10, and 12, 19.6% reported suicidal ideation and 8.2% reported suicide attempts in the preceding 12 months. Significant risk factors for suicidal ideation and attempts included being bullied, illegal substance or tobacco use in the previous month, and psychological distress. A significant protective factor for suicidal ideation and attempts was a supportive family environment. UDOH, local health departments, and other stakeholders are using these findings to develop tailored suicide prevention strategies that address multiple risk and protective factors for suicidal ideation and attempts. Resources such as CDC’s Preventing Suicide: A Technical Package of Policy, Programs, and Practices (2) can help states and communities identify strategies and approaches using the best available evidence to prevent suicide, which include tailored strategies for youths.

    • Laboratory Sciences

      1. Taxonomy of the order Mononegavirales: update 2018External
        Amarasinghe GK, Arechiga Ceballos NG, Banyard AC, Basler CF, Bavari S, Bennett AJ, Blasdell KR, Briese T, Bukreyev A, Cai Y, Calisher CH, Campos Lawson C, Chandran K, Chapman CA, Chiu CY, Choi KS, Collins PL, Dietzgen RG, Dolja VV, Dolnik O, Domier LL, Durrwald R, Dye JM, Easton AJ, Ebihara H, Echevarria JE, Fooks AR, Formenty PB, Fouchier RA, Freuling CM, Ghedin E, Goldberg TL, Hewson R, Horie M, Hyndman TH, Jiang D, Kityo R, Kobinger GP, Kondo H, Koonin EV, Krupovic M, Kurath G, Lamb RA, Lee B, Leroy EM, Maes P, Maisner A, Marston DA, Mor SK, Muller T, Muhlberger E, Ramirez VM, Netesov SV, Ng TF, Nowotny N, Palacios G, Patterson JL, Paweska JT, Payne SL, Prieto K, Rima BK, Rota P, Rubbenstroth D, Schwemmle M, Siddell S, Smither SJ, Song Q, Song T, Stenglein MD, Stone DM, Takada A, Tesh RB, Thomazelli LM, Tomonaga K, Tordo N, Towner JS, Vasilakis N, Vazquez-Moron S, Verdugo C, Volchkov VE, Wahl V, Walker PJ, Wang D, Wang LF, Wellehan JF, Wiley MR, Whitfield AE, Wolf YI, Ye G, Zhang YZ, Kuhn JH.
        Arch Virol. 2018 Apr 11.

        In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

      2. Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm formsExternal
        Hashemi MM, Rovig J, Holden BS, Taylor MF, Weber S, Wilson J, Hilton B, Zaugg AL, Ellis SW, Yost CD, Finnegan PM, Kistler CK, Berkow EL, Deng S, Lockhart SR, Peterson M, Savage PB.
        J Antimicrob Chemother. 2018 Apr 4.

        Background: Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals. Objectives: Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants. Materials and methods: A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins. Results: Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues. Conclusions: Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi.

      3. 1. Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. 2. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to an aerosol generated from 4,4′-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 and 24 h post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to the protein content of the cellular fraction of the lavage fluid. 3. Following MDI aerosol exposure, expression of the number of proteins with immunological or xenobiotic metabolism relevance is increased, including endoplasmin, cytochrome P450 and argininosuccinate synthase. Western blot analysis indicated MDI-conjugated protein in the lavage fluid, which was identified as serum albumin. 4. Tandem mass spectrometry analysis of MDI-albumin revealed MDI conjugation occurs at a dilysine motif at Lys525, as well as at a glutamine-lysine motif at Lys414, in good agreement with previously published in vitro data on diisocyanate-conjugated serum albumin.

      4. Yellow fever (YF) is a reemerging public health threat with frequent outbreaks prompting large vaccination campaigns in endemic regions of Africa and South America. Specific detection of vaccine-related adverse events is resource-intensive, time-consuming and difficult to achieve during an outbreak. To address this, we have developed a highly transferable, rapid yellow fever virus (YFV) vaccine-specific real-time RT-PCR assay that distinguishes vaccine from wild-type lineages. The assay utilizes a specific hydrolysis probe that includes locked nucleic acids to enhance specific discrimination of the YFV 17D vaccine strain genome. Promisingly, sensitivity and specificity analyses reveal this assay to be highly specific to vaccine strain(s) when tested on clinical samples and YFV cell culture isolates of global origin. Taken together, our data suggest the utility of this assay for use in laboratories of varied capacity for the identification and differentiation of vaccine-related adverse events from wild-type infections of both African and South American origin.

      5. Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometryExternal
        Kuklenyik Z, Jones JI, Gardner MS, Schieltz DM, Parks BA, Toth CA, Rees JC, Andrews ML, Carter K, Lehtikoski AK, McWilliams LG, Williamson YM, Bierbaum KP, Pirkle JL, Barr JR.
        PLoS One. 2018 ;13(4):e0194797.

        Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples.

      6. INTRODUCTION: The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. METHODS: Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for </= 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA). RESULTS: Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. CONCLUSIONS: Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

      7. Aspergillus fumigatus viability drives allergic responses to inhaled conidiaExternal
        Nayak AP, Croston TL, Lemons AR, Goldsmith WT, Marshall NB, Kashon ML, Germolec DR, Beezhold DH, Green BJ.
        Ann Allergy Asthma Immunol. 2018 Apr 13.

        BACKGROUND: Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. OBJECTIVE: A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. METHODS: Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. RESULTS: Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-gamma (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. CONCLUSION: Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease.

      8. Extensive T cell cross-reactivity between diverse seasonal influenza strains in the ferret modelExternal
        Reber AJ, Music N, Kim JH, Gansebom S, Chen J, York I.
        Sci Rep. 2018 Apr 17;8(1):6112.

        Influenza virus causes widespread, yearly epidemics by accumulating surface protein mutations to escape neutralizing antibodies established from prior exposure. In contrast to antibody epitopes, T cell mediated immunity targets influenza epitopes that are more highly conserved and have potential for cross-protection. The extent of T cell cross-reactivity between a diverse array of contemporary and historical influenza strains was investigated in ferrets challenged with 2009 pandemic H1N1 influenza or the seasonal H3N2 strain, A/Perth/16/2009. Post-challenge cell-mediated immune responses demonstrated extensive cross-reactivity with a wide variety of contemporary and historical influenza A strains as well as influenza B. Responses in peripheral blood were undetectable by 36d post-challenge, but cross-reactivity persisted in spleen. The strongest responses targeted peptides from the NP protein and demonstrated cross-reactivity in both the CD4+ and CD8+ T cell populations. Cross-reactive CD4+ T cells also targeted HA and NA epitopes, while cross-reactive CD8+ T cells targeted internal M1, NS2, and PA. T cell epitopes demonstrated extensive cross-reactivity between diverse influenza strains in outbred animals, with NP implicated as a significant antigenic target demonstrating extensive cross-reactivity for both CD4+ and CD8+ T cells.

      9. Paradox of serial interferon-gamma release assays: variability width more important than specificity sizeExternal
        Stout JE, Belknap R, Wu YJ, Ho CS.
        Int J Tuberc Lung Dis. 2018 May 1;22(5):518-523.

        SETTING: Serial screening for latent tuberculous infection (LTBI) is commonly performed in certain populations, such as health care workers. The high apparent conversion rate in some studies of interferon-gamma release assays is puzzling given the claimed high specificity of these tests. OBJECTIVE: To understand how test-retest variability, specificity, and underlying LTBI prevalence affect observed outcomes of repeated testing for LTBI. DESIGN: Mathematical model assuming constant test sensitivity and specificity over time and no new infections. RESULTS: Test-retest variability had a large effect on the observed proportion of conversions (initial negative test, followed by a positive test) and reversions (initial positive test, followed by a negative test). For example, a test with 70% specificity and 5% test-retest variability would be associated with a conversion rate of 3.7% and a reversion rate of 7.7%, while a test with 95% specificity but 10% test-retest variability would be associated with a conversion rate of 5.5% and a reversion rate of 57%, assuming that both tests are 80% sensitive and underlying LTBI prevalence was 5%. CONCLUSION: Test-retest variability is a key parameter that should be reported for tests used for serial screening for LTBI. Reducing test-retest variability can reduce false-positive and false-negative results.

      10. Spatial and temporal dynamics of a pulsed spark microplasma used for aerosol analysisExternal
        Zheng L, Kulkarni P, Diwakar P.
        Spectrochimica Acta – Part B Atomic Spectroscopy. 2018 ;144:55-62.

        The spatial and temporal dynamics of a pulsed, electrical spark microplasma used for spectrochemical analysis of aerosols was investigated. The spark discharge was generated by applying a high voltage pulse between a coaxial anode and cathode. Aerosol particles of black carbon were collected on the cathode for 2 min, following which the pulsed microplasma was introduced, leading to ablation and atomization of the collected particles. The space- and time-resolved emission spectra showed that the atomic emission signal from the carbon species originated from the region close to the cathode surface during the early evolution of the microplasma. The C I and C II atomic emission reached peak intensities at 11 and 6 micros delay time, respectively. Peak emission intensities occurred between 0.5-1.3 mm above the cathode surface. The average excitation temperature and the electron number density of the spark microplasma were estimated to be 23,000 K, and 1.6 x 1017 cm-3, respectively. The effects of pulse energy on the excitation temperature and electron density were also investigated. The results provide insights into the dynamics of the pulsed spark microplasma and are helpful in optimizing elemental analysis of aerosols using this technique.

      11. The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfateExternal
        Zucki F, Morata TC, Duarte JL, Ferreira MC, Salgado MH, Alvarenga KF.
        Braz J Otorhinolaryngol. 2018 Mar – Apr;84(2):150-158.

        INTRODUCTION: The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. OBJECTIVE: To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. METHODS: 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. RESULTS: We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r=0.951; p<0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100mg/L), but not for the group exposed to the higher concentration (400mg/L). CONCLUSION: This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect.

    • Maternal and Child Health

      1. Marijuana use during and after pregnancy and association of prenatal use on birth outcomes: A population-based studyExternal
        Ko JY, Tong VT, Bombard JM, Hayes DK, Davy J, Perham-Hester KA.
        Drug Alcohol Depend. 2018 Mar 29;187:72-78.

        BACKGROUND: We sought to describe the correlates of marijuana use during and after pregnancy, and to examine the independent relationship between prenatal marijuana use and infant outcomes. STUDY DESIGN: We used state-specific data from the Pregnancy Risk Assessment Monitoring System (N=9013) to describe correlates of self-reported prenatal and postpartum marijuana use. We estimated differences in mean infant birth weight and gestational age among prenatal marijuana users and nonusers, controlling for relevant covariates (i.e., cigarette smoking). RESULTS: Respectively, 4.2% (95% CI: 3.8-4.7) and 6.8% (95% CI: 6.0-7.7) of women reported using marijuana during and after pregnancy. Compared to nonusers, prenatal marijuana users were more likely to be </=24years; non-Hispanic white, not married, have <12years of education, have Medicaid/IHS/Other insurance, be on WIC during pregnancy, have annual household income <$20,000, cigarette smokers, and alcohol drinkers during pregnancy (p-values<0.05). After adjustment, no differences in gestational age or birthweight were observed. Postpartum users were more likely to smoke cigarettes (48.7% vs. 20.3%), experience postpartum depressive symptoms (14.0% vs. 9.0%), and breastfeed for <8 weeks (34.9% vs. 18.1%). CONCLUSION: Co-use of substances was common among prenatal and postpartum marijuana users. Prenatal marijuana use was not independently associated with lower average birthweight or gestational age. Postpartum marijuana use was associated with depressive symptoms and shorter breastfeeding duration. Surveillance of marijuana use among pregnant and postpartum women is critical to better understanding the relationship of marijuana use with birth outcomes, and postpartum experiences such as depression and breastfeeding.

      2. OBJECTIVE: To examine the financial burdens and mental health needs of families of children with special healthcare needs (CSHCN) with congenital heart disease (CHD). METHODS: Data from the 2009-2010 National Survey of Children with Special Health Care Needs (NS-CSHCN) were used to examine parent-reported financial burdens (out-of-pocket expenses, financial problems, employment impact, caregiving hours) and family members’ need for mental health services in families of CSHCN with CHD. Multivariable logistic regression was used to compare financial burdens and family members’ need for mental health services among CSHCN with and without CHD. Among CSHCN with CHD, multivariable logistic regression, stratified by age (0-5 and 6-17 years), was used to assess characteristics associated with the outcomes. RESULTS: Overall, families of 89.1% of CSHCN with CHD experienced at least one financial burden and 14.9% needed mental health services due to the child’s condition. Compared with CSHCN without CHD, those with CHD had families with a higher prevalence of all financial burdens (adjusted prevalence ratio [aPR] range: 1.4-1.8) and similar family member need for mental health services (aPR = 1.3, 95% CI [1.0, 1.6]). Across both age groups, insurance type, activity limitations, and comorbidities were significantly associated with financial burdens and/or family members’ need for mental health services. CONCLUSIONS: CSHCN with CHD, compared with those without CHD, lived in families with more financial burdens. Interventions that reduce financial burdens and improve mental health of family members are needed, especially among CSHCN with CHD who are uninsured and have comorbidities or activity limitations.

      3. BACKGROUND: The World Health Organization’s integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. We aimed to determine if a conditional follow-up visit was non-inferior to a universal follow-up visit for these children. METHODS AND FINDINGS: We conducted a cluster-randomized, community-based non-inferiority trial among children 2-59 months old presenting to community health workers (CHWs) with non-severe unclassified fever in Tanganyika Province, Democratic Republic of the Congo. Clusters (n = 28) of CHWs were randomized to advise caregivers to either (1) return for a follow-up visit on day 3 following the initial consultation on day 1, regardless of illness resolution (as per current WHO guidelines; universal follow-up group) or (2) return for a follow-up visit on day 3 only if illness continued (conditional follow-up group). Children in both arms were assessed again at day 8, and classified as a clinical failure if fever (caregiver-reported), malaria, diarrhea, pneumonia, or decline of health status (development of danger signs, hospitalization, or death) was noted (failure definition 1). Alternative failure definitions were examined, whereby caregiver-reported fever was first restricted to caregiver-reported fever of at least 3 days (failure definition 2) and then replaced with fever measured via axillary temperature (failure definition 3). Study participants, providers, and investigators were not masked. Among 4,434 enrolled children, 4,141 (93.4%) met the per-protocol definition of receipt of the arm-specific advice from the CHW and a timely day 8 assessment (universal follow-up group: 2,210; conditional follow-up group: 1,931). Failure was similar (difference: -0.7%) in the conditional follow-up group (n = 188, 9.7%) compared to the universal follow-up group (n = 230, 10.4%); however, the upper bound of a 1-sided 95% confidence interval around this difference (-infinity, 5.1%) exceeded the prespecified non-inferiority margin of 4.0% (non-inferiority p = 0.089). When caregiver-reported fever was restricted to fevers lasting >/=3 days, failure in the conditional follow-up group (n = 159, 8.2%) was similar to that in the universal follow-up group (n = 200, 9.1%) (difference: -0.8%; 95% CI: -infinity, 4.1%; p = 0.053). If caregiver-reported fever was replaced by axillary temperature measurement in the definition of failure, failure in the conditional follow-up group (n = 113, 5.9%) was non-inferior to that in the universal follow-up group (n = 160, 7.2%) (difference: -1.4%; 95% CI: -infinity, 2.5%; p = 0.012). In post hoc analysis, when the definition of failure was limited to malaria, diarrhea, pneumonia, development of danger signs, hospitalization, or death, failure in the conditional follow-up group (n = 108, 5.6%) was similar to that in the universal follow-up group (n = 147, 6.7%), and within the non-inferiority margin (95% CI: -infinity, 2.9%; p = 0.017). Limitations include initial underestimation of the proportion of clinical failures as well as substantial variance in cluster-specific failure rates, reducing the precision of our estimates. In addition, heightened security concerns slowed recruitment in the final months of the study. CONCLUSIONS: We found that advising caregivers to return only if children worsened or remained ill on day 3 resulted in similar rates of caregiver-reported fever and other clinical outcomes on day 8, compared to advising all caregivers to return on day 3. Policy-makers could consider revising guidelines for management of uncomplicated fever within the iCCM framework. TRIAL REGISTRATION: ClinicalTrials.gov NCT02595827.

      4. Antibiotics and risk for birth defectsExternal
        Tinker SC, Crider KS, Ailes EC.
        Br J Clin Pharmacol. 2018 Apr 16.

        [No abstract]

    • Mining

      1. Analysis of monitored ground support and rock mass response in a longwall tailgate entryExternal
        Esterhuizen GS, Gearhart DF, Tulu IB.
        Int J Min Sci Technol. 2018 Jan;28(1):43-51.

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

    • Nutritional Sciences

      1. The effects of a lipid-based nutrient supplement and antiretroviral therapy in a randomized controlled trial on iron, copper, and zinc in milk from HIV-infected Malawian mothers and associations with maternal and infant biomarkersExternal
        Hampel D, Shahab-Ferdows S, Gertz E, Flax VL, Adair LS, Bentley ME, Jamieson DJ, Tegha G, Chasela CS, Kamwendo D, van der Horst CM, Allen LH.
        Matern Child Nutr. 2018 Apr;14(2):e12503.

        We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (</=30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal alpha-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation.

      2. Adolescent sugar-sweetened beverage intake is associated with parent intake, not knowledge of health risksExternal
        Lundeen EA, Park S, Onufrak S, Cunningham S, Blanck HM.
        Am J Health Promot. 2018 Jan 1:890117118763008.

        PURPOSE: To examine associations of adolescent sugar-sweetened beverage (SSB) intake with parent SSB intake and parent and adolescent knowledge of SSB-related health risks. DESIGN: Quantitative, cross-sectional. SETTING: 2014 SummerStyles survey. SUBJECTS: Nine hundred and ninety parent and adolescent (12-17 years) pairs. MEASURES: The outcome was self-reported adolescent intake (0, >0 to <1, or >/=1 time/day) of SSBs (soda, fruit drinks, sports/energy drinks, other SSBs). The exposures were self-reported parent SSB intake (0, >0 to <1, >/=1 to <2, or >/=2 times/day) and parent and adolescent knowledge of SSB-related health risks (weight gain, diabetes, and dental caries). ANALYSIS: Separate multinomial logistic regression models were used to estimate adjusted odds ratios (aORs) for adolescent SSB intake >/=1 time/day (ref: 0 times/day), according to (1) parent SSB intake and (2) parent and (3) adolescent knowledge. RESULTS: About 31% of adolescents consumed SSBs >/=1 time/day, and 43.2% of parents consumed SSBs >/=2 times/day. Adolescent and parent knowledge that SSB intake is related to health conditions ranged from 60.7% to 80.4%: weight gain (75.0% and 80.4%, respectively), diabetes (60.7% and 71.4%, respectively), and dental caries (77.5% and 72.9%, respectively). In adjusted models, adolescent SSB intake >/=1 time/day was associated with parent intake >/=2 times/day (aOR = 3.30; 95% confidence interval = 1.62-6.74) but not with parent or adolescent knowledge of health risks. CONCLUSION: Parental SSB intake may be an important factor in understanding adolescent behavior; knowledge of SSB-related health conditions alone may not influence adolescent SSB behavior.

    • Occupational Safety and Health

      1. Tobacco and other occupational exposures among hookah bar workersExternal
        Al-Faham Z, LeBouf RF, Nett RJ.
        Am J Ind Med. 2018 Apr 14.

        [No abstract]

      2. BACKGROUND: There is sparse and inconsistent evidence of an association between styrene exposure and cancer. METHODS: This study examines mortality patterns in a previously studied cohort of 5201 workers employed in two Washington boat-building facilities, extending follow-up 5 years. Standardized mortality ratios (SMR) were calculated using state rates as referent. Cox regression calculated rate ratios (RR) per year employed in styrene-exposed exposed jobs. RESULTS: No excess deaths from lymphohematopoietic cancers (LHCs) were observed (SMR: 0.99, 95%CI: 0.74-1.30) when compared to the referent population; however, the relative risk increased with duration of employment in internal analyses. Conversely, lung cancer mortality was significantly elevated (SMR: 1.24, 95%CI: 1.08-1.41), but there was no evidence of a dose-response relationship. CONCLUSION: We found evidence that occupational exposure to styrene was associated with increased LHC risk, while no such association was observed for lung cancer.

      3. Work aggravated asthma in Great Britain: a cross-sectional postal surveyExternal
        Bradshaw L, Sumner J, Delic J, Henneberger P, Fishwick D.
        Prim Health Care Res Dev. 2018 Apr 12:1-9.

        OBJECTIVE: Work aggravated asthma (WAA), asthma made worse by but not caused by workplace exposures, can have a negative impact on personal, social, financial and societal costs. There is limited data on prevalence levels of WAA in Great Britain (GB). The objective of this study was to estimate the prevalence of WAA in GB, and to assess its potential causes.Materials and methodsA cross-sectional postal questionnaire study was carried out. A total of 1620 questionnaires were sent to three populations of adults with asthma. The questionnaire recorded; demographic details, current job, self-reported health status, presence of asthma and respiratory symptoms, duration and severity of symptoms and medication requirements. Questions relating to work environment and employers’ actions were included, and each participant completed an assessment of health-related quality of life using the EuroQol Research Foundation EQ-5D. RESULTS: There were 207 completed questionnaires; response rates were 6% primary care, 45% secondary care and 71% Asthma UK. This represented a 13% overall response rate. Self-reported prevalence of WAA was 33% (95% CI 24.4-41.6%). In all, 19% of workers had changed their job because of breathing problems. Workers with WAA reported higher levels of work-related stress. Quality of life using the EQ-5D utility index was lower in those with WAA. CONCLUSION: WAA is a common problem in asthmatics in GB. This result is in keeping with international prevalence rates. Further research could assist the understanding of the most significant aggravants to asthma at work and help define appropriate interventions by workplaces.

      4. Coaches spend long hours training gymnasts of all ages aided by polyurethane foam used in loose blocks, mats, and other padded equipment. Polyurethane foam can contain flame retardant additives such as polybrominated diphenyl ethers (PBDEs), to delay the spread of fires. However, flame retardants have been associated with endocrine disruption and carcinogenicity. The National Institute for Occupational Safety and Health (NIOSH) evaluated employee exposure to flame retardants in four gymnastics studios utilized by recreational and competitive gymnasts. We evaluated flame retardant exposure at the gymnastics studios before, during, and after the replacement of foam blocks used in safety pits with foam blocks certified not to contain several flame retardants, including PBDEs. We collected hand wipes on coaches to measure levels of flame retardants on skin before and after their work shift. We measured flame retardant levels in the dust on window glass in the gymnastics areas and office areas, and in the old and new foam blocks used throughout the gymnastics studios. We found statistically higher levels of 9 out of 13 flame retardants on employees’ hands after work than before, and this difference was reduced after the foam replacement. Windows in the gymnastics areas had higher levels of 3 of the 13 flame retardants than windows outside the gymnastics areas, suggesting that dust and vapor containing flame retardants became airborne. Mats and other padded equipment contained levels of bromine consistent with the amount of brominated flame retardants in foam samples analyzed in the laboratory. New blocks did not contain PBDEs, but did contain the flame retardants 2-ethylhexyl 2,3,4,5-tetrabromobenzoate and 2-ethylhexyl 2,3,4,5-tetrabromophthalate. We conclude that replacing the pit foam blocks eliminated a source of PBDEs, but not 2-ethylhexyl 2,3,4,5-tetrabromobenzoate and 2-ethylhexyl 2,3,4,5-tetrabromophthalate. We recommend ways to further minimize employee exposure to flame retardants at work and acknowledge the challenges consumers have identifying chemical contents of new products.

      5. OBJECTIVE: Asthma severity is defined as the intensity of treatment required to achieve good control of asthma symptoms. Studies have shown that work-related asthma (WRA) can be associated with poorer asthma control and more severe symptoms than non-WRA. Associations between asthma medications and WRA status were assessed using data from the 2012-2013 Asthma Call-back Survey among ever-employed adults (>/=18 years) with current asthma from 29 states. METHODS: Persons with WRA had been told by a physician that their asthma was work-related. Persons with possible WRA had asthma caused or made worse by their current or previous job, but did not have physician-diagnosed WRA. Asthma medications were classified as controller (i.e., long-acting beta-agonist, inhaled corticosteroid, oral corticosteroid, cromolyn/nedocromil, leukotriene pathway inhibitor, methylxanthine, anti-cholinergics) and rescue (i.e., short-acting beta-agonist). Demographic and clinical characteristics were examined. Associations between asthma medications and WRA status were assessed using a multivariate logistic regression to calculate adjusted prevalence ratios (PRs). RESULTS: Among an estimated 15 million ever-employed adults with current asthma, 14.7% had WRA and an additional 40.4% had possible WRA. Compared with adults with non-WRA, those with WRA were more likely to have taken anti-cholinergics (PR = 1.80), leukotriene pathway inhibitor (PR = 1.59), and methylxanthine (PR = 4.76), and those with possible WRA were more likely to have taken methylxanthine (PR = 2.85). CONCLUSIONS: Results provide additional evidence of a higher proportion of severe asthma among adults with WRA compared to non-WRA. To achieve optimal asthma control, adults with WRA may require additional intervention, such as environmental controls or removal from the workplace exposure.

      6. Fatal chlorine gas exposure at a metal recycling facility: Case reportExternal
        Harvey RR, Boylstein R, McCullough J, Shumate A, Yeoman K, Bailey RL, Cummings KJ.
        Am J Ind Med. 2018 Apr 12.

        At least four workers at a metal recycling facility were hospitalized and one died after exposure to chlorine gas when it was accidentally released from an intact, closed-valved cylinder being processed for scrap metal. This unintentional chlorine gas release marks at least the third such incident at a metal recycling facility in the United States since 2010. We describe the fatal case of the worker whose clinical course was consistent with acute respiratory distress syndrome (ARDS) following exposure to high concentrations of chlorine gas. This case report emphasizes the potential risk of chlorine gas exposure to metal recycling workers by accepting and processing intact, closed-valved containers. The metal recycling industry should take steps to increase awareness of this established risk to prevent future chlorine gas releases. Additionally, public health practitioners and clinicians should be aware that metal recycling workers are at risk for chlorine gas exposure.

      7. OBJECTIVE: The purpose was to estimate the prevalence of hearing loss for noise-exposed U.S. workers within the Health Care and Social Assistance (HSA) sector. METHODS: Audiograms for 1.4 million workers (8702 within HSA) from 2003 to 2012 were examined. Prevalences and adjusted risks for hearing loss as compared with a reference industry were estimated for the HSA sector and all industries combined. RESULTS: While the overall HSA sector prevalence for hearing loss was 19%, the prevalences in the Medical Laboratories subsector and the Offices of All Other Miscellaneous Health Practitioners subsector were 31% and 24%, respectively. The Child Day Care Services subsector had a 52% higher risk than the reference industry. CONCLUSION: High-risk industries for hearing loss exist within the HSA sector. Further work is needed to identify the sources of noise exposure and protect worker hearing.

      8. In 2010, an estimated 8.2% of U.S. adults had current asthma, and among these persons, 49.1% had had an asthma attack during the past year (1). Workplace exposures can cause asthma in a previously healthy worker or can trigger asthma exacerbations in workers with current asthma* (2). To assess the industry- and occupation-specific prevalence of current asthma, asthma attacks, and asthma-related emergency department (ED) visits among working adults, CDC analyzed 2011-2016 National Health Interview Survey (NHIS) data for participants aged >/=18 years who, at the time of the survey, were employed at some time during the 12 months preceding the interview. During 2011-2016, 6.8% of adults (11 million) employed at any time in the past 12 months had current asthma; among those, 44.7% experienced an asthma attack, and 9.9% had an asthma-related ED visit in the previous year. Current asthma prevalence was highest among workers in the health care and social assistance industry (8.8%) and in health care support occupations (8.8%). The increased prevalence of current asthma, asthma attacks, and asthma-related ED visits in certain industries and occupations might indicate increased risks for these health outcomes associated with workplace exposures. These findings might assist health care and public health professionals in identifying workers in industries and occupations with a high prevalence of current asthma, asthma attacks, and asthma-related ED visits who should be evaluated for possible work-related asthma. Guidelines intended to promote effective management of work-related asthma are available (2,3).

      9. Safe-in-sound award recognizes innovations in hearing loss preventionExternal
        Morata TC, Casto KL.
        Hearing Journal. 2018 ;71(4):34.

        [No abstract]

      10. Acute metam sodium poisoning caused by occupational exposure at a flower farm – Uganda, October 2016External
        Nakubulwa S, Kusiima J, Kadobera D, Mutyoba JN, Ario AR, Zhu BP.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 13;67(14):414-417.

        On October 25, 2016, media reports alerted the Uganda Ministry of Health to an outbreak of >80 cases of vomiting, syncope, and acute diarrhea among workers at a flower farm in central Uganda; 27 workers were hospitalized. On November 1, an investigation was undertaken by the Uganda Public Health Fellowship Program.* A case-control study found that working inside greenhouse 7, which had been fumigated with the organosulfur compound metam sodium the night of October 13, was strongly associated with illness. Employees who worked in this greenhouse during October 14-21 reported a strong “suffocating” smell in the greenhouse. Investigation revealed that, in violation of safety protocols, workers did not properly cover the soil after fumigation, allowing vapors to become trapped inside the greenhouse. The farm management, unaware of the lapse, failed to inform workers to avoid the vicinity of the fumigation. Respiratory protective measures were not routinely available for workers, which likely contributed to the severity and extent of the outbreak. Although metam sodium is generally considered to be of low risk when used according to manufacturer’s instructions (1), occupational exposure in the absence of recommended safety measures can have serious health consequences. The investigation highlighted the importance of identifying potential occupational hazards to workers, as well as establishing safety protocols in occupational settings, training workers at risk, such as pesticide sprayers and flower pickers,(dagger) and ensuring enforcement of safety protocols. After this outbreak, the farm management reviewed, revised, and trained the workers on safety protocols to prevent future outbreaks.

      11. In vitro toxicological evaluation of surgical smoke from human tissueExternal
        Sisler JD, Shaffer J, Soo JC, LeBouf RF, Harper M, Qian Y, Lee T.
        J Occup Med Toxicol. 2018 ;13:12.

        Background: Operating room personnel have the potential to be exposed to surgical smoke, the by-product of using electrocautery or laser surgical device, on a daily basis. Surgical smoke is made up of both biological by-products and chemical pollutants that have been shown to cause eye, skin and pulmonary irritation. Methods: In this study, surgical smoke was collected in real time in cell culture media by using an electrocautery surgical device to cut and coagulate human breast tissues. Airborne particle number concentration and particle distribution were determined by direct reading instruments. Airborne concentration of selected volatile organic compounds (VOCs) were determined by evacuated canisters. Head space analysis was conducted to quantify dissolved VOCs in cell culture medium. Human small airway epithelial cells (SAEC) and RAW 264.7 mouse macrophages (RAW) were exposed to surgical smoke in culture media for 24 h and then assayed for cell viability, lactate dehydrogenase (LDH) and superoxide production. Results: Our results demonstrated that surgical smoke-generated from human breast tissues induced cytotoxicity and LDH increases in both the SAEC and RAW. However, surgical smoke did not induce superoxide production in the SAEC or RAW. Conclusion: These data suggest that the surgical smoke is cytotoxic in vitro and support the previously published data that the surgical smoke may be an occupational hazard to healthcare workers.

      12. Asthma among household youth on racial minority operated farms – United States, 2008External
        Syamlal G, Hendricks K, Mazurek JM.
        J Agromedicine. 2018 ;23(2):144-153.

        OBJECTIVES: Youth on farms are at risk for injuries and illnesses, including asthma, which continues to disproportionately affect minority groups. METHODS: For this study, the 2008 Minority Farm Operator Childhood Agricultural Injury Survey (M-CAIS) data were used to estimate the prevalence of asthma among youth aged 0-19 years living on racial minority-operated farms. Youth were considered to have a lifetime diagnosis of asthma based on an affirmative response to the question “Has he/she ever been diagnosed as having asthma by a health professional?” RESULTS: In 2008, of the estimated 37,400 youth (0-19 years) who lived on racial minority operated farms, 11% had asthma. Asthma prevalence was highest among males (13%) and youth 10-19 years of age (12%). Asthma prevalence among youth varied by race, ranging from 13% among household youth living on Black/African American operated farms to 7% among youth living on Asian/Native Hawaiian/Pacific Islander operated farms. In 2008, nearly half (46%) of household youth (0-19 years) worked on the farm. The odds of having asthma were higher among working youth compared with non-working youth (POR, 1.5; 95% CI: 1.3-1.8). CONCLUSION: Disparities in asthma among youth living or working on racial minority-operated farms were observed. These findings may assist agricultural safety and health researchers, practitioners, and educators in identifying and designing targeted interventions to reduce asthma burden among youth on racial minority-operated farms.

    • Occupational Safety and Health – Mining

      1. Miners implement corrective actions in response to CPDM dust dataExternal
        Haas EJ, Colinet JF.
        Coal Age. 2018 ;123(2):36-38.

        [No abstract]

      2. Experimental study on the confinement-dependent characteristics of a Utah coal considering the anisotropy by cleatsExternal
        Kim BH, Walton G, Larson MK, Berry S.
        Int J Rock Mech Min Sci (1997). 2018 ;105:182-191.

        Characterizing a coal from an engineering perspective for design of mining excavations is critical in order to prevent fatalities, as underground coal mines are often developed in highly stressed ground conditions. Coal pillar bursts involve the sudden expulsion of coal and rock into the mine opening. These events occur when relatively high stresses in a coal pillar, left for support in underground workings, exceed the pillar’s load capacity causing the pillar to rupture without warning. This process may be influenced by cleating, which is a type of joint system that can be found in coal rock masses. As such, it is important to consider the anisotropy of coal mechanical behavior. Additionally, if coal is expected to fail in a brittle manner, then behavior changes, such as the transition from extensional to shear failure, have to be considered and reflected in the adopted failure criteria. It must be anticipated that a different failure mechanism occurs as the confinement level increases and conditions for tensile failure are prevented or strongly diminished. The anisotropy and confinement dependency of coal behavior previously mentioned merit extensive investigation. In this study, a total of 84 samples obtained from a Utah coal mine were investigated by conducting both unconfined and triaxial compressive tests. The results showed that the confining pressure dictated not only the peak compressive strength but also the brittleness as a function of the major to the minor principal stress ratio. Additionally, an s-shaped brittle failure criterion was fitted to the results, showing the development of confinement-dependent strength. Moreover, these mechanical characteristics were found to be strongly anisotropic, which was associated with the orientation of the cleats relative to the loading direction.

      3. Interstitial lung diseases in the U.S. mining industry: Using MSHA data to examine trends and the prevention effects of compliance with health regulations, 1996-2015External
        Yorio PL, Laney AS, Halldin CN, Blackley DJ, Moore SM, Wizner K, Radonovich LJ, Greenawald LA.
        Risk Anal. 2018 Apr 12.

        Given the recent increase in dust-induced lung disease among U.S. coal miners and the respiratory hazards encountered across the U.S. mining industry, it is important to enhance an understanding of lung disease trends and the organizational contexts that precede these events. In addition to exploring overall trends reported to the Mine Safety and Health Administration (MSHA), the current study uses MSHA’s enforcement database to examine whether or not compliance with health regulations resulted in fewer mine-level counts of these diseases over time. The findings suggest that interstitial lung diseases were more prevalent in coal mines compared to other mining commodities, in Appalachian coal mines compared to the rest of the United States, and in underground compared to surface coal mines. Mines that followed a relevant subset of MSHA’s health regulations were less likely to report a lung disease over time. The findings are discussed from a lung disease prevention strategy perspective.

    • Parasitic Diseases

      1. Updated CDC recommendations for using artemether-lumefantrine for the treatment of uncomplicated malaria in pregnant women in the United StatesExternal
        Ballard SB, Salinger A, Arguin PM, Desai M, Tan KR.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 13;67(14):424-431.

        Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1). However, limited availability of quinine and increasing resistance to mefloquine restrict these options. Strong evidence now demonstrates that artemether-lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy. The World Health Organization (WHO) has endorsed artemisinin-based combination therapies (ACTs), such as AL, for treatment of uncomplicated malaria during the second and third trimesters of pregnancy and is currently considering whether to add ACTs, including AL, as an option for malaria treatment during the first trimester (2,3). This policy note reviews the evidence and updates CDC recommendations to include AL as a treatment option for uncomplicated malaria during the second and third trimesters of pregnancy and during the first trimester of pregnancy when other treatment options are unavailable. These updated recommendations reflect current evidence and are consistent with WHO treatment guidelines.

      2. Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infectionsExternal
        Early AM, Lievens M, MacInnis BL, Ockenhouse CF, Volkman SK, Adjei S, Agbenyega T, Ansong D, Gondi S, Greenwood B, Hamel M, Odero C, Otieno K, Otieno W, Owusu-Agyei S, Asante KP, Sorgho H, Tina L, Tinto H, Valea I, Wirth DF, Neafsey DE.
        Nat Commun. 2018 Apr 11;9(1):1381.

        Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.

      3. Toxoplasma gondii infection in the United States, 2011-2014External
        Jones JL, Kruszon-Moran D, Elder S, Rivera HN, Press C, Montoya JG, McQuillan GM.
        Am J Trop Med Hyg. 2018 Feb;98(2):551-557.

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

      4. Universal versus conditional third day follow-up visit for children with nonsevere unclassified fever at the community level in Ethiopia: Protocol for a cluster randomized noninferiority trialExternal
        Kallander K, Alfven T, Workineh AA, Hailemariam A, Petzold M, Getachew D, Barat L, Steinhardt LC, Gutman JR.
        JMIR Res Protoc. 2018 Apr 12;7(4):e99.

        BACKGROUND: Under the World Health Organization’s integrated community case management strategy, febrile children seen by community health workers (on day 1) without a diagnosable illness and without danger signs are advised to return on day 3, regardless of symptom resolution. This advice might be unnecessary and place additional time and cost burdens on caregivers and community health workers. However, the safety of not following up with respect to children with unclassified fever is unknown. OBJECTIVE: The objective of this study is to establish the safety of conditional follow-up of nonsevere unclassified fever, that is, nonsevere illness with fever, no malaria, pneumonia, diarrhea, or danger signs, compared with universal follow-up on day 3, through a 2-arm cluster randomized controlled noninferiority trial. METHODS: The study is being conducted in 3 districts in southwest Ethiopia. A total of 25 health facilities are randomized to one of the 2 intervention arms; all 144 health posts and 284 community health workers are included. All enrolled children are followed-up after 1 week (on day 8) for re-assessment. If still sick on day 8, additional follow-up takes place after 2 weeks (day 15) and 1 month (day 29). To demonstrate that there is no significant increase in the percentage of children deteriorating clinically, the sample size needed for a noninferiority margin of 4%, a power of 80%, an alpha of 5%, and a design effect of 3 is 4284 children with unclassified fever. Main outcome is treatment failure on day 8, defined as death, hospitalization, one or more danger signs, or persistent fever. RESULTS: The project was funded in 2015 and enrollment was completed 2016. Data analysis is currently under way, and the first results are expected to be submitted for publication in 2018. CONCLUSIONS: This study addresses the question as to whether there is any benefit in recommending universal follow-up among children seen for nonsevere unclassified fever, or whether parents can be counseled to return in the event of persistent fever, using a cluster randomized controlled trial design embedded in a national program. Outcomes will be relevant for policy makers and are important for the evaluation of current and future World Health Organization guidelines for the management of children with fever. TRIAL REGISTRATION: ClinicalTrials.gov NCT02926625; https://clinicaltrials.gov/ct2/show/NCT02926625 (Archived by WebCite at http://www.webcitation.org/6xrQWn50t).

      5. Emergence and spread of kelch13 mutations associated with artemisinin resistance in Plasmodium falciparum parasites in 12 Thai provinces from 2007 to 2016External
        Kobasa T, Talundzic E, Sug-Aram R, Boondat P, Goldman IF, Lucchi NW, Dharmarak P, Sintasath D, Fukuda M, Whistler T, MacArthur J, Udhayakumar V, Prempree P, Chinanonwait N.
        Antimicrob Agents Chemother. 2018 Apr;62(4).

        Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The P. falciparumkelch13 gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify P. falciparum kelch13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of P. falciparum kelch13 mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

      6. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trialExternal
        Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong’o BO, Chen T, Bousema T, Slater HC, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, Ter Kuile FO.
        Lancet Infect Dis. 2018 Mar 27.

        BACKGROUND: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150-200 mug/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 mug/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment. METHODS: We did a randomised, double-blind, placebo-controlled, superiority trial at the Jaramogi Oginga Odinga Teaching and Referral Hospital (Kisumu, Kenya). Adults (aged 18-50 years) were eligible if they had confirmed symptomatic uncomplicated Plasmodium falciparum malaria and agreed to the follow-up schedule. Participants were randomly assigned (1:1:1) using sealed envelopes, stratified by sex and body-mass index (men: <21 vs >/=21 kg/m(2); women: <23 vs >/=23 kg/m(2)), with permuted blocks of three, to receive 3 days of ivermectin 300 mug/kg per day, ivermectin 600 mug/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353. FINDINGS: Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 mug/kg per day (n=47), ivermectin 300 mug/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 mug/kg per day risk ratio [RR] 2.26, 95% CI 1.93-2.65, p<0.0001; hazard ratio [HR] 6.32, 4.61-8.67, p<0.0001; ivermectin 300 mug/kg per day RR 2.18, 1.86-2.57, p<0.0001; HR 4.21, 3.06-5.79, p<0.0001). Mosquito mortality remained significantly increased 28 days post treatment (ivermectin 600 mug/kg per day RR 1.23, 1.01-1.50, p=0.0374; and ivermectin 300 mug/kg per day 1.21, 1.01-1.44, p=0.0337). Five (11%) of 45 patients receiving ivermectin 600 mug/kg per day, two (4%) of 48 patients receiving ivermectin 300 mug/kg per day, and none of 46 patients receiving placebo had one or more treatment-related adverse events. INTERPRETATION: Ivermectin at both doses assessed was well tolerated and reduced mosquito survival for at least 28 days after treatment. Ivermectin 300 mug/kg per day for 3 days provided a good balance between efficacy and tolerability, and this drug shows promise as a potential new tool for malaria elimination. FUNDING: Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC).

      7. Next-generation sequencing and bioinformatics protocol for malaria drug resistance marker surveillanceExternal
        Talundzic E, Ravishankar S, Kelley J, Patel D, Plucinski M, Schmedes S, Ljolje D, Clemons B, Madison-Antenucci S, Arguin PM, Lucchi NW, Vannberg F, Udhayakumar V.
        Antimicrob Agents Chemother. 2018 Apr;62(4).

        The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug-resistant parasites. To take advantage of this technology, an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance in P. falciparum, called malaria resistance surveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing. MaRS enables researchers to simultaneously collect data on allele frequencies of multiple full-length P. falciparum drug resistance genes (crt, mdr1, k13, dhfr, dhps, and the cytochrome b gene), as well as the mitochondrial genome. Information is captured at the individual patient level for both known and potential new single nucleotide polymorphisms associated with drug resistance. The MaRS pipeline was validated using 245 imported malaria cases that were reported to the Centers for Disease Control and Prevention (CDC). The chloroquine resistance crt CVIET genotype (mutations underlined) was observed in 42% of samples, the highly pyrimethamine-resistant dhpsIRN triple mutant in 92% of samples, and the sulfadoxine resistance dhps mutation SGEAA in 26% of samples. The mdr1 NFSND genotype was found in 40% of samples. With the exception of two cases imported from Cambodia, no artemisinin resistance k13 alleles were identified, and 99% of patients carried parasites susceptible to atovaquone-proguanil. Our goal is to implement MaRS at the CDC for routine surveillance of imported malaria cases in the United States and to aid in the adoption of this system at participating state public health laboratories, as well as by global partners.

      8. Socioeconomic health inequality in malaria indicators in rural western Kenya: evidence from a household malaria survey on burden and care-seeking behaviourExternal
        Were V, Buff AM, Desai M, Kariuki S, Samuels A, Ter Kuile FO, Phillips-Howard PA, Kachur SP, Niessen L.
        Malar J. 2018 Apr 16;17(1):166.

        BACKGROUND: Health inequality is a recognized barrier to achieving health-related development goals. Health-equality data are essential for evidence-based planning and assessing the effectiveness of initiatives to promote equity. Such data have been captured but have not always been analysed or used to manage programming. Health data were examined for microeconomic differences in malaria indices and associated malaria control initiatives in western Kenya. METHODS: Data was analysed from a malaria cross-sectional survey conducted in July 2012 among 2719 people in 1063 households in Siaya County, Kenya. Demographic factors, history of fever, malaria parasitaemia, malaria medication usage, insecticide-treated net (ITN) use and expenditure on malaria medications were collected. A composite socioeconomic status score was created using multiple correspondence analyses (MCA) of household assets; households were classified into wealth quintiles and dichotomized into poorest (lowest 3 quintiles; 60%) or less-poor (highest 2 quintiles; 40%). Prevalence rates were calculated using generalized linear modelling. RESULTS: Overall prevalence of malaria infection was 34.1%, with significantly higher prevalence in the poorest compared to less-poor households (37.5% versus 29.2%, adjusted prevalence ratio [aPR] 1.23; 95% CI = 1.08-1.41, p = 0.002). Care seeking (aPR = 0.95; 95% CI 0.87-1.04, p = 0.229), medication use (aPR = 0.94; 95% CI 0.87-1.00, p = 0.087) and ITN use (aPR = 0.96; 95% CI = 0.87-1.05, p = 0.397) were similar between households. Among all persons surveyed, 36.4% reported taking malaria medicines in the prior 2 weeks; 92% took artemether-lumefantrine, the recommended first-line malaria medication. In the poorest households, 4.9% used non-recommended medicines compared to 3.5% in less-poor (p = 0.332). Mean and standard deviation [SD] for expenditure on all malaria medications per person was US$0.38 [US$0.50]; the mean was US$0.35 [US$0.52] amongst the poorest households and US$0.40 [US$0.55] in less-poor households (p = 0.076). Expenditure on non-recommended malaria medicine was significantly higher in the poorest (mean US$1.36 [US$0.91]) compared to less-poor households (mean US$0.98 [US$0.80]; p = 0.039). CONCLUSIONS: Inequalities in malaria infection and expenditures on potentially ineffective malaria medication between the poorest and less-poor households were evident in rural western Kenya. Findings highlight the benefits of using MCA to assess and monitor the health-equity impact of malaria prevention and control efforts at the microeconomic level.

    • Reproductive Health

      1. Examining the contraceptive decisions of young, HIV-infected women: a qualitative studyExternal
        Brown JL, Haddad LB, Gause NK, Cordes S, Bess C, King CC, Hatfield-Timajchy K, Chakraborty R, Kourtis A.
        Women Health. 2018 Apr 6.

        This study qualitatively examined factors that influenced contraceptive choices in a sample of young, HIV-infected women. Individual qualitative interviews were conducted among 30 vertically- and horizontally-HIV-infected women (n = 26 African American) from the ages of 14 to 24 years (Mean age = 20.9 years). We recruited sample groups with the following characteristics: (a) current contraceptive/condom use with >/=1 child (n = 11); (b) current contraceptive/condom use with no children (n = 12); and (c) no current contraceptive/condom use with no children (n = 7). A semi-structured interview guide was used to ask participants about factors influencing past and current contraceptive choices. Individual interviews were digitally recorded and transcribed verbatim; analyses to identify core themes were informed by the Grounded Theoretical approach. Young, HIV-infected women did not identify their HIV serostatus or disease-related concerns as influential in their contraceptive decisions. However, they reported that recommendations from healthcare providers and input from family and friends influenced their contraceptive choices. They also considered a particular method’s advantages (e.g., menstrual cycle improvements) and disadvantages (e.g., increased pill burden) when selecting a method. Findings suggested that HIV-infected young women’s contraceptive decisions were influenced by factors other than those related to their infection.

      2. Assisted reproductive technology with donor sperm: national trends and perinatal outcomesExternal
        Gerkowicz SA, Crawford SB, Hipp HS, Boulet SL, Kissin DM, Kawwass JF.
        Am J Obstet Gynecol. 2018 Apr;218(4):421.e1-421.e10.

        BACKGROUND: Information regarding the use of donor sperm in assisted reproductive technology, as well as subsequent treatment and perinatal outcomes, remains limited. Outcome data would aid patient counseling and clinical decision making. OBJECTIVES: The objectives of the study were to report national trends in donor sperm utilization and live birth rates of donor sperm-assisted reproductive technology cycles in the United States and to compare assisted reproductive technology treatment and perinatal outcomes between cycles using donor and nondonor sperm. We hypothesize these outcomes to be comparable between donor and nondonor sperm cycles. STUDY DESIGN: This was a retrospective cohort study using data from all US fertility centers reporting to the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology Surveillance System, accounting for approximately 98% of assisted reproductive technology cycles (definition excludes intrauterine insemination). The number and percentage of assisted reproductive technology cycles using donor sperm and rates of pregnancy, live birth, preterm birth (<37 weeks), and low birthweight (<2500 g) were the primary outcomes measured. Treatments assessed include use of donor vs nondonor sperm. The trends analysis included all banking and fresh assisted reproductive technology cycles using donor and autologous oocytes performed between 1996 and 2014 (n = 1,710,034). The outcomes analysis was restricted to include only fresh autologous cycles performed between 2010 and 2014 (n = 437,569) to focus on cycles with a potential outcome and cycles reflective of current practice, thereby improving the clinical relevance. Cycles canceled prior to retrieval were excluded. Statistical analysis included linear regression to explore polynomial trends and log-binomial regression to estimate relative risk for outcomes among cycles using donor and nondonor sperm. RESULTS: Of all banking and fresh donor and autologous oocyte assisted reproductive technology cycles performed between 1996 and 2014, 74,892 (4.4%) used donor sperm. In 2014, 7351 assisted reproductive technology cycles using donor sperm were performed, as compared with 1763 in 1996 (6.2% vs 3.8% of all cycles). Among all autologous oocyte cycles performed between 2010 and 2014, the live birth rate was lower for donor sperm (27.9%) than nondonor sperm cycles (32.5%); however, after adjustment for maternal age, donor sperm use was associated with an increased likelihood of live birth (adjusted relative risk, 1.06, 95% confidence interval, 1.01-1.10). Per transfer, there was no significant difference in live birth rates for donor vs nondonor sperm (31.9% vs 36.8%; adjusted relative risk, 1.04, 95% confidence interval, 0.998-1.09). Per singleton live birth, there was no significant difference in preterm birth (11.5% vs 11.8%; adjusted relative risk, 0.98, 95% confidence interval, 0.90-1.06); however, low birthweight delivery was slightly lower in donor sperm cycles (8.8% vs 9.4%; adjusted relative risk, 0.91, 95% confidence interval, 0.83-0.99). CONCLUSION: Donor sperm use in assisted reproductive technology has increased in the United States, accounting for approximately 6% of all assisted reproductive technology cycles in 2014. Assisted reproductive technology treatment and perinatal outcomes were clinically similar in donor and nondonor sperm cycles.

      3. Making the case: The importance of using 10 key preconception indicators in understanding the health of women of reproductive ageExternal
        Kroelinger CD, Okoroh EM, Boulet SL, Olson CK, Robbins CL.
        J Womens Health (Larchmt). 2018 Apr 9.

        In 2006, the Preconception Care (PCC) Work Group and the Select Panel on PCC published 10 recommendations promoting preconception health (PCH) and healthcare for women of reproductive age. In the years following the recommendations, much research focused on specific PCH behaviors, clinical provision of care, and care financing, but no comprehensive, well-defined set of indicators was identified. In 2011, seven states developed a set of 45 PCH indicators; however, to date, no one publication has assessed the usefulness of all 45 indicators in addressing PCH. This report makes the case for reducing the original 45 indicators to a condensed set of 10 for national and state reporting by describing the use of the 45 indicators to date, describing development of evaluation criteria for narrowing the number of indicators, and identifying gaps in indicator development for provision of PCC. Using the condensed set, states can set priorities, revise and develop programs and policies, implement system changes, and better allocate resources to support interventions to improve the health of women of reproductive age during the preconception and interconception periods.

      4. This chapter reviews the historical development of indicators to identify severe maternal morbidity/maternal near miss (SMM/MNM), and their use for public health surveillance, research, and clinical audit. While there has been progress toward identifying standard definitions for SMM/MNM within countries, there remain inconsistencies in the definition of SMM/MNM indicators and their application between countries. Using these indicators to screen for events that then trigger a clinical audit may both under identify select SMM/MNM (false negative)and over identify select SMM/MNM (false positive). Thus, indicators which support the efficient identification of SMM/MNM for the purpose of facility-based clinical audits are still needed.

      5. Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry studyExternal
        Litzky JF, Boulet SL, Esfandiari N, Zhang Y, Kissin DM, Theiler RN, Marsit CJ.
        J Assist Reprod Genet. 2018 Apr 10.

        PURPOSE: In vitro fertilization (IVF) infants have lower birthweights than their peers, predisposing them to long-term health consequences. Blastocyst transfer (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to date, however, have been inconclusive regarding BT’s effects on birthweight. METHODS: Participants included all US autologous, single-gestation, fresh embryo transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N = 124,154) from the National Assisted Reproductive Technology Surveillance System. Generalized linear models including obstetric history, maternal demographics, and infant sex and gestational age were used to compare birthweight outcomes for infants born following BT (N = 67,169) with infants born following CT (N = 56,985) and to test for an interaction between transfer stage and single embryo transfer (SET). RESULTS: Infants born following BT were 6 g larger than those born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04) and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between the groups. The interaction between SET and transfer stage was significant (p = 0.02). Among SET infants, BT was associated with 19.26 g increased birthweight compared to CT (p = 0.008). CONCLUSIONS: The increase in birthweights identified following BT is unlikely to be clinically relevant, as there were no differences in rates of macrosomia or LBW. These findings are clinically reassuring and indicate that the increasing use of BT is unlikely to further decrease the on average lower birthweights seen in IVF infants compared to their naturally conceived peers.

      6. Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infantsExternal
        Litzky JF, Boulet SL, Esfandiari N, Zhang Y, Kissin DM, Theiler RN, Marsit CJ.
        Am J Obstet Gynecol. 2018 Apr;218(4):433.e1-433.e10.

        BACKGROUND: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally conceived infants and are more likely to be born low birthweight (<2500 gr). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single-center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported. OBJECTIVES: The objective of this study was to compare the effect of frozen/thawed vs fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 g) and low birthweight (<2500 g). STUDY DESIGN: We used data from the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models. RESULTS: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142 g increase in birthweight compared with infants born after fresh embryo transfer (P < .001). An interaction between infant sex and embryo transfer type was significant (P < .0001), with frozen/thawed embryo transfer having a larger effect on male infants by 16 g. The adjusted risk of a macrosomic infant was 1.70 times higher (95% confidence interval, 1.64-1.76) following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95% confidence interval, 0.48-0.56) compared with fresh embryo transfer. CONCLUSION: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer, but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.

      7. Hormonal contraceptive use among women of older reproductive age: Considering risks and benefitsExternal
        Tepper NK, Godfrey EM, Folger SG, Whiteman MK, Marchbanks PA, Curtis KM.
        J Womens Health (Larchmt). 2018 Apr;27(4):413-417.

        As women approach menopause, fertility declines but pregnancy can still occur. Maternal and infant risks are increased among women of older reproductive age compared with younger women. A high proportion of pregnancies among women of older reproductive age are unintended and these pregnancies can also be associated with negative maternal and infant consequences. However, women and their healthcare providers may have concerns about risks associated with contraceptive use, particularly combined hormonal contraceptives, among women of older reproductive age who already may be at increased risk for conditions such as cardiovascular disease and breast cancer. Nonetheless, available evidence does not suggest that hormonal contraceptive use among women of older reproductive age substantially increases age-related risks of cardiovascular events or breast cancer. CDC recommends that contraception is still needed for women older than 44 years who have not reached menopause and wish to avoid pregnancy, and that based on age alone, all contraceptive methods are considered safe or generally safe for use by women of older reproductive age.

    • Substance Use and Abuse

      1. Fentanyl-associated illness among substance users – Fulton County, Georgia, 2015External
        Angela Parham M, Pomerleau AC, Peralta G, Drenzek CL, Edison LS.
        Am J Emerg Med. 2018 Mar 20.

        [No abstract]

      2. State Medicaid coverage for tobacco cessation treatments and barriers to accessing treatments – United States, 2015-2017External
        DiGiulio A, Jump Z, Yu A, Babb S, Schecter A, Williams KS, Yembra D, Armour BS.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 6;67(13):390-395.

        Cigarette smoking prevalence among Medicaid enrollees (25.3%) is approximately twice that of privately insured Americans (11.8%), placing Medicaid enrollees at increased risk for smoking-related disease and death (1). Medicaid spends approximately $39 billion annually on treating smoking-related diseases (2). Individual, group, and telephone counseling and seven Food and Drug Administration (FDA)-approved medications* are effective in helping tobacco users quit (3). Although state Medicaid coverage of tobacco cessation treatments improved during 2014-2015, coverage was still limited in most states (4). To monitor recent changes in state Medicaid cessation coverage for traditional (i.e., nonexpansion) Medicaid enrollees, the American Lung Association collected data on coverage of a total of nine cessation treatments: individual counseling, group counseling, and seven FDA-approved cessation medications(dagger) in state Medicaid programs during July 1, 2015-June 30, 2017. The American Lung Association also collected data on seven barriers to accessing covered treatments, such as copayments and prior authorization. As of June 30, 2017, 10 states covered all nine of these treatments for all enrollees, up from nine states as of June 30, 2015; of these 10 states, Missouri was the only state to have removed all seven barriers to accessing these cessation treatments. State Medicaid programs that cover all evidence-based cessation treatments, remove barriers to accessing these treatments, and promote covered treatments to Medicaid enrollees and health care providers would be expected to reduce smoking, smoking-related disease, and smoking-attributable federal and state health care expenditures (5-7).

      3. Hepatitis C in injection-drug users – a hidden danger of the opioid epidemicExternal
        Liang TJ, Ward JW.
        N Engl J Med. 2018 Mar 29;378(13):1169-1171.

        [No abstract]

      4. Cigarettes point of purchase patterns in 19 low-income and middle-income countries: Global Adult Tobacco Survey, 2008-2012External
        Mbulo L, Kruger J, Hsia J, Yin S, Salandy S, Orlan EN, Agaku I, Ribisl KM.
        Tob Control. 2018 Apr 5.

        BACKGROUND: There is little information on cigarette-purchasing behaviour among smokers globally. Understanding cigarette purchase and point-of-sale patterns can help guide the development and implementation of tobacco-control strategies in retail environments. OBJECTIVE: The purpose of this study was to identify where adults in 19 countries last purchased cigarettes. METHODS: Data were from 19 low-income and middle-income countries that conducted the Global Adult Tobacco Survey (GATS) during 2008-2012. GATS is a nationally representative household survey of adults aged 15 years or older using a standardised protocol to measure tobacco-related behaviours. Data were weighted to yield nationally representative estimates within each country and summarised by using descriptive statistics. RESULTS: Overall prevalence of current cigarette smoking ranged from 3.7% in Nigeria to 38.5% in the Russian Federation. Among current cigarette smokers, locations of last purchase were as follows: stores, from 14.6% in Argentina to 98.7% in Bangladesh (median=66.8%); street vendors, from 0% in Thailand to 35.7% in Vietnam (median=3.0%); kiosks, from 0.1% in Thailand to 77.3% in Argentina (median=16.1%); other locations, from 0.3% in China and Egypt to 57.5% in Brazil (median=2.6%). CONCLUSION: Cigarettes are purchased at various retail locations globally. However, stores and kiosks were the main cigarette purchase locations in 18 of the 19 countries assessed. Knowledge of where cigarette purchases occur could help guide interventions to reduce cigarette accessibility and use.

      5. State tobacco control expenditures and tax paid cigarette salesExternal
        Tauras JA, Xu X, Huang J, King B, Lavinghouze SR, Sneegas KS, Chaloupka FJ.
        PLoS One. 2018 ;13(4):e0194914.

        This research is the first nationally representative study to examine the relationship between actual state-level tobacco control spending in each of the 5 CDC’s Best Practices for Comprehensive Tobacco Control Program categories and cigarette sales. We employed several alternative two-way fixed-effects regression techniques to estimate the determinants of cigarette sales in the United States for the years 2008-2012. State spending on tobacco control was found to have a negative and significant impact on cigarette sales in all models that were estimated. Spending in the areas of cessation interventions, health communication interventions, and state and community interventions were found to have a negative impact on cigarette sales in all models that were estimated, whereas spending in the areas of surveillance and evaluation, and administration and management were found to have negative effects on cigarette sales in only some models. Our models predict that states that spend up to seven times their current levels could still see significant reductions in cigarette sales. The findings from this research could help inform further investments in state tobacco control programs.

    • Zoonotic and Vectorborne Diseases

      1. Estimating the numbers of pregnant women infected with Zika virus and infants with congenital microcephaly in Colombia, 2015-2017External
        Adamski A, Bertolli J, Castaneda-Orjuela C, Devine OJ, Johansson MA, Duarte MA, Tinker SC, Farr SL, Reyes MM, Tong VT, Garcia OE, Valencia D, Ortiz DA, Honein MA, Jamieson DJ, Martinez ML, Gilboa SM.
        J Infect. 2018 Apr 5.

        BACKGROUND: Colombia experienced a Zika virus (ZIKV) outbreak in 2015-2016. To assist with planning for medical and supportive services for infants affected by prenatal ZIKV infection, we used a model to estimate the number of pregnant women infected with ZIKV and the number of infants with congenital microcephaly from August 2015- August 2017. METHODS: We used nationally-reported cases of symptomatic ZIKV disease among pregnant women and information from the literature on the percent of asymptomatic infections to estimate the number of pregnant women with ZIKV infection occurring August 2015 – December 2016. We then estimated the number of infants with congenital microcephaly expected to occur August 2015 – August 2017. To compare to the observed counts of infants with congenital microcephaly due to all causes reported through the national birth defects surveillance system, the model was time limited to produce estimates for February – November 2016. FINDINGS: We estimated 1,140-2,160 (interquartile range [IQR]) infants with congenital microcephaly in Colombia, during August 2015 – August 2017, whereas 340-540 infants with congenital microcephaly would be expected in the absence of ZIKV. Based on the time limited version of the model, for February – November 2016, we estimated 650-1,410 infants with congenital microcephaly in Colombia. The 95% uncertainty interval for the latter estimate encompasses the 476 infants with congenital microcephaly reported during that approximate time frame based on national birth defects surveillance. INTERPRETATION: Based on modeled estimates, ZIKV infection during pregnancy in Colombia could lead to 3 to 4 times as many infants with congenital microcephaly in 2015-2017 as would have been expected in the absence of the ZIKV outbreak. FUNDING: This publication was made possible through support provided by the Bureau for Global Health, U.S. Agency for International Development under the terms of an Interagency Agreement with Centers for Disease Control and Prevention.

      2. Pet-associated Campylobacteriosis: A persisting public health concernExternal
        Campagnolo ER, Philipp LM, Long JM, Hanshaw NL.
        Zoonoses Public Health. 2018 May;65(3):304-311.

        Campylobacter is regarded as a leading cause of human bacterial gastroenteritis in the United States. We report on a case of laboratory-confirmed Campylobacter jejuni infection in the Commonwealth of Pennsylvania among members of a household living with a laboratory-confirmed but non-speciated Campylobacter-infected puppy. We describe an outbreak of likely dog-associated campylobacteriosis, the risk factors, potential routes of exposure and the clinical features in the exposed family members, which began shortly after exposure to the recently purchased dog. We also provide public health recommendations to prevent Campylobacter infections in veterinary care providers, pet owners and those planning to adopt pets in the future. Finally, this report underscores the importance of the One Health approach when public health responders, human and animal healthcare providers and clinical diagnostic laboratories are tasked with developing effective strategies when investigating, detecting and responding to zoonoses (diseases shared between animals and humans).

      3. Powassan virus disease in the United States, 2006-2016External
        Krow-Lucal ER, Lindsey NP, Fischer M, Hills SL.
        Vector Borne Zoonotic Dis. 2018 Mar 13.

        BACKGROUND: Powassan virus (POWV) is a tick-borne flavivirus that causes rare, but often severe, disease in humans. POWV neuroinvasive disease was added to the U.S. nationally notifiable disease list in 2001 and nonneuroinvasive disease was added in 2004. The only previous review of the epidemiology of POWV disease in the United States based on cases reported to the Centers for Disease Control and Prevention (CDC) covered the period from 1999 through 2005. METHODS: We describe the epidemiology and clinical features of laboratory-confirmed POWV disease cases reported to CDC from 2006 through 2016. RESULTS: There were 99 cases of POWV disease reported during the 11-year period, including 89 neuroinvasive and 10 nonneuroinvasive disease cases. There was a median of seven cases per year (range: 1-22), with the highest numbers of cases reported in 2011 (n = 16), 2013 (n = 15), and 2016 (n = 22). Cases occurred throughout the year, but peaked in May and June. Cases were reported primarily from northeastern and north-central states. Overall, 72 (73%) cases were in males and the median age was 62 years (range: 3 months-87 years). Of the 11 (11%) cases who died, all were aged >50 years. The average annual incidence of neuroinvasive POWV disease was 0.0025 cases per 100,000 persons. CONCLUSIONS: POWV disease can be a severe disease and has been diagnosed with increased frequency in recent years. However, this might reflect increased disease awareness, improved test availability, and enhanced surveillance efforts. Clinicians should consider POWV disease in patients presenting with acute encephalitis or aseptic meningitis who are resident in, or have traveled to, an appropriate geographic region.

      4. Rabies surveillance in the United States during 2016External
        Ma X, Monroe BP, Cleaton JM, Orciari LA, Yager P, Li Y, Kirby JD, Blanton JD, Petersen BW, Wallace RM.
        J Am Vet Med Assoc. 2018 Apr 15;252(8):945-957.

        OBJECTIVE To describe rabies and rabies-related events occurring during 2016 in the United States. DESIGN Observational study based on passive surveillance data. ANIMALS All animals submitted for rabies testing in the United States during 2016. PROCEDURES State and territorial public health programs provided data on animals submitted for rabies testing in 2016. Data were analyzed temporally and geographically to assess trends in domestic and sylvatic animal rabies cases. RESULTS During 2016, 50 states and Puerto Rico reported 4,910 rabid animals to the CDC, representing a 10.9% decrease from the 5,508 rabid animals reported in 2015. Of the 4,910 cases of animal rabies, 4,487 (91.4%) involved wildlife. Relative contributions by the major animal groups were as follows: 1,646 (33.5%) bats, 1,403 (28.6%) raccoons, 1,031 (21.0%) skunks, 313 (6.4%) foxes, 257 (5.2%) cats, 70 (1.4%) cattle, and 58 (1.2%) dogs. There was a 4.6% decrease in the number of samples submitted for testing in 2016, compared with the number submitted in 2015. No human rabies deaths were reported in 2016. CONCLUSIONS AND CLINICAL RELEVANCE Laboratory testing of animals suspected to be rabid remains a critical public health function and continues to be a cost-effective method to directly influence human rabies postexposure prophylaxis recommendations.

      5. Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue, and chikungunya virusesExternal
        Santiago GA, Vazquez J, Courtney S, Matias KY, Andersen LE, Colon C, Butler AE, Roulo R, Bowzard J, Villanueva JM, Munoz-Jordan JL.
        Nat Commun. 2018 Apr 11;9(1):1391.

        The emergence and spread of Zika virus (ZIKV) presented a challenge to the diagnosis of ZIKV infections in areas with transmission of dengue (DENV) and chikungunya (CHIKV) viruses. To facilitate detection of ZIKV infections, and differentiate these infections from DENV and CHIKV, we developed the Trioplex real-time RT-PCR assay (Trioplex assay). Here, we describe the optimization of multiplex and singleplex formats of the assay for a variety of chemistries and instruments to facilitate global standardization and implementation. We evaluated the analytical performance of all Trioplex modalities for detection of these three pathogens in serum and whole blood, and for ZIKV in urine. The limit of detection for the three viruses and in different RNA-extraction modalities is near 10(3) genome copy equivalents per milliliter (GCE/mL). Simultaneous testing of more than one specimen type from each patient provides a 6.4% additional diagnostic sensitivity. Overall, the high sensitivity of the Trioplex assay demonstrates the utility of this assay ascertaining Zika cases.

      6. Factors associated with prolonged viral shedding in patients with avian influenza A(H7N9) virus infectionExternal
        Wang Y, Guo Q, Yan Z, Zhou D, Zhang W, Zhou S, Li YP, Yuan J, Uyeki TM, Shen X, Wu W, Zhao H, Wu YF, Shang J, He Z, Yang Y, Zhao H, Hong Y, Zhang Z, Wu M, Wei T, Deng X, Deng Y, Cai LH, Lu W, Shu H, Zhang L, Luo H, Ing Zhou Y, Weng H, Song K, Yao L, Jiang M, Zhao B, Chi R, Guo B, Fu L, Yu L, Min H, Chen P, Chen S, Hong L, Mao W, Huang X, Gu L, Li H, Wang C, Cao B.
        J Infect Dis. 2018 Apr 10.

        Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

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CDC Science Clips Production Staff

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article’s inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article’s methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

Page last reviewed: January 31, 2019
Content source: Centers for Disease Control and Prevention