Issue 47, November 28, 2017

CDC Science Clips: Volume 9, Issue 47, November 28, 2017

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 ( The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Communicable Diseases
      1. *Brief report: Time from infection with the human immunodeficiency virus to diagnosis, United StatesExternal
        Hall HI, Song R, Szwarcwald CL, Green T.
        J Acquir Immune Defic Syndr. 2015 Jun 01;69(2):248-51.

        HIV testing efforts increased in recent years to reduce the percentage of persons with HIV unaware of their infection and to detect HIV early. An analysis of CD4 data from national HIV surveillance indicates that diagnosis delays decreased during 2003-2011; on average, persons diagnosed in 2011 had been infected 5.6 years before their diagnosis compared with 7.0 years among those diagnosed in 2003. Diagnosis delays were longer among females, blacks, Hispanics/Latinos, and older persons, but shorter among men who have sex with men, compared with their counterparts. Continued efforts to implement routine testing can help reduce diagnosis delays.

      2. *Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settingsExternal
        Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, Clark JE.
        MMWR Recomm Rep. 2006 Sep 22;55(Rr-14):1-17.

        These recommendations for human immunodeficiency virus (HIV) testing are intended for all health-care providers in the public and private sectors, including those working in hospital emergency departments, urgent care clinics, inpatient services, substance abuse treatment clinics, public health clinics, community clinics, correctional health-care facilities, and primary care settings. The recommendations address HIV testing in health-care settings only. They do not modify existing guidelines concerning HIV counseling, testing, and referral for persons at high risk for HIV who seek or receive HIV testing in nonclinical settings (e.g., community-based organizations, outreach settings, or mobile vans). The objectives of these recommendations are to increase HIV screening of patients, including pregnant women, in health-care settings; foster earlier detection of HIV infection; identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services; and further reduce perinatal transmission of HIV in the United States. These revised recommendations update previous recommendations for HIV testing in health-care settings and for screening of pregnant women (CDC. Recommendations for HIV testing services for inpatients and outpatients in acute-care hospital settings. MMWR 1993;42[No. RR-2]:1-10; CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2001;50[No. RR-19]:1-62; and CDC. Revised recommendations for HIV screening of pregnant women. MMWR 2001;50[No. RR-19]:63-85). Major revisions from previously published guidelines are as follows: For patients in all health-care settings HIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Persons at high risk for HIV infection should be screened for HIV at least annually. Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings. For pregnant women HIV screening should be included in the routine panel of prenatal screening tests for all pregnant women. HIV screening is recommended after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women.

      3. [No abstract]

      4. Antiretroviral therapy for the prevention of HIV-1 transmissionExternal
        Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, et al .
        N Engl J Med. 2016 Sep 01;375(9):830-9.

        BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. RESULTS: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 number, NCT00074581 .).

      5. Recommendations for HIV screening of gay, bisexual, and other men who have sex with men – United States, 2017External
        DiNenno EA, Prejean J, Irwin K, Delaney KP, Bowles K, Martin T, Tailor A, et al .
        MMWR Morb Mortal Wkly Rep. 2017 Aug 11;66(31):830-832.

        CDC’s 2006 recommendations for human immunodeficiency virus (HIV) testing state that all persons aged 13-64 years should be screened for HIV at least once, and that persons at higher risk for HIV infection, including sexually active gay, bisexual, and other men who have sex with men (MSM), should be rescreened at least annually (1). Authors of reports published since 2006, including CDC (2), suggested that MSM, a group that is at highest risk for HIV infection, might benefit from being screened more frequently than once each year. In 2013, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to specify an HIV rescreening interval but recommended annual screening for MSM as a reasonable approach (3). However, some HIV providers have begun to offer more frequent screening, such as once every 3 or 6 months, to some MSM. A CDC work group conducted a systematic literature review and held four expert consultations to review programmatic experience to determine whether there was sufficient evidence to change the 2006 CDC recommendation (i.e., at least annual HIV screening of MSM in clinical settings). The CDC work group concluded that the evidence remains insufficient to recommend screening more frequently than at least once each year. CDC continues to recommend that clinicians screen asymptomatic sexually active MSM at least annually. Each clinician can consider the benefits of offering more frequent screening (e.g., once every 3 or 6 months) to individual MSM at increased risk for acquiring HIV infection, weighing their patients’ individual risk factors, local HIV epidemiology, and local testing policies.

      6. Progression and Transmission of HIV/AIDS (PATH 2.0)External
        Gopalappa C, Farnham PG, Chen YH, Sansom SL.
        Med Decis Making. 2017 Feb;37(2):224-233.

        BACKGROUND: HIV transmission is the result of complex dynamics in the risk behaviors, partnership choices, disease stage and position along the HIV care continuum-individual characteristics that themselves can change over time. Capturing these dynamics and simulating transmissions to understand the chief sources of transmission remain important for prevention. METHODS: The Progression and Transmission of HIV/AIDS (PATH 2.0) is an agent-based model of a sample of 10,000 people living with HIV (PLWH), who represent all men who have sex with men (MSM) and heterosexuals living with HIV in the U.S.A. Persons uninfected were modeled as populations, stratified by risk and gender. The model included detailed individual-level data from several large national surveillance databases. The outcomes focused on average annual transmission rates from 2008 through 2011 by disease stage, HIV care continuum, and sexual risk group. RESULTS: The relative risk of transmission of those in the acute phase was nine-times [5th and 95th percentile simulation interval (SI): 7, 12] that of those in the non-acute phase, although, on average, those with acute infections comprised 1% of all PLWH. The relative risk of transmission was 24- to 50-times as high for those in the non-acute phase who had not achieved viral load suppression as compared with those who had. The relative risk of transmission among MSM was 3.2-times [SI: 2.7, 4.0] that of heterosexuals. Men who have sex with men and women generated 46% of sexually acquired transmissions among heterosexuals. CONCLUSIONS: The model results support a continued focus on early diagnosis, treatment and adherence to ART, with an emphasis on prevention efforts for MSM, a subgroup of whom appear to play a role in transmission to heterosexuals.

      7. Transmission rate modeling estimated secondary infections from those aware and unaware of their HIV infection. An estimated 49% of transmissions were from the 20% of persons living with HIV unaware of their infection. About eight transmissions would be averted per 100 persons newly aware of their infection; with more infections averted the higher the percentage of persons with viral suppression who can be linked to care. Improving all stages of HIV care would substantially reduce transmission rates.

      8. State-level estimates of HIV incidence, prevalence, and undiagnosed infectionsExternal
        Johnson AS, Song R, Hall HI.
        Poster session presented at: Conference on retroviruses and opportunistic infections; 2017 Feb 13-26; Seattle, WA. 2017 .

        [No abstract]

      9. PROBLEM/CONDITION: At the end of 2010, an estimated 872,990 persons in the United States were living with a diagnosis of human immunodeficiency virus (HIV) infection. Approximately one in four of the estimated HIV infections diagnosed in 2011 were attributed to heterosexual contact. Heterosexuals with a low socioeconomic status (SES) are disproportionately likely to be infected with HIV. REPORTING PERIOD: June-December 2010. DESCRIPTION OF SYSTEM: The National HIV Behavioral Surveillance System (NHBS) collects HIV prevalence and risk behavior data in selected metropolitan statistical areas (MSAs) from three populations at high risk for HIV infection: men who have sex with men, injecting drug users, and heterosexuals at increased risk for HIV infection. Data for NHBS are collected in rotating cycles in these three different populations. For the 2010 NHBS cycle among heterosexuals, men and women were eligible to participate if they were aged 18-60 years, lived in a participating MSA, were able to complete a behavioral survey in English or Spanish, and reported engaging in vaginal or anal sex with one or more opposite-sex partners in the 12 months before the interview. Persons who consented to participate completed an interviewer-administered, standardized questionnaire about HIV-associated behaviors and were offered anonymous HIV testing. Participants were sampled using respondent-driven sampling, a type of chain-referral sampling. Sampling focused on persons of low SES (i.e., income at the poverty level or no more than a high school education) because results of a pilot study indicated that heterosexual adults of low SES were more likely than those of high SES to be infected with HIV. To assess risk and testing experiences among persons at risk for acquiring HIV infection through heterosexual sex, analyses excluded participants who were not low SES, those who reported ever having tested positive for HIV, and those who reported recent (i.e., in the 12 months before the interview) male-male sex or injection drug use. This report summarizes unweighted data regarding HIV-associated risk, prevention, and testing behaviors from 9,278 heterosexual men and women interviewed in 2010 (the second cycle of NHBS data collection among heterosexuals). RESULTS: The median age of participants was 35 years; 47% were men. The majority of participants were black or African American (hereafter referred to as black) (72%) or Hispanic/Latino (21%). Most participants (men: 88%; women: 90%) reported having vaginal sex without a condom with one or more opposite-sex partners in the past 12 months; approximately one third (men: 30%; women: 29%) reported anal sex without a condom with one or more opposite-sex partners. The majority of participants (59%) reported using noninjection drugs in the 12 months before the interview; nearly one in seven (15%) had used crack cocaine. Although most participants (men: 71%; women: 77%) had ever been tested for HIV, this percentage was lower among Hispanic/Latino participants (men: 52%; women: 62%). Approximately one third (34%) of participants reported receiving free condoms in the 12 months before the interview; 11% reported participating in a behavioral HIV prevention program. INTERPRETATION: A substantial proportion of heterosexuals interviewed for the 2010 NHBS heterosexual cycle reported engaging in behaviors that increase the risk for HIV infection. However, HIV testing was suboptimal among the overall sample, including among groups disproportionately affected by HIV infection (i.e., blacks and Hispanics/Latinos). PUBLIC HEALTH ACTION: Increasing coverage of HIV testing and other HIV prevention services among heterosexuals at increased risk is important, especially among groups disproportionately affected by HIV infection, such as blacks and Hispanics/Latinos. The National HIV/AIDS Strategy for the United States delineates a coordinated national response to reduce infections and HIV-related health disparities among disproportionately affected groups. NHBS data can guide national and local planning efforts to maximize the impact of HIV prevention programs.

      10. Using CD4 data to estimate HIV incidence, prevalence, and percent of undiagnosed infections in the United StatesExternal
        Song R, Hall HI, Green TA, Szwarcwald CL, Pantazis N.
        J Acquir Immune Defic Syndr. 2017 Jan 01;74(1):3-9.

        INTRODUCTION: The incidence and prevalence of HIV infection are important measures of HIV trends; however, they are difficult to estimate because of the long incubation period between infection and symptom development and the relative infrequency of HIV screening. A new method is introduced to estimate HIV incidence, prevalence, and the number of undiagnosed infections in the United States using data from the HIV case surveillance system and CD4 test results. METHODS: Persons with HIV diagnosed during 2006-2013 and their CD4 test results were used to estimate the distribution of diagnosis delay from HIV infection to diagnosis based on a well-characterized CD4 depletion model. This distribution was then used to estimate HIV incidence, prevalence, and the number of undiagnosed infections. RESULTS: Applying this method, we estimated that the annual number of new HIV infections decreased after 2007, from 48,300 (95% confidence interval [CI]: 47,300 to 49,400) to 39,000 (95% CI: 36,600 to 41,400) in 2013. Prevalence increased from 923,200 (95% CI: 914,500 to 931,800) in 2006 to 1,104,600 (95% CI: 1,084,300 to 1,124,900) in 2013, whereas the proportion of undiagnosed infections decreased from 21.0% in 2006 (95% CI: 20.2% to 21.7%) to 16.4% (95% CI: 15.7% to 17.2%) in 2013. CONCLUSIONS: HIV incidence, prevalence, and undiagnosed infections can be estimated using HIV case surveillance data and information on first CD4 test result after diagnosis. Similar to earlier findings, the decreases in incidence and undiagnosed infections are encouraging but intensified efforts for HIV testing and treatment are needed to meet the goals of the National HIV/AIDS Strategy.

  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. Asthma prevalence trends by weight status among US children aged 2-19 years, 1988-2014External
        Akinbami LJ, Rossen LM, Fakhouri TH, Fryar CD.
        Pediatr Obes. 2017 Nov 12.

        BACKGROUND: Obesity is a risk factor for asthma. However, it is unclear if increased obesity prevalence contributed to rising childhood asthma prevalence. OBJECTIVE: To assess if population-level changes in weight status impacted asthma prevalence over time. METHODS: Using nationally representative 1988-2014 National Health and Nutrition Examination Survey data for 40 644 children aged 2-19 years, we analyzed asthma trends by weight status (body mass index age-specific percentiles determined using measured weight and height). Logistic regression and population attributable fraction were used to assess the association between obesity and asthma prevalence. RESULTS: Although obesity was a risk factor for asthma throughout the period, asthma prevalence increased only among children with normal weight; there was no interaction between weight status and time. The population attributable fraction for overweight/obesity rose from 8.5% in 1988-1994 to 11.9% in 2011-2014, but this increase was not significant (P = 0.44). CONCLUSIONS: Together, these data do not support a contribution of obesity trends to asthma prevalence trends.

      2. Counseling on sun protection and indoor tanningExternal
        Balk SJ, Gottschlich EA, Holman DM, Watson M.
        Pediatrics. 2017 Nov 10.

        BACKGROUND: The US Preventive Services Task Force recommends clinical counseling for individuals ages 10 to 24 years to decrease skin cancer risk. METHODS: A national, random sample of US American Academy of Pediatrics members practicing primary care in 2002 (response rate 55%) and 2015 (response rate 43%). Surveys explored attitudes and experiences regarding sun protection counseling; indoor tanning questions were added in 2015. chi2 tests compared demographics and counseling responses across years, and multivariable logistic regression models examined counseling predictors. RESULTS: More pediatricians in 2015 (34%) than in 2002 (23%) reported discussing sun protection during recent summer months with >/=75% of patients. This pattern held across all patient age groups (each P <.001). Female and suburban pediatricians counseled more; those in the South and West counseled less. More pediatricians in 2015 than in 2002 named time as a barrier. Sun protection ranked lowest among preventive topics in both years. In 2015, approximately one-third of pediatricians reported discussing indoor tanning at least once with 10 to 13 year-old patients; approximately half discussed this with older adolescents. Most (70%) did not know if their states had laws on minors’ indoor tanning access; those stating they knew whether a law existed counseled more. CONCLUSIONS: Although improved, sun protection counseling rates remain low. Indoor tanning counseling can be improved. Because early-life exposure to UV radiation increases risk and clinician counseling can positively impact prevention behaviors, pediatricians have an important role in skin cancer prevention; counseling may save lives. Time constraints remain a barrier.

      3. Breast cancer related perceptions and practices of health professionals working in Brazil’s network of primary care unitsExternal
        Hallowell BD, Puricelli Perin DM, Simoes EJ, Paez DC, Parra DC, Brownson RC, Saraiya M.
        Prev Med. 2017 Nov 08.

        In 2004 the Brazilian National Cancer Institute (INCA) established breast cancer screening guidelines for women in Brazil: annual clinical breast exam for women age 40-49 and biennial mammogram for women age 50-69. Healthcare provider’s adherence to these guidelines is currently unknown. The objective of this study is to describe the perceptions and practices related to breast cancer screening among physicians, nurses, and health unit coordinators working in the network of primary healthcare units (HCUs) in Brazil. In 2011, 1600 primary HCUs were randomly sampled from all regions in Brazil. At each HCU the coordinator and one health professional were asked to participate in a telephone survey to gathered information on their knowledge, attitudes, and practices related to breast cancer screening. Participation rates for coordinators, physicians, and nurses were 78%, 34%, and 65% respectively. Health unit coordinators identified numerous barriers that prevent patients from receiving appropriate screening, many (44%) were unaware of INCA cancer screening guidelines. Despite a high perceived impact of INCA guidelines, a majority of physicians and nurses did not follow them. Most physicians and nurses recommended mammograms on an annual basis (~75%) and 50.9% of nurses and 25.1% of physicians initiated routine breast cancer screening in women under age 40. Physicians and nurses in Brazil screen at younger ages and more frequently than recommended by INCA guidelines. Given that primary HCUs are the source of health care for many women, interventions that educate healthcare providers on the appropriate ages and intervals for breast cancer screening may prove useful.

      4. Objectives: To compare estimated prevalence of past-year dental visit (PPYDV) among US adults aged >=18 years from the Behavioral Risk Factor Surveillance System (BRFSS) to estimates from the Medical Expenditure Panel Survey (MEPS), National Health Interview Survey (NHIS), and National Health and Nutrition Examination Survey (NHANES). Methods: We estimated PPYDV adjusted for covariates (age, race/ethnicity, education level, poverty status, edentulism) using BRFSS, MEPS, and NHIS 1999-2010, and NHANES 1999-2004. We tested trend in overall PPYDV for BRFSS, MEPS, and NHIS from 1999-2010. For 2002 and 2010, we calculated absolute differences (AD) and 95% confidence intervals (CI) in PPYDV between BRFSS and each of the other surveys overall and among subpopulations defined by covariates. We pooled NHANES 1999-2004 data for comparison with BRFSS 2002. Results: From 1999 to 2010, BRFSS (68.5% vs. 67.5%), MEPS (43.5% vs. 39.7%), and NHIS (63.3% vs. 59.7%) showed small but significant decreases in overall PPYDV. In 2002, estimates for overall PPYDV were highest for BRFSS (70.0%) and lowest for MEPS (43.9%) with estimates for NHIS (61.5%) and NHANES (1999-2004: 58.1%) in between; the largest AD (26.2%, 95% CI: 25.0%-27.3%) was between BRFSS and MEPS. ADs were consistent in 2002 and 2010, overall and by covariates, except among edentate persons, where PPYDV estimates from BRFSS and NHIS were similar. Conclusions: Estimates of PPYDV from BRFSS were notably higher than estimates from MEPS, NHIS, or NHANES except among the edentate. Trends in PPYDV over time, however, were consistent across all surveys.

      5. OBJECTIVE: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? METHODS: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. RESULTS: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (i.e., angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

      6. Widespread recent increases in county-level heart disease mortality across age groupsExternal
        Vaughan AS, Ritchey MD, Hannan J, Kramer MR, Casper M.
        Ann Epidemiol. 2017 Oct 28.

        PURPOSE: Recent national trends show decelerating declines in heart disease mortality, especially among younger adults. National trends may mask variation by geography and age. We examined recent county-level trends in heart disease mortality by age group. METHODS: Using a Bayesian statistical model and National Vital Statistics Systems data, we estimated overall rates and percent change in heart disease mortality from 2010 through 2015 for four age groups (35-44, 45-54, 55-64, and 65-74 years) in 3098 US counties. RESULTS: Nationally, heart disease mortality declined in every age group except ages 55-64 years. County-level trends by age group showed geographically widespread increases, with 52.3%, 58.5%, 69.1%, and 42.0% of counties experiencing increases with median percent changes of 0.6%, 2.2%, 4.6%, and -1.5% for ages 35-44, 45-54, 55-64, and 65-74 years, respectively. Increases were more likely in counties with initially high heart disease mortality and outside large metropolitan areas. CONCLUSIONS: Recent national trends have masked local increases in heart disease mortality. These increases, especially among adults younger than age 65 years, represent challenges to communities across the country. Reversing these trends may require intensification of primary and secondary prevention-focusing policies, strategies, and interventions on younger populations, especially those living in less urban counties.

    • Communicable Diseases
      1. Increased Kawasaki disease incidence associated with higher precipitation and lower temperatures, Japan, 1991-2004External
        Abrams JY, Blase JL, Belay EB, Uehara R, Maddox RA, Schonberger LB, Nakamura Y.
        Pediatr Infect Dis J. 2017 Nov 14.

        BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis which primarily affects children. The etiology of KD is unknown: while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well-documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. METHODS: The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiological surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5, and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. RESULTS: KD incidence was negatively associated with temperature in the previous 2, 3, 4, and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100mm was associated with increased KD incidence (rate ratio=1.012, 95% confidence interval=1.005-1.019) and an increase of monthly mean temperature by 1 degrees C was associated with decreased KD incidence (RR=0.984, 95% CI=0.978-0.990). CONCLUSIONS: KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

      2. Incidence of acute diarrhea-associated death among children < 5 years of age in Bangladesh, 2010-12External
        Ahmed M, Abedin J, Alam KF, Al Mamun A, Paul RC, Rahman M, Iuliano AD, Sturm-Ramirez K, Parashar U, Luby SP, Gurley ES.
        Am J Trop Med Hyg. 2017 Nov 06.

        Although acute diarrheal deaths have declined globally among children < 5 years, it may still contribute to childhood mortality as an underlying or contributing cause. The aim of this project was to estimate the incidence of acute diarrhea-associated deaths, regardless of primary cause, among children < 5 years in Bangladesh during 2010-12. We conducted a survey in 20 unions (administrative units) within the catchment areas of 10 tertiary hospitals in Bangladesh. Through social networks, our field team identified households where children < 5 years were reported to have died during 2010-12. Trained data collectors interviewed caregivers of the deceased children and recorded illness symptoms, health care seeking, and other information using an abbreviated international verbal autopsy questionnaire. We classified the deceased based upon the presence of diarrhea before death. We identified 880 deaths, of which 36 (4%) died after the development of acute diarrhea, 17 (2%) had diarrhea-only in the illness preceding death, and 19 (53%) had cough or difficulty breathing in addition to diarrhea. The estimated annual incidence of all-cause mortality in the unions < 13.6 km of the tertiary hospitals was 26 (95% confidence interval [CI] 16-37) per 1,000 live births compared with the mortality rate of 37 (95% CI 26-49) per 1,000 live births in the unions located >/= 13.6 km. Diarrhea contributes to childhood death at a higher proportion than when considering it only as the sole underlying cause of death. These data support the use of interventions aimed at preventing acute diarrhea, especially available vaccinations for common etiologies, such as rotavirus.

      3. Global infection prevention and control priorities 2018-22: a call for actionExternal
        Allegranzi B, Kilpatrick C, Storr J, Kelley E, Park BJ, Donaldson L.
        Lancet Glob Health. 2017 Dec;5(12):e1178-e1180.

        [No abstract]

      4. Research roadmap for tuberculosis transmission science: Where do we go from here and how will we know when we’re there?External
        Auld SC, Kasmar AG, Dowdy DW, Mathema B, Gandhi NR, Churchyard GJ, Rustomjee R, Shah NS.
        J Infect Dis. 2017 Nov 03;216(suppl_6):S662-s668.

        High rates of tuberculosis transmission are driving the ongoing global tuberculosis epidemic, and there is a pressing need for research focused on understanding and, ultimately, halting transmission. The ongoing tuberculosis-human immunodeficiency virus (HIV) coepidemic and rising rates of drug-resistant tuberculosis in parts of the world add further urgency to this work. Success in this research will require a concerted, multidisciplinary effort on the part of tuberculosis scientists, clinicians, programs, and funders and must span the research spectrum from biomedical sciences to the social sciences, public health, epidemiology, cost-effectiveness analyses, and operations research. Heterogeneity of tuberculosis disease, both among individual patients and among communities, poses a substantial challenge to efforts to interrupt transmission. As such, it is likely that effective interventions to stop transmission will require a combination of approaches that will vary across different epidemiologic settings. This research roadmap summarizes key gaps in our current understanding of transmission, as laid out in the preceding articles in this series. We also hope that it will be a call to action for the global tuberculosis community to make a sustained commitment to tuberculosis transmission science. Halting transmission today is an essential step on the path to end tuberculosis tomorrow.

      5. Risk factors and outcomes associated with multidrug-resistant Acinetobacter baumannii upon ICU admissionExternal
        Blanco N, Harris AD, Rock C, Johnson JK, Pineles L, Bonomo RA, Srinivasan A, Pettigrew MM, Thom KA.
        Antimicrob Agents Chemother. 2017 Nov 13.

        Introduction: Multi-drug resistant (MDR) Acinetobacter baumannii, associated with broad-spectrum antibiotic use, is an important nosocomial pathogen associated with morbidity and mortality. This study aimed to investigate the prevalence of MDR A. baumannii perirectal colonization among adult patients at ICU admission over a 5-year period, and to identify risk factors and outcomes associated with colonization. Methods: A retrospective cohort analysis of patients admitted to the medical (MICU) and surgical intensive care units (SICU) at the University of Maryland Medical Center from May 2005 to September 2009 was performed using perirectal surveillance cultures on admission. Poisson and logistic models were performed to identify associated risk factors and outcomes.Results: Four percent of the cohort were positive for MDR A. baumannii at ICU admission. Among patients admitted to the MICU, those positive at admission were more likely to be older, to have received antibiotics before ICU admission, and to have shorter length of stay prior to ICU admission. Among patients admitted to the SICU, those colonized were more likely to have at least one previous admission to our hospital. Patients positive at ICU admission were 15.2 times more likely to develop a subsequent positive clinical culture for A. baumannii and 1.4 times more likely to die during the current hospitalization.Discussion: Risk factors associated with MDR A. baumannii colonization differ by ICU-type. Colonization acts as a marker of disease severity, risk of developing a subsequent Acinetobacter infection, and dying during hospitalization. Therefore, active surveillance could guide empiric antibiotic selection and inform infection control practices.

      6. How well are U.S. primary care providers assessing whether their male patients have male sex partners?External
        Chavez PR, Wesolowski LG, Peters PJ, Johnson CH, Nasrullah M, Oraka E, August EM, DiNenno E.
        Prev Med. 2017 Nov 07.

        Identifying patients at-risk for HIV infection, such as men who have sex with men (MSM), is an important step in providing HIV testing and prevention interventions. It is unknown how primary care providers (PCPs) assess MSM status and related HIV-risk factors. We analyzed data from a panel-derived web-based survey for healthcare providers conducted in 2014 to describe how PCPs in the U.S. determined their patients’ MSM status. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to describe PCP characteristics associated with systematically determining MSM status (i.e., PCP used “a patient-completed questionnaire” or “routine verbal review of sex history”). Among the 1008 PCPs, 56% determined MSM status by routine verbal review of sexual history; 41% by patient disclosure; 39% by questions driven by symptoms/history; 23% by using a patient-completed questionnaire, and 9% didn’t determine MSM status. PCPs who systematically determined MSM status (n=665; 66%) were more likely to be female (aPR=1.16, CI=1.06-1.26), to be affiliated with a teaching hospital (aPR=1.15, CI=1.06-1.25), to routinely screen all patients aged 13-64 for HIV (aPR=1.29, CI=1.18-1.41), and to estimate that 6% or more of their male patients are MSM (aPR=1.14, CI=1.01-1.30). The majority of PCPs assessed MSM status and HIV risk factors through routine verbal reviews of sexual history. Implementing a systematic approach to identify MSM status and assess risk may allow PCPs to identify more patients needing frequent HIV testing and other preventive services, while mitigating socio-cultural barriers to obtaining such information.

      7. What we know about tuberculosis transmission: An overviewExternal
        Churchyard G, Kim P, Shah NS, Rustomjee R, Gandhi N, Mathema B, Dowdy D, Kasmar A, Cardenas V.
        J Infect Dis. 2017 Nov 03;216(suppl_6):S629-s635.

        Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission.

      8. Relating coccidioidomycosis (valley fever) incidence to soil moisture conditionsExternal
        Coopersmith EJ, Bell JE, Benedict K, Shriber J, McCotter O, Cosh MH.
        Geohealth. 2017 Apr 17;1:51-63.

        Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

      9. The evolution of HIV testing continuesExternal
        Delaney KP, Wesolowski LG, Owen SM.
        Sex Transm Dis. 2017 Dec;44(12):747-749.

        [No abstract]

      10. Integrated view of Vibrio cholerae in the AmericasExternal
        Domman D, Quilici ML, Dorman MJ, Njamkepo E, Mutreja A, Mather AE, Delgado G, Morales-Espinosa R, Grimont PA, Lizarraga-Partida ML, Bouchier C, Aanensen DM, Kuri-Morales P, Tarr CL, Dougan G, Parkhill J, Campos J, Cravioto A, Weill FX, Thomson NR.
        Science. 2017 Nov 10;358(6364):789-793.

        Latin America has experienced two of the largest cholera epidemics in modern history; one in 1991 and the other in 2010. However, confusion still surrounds the relationships between globally circulating pandemic Vibrio cholerae clones and local bacterial populations. We used whole-genome sequencing to characterize cholera across the Americas over a 40-year time span. We found that both epidemics were the result of intercontinental introductions of seventh pandemic El Tor V. cholerae and that at least seven lineages local to the Americas are associated with disease that differs epidemiologically from epidemic cholera. Our results consolidate historical accounts of pandemic cholera with data to show the importance of local lineages, presenting an integrated view of cholera that is important to the design of future disease control strategies.

      11. Addressing maternal health during CDC’s Ebola response in the United StatesExternal
        Ellington S, Perez M, Morof D, Zotti ME, Callaghan W, Meaney-Delman D, Glover M, Ha QC, Jamieson DJ.
        J Womens Health (Larchmt). 2017 Nov;26(11):1141-1145.

        Previous outbreaks suggest that pregnant women with Ebola virus disease (EVD) are at increased risk for severe disease and death. Healthcare workers who treat pregnant women with EVD are at increased risk of body fluid exposure. Despite the absence of pregnant women with EVD in the United States, CDC activated the Maternal Health Team (MHT), a functional unit dedicated to emergency preparedness and response issues, on October 18, 2014. We describe major activities of the MHT. A high-priority MHT activity was to publish guiding principles early in the response. The MHT also prepared guidance documents, provided guidance and technical support for hospital preparedness, and addressed inquiries. We analyzed maternal health inquiries received through CDC-INFO, MHT, and CDC’s Medical Investigations Team from August 2014 to December 2015. Internal call logs used to capture, monitor, and track inquiries for the three data sources were merged. Inquiries not related to maternal health issues and duplicates were removed. Each inquiry was categorized by route (email/phone), inquirer type, and topic. In total, 201 inquiries were received from clinicians, public health professionals, and the public. The predominant topic was related to infection control for high-risk situations such as labor and delivery. During the Ebola response, most inquiries were received via email rather than telephone, a notable shift compared to the H1N1 emergency response. Lessons learned during the H1N1 and Ebola responses are currently informing CDC’s Zika Response, an unprecedented emergency response primarily focused on reproductive health issues.

      12. The relationship between social support, HIV serostatus, and perceived likelihood of being HIV positive among self-settled female, foreign migrants in Cape Town, South AfricaExternal
        Giorgio M, Townsend L, Zembe Y, Cheyip M, Guttmacher S, Kapadia F, Mathews C.
        J Immigr Minor Health. 2017 Aug;19(4):883-890.

        Female cross-border migrants experience elevated risks for HIV, and migrants in South Africa may face additional risks due to the country’s underlying HIV prevalence. These risks may be mitigated by the receipt of social support. A behavioral risk-factor survey was administered using respondent-driven sampling. Multivariable regression models assessed the relationships between social support and two HIV outcomes: HIV serostatus and perceived HIV status. Low social support was not significantly associated with HIV status (aOR = 1.03, 95 % CI 0.43-2.46), but was significantly related to a perception of being HIV positive (aPR = 1.36, 95 % CI 1.04-1.78). Age, marital status, and education level were significantly associated with HIV serostatus. Illegal border-crossing, length of time in South Africa, anal sex, and transactional sex were significantly associated with aperception of being HIV positive. Future research should investigate how HIV risks and the receipt of social support change throughout the migration process.

      13. The target end date for the global elimination of trachoma as a public health problem is 2020. As countries begin the process for submitting their dossier for the validation of elimination of trachoma as a public health problem, strategies for post-validation surveillance must be considered. Seroprevalence of antibodies against antigens from the causative bacteria Chlamydia trachomatis (Ct) in young children has been shown to reflect trachomatous inflammation-follicular (TF) rates in both endemic and previously endemic settings. However, none of these studies has directly compared age seroprevalence in the same communities before and after mass drug administration (MDA) for trachoma. Here we report a marked shift in age seroprevalence curves in four villages in Kapilvastu District, Nepal, before and after MDA. Clinical examinations were performed and blood was taken before (N = 659) and 5 years after (N = 646) MDA. Rates of TF decreased from 17.6% in </= 9-year-olds before MDA (N = 52) to 0% in </= 9-year-olds (N = 73) after MDA. Positive antibody responses to Ct in the entire population decreased from 82.1% pre-MDA to 35.8% post-MDA, whereas those among </= 9-year-olds decreased from 59.6% to 4.1%. These data show that the postintervention decrease in TF was reflected in a drop in anti-Ct antibody responses, suggesting that antibody responses could be useful indicators for post-validation surveillance.

      14. HIV acquisition and transmission potential among African American men who have sex with men and women in three U.S. citiesExternal
        Joseph HA, Pan Y, Mendoza M, Harawa NT, Lauby J, Hosek SG, Bluthenthal RN, Milnamow M, Fernandez MI, Jeffries WL, Belcher L, Millett GA.
        Arch Sex Behav. 2017 Nov 09.

        Black men who have sex with men and women (BMSMW) are at increased HIV risk, but few efficacious interventions meet their unique needs. Three HIV prevention interventions were evaluated with a common protocol. Baseline data were pooled to describe sexual behavior involving transmission risk with male, female, and male-to-female transgender partners and identify factors associated with transmission risk. BMSMW from Los Angeles, Philadelphia, and Chicago who reported sexual risk and bisexual behavior in the past year were recruited via modified chain referral sampling and community recruitment. Baseline assessments were conducted via audio computer-assisted interview and sexual behaviors assessed over the past 3 months. From December 2010 to November 2012, 584 BMSMW were enrolled across the three cities. More than half (55%) were recruited by other participants. Overall, the mean age was 43 years. Seventy-five percent reported an annual income <$10,000 and selling sex was prevalent (31%). Three-quarters identified as bisexual. Thirty-nine percent were HIV-positive. Among HIV-positive participants, 46% reported sex without condoms with HIV-negative or unknown male partners and 45% with HIV-negative or unknown female partners. Overall, factors associated with sex without condoms included network size, education, income, sexual orientation identification, HIV status, exchange sex, homonegativity, and social support. Findings support the need for enhanced HIV prevention efforts for this population. Future studies should examine contextual factors in addition to individual risk behaviors to inform the development and implementation of promising strategies to prevent HIV and promote the overall health and wellness of BMSMW and their sexual partners.

      15. Injection-related risk behavior and engagement in outreach, intervention and prevention services across 20 US citiesExternal
        Mackesy-Amiti ME, Boodram B, Spiller MW, Paz-Bailey G, Prachand N, Broz D.
        J Acquir Immune Defic Syndr. 2017 Jul 01;75 Suppl 3:S316-s324.

        BACKGROUND: Monitoring the effects of HIV prevention efforts on risk behaviors among persons who inject drugs is a key to inform prevention programs and policy. METHODS: Using data from the 2012 National HIV Behavioral Surveillance interviews with persons who inject drugs across 20 US cities (n = 10,171), we conducted latent class analysis to identify injection risk classes and assess the relationship between engagement in prevention services and injection-related risk behavior. We conducted stratified analyses to examine the consistency of these associations across different geographical regions. RESULTS: The latent class analysis identified 6 distinct classes of injection-related risk behavior. The class structure was consistent across regions of the United States, but the distribution of risk classes varied significantly across regions. With covariate adjustment, the South had the most high-risk behavior (21%) and the Midwest had the least (6%). Participation in syringe access services and other prevention services was the lowest in the South. Syringe access was associated with a significantly lower likelihood of membership in the highest risk class in all regions except the Midwest. Participation in individual or group intervention with a practical skills component was associated with less risky injection behavior in all regions except the Northeast. Interventions that featured only safer injection information and discussion had no relationship with risk class. CONCLUSIONS: Our findings support evidence of the effectiveness of syringe service programs and safer injection skills training in reducing high-risk injection behavior and underscore the need to improve access to these prevention interventions in the South of the United States.

      16. Drivers of tuberculosis transmissionExternal
        Mathema B, Andrews JR, Cohen T, Borgdorff MW, Behr M, Glynn JR, Rustomjee R, Silk BJ, Wood R.
        J Infect Dis. 2017 Nov 03;216(suppl_6):S644-s653.

        Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon gamma-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.

      17. BACKGROUND: The response to the 2014-2016 Ebola epidemic included an unprecedented effort from federal, state, and local public health authorities to monitor the health of travelers entering the United States from countries with Ebola outbreaks. The Check and Report Ebola (CARE) Hotline, a novel approach to monitoring, was designed to enable travelers to report their health status daily to an interactive voice recognition (IVR) system. The system was tested with 70 Centers for Disease Control and Prevention (CDC) federal employees returning from deployments in outbreak countries. OBJECTIVE: The objective of this study was to describe the development of the CARE Hotline as a tool for postarrival monitoring and examine the usage characteristics and user experience of the tool during a public health emergency. METHODS: Data were obtained from two sources. First, the CARE Hotline system produced a call log which summarized the usage characteristics of all 70 users’ daily health reports. Second, we surveyed federal employees (n=70) who used the CARE Hotline to engage in monitoring. A total of 21 (21/70, 30%) respondents were included in the survey analytic sample. RESULTS: While the CARE Hotline was used for monitoring, 70 users completed a total of 1313 calls. We found that 94.06% (1235/1313) of calls were successful, and the average call time significantly decreased from the beginning of the monitoring period to the end by 32 seconds (Z score=-6.52, P<.001). CARE Hotline call log data were confirmed by user feedback; survey results indicated that users became more familiar with the system and found the system easier to use, from the beginning to the end of their monitoring period. The majority of the users were highly satisfied (90%, 19/21) with the system, indicating ease of use and convenience as primary reasons, and would recommend it for future monitoring efforts (90%, 19/21). CONCLUSIONS: The CARE Hotline garnered high user satisfaction, required minimal reporting time from users, and was an easily learned tool for monitoring. This phone-based technology can be modified for future public health emergencies.

      18. Non-disclosure to male partners and incomplete PMTCT regimens associated with higher risk of mother-to-child HIV transmission: a national survey in KenyaExternal
        McGrath CJ, Singa B, Langat A, Kinuthia J, Ronen K, Omolo D, Odongo BE, Wafula R, Muange P, Katana A, Ng’anga L, John-Stewart GC.
        AIDS Care. 2017 Nov 11:1-9.

        Health worker experience and community support may be higher in high HIV prevalence regions than low prevalence regions, leading to improved prevention of mother-to-child HIV transmission (PMTCT) programs. We evaluated 6-week and 9-month infant HIV transmission risk (TR) in a high prevalence region and nationally. Population-proportionate-to-size sampling was used to select 141 clinics in Kenya, and mobile teams surveyed mother-infant pairs attending 6-week and 9-month immunizations. HIV DNA testing was performed on HIV-exposed infants. Among 2521 mother-infant pairs surveyed nationally, 2423 (94.7%) reported HIV testing in pregnancy or prior diagnosis, of whom 200 (7.4%) were HIV-infected and 188 infants underwent HIV testing. TR was 8.8% (4.0%-18.3%) in 6-week and 8.9% (3.2%-22.2%) in 9-month cohorts including mothers with HIV diagnosed postpartum, of which 53% of infant infections were due to previously undiagnosed mothers. Of 276 HIV-exposed infants in the Nyanza survey, TR was 1.4% (0.4%-5.3%) at 6-week and 5.1% (2.5%-9.9%) at 9-months. Overall TR was lower in Nyanza, high HIV region, than nationally (3.3% vs. 7.2%, P = 0.02). HIV non-disclosure to male partners and incomplete ARVs were associated with TR in both surveys [aOR = 12.8 (3.0-54.3); aOR = 5.6 (1.2-27.4); aOR = 4.5 (1.0-20.0), aOR = 2.5, (0.8-8.4), respectively]. TR was lower in a high HIV prevalence region which had better ARV completion and partner HIV disclosure, possibly due to programmatic efficiencies or community/peer/partner support. Most 9-month infections were among infants of mothers without prior HIV diagnosis. Strategies to detect incident or undiagnosed maternal infections will be important to achieve PMTCT.

      19. Microbial diversity of genital ulcers of HSV-2 seropositive womenExternal
        Mehta SD, Pradhan AK, Green SJ, Naqib A, Odoyo-June E, Gaydos CA, Barry S, Landay A, Bailey RC.
        Sci Rep. 2017 Nov 13;7(1):15475.

        We measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T. pallidum from none; one woman showed serologic evidence of syphilis. Overall, 63% of women were HIV-positive and 49% had an uncircumcised male sex partner. By both multiple group testing and regression, Porphyromonas (FDR p-value = 0.02), Prevotella (FDR p-value = 0.03), Anaerococcus (FDR p-value = 0.07), and Dialister (FDR p-value = 0.09) were detected at higher relative abundance in HSV-2 PCR-positive than negative ulcers. The presence of HSV-2 in a lesion was associated with presumed bacterial agents of Bacterial vaginosis. Differences in bacterial communities may contribute to HSV-2 ulcer pathogenesis, severity, or prolonged healing. If these results are confirmed, future studies may consider the influence of BV treatment on women’s GUD and HSV-2 incidence and recurrence.

      20. Scaling up HIV viral load – lessons from the large-scale implementation of HIV early infant diagnosis and CD4 testingExternal
        Peter T, Zeh C, Katz Z, Elbireer A, Alemayehu B, Vojnov L, Costa A, Doi N, Jani I.
        J Int AIDS Soc. 2017 Nov;20 Suppl 7:9-15.

        INTRODUCTION: The scale-up of effective HIV viral load (VL) testing is an urgent public health priority. Implementation of testing is supported by the availability of accurate, nucleic acid based laboratory and point-of-care (POC) VL technologies and strong WHO guidance recommending routine testing to identify treatment failure. However, test implementation faces challenges related to the developing health systems in many low-resource countries. The purpose of this commentary is to review the challenges and solutions from the large-scale implementation of other diagnostic tests, namely nucleic-acid based early infant HIV diagnosis (EID) and CD4 testing, and identify key lessons to inform the scale-up of VL. DISCUSSION: Experience with EID and CD4 testing provides many key lessons to inform VL implementation and may enable more effective and rapid scale-up. The primary lessons from earlier implementation efforts are to strengthen linkage to clinical care after testing, and to improve the efficiency of testing. Opportunities to improve linkage include data systems to support the follow-up of patients through the cascade of care and test delivery, rapid sample referral networks, and POC tests. Opportunities to increase testing efficiency include improvements to procurement and supply chain practices, well connected tiered laboratory networks with rational deployment of test capacity across different levels of health services, routine resource mapping and mobilization to ensure adequate resources for testing programs, and improved operational and quality management of testing services. If applied to VL testing programs, these approaches could help improve the impact of VL on ART failure management and patient outcomes, reduce overall costs and help ensure the sustainable access to reduced pricing for test commodities, as well as improve supportive health systems such as efficient, and more rigorous quality assurance. These lessons draw from traditional laboratory practices as well as fields such as logistics, operations management and business. CONCLUSIONS: The lessons and innovations from large-scale EID and CD4 programs described here can be adapted to inform more effective scale-up approaches for VL. They demonstrate that an integrated approach to health system strengthening focusing on key levers for test access such as data systems, supply efficiencies and network management. They also highlight the challenges with implementation and the need for more innovative approaches and effective partnerships to achieve equitable and cost-effective test access.

      21. Incidence of hepatitis C virus infection in the Human Immunodeficiency Virus Outpatient Study Cohort, 2000-2013External
        Samandari T, Tedaldi E, Armon C, Hart R, Chmiel JS, Brooks JT, Buchacz K.
        Open Forum Infect Dis. 2017 Spring;4(2):ofx076.

        BACKGROUND: There are few recent studies of incident hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected patients in the United States. METHODS: We studied HIV Outpatient Study (HOPS) participants seen in 9 HIV-specialty clinics who had >/=1 clinical encounter during 2000-2013 and >/=2 HCV-related tests, the first of which was a negative HCV antibody test (Ab). Hepatitis C virus incident cases were identified by first positive HCV Ab, viral load, or genotype. We assessed rates of incident HCV overall, by calendar intervals, and by demographic and HIV risk strata, and we explored risk factors for incident HCV using Cox proportional hazards models. RESULTS: The 1941 eligible patients (median age 40 years, 23% female, 61% men who had sex with men [MSM], and 3% persons who injected drugs [PWID]) experienced 102 (5.3%) incident HCV infections for an overall incidence of 1.07 (95% confidence interval [CI], 0.87-1.30) per 100 person-years (py). Hepatitis C virus incidence decreased from 1.83 in 2000-2003 to 0.88 in 2011-2013 (P = .024), with decreases observed (P < .05) among PWID and heterosexuals, but not among MSM. Overall, MSM comprised 59% of incident cases, and PWID were at most risk for incident HCV infection (adjusted hazard ratio [aHR] for PWID = 4.62 and 95% CI = 2.11-10.13; for MSM, aHR = 1.48 and 95% CI = 0.86-2.55 compared with heterosexuals). CONCLUSIONS: Among HIV-infected patients in care during 2000-2013, incidence of HCV infection exceeded 1 case per 100 py. Our findings support recommendations for annual HCV screenings for HIV-infected persons, including persons with only MSM risk, to enable HCV diagnosis and treatment for coinfected individuals.

      22. Young men who have sex with men at high risk for HIV, Bangkok MSM Cohort Study, Thailand 2006-2014External
        Thienkrua W, van Griensven F, Mock PA, Dunne EF, Raengsakulrach B, Wimonsate W, Howteerakul N, Ungsedhapand C, Chiwarakorn A, Holtz TH.
        AIDS Behav. 2017 Nov 14.

        High HIV incidence has been reported in young men who have sex with men (YMSM) in North America and Western Europe, but there are limited data from Southeast Asia suggesting MSM may be the driver of the HIV epidemic in this region. We described HIV incidence and risk factors among 494 YMSM enrolled in a cohort study in Bangkok, Thailand. The HIV incidence was 7.4 per 100 person-years. In multivariable analysis, reporting use of an erectile dysfunction drug in combination with club drugs, having receptive or both insertive and receptive anal intercourse with men, having hepatitis A infection, having rectal Chlamydia trachomatis, having hepatitis B infection prior to HIV seroconversion, and reporting not always using condoms with male steady partners were significantly associated with HIV incidence in YMSM. Reduction in new HIV infections in YMSM are critical to reach targets set by Thailand and the region.

      23. Importance and contribution of community, social, and healthcare risk factors for hepatitis C infection in PakistanExternal
        Trickey A, May MT, Davies C, Qureshi H, Hamid S, Mahmood H, Saeed Q, Hickman M, Glass N, Averhoff F, Vickerman P.
        Am J Trop Med Hyg. 2017 Oct 16.

        Pakistan has a high prevalence of hepatitis C virus (HCV) infection, estimated at 4.9% (2,290/46,843) in the 2007 national HCV seroprevalence survey. We used data from this survey to assess the importance of risk factor associations with HCV prevalence in Pakistan. Exposures were grouped as community (going to the barbers, sharing smoking equipment, having an ear/nose piercing, tattoo, or acupuncture), healthcare (ever having hemodialysis, blood transfusion, or >/= 5 injections in the last year), demographic (marital status and age), and socio-economic (illiterate or laborer). We used mutually adjusted multivariable regression analysis, stratified by sex, to determine associations with HCV infection, their population attributable fraction, and how risk of infection accumulates with multiple exposures. Strength of associations was assessed using adjusted odds ratios (aOR). Community [aOR females 1.5 (95% confidence interval [CI]: 1.2, 1.8); males 1.2 (1.1, 1.4)] and healthcare [females 1.4 (1.2, 1.6); males 1.2 (1.1, 1.4)] exposures, low socio-economic status [females 1.6 (1.3, 1.80); males 1.3 (1.2, 1.5)], and marriage [females 1.5 (1.2, 1.9); males 1.4 (1.1, 1.8)] were associated with increased HCV infection. Among married women, the number of children was associated with an increase in HCV infection; linear trend aOR per child 1.06 (1.01, 1.11). Fewer infections could be attributed to healthcare exposures (females 13%; males 6%) than to community exposures (females 25%; males 9%). Prevalence increased from 3% to 10% when cumulative exposures increased from 1 to >/= 4 [aOR per additional exposure for females 1.5 (1.4, 1.6); males 1.2 (1.2, 1.3)]. A combination of community, healthcare, and other factors appear to drive the Pakistan HCV epidemic, highlighting the need for a comprehensive array of prevention strategies.

      24. Safe sexual behaviors and anti-retroviral use help prevent HIV transmission. In this cross-sectional study, we assessed correlates of anti-retroviral (ART) status and transmission risk (a constructed variable) among a convenience sample of n = 1041 HIV-positive women (pre-intervention) enrolled in an evidence-based intervention at four CBOs. Multinomial logistic regression models were used. Younger women and those diagnosed with HIV in the last 5 years more often reported that they had not been prescribed ART. Self-reported non-adherence to ART was less frequently reported among women who were older, had a higher HIV knowledge, and those with attitudes/beliefs supportive of condom use. The highest-risk transmission group (condomless sex with HIV-negative/unknown partner and not prescribed or non-adherent to ART) was associated with younger age, attitudes/beliefs less supportive of condom use, and low self-efficacy discussing condom use. Our findings inform HIV prevention efforts among similar populations of HIV-positive women enrolled in interventions at CBOs.

      25. Duration of antibiotic use among adults with uncomplicated community-acquired pneumonia requiring hospitalization in the United StatesExternal
        Yi SH, Hatfield KM, Baggs J, Hicks LA, Srinivasan A, Reddy S, Jernigan JA.
        Clin Infect Dis. 2017 Nov 06.

        Background: Previous studies suggest duration of antibiotic therapy for community-acquired pneumonia (CAP) often exceeds national recommendations and might represent an important opportunity to improve antibiotic stewardship nationally. The objective of this study was to determine average length of antibiotic therapy (LOT) for patients treated for uncomplicated CAP in US hospitals and proportion of patients with excessive durations. Methods: Records of retrospective cohorts of patients 18-64 years with private insurance and >/=65 years with Medicare hospitalized for CAP in 2012-13 were utilized. Inpatient LOT was estimated as a function of LOS using MarketScan(R) Hospital Drug Database data. Outpatient LOT was based on prescriptions filled at discharge. Data were obtained from MarketScan(R) Commercial Claims and Encounters and 100% Medicare claims and Part D event files. Excessive duration was defined as outpatient LOT >3 days. Results: Inclusion criteria were met for 22,128 patients 18-64 years across 2,100 hospitals and 130,746 patients >/=65 years across 3,227 hospitals. Median total LOT was 9.5 days. LOT exceeded recommended duration for 74% of patients 18-64 years and 71% of patients >/=65 years. Patients 18-64 years received a median (quartile 1 -quartile 3) 6 (3-7) days outpatient LOT and those >/=65 years 5 (3-7) days. Conclusions: In this nationwide sample of patients hospitalized for uncomplicated CAP, median total LOT was just under 10 days, with over 70% of patients having likely excessive treatment duration. Better adherence to recommended duration of therapy for CAP by improving prescribing at hospital discharge may be an important target for antibiotic stewardship programs.

    • Disease Reservoirs and Vectors
      1. Rat fall surveillance coupled with vector control and community education as a plague prevention strategy in the West Nile Region, UgandaExternal
        Boegler KA, Atiku LA, Enscore RE, Apangu T, Mpanga JT, Acayo S, Kaggwa J, Mead PS, Yockey BM, Kugeler KJ, Schriefer ME, Horiuchi K, Gage KL, Eisen RJ.
        Am J Trop Med Hyg. 2017 Oct 23.

        Plague, primarily a disease of rodents, is most frequently transmitted by fleas and causes potentially fatal infections in humans. In Uganda, plague is endemic to the West Nile region. Primary prevention for plague includes control of rodent hosts or flea vectors, but targeting these efforts is difficult given the sporadic nature of plague epizootics in the region and limited resource availability. Here, we present a community-based strategy to detect and report rodent deaths (rat fall), an early sign of epizootics. Laboratory testing of rodent carcasses is used to trigger primary and secondary prevention measures: indoor residual spraying (IRS) and community-based plague education, respectively. During the first 3 years of the program, individuals from 142 villages reported 580 small mammal deaths; 24 of these tested presumptive positive for Yersinia pestis by fluorescence microscopy. In response, for each of the 17 affected communities, village-wide IRS was conducted to control rodent-associated fleas within homes, and community sensitization was conducted to raise awareness of plague signs and prevention strategies. No additional presumptive Y. pestis-positive carcasses were detected in these villages within the 2-month expected duration of residual activity for the insecticide used in IRS. Despite comparatively high historic case counts, no human plague cases were reported from villages participating in the surveillance program; five cases were reported from elsewhere in the districts. We evaluate community participation and timeliness of response, report the frequency of human plague cases in participating and surrounding villages, and evaluate whether a program such as this could provide a sustainable model for plague prevention in endemic areas.

    • Environmental Health
      1. Has the question of e-waste opened a Pandora’s box? An overview of unpredictable issues and challengesExternal
        Bakhiyi B, Gravel S, Ceballos D, Flynn MA, Zayed J.
        Environ Int. 2018 Jan;110:173-192.

        Despite regulatory efforts and position papers, electrical and electronic waste (e-waste) remains ill-managed as evidenced by the extremely low rates of proper e-waste recycling (e-recycling) worldwide, ongoing illegal shipments to developing countries and constantly reported human health issues and environmental pollution. The objectives of this review are, first, to expose the complexity of e-waste problems, and then to suggest possible upstream and downstream solutions. Exploring e-waste issues is akin to opening a Pandora’s box. Thus, a review of prevailing e-waste management practices reveals complex and often intertwined gaps, issues and challenges. These include the absence of any consistent definition of e-waste to date, a prevalent toxic potential still involving already banned or restricted hazardous components such as heavy metals and persistent and bioaccumulative organic compounds, a relentless growth in e-waste volume fueled by planned obsolescence and unsustainable consumption, problematic e-recycling processes, a fragile formal e-recycling sector, sustained and more harmful informal e-recycling practices, and more convoluted and unpredictable patterns of illegal e-waste trade. A close examination of the e-waste legacy contamination reveals critical human health concerns, including significant occupational exposure during both formal and informal e-recycling, and persistent environmental contamination, particularly in some developing countries. However, newly detected e-waste contaminants as well as unexpected sources and environmental fates of contaminants are among the emerging issues that raise concerns. Moreover, scientific knowledge gaps remain regarding the complexity and magnitude of the e-waste legacy contamination, specifically, a comprehensive characterization of e-waste contaminants, information on the scale of legacy contamination in developing countries and on the potential environmental damage in developed countries, and a stronger body of evidence of adverse health effects specifically ascribed to e-waste contaminants. However, the knowledge accumulated to date is sufficient to raise awareness and concern among all stakeholders. Potential solutions to curb e-waste issues should be addressed comprehensively, by focusing on two fronts: upstream and downstream. Potential upstream solutions should focus on more rational and eco-oriented consumer habits in order to decrease e-waste quantities while fostering ethical and sustained commitments from manufacturers, which include a limited usage of hazardous compounds and an optimal increase in e-waste recyclability. At the downstream level, solutions should include suitable and pragmatic actions to progressively reduce the illegal e-waste trade particularly through international cooperation and coordination, better enforcement of domestic laws, and monitoring in both exporting and receiving countries, along with the supervised integration of the informal sector into the recycling system of developing countries and global expansion of formal e-waste collection and recycling activities. Downstream solutions should also introduce stronger reverse logistics, together with upgraded, more affordable, and eco-friendly and worker-friendly e-recycling technologies to ensure that benefits are derived fully and safely from the great economic potential of e-waste.

      2. 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. 2017 Nov 08;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.

    • Epidemiology and Surveillance
      1. Will participatory syndromic surveillance work in Latin America? Piloting a mobile approach to crowdsource influenza-like illness data in GuatemalaExternal
        Prieto JT, Jara JH, Alvis JP, Furlan LR, Murray CT, Garcia J, Benghozi PJ, Kaydos-Daniels SC.
        JMIR Public Health Surveill. 2017 Nov 14;3(4):e87.

        BACKGROUND: In many Latin American countries, official influenza reports are neither timely nor complete, and surveillance of influenza-like illness (ILI) remains thin in consistency and precision. Public participation with mobile technology may offer new ways of identifying nonmedically attended cases and reduce reporting delays, but no published studies to date have assessed the viability of ILI surveillance with mobile tools in Latin America. We implemented and assessed an ILI-tailored mobile health (mHealth) participatory reporting system. OBJECTIVE: The objectives of this study were to evaluate the quality and characteristics of electronically collected data, the user acceptability of the symptom reporting platform, and the costs of running the system and of identifying ILI cases, and to use the collected data to characterize cases of reported ILI. METHODS: We recruited the heads of 189 households comprising 584 persons during randomly selected home visits in Guatemala. From August 2016 to March 2017, participants used text messages or an app to report symptoms of ILI at home, the ages of the ILI cases, if medical attention was sought, and if medicines were bought in pharmacies. We sent weekly reminders to participants and compensated those who sent reports with phone credit. We assessed the simplicity, flexibility, acceptability, stability, timeliness, and data quality of the system. RESULTS: Nearly half of the participants (47.1%, 89/189) sent one or more reports. We received 468 reports, 83.5% (391/468) via text message and 16.4% (77/468) via app. Nine-tenths of the reports (93.6%, 438/468) were received within 48 hours of the transmission of reminders. Over a quarter of the reports (26.5%, 124/468) indicated that at least someone at home had ILI symptoms. We identified 202 ILI cases and collected age information from almost three-fifths (58.4%, 118/202): 20 were aged between 0 and 5 years, 95 were aged between 6 and 64 years, and three were aged 65 years or older. Medications were purchased from pharmacies, without medical consultation, in 33.1% (41/124) of reported cases. Medical attention was sought in 27.4% (34/124) of reported cases. The cost of identifying an ILI case was US $6.00. We found a positive correlation (Pearson correlation coefficient=.8) between reported ILI and official surveillance data for noninfluenza viruses from weeks 41 (2016) to 13 (2017). CONCLUSIONS: Our system has the potential to serve as a practical complement to respiratory virus surveillance in Guatemala. Its strongest attributes are simplicity, flexibility, and timeliness. The biggest challenge was low enrollment caused by people’s fear of victimization and lack of phone credit. Authorities in Central America could test similar methods to improve the timeliness, and extend the breadth, of disease surveillance. It may allow them to rapidly detect localized or unusual circulation of acute respiratory illness and trigger appropriate public health actions.

      2. Assessing the potential for bias from nonresponse to a study follow-up interview: An example from the Agricultural Health StudyExternal
        Rinsky JL, Richardson DB, Wing S, Beard JD, Alavanja M, Beane Freeman LE, Chen H, Henneberger PK, Kamel F, Sandler DP, Hoppin JA.
        Am J Epidemiol. 2017 ;186(4):395-404.

        Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.

    • Food Safety
      1. Foodborne cryptosporidiosisExternal
        Ryan U, Hijjawi N, Xiao L.
        Int J Parasitol. 2017 Nov 07.

        Foodborne illness, the majority of which is caused by enteric infectious agents, costs global economies billions of dollars each year. The protozoan parasite Cryptosporidium is particularly suited to foodborne transmission and is responsible for >8million cases of foodborne illness annually. Procedures have been developed for sensitive detection of Cryptosporidium oocysts on fresh produce and molecular diagnostic assays have been widely used in case linkages and infection source tracking, especially during outbreak investigations. The integrated use of advanced diagnostic techniques with conventional epidemiological studies is essential to improve our understanding of the occurrence, source and epidemiology of foodborne cryptosporidiosis. The implementation of food safety management tools such as Good Hygienic Practices (GHP), Hazard Analysis and Critical Control Points (HACCP), and Quantitative Microbial Risk Assessment (QMRA) in industrialised nations and Water, Sanitation, and Hygiene (WASH) in developing countries is central for prevention and control and foodborne cryptosporidiosis in the future.

    • Genetics and Genomics
      1. Emergence of double- and triple-gene reassortant G1P[8] rotaviruses possessing a DS-1-like backbone post rotavirus vaccine introduction in MalawiExternal
        Jere KC, Chaguza C, Bar-Zeev N, Lowe J, Peno C, Kumwenda B, Nakagomi O, Tate JE, Parashar UD, Heyderman RS, French N, Cunliffe NA, Miren IG.
        J Virol. 2017 Nov 15.

        To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunisation programmes. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunisation schedule in 2012. Utilising a surveillance platform of hospitalised rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 – 2012) and after (2013 – 2014) vaccine introduction. Analysis of whole genomes obtained through next generation sequencing revealed that all randomly-selected pre-vaccine G1P[8] strains sequenced (n=32) possessed a Wa-like genetic constellation, whereas post-vaccine G1P[8] strains (n=18) had a DS-1-like constellation. Phylodynamic analyses indicated that post-vaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990’s, hence classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981-1994; their evolutionary rates ranged from 9.7 x 10-4-4.1 x 10-3 nucleotide/substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation.ImportanceThe error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine-escape mutants. While multiple African countries have introduced rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the post-vaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998-2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting limited effect in recognition of G1 specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation.

      2. Genomic history of the seventh pandemic of cholera in AfricaExternal
        Weill FX, Domman D, Njamkepo E, Tarr C, Rauzier J, Fawal N, Keddy KH, Salje H, Moore S, Mukhopadhyay AK, Bercion R, Luquero FJ, Ngandjio A, Dosso M, Monakhova E, Garin B, Bouchier C, Pazzani C, Mutreja A, Grunow R, Sidikou F, Bonte L, Breurec S, Damian M, Njanpop-Lafourcade BM, Sapriel G, Page AL, Hamze M, Henkens M, Chowdhury G, Mengel M, Koeck JL, Fournier JM, Dougan G, Grimont PA, Parkhill J, Holt KE, Piarroux R, Ramamurthy T, Quilici ML, Thomson NR.
        Science. 2017 Nov 10;358(6364):785-789.

        The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa.

    • Health Economics
      1. Cost-effectiveness of maternal GBS immunization in low-income sub-Saharan AfricaExternal
        Russell LB, Kim SY, Cosgriff B, Pentakota SR, Schrag SJ, Sobanjo-Ter Meulen A, Verani JR, Sinha A.
        Vaccine. 2017 Nov 09.

        BACKGROUND: A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown. METHODS: We used a decision tree model, with Markov nodes to project infants’ lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy. RESULTS: At coverage equal to the proportion of pregnant women with>/=4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries’ GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses. CONCLUSION: Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable.

    • Healthcare Associated Infections
      1. Risk of subsequent sepsis within 90 days of a previous hospital stay by type of antibiotic exposureExternal
        Baggs J, Jernigan JA, Halpin AL, Epstein LH, Hatfield KM, McDonald LC.
        Clin Infect Dis. 2017 Nov 09.

        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, determined a priori, during the initial hospital stay and risk of post-discharge 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 ICD-9-CM discharge diagnosis of severe sepsis (995.92) or septic shock (785.52). Results: Among 516 hospitals, we randomly selected a single stay for eligible patients. Of those, 0.17% developed severe sepsis/septic shock within 90 days after discharge. The risk of sepsis associated with exposure to our high risk antibiotics was 65% higher compared to 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 or increased quantities of antibiotics during hospitalization. Given 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, CDI and other adverse effects, but also reduce unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

    • Immunity and Immunization
      1. School-based influenza vaccination: Health and economic impact of Maine’s 2009 influenza vaccination programExternal
        Basurto-Davila R, Meltzer MI, Mills DA, Beeler Asay GR, Cho BH, Graitcer SB, Dube NL, Thompson MG, Patel SA, Peasah SK, Ferdinands JM, Gargiullo P, Messonnier M, Shay DK.
        Health Serv Res. 2017 Dec;52 Suppl 2:2307-2330.

        OBJECTIVE: To estimate the societal economic and health impacts of Maine’s school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. DATA SOURCES: Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. STUDY DESIGN: We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program’s impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. DATA COLLECTION: We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. PRINCIPAL FINDINGS: The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. CONCLUSIONS: SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups.

      2. Early impact of rotavirus vaccination in children less than five years of age in MozambiqueExternal
        de Deus N, Chilaule JJ, Cassocera M, Bambo M, Langa JS, Sitoe E, Chissaque A, Anapakala E, Sambo J, Guimaraes EL, Bero DM, Joao ED, Cossa-Moiane I, Mwenda JM, Weldegebriel GG, Parashar UD, Tate JE.
        Vaccine. 2017 Nov 08.

        BACKGROUND: Mozambique introduced rotavirus vaccine (Rotarix, GSK Biologicals) in the National Immunization Program in September 2015 with the objective of reducing the burden of total diarrheal disease and specifically severe rotavirus disease. This study aimed to evaluate the early impact of rotavirus vaccine in reducing all-cause diarrhea and rotavirus-specific hospitalizations. METHODS: We analysed stool specimens collected from children under five years old, between January 2014 and June 2017 within the National Surveillance for Acute Diarrhea. We compared annual changes in rotavirus positivity, median age of children hospitalized for rotavirus and the number of all-cause for diarrheal hospitalizations. Rotavirus detection was performed using enzyme immunoassay. RESULTS: During this period, 1296 samples were collected and analyzed. Rotavirus positivity before vaccine introduction was 40.2% (39/97) in 2014 and 38.3% (225/588) in 2015, then after vaccine introduction reduced to 12.2% and 13.5% in 2016 and 2017, respectively. The median age of children hospitalized for rotavirus was 9 and 11 months in 2014 and 2015 and 10 months in 2016 and 2017. Rotavirus hospitalizations exhibited a seasonal peak prior to vaccine introduction, between June and September in 2014 and 2015, coinciding with winter period in Mozambique. After vaccine introduction, the peak was delayed until August to December in 2016 and was substantially diminished. There was a reduction in all-cause acute diarrhea hospitalizations in children aged 0-11 months after vaccine introduction. CONCLUSION: We observed a reduction in rotavirus positivity and in the number of all-cause diarrhea hospitalizations after vaccine introduction. The data suggest rotavirus vaccine is having a positive impact on the control of rotavirus diarrheal disease in Mozambique.

      3. Current epidemiology and trends in meningococcal disease – United States, 1996-2015External
        MacNeil JR, Blain AE, Wang X, Cohn AC.
        Clin Infect Dis. 2017 Nov 08.

        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, 7,924 cases of meningococcal disease were reported to NNDSS, resulting in an average annual incidence of 0.26 cases per 100,000 population; 14.9% of cases were fatal. Among cases with serogroup information, 2,290 (35.8%) were serogroup B, 1,827 (28.5%) were serogroup Y, 1,457 (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 1996-2015, 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.

      4. Imputing the direct and indirect effectiveness of childhood pneumococcal conjugate vaccine against invasive pneumococcal disease by surveying temporal changes in nasopharyngeal pneumococcal colonizationExternal
        Nzenze SA, Madhi SA, Shiri T, Klugman KP, De Gouveia L, Moore DP, Karstaedt AS, Tempia S, Nunes MC, Von Gottberg A.
        Am J Epidemiol. 2017 ;186(4):435-444.

        The limited capability in most low- to middle-income countries to study the benefit of pneumococcal conjugate vaccine (PCV) in protecting against invasive pneumococcal disease (IPD) calls for alternate strategies to assess this. We used a mathematical model to predict the direct and indirect effectiveness of PCV by analyzing serotypespecific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005 to 2012 and colonization studies undertaken in human immunodeficiency virus (HIV)-uninfected and HIV-infected child-mother dyads from 2007 to 2009 (pre-PCV era), in 2010 (7-valent PCV era), and in 2012 (13-valent PCV era). We compared the model-predicted changes in IPD incidence with observed changes in IPD incidence, according to HIV status, in children aged 3 months-5 years and in women aged 18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCVunvaccinated children and adults, but not among children under age 24 months. Surveillance of colonization prior to and following PCV use can be used to impute the indirect protection afforded by PCV in unvaccinated age groups, including those in high-HIV-prevalence settings. Copyright ? The Author(s) 2017.

      5. Immunogenicity of different routine poliovirus vaccination schedules: A randomized controlled trial, Karachi, PakistanExternal
        Saleem AF, Mach O, Yousafzai MT, Khan A, Weldon WC, Oberste MS, Zaidi SS, Alam MM, Quadri F, Sutter RW, Zaidi AK.
        J Infect Dis. 2017 Nov 06.

        Background: We assessed immunity against polioviruses induced with new Pakistani immunization schedule and compared it with alternative immunization schedules. Methods: Newborns were randomized to receive one of the following vaccination schedules, administered at birth, 6, 10, and 14 weeks of age. Arm A: 4x IPV; Arm B: 4x bOPV; Arm C and D: bOPV, bOPV, bOPV, bOPV+ inactivated poliovirus vaccine (IPV); Arm E: 4x trivalent oral poliovirus vaccine (tOPV). At 22 weeks of age, children received one challenge dose of tOPV, and children in arm D received one additional IPV dose. Sera were analyzed for presence of polio neutralizing antibodies at birth, 14, and 22 weeks of age. Results: Study arms A-E, the seroconversion for PV1 at 22 weeks of age was 80%, 97%, 94%, 96%, 94% respectively; for PV2: 84%, 19%, 53%, 49%, 93%; and for PV3: 93%, 94%, 98%, 94%, 85%. Interpretation: Current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2.

    • Injury and Violence
      1. The experience of violence against children in domestic servitude in Haiti: Results from the Violence Against Children Survey, Haiti 2012External
        Gilbert L, Reza A, Mercy J, Lea V, Lee J, Xu L, Marcelin LH, Hast M, Vertefeuille J, Domercant JW.
        Child Abuse and Neglect. 2018 February;76:184-193.

        Background There have been estimates that over 150,000 Haitian children are living in servitude. Child domestic servants who perform unpaid labor are referred to as “restaveks.” Restaveks are often stigmatized, prohibited from attending school, and isolated from family placing them at higher risk for experiencing violence. In the absence of national data on the experiences of restaveks in Haiti, the study objective was to describe the sociodemographic characteristics of restaveks in Haiti and to assess their experiences of violence in childhood. Methods The Violence Against Children Survey was a nationally representative, cross-sectional household survey of 13-24 year olds (n = 2916) conducted May-June 2012 in Haiti. A stratified three-stage cluster design was used to sample households and camps containing persons displaced by the 2010 earthquake. Respondents were interviewed to assess lifetime prevalence of physical, emotional, and sexual violence occurring before age 18. Chi-squared tests were used to assess the association between having been a restavek and experiencing violence in childhood. Findings In this study 17.4% of females and 12.2% of males reported having been restaveks before age 18. Restaveks were more likely to have worked in childhood, have never attended school, and to have come from a household that did not have enough money for food in childhood. Females who had been restaveks in childhood had higher odds of reporting childhood physical (OR 2.04 [1.40-2.97]); emotional (OR 2.41 [1.80-3.23]); and sexual violence (OR 1.86 [95% CI 1.34-2.58]) compared to females who had never been restaveks. Similarly, males who had ever been restaveks in childhood had significantly increased odds of emotional violence (OR 3.06 [1.99-4.70]) and sexual violence (OR 1.85 [1.12-3.07]) compared to males who had never been restaveks, but there was no difference in childhood physical violence. Interpretation This study demonstrates that child domestic servants in Haiti experience higher rates of childhood violence and have less access to education and financial resources than other Haitian children. These findings highlight the importance of addressing both the lack of human rights law enforcement and the poor economic circumstances that allow the practice of restavek to continue in Haiti.

      2. Injuries from physical abuse: National Survey of Children’s Exposure to Violence I-IIIExternal
        Simon TR, Shattuck A, Kacha-Ochana A, David-Ferdon CF, Hamby S, Henly M, Merrick MT, Turner HA, Finkelhor D.
        Am J Prev Med. 2017 Nov 10.

        INTRODUCTION: Official data sources do not provide researchers, practitioners, and policy makers with complete information on physical injury from child abuse. This analysis provides a national estimate of the percentage of children who were injured during their most recent incident of physical abuse. METHODS: Pooled data from three cross-sectional national telephone survey samples (N=13,052 children) included in the National Survey of Children’s Exposure to Violence completed in 2008, 2011, and 2014 were used. RESULTS: Analyses completed in 2016 indicate that 8.4% of children experienced physical abuse by a caregiver. Among those with injury data, 42.6% were injured in the most recent incident. No differences in injury were observed by sex, age, race/ethnicity, or disability status. Victims living with two parents were less likely to be injured (27.1%) than those living in other family structures (53.8%-59%, p<0.001). Incidents involving an object were more likely to result in injury (59.3% vs 38.5%, p<0.05). Injured victims were significantly more likely to experience substantial fear (57.3%) than other victims (34.4%, p<0.001). CONCLUSIONS: A substantial percentage of physical abuse victims are physically hurt to the point that they still feel pain the next day, are bruised, cut, or have a broken bone. Self-report data indicate this is a more common problem than official data sources suggest. The lack of an object in an incident of physical abuse does not protect a child from injury. The results underscore the impact of childhood physical abuse and the importance of early prevention activities.

    • Laboratory Sciences
      1. CXC chemokines exhibit bactericidal activity against multidrug-resistant gram-negative pathogensExternal
        Crawford MA, Fisher DJ, Leung LM, Lomonaco S, Lascols C, Cannatelli A, Giani T, Rossolini GM, Doi Y, Goodlett DR, Allard MW, Sharma SK, Khan E, Ernst RK, Hughes MA.
        MBio. 2017 Nov 14;8(6).

        The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens.IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant “superbugs.”

      2. Development of an inexpensive RGB color sensor for the detection of hydrogen cyanide gasExternal
        Greenawald LA, Boss GR, Snyder JL, Reeder A, Bell S.
        ACS Sens. 2017 Oct 27;2(10):1458-1466.

        An inexpensive red, green, blue (RGB) color sensor was developed for detecting low ppm concentrations of hydrogen cyanide gas. A piece of glass fiber filter paper containing monocyanocobinamide [CN(H2O)Cbi] was placed directly above the RGB color sensor and an on chip LED. Light reflected from the paper was monitored for RGB color change upon exposure to hydrogen cyanide at concentrations of 1.0-10.0 ppm as a function of 25%, 50%, and 85% relative humidity. A rapid color change occurred within 10 s of exposure to 5.0 ppm hydrogen cyanide gas (near the NIOSH recommended exposure limit). A more rapid color change occurred at higher humidity, suggesting a more effective reaction between hydrogen cyanide and CN(H2O)Cbi. The sensor could provide the first real time respirator end-of-service-life alert for hydrogen cyanide gas.

      3. Evaluation of two matrices for long-term, ambient storage of bacterial DNAExternal
        Miernyk KM, DeByle CK, Rudolph KM.
        Biopreserv Biobank. 2017 Nov 13.

        BACKGROUND: Culture-independent molecular analyses allow researchers to identify diverse microorganisms. This approach requires microbiological DNA repositories. The standard for DNA storage is liquid nitrogen or ultralow freezers. These use large amounts of space, are costly to operate, and could fail. Room temperature DNA storage is a viable alternative. In this study, we investigated storage of bacterial DNA using two ambient storage matrices, Biomatrica DNAstable(R) Plus and GenTegra(R) DNA. METHODS: We created crude and clean DNA extracts from five Streptococcus pneumoniae isolates. Extracts were stored at -30 degrees C (our usual DNA storage temperature), 25 degrees C (within the range of temperatures recommended for the products), and 50 degrees C (to simulate longer storage time). Samples were stored at -30 degrees C with no product and dried at 25 degrees C and 50 degrees C with no product, in Biomatrica DNAstable Plus or GenTegra DNA. We analyzed the samples after 0, 1, 2, 4, 8, 16, 32, and 64 weeks using the Nanodrop 1000 to determine the amount of DNA in each aliquot and by real-time PCR for the S. pneumoniae genes lytA and psaA. Using a 50 degrees C storage temperature, we simulated 362 weeks of 25 degrees C storage. RESULTS: The average amount of DNA in aliquots stored with a stabilizing matrix was 103%-116% of the original amount added to the tubes. This is similar to samples stored at -30 degrees C (average 102%-121%). With one exception, samples stored with a stabilizing matrix had no change in lytA or psaA cycle threshold (Ct) value over time (Ct range </=2.9), similar to samples stored at -30 degrees C (Ct range </=3.0). Samples stored at 25 degrees C with no stabilizing matrix had Ct ranges of 2.2-5.1. CONCLUSION: DNAstable Plus and GenTegra DNA can protect dried bacterial DNA samples stored at room temperature with similar effectiveness as at -30 degrees C. It is not effective to store bacterial DNA at room temperature without a stabilizing matrix.

      4. Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625-2%), evaluated by ear swelling in female BALB/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. Phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells, and dendritic cells in the draining lymph nodes (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4+ T-cell and CD8+ T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE+ B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.

      5. Multiplexed biomarker panels discriminate Zika and Dengue virus infection in humansExternal
        Song G, Rho HS, Pan J, Ramos P, Yoon KJ, Medina FA, Lee EM, Eichinger DJ, Ming GL, Munoz-Jordan JL, Tang H, Pino I, Song H, Qian J, Zhu H.
        Mol Cell Proteomics. 2017 Nov 15.

        Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas. We have developed a ZIKV/DENV protein array and tested it with serum samples collected from ZIKV- and DENV-infected patients and healthy subjects in Puerto Rico. Our analyses reveal a biomarker panel that are capable of discriminating ZIKV and DENV infections with high accuracy, including Capsid protein from African ZIKV strain MR766, and other 5 pair of proteins (NS1, NS2A, NS3, NS4B and NS5) from ZIKV and DENV respectively. Both sensitivity and specificity of the test for ZIKV from DENV are around 90%. We propose that the ZIKV/DENV protein array will be used in future studies to discriminate patients infected with ZIKV from DENV.

      6. Toxicity evaluations of nanoclays and thermally degraded byproducts through spectroscopical and microscopical approachesExternal
        Wagner A, Eldawud R, White A, Agarwal S, Stueckle TA, Sierros KA, Rojanasakul Y, Gupta RK, Dinu CZ.
        Biochim Biophys Acta. 2017 01 Jan;Part A. 1861(1):3406-3415.

        Background Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is incorporated into polymers to form nanocomposites with enhanced mechanical strength, barrier, and flammability properties used for food packaging, automotive, and medical devices. However, with implementation in such consumer applications, the interaction of montmorillonite-based composites or derived byproducts with biological systems needs to be investigated. Methods Herein we examined the potential of Cloisite Na<sup>+</sup> (pristine) and Cloisite 30B (organically modified montmorillonite nanoclay) and their thermally degraded byproducts’ to induce toxicity in model human lung epithelial cells. The experimental set-up mimicked biological exposure in manufacturing and disposal areas and employed cellular treatments with occupationally relevant doses of nanoclays previously characterized using spectroscopical and microscopical approaches. For nanoclay-cellular interactions and for cellular analyses respectively, biosensorial-based analytical platforms were used, with induced cellular changes being confirmed via live cell counts, viability assays, and cell imaging. Results Our analysis of byproducts’ chemical and physical properties revealed both structural and functional changes. Real-time high throughput analyses of exposed cellular systems confirmed that nanoclay induced significant toxic effects, with Cloisite 30B showing time-dependent decreases in live cell count and cellular viability relative to control and pristine nanoclay, respectively. Byproducts produced less toxic effects; all treatments caused alterations in the cell morphology upon exposure. Conclusions Our morphological, behavioral, and viability cellular changes show that nanoclays have the potential to produce toxic effects when used both in manufacturing or disposal environments. General significance The reported toxicological mechanisms prove the extensibility of a biosensorial-based platform for cellular behavior analysis upon treatment with a variety of nanomaterials.

      7. We investigated the effects of isolated meniscectomy on tibiofemoral skeletal kinematics and cartilage contact arthrokinematics in vivo. We recruited nine patients who had undergone isolated medial or lateral meniscectomy, and used a dynamic stereo-radiography (DSX) system to image the patients’ knee motion during decline walking. A volumetric model-based tracking process determined 3D tibiofemoral kinematics from the recorded DSX images. Cartilage contact arthrokinematics was derived from the intersection between tibial and femoral cartilage models co-registered to the bones. The kinematics and arthrokinematics were analyzed for early stance and loading response phase (30% of a gait cycle), comparing the affected and intact knees. Results showed that four patients with medial meniscectomy had significantly greater contact centroid excursions in the meniscectomized medial compartments while five patients with lateral meniscectomy had significantly greater cartilage contact area and lateral shift of contact centroid path in the meniscectomized lateral compartments, comparing to those of the same compartments in the contralateral intact knees. No consistent difference however was identified in the skeletal kinematics. The current study demonstrated that cartilage-based intra-articular arthrokinematics is more sensitive and insightful than the skeletal kinematics in assessing the meniscectomy effects.

    • Maternal and Child Health
      1. OBJECTIVE: To characterize lifetime and current rates of attention-deficit/hyperactivity disorder (ADHD) treatments among US children and adolescents with current ADHD and describe the association of these treatments with demographic and clinical factors. STUDY DESIGN: Data are from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome, a follow-back survey of parents from the 2011-2012 National Survey of Children’s Health. Weighted analyses focused on receipt of ADHD treatment among children aged 4-17 years with current ADHD (n = 2495) by 4 treatment types: medication, school supports, psychosocial interventions, and alternative treatments. RESULTS: Medication and school supports were the most common treatments received, with two-thirds of children and adolescents with ADHD currently receiving each treatment. Social skills training was the most common psychosocial treatment ever received (39%), followed by parent training (31%), peer intervention (30%), and cognitive behavioral therapy (20%). Among alternative treatments, 9% were currently taking dietary supplements, and 11% had ever received neurofeedback. Most children (67%) had received at least 2 of the following: current medication treatment, current school supports, or lifetime psychosocial treatment; 7% had received none of these 3 treatment types. CONCLUSIONS: A majority of school-aged children and adolescents with ADHD received medication treatment and school supports, whereas fewer received recommended psychosocial interventions. Efforts to increase access to psychosocial treatments may help close gaps in service use by groups currently less likely to receive treatment, which is important to ensure that the millions of school-aged US children diagnosed with ADHD receive quality treatment.

      2. Adding folic acid to corn masa flour: Partnering to improve pregnancy outcomes and reduce health disparitiesExternal
        Flores AL, Cordero AM, Dunn M, Sniezek JE, Arce MA, Crider KS, Tinker S, Pellegrini C, Carreon R, Estrada J, Struwe S, Boyle C.
        Prev Med. 2017 Nov 08.

        Although strides have been made in preventing neural tube defects (NTDs), Hispanic women remain more likely to have a baby born with an NTD and less likely to know the benefits of, or consume, folic acid than women of other race/ethnic groups. In 1998, the U.S. Food and Drug Administration (FDA) mandated that all enriched cereal grain products be fortified with folic acid; however, corn masa flour (CMF), used to make many corn products that are a diet staple of many Hispanic groups, was not included under this regulation. In 2006, a Working Group began a collaboration to address this disparity by pursuing a petition to FDA to allow folic acid to be added voluntarily to CMF. The petition process was a monumental effort that required collaboration and commitment by partners representing the affected population, manufacturers, scientists, and others. The petition was approved in 2016 and folic acid is now added to CMF products, with expected results of more women achieving the recommended daily folic acid intake, more infants born per year without an NTD, and millions of dollars in direct medical expenditures averted. This 10-year public-private partnership brought together diverse groups that traditionally have different goals. The Working Group continues to work toward ensuring that fortified CMF products are available to the consumer, with the end goal of achieving a reduction in NTD-affected pregnancies.

      3. Variation in bowel and bladder continence across US spina bifida programs: A descriptive studyExternal
        Freeman KA, Castillo H, Castillo J, Liu T, Schechter M, Wiener JS, Thibadeau J, Ward E, Brei T.
        J Pediatr Rehabil Med. 2017 Oct 20.

        PURPOSE: Continence is low in individuals with spina bifida, but published prevalence varies markedly across studies. The objective of this study was to examine bladder and bowel continence among patients served by multidisciplinary clinics participating in the National Spina Bifida Patient Registry and to examine whether variation in prevalence exists across clinics. METHODS: Data were obtained from patients 5 years and older from March 2009 to December 2012. Data were gathered at clinic visits using standardized definitions. RESULTS: Data from 3252 individuals were included. Only 40.8% of participants were continent of urine; 43% were continent of stool. Bladder and bowel continence differed by spina bifida type, with those with myelomeningocele having significantly lower reported prevalence of continence than those with other forms of spina bifida. Bladder and bowel continence varied across registry sites. Adjustment based on demographic and condition-specific variables did not make substantive differences in prevalence observed. CONCLUSION: Less than half of spina bifida patients served in multidisciplinary clinics report bladder or bowel continence. Variability in prevalence was observed across clinics. Further research is needed to examine if clinic-specific variables (e.g., types of providers, types of interventions used) account for the observed variation.

      4. Evaluation of spina bifida transitional care practices in the United StatesExternal
        Kelly MS, Thibadeau J, Struwe S, Ramen L, Ouyang L, Routh J.
        J Pediatr Rehabil Med. 2017 Oct 20.

        PURPOSE: Recent studies have revealed that the lack of continuity in preparing patients with spina bifida to transition into adult-centered care may have detrimental health consequences. We sought to describe current practices of transitional care services offered at spina bifida clinics in the US. METHODS: Survey design followed the validated transitional care survey by the National Cystic Fibrosis center. Survey was amended for spina bifida. Face validity was completed. Survey was distributed to registered clinics via the Spina Bifida Association. Results were analyzed via descriptive means. RESULTS: Total of 34 clinics responded. Over 90 characteristics were analyzed per clinic. The concept of transition is discussed with most patients. Most clinics discuss mobility, bowel and bladder management, weight, and education plans consistently. Most do not routinely evaluate their process or discuss insurance coverage changes with patients. Only 30% communicate with the adult providers. Sexuality, pregnancy and reproductive issues are not readily discussed in most clinics. Overall clinics self-rate themselves as a 5/10 in their ability to provide services for their patients during transition. CONCLUSIONS: Characteristics of current transitional care services and formal transitional care programs at US clinics show wide variances in what is offered to patients and families.

      5. Periconceptional maternal fever, folic acid intake, and the risk for neural tube defectsExternal
        Kerr SM, Parker SE, Mitchell AA, Tinker SC, Werler MM.
        Ann Epidemiol. 2017 Nov 02.

        PURPOSE: Previous studies have shown an association between maternal fever in early pregnancy and neural tube defects (NTDs) such as spina bifida. Periconceptional folic acid intake has been shown to reduce the risk of these outcomes. METHODS: Using data from the Slone Epidemiology Center Birth Defects Study (1998-2015), we examined the impact of folic acid on the relationship between maternal fever in the periconceptional period (28 days before and after the last menstrual period) and NTDs. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Mothers of 375 cases and 8247 nonmalformed controls were included. We observed an elevated risk for NTDs for fever in the periconceptional period (OR: 2.4; 95% CI: 1.5-4.0). This association was weaker for mothers who reported consuming the recommended amount of folic acid (>/=400 mug per day; OR: 1.8; 95% CI: 0.8-4.0) than mothers with low folic acid intake (<400 mug per day; OR: 4.2; 95% CI: 2.2-8.2). CONCLUSIONS: Our data support an association between maternal periconceptional fever and an increased risk for NTDs and also provide evidence that this association was attenuated for mothers who reported consuming folic acid at recommended levels in the periconceptional period.

      6. Longitudinal study of bladder continence among people with spina bifida in the National Spina Bifida Patient RegistryExternal
        Liu T, Ouyang L, Thibadeau J, Wiener JS, Routh JC, Castillo H, Castillo J, Freeman KA, Sawin KJ, Smith K, Van Speybroeck A, Valdez R.
        J Urol. 2017 Nov 10.

        PURPOSE: Achieving bladder continence among people with Spina bifida is a lifetime management goal. We investigated bladder continence status over time and factors associated with this status among people with SB. MATERIALS AND METHODS: We used National Spina Bifida Patient Registry data collected from 2009 through 2015 and applied generalized estimating equation models to analyze factors associated with bladder continence status. RESULTS: This analysis included 5,250 participants with SB in a large, multi-institutional patient registry who contributed 12,740 annual clinic visit records during the study period. At last follow-up, mean age was 16.6 years, 22.4% of the participants had undergone bladder continence surgery, 92.6% used some form of bladder management, and 45.8% reported bladder continence. In a multivariable regression model, the likelihood of bladder continence was significantly higher among those who were older, female, non-Hispanic white, had a non-myelomeningocele diagnosis, a lower level of lesion, a higher mobility level, and private insurance. Both continence surgery history and current management were also associated with continence independent of all other factors (adjusted ORs and 95% CI: 1.9, 1.7 – 2.1, and 3.8, 3.2 – 4.6, respectively). The association between bladder management and continence was stronger for those with a myelomeningocele diagnosis (adjusted OR=4.6) than with non-myelomeningocele (OR= 2.8). CONCLUSIONS: In addition to demographic, social, and clinical factors, surgical intervention and bladder management are significantly and independently associated with bladder continence status among people with SB. The association between bladder management and continence was stronger among people with myelomeningocele.

      7. Intelligence and academic achievement with asymptomatic congenital cytomegalovirus infectionExternal
        Lopez AS, Lanzieri TM, Claussen AH, Vinson SS, Turcich MR, Iovino IR, Voigt RG, Caviness AC, Miller JA, Williamson WD, Hales CM, Bialek SR, Demmler-Harrison G.
        Pediatrics. 2017 Nov;140(5).

        OBJECTIVES: To examine intelligence, language, and academic achievement through 18 years of age among children with congenital cytomegalovirus infection identified through hospital-based newborn screening who were asymptomatic at birth compared with uninfected infants. METHODS: We used growth curve modeling to analyze trends in IQ (full-scale, verbal, and nonverbal intelligence), receptive and expressive vocabulary, and academic achievement in math and reading. Separate models were fit for each outcome, modeling the change in overall scores with increasing age for patients with normal hearing (n = 78) or with sensorineural hearing loss (SNHL) diagnosed by 2 years of age (n = 11) and controls (n = 40). RESULTS: Patients with SNHL had full-scale intelligence and receptive vocabulary scores that were 7.0 and 13.1 points lower, respectively, compared with controls, but no significant differences were noted in these scores among patients with normal hearing and controls. No significant differences were noted in scores for verbal and nonverbal intelligence, expressive vocabulary, and academic achievement in math and reading among patients with normal hearing or with SNHL and controls. CONCLUSIONS: Infants with asymptomatic congenital cytomegalovirus infection identified through newborn screening with normal hearing by age 2 years do not appear to have differences in IQ, vocabulary or academic achievement scores during childhood, or adolescence compared with uninfected children.

      8. Bowel management and continence in adults with spina bifida: Results from the National Spina Bifida Patient Registry 2009-15External
        Wiener JS, Suson KD, Castillo J, Routh JC, Tanaka S, Liu T, Ward E, Thibadeau J, Joseph D, Registry N.
        J Pediatr Rehabil Med. 2017 Oct 20.

        INTRODUCTION: Advances in care have allowed most children with spina bifida (SB) to live to adulthood. The majority have neuropathic bowel dysfunction (NBD), resulting in constipation, incontinence, and diminished quality of life. We sought to 1) describe contemporary NBD management and continence outcomes of adults with SB; 2) describe differences from younger patients; and 3) assess for association with socio-economic factors. METHODS: We analyzed data on NBD management and continence from the National Spina Bifida Patient Registry (NSBPR). Patients were segregated into young children (5-11 years), adolescents (12-19 years), and adults (20 years and older). A strict definition of continence was utilized. Statistical analysis compared cohorts by gender, ethnicity, SB type, lesion level, insurance status, educational attainment, employment status, and continence. RESULTS: A total of 5209 SB patients were included, of whom 1370 (26.3%) were adults. Management and continence varied by age and SB type. Oral medication use did not differ between groups (5.2-6.6%). Suppositories and rectal enemas were used only by 11.5% of adults, which was significantly less than among school-aged children. Antegrade enemas were used by 17.7% of adults which was significantly less than among adolescents (27.2%). Adults were more likely to use digital stimulation or disimpaction or have undergone a colostomy. Bowel continence was reported by 58.3% of overall adult cohort: 55.6% of adults with myelomeningocele and 74.9% with non-myelomeningocele. Bowel continence was significantly associated with employment (p= 0.0002), private insurance (p= 0.0098), non-myelomeningocele type of SB (p= 0.0216) and educational attainment (p= 0.0324) on univariate analysis but only with employment on multivariable logistic regression (p= 0.0027). CONCLUSIONS: Bowel management techniques differed between adults and younger patients with SB. Bowel continence was reported by over half of SB adults and was associated with socio-economic factors.

    • Nutritional Sciences
      1. Neighborhood prices of healthier and unhealthier foods and associations with diet quality: Evidence from the Multi-Ethnic Study of AtherosclerosisExternal
        Kern DM, Auchnicloss AH, Stehr MF, Roux AV, Moore LV, Kanter GP, Robinson LF.
        Int J Environ Res Public Health. 2017 Nov 16;14(11).

        It is known that the price of food influences the purchasing and consumption decisions of individuals; however, little work has examined if the price of healthier food relative to unhealthier food in an individual’s neighborhood is associated with overall dietary quality while using data from multiple regions in the United States. Cross-sectional person-level data came from The Multi-Ethnic Study of Atherosclerosis (exam 5, 2010-2012 n = 2765); a food frequency questionnaire assessed diet. Supermarket food/beverage prices came from Information Resources Inc. (n = 794 supermarkets). For each individual, the average price of select indicators of healthier foods (vegetables, fruits, dairy) and unhealthier foods (soda, sweets, salty snacks), as well as their ratio, was computed for supermarkets within three miles of the person’s residential address. Logistic regression estimated odds ratios of a high-quality diet (top quintile of Healthy Eating Index 2010) associated with healthy-to-unhealthy price ratio, adjusted for individual and neighborhood characteristics. Sensitivity analyses used an instrumental variable (IV) approach. Healthier foods cost nearly twice as much as unhealthier foods per serving on average (mean healthy-to-unhealthy ratio = 1.97 [SD 0.14]). A larger healthy-to-unhealthy price ratio was associated with lower odds of a high-quality diet (OR = 0.76 per SD increase in the ratio, 95% CI = [0.64-0.9]). IV analyses largely confirmed these findings although-as expected with IV adjustment-confidence intervals were wide (OR = 0.82 [0.57-1.19]). Policies to address the large price differences between healthier and unhealthy foods may help improve diet quality in the United States.

      2. Total sugar-sweetened beverage intake among US adults was lower when measured using a 1-question versus 4-question screenerExternal
        Lundeen EA, Park S, Dooyema C, Blanck HM.
        Am J Health Promot. 2017 Jan 01:890117117736957.

        PURPOSE: To compare the performance of a 1-question survey screener measuring total sugar-sweetened beverage (SSB) intake to a screener measuring SSB types separately using 4 questions. DESIGN: Cross-sectional. SETTING: Web-based 2014 SummerStyles survey. PARTICIPANTS: A total of 4167 US adults (>/=18 years). MEASURES: Frequency of SSB intake measured using a 1-question screener was compared to frequency using a 4-question screener (regular soda, fruit drinks, sports/energy drinks, sweetened coffee/tea). SSB intake (number of time/day) was categorized as 0, >0 to <1, and >/=1 time/day; difference in mean intake was calculated between 4 questions versus 1. ANALYSIS: Paired t tests were used, and agreement was evaluated using weighted kappa and Lin’s concordance correlation coefficient (CCC). RESULTS: Mean SSB intake was 1.7 (95% confidence interval [CI]: 1.65-1.79) times/day using 4 questions and 0.6 (95% CI: 0.56-0.62) times/day using 1 question ( P < .001). Intake frequency based on 4 questions versus 1 was 16.0% versus 38.5% for 0 time/day, 15.6% versus 42.5% for >0 to <1 time/day, and 68.4% versus 18.9% for >/=1 time/day. There was fair agreement for the 3 SSB intake categories (kappa: .27) and poor absolute agreement between the 2 continuous measures (Lin’s CCC: 0.31). CONCLUSION: Daily SSB intake was significantly lower using a 1-question screener versus a 4-question screener. Researchers should assess SSB types separately or consider that daily SSB intake is likely underestimated with 1 question.

    • Occupational Safety and Health
      1. Current and new challenges in occupational lung diseasesExternal
        De Matteis S, Heederik D, Burdorf A, Colosio C, Cullinan P, Henneberger PK, Olsson A, Raynal A, Rooijackers J, Santonen T, Sastre J, Schlunssen V, van Tongeren M, Sigsgaard T.
        Eur Respir Rev. 2017 Dec 31;26(146).

        Occupational lung diseases are an important public health issue and are avoidable through preventive interventions in the workplace. Up-to-date knowledge about changes in exposure to occupational hazards as a result of technological and industrial developments is essential to the design and implementation of efficient and effective workplace preventive measures. New occupational agents with unknown respiratory health effects are constantly introduced to the market and require periodic health surveillance among exposed workers to detect early signs of adverse respiratory effects. In addition, the ageing workforce, many of whom have pre-existing respiratory conditions, poses new challenges in terms of the diagnosis and management of occupational lung diseases. Primary preventive interventions aimed to reduce exposure levels in the workplace remain pivotal for elimination of the occupational lung disease burden. To achieve this goal there is still a clear need for setting standard occupational exposure limits based on transparent evidence-based methodology, in particular for carcinogens and sensitising agents that expose large working populations to risk. The present overview, focused on the occupational lung disease burden in Europe, proposes directions for all parties involved in the prevention of occupational lung disease, from researchers and occupational and respiratory health professionals to workers and employers.

      2. Old adversaries in new placesExternal
        Henneberger PK, Weissman DN.
        Occup Environ Med. 2017 Nov 10.

        [No abstract]

      3. Toward an asbestos ban in the United StatesExternal
        Lemen RA, Landrigan PJ.
        Int J Environ Res Public Health. 2017 Oct 26;14(11).

        Many developed countries have banned the use of asbestos, but not the United States. There have, however, been multiple efforts in the US to establish strict exposure standards, to limit asbestos use, and to seek compensation through the courts for asbestos-injured workers’ In consequence of these efforts, asbestos use has declined dramatically, despite the absence of a legally mandated ban. This manuscript presents a historical review of these efforts.

      4. Police stressors and health: a state-of-the-art reviewExternal
        Violanti JM, Charles LE, McCanlies E, Hartley TA, Baughman P, Andrew ME, Fekedulegn D, Ma CC, Mnatsakanova A, Burchfiel CM.
        Policing. 2017 ;40(4):642-656.

        Purpose: The purpose of this paper is to provide a state-of-the-art review on the topic of police stressors and associated health outcomes. Recent empirical research is reviewed in the areas of workplace stress, shift work, traumatic stress, and health. The authors provide a comprehensive table outlining occupational exposures and related health effects in police officers. Design/methodology/approach: A review of recent empirical research on police stress and untoward psychological and physiological health outcomes in police officers. Findings: The results offer a conceptual idea of the empirical associations between stressful workplace exposures and their impact on the mental and physical well-being of officers. Research limitations/implications: A key limitation observed in prior research is the cross-sectional study design; however, this serves as a motivator for researchers to explore these associations utilizing a longitudinal study design that will help determine causality. Originality/value: This review provides empirical evidence of both mental and physical outcomes associated with police stress and the processes involved in both. Research findings presented in this paper are based on sound psychological and medical evidence among police officers.

      5. Vibrations transmitted from human hands to upper arm, shoulder, back, neck, and headExternal
        Xu XS, Dong RG, Welcome DE, Warren C, McDowell TW, Wu JZ.
        Int J Ind Ergon. 2017 Dec;62:1-12.

        Some powered hand tools can generate significant vibration at frequencies below 25 Hz. It is not clear whether such vibration can be effectively transmitted to the upper arm, shoulder, neck, and head and cause adverse effects in these substructures. The objective of this study is to investigate the vibration transmission from the human hands to these substructures. Eight human subjects participated in the experiment, which was conducted on a 1-D vibration test system. Unlike many vibration transmission studies, both the right and left hand-arm systems were simultaneously exposed to the vibration to simulate a working posture in the experiment. A laser vibrometer and three accelerometers were used to measure the vibration transmitted to the substructures. The apparent mass at the palm of each hand was also measured to help in understanding the transmitted vibration and biodynamic response. This study found that the upper arm resonance frequency was 7-12 Hz, the shoulder resonance was 7-9 Hz, and the back and neck resonances were 6-7 Hz. The responses were affected by the hand-arm posture, applied hand force, and vibration magnitude. The transmissibility measured on the upper arm had a trend similar to that of the apparent mass measured at the palm in their major resonant frequency ranges. The implications of the results are discussed. Relevance to industry: Musculoskeletal disorders (MSDs) of the shoulder and neck are important issues among many workers. Many of these workers use heavy-duty powered hand tools. The combined mechanical loads and vibration exposures are among the major factors contributing to the development of MSDs. The vibration characteristics of the body segments examined in this study can be used to help understand MSDs and to help develop more effective intervention methods.

    • Parasitic Diseases
      1. Angiostrongylus cantonensis Eosinophilic meningitis in an infant, Tennessee, USAExternal
        Flerlage T, Qvarnstrom Y, Noh J, Devincenzo JP, Madni A, Bagga B, Hysmith ND.
        Emerg Infect Dis. 2017 Oct;23(10):1756-1758.

        Angiostrongylus cantonensis, the rat lungworm, is the most common infectious cause of eosinophilic meningoencephalitis worldwide. This parasite is endemic to Southeast Asia and the Pacific Islands, and its global distribution is increasing. We report A. cantonensis meningoencephalitis in a 12-month-old boy in Tennessee, USA, who had not traveled outside of southwestern Tennessee or northwestern Mississippi.

      2. Laboratory diagnosis of parasites from the gastrointestinal tractExternal
        Garcia LS, Arrowood M, Kokoskin E, Paltridge GP, Pillai DR, Procop GW, Ryan N, Shimizu RY, Visvesvara G.
        Clin Microbiol Rev. 2018 Jan;31(1).

        This Practical Guidance for Clinical Microbiology document on the laboratory diagnosis of parasites from the gastrointestinal tract provides practical information for the recovery and identification of relevant human parasites. The document is based on a comprehensive literature review and expert consensus on relevant diagnostic methods. However, it does not include didactic information on human parasite life cycles, organism morphology, clinical disease, pathogenesis, treatment, or epidemiology and prevention. As greater emphasis is placed on neglected tropical diseases, it becomes highly probable that patients with gastrointestinal parasitic infections will become more widely recognized in areas where parasites are endemic and not endemic. Generally, these methods are nonautomated and require extensive bench experience for accurate performance and interpretation.

      3. Efficacy of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Cruzeiro do Sul, Brazil, 2016External
        Itoh M, Negreiros do Valle S, Farias S, Holanda de Souza TM, Rachid Viana GM, Lucchi N, Chenet S, Marchesini P, Povoa M, Faria ES, Macedo de Oliveira A.
        Am J Trop Med Hyg. 2017 Nov 06.

        We evaluated the therapeutic efficacy of artemether-lumefantrine (AL) fixed-dose combination to treat uncomplicated Plasmodium falciparum malaria in Cruzeiro do Sul, Acre State, in the Amazon region of Brazil. Between December 2015 and May 2016, we enrolled 79 patients, 5-79 years old with fever or history of fever in the previous 48 hours and P. falciparum monoinfection confirmed by microscopy. Attempts were made to provide direct observation or phone reminders for all six doses of AL, and patients were followed-up for 28 days. AL was well tolerated, with no adverse events causing treatment interruption. All but one of the 74 patients who completed the 28-day follow-up had an adequate clinical and parasitologic response = 98.6% (95% CI: 93.2-100%). We could not amplify the one isolate of the case with recurrent infection to differentiate between recrudescence and reinfection. Five (6.3%) patients demonstrated persistent asexual parasitemia on Day 3, but none met definition for early treatment failure. We found no mutations in selected kelch13 gene domains, known to be associated with artemisinin resistance in P. falciparum isolates from Day 0. These results strongly support the continued use of AL as a first-line therapy for uncomplicated P. falciparum malaria in Acre. Routine monitoring of in vivo drug efficacy coupled with molecular surveillance of drug resistance markers remains critical.

      4. Production and characterization of monoclonal antibodies against Encephalitozoon intestinalis and Encephalitozoon sp. spores and their developmental stagesExternal
        Izquierdo F, Moura H, Bornay-Llinares FJ, Sriram R, Hurtado C, Magnet A, Fenoy S, Visvesvara G, Del Aguila C.
        Parasit Vectors. 2017 Nov 09;10(1):560.

        BACKGROUND: Microsporidia are intracellular obligate parasites traditionally associated with immunosuppressed patients; their detection in immunocompetent patients has increased, highlighting their possible importance as emerging pathogens. Detection of spores in stools, urine, body fluids and tissues is difficult and immunological techniques such as immunofluorescence have proved to be a useful and reliable tool in the diagnosis of human microsporidiosis. For this reason, we have produced and characterized monoclonal antibodies (MAbs) specific for Encephalitozoon intestinalis (the second most frequent microsporidian infecting humans), and other Encephalitozoon species, that can be used in different diagnostic techniques. RESULTS: Seven MAbs were selected in accordance with their optical density (OD). Four (4C4, 2C2, 2E5 and 2H2) were isotype IgG2a; two (3A5 and 3C9) isotype IgG3, and one Mab, 1D7, IgM isotype. The selected monoclonal antibody-secreting hybridomas were characterized by indirect immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), Western blot, immunoelectron microscopy (Immunogold) and in vitro cultures. The study by IFAT showed different behavior depending on the MAbs studied. The MAbs 4C4, 2C2, 2E5 and 2H2 showed reactivity against epitopes in the wall of the spore (exospore and endospore) epitopes located in Encephalitozoon sp. spores, whereas the MAbs 3A5, 1D7 and 3C9 showed reactivity against internal epitopes (cytoplasmic contents or sporoplasm) of E. intestinalis spores. All MAbs recognized the developing parasites in the in vitro cultures of E. intestinalis. Additionally, 59 formalin-fixed stool samples that had been previously analyzed were screened, with 26 (44%) presenting microsporidian spores (18 samples with E. intestinalis and 8 samples with Enterocytozoon bieneusi). Detection of microsporidian spores by microscopy was performed using Calcofluor stain, Modified Trichrome, Quick-Hot Gram Chromotrope, as well as IFAT using MAbs 4C4, 2C2, 2E5 and 2H2. The 4 MAbs tested clearly recognized the larger spores corresponding to E. intestinalis, but showed no reactivity with Enterocytozoon bieneusi spores. The mass spectrometry and proteomic study revealed that the Mabs 4C4, 2C2, 2E5 and 2H2 recognized the Spore Wall Protein 1 (SWP1) as the antigenic target. CONCLUSIONS: The IFAT-positive MAbs exhibited excellent reactivity against spores and developmental stages, permitting their use in human and animal diagnosis. The epitopes recognized (exospore, endospore and cytoplasmic contents) by the different MAbs developed need further study, and may reveal potential targets for vaccine development, immunotherapy and chemotherapy.

      5. BACKGROUND: Multi-drug-resistant Plasmodium falciparum threatens malaria elimination efforts in Cambodia and the Greater Mekong Subregion (GMS). Malaria burden in the GMS is higher among certain high-risk demographic groups in Cambodia, especially among migrant and mobile populations (MMPs). This respondent driven sampling (RDS) study was conducted in order to determine malaria knowledge, treatment-seeking behaviours and preventive practices among two MMP groups in Western Cambodia. METHODS: An RDS survey of MMPs was implemented in four purposively-selected communes along the Thai-Cambodia border; two in Veal Veang District and two in Pailin Province, chosen due to their sizeable MMP groups, their convenience of access, and their proximity to Thailand, which allowed for comparison with RDS studies in Thailand. RESULTS: There were 764 participants in Pailin Province and 737 in Veal Veang District. Health messages received in Veal Veang were most likely to come from billboards (76.5%) and family and friends (57.7%), while in Pailin they were most likely to come from sources like radio (57.1%) and television (31.3%). Knowledge of malaria transmission by mosquito and prevention by bed net was above 94% in both locations, but some misinformation regarding means of transmission and prevention methods existed, predominantly in Veal Veang. Ownership of treated bed nets was lower in Pailin than in Veal Veang (25.3% vs 53.2%), while reported use the night before the survey was higher in Pailin than in Veal Veang (57.1% vs 31.6%). Use of private sector health and pharmaceutical services was common, but 81.1% of patients treated for malaria in Pailin and 86.6% in Veal Veang had received a diagnostic test. Only 29.6% of patients treated in Pailin and 19.6% of those treated in Veal Veng reported receiving the indicated first-line treatment. DISCUSSION: Barriers in access to malaria prevention and case management were common among MMPs, with marked variation by site. Resolving both nation-wide and MMP-specific challenges will require targeted interventions that take into account this heterogeneity.

    • Reproductive Health
      1. Sexual and reproductive health care receipt among young males aged 15-24External
        Marcell AV, Gibbs SE, Pilgrim NA, Page KR, Arrington-Sanders R, Jennings JM, Loosier PS, Dittus PJ.
        J Adolesc Health. 2017 Nov 08.

        PURPOSE: This study aimed to describe young men’s sexual and reproductive health care (SRHC) receipt by sexual behavior and factors associated with greater SRHC receipt. METHODS: There were 427 male patients aged 15-24 who were recruited from 3 primary care and 2 sexually transmitted disease (STD) clinics in 1 urban city. Immediately after the visit, the survey assessed receipt of 18 recommended SRHC services across four domains: screening history (sexual health, STD/HIV test, family planning); laboratories (STDs/HIV); condom products (condoms/lubrication); and counseling (STD/HIV risk reduction, family planning, condoms); in addition, demographic, sexual behavior, and visit characteristics were examined. Multivariable Poisson regressions examined factors associated with each SRHC subdomain adjusting for participant clustering within clinics. RESULTS: Of the participants, 90% were non-Hispanic black, 61% were aged 20-24, 90% were sexually active, 71% had female partners (FPs), and 20% had male or male and female partners (M/MFPs). Among sexually active males, 1 in 10 received all services. Half or more were asked about sexual health and STD/HIV tests, tested for STDs/HIV, and were counseled on STD/HIV risk reduction and correct condom use. Fewer were asked about family planning (23%), were provided condom products (32%), and were counseled about family planning (35%). Overall and for each subdomain, never sexually active males reported fewer services than sexually active males. Factors consistently associated with greater SRHC receipt across subdomains included having M/MFPs versus FPs, routine versus non-STD-acute visit, time alone with provider without parent, and seen at STD versus primary care clinic. Males having FPs versus M/MFPs reported greater family planning counseling. CONCLUSIONS: Findings have implications for improving young men’s SRHC delivery beyond the narrow scope of STD/HIV care.

      2. BACKGROUND: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce effectiveness of hormonal contraception (HC). OBJECTIVES: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and clinicaltrials. gov through May, 2017. SELECTION CRITERIA: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics, or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively. MAIN RESULTS: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. Rifaximin and rifalazil did not alter hormone PK in one study each. CONCLUSIONS: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins. This article is protected by copyright. All rights reserved.

    • Substance Use and Abuse
      1. Background: We investigated the relationship between receptivity to electronic cigarette (e-cigarette) advertisements at baseline and e-cigarette use at follow-up among adult baseline non-users of cigarettes and e-cigarettes. Methods: A nationally representative online panel was used to survey non-users of cigarettes and e-cigarettes (n = 2191) at baseline and 5-month follow-up. At baseline, respondents were shown an e-cigarette advertisement and asked if they were aware of it (exposure). Among those exposed, receptivity was self-rated for each ad using a validated scale of 1 to 5 for agreement with each of six items: “worth remembering,” “grabbed my attention,” “powerful,” “informative,” “meaningful,” and “convincing.” Logistic regression was used to measure the relationship between receptivity at baseline and e-cigarette use at follow-up. Results: Among baseline non-users of cigarettes and e-cigarettes, 16.6% reported exposure to e-cigarette advertisements at baseline; overall mean receptivity score was 2.77. Among baseline non-users who reported exposure to e-cigarette advertisements, incidence of e-cigarette use at follow-up was 2.7%; among baseline non-users who reported not being exposed to e-cigarette advertisements, incidence of e-cigarette use at follow-up was 1.3%. The attributable risk percentage for e-cigarette initiation from e-cigarette advertisement exposure was 59.3%; the population attributable risk percentage from e-cigarette advertisement exposure was 22.6%. Receptivity at baseline was associated with e-cigarette use at follow-up (aOR = 1.57; 95% CI = 1.04-2.37). Conclusions: Receptivity to e-cigarette advertisements at baseline was associated with greater odds of e-cigarette use at follow-up among baseline non-users of cigarettes and e-cigarettes. Understanding the role of advertising in e-cigarette initiation could help inform public health policy.

      2. Emergency department visits involving opioid overdoses, U.S., 2010-2014External
        Guy GP, Pasalic E, Zhang K.
        Am J Prev Med. 2017 Nov 10.

        [No abstract]

      3. Caffeine concentrations in coffee, tea, chocolate, and energy drink flavored e-liquidsExternal
        Lisko JG, Lee GE, Kimbrell JB, Rybak ME, Valentin-Blasini L, Watson CH.
        Nicotine Tob Res. 2017 Apr 01;19(4):484-492.

        Introduction: Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive. Methods: A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer. Results: Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection [LOD] – 0.04 microg/g). Detectable caffeine concentrations ranged from 3.3 microg/g to 703 microg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 microg/g to 9290 microg/g). Conclusions: E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee. Implications: This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine.

      4. Patterns of e-cigarette use frequency -N ational Adult Tobacco Survey, 2012-2014External
        Sharapova SR, Singh T, Agaku IT, Kennedy SM, King BA.
        Am J Prev Med. 2017 Nov 03.

        INTRODUCTION: Accounting for occasional or intermittent e-cigarette use has yielded higher estimates of current use among U.S. adults. However, frequency of e-cigarette use by population subgroups is not well described. This study assessed e-cigarette use frequency by sociodemographic characteristics and other tobacco product use among U.S. adults. METHODS: This study analyzed combined data from the 2012-2013 (n=60,192) and 2013-2014 (n=75,233) National Adult Tobacco Survey, a telephone-based survey of U.S. adults aged >/=18 years, to assess frequency of e-cigarette use (daily, some days, rarely) by sex, age, race/ethnicity, education, annual household income, U.S. region, marital status, sexual orientation, and cigarette smoking and other tobacco product use (cigars, cigarillos, little filtered cigars; traditional pipes; water pipes; and chewing tobacco, snuff, dip, snus, and dissolvable tobacco products). Analyses took place in 2016. RESULTS: Among current e-cigarette users, 19.3% used daily, 29.3% used some days, and 51.4% used rarely. Daily use was lowest among younger adults, Hispanics, and those who were single, never married, or not living with a partner; and greatest among non-Hispanic Asians (p<0.0001). Among current e-cigarette users, 25.3% were cigarette-only smokers, 52.8% smoked cigarettes and used other tobacco products, 5.5% used other tobacco products only, 6.5% were former cigarette-only smokers, 6.7% were former users of cigarettes and other tobacco products, 1.3% were former other tobacco product users only, and 1.8% never used cigarettes or other tobacco products. CONCLUSIONS: E-cigarette use frequency varies by sociodemographic characteristics and other tobacco use. Further surveillance, particularly related to frequency of e-cigarette use and its impact on cigarette cessation, could inform public health policy, planning, and practice.

      5. Income inequality and US children’s secondhand smoke exposure: Distinct associations by race-ethnicityExternal
        Shenassa ED, Rossen LM, Cohen J, Morello-Frosch R, Payne-Sturges DC.
        Nicotine Tob Res. 2017 Nov 01;19(11):1292-1299.

        Introduction: Prior studies have found considerable racial and ethnic disparities in secondhand smoke (SHS) exposure. Although a number of individual-level determinants of this disparity have been identified, contextual determinants of racial and ethnic disparities in SHS exposure remain unexamined. The objective of this study was to examine disparities in serum cotinine in relation to area-level income inequality among 14 649 children from the National Health and Nutrition Examination Survey. Methods: We fit log-normal regression models to examine disparities in serum cotinine in relation to Metropolitan Statistical Areas level income inequality among 14 649 nonsmoking children aged 3-15 from the National Health and Nutrition Examination Survey (1999-2012). Result: Non-Hispanic black children had significantly lower serum cotinine than non-Hispanic white children (-0.26; 95% CI: -0.38, -0.15) in low income inequality areas, but this difference was attenuated in areas with high income inequality (0.01; 95% CI: -0.16, 0.18). Serum cotinine declined for non-Hispanic white and Mexican American children with increasing income inequality. Serum cotinine did not change as a function of the level of income inequality among non-Hispanic black children. Conclusions: We have found evidence of differential associations between SHS exposure and income inequality by race and ethnicity. Further examination of environments which engender SHS exposure among children across various racial/ethnic subgroups can foster a better understanding of how area-level income inequality relates to health outcomes such as levels of SHS exposure and how those associations differ by race/ethnicity. Implications: In the United States, the association between children’s risk of SHS exposure and income inequality is modified by race/ethnicity in a manner that is inconsistent with theories of income inequality. In overall analysis this association appears to be as predicted by theory. However, race-specific analyses reveal that higher levels of income inequality are associated with lower levels of SHS exposure among white children, while levels of SHS exposure among non-Hispanic black children are largely invariant to area-level income inequality. Future examination of the link between income inequality and smoking-related health outcomes should consider differential associations across racial and ethnic subpopulations.

      6. Assessment of reactive oxygen species generated by electronic cigarettes using acellular and cellular approachesExternal
        Zhao J, Zhang Y, Sisler JD, Shaffer J, Leonard SS, Morris AM, Qian Y, Bello D, Demokritou P.
        J Hazard Mater. 2018 15 Feb;344:549-557.

        Electronic cigarettes (e-cigs) have fast increased in popularity but the physico-chemical properties and toxicity of the generated emission remain unclear. Reactive oxygen species (ROS) are likely present in e-cig emission and can play an important role in e-cig toxicity. However, e-cig ROS generation is poorly documented. Here, we generated e-cig exposures using a recently developed versatile exposure platform and performed systematic ROS characterization on e-cig emissions using complementary acellular and cellular techniques: 1) a novel acellular Trolox-based mass spectrometry method for total ROS and hydrogen peroxide (H2O2) detection, 2) electron spin resonance (ESR) for hydroxyl radical detection in an acellular and cellular systems and 3) in vitro ROS detection in small airway epithelial cells (SAEC) using the dihydroethidium (DHE) assay. Findings confirm ROS generation in cellular and acellular systems and is highly dependent on the e-cig brand, flavor, puffing pattern and voltage. Trolox method detected a total of 1.2-8.9 nmol H2O2eq/puff; H2O2 accounted for 12-68% of total ROS. SAEC cells exposed to e-cig emissions generated up to eight times more ROS compared to control. The dependency of e-cig emission profile on e-cig features and operational parameters should be taken into consideration in toxicological studies.

    • Zoonotic and Vectorborne Diseases
      1. Leptospirosis cases infected with uncommon serogroups, Puerto Rico, 2013-2015External
        Gorbea H, Garcia-Rivera EJ, Torres H, Lorenzi OD, Rivera A, Galloway RL, Sharp TM.
        Am J Trop Med Hyg. 2017 Nov 06.

        Leptospirosis is an emerging bacterial zoonosis that is endemic but underrecognized throughout the tropics. Through prospective surveillance for acute febrile illness (AFI) among patients who presented to the emergency department of a hospital located in an urban region of Puerto Rico, four patients with laboratory-confirmed leptospirosis were identified. All patients had signs and symptoms of AFI, including fever, headache, and dehydration. Three patients had leukocytosis with thrombocytopenia and were admitted to the hospital. One hospitalized patient presented with jaundice, icteric sclera, and hematuria and developed rhabdomyolysis, whereas another patient with pulmonary edema was admitted to the intensive care unit. Microscopic agglutination titers among the four patients were highest against serogroups Icterohaemorrhagiae (serovar Mankarso), Australis (serovar Bratislava), Bataviae (serovar Bataviae), and Canicola (serovar Canicola). These case reports demonstrate that infection with these apparently uncommon serogroups can result in illness ranging from mild to life-threatening.

      2. Acute Q fever case detection among acute febrile illness patients, Thailand, 2002-2005External
        Greiner AL, Bhengsri S, Million M, Edouard S, Thamthitiwat S, Clarke K, Kersh GJ, Gregory CJ, Raoult D, Parola P.
        Am J Trop Med Hyg. 2017 Nov 06.

        Acute Q fever cases were identified from a hospital-based acute febrile illness study conducted in six community hospitals in rural north and northeast Thailand from 2002 to 2005. Of 1,784 participants that underwent Coxiella burnetii testing, nine (0.5%) participants were identified in this case-series as acute Q fever cases. Eight case-patients were located in one province. Four case-patients were hospitalized. Median age was 13 years (range: 7-69); five were male. The proportion of children with acute Q fever infection was similar to adults (P = 0.17). This previously unrecognized at-risk group, school-age children, indicates that future studies and prevention interventions should target this population. The heterogeneity of disease burden across Thailand and milder clinical presentations found in this case-series should be considered in future studies. As diagnosis based on serology is limited during the acute phase of the disease, other diagnostic options, such as polymerase chain reaction, should be explored to improve acute case detection.

      3. Do animal exhibitors support and follow recommendations to prevent transmission of variant influenza at agricultural fairs? A survey of animal exhibitor households after a variant influenza virus outbreak in MichiganExternal
        Stewart RJ, Rossow J, Conover JT, Lobelo EE, Eckel S, Signs K, Stobierski MG, Trock SC, Fry AM, Olsen SJ, Biggerstaff M.
        Zoonoses Public Health. 2017 Nov 16.

        Influenza A viruses circulate in swine and can spread rapidly among swine when housed in close proximity, such as at agricultural fairs. Youth who have close and prolonged contact with influenza-infected swine at agricultural fairs may be at increased risk of acquiring influenza virus infection from swine. Animal and human health officials have issued written measures to minimize influenza transmission at agricultural exhibitions; however, there is little information on the knowledge, attitudes, and practice (KAP) of these measures among animal exhibitors. After an August 2016 outbreak of influenza A(H3N2) variant (“H3N2v”) virus infections (i.e., humans infected with swine influenza viruses) in Michigan, we surveyed households of animal exhibitors at eight fairs (including one with known H3N2v infections) to assess their KAP related to variant virus infections and their support for prevention measures. Among 170 households interviewed, most (90%, 151/167) perceived their risk of acquiring influenza from swine to be low or very low. Animal exhibitor households reported high levels of behaviours that put them at increased risk of variant influenza virus infections, including eating or drinking in swine barns (43%, 66/154) and hugging, kissing or snuggling with swine at agricultural fairs (31%, 48/157). Among several recommendations, including limiting the duration of swine exhibits and restricting eating and drinking in the animal barns, the only recommendation supported by a majority of households was the presence of prominent hand-washing stations with a person to monitor hand-washing behaviour (76%, 129/170). This is a unique study of KAP among animal exhibitors and highlights that animal exhibitor households engage in behaviours that could increase their risk of variant virus infections and have low support for currently recommended measures to minimize infection transmission. Further efforts are needed to understand the lack of support for recommended measures and to encourage healthy behaviours at fairs.

      4. Surveillance for Q fever endocarditis in the United States, 1999-2015External
        Straily A, Dahlgren FS, Peterson A, Paddock CD.
        Clin Infect Dis. 2017 Nov 13;65(11):1872-1877.

        Background: Q fever is a worldwide zoonosis caused by Coxiella burnetii. In some persons, particularly those with cardiac valve disease, infection with C. burnetii can cause a life-threatening infective endocarditis. There are few descriptive analyses of Q fever endocarditis in the United States. Methods: Q fever case report forms submitted during 1999-2015 were reviewed to identify reports describing endocarditis. Cases were categorized as confirmed or probable using criteria defined by the Council for State and Territorial Epidemiologists (CSTE). Demographic, laboratory, and clinical data were analyzed. Results: Of 140 case report forms reporting endocarditis, 49 met the confirmed definition and 36 met the probable definition. Eighty-two percent were male and the median age was 57 years (range, 16-87 years). Sixty-seven patients (78.8%) were hospitalized, and 5 deaths (5.9%) were reported. Forty-five patients (52.9%) had a preexisting valvulopathy. Eight patients with endocarditis had phase I immunoglobulin G antibody titers >800 but did not meet the CSTE case definition for Q fever endocarditis. Conclusions: These data summarize a limited set of clinical and epidemiological features of Q fever endocarditis collected through passive surveillance in the United States. Some cases of apparent Q fever endocarditis could not be classified by CSTE laboratory criteria, suggesting that comparison of phase I and phase II titers could be reexamined as a surveillance criterion. Prospective analyses of culture-negative endocarditis are needed to better assess the clinical spectrum and magnitude of Q fever endocarditis in the United States.

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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