Volume 10, Issue 29, August 7, 2018

CDC Science Clips: Volume 10, Issue 29, August 7, 2018

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

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

  1. CDC Vital Signs
    • Zika in Infants
      1. *US Zika Pregnancy and Infant Registry Website
        Centers for Disease Control and Prevention .
        Updated May 3, 2018. Accessed July 20, 2018. .

        The US Zika Pregnancy and Infant Registry is a collaborative and innovative system to learn about Zika virus infection during pregnancy and after birth. Information from the Registry is used to make recommendations for healthcare providers caring for families affected by Zika virus and plan for needed services.

      2. *Zika virus infection in pregnancy: Maternal, fetal, and neonatal considerationsExternal
        Zorrilla CD, Garcia Garcia I, Garcia Fragoso L, De La Vega A.
        J Infect Dis. 2017 Dec 16;216(suppl_10):S891-s896.

        An infection with the Zika virus (ZIKV) is usually mild, with nonspecific symptoms and most often asymptomatic. However, because of its causal relationship with severe congenital malformations, the ZIKV epidemic became an imperative for mobilization, renewed strategies for vector control, and biomedical research. A congenital Zika syndrome (CZS) has been characterized with 5 distinctive features that focus on brain development abnormalities (including microcephaly and brain calcifications), retinal manifestations, and defects on extremities including congenital contractures and hypertonia. The CZS could be just “the tip of the iceberg”, pending the documentation of a spectrum of disease that could manifest later in life, from mild dysfunction to severe disease. It will be a matter of time for neurodevelopmental abnormalities, learning disabilities, and other unknown but yet-to-be-described outcomes to be associated with intrauterine ZIKV infection. In addition, ZIKV infection during pregnancy has been associated with other adverse outcomes. Reports mostly include ZIKV-affected pregnancies, and it will be difficult to clearly establish causality without appropriate control groups. We are summarizing some of the known or reported consequences of such infection during pregnancy. Women of reproductive age and particularly pregnant women are the most vulnerable to the adverse consequences of the ZIKV epidemic. Vector control programs need to be expanded to curtail new infections. Research is needed to develop safe and effective treatments, a preventive or therapeutic vaccine, and specific and sensitive tests and to diagnose and identify correlates of long-term immunity. Vaccines and treatments should be safe to be used in pregnancy. To do nothing would allow thousands of pregnant women to expose their fetuses to an infection that causes birth defects and other problems. Prenatal diagnosis technology development is necessary to be able to predict or diagnose adverse fetal outcomes related to ZIKV. Moreover, these tests should be used in a manner similar to the testing/screening method for neural tube defects and common chromosomal anomalies during prenatal care.

      3. Update: Interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection – United States, October 2017External
        Adebanjo T, Godfred-Cato S, Viens L, Fischer M, Staples JE, Kuhnert-Tallman W, Walke H, Oduyebo T, Polen K, Peacock G, Meaney-Delman D, Honein MA, Rasmussen SA, Moore CA.
        MMWR Morb Mortal Wkly Rep. 2017 Oct 20;66(41):1089-1099.

        CDC has updated its interim guidance for U.S. health care providers caring for infants with possible congenital Zika virus infection (1) in response to recently published updated guidance for health care providers caring for pregnant women with possible Zika virus exposure (2), unknown sensitivity and specificity of currently available diagnostic tests for congenital Zika virus infection, and recognition of additional clinical findings associated with congenital Zika virus infection. All infants born to mothers with possible Zika virus exposure* during pregnancy should receive a standard evaluation at birth and at each subsequent well-child visit including a comprehensive physical examination, age-appropriate vision screening and developmental monitoring and screening using validated tools (3-5), and newborn hearing screen at birth, preferably using auditory brainstem response (ABR) methodology (6). Specific guidance for laboratory testing and clinical evaluation are provided for three clinical scenarios in the setting of possible maternal Zika virus exposure: 1) infants with clinical findings consistent with congenital Zika syndrome regardless of maternal testing results, 2) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers with laboratory evidence of possible Zika virus infection,(dagger) and 3) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers without laboratory evidence of possible Zika virus infection. Infants in the first two scenarios should receive further testing and evaluation for Zika virus, whereas for the third group, further testing and clinical evaluation for Zika virus are not recommended. Health care providers should remain alert for abnormal findings (e.g., postnatal-onset microcephaly and eye abnormalities without microcephaly) in infants with possible congenital Zika virus exposure without apparent abnormalities at birth.

      4. Proven benefits of early childhood interventionsExternal
        Karoly L, Kilburn M, Cannon J.
        Santa Monica, CA: RAND Corporation. 2005 .

        [No abstract]

      5. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric cliniciansExternal
        Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB, Ribeiro EM, Ventura LO, Neto NN, Arena JF, Rasmussen SA.
        JAMA Pediatr. 2017 Mar 1;171(3):288-295.

        Importance: Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations: We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE for Zika from inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement. Conclusions and Relevance: Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype-the congenital Zika syndrome-has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care.

      6. Zika virus and birth defects – reviewing the evidence for causalityExternal
        Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR.
        N Engl J Med. 2016 May 19;374(20):1981-7.

        [No abstract]

      7. Health and development at age 19-24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak – Brazil, 2017External
        Satterfield-Nash A, Kotzky K, Allen J, Bertolli J, Moore CA, Pereira IO, Pessoa A, Melo F, Santelli A, Boyle CA, Peacock G.
        MMWR Morb Mortal Wkly Rep. 2017 Dec 15;66(49):1347-1351.

        In November 2015, the Brazilian Ministry of Health (MOH) declared the Zika virus outbreak a public health emergency after an increase in microcephaly cases was reported in the northeast region of the country (1). During 2015-2016, 15 states in Brazil with laboratory-confirmed Zika virus transmission reported an increase in birth prevalence of microcephaly (2.8 cases per 10,000 live births), significantly exceeding prevalence in four states without confirmed transmission (0.6 per 10,000) (2). Although children with microcephaly and laboratory evidence of Zika virus infection have been described in early infancy (3), their subsequent health and development have not been well characterized, constraining planning for the care and support of these children and their families. The Brazilian MOH, the State Health Secretariat of Paraiba, and CDC collaborated on a follow-up investigation of the health and development of children in northeastern Brazil who were reported to national surveillance with microcephaly at birth. Nineteen children with microcephaly at birth and laboratory evidence of Zika virus infection were assessed through clinical evaluations, caregiver interviews, and review of medical records. At follow-up (ages 19-24 months), most of these children had severe motor impairment, seizure disorders, hearing and vision abnormalities, and sleep difficulties. Children with microcephaly and laboratory evidence of Zika virus infection have severe functional limitations and will require specialized care from clinicians and caregivers as they age.

      8. Pregnancy outcomes after maternal Zika virus infection during pregnancy – U.S. Territories, January 1, 2016-April 25, 2017External
        Shapiro-Mendoza CK, Rice ME, Galang RR, Fulton AC, VanMaldeghem K, Prado MV, Ellis E, Anesi MS, Simeone RM, Petersen EE, Ellington SR, Jones AM, Williams T, Reagan-Steiner S, Perez-Padilla J, Deseda CC, Beron A, Tufa AJ, Rosinger A, Roth NM, Green C, Martin S, Lopez CD, deWilde L, Goodwin M, Pagano HP, Mai CT, Gould C, Zaki S, Ferrer LN, Davis MS, Lathrop E, Polen K, Cragan JD, Reynolds M, Newsome KB, Huertas MM, Bhatangar J, Quinones AM, Nahabedian JF, Adams L, Sharp TM, Hancock WT, Rasmussen SA, Moore CA, Jamieson DJ, Munoz-Jordan JL, Garstang H, Kambui A, Masao C, Honein MA, Meaney-Delman D.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 16;66(23):615-621.

        Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territories(dagger) with local transmission of Zika virus reported 2,549 completed pregnancies( section sign) (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection( paragraph sign) (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).

      9. Description of 13 infants born during October 2015-January 2016 with congenital Zika virus infection without microcephaly at birth – BrazilExternal
        van der Linden V, Pessoa A, Dobyns W, Barkovich AJ, Junior HV, Filho EL, Ribeiro EM, Leal MC, Coimbra PP, Aragao MF, Vercosa I, Ventura C, Ramos RC, Cruz DD, Cordeiro MT, Mota VM, Dott M, Hillard C, Moore CA.
        MMWR Morb Mortal Wkly Rep. 2016 Dec 2;65(47):1343-1348.

        Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceara with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

      10. Response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndromeExternal
        Ventura LO, Lawrence L, Ventura CV, Dutton GN, Marinho P, Ferro PF, Gois AL, Dias NC, Ventura L, Moore CA, Hyvarinen L.
        J aapos. 2017 Dec;21(6):480-484.e1.

        PURPOSE: To describe the immediate response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndrome (CZS). METHODS: Children born between May and December 2015 with a confirmed diagnosis of CZS and enrolled in a multidisciplinary early intervention program were included in this study. All children received a comprehensive ophthalmic examination, including dynamic retinoscopy and cycloplegic refraction. Children were prescribed their full correction if they met the criteria for refractive error, and additional plus 3.00 overcorrection for strabismus, accommodative dysfunction, and/or low vision. Monocular and binocular visual responses to Lea Grating Test at 30 cm, with and without eyeglasses, were measured on day 1 of glasses wear. RESULTS: A total of 60 children were evaluated (mean age at evaluation, 11.5 +/- 1.1 months; range, 9.0-16.0 months). Lea Grating Test responses were abnormal in all children prior to spectacle correction. Hypoaccommodation was present in 17 of 21 children (81%). Overcorrection was prescribed for all children. Visual responses were subnormal even with glasses use; however, immediate improvement in binocular vision was found in 37 children (62%) and in 74 of 119 eyes (62.2%). For the monocular visual improvement, 27 of 115 eyes (23.5%) had structural abnormalities, and 44 of 115 eyes (38.3%) were structurally normal. There was a statistical difference between the cycloplegic refraction of the children in August and in November, including emmetropia (P = 0.001), hyperopia (P = 0.000), myopia (P = 0.007), and astigmatism (P = 0.004). CONCLUSIONS: Eyeglasses can improve visual acuity in children with CZS. Significant changes in their refractive status over time requires periodic updates.

  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. Application of a tool to identify undiagnosed hypertension – United States, 2016External
        Ciemins EL, Ritchey MD, Joshi VV, Loustalot F, Hannan J, Cuddeback JK.
        MMWR Morb Mortal Wkly Rep. 2018 Jul 27;67(29):798-802.

        Approximately 11 million U.S. adults with a usual source of health care have undiagnosed hypertension, placing them at increased risk for cardiovascular events (1-3). Using data from the National Health and Nutrition Examination Survey (NHANES), CDC developed the Million Hearts Hypertension Prevalence Estimator Tool, which allows health care delivery organizations (organizations) to predict their patient population’s hypertension prevalence based on demographic and comorbidity characteristics (2). Organizations can use this tool to compare predicted prevalence with their observed prevalence to identify potential underdiagnosed hypertension. This study applied the tool using medical billing data alone and in combination with clinical data collected among 8.92 million patients from 25 organizations participating in American Medical Group Association (AMGA) national learning collaborative* to calculate and compare predicted and observed adult hypertension prevalence. Using billing data alone revealed that up to one in eight cases of hypertension might be undiagnosed. However, estimates varied when clinical data were included to identify comorbidities used to predict hypertension prevalence or describe observed hypertension prevalence. These findings demonstrate the tool’s potential use in improving identification of hypertension and the likely importance of using both billing and clinical data to establish hypertension and comorbidity prevalence estimates and to support clinical quality improvement efforts.

      2. Cervical cancer screening intervals preferred by U.S. womenExternal
        Cooper CP, Saraiya M.
        Am J Prev Med. 2018 Jul 19.

        INTRODUCTION: Many U.S. women continue to be screened annually for cervical cancer, despite current guidelines that recommend 3- or 5-year screening intervals depending on screening modality and patient age. METHODS: Data from 2012 and 2015 web-based surveys of U.S. adults were analyzed in 2017 to investigate U.S. women’s cervical cancer screening preferences. The study was limited to women aged >/=18 years without a hysterectomy or cervical cancer diagnosis (2012 n=1,380, 2015 n=1,339). RESULTS: Women’s preference for 3- or 5-year screening intervals doubled during the study period (2012: 31.2%, 2015: 64.2%, p<0.001). The most preferred screening options in 2015 were co-testing every 3 years with the Pap and human papillomavirus tests (34.0%) and annual Pap testing (30.4%)-neither of which were recommended at that time or currently. Use of 3- and 5-year Pap testing intervals increased during the study period (2012: 6.9%, 2015: 12.9%, p<0.001), whereas annual Pap testing declined (2012: 48.5%, 2015: 35.6%, p<0.001). Among women who were regularly screened and preferred 3- or 5-year screening intervals, the minority reported screening practices that matched this preference (2012: 24.1%, 2015: 29.3%, p=0.71). CONCLUSIONS: Women’s preference for longer cervical cancer screening intervals has increased rapidly and outpaced utilization. At the same time, many women continue to be screened annually. Expanding appropriate screening may require increasing women’s and providers’ comfort with screening recommendations.

      3. Patterns and trends in cancer screening in the United StatesExternal
        Hall IJ, Tangka FK, Sabatino SA, Thompson TD, Graubard BI, Breen N.
        Prev Chronic Dis. 2018 Jul 26;15:E97.

        INTRODUCTION: We examined the prevalence of cancer screening reported in 2015 among US adults, adjusted for important sociodemographic and access-to-care variables. By using data from the National Health Interview Survey (NHIS) for 2000 through 2015, we examined trends in prevalence of cancer screening that adhered to US Preventive Services Task Force screening recommendations in order to monitor screening progress among traditionally underserved population subgroups. METHODS: We analyzed NHIS data from surveys from 2000 through 2015 to estimate prevalence and trends in use of recommended screening tests for breast, cervical, colorectal, and prostate cancers. We used logistic regression and report predictive margins for population subgroups adjusted for various socioeconomic and demographic variables. RESULTS: Colorectal cancer screening was the only test that increased during the study period. We found disparities in prevalence of test use among subgroups for all tests examined. Factors that reduced the use of screening tests included no contact with a doctor in the past year, no usual source of health care, and no insurance coverage. CONCLUSION: Understanding use of cancer screening tests among different population subgroups is vital for planning public health interventions with potential to increase screening uptake and reduce disparities in cancer morbidity and mortality. Overarching goals of Healthy People 2020 are to “achieve health equity, eliminate disparities, and improve the health of all groups.” Adjusted findings for 2015, compared with previous years, show persistent screening disparities, particularly among the uninsured, and progress for colorectal cancer screening only.

      4. The incidence and prevalence of adult primary Sjogren’s syndrome in New York CountyExternal
        Izmirly PM, Buyon JP, Wan I, Belmont HM, Sahl S, Salmon JE, Askanase A, Bathon JM, Geraldino-Pardilla L, Ali Y, Ginzler EM, Putterman C, Gordon C, Helmick CG, Parton H.
        Arthritis Care Res (Hoboken). 2018 Jul 25.

        OBJECTIVE: Extant epidemiologic data of primary Sjogren’s Syndrome (pSS) remains limited, particularly for racial/ethnic populations in the United States (US). The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of cases with Systemic Lupus Erythematosus and related diseases including pSS in Manhattan, was used to provide estimates of the incidence and prevalence of pSS across major racial/ethnic populations. METHODS: MLSP cases were identified from hospitals, rheumatologists, and population databases. Three case definitions were used for pSS: physician diagnosis, rheumatologist diagnosis, and modified pSS criteria. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess case under-ascertainment. RESULTS: By physician diagnosis, age-adjusted overall incidence and prevalence rates of pSS among adult Manhattan residents were 3.5 and 13.1 per 100,000 person-years. Capture-recapture adjustment increased incidence and prevalence rates (4.1 and 14.2). Based on physician diagnosis, incidence and prevalence rates were approximately 6 times higher among women than men (p<0.01). Incidence of pSS was statistically higher among non-Latina Asian (10.5) and non-Latina White women (6.2) compared with Latina women (3.2). Incidence was also higher among non-Latina Asian women compared with non-Latina Black women (3.3). Prevalence of pSS did not differ by race/ethnicity. Similar trends were observed when more restrictive case definitions were applied. CONCLUSION: Data from the MLSP revealed disparities in pSS incidence and prevalence by sex among Manhattan residents and differences in pSS incidence by race/ethnicity among women. These data also provided epidemiologic estimates for the major racial/ethnic populations in the US. This article is protected by copyright. All rights reserved.

      5. Hearing disability prevalence and risk factors in two recent national surveysExternal
        Li CM, Zhao G, Hoffman HJ, Town M, Themann CL.
        Am J Prev Med. 2018 Jul 18.

        INTRODUCTION: Hearing loss is a worldwide societal and public health concern. Globally, disabling hearing loss affects 538 million adults (men, 12.2%; women, 9.8%). This study examined the prevalence and risk factors associated with deafness or serious difficulty hearing in two nationally representative surveys. METHODS: Data were analyzed in 2017 from the 2016 Behavioral Risk Factor Surveillance System (BRFSS) and the 2014 National Health Interview Survey. The BRFSS collected data through telephone interviews. The 2014 National Health Interview Survey collected face-to-face household interview data that included a hearing health supplement in the Sample Adult Core. Both surveys asked adults aged >/=18 years the disability question on deafness or serious difficulty hearing as defined by the American Community Survey. Weighted prevalence, prevalence ratios, and 95% CIs were calculated. Logistic regression was used to adjust for sociodemographic and geographic characteristics. RESULTS: Prevalence of deafness or serious difficulty hearing was 5.8% (BRFSS) and 6.0% (National Health Interview Survey); males had a 60% higher prevalence than females. The prevalence was significantly associated with increasing age, lower educational level and income, and was higher among non-Hispanic whites than among non-Hispanic blacks and Hispanics. Deafness or serious difficulty hearing was strongly associated with increasing degree of self-reported trouble hearing in the National Health Interview Survey. The BRFSS state-specific prevalence varied from 3.8% to 13.3%, with higher prevalence in the most public health-challenged states according to America’s Health Rankings. CONCLUSIONS: The prevalence of deafness or serious difficulty hearing was approximately 6% in the National Health Interview Survey and BRFSS, but increased considerably for older, less advantaged individuals and in more public health-challenged states.

      6. Geographical, racial and socio-economic variation in life expectancy in the US and their impact on cancer relative survivalExternal
        Mariotto AB, Zou Z, Johnson CJ, Scoppa S, Weir HK, Huang B.
        PLoS One. 2018 ;13(7):e0201034.

        PURPOSE: Despite gains in life expectancy between 1992 to 2012, large disparities in life expectancy continue to exist in the United States between subgroups of the population. This study aimed to develop detailed life tables (LT), accounting for mortality differences by race, geography, and socio-economic status (SES), to more accurately measure relative cancer survival and life expectancy patterns in the United States. METHODS: We estimated an extensive set of County SES-LT by fitting Poisson regression models to deaths and population counts for U.S. counties by age, year, gender, race, ethnicity and county-level SES index. We reported life expectancy patterns and evaluated the impact of the County SES-LT on relative survival using data from the Surveillance Epidemiology and End Results (SEER) Program cancer registries. RESULTS: Between 1992 and 2012, the largest increase in life expectancy was among black men (6.8 years), however there were still large geographical differences. Life expectancy was highest for Asian or Pacific Islanders (API), and lowest for American Indians and Alaskan Natives (AIAN). In 2010, life expectancies by state ranged from 73 to 82 years for white males, 78 to 86 years for white females, 66 to 75 for black males, and 75 to 81 for black females. Comparisons of relative survival using National LT and the new County SES-LT showed that relative survival using County SES-LT improved relative survival estimates for some demographic groups, particularly in low and high SES areas, among Hispanics and AIAN, and among older male cancer patients. Relative survival using County SES-LT was 7.3% and 6.7% survival points closer to cause-specific survival compared to the National LT relative survival for AIAN and Hispanic cancer patients diagnosed between ages 75 and 84 years, respectively. Importantly, the County SES-LT relative survival estimates were higher in lower SES areas and lower in higher SES areas, reducing differences in relative survival comparisons. CONCLUSION: The use of these new socio-economic life tables (County SES-LT) can provide more accurate estimates of relative survival, improve comparisons of relative survival among registries, better illustrate disparities and cancer control efforts, and should be used as default for cancer relative survival using U.S. data.

      7. Incidence of primary liver cancer in American Indians and Alaska Natives, US, 1999-2009External
        Melkonian SC, Jim MA, Reilley B, Erdrich J, Berkowitz Z, Wiggins CL, Haverkamp D, White MC.
        Cancer Causes Control. 2018 Jul 20.

        PURPOSE: To evaluate liver cancer incidence rates and risk factor correlations in non-Hispanic AI/AN populations for the years 1999-2009. METHODS: We linked data from 51 central cancer registries with the Indian Health Service patient registration databases to improve identification of the AI/AN population. Analyses were restricted to non-Hispanic persons living in Contract Health Service Delivery Area counties. We compared age-adjusted liver cancer incidence rates (per 100,000) for AI/AN to white populations using rate ratios. Annual percent changes (APCs) and trends were estimated using joinpoint regression analyses. We evaluated correlations between regional liver cancer incidence rates and risk factors using Pearson correlation coefficients. RESULTS: AI/AN persons had higher liver cancer incidence rates than whites overall (11.5 versus 4.8, RR = 2.4, 95% CI 2.3-2.6). Rate ratios ranged from 1.6 (Southwest) to 3.4 (Northern Plains and Alaska). We observed an increasing trend among AI/AN persons (APC 1999-2009 = 5%). Rates of distant disease were higher in the AI/AN versus white population for all regions except Alaska. Alcohol use (r = 0.84) and obesity (r = 0.79) were correlated with liver cancer incidence by region. CONCLUSIONS: Findings highlight disparities in liver cancer incidence between AI/AN and white populations and emphasize opportunities to decrease liver cancer risk factor prevalence.

      8. INTRODUCTION: Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults. AIM: The aim of this study was to compare/characterize bleeding phenotype and provider interventions in postmenarchal adolescents < 18 years and premenopausal adults >/= 18 years with HMB and BD. METHODS: Patient demographics, BD, and provider interventions/therapy details for HMB were compared between both age groups enrolled in the Centers for Disease Control and Prevention (CDC) Female Universal Data Collection (UDC) surveillance project in United States hemophilia treatment centres. Cross-sectional descriptive analyses including frequency distributions, summary statistics, bivariate and logistic regression analyses were performed. RESULTS: Of 269 females (79 adolescents; median age 16 years, interquartile range (IQR) = 2; 190 adults; median age 27 years, IQR = 13) evaluated, BD distribution was similar in both groups. Compared to adolescents, adults more often had family history of bleeding (Adjusted odds ratios [AOR] = 2.6, 1.3-5.6), delay in diagnosis (AOR = 2.5, 1.2-4.9), bleeding with dental procedures (AOR = 2.0, 1.0-4.0), gastrointestinal bleeding (AOR = 4.6, 1.0-21.9), anaemia (AOR = 2.7, 1.4-5.2), utilized desmopressin less often (AOR = 0.4, 0.2-0.8) and underwent gynaecologic procedure/surgery more frequently (AOR = 5.9, 1.3-27.3). CONCLUSION: Bleeding phenotypes of adolescents and adults with HMB and BD were different with more frequent bleeding complications, anaemia, gynaecologic procedures/surgeries, less desmopressin use and more delay in diagnosing BD in adults. Longitudinal studies are needed to determine whether improved patient/provider awareness and education will translate to early diagnosis and timely management of BD/HMB in adolescents that may prevent/reduce future haematologic/gynaecologic complications.

      9. Health insurance status and clinical cancer screenings among U.S. adultsExternal
        Zhao G, Okoro CA, Li J, Town M.
        Am J Prev Med. 2018 Jan;54(1):e11-e19.

        INTRODUCTION: Health insurance coverage is linked to clinical preventive service use. This study examined cancer screenings among U.S. adults by health insurance status. METHODS: The Behavioral Risk Factor Surveillance System collected data on healthcare access and cancer screenings from 42 states and the District of Columbia in 2014. Data analyses were conducted in 2016. Participants’ health insurance status during the preceding 12 months was categorized as adequately insured, underinsured, or never insured. Primary type of insurance coverage was categorized as employer-based or Medicare (aged >/=65 years), self-purchased plan, Medicaid/Medicare (aged <65 years), and other public insurance. Clinical cancer screenings were assessed following the U.S. Preventive Services Task Force recommendations. RESULTS: Compared with adequately insured adults, underinsured and never insured women were 6% (p<0.001) and 41% (p<0.001) less likely to receive breast cancer screening, respectively; 1% (p<0.05) and 19% (p<0.001) less likely to receive cervical cancer screening, respectively; and 3% (p<0.01) and 47% (p<0.001) less likely to receive colorectal cancer screening, respectively; underinsured and never insured men were 6% (p<0.001) and 52% (p<0.001) less likely to receive colorectal cancer screening, respectively. Compared with adults with employer-based insurance/Medicare (aged >/=65 years), women with all other types of insurance were less likely to receive breast and cervical cancer screenings; women and men with self-purchased plans were less likely to receive colorectal cancer screening; however, men with other public insurance were more likely to receive colorectal cancer screening. CONCLUSIONS: Disparities in cancer screenings by health insurance status and type of insurance exist among U.S. adults. Greater efforts to increase screening rates and to reduce disparities in cancer screenings are an important strategy to help improve overall population health.

    • Communicable Diseases
      1. Typhoid fever: Way forwardExternal
        Bhutta ZA, Gaffey M, Crump JA, Steele D, Breiman RF, Mintz ED, Black RE, Luby SP, Levine MM.
        Am J Trop Med Hyg. 2018 Jul 25.

        The Tackling Typhoid supplement shows that typhoid fever continues to be a problem globally despite socioeconomic gains in certain settings. Morbidity remains high in many endemic countries, notably in sub-Saharan Africa and South Asia. In addition, antimicrobial resistance is a growing issue that poses a challenge for clinical management. The findings from this supplement revealed that outside of high-income countries, there were few reliable population-based estimates of typhoid and paratyphoid fever derived from surveillance systems. This indicates the need for monitoring systems that can also characterize the effectiveness of interventions, particularly in low- and middle-income settings. The country case studies indicated that gains in economic conditions, education, and environmental health may be associated with reductions in typhoid fever burden. Over the study period, the effect is mainly notable in countries with higher baseline levels of economic development, female literacy, and investments in public sanitation. High burden countries must continue to invest in strategies at the local level to address environmental factors such as access to safe drinking water and improved public sanitation that are known to interrupt transmission or diminish the risk of acquiring typhoid. Developing more effective vaccines and incorporating appropriate immunization strategies that target populations with the greatest risk could potentially alleviate disease burden.

      2. Salmonella enterica serotype Newport infections in the United States, 2004-2013: Increased incidence investigated through four surveillance systemsExternal
        Crim SM, Chai SJ, Karp BE, Judd MC, Reynolds J, Swanson KC, Nisler A, McCullough A, Gould LH.
        Foodborne Pathog Dis. 2018 Jul 23.

        Newport is the third most common Salmonella enterica serotype identified among the estimated 1.2 million human salmonellosis infections occurring annually in the United States. Risk factors for infection and food items implicated in outbreaks vary by antimicrobial resistance pattern. We conducted a descriptive analysis of data from four enteric disease surveillance systems capturing information on incidence, demographics, seasonality, geographic distribution, outbreaks, and antimicrobial resistance of Newport infections over a 10-year period from 2004 through 2013. Incidence increased through 2010, then declined to rates similar to those in the early years of the study. Incidence was highest in the South and among children <5 years old. Among isolates submitted for antimicrobial susceptibility testing, 88% were susceptible to all antimicrobials tested (pansusceptible) and 8% were resistant to at least seven agents, including ceftriaxone. Rates of pansusceptible isolates were also highest in the South and among young children, particularly in 2010. Pansusceptible strains of Newport have been associated with produce items and environmental sources, such as creek water and sediment. However, the role of environmental transmission of Newport in human illness is unclear. Efforts to reduce produce contamination through targeted legislation, as well as collaborative efforts to identify sources of contamination in agricultural regions, are underway.

      3. Self-testing, communication and information technology to promote HIV diagnosis among young gay and other men who have sex with men (MSM) in BrazilExternal
        De Boni RB, Lentini N, Santelli AC, Barbosa A, Cruz M, Bingham T, Cota V, Correa RG, Veloso VG, Grinsztejn B.
        J Int AIDS Soc. 2018 Jul;21 Suppl 5:e25116.

        [No abstract]

      4. Staffing reductions in state (SHD) and local health departments (LHD) in fiscal year 2012 were concentrated in disease investigation specialists (DIS) and clinicians (local) and DIS and administrative staff (state). LHDs with budget cuts, were significantly more likely to report reduced partner services if they had staffing reductions.

      5. Mumps outbreaks at four universities – Indiana, 2016External
        Golwalkar M, Pope B, Stauffer J, Snively A, Clemmons N.
        MMWR Morb Mortal Wkly Rep. 2018 Jul 27;67(29):793-797.

        From February to April 2016, the Indiana State Department of Health (ISDH) confirmed mumps outbreaks at four universities (three public and one private). All universities were located within 65 miles of Indianapolis; however, epidemiologic links among outbreaks were limited. ISDH and local health departments investigated the outbreaks and initiated control measures at all universities. A protocol describing recommended testing for mumps, testing priorities during the outbreak, and a preauthorization process for submitting specimens to the ISDH Laboratory (ISDHL) was developed and disseminated to providers and public health partners (1). Outbreaks at each university were declared over after two incubation periods* elapsed without identified cases; the last outbreak ended September 10, 2016. Among the 281 confirmed and probable cases identified, 216 (76.9%) persons had documentation of presumptive evidence of immunity(dagger) (2). At some universities, documentation of receipt of 2 doses of measles, mumps, rubella vaccine (MMR), which is a criterion for evidence of immunity, was not available and required substantial personnel time to verify. Implementation of policies for excluding susceptible persons from classes and other group settings was also difficult. The laboratory testing protocol increased the percentage of specimens testing positive and improved case detection. Outbreak-specific laboratory testing guidance on specimen collection for mumps confirmation and standardized vaccination documentation in highly vaccinated settings could aid outbreak management. Evaluation of exclusion policies might also be necessary. In 2018, the Advisory Committee on Immunization Practices (ACIP) published a recommendation that persons previously vaccinated with 2 doses of MMR who are determined by public health authorities to be part of a group at increased risk for infection during a mumps outbreak receive a third dose of MMR (3).

      6. Gaps and opportunities: measuring the key population cascade through surveys and services to guide the HIV responseExternal
        Hakim AJ, MacDonald V, Hladik W, Zhao J, Burnett J, Sabin K, Prybylski D, Garcia Calleja JM.
        J Int AIDS Soc. 2018 Jul;21 Suppl 5:e25119.

        INTRODUCTION: The UNAIDS 90-90-90 targets to diagnose 90% of people living with HIV, put 90% of them on treatment, and for 90% of them to have suppressed viral load have focused the international HIV response on the goal of eliminating HIV by 2030. They are also a constructive tool for measuring progress toward reaching this goal but their utility is dependent upon data availability. Though more than 25% of new infections are among key populations (KP)- sex workers, men who have sex with men, transgender people, people who inject drugs, and prisoners- and their sex partners, there is a dearth of treatment cascade data for KP. We assess the availability of cascade data and review the opportunities offered by biobehavioral and programme data to inform the HIV response. DISCUSSION: The emphasis on the collection of treatment cascade data among the general population in higher prevalence countries has not led to a similar increase in the availability of cascade data for KP. The limited data available for KP highlight large gaps in service uptake across the cascade, particularly in the first 90, awareness of HIV status. Biobehavioral surveys (BBS), with linked population size estimation, provide population-based data on the treatment cascade and should be conducted every two to three years in locations with services for KP. With the inclusion of viral load testing, these surveys are able to monitor the entire treatment cascade among KP regardless of whether these populations access HIV services targeting the general population or KP. BBS also reach people accessing services and those who do not, thereby providing a unique opportunity to learn about barriers to service uptake including stigma and discrimination. At the same time high-quality programme data can play a complementary role in identifying missed opportunities that can be addressed in real-time. CONCLUSIONS: Data are more important than ever for guiding the HIV response toward reaching 90-90-90 targets and eliminating HIV, particularly in the face of decreased funding for HIV and specifically for KP. Timely high-quality BBS data can be triangulated with high-quality programme data to provide a comprehensive picture of the epidemic response for KP.

      7. Epidemiology of severe acute respiratory illness and risk factors for influenza infection and clinical severity among adults in Malawi, 2011-2013External
        Ho A, Mallewa J, Peterson I, SanJoaquin M, Garg S, Bar-Zeev N, Menyere M, Alaerts M, Mapurisa G, Chilombe M, Nyirenda M, Lalloo DG, Rothe C, Widdowson MA, McMorrow M, French N, Everett D, Heyderman RS.
        Am J Trop Med Hyg. 2018 Jul 23.

        Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged >/= 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7-16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83-6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57-5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35-4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43-0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36-0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35-2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17-7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.

      8. Invasive Salmonella infections in adults are commonly treated with fluoroquinolones, a critically important antimicrobial class. Historically, quinolone resistance was the result of chromosomal mutations, but plasmid-mediated quinolone resistance (PMQR) has emerged and is increasingly being reported in Enterobacteriaceae worldwide. PMQR may facilitate the spread of quinolone resistance, lead to higher-level quinolone resistance, and make infections harder to treat. To better understand the epidemiology of PMQR in non-typhoidal Salmonella causing human infections in the United States, we looked at trends in quinolone resistance among isolates submitted to the Centers for Disease Control and Prevention. We reviewed demographic, exposure and outcome information for patients with isolates having a PMQR-associated phenotype during 2008-2014 and tested isolates for quinolone resistance mechanisms. We found that PMQR is emerging among non-typhoidal Salmonella causing human infections in the United States and that international travel, reptile and amphibian exposure, and food are likely sources of human infection.

      9. Latent classes of sexual risk behavior and engagement in outreach, intervention and prevention services among women who inject drugs across 20 U.S. citiesExternal
        Mackesy-Amiti ME, Boodram B, Handanagic S, Paz-Bailey G, Prachand NG, Broz D.
        J Acquir Immune Defic Syndr. 2018 Jul 20.

        BACKGROUND: Monitoring the effects of HIV prevention efforts among persons who inject drugs (PWID) is key to informing prevention programs and policy. METHODS: Data for this study came from the 2012 National HIV Behavioral Surveillance interviews with PWID across 20 U.S. cities. The present analyses include those who identified as female, ever had sex with a man, and were at risk for HIV infection (did not report a previous positive HIV test result) (n = 2,624). We conducted latent class analysis (LCA) to identify sexual risk classes, and modeled associations with engagement in HIV prevention services and HIV test results. RESULTS: We identified six classes of sexual risk behavior: 1) low risk, 2) monogamous, 3) casual partner, 4) multiple partner, 5) exchange sex, and 6) exchange plus main partner. The class distribution was similar across the mainland regions. Bisexual orientation and homelessness were significant predictors of higher risk class. HIV prevalence and participation in behavioral interventions did not vary significantly by risk class, while obtaining and using free condoms did. Independent of risk class, women in cities in the South were significantly less likely to use free condoms, and HIV prevalence was higher among non-Hispanic black women and women aged 40-49. CONCLUSIONS: Bisexual orientation and homelessness were predictors of higher risk. Condom distribution programs reached fewer women in cities in the South. Race and age disparities in HIV-positive rates persisted after adjusting for sexual risk class.

      10. Implementation of a Test, Treat, and Prevent HIV program among men who have sex with men and transgender women in Thailand, 2015-2016External
        Ongwandee S, Lertpiriyasuwat C, Khawcharoenporn T, Chetchotisak P, Thiansukhon E, Leerattanapetch N, Leungwaranan B, Manopaiboon C, Phoorisri T, Visavakum P, Jetsawang B, Poolsawat M, Nookhai S, Vasanti-Uppapokakorn M, Karuchit S, Kittinunvorakoon C, Mock P, Prybylski D, Sukkul AC, Roels T, Martin M.
        PLoS One. 2018 ;13(7):e0201171.

        INTRODUCTION: Antiretroviral therapy reduces the risk of serious illness among people living with HIV and can prevent HIV transmission. We implemented a Test, Treat, and Prevent HIV Program among men who have sex with men (MSM) and transgender women at five hospitals in four provinces of Thailand to increase HIV testing, help those who test positive start antiretroviral therapy, and increase access to pre-exposure prophylaxis (PrEP). METHODS: We implemented rapid HIV testing and trained staff on immediate antiretroviral initiation at the five hospitals and offered PrEP at two hospitals. We recruited MSM and transgender women who walked-in to clinics and used a peer-driven intervention to expand recruitment. We used logistic regression to determine factors associated with prevalent HIV infection and the decision to start antiretroviral therapy and PrEP. RESULTS: During 2015 and 2016, 1880 people enrolled. Participants recruited by peers were younger (p<0.0001), less likely to be HIV-infected (p<0.0001), and those infected had higher CD4 counts (p = 0.04) than participants who walked-in to the clinics. Overall, 16% were HIV-positive: 18% of MSM and 9% of transgender women; 86% started antiretroviral therapy and 46% of eligible participants started PrEP. A higher proportion of participants at hospitals with one-stop HIV services started antiretroviral therapy than other hospitals. Participants who started PrEP were more likely to report sex with an HIV-infected partner (p = 0.002), receptive anal intercourse (p = 0.02), and receiving PrEP information from a hospital (p<0.0001). CONCLUSIONS: We implemented a Test, Treat, and Prevent HIV Program offering rapid HIV testing and immediate access to antiretroviral therapy and PrEP. Peer-driven recruitment reached people at high risk of HIV and people early in HIV illness, providing an opportunity to promote HIV prevention services including PrEP and early antiretroviral therapy. Sites with one-stop HIV services had a higher uptake of antiretroviral therapy and PrEP.

      11. Trends in deaths due to syphilis, United States, 1968-2015External
        Peterman TA, Kidd SE.
        Sex Transm Dis. 2018 Jul 24.

        BACKGROUND: Before penicillin, the syphilis case-fatality rate was 10% within 40 years. Late complications, such as cardiovascular syphilis, were still common in the 1950s but now seem quite rare even though some infections likely go undetected. We studied trends in syphilis mortality as an indicator of trends in severe complications of syphilis. METHODS: We assessed underlying cause of death from U.S. death certificates for 1968-2015. We examined death trends by type of syphilis (cardiovascular, neuro, congenital, other). We compared trends in deaths to trends in primary and secondary syphilis from national STD surveillance data. RESULTS: During 1968-2015 there were 6,498 deaths attributed to syphilis; 4,149 males and 2,349 females. Annual syphilis deaths decreased from 586 in 1968 to 94 in 1984, then leveled off to between 24-46 since 1998. Between 1968 and 2015, the decrease in annual cardiovascular syphilis deaths (from 338 to 3) exceeded the decrease in annual neurosyphilis deaths (from 191 to 33). Congenital syphilis deaths (which do not include stillbirths) generally decreased from 28 to 2 per year. An increase in primary and secondary syphilis among women in the late 1980s was accompanied by a 4-fold increase in congenital syphilis deaths (from 9 in 1986 to 35 in 1990) but there was no subsequent increase in syphilis deaths among women. CONCLUSION: Adults now rarely die from syphilis. Increases in infections in the late 1980s did not lead to an increase in adult syphilis deaths. Congenital syphilis deaths still increase when syphilis increases among women.

      12. Pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-uninfected pregnant women: estimated coverage using risk-based versus regional prevalence approachesExternal
        Pintye J, Singa B, Wanyonyi K, Itindi J, Kinuthia J, Langat A, Nganga L, Katana A, Baeten J, McGrath CJ, John-Stewart GC.
        Sex Transm Dis. 2018 Jul 24.

        Antenatal register data from 62 clinics in 5 regions of Kenya were used to estimate women with HIV risk (partner HIV status, syphilis). With individual risk-guided PrEP offer in all regions, 39% of pregnant women nationally would be offered PrEP. PrEP offer to all women in high prevalence regions would result in 26%.

      13. Interactive effects of age and respiratory virus on severe lower respiratory infectionExternal
        Prasad N, Trenholme AA, Huang QS, Thompson MG, Pierse N, Widdowson MA, Wood T, Seeds R, Taylor S, Grant CC, Newbern EC.
        Epidemiol Infect. 2018 Jul 26:1-9.

        We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children 8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

      14. Introductory article on global burden and epidemiology of typhoid feverExternal
        Radhakrishnan A, Als D, Mintz ED, Crump JA, Stanaway J, Breiman RF, Bhutta ZA.
        Am J Trop Med Hyg. 2018 Jul 25.

        This article is the introduction to a 12-paper supplement on global trends in typhoid fever. The Tackling Typhoid (T2) project was initiated in 2015 to synthesize the existing body of literature on typhoidal salmonellae and study national and regional typhoid fever trends. In addition to a global systematic review, eight case studies were undertaken to examine typhoid and paratyphoid fever trends in endemic countries alongside changes in relevant contextual factors. Incidence variations exist both within and between regions with large subnational differences as well, suggesting that public health changes impacting typhoid and paratyphoid fevers in one setting may not have similar impacts in another. This supplement also brings to light the lack of national typhoid fever surveillance systems, inconsistencies in diagnostics, and the lack of typhoid fever associated morbidity and mortality data in many countries, making it difficult to accurately quantify and track burden of disease. To better understand typhoid fever there is a need for more high-quality data from resource-poor settings. The implementation of typhoid surveillance systems alongside the transition to blood-culture confirmation of cases, where possible, would aid in the improvement of data quality in low-income settings. The following supplement includes the results of our global systematic review, eight-country case study articles, a qualitative article informed by semistructured interviews, and a conclusion article on potential ways forward for typhoid control.

      15. Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort studyExternal
        Saha SK, Schrag SJ, El Arifeen S, Mullany LC, Shahidul Islam M, Shang N, Qazi SA, Zaidi AK, Bhutta ZA, Bose A, Panigrahi P, Soofi SB, Connor NE, Mitra DK, Isaac R, Winchell JM, Arvay ML, Islam M, Shafiq Y, Nisar I, Baloch B, Kabir F, Ali M, Diaz MH, Satpathy R, Nanda P, Padhi BK, Parida S, Hotwani A, Hasanuzzaman M, Ahmed S, Belal Hossain M, Ariff S, Ahmed I, Ibne Moin SM, Mahmud A, Waller JL, Rafiqullah I, Quaiyum MA, Begum N, Balaji V, Halen J, Nawshad Uddin Ahmed AS, Weber MW, Hamer DH, Hibberd PL, Sadeq-Ur Rahman Q, Mogan VR, Hossain T, McGee L, Anandan S, Liu A, Panigrahi K, Abraham AM, Baqui AH.
        Lancet. 2018 Jul 14;392(10142):145-159.

        BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95.4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI] 11.2-15.6) per 1000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5.4, 95% CrI 4.8-6.3 episodes per 1000 livebirths), followed by Ureaplasma spp (2.4, 1.6-3.2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation.

      16. The burden of hepatitis C virus infection in Punjab, India: A population-based serosurveyExternal
        Sood A, Suryaprasad A, Trickey A, Kanchi S, Midha V, Foster MA, Bennett E, Kamili S, Alvarez-Bognar F, Shadaker S, Surlikar V, Garg R, Mittal P, Sharma S, May MT, Vickerman P, Averhoff F.
        PLoS One. 2018 ;13(7):e0200461.

        INTRODUCTION: Hepatitis C virus (HCV) infection prevalence is believed to be elevated in Punjab, India; however, state-wide prevalence data are not available. An understanding of HCV prevalence, risk factors and genotype distribution can be used to plan control measures in Punjab. METHODS: A cross-sectional, state-wide, population-based serosurvey using a multi-stage stratified cluster sampling design was conducted October 2013 to April 2014. Children aged >/=5 years and adults were eligible to participate. Demographic and risk behavior data were collected, and serologic specimens were obtained and tested for anti-HCV antibody, HCV Ribonucleic acid (RNA) on anti-HCV positive samples, and HCV genotype. Prevalence estimates and adjusted odds ratios for risk factors were calculated from weighted data and stratified by urban/rural residence. RESULTS: 5,543 individuals participated in the study with an overall weighted anti-HCV prevalence of 3.6% (95% Confidence Interval [CI]: 3.0%-4.2%) and chronic infection (HCV Ribonucleic acid test positive) of 2.6% (95% CI: 2.0%-3.1%). Anti-HCV was associated with being male (adjusted odds ratio 1.52; 95% CI: 1.08-2.14), living in a rural area (adjusted odds ratio 2.53; 95% CI: 1.62-3.95) and was most strongly associated with those aged 40-49 (adjusted odds ratio 40-49 vs. 19-29-year-olds 3.41; 95% CI: 1.90-6.11). Anti-HCV prevalence increased with each blood transfusion received (adjusted odds ratio 1.36; 95% CI: 1.10-1.68) and decreased with increasing education, (adjusted odds ratio 0.37 for graduate-level vs. primary school/no education; 95% CI: 0.16-0.82). Genotype 3 (58%) was most common among infected individuals. DISCUSSION: The study findings, including the overall prevalence of chronic HCV infection, associated risk factors and demographic characteristics, and genotype distribution can guide prevention and control efforts, including treatment provision. In addition to high-risk populations, efforts targeting rural areas and adults aged >/=40 would be the most effective for identifying infected individuals.

      17. We examined Medicaid claims data during 2004-2013. The proportion of sexually-active females aged 15-25 years who had Pap testing or were pregnant significantly decreased during 2004-2013 (67.0% to 43.9%, p<0.05), resulting in a slowed increasing trend in overall chlamydia screening rates. Structural-level interventions for improving chlamydia screening are urgently needed.

      18. OBJECTIVE: The United States Public Health Service released clinical practice guidelines for daily oral preexposure prophylaxis (PrEP) in May 2014. Local health departments (LHDs) are expected to play a critical role in PrEP implementation. We surveyed LHDs to assess awareness of and interest in supporting PrEP implementation, what roles they were taking, or believed they should take, in supporting PrEP, and what resources would be required to do so. METHODS: LHDs were surveyed in 2015 to assess their engagement in PrEP implementation (n = 500). The study employed a cross-sectional survey design with a randomly selected stratified sample. RESULTS: Among responding LHDs (n = 284), 109 (29%, weighted proportion) reported engagement in PrEP implementation. LHDs serving large jurisdictions (population 500,000+) and located in the West were more likely to be engaged in PrEP implementation. Making referrals for PrEP (74%) and conducting education and outreach to community members (51%) were the activities most frequently reported by LHDs engaged in PrEP implementation; 45% anticipated expanding their level of engagement. Among LHDs not engaged in PrEP implementation, 13% expected to become engaged over the next four years, 46% were undecided, and 41% reported it was unlikely. Information about PrEP for health care providers and information about PrEP for health department staff were the most frequently reported resource needs for LHDs engaged and not engaged in PrEP implementation, respectively. CONCLUSIONS: PrEP implementation by LHDs was limited in 2015, three years after Food and Drug Administration approval and one year after the U.S. Public Health Service issued clinical practice guidelines. PrEP is a recently available intervention that is requiring LHDs to adjust existing HIV prevention efforts and service delivery models. Additional resources and implementation research is needed to effectively support PrEP scale-up by LHDs. Efforts must also be undertaken to increase PrEP awareness, knowledge, and implementation capacity among LHDs.

      19. Building the evidence base to optimize the impact of key population programming across the HIV cascadeExternal
        Wolf RC, Bingham T, Millett G, Wilcher R.
        J Int AIDS Soc. 2018 Jul;21 Suppl 5:e25146.

        [No abstract]

      20. Responses to hypothetical health scenarios overestimate healthcare utilization for common infectious syndromes: a cross-sectional survey, South Africa, 2012External
        Wong KK, Cohen AL, Martinson NA, Norris SA, Tempia S, von Mollendorf C, Walaza S, Madhi SA, McMorrow ML, Cohen C.
        BMC Infect Dis. 2018 Jul 25;18(1):344.

        BACKGROUND: Asking people how they would seek healthcare in a hypothetical situation can be an efficient way to estimate healthcare utilization, but it is unclear how intended healthcare use corresponds to actual healthcare use. METHODS: We performed a cross-sectional survey between August and September 2012 among households in Soweto and Klerksdorp, South Africa, to compare healthcare seeking behaviors intended for hypothetical common infectious syndromes (pneumonia, influenza-like illness [ILI], chronic respiratory illness, meningitis in persons of any age, and diarrhea in a child < 5 years old) with the self-reported healthcare use among patients with those syndromes. RESULTS: For most syndromes, the proportion of respondents who intended to seek healthcare at any facility or provider (99-100%) in a hypothetical scenario exceeded the proportion that did seek care (78-100%). More people intended to seek care for a child < 5 years old with diarrhea (186/188 [99%]) than actually did seek care (32/41 [78%], P < 0.01). Although most people faced with hypothetical scenarios intended to seek care with licensed medical providers such as hospitals and clinics (97-100%), patients who were ill reported lower use of licensed medical providers (55-95%). CONCLUSIONS: People overestimated their intended healthcare utilization, especially with licensed medical providers, compared with reported healthcare utilization among patients with these illnesses. Studies that measure intended healthcare utilization should consider that actual use of healthcare facilities may be lower than intended use.

      21. TB anywhere is TB everywhereExternal
        Wortham JM.
        Isr J Health Policy Res. 2018 Jul 20;7(1):40.

        To control and prevent outbreaks, public health programs in all countries, regardless of tuberculosis (TB) incidence, must maintain the capacity to perform core control and prevention activities. These include diagnosing and treating cases, contact investigations, and infection prevention and control activities. Congregate settings and healthcare facilities demand special attention, because of the potential for outbreaks associated with infectious cases in these settings. Since almost one-fourth of the world population is thought to be infected with Mycobacterium tuberculosis, enhanced efforts to diagnose and treat latent TB infection are needed to prevent future cases and accelerate progress towards TB elimination.

    • Disaster Control and Emergency Services
      1. OBJECTIVE: Emergency management and operations (EMO) personnel require up-to-date information to make informed decisions during natural and man-made disasters. However, information gaps present challenges for accessing human health risk assessment and risk management strategies for dermal exposure. This article describes the development of a decision support system, the Dermal Exposure Risk Management and Logic (DERMaL) eToolkit. DESIGN: The DERMaL eToolkit provides information on key resources used in emergency incidents. Resources were classified according to response phase, resource categories, and information category and evaluated on reliability, accessibility, and preference by subject matter experts in emergency management fields. These rankings were used to generate a value of information score, unique for each resource, which aids in developing reference lists for users during each incident phase. RESULTS: This tool will identify and prioritize information resources on dermal risks, and can readily find the most relevant information to suit EMO needs. CONCLUSION: The DERMaL eToolkit can be used as an aid in finding information resources targeted to scenario-driven needs by providing well-vetted and prioritized resources related to dermal hazards, exposure, and risk assessments for EMO.

      2. Background: The prevalence of common mental disorders increases in humanitarian emergencies while access to services to address them decreases. Problem Management Plus (PM+) is a brief five-session trans-diagnostic psychological WHO intervention employing empirically supported strategies that can be delivered by non-specialist lay-providers under specialist supervision to adults impaired by distress. Two recent randomized controlled trials in Pakistan and Kenya demonstrated the efficacy of individually delivered PM+. To make PM+ more scalable and acceptable in different contexts, it is important to develop a group version as well, with 6-8 participants in session. A study is needed to demonstrate the feasibility and acceptability of both the intervention in a new cultural context and the procedures to evaluate Group PM+ in a cluster randomized controlled trial. Methods: This protocol describes a feasibility trial to Group PM+ in Sindhuli, Nepal. This study will evaluate procedures for a cluster randomized controlled trial (c-RCT) with Village Development Committees (VDCs), which are the second smallest unit of government administration, as the unit of randomization. Adults with high levels of psychological distress and functional impairment will receive either Group PM+ (n = 60) or enhanced usual care (EUC; n = 60). Psychological distress, functional impairment, depression symptoms, posttraumatic stress disorder (PTSD) symptoms, and perceived problems will be measured during screening, pre-treatment baseline, and 7-10 days after the intervention. Qualitative data will be collected from beneficiaries, their families, local stakeholders, and staff to support quantitative data and to identify themes reporting that those involved and/or effected by Group PM+ perceived it as being acceptable, feasible, and useful. The primary objective of this trial is to evaluate the acceptability and feasibility of the intervention; to identify issues around implementation of local adaptation methods, training, supervision, and outcomes measures; and to assure that procedures are adequate for a subsequent effectiveness c-RCT. Discussion: Outcomes from this trial will contribute to optimizing feasibility and acceptability through cultural adaptation and contextualization of the intervention as well as refining the design for a c-RCT, which will evaluate the effectiveness of Group PM+ in Nepal. Trial registration: ClinicalTrials.gov identifier: NCT03359486.

      3. Challenges of service coordination for evacuees of Hurricane Maria through the National Disaster Medical SystemExternal
        Vora NM, Grober A, Goodwin BP, Davis MS, McGee C, Luckhaupt SE, Cockrill JA, Ready S, Bluemle LN, Brewer L, Brown A, Brown C, Clement J, Downie DL, Garner MR, Lerner R, Mahool M, Mojica SA, Nolen LD, Pedersen MR, Chappell-Reed MJ, Richards E, Smith J, Weekes KC, Dickinson J, Weir C, Bowman TI, Eckes J.
        J Emerg Manag. 2018 May/Jun;16(3):203-206.

        OBJECTIVE: To describe the challenges of service coordination through the National Disaster Medical System (NDMS) for Hurricane Maria evacuees, particularly those on dialysis. DESIGN: Public health report. SETTING: Georgia. REPORT: On November 25, 2017, there were 208 patients evacuated to Georgia in response to Hurricane Maria receiving NDMS support. Most were evacuated from the US Virgin Islands (97 percent) and the remaining from Puerto Rico (3 percent); 73 percent of these patients were on dialysis, all from the US Virgin Islands. From the beginning of the evacuation response through November 25, 2017, there were 282 patients evacuated to Georgia via NDMS, with a median length of coverage through NDMS for those on and not on dialysis of 60 and 16 days, respectively. CONCLUSION: The limited capacity and capability of dialysis centers currently in the US Virgin Islands are delaying the return to home of many Hurricane Maria evacuees who are on dialysis.

    • Epidemiology and Surveillance
      1. Overcoming challenges in school-wide survey administrationExternal
        Rasberry CN, Rose I, Kroupa E, Hebert A, Geller A, Morris E, Lesesne CA.
        Health Promot Pract. 2018 Jan;19(1):110-118.

        School-based surveys provide a useful method for gathering data from youth. Existing literature offers many examples of data collection through school-based surveys, and a small subset of literature describes methodological approaches or general recommendations for health promotion professionals seeking to conduct school-based data collection. Much less is available on real-life logistical challenges (e.g., minimizing disruption in the school day) and corresponding solutions. In this article, we fill that literature gap by offering practical considerations for the administration of school-based surveys. The protocol and practical considerations outlined in the article are based on a survey conducted with 11,681 students from seven large, urban public high schools in the southeast United States. We outline our protocol for implementing a school-based survey that was conducted with all students school-wide, and we describe six types of key challenges faced in conducting the survey: consent procedures, scheduling, locating students within the schools, teacher failure to administer the survey, improper administration of the survey, and minimizing disruption. For each challenge, we offer our key lessons learned and associated recommendations for successfully implementing school-based surveys, and we provide relevant tools for practitioners planning to conduct their own surveys in schools.

    • Food Safety
      1. Surveillance for foodborne disease outbreaks – United States, 2009-2015External
        Dewey-Mattia D, Manikonda K, Hall AJ, Wise ME, Crowe SJ.
        MMWR Surveill Summ. 2018 Jul 27;67(10):1-11.

        PROBLEM/CONDITION: Known foodborne disease agents are estimated to cause approximately 9.4 million illnesses each year in the United States. Although only a small subset of illnesses are associated with recognized outbreaks, data from outbreak investigations provide insight into the foods and pathogens that cause illnesses and the settings and conditions in which they occur. REPORTING PERIOD: 2009-2015 DESCRIPTION OF SYSTEM: The Foodborne Disease Outbreak Surveillance System (FDOSS) collects data on foodborne disease outbreaks, which are defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. Since the early 1960s, foodborne outbreaks have been reported voluntarily to CDC by state, local, and territorial health departments using a standard form. Beginning in 2009, FDOSS reporting was made through the National Outbreak Reporting System, a web-based platform launched that year. RESULTS: During 2009-2015, FDOSS received reports of 5,760 outbreaks that resulted in 100,939 illnesses, 5,699 hospitalizations, and 145 deaths. All 50 states, the District of Columbia, Puerto Rico, and CDC reported outbreaks. Among 2,953 outbreaks with a single confirmed etiology, norovirus was the most common cause of outbreaks (1,130 outbreaks [38%]) and outbreak-associated illnesses (27,623 illnesses [41%]), followed by Salmonella with 896 outbreaks (30%) and 23,662 illnesses (35%). Outbreaks caused by Listeria, Salmonella, and Shiga toxin-producing Escherichia coli (STEC) were responsible for 82% of all hospitalizations and 82% of deaths reported. Among 1,281 outbreaks in which the food reported could be classified into a single food category, fish were the most commonly implicated category (222 outbreaks [17%]), followed by dairy (136 [11%]) and chicken (123 [10%]). The food categories responsible for the most outbreak-associated illnesses were chicken (3,114 illnesses [12%]), pork (2,670 [10%]), and seeded vegetables (2,572 [10%]). Multistate outbreaks comprised only 3% of all outbreaks reported but accounted for 11% of illnesses, 34% of hospitalizations, and 54% of deaths. INTERPRETATION: Foodborne disease outbreaks provide information about the pathogens and foods responsible for illness. Norovirus remains the leading cause of foodborne disease outbreaks, highlighting the continued need for food safety improvements targeting worker health and hygiene in food service settings. Outbreaks caused by Listeria, Salmonella, and STEC are important targets for public health intervention efforts, and improving the safety of chicken, pork, and seeded vegetables should be a priority. PUBLIC HEALTH ACTION: The causes of foodborne illness should continue to be tracked and analyzed to inform disease prevention policies and initiatives. Strengthening the capacity of state and local health departments to investigate and report outbreaks will assist with these efforts through identification of the foods, etiologies, and settings linked to these outbreaks.

    • Global Health
      1. Analysis of joint external evaluations in the WHO Eastern Mediterranean RegionExternal
        Samhouri D, Ijaz K, Rashidian A, Chungong S, Flahault A, Babich SM, Mahjour J.
        East Mediterr Health J. 2018 Jul 17;24(5):477-487.

        Background: Joint External Evaluation (JEE) was developed as a new model of peer-to-peer expert external evaluations of IHR capacities using standardized approaches. Aims: This study aimed to consolidate findings of these assessments in the Eastern Mediterranean Region and assess their significance. Methods: Analysis of the data were conducted for 14 countries completing JEE in the Region. Mean JEE score for each of the 19 technical areas and for the overall technical areas were calculated. Bivariate and multivariate analyses were done to assess correlations with key health, socio-economic and health system indicators. Results: Mean JEE scores varied substantially across technical areas. The cumulative mean JEE (mean of indicator scores related to that technical area) was 3 (range: 1-4). Antimicrobial resistance, Biosecurity and Biosafety indicators obtained the lowest scores. Medical countermeasures, personnel deployment and linking public health with security capacities had the highest cumulative mean score of 4 (range: 2-5). JEE scores correlated with most of the key indicators examined. Countries with better health financing system, health service coverage and health status generally had higher JEE scores. Adolescent fertility rate, neonatal mortality ratio and net primary school enrollment ratio were primary factors within a country’s overall JEE score. Conclusions: An integrated multisectoral approach, including well-planned cross-cutting health financing system and coverage, are critical to address the key gaps identified by JEEs in order to ensure regional and global health security.

    • Health Behavior and Risk
      1. PURPOSE: The objective of this study was to examine the relationship between school involvement and connectedness with measures of sexual risk, substance use, and experience of violence among students who had sexual contact with the same sex or with both sexes. METHODS: A sample of middle school and high school students who participated in a study conducted in a large urban school district were selected based on their reported experience of having initiated sexual activity with same-sex partners. In classroom-based surveys, we assessed self-reported involvement in school-based activities and feelings of school connectedness, as well as self-reported sexual risk, substance use, and experience of violence. RESULTS: Significant protective associations were found between school involvement and lifetime alcohol and marijuana use, and between school connectedness and ever having been in a fight, feeling safe at school, and drug use other than marijuana (all p < .05). CONCLUSIONS: Findings suggest that efforts to increase school involvement and connectedness provide a starting point for addressing significant health and safety concerns among students with same-sex sexual activity.

    • Health Economics
      1. Cost and cost-effectiveness analysis of pre-exposure prophylaxis among men who have sex with men in two hospitals in ThailandExternal
        Suraratdecha C, Stuart RM, Manopaiboon C, Green D, Lertpiriyasuwat C, Wilson DP, Pavaputanon P, Visavakum P, Monkongdee P, Khawcharoenporn T, Tharee P, Kittinunvorakoon C, Martin M.
        J Int AIDS Soc. 2018 Jul;21 Suppl 5:e25129.

        INTRODUCTION: In 2014, the Government of Thailand recommended pre-exposure prophylaxis (PrEP) as an additional HIV prevention programme within Thailand’s National Guidelines on HIV/AIDS Treatment Prevention. However, to date implementation and uptake of PrEP programmes have been limited, and evidence on the costs and the epidemiological and economic impact is not available. METHODS: We estimated the costs associated with PrEP provision among men having sex with men (MSM) participating in a facility-based, prospective observational cohort study: the Test, Treat and Prevent HIV Programme in Thailand. We created a suite of scenarios to estimate the cost-effectiveness of PrEP and sensitivity of the results to the model input parameters, including PrEP programme effectiveness, PrEP uptake among high-risk and low-risk MSM, baseline and future antiretroviral therapy (ART) coverage, condom use, unit cost of delivering PrEP, and the discount rate. RESULTS: Drug costs accounted for 82.5% of the total cost of providing PrEP, followed by lab testing (8.2%) and personnel costs (7.8%). The estimated costs of providing the PrEP package in accordance with the national recommendation ranges from US$223 to US$311 per person per year. Based on our modelling results, we estimate that PrEP would be cost-effective when provided to either high-risk or all MSM. However, we found that the programme would be approximately 32% more cost-effective if offered to high-risk MSM than it would be if offered to all MSM, with an incremental cost-effectiveness ratio of US$4,836 per disability-adjusted life years (DALY) averted and US$7,089 per DALY averted respectively. Cost-effectiveness acceptability curves demonstrate that 80% of scenarios would be cost-effective when PrEP is provided solely to higher-risk MSM. CONCLUSION: We provide the first estimates on cost and cost-effectiveness of PrEP in the Asia-Pacific region, and offer insights on how to deliver PrEP in combination with ART. While the high drug cost poses a budgeting challenge, incorporating PrEP delivery into an existing ART programme could be a cost-effective strategy to prevent HIV infections among MSM in Thailand.

    • Healthcare Associated Infections
      1. We analyzed clinical microbiology laboratory practices for detection of multidrug-resistant Enterobacteriaceae in US short-stay acute-care hospitals using data from the National Healthcare Safety Network (NHSN) Annual Facility Survey. Half of hospitals reported testing for carbapenemases, and 1% performed routine polymyxin susceptibility testing using reference broth microdilution.

    • Immune System Disorders
      1. PURPOSE: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). We assessed the prevalence of granulomas in patients with PIDD. METHODS: We used the Truven Health MarketScan(R) 2005-2015 Commercial Claims and Encounters and 2006-2015 Medicaid databases and the US Immunodeficiency Network (USIDNET) PIDD registry (a program of the Immune Deficiency Foundation). Our study population consisted of persons age < 65 years with PIDD, defined as persons with >/= 2 claims with a diagnostic code for PIDD in MarketScan databases, or patients enrolled in USIDNET. Granulomas were identified using diagnostic codes in MarketScan or provider report in USIDNET. We calculated annual prevalence of PIDD and of granulomas among PIDD patients. RESULTS: We identified 247,474 and 40,395 persons with PIDD among commercially and Medicaid-insured persons, respectively. PIDD prevalence was 6.0/10,000 in 2005 and 11.7/10,000 in 2015 among commercially insured persons and 5.5/10,000 in 2006 and 9.6/10,000 in 2015 among Medicaid-insured persons. The prevalence of granulomas among PIDD patients was 1.2 and 1.5% among commercially and Medicaid-insured persons, respectively. In USIDNET, prevalence of granulomas was 4.4% (177/4021). The proportion with granulomas was similar across age groups in MarketScan, but varied from 2 to 9% in USIDNET. The reported prevalence of granulomas differed depending on PIDD condition: 1-2% in the MarketScan data and 0-13% in USIDNET. CONCLUSION: Granuloma prevalence in PIDD patients was 1-4%. Our study provides an estimate of the proportion of PIDD patients and suggests that granulomas are an uncommon occurrence among patients with PIDD.

    • Immunity and Immunization
      1. Tdap vaccination among healthcare personnel – 21 states, 2013External
        O’Halloran AC, Lu PJ, Meyer SA, Williams WW, Schumacher PK, Sussell AL, Birdsey JE, Boal WL, Sweeney MH, Luckhaupt SE, Black CL, Santibanez TA.
        Am J Prev Med. 2018 Jan;54(1):119-123.

        INTRODUCTION: Outbreaks of pertussis can occur in healthcare settings. Vaccinating healthcare personnel may be helpful in protecting healthcare personnel from pertussis and potentially limiting spread to others in healthcare settings. METHODS: Data from 21 states using the 2013 Behavioral Risk Factor Surveillance System industry/occupation module were analyzed in 2016. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination status was self-reported by healthcare personnel along with their occupation, healthcare setting/industry, demographics, and access to care factors. To compare groups, t-tests were used. The median state response rate was 44.0%. RESULTS: Among all healthcare personnel, 47.2% were vaccinated for Tdap. Physicians had higher Tdap coverage (66.8%) compared with all other healthcare personnel except nurse practitioners and registered nurses (59.5%), whose coverage did not statistically differ from that of physicians. Tdap vaccination coverage was higher among workers in hospitals (53.3%) than in long-term care facilities (33.3%) and other clinical settings, such as dentist, chiropractor, and optometrist offices (39.3%). Healthcare personnel who were younger, who had higher education, higher annual household income, a personal healthcare provider, and health insurance had higher Tdap vaccination coverage compared with reference groups. Tdap vaccination coverage among healthcare personnel in 21 states ranged from 30.6% in Mississippi to 65.9% in Washington. CONCLUSIONS: Improvement in Tdap vaccination among healthcare personnel is needed to potentially reduce opportunities for spread of pertussis in healthcare settings. On-site workplace vaccination, offering vaccines free of charge, and promoting vaccination may increase vaccination among healthcare personnel.

      2. Safety monitoring of ROTAVAC vaccine and etiological investigation of intussusception in India: study protocolExternal
        Reddy S, Nair NP, Giri S, Mohan VR, Tate JE, Parashar UD, Gupte MD, Arora R, Kang G.
        BMC Public Health. 2018 Jul 20;18(1):898.

        BACKGROUND: ROTAVAC, an indigenous rotavirus vaccine, was introduced in the universal immunization program of India in four states in 2016 and expanded to five more states in 2017. The clinical trial on efficacy of ROTAVAC did not detect an increased risk of intussusception, but the trial was not large enough to detect a small risk. This protocol paper describes the establishment and implementation of a surveillance system to monitor the safety of rotavirus vaccine and investigate the potential infectious etiologies of intussusception. METHODS: This is a multi-centric hospital-based active surveillance being conducted at 28 hospitals in nine states of India. Data gathered from surveillance will be used to assess the risk of intussusception after ROTAVAC administration and to determine the infectious etiologies of intussusception. For safety assessment of ROTAVAC vaccine, children aged less than two years with intussusception admitted at the sentinel hospitals are enrolled into surveillance, a case report form completed, and a copy of the vaccination card obtained. The risk of intussusception following rotavirus vaccination will be assessed using a self-controlled case-series design. The investigation for potential infectious etiologies of intussusception is through a matched case-control design. Children enrolled for the safety assessment serve as cases and for each case, an age, gender and location matched control is enrolled within 30 days of case enrollment. Stool specimens are obtained from cases and controls. All forms and specimens are sent to the referral laboratory for data entry, analysis, multiplexed molecular testing, and storage. DISCUSSION: Anticipated public health benefits of this surveillance include the generation of information useful to national government on safety of vaccine and to make future decisions on vaccine use through risk-benefit analysis. Investigating infectious agents may help to determine the potential infectious etiologies of intussusception.

    • Injury and Violence
      1. Cycle of violence among young Kenyan women: The link between childhood violence and adult physical intimate partner violence in a population-based surveyExternal
        Chiang L, Howard A, Gleckel J, Ogoti C, Karlsson J, Hynes M, Mwangi M.
        Child Abuse Negl. 2018 Jul 21;84:45-52.

        The aim of the current analysis is to elucidate the link between childhood experiences of violence and physical intimate partner violence in young adulthood in a national survey of young Kenyan women. In 2010, we conducted the Violence against Children Survey in Kenya, collecting retrospective reports from 13 to 24year old males and females (N=2928). The analysis presented here focused on females aged 18-24 who ever had an intimate partner (n=566). Young Kenyan women had statistically higher odds of experiencing physical intimate partner violence (IPV) in young adulthood if they had experienced any childhood violence (including sexual, emotional, or physical) [adjusted odds ratio (AOR)=3.1 CI: 1.2-7.9, p=0.02)], any childhood sexual violence (AOR=2.5, CI 1.3-4.9, p=0.006), or unwanted completed sex (including pressured or forced sex prior to age 18) (AOR=4.3, CI: 2.3-8.3, p<0.0001). Exposure to two (AOR=3.9, CI: 1.2-12.2, p=0.02) or three (AOR=5.0, CI: 1.4-18.1, p=0.01) types of violence in childhood was also associated with a significantly higher odds of experiencing adult physical IPV. Childhood violence is associated with increased odds of adult physical IPV among young women; efforts to prevent violence against children and provide appropriate care and support to adult survivors are critical to interrupt this cycle of violence.

      2. A sample of 109 college students completed a survey to assess how frequently they send or read text messages while driving. In a novel discounting task with a hypothetical scenario in which participants receive a text message while driving, they rated the likelihood of replying to a text message immediately versus waiting to reply until arriving at a destination. The scenario presented several delays to a destination and probabilities of a motor vehicle crash. The likelihood of waiting to reply decreased as a function of both the delay until the destination and the probability of a motor vehicle crash. Self-reported higher frequencies of texting while driving were associated with greater rates of both delay and probability discounting. The degree of delay discounting was altered as a function of the probability of a motor vehicle crash and vice versa. These results suggest that both delay and probability discounting are important underlying mechanisms of drivers’ decision to text while driving.

      3. 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. 2018 Jan;54(1):129-132.

        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. Development of anti-factor VIII (FVIII) inhibitory antibodies (inhibitors) is the most significant treatment complication of hemophilia A. Characteristics of the interaction between major histocompatibility complex (MHC) class II and FVIII peptides may influence FVIII antigen presentation to T cells and subsequent inhibitor development. We analyzed predicted HLA-DRB1, a subset of MHC class II, and FVIII peptide binding and its association with inhibitor development among subjects with nonsevere hemophilia A, including 20 cases (inhibitor titer >/= 1.0 BU/mL on 2 occasions or on 1 occasion with subsequent immune tolerance induction) and 37 controls (who had received FVIII infusions and did not develop inhibitor). Using the MHC-II Binding Predictions Tool (https://www.iedb.org), the binding affinity and core binding were determined for endogenous FVIII (eFVIII) and treatment FVIII (tFVIII). A tFVIII peptide was considered novel if it was predicted to bind and present a surface to the T-cell receptor that was unique from that presented by eFVIII. Having >10 novel HLA-DRB1 allele-tFVIII peptide combinations was associated with inhibitor development (adjusted odds ratio, 4.1; 95% confidence interval, 1.1-15.0). Cases and controls with p.Arg612Cys and p.Arg2169His demonstrated a high level of novel HLA-DRB1-tFVIII peptide combinations. Assessing the likelihood that tFVIII is presented to T cells in a novel fashion may be useful for understanding and ultimately reducing the risk for inhibitor development among patients with nonsevere hemophilia, particularly those with F8 mutations other than p.Arg612Cys and p.Arg2169His.

      2. Corticosterone potentiates DFP-induced neuroinflammation and affects high-order diffusion imaging in a rat model of Gulf War IllnessExternal
        Koo BB, Michalovicz LT, Calderazzo S, Kelly KA, Sullivan K, Killiany RJ, O’Callaghan JP.
        Brain Behav Immun. 2018 Jan;67:42-46.

        Veterans of the 1991 Gulf War were potentially exposed to a variety of toxic chemicals, including sarin nerve agent and pesticides, which have been suspected to be involved in the development of Gulf War Illness (GWI). Several of these exposures cause a neuroinflammatory response in mice, which may serve as a basis for the sickness behavior-like symptoms seen in veterans with GWI. Furthermore, conditions mimicking the physiological stress experienced during the war can exacerbate this effect. While neuroinflammation has been observed post-exposure using animal models, it remains a challenge to evaluate neuroinflammation and its associated cellular and molecular changes in vivo in veterans with GWI. Here, we evaluated neuroimmune-associated alterations in intact brains, applying our existing GWI mouse model to rats, by exposing them to 4days of corticosterone (CORT; 200mg/L in the drinking water), to mimic high physiological stress, followed by a single injection of the sarin nerve agent surrogate, diisopropyl fluorophosphate (DFP; 1.5mg/kg, i.p.). Then, we evaluated the neuroinflammatory responses using qPCR of cytokine mRNA and also examined brain structure with a novel high-order diffusion MRI. We found a CORT-enhancement of DFP-induced neuroinflammation, extending our mouse GWI model to the rat. High order diffusion MRI revealed different patterns among the different treatment groups. Particularly, while the CORT+DFP rats had more restricted spatial patterns in the hippocampus and the hypothalamus, the highest and most wide-spread differences were shown in DFP-treated rats compared to the controls in the thalamus, the amygdala, the piriform cortex and the ventral tegmental area. The association of these diffusion changes with neuroinflammatory cytokine expression indicates the potential for GW-relevant exposures to result in connectivity changes in the brain. By transferring this high order diffusion MRI into in vivo imaging in veterans with GWI, we can achieve further insights on the trajectories of the neuroimmune response over time and its impacts on behavior and potential neurological damage.

      3. Comparative proteomics of two Mycoplasma hyopneumoniae strains and Mycoplasma flocculare identified potential porcine enzootic pneumonia determinantsExternal
        Paes JA, Machado L, Dos Anjos Leal FM, de Moraes SN, Moura H, Barr JR, Ferreira HB.
        Virulence. 2018 Jul 20.

        Mycoplasma hyopneumoniae and Mycoplasma flocculare are genetically similar bacteria, which coinhabit the porcine respiratory tract. These mycoplasmas share most of the known virulence factors, but, while M. hyopneumoniae causes porcine enzootic pneumonia (PEP), M. flocculare is a commensal species. To identify potential PEP determinants and provide novel insights on mycoplasma-host interactions, the whole cell proteomes of two M. hyopneumoniae strains, one pathogenic (7448) and other non-pathogenic (J), and M. flocculare were compared. A cell fractioning approach combined with LC-MS/MS proteomics was used to analyze cytoplasmic and surface-enriched protein fractions. Average detection of ~50% of the predicted proteomes of M. hyopneumoniae 7448 and J, and M. flocculare was achieved. Many of the identified proteins were differentially represented in M. hyopneumoniae 7448 in comparison to M. hyopneumoniae J and M. flocculare, including potential PEP determinants, such as adhesins, proteases, and redox-balancing proteins, among others. The LC-MS/MS data also provided experimental validation for several genes previously regarded as hypothetical for all analyzed mycoplasmas, including some coding for proteins bearing virulence-related functional domains. The comprehensive proteome profiling of two M. hyopneumoniae strains and M. flocculare provided tens of novel candidates to PEP determinants or virulence factors, beyond those classically described.

      4. Methylprednisolone acetate induces, and Delta7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG miceExternal
        Patton JB, Bonne-Annee S, Deckman J, Hess JA, Torigian A, Nolan TJ, Wang Z, Kliewer SA, Durham AC, Lee JJ, Eberhard ML, Mangelsdorf DJ, Lok JB, Abraham D.
        Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):204-209.

        Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Delta7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.

      5. The surface tension of synthetic blood used for ASTM F1670 penetration testsExternal
        Portnoff L, Jaques PA, Furlong JL.
        J Test Eval. 2019 Mar;47(2).

        The ASTM F1670 test method, Standard Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Synthetic Blood, was based on research involving transmission of bloodborne pathogens (Hepatitis B, Hepatitis C, and HIV) in the 1980s. The test method details the measurement of synthetic blood penetration through garments. A key parameter affecting penetration is synthetic blood surface tension, which is measured via du Nouy ring tensiometer. However, little is known about the sources of variation impacting surface tension measurements. In this study, the synthetic blood used for ASTM F1670 was evaluated from within the ASTM F903 test apparatus, Standard Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Liquids, and with two mixing treatments. Measurements were compared against two outside laboratories and with two alternate tensiometric methods (pendant drop and capillary rise). It was found that using the methods specified in the ASTM F1670 test method, surface tension of the synthetic blood was not 40-44 dynes/cm as was expected. The surface tension was initially above 50 dynes/cm and declined to below 40 dynes/cm after 60 minutes. The surface tension within the penetration cell was relatively constant over time, showing that the surface tension measurements outside the penetration cell are not indicative of the surface tension within the apparatus during the test. Shaking the synthetic blood, a mixing procedure detailed in the ASTM F1670 test method, increased the surface tension. The increase was greatest in a container having more airspace. Du Nuoy ring measurements by the National Institute for Occupational Safety and Health compared to external labs were within 15 %. Testing with alternate methods showed that the “open to atmosphere” methods (ring and drop) began lower and declined rapidly when compared to the “closed to atmosphere” method (capillary). Results of this research will help amend the ASTM F1670 standard to better characterize the measurement and handling of synthetic blood used in the ASTM F1670 test and to provide a framework for consideration of test fluid used in future ASTM standards.

      6. IntroductionPersonal protective equipment (PPE) recommended for use in West Africa during the Ebola outbreak increased risk for heat illness, and countermeasures addressing this issue would be valuable.Hypothesis/ProblemThe purpose of this study was to examine the physiological impact and heat perception of four different personal cooling devices (PCDs) under impermeable PPE during low-intensity exercise in a hot and humid environment using thermal manikin modeling and human testing. METHODS: Six healthy male subjects walked on a treadmill in a hot/humid environment (32 degrees C/92% relative humidity [RH]) at three metabolic equivalents (METs) for 60 minutes wearing PPE recommended for use in West Africa and one of four different personal cooling devices (PCDs; PCD1, PCD2, PCD3, and PCD4) or no PCD for control (CON). The same ensembles were tested with thermal manikin modeling software in the same conditions to compare the results. RESULTS: All PCDs seemed to reduce physiological heat stress characteristics when worn under PPE compared to CON. Both the manikin and human testing provided similar results in core temperature (Tc) and heat sensation (HS) in both magnitude and relationship. While the manikin and human data provided similar skin temperature (Tsk) characterization, Tsk estimation by the manikin seemed to be slightly over-estimated. Weight loss, as estimated by the manikin, was under-estimated compared to the human measurement. CONCLUSION: Personal cooling device use in conjunction with impermeable PPE may be advantageous in mitigating physiological and perceptual burdens of heat stress. Evaluation of PCDs worn under PPE can be done effectively via human or manikin testing; however, Tsk may be over-estimated and weight loss may be under-estimated. Thermal manikin testing of PCDs may provide fast and accurate information to persons recommending or using PCDs with PPE. QuinnT, KimJH, SeoY, CocaA. Comparison of thermal manikin modeling and human subjects’ response during use of cooling devices under personal protective ensembles in the heat. Prehosp Disaster Med. 2018;33(3):279-287.

      7. Molecular detection of Cyclospora cayetanensis in human stool specimens using UNEX-based DNA extraction and real-time PCRExternal
        Qvarnstrom Y, Benedict T, Marcet PL, Wiegand RE, Herwaldt BL, da Silva AJ.
        Parasitology. 2018 Jun;145(7):865-870.

        Cyclospora cayetanensis is a coccidian parasite associated with diarrheal illness. In the USA, foodborne outbreaks of cyclosporiasis have been documented almost every year since the mid-1990s. The typical approach used to identify this parasite in human stools is an examination of acid-fast-stained smears under bright-field microscopy. UV fluorescence microscopy of wet mounts is more sensitive and specific than acid-fast staining but requires a fluorescence microscope with a special filter not commonly available in diagnostic laboratories. In this study, we evaluated a new DNA extraction method based on the Universal Nucleic Acid Extraction (UNEX) buffer and compared the performances of four published real-time polymerase chain reaction (PCR) assays for the specific detection of C. cayetanensis in stool. The UNEX-based method had an improved capability to recover DNA from oocysts compared with the FastDNA stool extraction method. The best-performing real-time PCR assay was a C. cayetanensis-specific TaqMan PCR that targets the 18S ribosomal RNA gene. This new testing algorithm should be useful for detection of C. cayetanensis in human stool samples.

      8. Development of colorimetric sensor array for diagnosis of tuberculosis through detection of urinary volatile organic compoundsExternal
        Sandlund J, Lim S, Queralto N, Huang R, Yun J, Taba B, Song R, Odero R, Ouma G, Sitati R, Murithi W, Cain KP, Banaei N.
        Diagn Microbiol Infect Dis. 2018 Jun 22.

        BACKGROUND: Top priorities for tuberculosis control and elimination include a simple, low-cost screening test using sputum and a non-sputum-based test in patients that do not produce sputum. The aim of this study was to evaluate the performance of a colorimetric sensor array (CSA) test, for analysis of volatile organic compounds in urine, in the diagnosis of pulmonary TB. MATERIAL AND METHODS: Urine samples were collected from individuals suspected of having pulmonary TB in Western Kenya. Reference methods included MGIT culture and/or Xpert MTB/RIF nucleic acid amplification test on sputa. Fresh urine samples were tested with the CSA, with acid and base and without an additive. The CSA were digitally imaged, and the resulting colorimetric response patterns were used for chemometric analysis. Sensitivity, specificity, and negative (NPV) and positive predictive (PPV) values were determined for HIV-positive and HIV-negative patients. RESULTS: In HIV-negative patients, the highest accuracy was obtained in urine samples pre-treated with a base, yielding a sensitivity, specificity, PPV, and NPV of 78.3% (65/83), 69.2% (54/78), 73.0% (n/89) and 75.0% (n/72). The highest sensitivity of 79.5% was achieved using sensor data from all three test conditions at a specificity of 65.4%. In HIV-positive subjects, the sensor performance was substantially lower with sensitivity, specificity, PPV, and NPV ranging from 48.3% to 62.3%, 54.1% to 74.0%, 55.9% to 64.2%, and 60.6% to 64.9%, respectively. CONCLUSION: The CSA fingerprint of urine headspace volatiles showed moderate accuracy in diagnosing TB in HIV-negative patients, but the sensor performance dropped substantially in HIV-coinfected patients. Further development of TB-responsive CSA indicators may improve the accuracy of CSA urine assay.

      9. Human immune cell engraftment does not alter development of severe acute Rift Valley fever in miceExternal
        Spengler JR, McElroy AK, Harmon JR, Coleman-McCray JD, Welch SR, Keck JG, Nichol ST, Spiropoulou CF.
        PLoS One. 2018 ;13(7):e0201104.

        Rift Valley fever (RVF) in humans is usually mild, but, in a subset of cases, can progress to severe hepatic and neurological disease. Rodent models of RVF generally develop acute severe clinical disease. Here, we inoculated humanized NSG-SGM3 mice with Rift Valley fever virus (RVFV) to investigate whether the presence of human immune cells in mice would alter the progression of RVFV infection to more closely model human disease. Despite increased human cytokine expression, including responses mirroring those seen in human disease, and decreased hepatic viral RNA levels at terminal euthanasia, both high- and low-dose RVFV inoculation resulted in lethal disease in all mice with comparable time-to-death as unengrafted mice.

      10. Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infectionExternal
        Trivedi S, Miao C, Al-Abdallat MM, Haddadin A, Alqasrawi S, Iblan I, Nsour MA, Alsanouri T, Ali SS, Rha B, Gerber SI, Payne DC, Tamin A, Thornburg NJ.
        J Med Virol. 2018 Feb;90(2):367-371.

        The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.

    • Maternal and Child Health
      1. Functional limitations and educational needs among children and adolescents with heart diseaseExternal
        Farr SL, Downing KF, Riehle-Colarusso T, Abarbanell G.
        Congenit Heart Dis. 2018 Jul 22.

        OBJECTIVE: To examine how cognitive and motor limitations in children with heart disease are associated with education and participation in extracurricular activities. DESIGN: Using 2009-2010 parent-reported data from the National Survey of Children with Special Health Care Needs (NS-CSHCN), we examined prevalence of five functional limitations (learning/concentration, communication, self-care, gross motor skills, and fine motor skills) by diagnosed heart disease status using chi-square tests and multivariable logistic regression. Among CSHCN with heart disease, we examined the associations between severity of each functional limitation and missing >/=11 days of school in the past year, receiving special education services, and interference with extracurricular activities. RESULTS: CSHCN with heart disease (n = 1,416), compared to CSHCN without (n = 28,385), more commonly had “a lot” of difficulty in the five functional areas (P < .01; adjusted odds ratios: 1.8-3.3). Among CSHCN with heart disease, “a lot” of difficulty with learning/concentration was most common (35%), followed by communication (21%), self-care (14%), gross motor skills (12%), and fine motor skills (10%). Among CSHCN with heart disease, compared to those without, respectively, 27% and 15% missed >/=11 days of school, 45% and 29% received special education services, and 49% and 29% experienced interference with extracurricular activities (P < .01 for all). Level of difficulty with the five functional areas was associated with receipt of special education services and participation in extracurricular activities (P < .001). CONCLUSION: These results support the American Heart Association recommendations to screen children with congenital heart disease for age-appropriate development and provide services when needed.

      2. Protecting mothers and babies – a delicate balancing actExternal
        Rasmussen SA, Barfield W, Honein MA.
        N Engl J Med. 2018 Jul 24.

        [No abstract]

      3. Integrated point-of-care testing (POCT) of HIV, syphilis, malaria and anaemia in antenatal clinics in western Kenya: A longitudinal implementation studyExternal
        Young N, Taegtmeyer M, Aol G, Bigogo GM, Phillips-Howard PA, Hill J, Laserson KF, Ter Kuile F, Desai M.
        PLoS One. 2018 ;13(7):e0198784.

        BACKGROUND: In sub-Saharan Africa, HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes. In Kenya, policy states women should be tested for all four conditions (malaria only if febrile) at first antenatal care (ANC) visit. In practice, while HIV screening is conducted, coverage of screening for the others is suboptimal and early pregnancy management of illnesses is compromised. This is particularly evident at rural dispensaries that lack laboratories and have parallel programmes for HIV, reproductive health and malaria, resulting in fractured and inadequate care for women. METHODS: A longitudinal eight-month implementation study integrating point-of-care diagnostic tests for the four conditions into routine ANC was conducted in seven purposively selected dispensaries in western Kenya. Testing proficiency of healthcare workers was observed at initial training and at three monthly intervals thereafter. Adoption of testing was compared using ANC register data 8.5 months before and eight months during the intervention. Fidelity to clinical management guidelines was determined by client exit interviews with success defined as >/=90% adherence. FINDINGS: For first ANC visits at baseline (n = 529), testing rates were unavailable for malaria, low for syphilis (4.3%) and anaemia (27.8%), and near universal for HIV (99%). During intervention, over 95% of first attendees (n = 586) completed four tests and of those tested positive, 70.6% received penicillin or erythromycin for syphilis, 65.5% and 48.3% received cotrimoxazole and antiretrovirals respectively for HIV, and 76.4% received artemether/lumefantrine, quinine or dihydroartemisinin-piperaquine correctly for malaria. Iron and folic supplements were given to nearly 90% of women but often at incorrect doses. CONCLUSIONS: Integrating point-of-care testing into ANC at dispensaries with established HIV testing programmes resulted in a significant increase in testing rates, without disturbing HIV testing rates. While more cases were detected and treated, treatment fidelity still requires strengthening and an integrated monitoring and evaluation system needs to be established.

    • Mining
      1. Evaluation of seismic potential in a longwall mine with massive sandstone roof under deep overburdenExternal
        Van Dyke MA, Su WH, Wickline J.
        Int J Min Sci Technol. 2018 Jan;28(1):115-119.

        A recent seismic event was recorded by a deep longwall mine in Virginia at 3.7 ML on the local magnitude scale and 3.4 MMS by the United States Geological Survey (USGS) in 2016. Further investigations by the National Institute for Occupational Safety and Health (NIOSH) and Coronado Coal researchers have shown that this event was associated with geological features that have also been associated with other, similar seismic events in Virginia. Detailed mapping and geological exploration in the mining area has made it possible to forecast possible locations for future seismic activity. In order to use the geology as a forecaster of mining-induced seismic events and their energy potential, two primary components are needed. The first component is a long history of recorded seismic events with accurately plotted locations. The second component is a high density of geologic data within the mining area. In this case, 181 events of 1.0 ML or greater were recorded by the mine’s seismic network between January, 2009, and October, 2016. Within the mining area, 897 geophysical logs, 224 core holes, and 1031 fiberscope holes were examined by mine geologists. From this information, it was found that overburden thickness, sandstone thickness, and sandstone quality contributed greatly to seismic locations. After the data was analyzed, a pattern became apparent indicating that the majority of seismic events occurred under specific conditions. Three forecast maps were created based on geology of previous seismic locations. The forecast maps have shown an accuracy of within 74%-89% when compared to the recorded 181 events that were 1.0ML or greater when considering three major geological criteria of overburden thickness of 579.12 mor greater, 6.096-12.192 m of sandstone within 15.24 m of the Pocahontas number 3 seam, and a longwall caving height of 4.572 m or less.

    • Nutritional Sciences
      1. Assessment of anthropometric data following investments to ensure quality: Kenya Demographic Health Surveys Case Study, 2008 to 2009 and 2014External
        Leidman E, Mwirigi LM, Maina-Gathigi L, Wamae A, Imbwaga AA, Bilukha OO.
        Food Nutr Bull. 2018 Jan 1:379572118783181.

        BACKGROUND: Evidence-based nutrition programs depend on accurate estimates of malnutrition derived from data collected in population representative surveys. The feasibility of obtaining accurate anthropometric data as part of national, multisectoral surveys has been a debated issue. OBJECTIVES: The study aimed to evaluate changes in anthropometric data quality corresponding to investments by the Kenya Ministry of Health and nutrition sector partners for the 2014 Kenya Demographic Health Survey. METHODS: Anthropometric data collected during the 2008 to 2009 and 2014 Kenya surveys were reanalyzed to assess standard parameters of quality: standard deviation, skewness, and kurtosis of z-score values for 3 anthropometric indicators (weight for height, height for age, and weight for age), percentage of children with missing measurements and outlier values, digit preference, and heaping of age. RESULTS: A total of 9936 households were selected in 2008 to 2009, and 39 679 households were selected in 2014. Standard deviation of z-scores for all 3 indicators was smaller in 2014 than in 2008 to 2009. Applying original Demographic and Health Survey exclusion criteria, weight for height z-scores were 1.16 in 2014, 10.1% narrower than 2008 to 2009. The percentage of outlying values declined significantly from 2008 to 2009 to 2014 for both height for age and weight for height ( P < .001). Digit preference scores in 2014 improved for both weight ( P = .011) and height ( P < .001) suggesting less rounding of terminal digits. CONCLUSIONS: All tests of data quality suggest an improvement in 2014 relative to 2008 to 2009, despite the complexity implied by the larger sample. This improvement corresponds with efforts to enhance training and supervision of anthropometry, suggesting a positive effect of these enhancements.

    • Occupational Safety and Health
      1. Assessment of influenza virus exposure and recovery from contaminated surgical masks and N95 respiratorsExternal
        Blachere FM, Lindsley WG, McMillen CM, Beezhold DH, Fisher EM, Shaffer RE, Noti JD.
        J Virol Methods. 2018 Jul 17.

        Healthcare workers (HCWs) are at significantly higher risk of exposure to influenza virus during seasonal epidemics and global pandemics. During the 2009 influenza pandemic, some healthcare organizations recommended that HCWs wear respiratory protection such as filtering facepiece respirators, while others indicated that facemasks such as surgical masks (SMs) were sufficient. To assess the level of exposure a HCW may possibly encounter, the aim of this study was to (1.) evaluate if SMs and N95 respirators can serve as “personal bioaerosol samplers” for influenza virus and (2.) determine if SMs and N95 respirators contaminated by influenza laden aerosols can serve as a source of infectious virus for indirect contact transmission. This effort is part of a National Institute for Occupational Safety and Health 5-year multidisciplinary study to determine the routes of influenza transmission in healthcare settings. A coughing simulator was programmed to cough aerosol particles containing influenza virus over a wide concentration range into an aerosol exposure simulation chamber virus/L of exam room air), and a breathing simulator was used to collect virus on either a SM or N95 respirator. Extraction buffers containing nonionic and anionic detergents as well as various protein additives were used to recover influenza virus from the masks and respirators. The inclusion of 0.1% SDS resulted in maximal influenza RNA recovery (41.3%) but with a complete loss of infectivity whereas inclusion of 0.1% bovine serum albumin resulted in reduced RNA recovery (6.8%) but maximal retention of virus infectivity (17.9%). Our results show that a HCW’s potential exposure to airborne influenza virus can be assessed in part through analysis of their SMs and N95 respirators, which can effectively serve as personal bioaerosol samplers.

      2. Burden of respiratory abnormalities in microwave popcorn and flavouring manufacturing workersExternal
        Fechter-Leggett ED, White SK, Fedan KB, Cox-Ganser JM, Cummings KJ.
        Occup Environ Med. 2018 Jul 25.

        OBJECTIVES: Diacetyl, a butter flavour compound used in food and flavouring production, is a respiratory toxin. We characterised the burden of respiratory abnormalities in workers at popcorn and flavouring manufacturing facilities that used diacetyl as evaluated through US National Institute for Occupational Safety and Health (NIOSH) health hazard evaluations. METHODS: We performed analyses describing the number and percentage of current and former workers from popcorn and flavouring manufacturing facilities where NIOSH administered a respiratory health questionnaire and spirometry testing who met case definitions of suspected flavouring-related lung disease. Case definitions were pathologist reported: lung biopsy pathology report stating supportive of/consistent with constrictive bronchiolitis or bronchiolitis obliterans; probable: obstructive/mixed spirometric pattern with forced expiratory volume in 1 s (FEV1) <60% predicted; possible: obstructive/mixed spirometric pattern with FEV1 >/=60% or any spirometric restriction; symptoms only: normal spirometry plus exertional dyspnoea or usual cough. RESULTS: During 2000-2012, NIOSH collected questionnaire and spirometry data on 1407 workers (87.0% current, 13.0% former) at nine facilities in eight states. After applying case definitions, 4 (0.3%) were classified as pathologist reported, 48 (3.4%) as probable, 234 (16.6%) as possible and 404 (28.7%) as symptoms only. The remaining 717 (51.0%) workers had normal spirometry without exertional dyspnoea or usual cough. Seven of 11 workers with biopsies did not meet the pathologist-reported case definition, although four met probable and three met possible. CONCLUSIONS: This approach demonstrates the substantial burden of respiratory abnormalities in these workers. A similar approach could quantify the burden of respiratory abnormalities in other industries that use diacetyl.

      3. Background: The United States Fire Administration (USFA) provides high-quality data for firefighter deaths (FFDs), but until now this data has not been analyzed for temporal trends. This analysis explores FFDs between 1990-2016 to determine high risk groups for outreach and training. Methods: Mortality rates were calculated using USFA information compared against the total number of deaths per-year. Rates were compared between 1990-2009 (early period) and 2010-2016 (recent period). Multinomial logistic regression was used to determine predictors of death in firefighters by age group (</=45 yrs. old and >45) and by work status (career vs volunteer). Results: Analysis of 3159 FFDs revealed a decline in crude-rate mortality between 1990-2009 and 2010-2016 (47.4 vs 35 FF deaths/million, p<0.0001). Firefighters </=45 yrs. old were less likely to die in the 2010s than in the 1990s-2000’s, (13.7 vs 24.7 FF deaths/million, p=0.0002). Trauma related deaths decreased (13.1 vs 8.1, p=0.0003) while CV-related deaths remained constant (19.4 vs 19.5, p=0.24). Regression analysis determined that volunteer firefighters were more likely to die from burns (OR 1.7, CI:1.2-2.4, P<0.0001) and trauma (OR 1.8, CI:1.5-2.2, p<0.0001) than career firefighters. Younger firefighters were also more likely to die from burns (OR 10.4, CI 6.9-15.6, P<0.0001) and trauma (OR 6.5, CI:5.4-7.8, p<0.0001). Conclusions: Although overall FFDs were lower after 2010, younger and volunteer firefighters saw an increase in burn and trauma related mortality. Cardiovascular related fatalities were consistent throughout the study. Future research should continue to make use of high-standard data to track FFDs and efficacy of interventions.

      4. Nonfatal injuries to firefighters treated in U.S. emergency departments, 2003-2014External
        Marsh SM, Gwilliam M, Konda S, Tiesman HM, Fahy R.
        Am J Prev Med. 2018 Jul 18.

        INTRODUCTION: Several studies of nonfatal firefighter injuries have been conducted but are limited by the inclusion criteria used and coverage. The aim of this study was to enhance current knowledge by providing national estimates of nonfatal injuries to firefighters treated in U.S. emergency departments. METHODS: Nonfatal injuries from 2003 through 2014 were extracted from the National Electronic Injury Surveillance System occupational supplement (NEISS-Work). NEISS-Work captures nonfatal occupational injuries, illnesses, and exposures treated in a sample of U.S. emergency departments. Nonfatal injury rates were calculated based on NEISS-Work counts (numerator) and counts from the National Fire Protection Association (denominator). Data were analyzed from 2016 through 2017. RESULTS: Between 2003 and 2014, an estimated 351,800 firefighters were treated in emergency departments for nonfatal injuries. The overall rate was 260 injuries per 10,000 firefighters. Career firefighters had an annual rate of 699 injuries per 10,000 firefighters; volunteers had a rate of 39 injuries per 10,000 firefighters. Leading injury events were fires and explosions (36%) and overexertion and bodily reactions (20%). A majority (38%) of injuries occurred during firefighting activities, 7% occurred during training, and 7% occurred during patient care. Sprains and strains accounted for the largest proportion of injuries in all three of these activities: 28% firefighting activities, 32% training, and 36% patient care. CONCLUSIONS: The results demonstrate that nonfatal injuries for firefighters remained high throughout the study period. The predominance of sprains and strains in all firefighting activities suggests the need for additional research and prevention needs in areas of improved fitness, safer body postures and movements, and situational awareness.

    • Parasitic Diseases
      1. The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysisExternal
        Commons RJ, Simpson JA, Thriemer K, Humphreys GS, Abreha T, Alemu SG, Anez A, Anstey NM, Awab GR, Baird JK, Barber BE, Borghini-Fuhrer I, Chu CS, D’Alessandro U, Dahal P, Daher A, de Vries PJ, Erhart A, Gomes MS, Gonzalez-Ceron L, Grigg MJ, Heidari A, Hwang J, Kager PA, Ketema T, Khan WA, Lacerda MV, Leslie T, Ley B, Lidia K, Monteiro WM, Nosten F, Pereira DB, Phan GT, Phyo AP, Rowland M, Saravu K, Sibley CH, Siqueira AM, Stepniewska K, Sutanto I, Taylor WR, Thwaites G, Tran BQ, Tran HT, Valecha N, Vieira JL, Wangchuk S, William T, Woodrow CJ, Zuluaga-Idarraga L, Guerin PJ, White NJ, Price RN.
        Lancet Infect Dis. 2018 Jul 19.

        BACKGROUND: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. METHODS: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310. FINDINGS: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34.8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32.4% (95% CI 29.8-35.1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0.82, 95% CI 0.69-0.97; p=0.021) and in children younger than 5 years (0.59, 0.41-0.86; p=0.0058). Adding primaquine reduced the risk of recurrence to 4.9% (95% CI 3.1-7.7) by day 42, which is lower than with chloroquine alone (AHR 0.10, 0.05-0.17; p<0.0001). INTERPRETATION: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax. FUNDING: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.

      2. Chagas disease (also known as American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi (1,2). Vectorborne transmission via skin or mucosal contact with the feces of infected triatomine bugs mainly occurs in rural areas of Latin America but has been reported in the southern United States (3). The parasite also is transmissible congenitally and via blood transfusion, organ transplantation, and accidental laboratory exposures. The two drugs used for treating Chagas disease are benznidazole and nifurtimox (1,2), which have been used in Latin America since the 1970s and 1960s, respectively. In the absence of commercially available drugs approved by the Food and Drug Administration (FDA), benznidazole and nifurtimox have been available exclusively through CDC, under Investigational New Drug (IND) treatment protocols. On August 29, 2017, FDA approved a benznidazole product (Chemo Research, SL, in care of Exeltis*) for treatment of Chagas disease (4), which became commercially available on May 14, 2018. Therefore, effective May 14, 2018, benznidazole is no longer available through the CDC-sponsored IND program. This report summarizes selected characteristics of patients for whom CDC released benznidazole through that program from October 2011, when the IND went into effect, until mid-May 2018. The majority of the 365 patients included in intention-to-treat analyses were chronically infected adults who were born and became infected in Latin America. Physician requests for benznidazole should now be directed to the drug company Exeltis. The CDC-sponsored IND for nifurtimox remains in effect to provide an alternative therapeutic option to benznidazole when clinically appropriate. CDC will continue to provide reference diagnostic testing for T. cruzi infection and teleconsultative services regarding Chagas disease.

      3. Molecular xenomonitoring for Wuchereria bancrofti in Culex quinquefasciatus in two districts in Bangladesh supports transmission assessment survey findingsExternal
        Irish SR, Al-Amin HM, Paulin HN, Mahmood A, Khan RK, Muraduzzaman AK, Worrell CM, Flora MS, Karim MJ, Shirin T, Shamsuzzaman AK, Tahmina S, Lenhart A, Dubray C.
        PLoS Negl Trop Dis. 2018 Jul;12(7):e0006574.

        BACKGROUND: Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) as a public health problem has been stopped. During the post-MDA period, transmission assessment surveys (TAS) are recommended by the World Health Organization to monitor the presence of the parasite in humans. Molecular xenomonitoring (MX), a method by which parasite infection in the mosquito population is monitored, has also been proposed as a sensitive method to determine whether the parasite is still present in the human population. The aim of this study was to conduct an MX evaluation in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were systematically collected from 180 trap sites per district and mosquito pools were tested for W. bancrofti using real-time PCR. A total of 23,436 intact mosquitoes, representing 31 species, were collected from the two districts, of which 10,344 (41%) were Culex quinquefasciatus, the vector of W. bancrofti in Bangladesh. All of the 594 pools of Cx. quinquefasciatus tested by real-time PCR were negative for the presence of W. bancrofti DNA. CONCLUSIONS/SIGNIFICANCE: This study suggested the absence of W. bancrofti in these districts. MX could be a sensitive tool to confirm interruption of LF transmission in areas considered at higher risk of recrudescence, particularly in countries like Bangladesh where entomological and laboratory capacity to perform MX is available.

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

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

    • Reproductive Health
      1. Social determinants and teen pregnancy prevention: Exploring the role of nontraditional partnershipsExternal
        Fuller TR, White CP, Chu J, Dean D, Clemmons N, Chaparro C, Thames JL, Henderson AB, King P.
        Health Promot Pract. 2018 Jan;19(1):23-30.

        Addressing the social determinants of health (SDOH) that influence teen pregnancy is paramount to eliminating disparities and achieving health equity. Expanding prevention efforts from purely individual behavior change to improving the social, political, economic, and built environments in which people live, learn, work, and play may better equip vulnerable youth to adopt and sustain healthy decisions. In 2010, the Centers for Disease Control and Prevention in partnership with the Office of Adolescent Health funded state- and community-based organizations to develop and implement the Teen Pregnancy Prevention Community-Wide Initiative. This effort approached teen pregnancy from an SDOH perspective, by identifying contextual factors that influence teen pregnancy and other adverse sexual health outcomes among vulnerable youth. Strategies included, but were not limited to, conducting a root cause analysis and establishing nontraditional partnerships to address determinants identified by community members. This article describes the value of an SDOH approach for achieving health equity, explains the integration of such an approach into community-level teen pregnancy prevention activities, and highlights two project partners’ efforts to establish and nurture nontraditional partnerships to address specific SDOH.

    • Substance Use and Abuse
      1. Differences in maternal smoking across successive pregnancies – dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysisExternal
        Albers L, von Kries R, Sobotzki C, Gao HJ, Buka SL, Clifton VL, Grzeskowiak LE, Oken E, Paus T, Pausova Z, Rifas-Shiman SL, Sharma AJ, Gilman SE.
        Obes Rev. 2018 Jul 23.

        INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings’ shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring’s BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring’s BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses >/=25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

      2. Awareness and ever use of “heat-not-burn” tobacco products among U.S. adults, 2017External
        Marynak KL, Wang TW, King BA, Agaku IT, Reimels EA, Graffunder CM.
        Am J Prev Med. 2018 Jul 18.

        INTRODUCTION: Heated tobacco products, sometimes marketed as “heat-not-burn” technology, represent a diverse class of products that heat leaf tobacco to produce an inhaled aerosol. Global sales of heated tobacco products are increasing; however, the extent of current heated tobacco product awareness and use in the U.S. is unknown. This study assessed awareness and ever use of heated tobacco products among U.S. adults. METHODS: Data were obtained from the 2017 SummerStyles, an Internet survey of U.S. adults aged >/=18 years (N=4,107). Respondents were given a description of heated tobacco products, then asked about awareness and ever use. In 2017, descriptive statistics were calculated overall and by sex, age, race/ethnicity, and cigarette smoking status. Logistic regression was used to calculate AORs. RESULTS: In 2017, a total of 5.2% of U.S. adults were aware of heated tobacco products, including 9.9% of current cigarette smokers. Overall, 0.7% of U.S. adults, including 2.7% of current smokers, reported ever use of heated tobacco products. Odds of ever use were higher among current smokers (AOR=6.18) than never smokers, and higher among adults aged <30 years (AOR=3.35) than those aged >/=30 years. CONCLUSIONS: As of July 2017, few U.S. adults had ever used heated tobacco products; however, about one in 20 were aware of the products, including one in ten cigarette smokers. The uncertain impact of heated tobacco products on individual- and population-level health warrants timely and accurate public health surveillance. These first estimates among U.S. adults can serve as a key baseline measure.

      3. Examining the high rate of cigarette smoking among adults with a GEDExternal
        Schoenborn CA, Stommel M, Lucas JW.
        Addict Behav. 2018 Feb;77:275-286.

        OBJECTIVES: We seek to identify characteristics of GED holders that explain their very high smoking rates compared with high school (HS) graduates. METHODS: We pooled data from the 2006-2014 National Health Interview Surveys (NHIS) for adults aged 25 and older (n=235,031) to describe cigarette smoking behaviors and smoking history for adults in six education categories, with a focus on comparing GED holders to HS graduates. Logistic regression was used to predict the odds of current cigarette smoking and successful quitting, accounting for demographic, employment, family/sociocultural, mental health, and other potential confounders. RESULTS: The smoking rate among adults with a GED (44.1%) was more than five times the rate for those with a college degree (8.3%) and almost twice the rate of adults whose highest level of education was a high school diploma (23.6%). GED holders were also more likely to have started smoking before the age of 15 (32.2%) compared with HS graduates (12.2%) (p<0.001). Even after controlling for 23 socio-demographic and health characteristics, GED holders retained significantly higher odds of current smoking compared to HS graduates (OR=1.73; 95% CI: 1.56, 1.93) and significantly lower odds of successful quitting (OR=0.83, 95% CI: 0.73, 0.94). CONCLUSIONS: GED holders had greater odds of being a current cigarette smoker, regardless of other characteristics that usually explain smoking. Earlier smoking initiation among GED holders, in combination with lower odds of quitting, contributed to their higher current smoking rate.

      4. Attitudes toward smoke-free public housing among U.S. adults, 2016External
        Wang TW, Lemos PR, McNabb S, King BA.
        Am J Prev Med. 2018 Jan;54(1):113-118.

        INTRODUCTION: Effective February 2017, the U.S. Department of Housing and Urban Development published a rule requiring each public housing agency to implement a smoke-free policy within 18 months. This study assessed the prevalence and determinants of favorability toward smoke-free public housing among U.S. adults. METHODS: Data from 2016 Summer Styles, a nationally representative web-based survey conducted among adults (N=4,203) were analyzed in 2017. Participants were asked: Do you favor or oppose prohibiting smoking in public housing, including all indoor areas of living units, common areas, and office buildings, as well as in all outdoor areas within 25 feet of buildings? Multivariate Poisson regression was used to calculate adjusted prevalence ratios of favorability (strongly or somewhat). RESULTS: Overall, 73.7% of respondents favored smoke-free public housing. Favorability was 44.3% among current cigarette smokers, 73.2% among former smokers, and 80.4% among never smokers. The adjusted likelihood of favorability was greater among non-Hispanic, non-black racial/ethnic minorities than whites, and among those in the West than the Northeast (p<0.05). Favorability was lower among adults with a high school education or less compared with those with a college degree, adults with annual household income <$15,000 than those with income >/=$60,000, multiunit housing residents than non-multiunit housing residents, current cigarette smokers than never smokers, and current non-cigarette tobacco product users than never users (p<0.05). CONCLUSIONS: Most U.S. adults favor prohibiting smoking in public housing. These data can inform the implementation and sustainment of smoke-free policies to reduce the public health burden of tobacco smoking in public housing.

    • Zoonotic and Vectorborne Diseases
      1. A case of Lassa fever diagnosed at a community hospital – Minnesota 2014External
        Choi MJ, Worku S, Knust B, Vang A, Lynfield R, Mount MR, Objio T, Brown S, Griffith J, Hulbert D, Lippold S, Ervin E, Stroher U, Holzbauer S, Slattery W, Washburn F, Harper J, Koeck M, Uher C, Rollin P, Nichol S, Else R, DeVries A.
        Open Forum Infect Dis. 2018 Jul;5(7):ofy131.

        Background: In April 2014, a 46-year-old returning traveler from Liberia was transported by emergency medical services to a community hospital in Minnesota with fever and altered mental status. Twenty-four hours later, he developed gingival bleeding. Blood samples tested positive for Lassa fever RNA by reverse transcriptase polymerase chain reaction. Methods: Blood and urine samples were obtained from the patient and tested for evidence of Lassa fever virus infection. Hospital infection control personnel and health department personnel reviewed infection control practices with health care personnel. In addition to standard precautions, infection control measures were upgraded to include contact, droplet, and airborne precautions. State and federal public health officials conducted contract tracing activities among family contacts, health care personnel, and fellow airline travelers. Results: The patient was discharged from the hospital after 14 days. However, his recovery was complicated by the development of near complete bilateral sensorineural hearing loss. Lassa virus RNA continued to be detected in his urine for several weeks after hospital discharge. State and federal public health authorities identified and monitored individuals who had contact with the patient while he was ill. No secondary cases of Lassa fever were identified among 75 contacts. Conclusions: Given the nonspecific presentation of viral hemorrhagic fevers, isolation of ill travelers and consistent implementation of basic infection control measures are key to preventing secondary transmission. When consistently applied, these measures can prevent secondary transmission even if travel history information is not obtained, not immediately available, or the diagnosis of a viral hemorrhagic fever is delayed.

      2. Sexual transmission of Zika virus and other flaviviruses: A living systematic reviewExternal
        Counotte MJ, Kim CR, Wang J, Bernstein K, Deal CD, Broutet NJ, Low N.
        PLoS Med. 2018 Jul;15(7):e1002611.

        BACKGROUND: Health authorities in the United States and Europe reported an increasing number of travel-associated episodes of sexual transmission of Zika virus (ZIKV) following the 2015-2017 ZIKV outbreak. This, and other scientific evidence, suggests that ZIKV is sexually transmissible in addition to having its primary mosquito-borne route. The objective of this systematic review and evidence synthesis was to clarify the epidemiology of sexually transmitted ZIKV. METHODS AND FINDINGS: We performed a living (i.e., continually updated) systematic review of evidence published up to 15 April 2018 about sexual transmission of ZIKV and other arthropod-borne flaviviruses in humans and other animals. We defined 7 key elements of ZIKV sexual transmission for which we extracted data: (1) rectal and vaginal susceptibility to infection, (2) incubation period following sexual transmission, (3) serial interval between the onset of symptoms in a primary and secondary infected individuals, (4) duration of infectiousness, (5) reproduction number, (6) probability of transmission per sex act, and (7) transmission rate. We identified 1,227 unique publications and included 128, of which 77 presented data on humans and 51 presented data on animals. Laboratory experiments confirm that rectal and vaginal mucosae are susceptible to infection with ZIKV and that the testis serves as a reservoir for the virus in animal models. Sexual transmission was reported in 36 human couples: 34/36 of these involved male-to-female sexual transmission. The median serial symptom onset interval in 15 couples was 12 days (interquartile range: 10-14.5); the maximum was 44 days. We found evidence from 2 prospective cohorts that ZIKV RNA is present in human semen with a median duration of 34 days (95% CI: 28-41 days) and 35 days (no CI given) (low certainty of evidence, according to GRADE). Aggregated data about detection of ZIKV RNA from 37 case reports and case series indicate a median duration of detection of ZIKV of 40 days (95% CI: 30-49 days) and maximum duration of 370 days in semen. In human vaginal fluid, median duration was 14 days (95% CI: 7-20 days) and maximum duration was 37 days (very low certainty). Infectious virus in human semen was detected for a median duration of 12 days (95% CI: 1-21 days) and maximum of 69 days. Modelling studies indicate that the reproduction number is below 1 (very low certainty). Evidence was lacking to estimate the incubation period or the transmission rate. Evidence on sexual transmission of other flaviviruses was scarce. The certainty of the evidence is limited because of uncontrolled residual bias. CONCLUSIONS: The living systematic review and sexual transmission framework allowed us to assess evidence about the risk of sexual transmission of ZIKV. ZIKV is more likely transmitted from men to women than from women to men. For other flaviviruses, evidence of sexual transmissibility is still absent. Taking into account all available data about the duration of detection of ZIKV in culture and from the serial interval, our findings suggest that the infectious period for sexual transmission of ZIKV is shorter than estimates from the earliest post-outbreak studies, which were based on reverse transcription PCR alone.

      3. One million dog vaccinations recorded on mHealth innovation used to direct teams in numerous rabies control campaignsExternal
        Gibson AD, Mazeri S, Lohr F, Mayer D, Burdon Bailey JL, Wallace RM, Handel IG, Shervell K, Bronsvoort BM, Mellanby RJ, Gamble L.
        PLoS One. 2018 ;13(7):e0200942.

        BACKGROUND: Canine transmitted rabies kills an estimated 59,000 people annually, despite proven methods for elimination through mass dog vaccination. Challenges in directing and monitoring numerous remote vaccination teams across large geographic areas remain a significant barrier to the up-scaling of focal vaccination programmes to sub-national and national level. Smartphone technology (mHealth) is increasingly being used to enhance the coordination and efficiency of public health initiatives in developing countries, however examples of successful scaling beyond pilot implementation are rare. This study describes a smartphone app and website platform, “Mission Rabies App”, used to co-ordinate rabies control activities at project sites in four continents to vaccinate over one million dogs. METHODS: Mission Rabies App made it possible to not only gather relevant campaign data from the field, but also to direct vaccination teams systematically in near real-time. The display of user-allocated boundaries on Google maps within data collection forms enabled a project manager to define each team’s region of work, assess their output and assign subsequent areas to progressively vaccinate across a geographic area. This ability to monitor work and react to a rapidly changing situation has the potential to improve efficiency and coverage achieved, compared to regular project management structures, as well as enhancing capacity for data review and analysis from remote areas. The ability to plot the location of every vaccine administered facilitated engagement with stakeholders through transparent reporting, and has the potential to motivate politicians to support such activities. RESULTS: Since the system launched in September 2014, over 1.5 million data entries have been made to record dog vaccinations, rabies education classes and field surveys in 16 countries. Use of the system has increased year-on-year with adoption for mass dog vaccination campaigns at the India state level in Goa and national level in Haiti. CONCLUSIONS: Innovative approaches to rapidly scale mass dog vaccination programmes in a sustained and systematic fashion are urgently needed to achieve the WHO, OIE and FAO goal to eliminate canine-transmitted human deaths by 2030. The Mission Rabies App is an mHealth innovation which greatly reduces the logistical and managerial barriers to implementing large scale rabies control activities. Free access to the platform aims to support pilot campaigns to better structure and report on proof-of-concept initiatives, clearly presenting outcomes and opportunities for expansion. The functionalities of the Mission Rabies App may also be beneficial to other infectious disease interventions.

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