Volume 11, Issue 35 September 3, 2019

CDC Science Clips: Volume 11, Issue 35, September 3, 2019

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

This week Science Clips is pleased to feature articles on tuberculosis (TB) in the United States.

For the past 25 years, with one exception (2015), the number of new TB cases being reported in the United States has decreased annually. However, the pace of decline in U.S. TB incidence rates has slowed, prompting extensive epidemiologic investigation to understand the reasons for this trend.

The articles featured below have helped the public health community to understand the changing epidemiology of TB in the United States, as well as to identify strategies for accelerating the decline once more. Topics covered in these articles include:

  • comparison of the epidemiology of TB in recent years with when the incidence rate was decreasing more quickly
  • detailed analysis of the characteristics of certain subpopulations with TB
  • modeling of potential future changes in TB epidemiology
  • economic analyses, and
  • evaluation of prevention strategies.

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Communicable Diseases – Tuberculosis in the United States
      1. Changes in tuberculosis epidemiology, United States, 1993-2017external icon
        Armstrong LR, Winston CA, Stewart B, Tsang CA, Langer AJ, Navin TR.
        Int J Tuberc Lung Dis. 2019 Jul 1;23(7):797-804.
        BACKGROUND: After 20 years of steady decline, the pace of decline of tuberculosis (TB) incidence in the United States has slowed.METHODS: Trends in TB incidence rates and case counts since 1993 were assessed using national US surveillance data. Patient characteristics reported during 2014-2017 were compared with those for 2010-2013.RESULTS: TB rates and case counts slowed to an annual decline of respectively 2.2% (95%CI -3.4 to -1.0) and 1.5% (95%CI -2.7 to -0.3) since 2012, with decreases among US-born persons and no change among non-US-born persons. Overall, persons with TB diagnosed during 2014-2017 were older, more likely to have combined pulmonary and extra-pulmonary disease than extra-pulmonary disease alone, more likely to be of non-White race, and less likely to have human immunodeficiency virus infection, or cavitary pulmonary disease. During 2014-2017, non-US-born persons with TB were more likely to have diabetes mellitus, while the US-born were more likely to have smear-positive TB and use non-injecting drugs.CONCLUSION: Changes in epidemiologic trends are likely to affect TB incidence in the coming decades. The Centers for Disease Control and Prevention has called for increased attention to TB prevention through the detection and treatment of latent tuberculous infection.

      2. BACKGROUND: Understanding tuberculosis epidemiology among children and adolescents informs treatment and prevention efforts, and efforts to eliminate disparities in tuberculosis incidence and mortality. We sought to describe the epidemiology of children and adolescents with tuberculosis disease in the USA, including tuberculosis incidence rates by parental country of birth and for US territories and freely associated states, which have not been previously described. METHODS: We analysed data for children aged younger than 15 years and adolescents aged 15-17 years with tuberculosis disease reported to the National Tuberculosis Surveillance System during 2007-17, and calculated tuberculosis incidence rates using population estimates from the US Census Bureau. FINDINGS: During 2010-17, 6072 tuberculosis cases occurred among children and adolescents; of these, 5175 (85%) of 6072 occurred in the 50 US states or the District of Columbia and 897 (15%) of 6072 in US-affiliated islands. In US states, 3520 (68%) of 5175 cases occurred among US-born people overall, including 2977 (76%) of 3896 children and 543 (42%) of 1279 adolescents. The incidence rate among children and adolescents was 1.0 per 100 000 person-years during 2007-17 and declined 47.8% (95% CI -51.4 to -44.1) during this period. We observed disproportionately high tuberculosis rates among children and adolescents of all non-white racial or ethnic groups, people living in US-affiliated islands, and children born in or with parents from tuberculosis-endemic countries. INTERPRETATION: Overall, tuberculosis incidence among children and adolescents in the USA is low and steadily declining, but additional efforts are needed to eliminate disparities in incidence and mortality. FUNDING: US Centers for Disease Control and Prevention.

      3. Tuberculosis among healthcare personnel, United States, 2010-2016external icon
        Mongkolrattanothai T, Lambert LA, Winston CA.
        Infect Control Hosp Epidemiol. 2019 Jun;40(6):701-704.
        We describe characteristics of US healthcare personnel (HCP) diagnosed with tuberculosis (TB). Among 64,770 adults with TB during 2010-2016, 2,460 (4%) were HCP. HCP with TB were more likely to be born outside of the United States, and less likely to have TB attributed to recent transmission, than non-HCP.

      4. Outlook for tuberculosis elimination in California: An individual-based stochastic modelexternal icon
        Goodell AJ, Shete PB, Vreman R, McCabe D, Porco TC, Barry PM, Flood J, Marks SM, Hill A, Cattamanchi A, Kahn JG.
        PLoS One. 2019 ;14(4):e0214532.
        RATIONALE: As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI). OBJECTIVES: To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California. METHODS: We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained. MEASUREMENTS AND MAIN RESULTS: In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY. CONCLUSIONS: Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.

      5. OBJECTIVES: To investigate treatment outcomes and associated characteristics of persons experiencing homelessness who received 12-weekly doses of directly observed isoniazid and rifapentine (3HP/DOT) treatment for latent TB infection (LTBI). METHODS: Among homeless persons treated with 3HP/DOT during July 2011 -June 2015 in 11 U.S. TB programs, we conducted descriptive analyses of observational data, and identified associations between sociodemographic factors and treatment outcomes. Qualitative interviews were conducted to understand programmatic experiences. RESULTS: Of 393 persons experiencing homelessness (median age: 50 years; range: 13-74 years), 301 (76.6%) completed treatment, 55 (14.0%) were lost to follow-up, 18 (4.6%) stopped because of an adverse event (AE), and 19 (4.8%) stopped after relocations or refusing treatment. Eighty-one (20.6%) had at least one AE. Persons aged >/=65 were more likely to discontinue treatment than persons aged 31-44 years. Programs reported difficulty in following up with persons experiencing homelessness because of relocations, mistrust, and alcohol or drug use. CONCLUSIONS: This study demonstrates the feasibility of administering the 3HP/DOT LTBI regimen to persons experiencing homelessness, a high-risk population.

      6. Estimates of testing for latent tuberculosis infection and cost, United States, 2013external icon
        Marks SM, Woodruff RY, Owusu-Edusei K, Asay GR, Hill AN.
        Public Health Rep. 2019 Sep/Oct;134(5):522-527.
        OBJECTIVES: Tracking trends in the testing of latent tuberculosis infection (LTBI) can help measure tuberculosis elimination efforts in the United States. The objectives of this study were to estimate (1) the annual number of persons tested for LTBI and the number of LTBI tests conducted, by type of test and by public, private, and military sectors, and (2) the cost of LTBI testing in the United States. METHODS: We searched the biomedical literature for published data on private-sector and military LTBI testing in 2013, and we used back-calculation to estimate public-sector LTBI testing. To estimate costs, we applied Medicare-allowable reimbursements in 2013 by test type. RESULTS: We estimated an average (low-high) 13.3 million (11.3-15.4 million) persons tested for LTBI and 15.3 million (12.9-17.7 million) LTBI tests, of which 13.2 million (11.1-15.3 million) were tuberculin skin tests and 2.1 million (1.8-2.4 million) were interferon-gamma release assays (IGRAs). Eighty percent of persons tested were in the public sector, 18% were in the private sector, and 2% were in the military. Costs of LTBI tests and of chest radiography totaled $314 million (range, $256 million to $403 million). CONCLUSIONS: To achieve tuberculosis elimination, millions more persons will need to be tested in all sectors. By targeting testing to only those at high risk of tuberculosis and by using more specific IGRA tests, the incidence of tuberculosis in the United States can be reduced and resources can be more efficiently used.

      7. Simple estimates for local prevalence of latent tuberculosis infection, United States, 2011-2015external icon
        Haddad MB, Raz KM, Lash TL, Hill AN, Kammerer JS, Winston CA, Castro KG, Gandhi NR, Navin TR.
        Emerg Infect Dis. 2018 Oct;24(10):1930-1933.
        We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

      8. Changes in tuberculosis disparities at a time of decreasing tuberculosis incidence in the United States, 1994-2016external icon
        Khan A, Marks S, Katz D, Morris SB, Lambert L, Magee E, Bowman S, Grant G.
        Am J Public Health. 2018 Nov;108(S4):S321-s326.
        OBJECTIVES: To assess national progress in reducing disparities in rates of tuberculosis (TB) disease, which disproportionately affects minorities. METHODS: We used Centers for Disease Control and Prevention (CDC) surveillance data and US Census data to calculate TB rates for 1994 through 2016 by race/ethnicity, national origin, and other TB risk factors. We assessed progress in reducing disparities with rate ratios (RRs) and indexes of disparity, defined as the average of the differences between subpopulation and all-population TB rates divided by the all-population rate. RESULTS: Although TB rates decreased for all subpopulations, RRs increased or stayed the same for all minorities compared with Whites. For racial/ethnic groups, indexes of disparity decreased from 1998 to 2008 (P < .001) but increased thereafter (P = .33). The index of disparity by national origin increased an average of 1.5% per year. CONCLUSIONS: Although TB rates have decreased, disparities have persisted and even increased for some populations. To address the problem, the CDC’s Division of TB Elimination has focused on screening and treating latent TB infection, which is concentrated among minorities and is the precursor for more than 85% of TB cases in the United States.

      9. Tuberculosis incidence among populations at high risk in California, Florida, New York, and Texas, 2011-2015external icon
        Cherng ST, Shrestha S, Reynolds S, Hill AN, Marks SM, Kelly J, Dowdy DW.
        Am J Public Health. 2018 Nov;108(S4):S311-s314.
        OBJECTIVES: To illustrate the magnitude of between-state heterogeneities in tuberculosis (TB) incidence among US populations at high risk for TB that may help guide state-specific strategies for TB elimination. METHODS: We used data from the National Tuberculosis Surveillance System and other public sources from 2011 to 2015 to calculate TB incidence in every US state among people who were non-US-born, had diabetes, or were HIV-positive, homeless, or incarcerated. We then estimated the proportion of TB cases that reflected the difference between each state’s reported risk factor-specific TB incidence and the lowest incidence achieved among 4 states (California, Florida, New York, Texas). We reported these differences for the 4 states and also calculated and aggregated across all 50 states to quantify the total percentage of TB cases nationally that reflected between-state differences in risk factor-specific TB incidence. RESULTS: On average, 24% of recent TB incidence among high-risk US populations reflected heterogeneity at the state level. The populations that accounted for the greatest percentage of heterogeneity-reflective cases were non-US-born individuals (51%) and patients with diabetes (24%). CONCLUSIONS: State-level differences in TB incidence among key populations provide clues for targeting state-level interventions.

      10. Age-Period-Cohort Analyses of Tuberculosis Incidence Rates by Nativity, United States, 1996-2016external icon
        Iqbal SA, Winston CA, Bardenheier BH, Armstrong LR, Navin TR.
        Am J Public Health. 2018 Nov;108(S4):S315-s320.
        OBJECTIVES: To assess changes in US tuberculosis (TB) incidence rates by age, period, and cohort effects, stratified according to race/ethnicity and nativity. METHODS: We used US National Tuberculosis Surveillance System data for 1996 to 2016 to estimate trends through age-period-cohort models. RESULTS: Controlling for cohort and period effects indicated that the highest rates of TB incidence occurred among those 0 to 5 and 20 to 30 years of age. The incidence decreased by age for successive birth cohorts. There were greater estimated annual percentage decreases among US-born individuals (-7.3%; 95% confidence interval [CI] = -7.5, -7.1) than among non-US-born individuals (-4.3%; 95% CI = -4.5, -4.1). US-born individuals older than 25 years exhibited the largest decreases, a pattern that was not reflected among non-US-born adults. In the case of race/ethnicity, the greatest decreases by nativity were among US-born Blacks (-9.3%; 95% CI = -9.6, -9.1) and non-US-born Hispanics (-5.7%; 95% CI = -6.0, -5.5). CONCLUSIONS: TB has been decreasing among all ages, races and ethnicities, and consecutive cohorts, although these decreases are less pronounced among non-US-born individuals.

      11. Number and cost of hospitalizations with principal and secondary diagnoses of tuberculosis, United Statesexternal icon
        Aslam MV, Owusu-Edusei K, Marks SM, Asay GR, Miramontes R, Kolasa M, Winston CA, Dietz PM.
        Int J Tuberc Lung Dis. 2018 Dec 1;22(12):1495-1504.
        OBJECTIVE: To estimate the number and cost of hospitalizations with a diagnosis of active tuberculosis (TB) disease in the United States. METHODS: We analyzed the 2014 National In-Patient Sample using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes to identify hospitalizations with a principal (TB-PD) or any secondary discharge (TB-SD) TB diagnosis. We used a generalized linear model with log link and gamma distribution to estimate the cost per TB-PD and TB-SD episode adjusted for patient demographics, insurer, clinical elements, and hospital characteristics. RESULTS: We estimated 4985 TB-PD and 6080 TB-SD hospitalizations nationwide. TB-PD adjusted averaged $16 695 per episode (95%CI $16 168-$17 221). The average for miliary/disseminated TB ($22 498, 95%CI $21 067-$23 929) or TB of the central nervous system ($28 338, 95%CI $25 836-$30 840) was significantly greater than for pulmonary TB ($14 819, 95%CI $14 284-$15 354). The most common principal diagnoses for TB-SD were septicemia (n = 965 hospitalizations), human immunodeficiency virus infection (n = 610), pneumonia (n = 565), and chronic obstructive pulmonary disease and bronchiectasis (COPD-B, n = 150). The adjusted average cost per TB-SD episode was $15 909 (95%CI $15 337-$16 481), varying between $8687 (95%CI $8337-$9036) for COPD-B and $23 335 (95%CI $21 979-$24 690) for septicemia. TB-PD cost the US health care system $123.4 million (95%CI $106.3-$140.5) and TB-SD cost $141.9 million ($128.4-$155.5), of which Medicaid/Medicare covered respectively 67.2% and 69.7%. CONCLUSIONS: TB hospitalizations result in substantial costs within the US health care system.

      12. The impact of migration on tuberculosis in the United Statesexternal icon
        Menzies NA, Hill AN, Cohen T, Salomon JA.
        Int J Tuberc Lung Dis. 2018 Dec 1;22(12):1392-1403.
        Due to greater exposure to Mycobacterium tuberculosis infection before migration, migrants moving to low-incidence settings can experience substantially higher tuberculosis (TB) rates than the native-born population. This review describes the impact of migration on TB epidemiology in the United States, and how the TB burden differs between US-born and non-US-born populations. The United States has a long history of receiving migrants from other parts of the world, and TB among non-US-born individuals now represents the majority of new TB cases. Based on an analysis of TB cases among individuals from the top 30 countries of origin in terms of non-US-born TB burden between 2003 and 2015, we describe how TB risks vary within the non-US-born population according to age, years since entry, entry year, and country of origin. Variation along each of these dimensions is associated with more than 10-fold differences in the risk of developing active TB, and this risk is also positively associated with TB incidence estimates for the country of origin and the composition of the migrant pool in the entry year. Approximately 87 000 lifetime TB cases are predicted for the non-US-born population resident in the United States in 2015, and 5800 lifetime cases for the population entering the United States in 2015.

  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. Good health and wellness in Indian Country: A new partnership and approachexternal icon
        Bauer UE, Espey DK.
        Prev Chronic Dis. 2019 Aug 15;16:E110.

        [No abstract]

      2. Leveraging the strength of comprehensive cancer control coalitions to support policy, systems, and environmental changeexternal icon
        Moore A, Villalobos A, Gardner AL, Staples C, Shafir S.
        Cancer Causes Control. 2019 Aug 21.
        Strategies that facilitate change to policy, systems, and environmental (PSE) changes can enable behaviors and practices that lead to cancer risk reduction, early detection, treatment access, and improved quality of life among survivors. Comprehensive cancer control is a coordinated collaborative approach to reduce cancer burden and operationalizes PSE change strategies for this purpose. Efforts to support these actions occur at the national, state, and local levels. Resources integral to bolstering strategies for sustainable cancer control include coordination and support from national organizations committed to addressing the burden of cancer, strong partnerships at the state and local levels, funding and resources, an evidence-based framework and program guidance, and technical assistance and training opportunities to build capacity. The purpose of this paper is to describe the impact of public policy, public health programming, and technical assistance and training on the use of PSE change interventions in cancer control. It also describes the foundations for and examples of successes achieved by comprehensive cancer control programs and coalitions using PSE strategies.

      3. Creating a public health community of practice to support American Indian and Alaska Native communities in addressing chronic diseaseexternal icon
        Williams SL, Kaigler A, Armistad A, Espey DK, Struminger BB.
        Prev Chronic Dis. 2019 Aug 15;16:E109.

        [No abstract]

    • Communicable Diseases
      1. Informing data to care: Contacting persons sampled for the Medical Monitoring Projectexternal icon
        Beer L, Bosh KA, Chowdhury PP, Craw J, Nyaku MA, Luna-Gierke RE, Sanders CC, Shouse RL.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S6-s12.
        BACKGROUND: Data to care (D2C) is a public health strategy that uses HIV surveillance and other data to identify persons in need of HIV medical care. The Medical Monitoring Project (MMP), which uses similar methods to contact and recruit HIV-positive persons, may inform predictors of successful contact for D2C programs. SETTING: MMP is a Centers for Disease Control and Prevention-funded surveillance system that collects nationally representative data on adults with diagnosed HIV in the United States and Puerto Rico. METHODS: Using MMP’s 2016 data collection cycle, we present contact rates (ie, proportion of HIV-positive persons successfully contacted for MMP) by the age of contact information and age of laboratory test results available from HIV surveillance data. RESULTS: Nationally, 27.6% of eligible persons did not have a recorded laboratory test performed within the past year (project area range: 10.8%-54.6%). The national contact rate among persons with laboratory tests older than 1 year was 37.0% (project area range: 16.5%-67.1%). Higher contact rates were found among persons with more recent laboratory tests. Similar results were found by the age of contact information. Nationally, the most common reason for MMP ineligibility was that the person was deceased; the most common reason for not being contacted was lack of correct contact information. CONCLUSIONS: MMP findings suggest that D2C programs would benefit from efforts to improve the quality of HIV surveillance data and local surveillance practices-in particular, death ascertainment, the completeness of laboratory reporting, and the routine updating of contact information. Strengthening collaboration and integration with existing MMP programs may be beneficial.

      2. Pharmacy data as an alternative data source for implementation of a data to care strategyexternal icon
        Byrd KK, Camp NM, Iqbal K, Weidle PJ.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S53-s56.
        BACKGROUND: Data to Care (D2C) is a strategy for using health departments’ HIV surveillance data (HIV viral load and CD4 laboratory reports) to identify and re-engage not-in-care persons with HIV. In the current D2C model, there is a delay in the identification of persons not in care due to the time interval between recommended monitoring tests (ie, every 3-6 months) and the subsequent reporting of these tests to the health department. METHODS: Pharmacy claims and fulfillment data can be used to identify persons with HIV who have stopped filling antiretroviral therapy and are at risk of falling out of care. Because most antiretrovirals (ARVs) are prescribed as a 30-day supply of medication, these data can be used to identify persons who are not filling their medications on a monthly basis. The use of pharmacy claims data to identify persons not filling ARV prescriptions is an example of how “big data” can be used to conduct a modified D2C model. RESULTS: Although a D2C strategy using pharmacy data has not been broadly implemented, a few health departments are implementing demonstration projects using this strategy. As the projects progress, processes and outcomes can be evaluated. CONCLUSIONS: Tracking ARV refill data can be a more real-time indicator of poor adherence and can help identify HIV-infected persons at risk of falling out of HIV medical care.

      3. Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by a meta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77% (no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease.

      4. Predicted effectiveness of daily and non-daily PrEP for MSM based on sex and pill-taking patterns from HPTN 067/ADAPTexternal icon
        Dimitrov D, Moore JR, Wood D, Mitchell KM, Li M, Hughes JP, Donnell DJ, Mannheimer S, Holtz TH, Grant RM, Boily MC.
        Clin Infect Dis. 2019 Aug 22.
        BACKGROUND: HPTN 067/ADAPT evaluated the feasibility of daily and non-daily HIV pre-exposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York, U.S. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. METHODS: An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the iPrEx trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. RESULTS: We estimated that PrEP was highly protective (85%-96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%-88% efficacy) than in Harlem (62%-81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85% and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8-9 percentage points in Harlem and by 5-9 percentage points in Bangkok across regimens. CONCLUSIONS: Our analysis suggests that PrEP was more effective among MSM in Thailand than in the U.S. as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, non-daily PrEP was less effective than daily PrEP, especially in the U.S. where the sex act coverage associated with daily use was substantially higher.

      5. High prevalence of disability and HIV risk among low socioeconomic status urban adults, 17 U.S. citiesexternal icon
        Doyle KE, Sionean C, Paz-Bailey G, Hollis ND, Kanny D, Wejnert C.
        Disabil Health J. 2019 Aug 13:100834.
        BACKGROUND: In the United States, approximately 10% of adults 18-64 years are disabled. However, there is scarce literature on the associations between disability and HIV risk. OBJECTIVE: To assess disability prevalence and its associations to health and HIV risk factors among low socioeconomic status (SES) (</=high school education or</=poverty guidelines) urban adults. METHODS: We assessed disability prevalence from a cross-sectional sample of low SES urban heterosexually active adults at risk for HIV participating in the 2016 National HIV Behavioral Surveillance (NHBS) and calculated crude and adjusted prevalence ratios and 95% confidence intervals of disability for health and HIV risk behaviors. RESULTS: In the NHBS sample, 39.6% of participants reported any disability. Disability was associated with health care utilization and risk behaviors, even when adjusting for demographics. Participants with disabilities were more likely to have condomless sex with a casual partner and engage in exchange sex. CONCLUSIONS: Low SES urban heterosexually active adults reported high prevalence of disabilities and differences in health, health care utilization, and risk factors. Disability might contribute to sexual risk behaviors that increase the likelihood of HIV infection. Further investigations into the intersection of disability and HIV risk are needed, especially in poor communities often excluded from national assessments.

      6. Can the United States achieve 90-90-90?external icon
        Hall HI, Brooks JT, Mermin J.
        Curr Opin HIV AIDS. 2019 Aug 13.
        PURPOSE OF REVIEW: To summarize recent trends in knowledge of HIV status, care and viral suppression, and the status of implementation of relevant contextual requirements for the United States to achieve the 90-90-90 goals. Recently, the US government announced a plan to decrease HIV incidence by over 90% by 2030. Reaching this goal may require higher targets than 90-90-90. RECENT FINDINGS: The United States is on course to reach 90-90-90 goals in the near future, with 86% of persons with HIV aware of their infection, 74% of persons with diagnosed infection in care, and 83% of persons in care with viral suppression in 2016. Some high-burden subnational jurisdictions have already achieved these goals. SUMMARY: The United States is likely to reach 90-90-90 targets in the near future. However, to reduce HIV incidence by at least 90% by 2030, the United States will need to rapidly meet the new 95-95-95 targets and deploy a comprehensive strategy with novel approaches to testing, retaining persons with HIV on treatment, and preventing new infections with preexposure prophylaxis and comprehensive syringe services programs.

      7. Correlates of HIV infection in adolescent girls and young women in Lesotho: results from a population-based surveyexternal icon
        Low A, Thin K, Davia S, Mantell J, Koto M, McCracken S, Ramphalla P, Maile L, Ahmed N, Patel H, Parekh B, Fida N, Schwitters A, Frederix K.
        Lancet HIV. 2019 Aug 14.
        BACKGROUND: HIV acquisition remains high among adolescent girls and young women (AGYW, aged 15-24 years) in sub-Saharan Africa. We aimed to estimate prevalence and incidence of HIV in AGYW and to identify correlates of HIV infection by using data from the Lesotho Population-based HIV Impact Assessment (LePHIA). METHODS: LePHIA was a nationally representative survey of adults and children based on a multistage cluster sampling method with random selection of enumeration areas and households. All adults aged 15 years and older who had slept in the household the night before were eligible for participation; participants completed an interview and HIV testing. We estimated incidence with the HIV-1 limiting antigen avidity enzyme immunoassay combined with viral load and examined the association between demographic and behavioural variables (including characteristics of cohabitating mothers and sexual partners, when available) and prevalence and incidence among AGYW using logistic regression, incorporating survey weights. FINDINGS: We interviewed 8824 households, including 2358 AGYW who were tested for HIV infection. Weighted HIV prevalence was 11.1% (95% CI 9.7-12.5) in the overall population (273 of 2358 AGYW), 5.7% (4.1-7.2) in adolescent girls aged 15-19 years (64 of 1156), and 16.7% (14.4-19.0) in women aged 20-24 years (209 of 1212). Annualised HIV incidence was 1.8% (0.8-2.8). Correlates of prevalent infection include reporting a history of anal sex (adjusted odds ratio [aOR] 3.08, 1.11-8.57), having lived outside Lesotho in the past year (1.86, 1.01-3.42), having a partner suspected or known to be HIV positive (11.7, 6.0-22.5), and having two or more lifetime sexual partners (1.84, 1.21-2.78, for 2-3 lifetime sexual partners; 2.44, 1.45-4.08, for >/=4 lifetime sexual partners). For the 570 AGYW living with their mothers, maternal education was negatively associated with HIV prevalence in their daughters (aOR 0.36, 0.15-0.82, per increase in level attended). For AGYW with a cohabitating partner, the factors associated with AGYW infection were partner age (OR 4.54, 1.30-15.80, for partners aged 35-49 years, although the OR was no longer significant when adjusted for HIV status of partner), HIV status (aOR 11.22, 4.05-31.05), lack of viral load suppression (OR 0.16, 0.04-0.66), and partner employment in the past year (aOR 3.41, 1.12-10.42). INTERPRETATION: The findings confirm the importance of improving the treatment cascade in male partners and targeting preventive interventions to AGYW who are at increased risk. A regional approach to prevention could mitigate the effect of migration on transnational spread of HIV. FUNDING: President’s Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

      8. Operationalizing a data to care strategy in Michigan through cross-agency collaborationsexternal icon
        Macomber KE, Viall A, Ramakrishnan V, Wilson J, Brandt MG, Kinsinger L, Kreiner M, Curtis T, Copeland R, Staudacher A, Neff D.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S69-s73.
        BACKGROUND: For persons with HIV infection (PWH), viral load suppression is essential to maintaining health and reducing the likelihood of HIV transmission. Data to Care (D2C) is an important strategy for improving HIV outcomes but may be resource-intensive to execute. SETTING: In 2016, Michigan joined the HIV Health Improvement Affinity Group to strengthen D2C partnerships between its Medicaid and HIV program. Goals included establishing routine data sharing, matching data sources to understand health outcomes, and collaborating to turn data into action. METHODS: Michigan established data use agreements to assess gaps in care for PWH enrolled in Medicaid. The HIV Surveillance Program used Link Plus to match surveillance records on PWH to Medicaid’s active beneficiary file to identify PWH who were beneficiaries as of December 31, 2015. RESULTS: Matching the 2,300,877 Michigan Medicaid beneficiaries with the 15,845 PWH in HIV surveillance yielded 4822 matched PWH enrolled in Medicaid in 2015. Of Medicaid beneficiaries with HIV, 597 had no evidence of receiving HIV care, representing 20% of all Michigan residents with HIV and not in care in 2015. CONCLUSION: D2C is an effective strategy for improving HIV care continuum outcomes but can be relatively inefficient if implementation models rely solely on public health infrastructure. Through the HIV Health Improvement Affinity Group, Michigan’s Medicaid and HIV programs leveraged their combined data assets to evaluate and improve care quality and outcomes for PWH on Medicaid. Partnerships between Medicaid and public health offer attractive mechanisms for potentially increasing efficiency and effectiveness of D2C investments.

      9. Progress toward poliomyelitis eradication – Afghanistan, January 2018-May 2019external icon
        Martinez M, Shukla H, Nikulin J, Mbaeyi C, Jorba J, Ehrhardt D.
        MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):729-733.
        Since October 2016, Afghanistan and Pakistan have been the only countries with reported cases of wild poliovirus type 1 (WPV1) (1). In Afghanistan, although the number of cases had declined during 2013-2016, the polio eradication program experienced challenges during 2017-2019. This report describes polio eradication activities and progress in Afghanistan during January 2018-May 2019 and updates previous reports (2,3). During May-December 2018, insurgent groups (antigovernment elements) banned house-to-house vaccination in most southern and southeastern provinces, leaving approximately 1 million children inaccessible to oral poliovirus vaccine (OPV) administration. During January-April 2019, vaccination targeting children at designated community sites (site-to-site vaccination) was permitted; however, at the end of April 2019, vaccination campaigns were banned nationally. During 2018, a total of 21 WPV1 cases were reported in Afghanistan, compared with 14 during 2017. During January-May 2019, 10 WPV1 cases were reported (as of May 31), compared with eight during January-May 2018. Sewage sample-testing takes place at 20 sites in the highest-risk areas for poliovirus circulation; 17 have detected WPV1 since January 2017, primarily in the southern and eastern provinces. Continued discussion with antigovernment elements to resume house-to-house campaigns is important to achieving polio eradication in Afghanistan. To increase community support for vaccination, collaboration among humanitarian service agencies to address other urgent health and basic needs is critical.

      10. Data to care: Lessons learned from delivering technical assistance to 20 health departmentsexternal icon
        Mokotoff ED, Green Ruth K, Benbow N, Sweeney P, Nelson Sapiano T, McNaghten AD.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S74-s79.
        BACKGROUND: Data to Care (D2C) is a public health strategy that uses HIV surveillance and other data to identify persons living with HIV who are “not in care” to link them to medical care or other services. To support health department implementation of D2C, the Centers for Disease Control and Prevention supported direct technical assistance (TA) to build health department D2C capacity. METHODS: Between 2013 and 2017, 2 contracting organizations worked with the Centers for Disease Control and Prevention to provide intensive D2C TA to 20 US health departments. A requirement for applying for TA was the mandatory reporting of all CD4 T-lymphocyte and HIV viral load test results by laboratories to the health department’s HIV surveillance system. Health department selection criteria included organizational factors; jurisdiction laws/policies about data confidentiality and sharing; and HIV morbidity level. RESULTS: Peer-to-peer consultation, technical consultation, training, information transfer, materials development, materials distribution, and technology transfer were methods used for delivering TA based on the health department’s needs and preferences. TA supported health department progress in areas such as confidentiality and data security, stakeholder engagement, quality of HIV surveillance data, data sharing, staffing resources, creating “not-in-care” lists, and program evaluation. CONCLUSION: Developing D2C programs is not a linear process, and there is no one standardized approach. Health departments made the most rapid progress when TA included peer-to-peer support among health departments. Participation in this project facilitated, in some cases for the first time, collaboration between staff across HIV surveillance, prevention, and care programs.

      11. Late diagnosis of hepatitis C virus infection, 2014-2016: continuing missed intervention opportunitiesexternal icon
        Moorman AC, Xing J, Rupp LB, Gordon SC, Lu M, Spradling PR, Boscarino JA, Schmidt MA, Daida YG, Teshale EH.
        Am J Manag Care. 2019 Aug;25(8):369-374.
        OBJECTIVES: Chronic hepatitis C virus (HCV) infection is typically asymptomatic until severe liver disease occurs and even then can remain undiagnosed for some time; thus, screening and treatment of asymptomatic persons are needed to prevent poor outcomes. In a previous analysis of data from between 2006 and 2011, we found that 17% of newly diagnosed HCV infections in 4 large health systems were among persons with cirrhosis and/or end-stage liver disease, termed “late diagnosis.” We sought to determine the proportion with late diagnosis during 2014-2016, after release of CDC baby boomer (1945-1965 birth cohort) testing guidelines in 2012. STUDY DESIGN: The cohort was based on analysis of electronic health records and administrative data of about 2.7 million patients visiting the same healthcare systems during 2014-2016. METHODS: Among persons with newly diagnosed chronic HCV infection during 2014-2016, we analyzed data collected up to January 1, 2017. RESULTS: Among 2695 patients with newly diagnosed HCV infection, 576 (21.4%) had late diagnosis. Most were born between 1945 and 1965 (n = 1613 [59.9%]), and among these, 27.6% had late diagnosis. Patients with versus without late diagnosis had equally lengthy prediagnosis observation in the health systems (mean and median, 9.1 and 9.1 vs 8.3 and 7.8 years, respectively) but were more likely to have a postdiagnosis hospitalization (32.5% vs 12.5%; P <.001) with greater number of hospital days (358.8 vs 78.5 per 100 person-years; P <.001). CONCLUSIONS: More than one-fifth of patients with newly diagnosed HCV infection during 2014-2016-and more than a quarter of those born between 1945 and 1965-had late diagnosis despite many years of in-system care, an increase of 5 percentage points since 2006-2011, after the interim initiation of age-based screening recommendations. Our data highlight missed opportunities for diagnosis and therapeutic intervention before the onset of severe liver disease, which is associated with high cost and diminished outcomes.

      12. Improving HIV surveillance data by using the ATra Black Box System to assist regional deduplication activitiesexternal icon
        Ocampo JM, Hamp A, Rhodes A, Smart JC, Pemmaraju R, Poschman K, Hess KL, Bhattacharjee R, Flynn C, Anderson BJ, Dowling JE, Maccormack F, Doshi R, Lum G, Maddox L, Moncur B, Barnhart JE, Maxwell J, Aurand SB, Hogan V, Wills D, Prowell S, Kassaye SG, Karn HE, Laffoon BT, Collmann J.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S13-s19.
        BACKGROUND: Focused attention on Data to Care underlines the importance of high-quality HIV surveillance data. This study identified the number of total duplicate and exact duplicate HIV case records in 9 separate Enhanced HIV/AIDS Reporting System (eHARS) databases reported by 8 jurisdictions and compared this approach to traditional Routine Interstate Duplicate Review resolution. METHODS: This study used the ATra Black Box System and 6 eHARS variables for matching case records across jurisdictions: last name, first name, date of birth, sex assigned at birth (birth sex), social security number, and race/ethnicity, plus 4 system-calculated values (first name Soundex, last name Soundex, partial date of birth, and partial social security number). RESULTS: In approximately 11 hours, this study matched 290,482 cases from 799,326 uploaded records, including 55,460 exact case pairs. Top case pair overlaps were between NYC and NYS (51%), DC and MD (10%), and FL and NYC (6%), followed closely by FL and NYS (4%), FL and NC (3%), DC and VA (3%), and MD and VA (3%). Jurisdictions estimated that they realized a combined 135 labor hours in time efficiency by using this approach compared with manual methods previously used for interstate duplication resolution. DISCUSSION: This approach discovered exact matches that were not previously identified. It also decreased time spent resolving duplicated case records across jurisdictions while improving accuracy and completeness of HIV surveillance data in support of public health program policies. Future uses of this approach should consider standardized protocols for postprocessing eHARS data.

      13. Lessons learned from community-based tuberculosis case-finding in western Kenyaexternal icon
        Okelloh D, Achola M, Opole J, Ogwang C, Agaya J, Sifuna P, McHembere W, Cowden J, Heilig M, Borgdorff MW, Yuen CM, Cain KP.
        Public Health Action. 2019 Jun 21;9(2):53-57.
        Setting: Although Kenya has a high burden of tuberculosis (TB), only 46% of cases were diagnosed in 2016. Objective: To identify strategies for increasing attendance at community-based mobile screening units. Design: We analysed operational data from a cluster-randomised trial, which included community-based mobile screening implemented during February 2015-April 2016. Community health volunteers (CHVs) recruited individuals with symptoms from the community, who were offered testing for human immunodeficiency virus (HIV) and sputum collection for Xpert((R)) MTB/RIF testing. We compared attendance across different mobile unit sites using Wilcoxon rank-sum test. Results: A total of 1424 adults with symptoms were screened at 25 mobile unit sites. The median total attendance among sites was 54 (range 6-134, interquartile range [IQR] 24-84). The median yields of TB diagnoses and new HIV diagnoses were respectively 2.4% (range 0.0-16.7, IQR 0.0-5.3) and 2.5% (range 0.0-33.3, IQR 1.2-4.2). Attendance at urban sites was variable; attendance at rural sites where CHVs were paid a daily minimum wage was significantly higher than at rural sites where CHVs were paid a nominal monthly stipend (P < 0.001). Conclusion: Mobile units were most effective and efficient when implemented as a single event with community health workers who are paid a daily wage.

      14. Human papillomavirus-attributable cancers – United States, 2012-2016external icon
        Senkomago V, Henley SJ, Thomas CC, Mix JM, Markowitz LE, Saraiya M.
        MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):724-728.
        Human papillomavirus (HPV) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx (1).* Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer (2). In the United States, the 9-valent HPV vaccine (9vHPV) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts. CDC analyzed data from the U.S. Cancer Statistics (USCS)(dagger) to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012-2016 (3,4). An average of 43,999 HPV-associated cancers were reported annually, and an estimated 34,800 (79%) of those cancers were attributable to HPV. Of these 34,800 cancers, an estimated 32,100 (92%) were attributable to the types targeted by 9vHPV, with 19,000 occurring among females and 13,100 among males. The most common were cervical (9,700) and oropharyngeal cancers (12,600). The number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 to 3,270 per year. HPV vaccination is an important strategy that could prevent these cancers, but during 2018, only half of adolescents were up to date on HPV vaccination (5). These surveillance data from population-based cancer registries can be used to inform the planning for, and monitor the long-term impact of, HPV vaccination and cancer screening efforts nationally and within states.

      15. HIV data to care-using public health data to improve HIV care and preventionexternal icon
        Sweeney P, DiNenno EA, Flores SA, Dooley S, Shouse RL, Muckleroy S, Margolis AD.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S1-s5.
        BACKGROUND: “Data to Care” (D2C) is a public health strategy that uses surveillance and other data to improve continuity of HIV care for persons with HIV (PWH) by identifying those who are in need of medical care or other services and facilitating linkage to these services. The primary goal of D2C is to increase the number of PWH who are engaged in care and virally suppressed. METHODS: Data to Care can be implemented using several approaches. Surveillance-based D2C is usually initiated by health departments, using HIV surveillance and other data to identify those not in care. Health care providers may also initiate D2C by identifying patients who may have fallen out of care and working collaboratively with health departments to investigate, locate, and relink the patients to medical care or other needed services. RESULTS: Although D2C is a relatively new strategy, health department D2C programs have reported both promising results (eg, improved surveillance data quality and successful linkage to or re-engagement in care for PWH) and challenges (eg, incomplete or inaccurate data in surveillance systems, barriers to data sharing, and limitations of existing data systems). CONCLUSIONS: Data to Care is expected to enable health departments to move closer toward achieving national HIV prevention goals. However, additional information on appropriate implementation practices at each step of the D2C process is needed. This JAIDS Special Supplement explores how CDC funding to state health departments (eg, technical assistance and demonstration projects), and partnerships across federal agencies, are advancing our knowledge of D2C.

    • Disaster Control and Emergency Services
      1. Medical countermeasure stockpiles in the United States are designed to support healthcare workers and the public during public health emergencies; they include supplies of personal protective equipment (PPE). As part of typical PPE manufacturing processes, appropriate test methods are used to ensure that the devices provide adequate protective performance. At the time of manufacture, performance is often measured and weighed against an objective standard of quality, resulting in a pass or fail attribute being assigned to individual PPE items and thence to production lots. Incorporating periodic performance testing for stockpiled PPE can ensure that they maintain their protective qualities and integrity over time while in storage. There is an absence of guidance regarding how to design quality assurance programs for stockpiled PPE. The applicability of the Lot Quality Assurance Sampling (LQAS) approach to stockpiled PPE was examined in a previous study that compared and contrasted different sample sizes in recovering the true percentage of defective units in large lots in the LQAS framework. The current study carries this line of inquiry forward by integrating PPE degradation over time and comparing different sampling time intervals in recovering the true underlying degradation rate. The results suggest that product degradation is more easily detected when tested at shorter time intervals and for higher degradation rates. They further suggest that sampling interval groupings can be made based on the proficiency with which they recover the true underlying degradation rate.

      2. Heat-related knowledge, perceptions, and barriers among oil spill cleanup respondersexternal icon
        Jacklitsch BL, King KA, Vidourek RA, Merianos AL.
        Safety Science. 2019 2019/12/01/;120:666-671.
        Despite increased risk for heat-related illnesses (HRI) among oil spill cleanup responders, little research has examined factors related to the issue. This study assessed occupational heat-related knowledge, perceptions, and barriers among responders during cleanup activities. A total of 65 responders completed an online survey which examined occupational heat stress during cleanup activities. Of the respondents, most had 25 or more years’ experience, worked for companies with 19 or fewer employees, were not classified as safety and health professionals, had a Bachelor?s degree or higher, and worked in the northern or central regions of the United States. While most respondents were knowledgeable of heat stress, the items in which respondents were least knowledgeable were: identifying the difference between heat exhaustion and heat stroke, the appropriate use of salt tablets, the effects of air conditioning on acclimatization, and previous heat-related illness (HRI) as a risk factor. For knowledge of heat stress, there was a significant difference in the employment classification scores for non-safety and health professionals and safety and health professionals. Respondents reported that they tended to perceive that heat stress can be severe and that HRI?s may affect workers. Regarding self-efficacy, most respondents felt confident in contacting emergency medical services for HRI, recognizing signs and symptoms of HRI, and knowing what to do if a coworker became ill. Oil spill cleanup responders are at high risk for HRI, injury, and death and findings illustrate the need to improve heat stress knowledge within training programs with emphasis on non-professionals.

      3. Mechanisms of resiliency against depression following the Deepwater Horizon oil spillexternal icon
        Kaufman JA, Goldman ZE, Sharpe JD, Wolkin AF, Gribble MO.
        J Environ Psychol. 2019 ;65.
        Prior studies of oil spills have reported adverse impacts on mental health, but have not examined some potentially important moderators. In this cross-sectional analysis of n = 38,361 responses to the 2010-2011 Gulf States Population Survey, we assessed the association of direct oil contact with depression severity following the Deepwater Horizon oil spill, and modification by self-mastery, emotional support, and cleanup participation using Tobit regression models accounting for the complex survey design. Oil contact was associated with increased depression severity. Among respondents with oil contact, depression was more severe for those reporting lower self-mastery. However, respondents with oil contact had lower depression severity if they participated in cleanup efforts, compared to exposed individuals who did not participate. This potential protective effect was larger for respondents with lower self-mastery. Our results are consistent with the notion that participation in recovery efforts may reduce depressive symptoms following oil spills among impacted individuals.

    • Environmental Health
      1. Per- and polyfluoroalkyl substance plasma concentrations and bone mineral density in midchildhood: A cross-sectional study (Project Viva, United States)external icon
        Cluett R, Seshasayee SM, Rokoff LB, Rifas-Shiman SL, Ye X, Calafat AM, Gold DR, Coull B, Gordon CM, Rosen CJ, Oken E, Sagiv SK, Fleisch AF.
        Environ Health Perspect. 2019 Aug;127(8):87006.
        BACKGROUND: Identifying factors that impair bone accrual during childhood is a critical step toward osteoporosis prevention. Exposure to per- and polyfluoroalkyl substances (PFASs) has been associated with lower bone mineral density, but data are limited, particularly in children. METHODS: We studied 576 children in Project Viva, a Boston-area cohort of mother/child pairs recruited prenatally from 1999 to 2002. We quantified plasma concentrations of several PFASs and measured areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) in midchildhood. We used linear regression to examine associations between plasma concentrations of individual PFASs and aBMD z-score. We used weighted quantile sum (WQS) regression to examine the association of the PFAS mixture with aBMD z-score. All models were adjusted for maternal age, education, annual household income, census tract median household income, and child age, sex, race/ethnicity, dairy intake, physical activity, and year of blood draw. RESULTS: Children were [[Formula: see text]] [Formula: see text] of age. The highest PFAS plasma concentrations were of perfluorooctanesulfonic acid (PFOS) {median [interquartile range (IQR)]: 6.4 (5.6) ng/mL} and perfluorooctanoic acid (PFOA) [median (IQR): 4.4 (3.2) ng/mL]. Using linear regression, children with higher plasma concentrations of PFOA, PFOS, and perfluorodecanoate (PFDA) had lower aBMD z-scores [e.g., [Formula: see text]: [Formula: see text]; 95% confidence interval (CI): [Formula: see text], [Formula: see text] per doubling of PFOA]. The PFAS mixture was negatively associated with aBMD z-score ([Formula: see text]: [Formula: see text]; 95% CI: [Formula: see text], [Formula: see text] per IQR increment of the mixture index). CONCLUSIONS: PFAS exposure may impair bone accrual in childhood and peak bone mass, an important determinant of lifelong skeletal health.

      2. Environmental phthalate exposure and preterm birth in the PROTECT birth cohortexternal icon
        Ferguson KK, Rosen EM, Rosario Z, Feric Z, Calafat AM, McElrath TF, Velez Vega C, Cordero JF, Alshawabkeh A, Meeker JD.
        Environ Int. 2019 Aug 17;132:105099.
        BACKGROUND: Preterm birth is a global public health issue and rates in Puerto Rico are consistently among the highest in the USA. Exposures to environmental contaminants might be a contributing factor. METHODS: In a preliminary analysis from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (n=1090), we investigated the association between urinary phthalate metabolite concentrations measured at three study visits (targeted at 20, 24, and 28weeks of gestation) individually and averaged over pregnancy with gestational age at delivery and preterm birth. We additionally assessed differences in associations by study visit and among preterm births with a spontaneous delivery. RESULTS: Compared to women in the general USA population, urinary concentrations of metabolites of di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP) were higher among pregnant women in Puerto Rico. Interquartile range (IQR) increases in pregnancy-averages of urinary metabolites of DBP and DiBP were associated with shorter duration of gestation and increased odds of preterm birth. An IQR increase in mono-n-butyl phthalate (MBP), a metabolite of DBP, was associated with 1.55days shorter gestation (95% confidence interval [CI]=-2.68, -0.42) and an odds ratio (OR) of 1.42 (95% confidence interval [CI]: 1.07, 1.88) for preterm birth. An IQR increase in mono-isobutyl phthalate (MiBP), a metabolite of DiBP, was associated with 1.16days shorter gestation (95% CI=-2.25, -0.08) and an OR of 1.32 (95% CI: 1.02, 1.71) for preterm birth. Associations were greatest in magnitude for urinary concentrations measured at the second study visit (median 23weeks gestation). DiBP metabolite associations were greatest in magnitude in models of spontaneous preterm birth. No associations were detected with other phthalate metabolites, including those of di-2-ethylhexyl phthalate. CONCLUSION: Among pregnant women in the PROTECT cohort, DBP and DiBP metabolites were associated with increased odds of preterm birth. These exposures may be contributing to elevated rates of preterm birth observed in Puerto Rico.

      3. Urinary triclosan concentrations and semen quality among men from a fertility clinicexternal icon
        Nassan FL, Minguez-Alarcon L, Williams PL, Dadd R, Petrozza JC, Ford JB, Calafat AM, Hauser R.
        Environ Res. 2019 Aug 6;177:108633.
        BACKGROUND: Triclosan, a widely-used antimicrobial in personal care products, has shown endocrine disrupting activity in experimental studies. However, there is limited evidence from epidemiologic studies on health effects. OBJECTIVE: To examine the association between urinary triclosan concentrations and semen quality. METHODS: A total of 262 men enrolled in the Environmental and Reproductive Health (EARTH) Study provided 581 paired urine and semen samples (2009-2017). Urinary triclosan concentrations were quantified and semen analysis was evaluated according to WHO guidelines. We used linear mixed regression models to estimate the associations between specific gravity-adjusted urinary triclosan concentrations with semen parameters, with a random intercept to account for multiple samples per man and adjusting for age, body mass index (BMI), smoking, physical activity, sexual abstinence time, and season and year of samples’ collection. RESULTS: Men had a mean (standard deviation) age of 36.6 (5.24) years and BMI of 27.9 (5.94) kg/m(2). Seventy four percent of the samples had detectable (>2.3mug/L) concentrations. We did not observe significant dose response trends between SG-adjusted urinary triclosan concentrations and semen parameters. However, in the adjusted analysis, compared to men with non-detectable triclosan concentrations in the lowest quartile, those in the second, third, and fourth quartiles had -1.32% (95%CI: -2.04, -0.59), -0.91% (95%CI: -1.63, -0.18), and -0.46% (95%CI: -1.25, 0.33) lower percent morphologically normal sperm, respectively. Similarly, a lower percentage of morphologically normal sperm was found among men with detectable triclosan concentrations, compared to men with non-detectable triclosan [-0.96% (95% CI: -1.57, -0.35)]. In sensitivity analyses, there was stronger negative associations on the percent morphologically normal sperm in the earlier time period due to the significant negative trend in detectable triclosan concentrations over time. CONCLUSION: Despite the lack of observed dose response relationship, we found consistent patterns of lower percent morphologically normal sperm for men with urinary triclosan in the 2nd or 3rd quartile compared to undetectable concentrations.This association was stronger for samples obtained prior to 2013 when triclosan was more often detectable in urine.

      4. Etiological contact allergen chemical identification and confirmationexternal icon
        Siegel PD, Law BF, Warshaw EM.
        Dermatitis. 2019 Aug 19.
        Identification of the etiological chemical agent(s) associated with a case(s) of allergic contact dermatitis (ACD) is important for both patient management and public health surveillance. Traditional patch testing can identify chemical allergens to which the patient is allergic. Confirmation of allergen presence in the causative ACD-associated material is presently dependent on labeling information, which may not list the allergenic chemical on the product label or safety data sheet. Dermatologists have expressed concern over the lack of laboratory support for chemical allergen identification and possibly quantification from patients’ ACD-associated products. The aim of the study was to provide the clinician a primer to better understand the analytical chemistry of contact allergen confirmation and unknown identification, including types of analyses, required instrumentation, identification levels of confidence decision tree, limitations, and costs.

    • Epidemiology and Surveillance
      1. We discuss alternative estimators of the population total given a dual-frame random-digit-dial (RDD) telephone survey in which samples are selected from landline and cell phone sampling frames. The estimators are subject to sampling and nonsampling errors. To reduce sampling variability when an optimum balance of landline and cell phone samples is not feasible, we develop an application of shrinkage estimation. We demonstrate the implications for survey weighting of a differential nonresponse mechanism by telephone status. We illustrate these ideas using data from the National Immunization Survey-Child, a large dual-frame RDD telephone survey sponsored by the Centers for Disease Control and Prevention and conducted to measure the vaccination status of American children aged 19 to 35 months.

    • Food Safety
      1. Outbreak of Salmonella Newport infections with decreased susceptibility to azithromycin linked to beef obtained in the United States and soft cheese obtained in Mexico – United States, 2018-2019external icon
        Plumb ID, Schwensohn CA, Gieraltowski L, Tecle S, Schneider ZD, Freiman J, Cote A, Noveroske D, Kolsin J, Brandenburg J, Chen JC, Tagg KA, White PB, Shah HJ, Francois Watkins LK, Wise ME, Friedman CR.
        MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):713-717.
        In September 2018, CDC identified Salmonella enterica serotype Newport (Newport) infections that were multidrug resistant (MDR), with decreased susceptibility to azithromycin, a recommended oral treatment agent. Until 2017, decreased susceptibility to azithromycin had occurred in fewer than 0.5% of Salmonella isolates from U.S. residents. This report summarizes the investigation of a multistate MDR Salmonella outbreak conducted by CDC, state and local health departments, and the U.S. Department of Agriculture’s Food Safety and Inspection Service. During June 2018-March 2019, 255 cases of infection with the outbreak strain were identified in 32 states; 43% of patients (89 of 206 with information on travel) reported recent travel to Mexico. Infections were linked to consumption of soft cheese obtained in Mexico and beef obtained in the United States. Consumers should avoid eating soft cheese that could be made from unpasteurized milk, regardless of the source of the cheese. When preparing beef, a food thermometer should be used to ensure that appropriate cooking temperatures are reached. When antibiotic treatment is needed for a patient, clinicians should choose antibiotics based on susceptibility testing wherever possible.

      2. Swallowing problems and dietary supplements: Data From U.S. Food and Drug Administration Adverse Event Reports, 2006-2015external icon
        Punzalan C, Budnitz DS, Chirtel SJ, Geller AI, Jones OE, Mozersky RP, Wolpert B.
        Ann Intern Med. 2019 Aug 20.

        [No abstract]

    • Health Disparities
      1. There is disproportionate risk for violence conditioned on inequities due to race, socioeconomic status, gender, and where people live. Consequently, some communities are more vulnerable to violence and its repercussions than other communities. This study aims to share indicators that might be useful for violence prevention researchers interested in measuring structural or social determinants that position communities for differential risk of experiencing violence. An existing database of indicators identified in a previous review was reassessed for measures of factors that shape community structures and conditions, which place people at risk for violence. Indicators of 86 community constructs are reported. These indicators may help to advance the field by offering innovative metrics that can be used to investigate further the structural and social determinants that serve as root causes of inequities in violence risk.

      2. A housing mobility program’s impacts on teen and young adult parentingexternal icon
        Fuller TR, Sciandra M, Koumans EH, Boulet SL, Warner L, Cox S, Gennetian LA.
        SSM – Population Health. 2019 ;9.
        Objective: To assess the impact of Moving to Opportunity for Fair Housing Demonstration Program (MTO) implemented in 1994 in five U.S. cities (Baltimore, Boston, Chicago, Los Angeles, and New York City) on teen births. Methods: We analyzed baseline and long-term evaluation data for youth (ages 13-20) and young adults (ages 21-30) (N = 7861) who were children or teens at baseline. We used regression analyses to estimate the impact of housing vouchers on having a teen birth. Results: Overall, MTO had no significant effect on teen births. However, among young adults whose parent had a child before age 20, the proportion with a teen birth themselves was 21% lower among those offered housing vouchers to low-poverty neighborhoods with no restrictions compared to those not offered housing vouchers (p < 0.05). Conclusion: MTO appeared to decrease intergenerational teen births among young adults. Further exploration of housing relocation may help untangle risks and protective factors for reducing intergenerational teen births. Public health implications: Reducing intergenerational teen births is important, especially among those facing economic, environmental, and health risks. Comprehensive programs addressing multiple social determinants of health are vital to reducing teen births.

      3. Societal determinants of violent death: The extent to which social, economic, and structural characteristics explain differences in violence across Australia, Canada, and the United Statesexternal icon
        Wilkins NJ, Zhang X, Mack KA, Clapperton AJ, Macpherson A, Sleet D, Kresnow-Sedacca MJ, Ballesteros MF, Newton D, Murdoch J, Mackay JM, Berecki-Gisolf J, Marr A, Armstead T, McClure R.
        SSM Popul Health. 2019 Aug;8:100431.
        In this ecological study, we attempt to quantify the extent to which differences in homicide and suicide death rates between three countries, and among states/provinces within those countries, may be explained by differences in their social, economic, and structural characteristics. We examine the relationship between state/province level measures of societal risk factors and state/province level rates of violent death (homicide and suicide) across Australia, Canada, and the United States. Census and mortality data from each of these three countries were used. Rates of societal level characteristics were assessed and included residential instability, self-employment, income inequality, gender economic inequity, economic stress, alcohol outlet density, and employment opportunities). Residential instability, self-employment, and income inequality were associated with rates of both homicide and suicide and gender economic inequity was associated with rates of suicide only. This study opens lines of inquiry around what contributes to the overall burden of violence-related injuries in societies and provides preliminary findings on potential societal characteristics that are associated with differences in injury and violence rates across populations.

    • Health Economics
      1. Shape Up Somerville’s return on investment: Multi-group exposure generates net-benefits in a child obesity interventionexternal icon
        Coffield E, Nihiser A, Carlson S, Collins J, Cawley J, Lee S, Economos C.
        Preventive Medicine Reports. 2019 ;16.
        Community-based interventions may reduce and prevent childhood obesity by transforming the environments in which children live, learn, and play through a series of interventions implemented throughout the community that encourage healthy behaviors. While empirical support is building for the effectiveness of such interventions, little is known about the economic costs and benefits of community-wide childhood obesity interventions. This study examined whether the benefits of a community-wide, child-focused, obesity prevention intervention, Shape Up Somerville: Eat Smart Play Hard (SUS), exceeded its costs by estimating its return on investment. The SUS intervention study occurred in Somerville, Massachusetts (and in two additional geographic areas, which were the study’s control group) during the 2003/04 and 2004/05 school years. We estimated SUS’s costs using SUS data over the two-year intervention. We estimated benefits (i.e., healthcare costs and productivity losses averted for children and their parents) over a ten-year time horizon using SUS effectiveness results and other sources. SUS generated an estimated $1.51 in savings for every $1.00 invested in the program (return on investment of $0.51). Over ten years, the estimated costs averted were over $500,000 with net benefits of $197,120 (2014 dollars). SUS was estimated to be a cost-saving intervention when examined over a ten-year time horizon. The excess benefits generated by SUS likely arose from the community-wide nature of the intervention which extended exposure (and estimated benefits) beyond children to parents as well. These results illustrate that allocating resources to community-wide, child-focused obesity prevention interventions may be a beneficial investment.

      2. Short-term outcomes and lessons learned from the federal HIV Health Improvement Affinity Group for State Medicaid/Children’s Health Insurance Program Agencies and state health departmentsexternal icon
        Davies C, Klein PW, Okoye ID, Heitgerd J, Shapatava E, Ihiasota I, Browne MN, Viall A, Stockmann D, Hauck H.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S62-s68.
        BACKGROUND: Medicaid is the single largest source of health care coverage for people living with HIV (PLWH) in the United States. Therefore, high-quality HIV care and associated viral suppression among Medicaid beneficiaries have the potential to greatly impact the HIV epidemic. The HIV Health Improvement Affinity Group (HHIAG) supported state efforts to improve health outcomes for PLWH enrolled in Medicaid through new or enhanced collaborations between state public health departments and state Medicaid agencies. METHODS: Supported by multiple federal health agencies for 1 year, state health department and Medicaid staff from 19 states participated in state-to-state learning and sharing of promising approaches. This evaluation assessed the HHIAG’s processes, short-term outcomes, and lessons learned through review of state materials, a web survey, and telephone interviews. RESULTS: Of the 19 states, 13 (68%) ultimately established new, or refined existing, data-sharing agreements between Medicaid and public health departments. Nearly all states with data-sharing agreements successfully matched the data or streamlined the data-matching process (n = 12/13). Two-thirds of states (67%, n = 8/12) with matched data generated an HIV care continuum for state Medicaid/Children’s Health Insurance Program beneficiaries; 75% (n = 6/8) of these states also initiated quality improvement activities. CONCLUSIONS: The HHIAG created an unique opportunity for multiple federal agencies and states to collaborate and implement data-driven, state-specific solutions to improve care delivery and, ultimately, clinical outcomes for PLWH. The HHIAG model has the potential to be replicated to address other public health issues that cross agency and institutional boundaries, such as hepatitis C.

      3. A limited number of patients, commonly termed super-utilizers, account for the bulk of health care expenditures. Multiple criteria for identifying super-utilizers exist, but no standard methodology is available for determining which criteria should be used for a specific population. Application is often arbitrary, and poorly aligned super-utilizer criteria might result in misallocation of resources and diminished effects of interventions. This study sought to apply an innovative, data-driven approach to classify super-utilizers among Utah Medicaid beneficiaries. The authors conducted a literature review of research methods to catalogue applied super-utilizer criteria. The most commonly used criteria were applied to Utah Medicaid beneficiaries enrolled during July 1, 2016-June 30, 2017, using their previous 12 months of claims data (N = 309,921). The k-medoids algorithm cluster analysis was used to find groups of beneficiaries with similar characteristic based on criteria from the literature. In all, 180 super-utilizer criteria were identified in the literature, 21 of which met the inclusion criteria. When these criteria were applied to Utah Medicaid data, 5 distinct subpopulation clusters were found: non-super-utilizers (n = 163,118), beneficiaries with multiple chronic or mental health conditions (n = 68,054), beneficiaries with a single chronic health condition (n = 43,939), emergency department super-utilizers with chronic or mental health conditions (n = 7809), and beneficiaries with uncomplicated hospitalizations (n = 27,001). This study demonstrates how cluster analysis can aid in selecting characteristics from the literature that systematically differentiate super-utilizer groups from other beneficiaries. This methodology might be useful to health care systems for identifying super-utilizers within their patient populations.

      4. Implementing data to care – what are the costs for the health department?external icon
        Neblett Fanfair R, Shrestha RK, Randall L, Lucas C, Nichols L, Camp NM, Brady K, Jenkins H, Altice F, Villanueva M, DeMaria A.
        J Acquir Immune Defic Syndr. 2019 Sep 1;82 Suppl 1:S57-s61.
        BACKGROUND: The Cooperative Re-Engagement Controlled Trial (CoRECT) is a randomized controlled trial that uses a combined health department-provider data to care (D2C) model to identify out-of-care HIV-infected persons. We present cost data for programmatic aspects of the trial during the start-up period (first 30 days of the study). METHODS: We used microcosting methods to estimate health department start-up costs. We collected start-up cost data between September 2016 and December 2016; 3 health departments completed a form to capture expenses for the initial 30 days of study implementation; the start date varied by health department. All costs are expressed in 2016 US dollars. RESULTS: Among the 3 health departments, the total start-up costs ranged from $14,145 to $26,058. Total start-up labor hours ranged from 224 to 640 hours. CONCLUSIONS: As D2C expands nationally with cooperative agreement, PS 18-1802 health departments may be able to use a similar analysis to consider the labor, time, and resources needed to implement D2C within their jurisdiction.

    • Healthcare Associated Infections
      1. Effect of bismuth subsalicylate vs placebo on use of antibiotics among adult outpatients with diarrhea in Pakistan: A randomized clinical trialexternal icon
        Bowen A, Agboatwalla M, Pitz A, Salahuddin S, Brum J, Plikaytis B.
        JAMA Netw Open. 2019 Aug 2;2(8):e199441.
        Importance: Many of the 4.5 billion annual episodes of diarrhea are treated unnecessarily with antibiotics; prevalence of antibiotic resistance among diarrheal pathogens is increasing. Knowledge-based antibiotic stewardship interventions typically yield little change in antibiotic use. Objective: To compare antibiotic use among adult outpatients with diarrhea given bismuth subsalicylate (BSS) or placebo. Design, Setting, and Participants: This randomized clinical trial took place from April to October 2014. Participants were patients aged 15 to 65 years with acute, nonbloody diarrhea from 22 outpatient clinics in Karachi, Pakistan. Participants were interviewed about symptoms and health care utilization during the 5 days after enrollment. Group assignment was concealed from participants, field staff, and the statistician. Primary analysis occurred from August to September 2015. Interventions: Participants were randomly assigned (1:1) to receive BSS or placebo for 48 hours or less. Main Outcomes and Measures: Use of systemic antibiotics within 5 days of enrollment. Secondary outcomes included measures of duration and severity of illness. Results: Among eligible patients, 39 declined to participate, 440 enrolled, and 1 enrolled participant was lost to follow-up, for a total of 439 patients included in the analysis. Median (interquartile range) participant age was 32 (23-45) years and 187 (43%) were male. Two hundred twenty patients were randomized to BSS and 220 were randomized to placebo. Overall, 54 participants (12%) used systemic antibiotics (16% in the placebo group and 9% in the BSS group); all antibiotic use followed consultation with a physician. Use of any antibiotic was significantly lower in the BSS group (20 of 220 vs 34 of 219 patients; odds ratio [OR], 0.54; 95% CI, 0.30-0.98), as was use of fluoroquinolones (8 of 220 vs 20 of 219 patients; OR, 0.38; 95% CI, 0.16-0.88). Rates of care seeking and hospitalization were similar between groups and no difference was detected in timing of diarrhea resolution. However, those in the BSS group less commonly received intravenous rehydration (14 of 220 vs 27 of 219 patients; OR, 0.48; 95% CI, 0.25-0.95) and missed less work (median [interquartile range], 0 [0-1] vs 1 [0-1] day; P = .04) during follow-up. Conclusions and Relevance: This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea. Encouraging health care professionals in such settings to recommend BSS as frontline treatment for adults with diarrhea, and promoting BSS for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally. Trial Registration: identifier: NCT02047162.

      2. Creation of a geospatially explicit, agent-based model of a regional healthcare network with application to Clostridioides difficile infectionexternal icon
        Rhea S, Hilscher R, Rineer JI, Munoz B, Jones K, Endres-Dighe SM, DiBiase LM, Sickbert-Bennett EE, Weber DJ, MacFarquhar JK, Dubendris H, Bobashev G.
        Health Secur. 2019 Jul/Aug;17(4):276-290.
        Agent-based models (ABMs) describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. ABMs are increasingly used to study healthcare-associated infections (ie, infections acquired during admission to a healthcare facility), including Clostridioides difficile infection, currently the most common healthcare-associated infection in the United States. The overall burden and transmission dynamics of healthcare-associated infections, including C difficile infection, may be influenced by community sources and movement of people among healthcare facilities and communities. These complex dynamics warrant geospatially explicit ABMs that extend beyond single healthcare facilities to include entire systems (eg, hospitals, nursing homes and extended care facilities, the community). The agents in ABMs can be built on a synthetic population, a model-generated representation of the actual population with associated spatial (eg, home residence), temporal (eg, change in location over time), and nonspatial (eg, sociodemographic features) attributes. We describe our methods to create a geospatially explicit ABM of a major regional healthcare network using a synthetic population as microdata input. We illustrate agent movement in the healthcare network and the community, informed by patient-level medical records, aggregate hospital discharge data, healthcare facility licensing data, and published literature. We apply the ABM output to visualize agent movement in the healthcare network and the community served by the network. We provide an application example of the ABM to C difficile infection using a natural history submodel. We discuss the ABM’s potential to detect network areas where disease risk is high; simulate and evaluate interventions to protect public health; adapt to other geographic locations and healthcare-associated infections, including emerging pathogens; and meaningfully translate results to public health practitioners, healthcare providers, and policymakers.

    • Immunity and Immunization
      1. Immunogenicity of fractional-dose vaccine during a yellow fever outbreak – final reportexternal icon
        Casey RM, Harris JB, Ahuka-Mundeke S, Dixon MG, Kizito GM, Nsele PM, Umutesi G, Laven J, Kosoy O, Paluku G, Gueye AS, Hyde TB, Ewetola R, Sheria GK, Muyembe-Tamfum JJ, Staples JE.
        N Engl J Med. 2019 Aug 1;381(5):444-454.
        BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS: A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

      2. Predictors for influenza vaccination among Thai pregnant woman: The role of physicians in increasing vaccine uptakeexternal icon
        Kaoiean S, Kittikraisak W, Suntarattiwong P, Ditsungnoen D, Phadungkiatwatana P, Srisantiroj N, Asavapiriyanont S, Chotpitayasunondh T, Dawood FS, Lindblade KA.
        Influenza Other Respir Viruses. 2019 Aug 16.
        BACKGROUND: Physician recommendation and attitudes and beliefs of pregnant women toward influenza and vaccination may influence vaccine uptake during pregnancy. We examined how physician recommendation and health beliefs of pregnant women may jointly affect influenza vaccination during pregnancy. METHODS: Thai pregnant women aged >/=18 years and >13 gestational weeks attending antenatal care (ANC) clinics, and ANC physicians were recruited during May-August 2015. Women and physicians, linked using unique identifiers, provided data on demographic, health and work history, knowledge, attitudes, and beliefs toward influenza and vaccination, based on Health Belief Model constructs. Physicians also provided data on their practices in recommending influenza vaccination during pregnancy. Prevalence ratios for the association between knowledge, attitudes and beliefs of pregnant women, physician recommendation and documented receipt of vaccination within 30 days of the visit were calculated. RESULTS: Among 610 women, the median age was 27 years; 266 (44%) and 344 (56%) were in the second and third trimesters, respectively. Twenty-one (3%) had pre-existing conditions. Of 60 physicians with the median years of practice of 5; 17 (28%) reported frequently/usually/always recommending influenza vaccine to their pregnant patients, while 43 (72%) reported never/rarely/sometimes recommending the vaccine. Controlling for the pregnant women’s knowledge and beliefs, pregnant women whose physician recommended influenza vaccination were 2.3 times (95% confidence interval 1.4-3.8) more likely to get vaccinated. CONCLUSIONS: In this study, physician recommendation was the only significant factor associated with influenza vaccine uptake among Thai pregnant women. Understanding physicians’ motivation/barrier to recommending influenza vaccination to pregnant women may increase coverage.

      3. Factors associated with missed and delayed DTP3 vaccination in children aged 12-59 months in two communities in South Africa, 2012-2013external icon
        Mthiyane TN, Cohen C, Norris SA, Walaza S, Tempia S, Cohen AL, von Gottberg A, von Mollendorf C.
        S Afr Med J. 2019 ;109(8):562-569.
        Background. Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting. Objectives. To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12-59 months in two SA communities. Methods. We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged <5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression. Results. Of a total of 847 eligible children aged 12-59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7-23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4-6.3) or 2011 (aOR 2.7, 95% CI 1.3-5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3-0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6-7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged <5 years in a household (aOR 2.4, 95% CI 1.2-4.9) compared with one child, and household monthly income <ZAR500 (aOR 3.4, 95% CI 1.1-11.4) compared with >/=ZAR2 000. Conclusions. Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination.

      4. Measurement of birth outcomes in analyses of the impact of maternal influenza vaccinationexternal icon
        Rolfes MA, Vonglokham P, Khanthamaly V, Chitry B, Pholsena V, Chitranondh V, Mirza SA, Moen A, Bresee JS, Xeuatvongsa A, Olsen SJ.
        Influenza Other Respir Viruses. 2019 Aug 19.
        BACKGROUND: The estimated association of maternal influenza vaccination and birth outcomes may be sensitive to methods used to define preterm birth or small-for-gestational age (SGA). METHODS: In a cohort of pregnant women in Lao People’s Democratic Republic, we estimated gestational age from: (a) date of last menstrual period (LMP), (b) any prenatal ultrasound, (c) first trimester ultrasound, (d) Ballard Score at delivery, and (e) an algorithm combining LMP and ultrasound. Infants were classified as SGA at birth using a Canadian, global, and equation-based growth reference. We estimated the association of maternal influenza vaccination and birth outcomes, by influenza activity, using multivariable log-binomial regression and Cox proportional hazards regression with vaccination as a time-varying exposure. RESULTS: The frequency of preterm birth in the cohort varied by method to estimate gestational age, from 5% using Ballard Score to 15% using any ultrasound. Using LMP, any ultrasound, or the algorithm, we found statistically significant reductions in preterm birth among vaccinated women during periods of high influenza activity and statistically significant increases in SGA, using a Canadian growth reference. We did not find statistically significant associations with SGA when using global or equation-based growth references. CONCLUSIONS: The association of maternal influenza vaccination and birth outcomes was most affected by the choice of a growth reference used to define SGA at birth. The association with pre-term birth was present and consistent across multiple statistical approaches. Future studies of birth outcomes, specifically SGA, should carefully consider the potential for bias introduced by measurement choice.

      5. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years – United States, 2018external icon
        Walker TY, Elam-Evans LD, Yankey D, Markowitz LE, Williams CL, Fredua B, Singleton JA, Stokley S.
        MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):718-723.
        The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of persons aged 11-12 years to protect against certain diseases, including human papillomavirus (HPV)-associated cancers, meningococcal disease, and pertussis (1). A booster dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended at age 16 years, and serogroup B meningococcal vaccine (MenB) may be administered to persons aged 16-23 years (1). To estimate vaccination coverage among adolescents in the United States, CDC analyzed data from the 2018 National Immunization Survey-Teen (NIS-Teen) which included 18,700 adolescents aged 13-17 years.* During 2017-2018, coverage with >/=1 dose of HPV vaccine increased from 65.5% to 68.1%, and the percentage of adolescents up-to-date(dagger) with the HPV vaccine series increased from 48.6% to 51.1%, although the increases were only observed among males. Vaccination coverage increases were also observed for >/=1 MenACWY dose (from 85.1% to 86.6%) and >/=2 MenACWY doses (from 44.3% to 50.8%). Coverage with tetanus and reduced diphtheria toxoids and acellular pertussis vaccine (Tdap) remained stable at 89%. Disparities in coverage by metropolitan statistical area (MSA)( section sign) and health insurance status identified in previous years persisted (2). Coverage with >/=1 dose of HPV vaccine was higher among adolescents whose parents reported receiving a provider recommendation; however, prevalence of parents reporting receiving a recommendation for adolescent HPV vaccination varied by state (range = 60%-91%). Supporting providers to give strong recommendations and effectively address parental concerns remains a priority, especially in states and rural areas where provider recommendations were less commonly reported.

    • Laboratory Sciences
      1. Enteropathogen antibody dynamics and force of infection among children in low-resource settingsexternal icon
        Arnold BF, Martin DL, Juma J, Mkocha H, Ochieng JB, Cooley GM, Omore R, Goodhew EB, Morris JF, Costantini V, Vinje J, Lammie PJ, Priest JW.
        Elife. 2019 Aug 19;8.
        Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles demonstrated significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest antibody response can be used to measure population-level transmission of diverse enteropathogens in serologic surveillance.

      2. Development of a World Health Organization International Reference Panel for different genotypes of hepatitis E virus for nucleic acid amplification testingexternal icon
        Baylis SA, Hanschmann KO, Matsubayashi K, Sakata H, Roque-Afonso AM, Kaiser M, Corman VM, Kamili S, Aggarwal R, Trehanpati N, Gartner T, Thomson EC, Davis CA, da Silva Filipe A, Abdelrahman TT, Blumel J, Terao E.
        J Clin Virol. 2019 May 14.
        BACKGROUND: Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. OBJECTIVES: The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. STUDY DESIGN: The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1(st) World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. RESULTS: The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. CONCLUSIONS: Based on the results of the collaborative study the panel (code number 8578/13) was established as the “1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays” by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV.

      3. Strongyloidiasis is caused by the human infective nematodes Strongyloides stercoralis, Strongyloides fuelleborni subsp. fuelleborni and Strongyloides fuelleborni subsp. kellyi. The zoonotic potential of S. stercoralis and the potential role of dogs in the maintenance of strongyloidiasis transmission has been a topic of interest and discussion for many years. In Australia, strongyloidiasis is prevalent in remote socioeconomically disadvantaged communities in the north of the continent. Being an isolated continent that has been separated from other regions for a long geological period, description of diversity of Australian Strongyloides genotypes adds to our understanding of the genetic diversity within the genus. Using PCR and amplicon sequencing (Illumina sequencing technology), we sequenced the Strongyloides SSU rDNA hyper-variable I and hyper-variable IV regions using Strongyloides-specific primers, and a fragment of the mtDNA cox1 gene using primers that are broadly specific for Strongyloides sp. and hookworms. These loci were amplified from DNA extracted from Australian human and dog faeces, and one human sputum sample. Using this approach, we confirm for the first time that potentially zoonotic S. stercoralis populations are present in Australia, suggesting that dogs represent a potential reservoir of human strongyloidiasis in remote Australian communities.

      4. Distribution of Taenia solium diagnostic glycoproteins in the different developmental stages of the parasiteexternal icon
        Cruz-Rivera M, Torres J, Carrillo-Farga J, Wilkins PP, Flisser A, Mendlovic F.
        J Parasitol. 2019 Aug;105(4):642-650.
        Taenia solium is a helminth parasite that causes 2 diseases in humans: cysticercosis and taeniasis. The establishment of T. solium metacestodes in the central nervous system causes neurocysticercosis, while development of the adult tapeworm in the small intestine causes taeniasis. Serological diagnosis of neurocysticercosis is performed by Western blot with an enriched fraction of glycoproteins that has been extensively used for clinical diagnosis and epidemiological surveys. The lectin-bound fraction that is used for this assay contains 7 antigenic glycoproteins. These antigenic proteins are considered to be highly specific for cysticercosis when tested with heterologous parasitic diseases. However, recent studies show that people with taeniasis have cross-reactive antibodies against the neurocysticercosis diagnostic glycoproteins and vice versa. Nevertheless, it is not known if these diagnostic proteins are expressed in the adult stage of the parasite. In this paper, we describe the location of 3 of these glycoproteins in T. solium adults and cysticerci using polyclonal antibodies raised against a synthetic peptide based on the amino acid sequence of TS14, a recombinant protein T24H, and the native GP50. The glycoproteins’ distribution was different in invaginated and evaginated cysticerci as well as in adult tapeworms. Specifically, the 3 glycoproteins studied were differentially expressed during embryogenesis. Our findings indicate that expression of the diagnostic glycoproteins is developmentally regulated; this is noteworthy since these glycoproteins are considered specific for the diagnosis of neurocysticercosis but nevertheless are present in different structures throughout the development of T. solium. Here we describe the glycoprotein expression and localization, which can be important in understanding their biological functions. In addition, our results help clarify the cross-reaction observed between people with neurocysticercosis and taeniasis to TS14, T24H, and GP50, which are used as diagnostic antigens for neurocysticercosis.

      5. Validating the NCBI AMRFinder Tool and Resistance Gene Database using antimicrobial resistance genotype-phenotype correlations in a collection of NARMS isolatesexternal icon
        Feldgarden M, Brover V, Haft DH, Prasad AB, Slotta DJ, Tolstoy I, Tyson GH, Zhao S, Hsu CH, McDermott PF, Tadesse DA, Morales C, Simmons M, Tillman G, Wasilenko J, Folster JP, Klimke W.
        Antimicrob Agents Chemother. 2019 Aug 19.
        Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify AMR genes in whole genome sequences, the National Center for Biotechnology Information (NCBI) has produced AMRFinder, a tool that identifies AMR genes using a high-quality curated AMR gene reference database. The Bacterial Antimicrobial Resistance Reference Gene Database consists of up-to-date gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, it contains 4,579 antimicrobial resistance proteins and more than 560 HMMs.Here, we describe AMRFinder and its associated database. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder and resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions.To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene detection system. Most gene calls were identical, but there were 1,229 gene symbol differences (8.8%) between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that Resfinder found, while Resfinder missed 216 loci AMRFinder identified. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system.

      6. Use of TaqMan Array card for the detection of respiratory viral pathogens in children under 5 years old hospitalised with acute medical illness in Ballabgarh, Haryana, Indiaexternal icon
        Gaur B, Saha S, Iuliano AD, Rai SK, Krishnan A, Jain S, Whitaker B, Winchell J, Lal RB, Broor S.
        Indian J Med Microbiol. 2019 Jan-Mar;37(1):105-108.
        Historical specimens collected from hospitalized children were tested for the following 13 viruses: influenza A and B; respiratory syncytial virus (RSV); parainfluenza viruses 1-3; human metapneumovirus; rhinovirus; coronaviruses 229E, OC43, NL63 and HKU1 and Adenovirus using monoplex real-time reverse transcriptase polymerase chain reaction (rRT-PCR). They were retested using TaqMan Array Card (TAC), a micro-fluidic system, capable of simultaneous multi-pathogen testing, to evaluate its sensitivity and specificity against monoplex rRT-PCR. TAC showed high sensitivity (71%-100%) and specificity (98%-100%) for these viruses in comparison to monoplex rRT-PCR. Multi-specimen detection with high sensitivity and specificity makes TAC a potentially useful tool for both surveillance and outbreak investigations.

      7. Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with Phenylketonuriaexternal icon
        Moat SJ, Schulenburg-Brand D, Lemonde H, Bonham JR, Weykamp CW, Mei JV, Shortland GS, Carling RS.
        J Inherit Metab Dis. 2019 Aug 21.
        Analysis of blood phenylalanine is central to the monitoring of patients with phenylketonuria (PKU) and age-related phenylalanine target treatment-ranges (0-12 years; 120-360 mumol/L, and > 12 years; 120-600 mumol/L) are recommended in order to prevent adverse neurological outcomes. These target treatment-ranges are based upon plasma phenylalanine concentrations. However, patients are routinely monitored using dried bloodspot (DBS) specimens due to the convenience of collection. Significant differences exist between phenylalanine concentrations in plasma and DBS, with phenylalanine concentrations in DBS specimens analysed by flow-injection analysis tandem mass spectrometry (FIA-MS/MS) reported to be 18-28% lower than paired plasma concentrations analysed using ion-exchange chromatography (IEC). DBS specimens with phenylalanine concentrations of 360 mumol/L and 600 mumol/L, at the critical upper-target treatment-range thresholds would be plasma equivalents of 461 mumol/L and 768 mumol/L respectively, when a reported difference of 28% is taken into account. Furthermore, analytical test imprecision and bias in conjunction with pre-analytical factors such as volume and quality of blood applied to filter paper collection devices to produce DBS specimens affect the final test results. Reporting of inaccurate patient results when comparing DBS results to target treatment-ranges based on plasma concentrations, together with inter-laboratory imprecision could have a significant impact on patient management resulting in inappropriate dietary change and potentially adverse patient outcomes. This review is intended to provide perspective on the issues related to the measurement of phenylalanine in blood specimens and to provide direction for the future needs of PKU patients to ensure reliable monitoring of metabolic control using the target treatment-ranges. This article is protected by copyright. All rights reserved.

      8. Impact of nucleic acid extraction platforms on hepatitis virus genome detectionexternal icon
        Pauly MD, Kamili S, Hayden TM.
        J Virol Methods. 2019 Aug 13;273:113715.
        Detection and quantification of viral nucleic acids are important for diagnosing current viral infections and monitoring response to antiviral therapy. Automated nucleic acid extraction and purification platforms are routinely used during the first step in these processes in clinical and research laboratories. Here, we compare the extraction efficiencies of four MagNA Pure magnetic bead-based nucleic acid extraction platforms and associated kits using samples positive for nucleic acids from HAV, HBV, HCV, HDV, and HEV. These five hepatitis viruses are diverse in their virion structures and type of nucleic acid that compose their genomes. We found that the most efficient nucleic acid extraction platform and corresponding kit, when averaged across all tested viruses, was the MagNA Pure 96, which yielded twice as much detectable nucleic acid as the other platforms. However, the relative efficiencies of the different platforms varied by virus type, suggesting that an extraction platform that is more efficient for one virus type will not necessarily function better with a different virus type. Our results show that the choice of a nucleic acid extraction platform influences the sensitivity of the methodology and has the potential to generate false-negative results especially in samples with low levels of viral nucleic acids.

      9. Rapid presumptive identification of Bacillus anthracis Isolates using the Tetracore RedLine Alert Testexternal icon
        Pillai SP, Prentice KW, Ramage JG, DePalma L, Sarwar J, Parameswaran N, Bell M, Plummer A, Santos A, Singh A, Pillai CA, Thirunavvukarasu N, Manickam G, Avila JR, Sharma SK, Hoffmaster A, Anderson K, Morse SA, Venkateswaran KV, Hodge DR.
        Health Secur. 2019 Jul/Aug;17(4):334-343.
        A comprehensive laboratory evaluation of the Tetracore RedLine Alert test, a lateral flow immunoassay (LFA) for the rapid presumptive identification of Bacillus anthracis, was conducted at 2 different test sites. The study evaluated the sensitivity of this assay using 16 diverse strains of B. anthracis grown on sheep blood agar (SBA) plates. In addition, 83 clinically relevant microorganisms were tested to assess the specificity of the RedLine Alert test. The results indicated that the RedLine Alert test for the presumptive identification of B. anthracis is highly robust, specific, and sensitive. RedLine Alert is a rapid test that has applicability for use in a clinical setting for ruling-in or ruling-out nonhemolytic colonies of Bacillus spp. grown on SBA medium as presumptive isolates of B. anthracis.

      10. Introduction: Heat stabilization treatment preserves the in vivo state of biological samples by rapidly inactivating enzymes that cause degradation of proteins and nucleic acids. Historically, proteomics studies used this technique as an alternative to chemical fixation. More recently, microbiologists discovered that heat stabilization treatment rapidly inactivates pathogens present in tissue samples and preserves deoxyribonucleic acid (DNA) in the tissue. However, these recent studies did not investigate the inactivation of high-density bacterial suspensions and the quality of bacterial DNA. Methods and Results: High-density suspensions of Escherichia coli (&gt;109 cfu/mL) were completely inactivated by heat stabilization treatment using the Denator Stabilizor T1 instrument at 72C and 95C for 45 seconds. Using the heat stabilization instrument, a panel of 30 species, 20 Gram-negative and 10 non-endospore-forming Gram-positive species, were fully inactivated by treatment (95C for 45 seconds). DNA was isolated from bacterial suspensions of Gram-negative bacteria, including E. albertii, E. coli, Shigella dysenteriae, and S. flexneri, following inactivation via heat stabilization treatment and without treatment. DNA isolated following heat stabilization treatment was fully compatible with all downstream molecular applications tested, including next-generation sequencing, pulsed-field gel electrophoresis, multiplex polymerase chain reaction (PCR), and real-time PCR. Conclusions and Discussion: Heat stabilization treatment of Gram-negative and non-endospore-forming Gram-positive pathogens completely inactivates high-density bacterial suspensions. This treatment is compatible with downstream DNA molecular assays, including next-generation sequencing, pulsed-field gel electrophoresis, and PCR. Inactivation by heat stabilization is a rapid process that may increase safety by decreasing risks for laboratory-associated infections and risks associated with transportation of infectious materials.

      11. Adverse effects profile of dicycloplatin (DCP) offers chemotherapeutic advantage over cisplatin and carboplatinexternal icon
        Yu JJ, Hogan T, Morley C, Crigger C, Jiao S, Williams DJ, Salkini MW, Yang X, Liang X, Yan B, Cecil C, Winn AC, Zheng J, Guo YI, Jiang BH, Washington IM.
        Anticancer Res. 2019 Aug;39(8):4455-4462.
        BACKGROUND/AIM: Platinum-based chemotherapy often fails due to its severe adverse effects. The aim of this study was to examine the adverse effects profile and efficacy of dicycloplatin and compare them to those of cisplatin and carboplatin. MATERIALS AND METHODS: Cystoscopy surveillance of the first American cancer patient treated with dicycloplatin was performed quarterly. In vitro and in vivo studies were conducted using immunoblotting and flow cytometry to assess immune status of spleen and bone marrow of mice treated with dicycloplatin, cisplatin and carboplatin. RESULTS: The American patient did not suffer clinically significant myelosuppression; dicycloplatin has sustained remission in this patient to date. Experimental studies showed that dicycloplatin is less toxic to bone marrow and spleen of mice than cisplatin and carboplatin. CONCLUSION: Dicycloplatin is a promising drug in cancer chemotherapy with less aggressive side-effects than those typically associated with cisplatin and carboplatin. This is an important therapeutic advantage in cancer chemotherapy. Clinical investigation of dicycloplatin as an alternative to cisplatin or carboplatin is warranted.

    • Maternal and Child Health
      1. Periconceptional folic acid and risk for neural tube defects among higher risk pregnanciesexternal icon
        Petersen JM, Parker SE, Benedum CM, Mitchell AA, Tinker SC, Werler MM.
        Birth Defects Res. 2019 Aug 21.
        BACKGROUND: Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 mug daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 mug for this and other higher risk groups is unclear. METHODS: In the case-control Slone Birth Defects Study (1988-2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet (“total folate”). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression. RESULTS: Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD-affected pregnancy supplemented with 4,000 mug. CONCLUSIONS: Our findings reinforce that all women of childbearing potential should consume at least 400 mug FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.

    • Occupational Safety and Health
      1. Artificial intelligence (AI) is a broad transdisciplinary field with roots in logic, statistics, cognitive psychology, decision theory, neuroscience, linguistics, cybernetics, and computer engineering. The modern field of AI began at a small summer workshop at Dartmouth College in 1956. Since then, AI applications made possible by machine learning (ML), an AI subdiscipline, include Internet searches, e-commerce sites, goods and services recommender systems, image and speech recognition, sensor technologies, robotic devices, and cognitive decision support systems (DSSs). As more applications are integrated into everyday life, AI is predicted to have a globally transformative influence on economic and social structures similar to the effect that other general-purpose technologies, such as steam engines, railroads, electricity, electronics, and the Internet, have had. Novel AI applications in the workplace of the future raise important issues for occupational safety and health. This commentary reviews the origins of AI, use of ML methods, and emerging AI applications embedded in physical objects like sensor technologies, robotic devices, or operationalized in intelligent DSSs. Selected implications on the future of work arising from the use of AI applications, including job displacement from automation and management of human-machine interactions, are also reviewed. Engaging in strategic foresight about AI workplace applications will shift occupational research and practice from a reactive posture to a proactive one. Understanding the possibilities and challenges of AI for the future of work will help mitigate the unfavorable effects of AI on worker safety, health, and well-being.

      2. Motor vehicle crashes (MVCs) are consistently the leading cause of work-related fatalities for all industries combined. They comprise the majority of workplace fatalities for occupations involved in transportation/material moving and are one of the leading causes of death for many occupations which involve driving, but where driving is not the primary job duty. Nonfatal work-related MVCs also have substantial injury and economic consequences for workers and employers. This study used data from 70 companies from a range of industries to assess the relationship between companies’ self-reported fleet safety management practices/policies and collision/injury metrics. Several practices were found to be statistically significantly related to collision/injury metrics, including mobile phone record checking, fatigue mitigation practices, provision of driver training, and collision response procedures. Implications of these findings and suggestions for future research are discussed.

      3. Suicides and deaths of undetermined intent among veterinary professionals from 2003 through 2014external icon
        Witte TK, Spitzer EG, Edwards N, Fowler KA, Nett RJ.
        J Am Vet Med Assoc. 2019 Sep 1;255(5):595-608.
        OBJECTIVE: To analyze data for death of veterinary professionals and veterinary students, with manner of death characterized as suicide or undetermined intent from 2003 through 2014. SAMPLE: Death records for 202 veterinary professionals and veterinary students. PROCEDURES: Decedents employed as veterinarians, veterinary technicians or technologists, or veterinary assistants or laboratory animal caretakers and veterinary students who died by suicide or of undetermined intent were identified through retrospective review of National Violent Death Reporting System records. Standardized mortality ratios (SMRs) and 95% confidence intervals were calculated, and mechanisms and circumstances of death were compared among veterinary occupational groups. RESULTS: 197 veterinary professionals and 5 veterinary students had deaths by suicide or of undetermined intent. Among decedents employed at the time of death, SMRs for suicide of male and female veterinarians (1.6 and 2.4, respectively) and male and female veterinary technicians or technologists (5.0 and 2.3, respectively) were significantly greater than those for the general US population, whereas SMRs for suicide of male and female veterinary assistants or laboratory animal caretakers were not. Poisoning was the most common mechanism of death among veterinarians; the drug most commonly used was pentobarbital. For most (13/18) veterinarians who died of pentobarbital poisoning, the death-related injury occurred at home. When decedents with pentobarbital poisoning were excluded from analyses, SMRs for suicide of male and female veterinarians, but not veterinary technicians or technologists, did not differ significantly from results for the general population. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested higher SMRs for suicide among veterinarians might be attributable to pentobarbital access. Improving administrative controls for pentobarbital might be a promising suicide prevention strategy among veterinarians; however, different strategies are likely needed for veterinary technicians or technologists.

    • Occupational Safety and Health – Mining
      1. Slips, trips, and falls (STFs) pose a significant financial burden to employers and account for over 33% of the total nonfatal workers’ compensation cost in the United States. Previous analyses documenting the burden of STF incidents in the mining industry have focused on occupational fatalities or STFs during equipment ingress, egress. There is limited information on the burden of nonfatal STF incidents in the mining industry and most of it is outdated. Hence, to increase awareness and highlight the importance of STFs in the mining industry, this analysis documents the burden associated with nonfatal STF incidents at surface stone, sand, and gravel (SSG) mines from 2008 through 2017. In this time frame, nonfatal STF incidents occurred at a rate of 62 per 10,000 full-time equivalent (FTE) employees per year. Pits had a higher prevalence of injuries, but plants had a higher incidence rate. In addition, nonfatal STF incidents at surface SSG mines led to approximately 23,800 total days lost per year with an estimated cost to the mining industry of $17.5 million per year. Assessed violations that are not related to reported injuries but are related to STF hazards identified during Mine Safety and Health Administration (MSHA) inspections cost the mining industry approximately $3 million per year from 2013 through 2017. Based on the data analyzed in this study, falls to the lower level pose a higher burden in terms of cost; however, falls to the same level have a higher number of incidents and incidence rate.

    • Substance Use and Abuse
      1. Awareness and use of e-cigarettes among urban residents in Chinaexternal icon
        Zhao L, Mbulo L, Palipudi K, Wang J, King B.
        Tob Induc Dis. 2019 ;17(July).
        INTRODUCTION The long-term health effects of e-cigarettes are uncertain, and data on e-cigarette use among Chinese adults are limited. This study examined the prevalence and correlates of e-cigarette awareness and use among urban residents in China. Data came from the China City Adult Tobacco Survey (CCATS), a city-representative household survey conducted using electronic tablets during 2013-2014 in 14 major Chinese cities. METHODS CCATS used multistage geographically clustered samples with standardized survey protocols and questionnaire to ensure data comparability. Overall, 31151 adults completed the survey, with sample size varying from 1977 to 3838 across cities, and survey response rates ranging from 79.8% to 97.5%. Respondents were considered current e-cigarette users if they self-reported using e-cigarettes ‘daily’ or ‘less than daily’ at the time of the survey. Descriptive statistics and multivariate logistic regression were conducted. Assessed correlates included: age, education, quit attempts in past 12 months, cigarettes smoked per day, and monthly expenditures on cigarettes. RESULTS Overall, 46.7% of respondents were aware of e-cigarettes, 2.9% ever used, and 0.8% currently used. Most current e-cigarette users (93.0%) also currently smoked tobacco. Among male current tobacco smokers, adjusted odds ratio (AOR) of current e-cigarette use was higher among those aged 15-29 (AOR=2.5; 95% CI: 1.5-4.3) or 30-49 (AOR=1.9; 95% CI: 1.0-3.4) than those >/=50 years; those who attempted to quit in the past 12 months than those who did not (AOR=4.7; 95% CI: 2.2-10.1); those with a college degree (AOR=3.4; 95% CI: 1.9-6.2) or just finished high school (AOR=2.2; 95% CI: 1.2-4.2) than those who did not finish high school; and those who smoked >/=15 cigarettes per day (AOR=2.8; 95% CI: 1.4-5.6) than those who smoked fewer. CONCLUSIONS These findings reveal that during 2013-2014, many urban Chinese adults were aware of e-cigarettes, while use was relatively low and most current users also smoked tobacco. Continued monitoring of e-cigarettes could help inform public health policy, planning, and practice.

    • Zoonotic and Vectorborne Diseases
      1. Epidemiology of dengue, chikungunya, and Zika virus disease in the U.S. states and territories, 2017external icon
        Adams LE, Martin SW, Lindsey NP, Lehman JA, Rivera A, Kolsin J, Landry K, Staples JE, Sharp TM, Paz-Bailey G, Fischer M.
        Am J Trop Med Hyg. 2019 Aug 19.
        Dengue, chikungunya, and Zika viruses, primarily transmitted by Aedes species mosquitoes, have caused large outbreaks in the Americas, leading to travel-associated cases and local mosquito-borne transmission in the United States. We describe the epidemiology of dengue, chikungunya, and noncongenital Zika virus disease cases reported from U.S. states and territories in 2017, including 971 dengue cases, 195 chikungunya cases, and 1,118 Zika virus disease cases. Cases of all three diseases reported from the territories were reported as resulting from local mosquito-borne transmission. Cases reported from the states were primarily among travelers, with only seven locally acquired mosquito-transmitted Zika virus disease cases reported from Texas (n = 5) and Florida (n = 2). In the territories, most dengue cases (n = 508, 98%) were reported from American Samoa, whereas the majority of chikungunya (n = 39, 100%) and Zika virus disease (n = 620, 93%) cases were reported from Puerto Rico. Temporally, the highest number of Zika virus disease cases occurred at the beginning of the year, followed by a sharp decline, mirroring decreasing case numbers across the Americas following large outbreaks in 2015 and 2016. Dengue and chikungunya cases followed a more seasonal pattern, with higher case numbers from July through September. Travelers to the United States and residents of areas with active virus transmission should be informed of both the ongoing risk from dengue, chikungunya, and Zika virus disease and personal protective measures to lower their risk of mosquito bites and to help prevent the spread of these diseases.

      2. Knowledge, attitudes, and behaviors regarding tick-borne disease prevention in endemic areasexternal icon
        Niesobecki S, Hansen A, Rutz H, Mehta S, Feldman K, Meek J, Niccolai L, Hook S, Hinckley A.
        Ticks Tick Borne Dis. 2019 Jul 29:101264.
        As part of a TickNET collaboration we evaluated the knowledge, attitudes, and behaviors related to tick-borne disease (TBD) prevention among persons living in endemic areas of Connecticut (CT) and Maryland (MD). Up-to-date information on the use of various prevention methods, as well as attitudes toward available and potential prevention options, is critical for effective promotion of recommended behaviors. During 2016-2017, printed invitations were mailed via the post office to 27,029 households requesting participation in an online survey regarding knowledge of TBD, risk perceptions, and prevention behaviors. Prevention behaviors included tick checks, showering/bathing, insect repellents, pet tick control, and chemical or natural pesticide use on residential properties. Associations of sociodemographic characteristics and knowledge and attitude variables with prevention behaviors were assessed in unadjusted analyses and multivariable models to calculate adjusted odds ratios (aOR). Participants were also asked if they would be willing to get a Lyme disease (LD) vaccine, if one becomes available. Overall, 1883 (7%) persons completed the survey. Participants reported using preventive behaviors most of the time or always as follows: pet tick control (83%), tick checks (58%), showering/bathing (42%), insect repellent (31%), and chemical (23%) or natural (15%) pesticides on property. Self-rated knowledge of LD, perceived prevalence of LD, perceived severity of LD, and perceived likelihood of contracting LD or another TBD were significantly (p < 0.05) associated with performing a tick check [aOR 2.5, aOR 1.71, aOR 1.36, aOR 1.83, respectively]. Female gender and perceived prevalence of LD were significantly associated with applying insect repellent [aOR 1.56, aOR 1.64, respectively]. Perceived prevalence of LD was significantly associated with showering or bathing, insect repellents, and pet tick control [aOR 1.42, aOR 1.64, aOR 1.92, respectively]. Income > $100,000 was significantly associated with applying a chemical or natural pesticide to one’s property [aOR 1.29, aOR 1.40, respectively]. A majority of respondents (84%) reported that they were very likely or somewhat likely to get a LD vaccine if one were available. Few behaviors (tick checks and pet tick control) were reported to be practiced by more than half of the respondents living in LD endemic areas. Perceived prevalence of LD was the only factor associated with performing most of the prevention behaviors (tick checks, showering/bathing, use of insect repellents, and pet tick control). Use of chemical or natural pesticides appears to be driven by income. Greater efforts are needed to encourage use of prevention behaviors in endemic areas, and this may be facilitated by increasing awareness of local prevalence.

      3. Views and experiences of travelers from US states to Zika-affected areasexternal icon
        SteelFisher GK, Caporello H, Blendon RJ, Ben-Porath EN, Lubell K, Friedman AL, Holton K, Smith BJ, McGowan E, Schafer T.
        Health Secur. 2019 Jul/Aug;17(4):307-323.
        Travelers to areas with Zika virus transmission are at risk of infection and of transmitting the virus after returning home. While protective behaviors during and after travel can reduce these risks, information about traveler practices or underlying views is limited. We examined these issues using data from the first representative poll of travelers from US states to Zika-affected areas, including US territories and Miami, Florida, conducted December 1 to 23, 2016. We analyzed results among all travelers (n = 1,285) and 2 subgroups at risk for pregnancy-related complications: (1) travelers in households where someone was pregnant or considering pregnancy (n = 72), and (2) other travelers of reproductive age (n = 631). We also examined results among those with different levels of awareness and knowledge about Zika virus. Results show that in households where someone was pregnant or considering pregnancy, awareness of Zika in the destination, concern about infection, and adoption of protective behaviors was relatively high. That said, sizable shares of travelers as a whole did not know information about asymptomatic and sexual transmission or post-travel behaviors. Further, concern about getting infected during travel was low among travelers as a whole, including other travelers of reproductive age. Few travelers consistently adopted protective behaviors during or after travel. Even among travelers who were aware of Zika in their destination and knew how to protect themselves, adoption of protective behaviors was only slightly higher. Findings from this poll suggest communications may be more effective if tailored to different levels of true and perceived risk. To address gaps in knowledge about transmission and post-travel protective behaviors, messaging should include facts and acknowledge the complexities of novel information and social context. Consideration should also be given to emphasizing other benefits of Zika protective behaviors or prioritizing behaviors that are most feasible.

      4. Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of Indiaexternal icon
        Vasanthapuram R, Shahul Hameed SK, Desai A, Mani RS, Reddy V, Velayudhan A, Yadav R, Jain A, Saikia L, Borthakur AK, Mohan DG, Bandyopadhyay B, Bhattacharya N, Dhariwal AC, Sen PK, Venkatesh S, Prasad J, Laserson K, Srikantiah P.
        Int J Infect Dis. 2019 Jul;84s:S19-s24.
        BACKGROUND: Acute encephalitis syndrome (AES) surveillance in India has indicated that Japanese encephalitis virus (JEV) accounts for 5-35% of AES cases annually; the etiology remains unknown in the remaining cases. We implemented comprehensive AES surveillance to identify other etiological agents of AES, with emphasis on dengue virus. METHODS: Serum and cerebrospinal fluid (CSF) specimens were collected from patients enrolled prospectively in AES surveillance from 2014-2017 at selected sites of three high burden states of India. All samples were initially tested for JEV IgM. Specimens negative for JEV by serology were tested for IgM to scrub typhus, dengue virus (DEN), and West Nile virus; all JEV IgM-negative CSF samples were tested by PCR for S. pneumoniae, N. meningitidis, H. influenzae, herpes simplex virus type 1, enteroviruses and DEN. RESULTS: Of 10,107 AES patients, an etiology could be established in 49.2% of patients including JEV (16%), scrub typhus (16%) and DEN (5.2%) as the top three agents. Amongst the DEN positive cases (359/6892), seven (2%) were positive only for dengue virus RNA: one in serum and six in CSF. CONCLUSION: Amongst the pathogens identified, dengue accounted for 5% of all AES cases and was one of the three common etiological agents. These results underscore the importance of including dengue virus in routine testing of AES cases.

      5. Long-term outcomes of Guillain-Barre syndrome possibly associated with Zika virus infectionexternal icon
        Walteros DM, Soares J, Styczynski AR, Abrams JY, Galindo-Buitrago JI, Acosta-Reyes J, Bravo-Ribero E, Arteta ZE, Solano-Sanchez A, Prieto FE, Gonzalez-Duarte M, Navarro-Lechuga E, Salinas JL, Belay ED, Schonberger LB, Damon IK, Ospina ML, Sejvar JJ.
        PLoS One. 2019 ;14(8):e0220049.
        BACKGROUND: This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barre syndrome (GBS) in Barranquilla, Colombia. METHODS: Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS. RESULTS: Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of >/= 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group. CONCLUSIONS: Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.

      6. Public health management of persons under investigation for Ebola virus disease in New York City, 2014-2016external icon
        Winters A, Iqbal M, Benowitz I, Baumgartner J, Vora NM, Evans L, Link N, Munjal I, Ostrowsky B, Ackelsberg J, Balter S, Dentinger C, Fine AD, Harper S, Landman K, Laraque F, Layton M, Slavinski S, Weiss D, Rakeman JL, Hughes S, Varma JK, Lee EH.
        Public Health Rep. 2019 Aug 19:33354919870200.
        During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.

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

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