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Volume 12, Issue, 3 January 28, 2020

CDC Science Clips: Volume 12, Issue 3, January 28, 2020

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!

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Tracking cardiac rehabilitation participation and completion among Medicare beneficiaries to inform the efforts of a national initiativeexternal icon
        Ritchey MD, Maresh S, McNeely J, Shaffer T, Jackson SL, Keteyian SJ, Brawner CA, Whooley MA, Chang T, Stolp H, Schieb L, Wright J.
        Circ Cardiovasc Qual Outcomes. 2020 Jan;13(1):e005902.
        BACKGROUND: Despite cardiac rehabilitation (CR) being shown to improve health outcomes among patients with heart disease, its use has been suboptimal. In response, the Million Hearts Cardiac Rehabilitation Collaborative developed a road map to improve CR use, including increasing participation rates to >/=70% by 2022. This observational study provides current estimates to measure progress and identifies the populations and regions most at risk for CR service underutilization. METHODS AND RESULTS: We identified Medicare fee-for-service beneficiaries who were CR eligible in 2016, and assessed CR participation (>/=1 CR session attended), timely initiation (participation within 21 days of event), and completion (>/=36 sessions attended) through 2017. Measures were assessed overall, by beneficiary characteristics and geography, and by primary CR-qualifying event type (acute myocardial infarction hospitalization; coronary artery bypass surgery; heart valve repair/replacement; percutaneous coronary intervention; or heart/heart-lung transplant). Among 366 103 CR-eligible beneficiaries, 89 327 (24.4%) participated in CR, of whom 24.3% initiated within 21 days and 26.9% completed CR. Eligibility was highest in the East South Central Census Division (14.8 per 1000). Participation decreased with increasing age, was lower among women (18.9%) compared with men (28.6%; adjusted prevalence ratio: 0.91 [95% CI, 0.90-0.93]) was lower among Hispanics (13.2%) and non-Hispanic blacks (13.6%) compared with non-Hispanic whites (25.8%; adjusted prevalence ratio: 0.63 [0.61-0.66] and 0.70 [0.67-0.72], respectively), and varied by hospital referral region and Census Division (range: 18.6% [East South Central] to 39.1% [West North Central]) and by qualifying event type (range: 7.1% [acute myocardial infarction without procedure] to 55.3% [coronary artery bypass surgery only]). Timely initiation varied by geography and qualifying event type; completion varied by geography. CONCLUSIONS: Only 1 in 4 CR-eligible Medicare beneficiaries participated in CR and marked disparities were observed. Reinforcement of current effective strategies and development of new strategies will be critical to address the noted disparities and achieve the 70% participation goal.

    • Communicable Diseases
      • Diabetes mellitus, hypertension, and death among 32 patients with MERS-CoV infection, Saudi Arabiaexternal icon
        Alanazi KH, Abedi GR, Midgley CM, Alkhamis A, Alsaqer T, Almoaddi A, Algwizani A, Ghazal SS, Assiri AM, Jokhdar H, Gerber SI, Alabdely H, Watson JT.
        Emerg Infect Dis. 2020 Jan;26(1):166-168.
        Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.

      • Policies, practices and barriers to implementing tuberculosis preventive treatment-35 countries, 2017external icon
        Surie D, Interrante JD, Pathmanathan I, Patel MR, Anyalechi G, Cavanaugh JS, Kirking HL.
        Int J Tuberc Lung Dis. 2019 Dec 1;23(12):1308-1313.
        BACKGROUND: Tuberculosis preventive treatment (TPT) reduces the development of tuberculosis (TB) disease and mortality in people living with human immunodeficiency virus (HIV) infection. Despite this known effectiveness, global uptake of TPT has been slow. We aimed to assess current status of TPT implementation in countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR).METHODS: We surveyed TB-HIV program staff at US Centers for Disease Control and Prevention (CDC) country offices in 42 PEPFAR-supported countries about current TPT policies, practices, and barriers to implementation. Surveys completed from July to December 2017 were analyzed.RESULTS: Of 42 eligible PEPFAR-supported countries, staff from 35 (83%) CDC country offices completed the survey. TPT was included in national guidelines in 33 (94%) countries, but only 21 (60%) reported nationwide programmatic TPT implementation. HIV programs led TPT implementation in 20/32 (63%) countries, but TB programs led drug procurement in 18/32 (56%) countries. Stock outs were frequent, as 21/28 (75%) countries reported at least one isoniazid stock out in the previous year.CONCLUSION: Despite widespread inclusion of TPT in guidelines, programmatic TPT implementation lags. Successful scale-up of TPT requires uninterrupted drug supply chains facilitated by improved leadership and coordination between HIV and TB programs.

    • Disease Reservoirs and Vectors
    • Health Disparities
      • BACKGROUND: In 2016, persons aged 13-29 years represented 23.1% of the U.S. population, yet accounted for 41.7% of HIV diagnoses. Racial/ethnic minorities are disproportionally affected by HIV. Sustaining viral suppression helps persons living with diagnosed HIV infection (PLWDH) stay healthy and reduces the risk of transmitting HIV. We examined racial/ethnic disparities in sustained viral suppression and transmission risk potential among PLWDH aged 13-29 years. METHODS: We analyzed data from the National HIV Surveillance System reported through December 2018 from 42 jurisdictions with complete laboratory reporting. We included persons aged 13-29 years who received an HIV diagnosis by December 31, 2015, most recently resided in one of the 42 jurisdictions, and were alive at the end of 2016. Sustained viral suppression was defined as viral load <200 copies/mL for all tests in 2016. Transmission risk potential was estimated using the number of days with viral loads >1,500 copies/mL. RESULTS: Of the 90,812 PLWDH aged 13-29 years included in the analysis, 41.5% had sustained viral suppression in 2016. Across age, sex, and most transmission categories, blacks had the lowest prevalence of sustained viral suppression. Among the 28,154 who were in care but without sustained viral suppression, the average number of days with viral load >1,500 copies/mL was 206 days (56.4% of the 12-month period). CONCLUSION: Sustained viral suppression was suboptimal and transmission risk potential was high for PLWDH aged 13-29 years. Racial/ethnic disparities were apparent, calling for strengthening tailored interventions to improve care outcomes.

    • Immunity and Immunization
      • Effects of influenza vaccination in the United States during the 2018-2019 influenza seasonexternal icon
        Chung JR, Rolfes MA, Flannery B, Prasad P, O'Halloran A, Garg S, Fry AM, Singleton JA, Patel M, Reed C.
        Clin Infect Dis. 2020 Jan 6.
        BACKGROUND: Current multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018-2019 influenza season in the US included prolonged circulation of both A(H1N1)pdm09 viruses well-matched to the vaccine strain, and A(H3N2) viruses the majority of which were mismatched to the vaccine. We estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. METHODS: We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UI) of influenza-associated outcomes prevented by vaccination in the US. The model incorporated age-specific estimates of national 2018-2019 influenza vaccine coverage, influenza virus-specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. RESULTS: Influenza vaccination prevented an estimated 4.4 million (95% UI: 3.4 million-7.1 million) illnesses, 2.3 million (95% UI: 1.8 million-3.8 million) medical visits, 58,000 (95% UI: 30,000-156,000) hospitalizations, and 3,500 (95% UI: 1,000-13,000) deaths due to influenza viruses during the US 2018-2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among young children aged 6 months-4 years. CONCLUSIONS: Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the US, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated health care utilization even in a season in which a vaccine component does not match to a circulating virus.

    • Injury and Violence
      • Intimate partner violence around the time of pregnancy and postpartum contraceptive useexternal icon
        Stevenson AA, Bauman BL, Zapata LB, Ahluwalia IB, Tepper NK.
        Womens Health Issues. 2020 Jan 3.
        OBJECTIVES: We sought to examine postpartum contraceptive use among women who reported physical intimate partner violence (IPV) during or within 12 months before pregnancy compared with women who did not report physical IPV and to identify factors associated with nonuse of contraception among women who reported physical IPV. METHODS: Data were obtained from women with a recent live birth from 2012 to 2015 who participated in the Pregnancy Risk Assessment and Monitoring System. We described characteristics of women and postpartum contraceptive use by method effectiveness (most effective [female sterilization, male sterilization, intrauterine device, implant], moderately effective [injectable, pill, patch, ring], less effective [condoms, natural family planning, withdrawal, other]) or no method, stratified by reported physical IPV. Multivariable logistic regression was used to examine characteristics associated with nonuse of contraception among women who reported physical IPV. RESULTS: The proportion of women using most or moderately effective contraception was similar for women reporting and not reporting physical IPV. Less effective contraceptive use was lower among women who reported physical IPV (13.9%) than who did not report physical IPV (25.1%) (p < .001). Nonuse was higher among women who reported physical IPV (33%) than who did not report physical IPV (21%) (p < .001). Having no health insurance at the time of survey and experiencing traumatic stress within 12 months before delivery were associated with nonuse of contraception among women who reported physical IPV. CONCLUSIONS: The higher proportion of contraception nonuse among women who reported physical IPV indicates a potential unmet need for contraception among this vulnerable population. Recommended screening for IPV and counseling about the full range of contraceptive methods should begin during pregnancy and continue through the postpartum period.

    • Laboratory Sciences
      • Viruses in the Built Environment (VIBE) meeting reportexternal icon
        Prussin AJ, Belser JA, Bischoff W, Kelley ST, Lin K, Lindsley WG, Nshimyimana JP, Schuit M, Wu Z, Bibby K, Marr LC.
        Microbiome. 2020 Jan 4;8(1):1.
        BACKGROUND: During a period of rapid growth in our understanding of the microbiology of the built environment in recent years, the majority of research has focused on bacteria and fungi. Viruses, while probably as numerous, have received less attention. In response, the Alfred P. Sloan Foundation supported a workshop entitled "Viruses in the Built Environment (VIBE)," at which experts in environmental engineering, environmental microbiology, epidemiology, infection prevention, fluid dynamics, occupational health, metagenomics, and virology convened to synthesize recent advances and identify key research questions and knowledge gaps regarding viruses in the built environment. RESULTS: Four primary research areas and funding priorities were identified. First, a better understanding of viral communities in the built environment is needed, specifically which viruses are present and their sources, spatial and temporal dynamics, and interactions with bacteria. Second, more information is needed about viruses and health, including viral transmission in the built environment, the relationship between virus detection and exposure, and the definition of a healthy virome. The third research priority is to identify and evaluate interventions for controlling viruses and the virome in the built environment. This encompasses interactions among viruses, buildings, and occupants. Finally, to overcome the challenge of working with viruses, workshop participants emphasized that improved sampling methods, laboratory techniques, and bioinformatics approaches are needed to advance understanding of viruses in the built environment. CONCLUSIONS: We hope that identifying these key questions and knowledge gaps will engage other investigators and funding agencies to spur future research on the highly interdisciplinary topic of viruses in the built environment. There are numerous opportunities to advance knowledge, as many topics remain underexplored compared to our understanding of bacteria and fungi. Video abstract.

    • Maternal and Child Health
      • Assessing pregnancy, gestational complications, and co-morbidities in women with congenital heart defects (Data from ICD-9-CM Codes in 3 US Surveillance Sites)external icon
        Raskind-Hood C, Saraf A, Riehle-Colarusso T, Glidewell J, Gurvitz M, Dunn JE, Lui GK, Van Zutphen A, McGarry C, Hogue CJ, Hoffman T, Rodriguez Iii FH, Book WM.
        Am J Cardiol. 2019 Dec 9.
        Improved treatment of congenital heart defects (CHDs) has resulted in women with CHDs living to childbearing age. However, no US population-based systems exist to estimate pregnancy frequency or complications among women with CHDs. Cases were identified in multiple data sources from 3 surveillance sites: Emory University (EU) whose catchment area included 5 metropolitan Atlanta counties; Massachusetts Department of Public Health (MA) whose catchment area was statewide; and New York State Department of Health (NY) whose catchment area included 11 counties. Cases were categorized into one of 5 mutually exclusive CHD severity groups collapsed to severe versus not severe; specific ICD-9-CM codes were used to capture pregnancy, gestational complications, and nongestational co-morbidities in women, age 11 to 50 years, with a CHD-related ICD-9-CM code. Pregnancy, CHD severity, demographics, gestational complications, co-morbidities, and insurance status were evaluated. ICD-9-CM codes identified 26,655 women with CHDs, of whom 5,672 (21.3%, range: 12.8% in NY to 22.5% in MA) had codes indicating a pregnancy. Over 3 years, age-adjusted proportion pregnancy rates among women with severe CHDs ranged from 10.0% to 24.6%, and 14.2% to 21.7% for women with nonsevere CHDs. Pregnant women with CHDs of any severity, compared with nonpregnant women with CHDs, reported more noncardiovascular co-morbidities. Insurance type varied by site and pregnancy status. These US population-based, multisite estimates of pregnancy among women with CHD indicate a substantial number of women with CHDs may be experiencing pregnancy and complications. In conclusion, given the growing adult population with CHDs, reproductive health of women with CHD is an important public health issue.

    • Reproductive Health
      • Importance: Pelvic examination is no longer recommended for asymptomatic, nonpregnant women and may cause harms such as false-positive test results, overdiagnosis, anxiety, and unnecessary costs. The bimanual pelvic examination (BPE) is an invasive and controversial examination component. Cervical cancer screening is not recommended for women younger than 21 years. Objectives: To estimate prevalence of potentially unnecessary BPE and Papanicolaou (Pap) tests performed among adolescent girls and women younger than 21 years (hereinafter referred to as young women) in the United States and to identify factors associated with receiving these examinations. Design, Setting, and Participants: A cross-sectional analysis of the National Survey of Family Growth from September 2011 through September 2017 focused on a population-based sample of young women aged 15 to 20 years (n = 3410). The analysis used survey weights to estimate prevalence and the number of people represented in the US population. Data were analyzed from December 21, 2018, through September 3, 2019. Main Outcomes and Measures: Receipt of a BPE or a Pap test in the last 12 months and the proportion of potentially unnecessary examinations and tests. Results: Responses from 3410 young women aged 15 to 20 years were included in the analysis with 6-year sampling weights applied. Among US young women aged 15 to 20 years represented during the 2011-2017 study period, 4.8% (95% CI, 3.9%-5.9%) were pregnant, 22.3% (95% CI, 20.1%-24.6%) had undergone STI testing, and 4.5% (95% CI, 3.6%-5.5%) received treatment or medication for an STI in the past 12 months (Table 1). Only 2.0% (95% CI, 1.4%-2.9%) reported using an IUD, and 33.5% (95% CI, 30.8%-36.4%) used at least 1 other type of hormonal contraception in the past 12 months. Among US young women aged 15 to 20 years who were surveyed in the years 2011 through 2017, approximately 2.6 million (22.9%; 95% CI, 20.7%-25.3%) reported having received a BPE in the last 12 months. Approximately half of these examinations (54.4%; 95% CI, 48.8%-59.9%) were potentially unnecessary, representing an estimated 1.4 million individuals. Receipt of a BPE was associated with having a Pap test (adjusted prevalence ratio [aPR], 7.12; 95% CI, 5.56-9.12), testing for sexually transmitted infections (aPR, 1.60; 95% CI, 1.34-1.90), and using hormonal contraception other than an intrauterine device (aPR, 1.31; 95% CI, 1.11-1.54). In addition, an estimated 2.2 million young women (19.2%; 95% CI, 17.2%-21.4%) reported having received a Pap test in the past 12 months, and 71.9% (95% CI, 66.0%-77.1%) of these tests were potentially unnecessary. Conclusions and Relevance: This analysis found that more than half of BPEs and almost three-quarters of Pap tests performed among young women aged 15 to 20 years during the years 2011 through 2017 were potentially unnecessary, exposing women to preventable harms. The results suggest that compliance with the current professional guidelines regarding the appropriate use of these examinations and tests may be lacking.

    • Substance Use and Abuse
      • AIMS: To examine trends and recent changes in non-fatal and fatal stimulant overdose rates with and without opioids to improve the descriptive characterization of the US overdose epidemic. DESIGN: Secondary analysis of non-fatal (2006-16) and fatal (2006-17) drug overdose trends, focusing on the most recent years of data available to examine rate changes by demographics (2015-16 for non-fatal and 2016-17 for fatal). SETTING: Non-fatal drug overdoses from the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample; drug overdose deaths from the National Vital Statistics System. PARTICIPANTS/CASES: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes for cocaine, psychostimulants and opioids were used to classify non-fatal drug overdoses. Drug overdose deaths were identified using ICD-10 multiple cause-of-death codes for cocaine, psychostimulants, all opioids, heroin and synthetic opioids. MEASUREMENTS: Percentage of changes in age-adjusted non-fatal and fatal rates of cocaine and psychostimulant-involved drug overdose with and without opioids. FINDINGS: Overall, cocaine-involved non-fatal overdose rates with an opioid increased from 2006 to 2016 [annual percentage change (APC) = 14.7], while rates without an opioid increased from 2006 to 2012 (APC = 11.3) and then remained stable (APC = -7.5). Psychostimulant-involved non-fatal rates with and without an opioid increased from 2006 to 2016 (APC = 49.9 with opioids; 13.9 without opioids). Cocaine-involved death rates with and without opioids increased from 2014 to 2017 (APC = 46.0 with opioids, 23.6 without opioids). Psychostimulant-involved death rates with opioids increased from 2010 to 2015 (APC = 28.6), with a dramatic increase from 2015 to 2017 (APC = 50.5), while rates without opioids increased from 2008 to 2017 (APC = 22.6). In 2016, 27% of non-fatal cocaine- and 14% of psychostimulant-involved overdoses included a reported opioid; 72.7% of cocaine- and 50.3% of psychostimulant-involved deaths involved an opioid in 2017. From 2015 to 2016, cocaine-involved and psychostimulant-involved non-fatal overdose rates with an opioid increased 17.0 and 5.9%, respectively; cocaine-involved and psychostimulant-involved non-fatal overdoses without opioids decreased 13.6 and increased 18.9%, respectively. Death rates involving stimulants increased with and without opioids from 2016 to 2017 (cocaine with and without opioids = 37.7 and 23.3%; psychostimulants with and without opioids = 52.2 and 23.0%). Death rates involving stimulants with synthetic opioids increased dramatically from 2016 to 2017 (1.3-2.3 per 100 000 for cocaine and 0.3-0.8 for psychostimulants). CONCLUSIONS: While increases in cocaine-involved deaths in the United States from 2006 seem to be driven by opioids, particularly synthetic opioids, increases in non-fatal and fatal overdoses involving psychostimulants are occurring with and without opioids.

    • Zoonotic and Vectorborne Diseases
      • Nutritional care for patients with Ebola virus diseaseexternal icon
        Ververs M, Gabra M.
        Emerg Infect Dis. 2020 Jan;26(1):20-25.
        During the Ebola virus disease (EVD) outbreak of 2014-2016 in West Africa, practitioners faced challenges providing nutritional care for patients in Ebola treatment units (ETUs). The current EVD outbreak in the Democratic Republic of the Congo demonstrates the need to understand lessons learned from previous outbreaks and to update nutritional guidelines. We conducted a literature review to identify articles that included nutrition as an integral part of supportive care. We found little information on the specific nutritional care or practical challenges within an ETU. This review showed that nutritional care for EVD patients is poorly described, and therefore the optimal composition and implementation of nutritional care remain unknown. We recommend that researchers and practitioners share specific and practical details of their experiences in providing nutritional support within ETUs to expand the knowledge base and ultimately improve the nutritional care for an increasingly prevalent patient population.


  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. Cocaine, polysubstance abuse and oral health outcomes, NHANES 2009-2014external icon
        Bahdila D, Aldosari M, Abdullah A, Nelson JL, Hegazi F, Badamia R, Alhazmi H, Chandel T, Odani S, Vardavas CI, Agaku IT.
        J Periodontol. 2020 Jan 10.
        BACKGROUND: Cocaine is the second most abused illicit drug in the United States (U.S.). To date, no study has examined the association between cocaine use and oral health with a nationally representative sample. Our study examined the association between cocaine use-singly and with other substances - and oral health outcomes, including periodontitis and untreated caries, among U.S. adults. METHODS: Data for 11,753 individuals, aged >/= 30 years, who completed a periodontal examination, in the 2009-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed. Descriptive analyses and multivariable binary logistic regression analyses were conducted on weighted data. RESULTS: Overall, 17.0% (20.5 million) of U.S. adults aged >/= 30 years had ever used cocaine, with higher likelihood seen among males, non-Hispanic whites, and those living in poverty. Current cocaine use prevalence was 2.6% (3.2 million). By number of co-used substances, the odds of having any periodontitis were higher among cocaine users who consumed three or more other substances (Adjusted OR = 2.47; 95%CI = 1.15-5.30) when compared to solely cocaine users. By type of substance co-used, odds of having untreated caries were greater among those reporting cigarettes (Adjusted OR = 1.94; 95%CI = 1.21-3.11) or methamphetamine (Adjusted OR = 5.40; 95%CI = 1.92-15.14) usage. Odds of any periodontitis were higher among those reported ancillary cigarette use (Adjusted OR = 2.84; 95%CI = 1.60-5.04) compared with cocaine-only users. CONCLUSION: In addition to a positive association between periodontal disease, dental caries and cocaine use, select co-usage elevated the risk of oral disease. Patients should be screened for and counseled regarding substance abuse to facilitate a successful quit. This article is protected by copyright. All rights reserved.

      2. History of cardiovascular disease, intensive lifestyle intervention, and cardiovascular outcomes in the Look AHEAD Trialexternal icon
        Lewis CE, Bantle JP, Bertoni AG, Blackburn G, Brancati FL, Bray GA, Cheskin LJ, Curtis JM, Egan C, Evans M, Foreyt JP, Ghazarian S, Barone Gibbs B, Glasser SP, Gregg EW, Hazuda HP, Hesson L, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Kitzman D, Knowler WC, Lipkin E, Michaels S, Montez MG, Nathan DM, Nyenwe E, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin DM, Ryan DH, Wadden TA, Wagenknecht LE, Wyatt H, Wing RR, Yanovski SZ.
        Obesity (Silver Spring). 2020 Jan 3.
        OBJECTIVE: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). METHODS: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. RESULTS: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P </= 0.001) in the ILI group. CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

      3. Background: Exacerbation of asthma symptoms increases the likelihood of emergency department (ED) visits and hospitalizations. Because the ED is an important healthcare resource for immediate asthma care with acute exacerbations, we identify those populations most likely to seek ED treatment for asthma and describe the asthma burden for post-ED visit hospitalizations and critical care units.Methods: We examined the characteristics of asthma-related ED visits and hospital admissions and assessed the association between them using multivariable logistic regression models by analyzing data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) during 2010-2015.Results: Of all ED visits, 1.32% were asthma-related; of all ED visits that resulted in hospitalization, 1.12% were asthma-related and, of all ED visits that resulted in admission to a critical care unit, 1.20% were asthma related.The percentages of asthma-related ED visits and post-ED hospitalizations (H) were greater among children (adjusted prevalence ratio: ED: 2.28 [1.96.29-2.65]; H: 8.75 [5.93-12.92]) than among adults and greater for blacks (ED: (2.26 [1.97-2.60]; H: 3.25 [2.07-5.12]) and Hispanics (ED: (1.74 [1.47-2.08]; H: 2.424 [1.46-4.00]) than for whites. The percentage of ED visits was also greater for those covered by Medicaid or the Children's Health Insurance Program (CHIP) than by private insurance.Conclusions: Both asthma-related ED visits and post-ED hospitalizations were greater for children, blacks, and Hispanics. ED visits were also greater for Medicaid/CHIP. These findings might help prompt future studies on identifying additional potential risk factors for frequent ED visits among disproportionally affected subpopulations.

      4. Women's reports of dense breast notification following mammography: Findings from the 2015 National Health Interview Surveyexternal icon
        Richards TB, Dasari S, Sabatino SA, Qin J, Miller JW, White MC.
        J Gen Intern Med. 2020 Jan 6.

      5. Comorbid chronic conditions among older adults with subjective cognitive decline, United States, 2015-2017external icon
        Taylor CA, Bouldin ED, Greenlund KJ, McGuire LC.
        Innov Aging. 2020 ;4(1):igz045.
        Background and Objectives: Subjective cognitive decline (SCD), the self-reported experience of worsening or more frequent confusion or memory loss, may be associated with the development or worsening of chronic conditions or complicating their self-management. The objectives of this study were to (i) establish the prevalence of chronic conditions and multiple chronic conditions among adults with SCD, and (ii) compare the prevalence of chronic conditions among people with and without SCD and SCD-related functional limitations. Research Design and Methods: Data were analyzed from the Cognitive Decline module of the Behavioral Risk Factor Surveillance System administered in 49 states, DC, and Puerto Rico during 2015-2017. Analyses included 220,221 respondents aged 45 years or older who answered the SCD screening question and reported their chronic conditions. Weighted estimates were calculated and chi-square tests were used for comparisons. Results: Persons with a history of stroke, heart disease, and chronic obstructive pulmonary disorder had significantly higher prevalence of SCD compared to those without. The prevalence of having at least one chronic condition was higher among adults with SCD compared to adults without SCD in each age group (45-64 years: 77.4% vs 47.1%, p < .001; >/=65 years: 86.3% vs 73.5%, p < .001). Among those with SCD, the prevalence of an SCD-related functional limitation was higher among those with at least one chronic condition compared to those with none (45-64 years: 63.3% vs 42.4%, p < .001; >/=65 years: 40.0% vs 25.1%, p < .001). Only half of adults with SCD and a chronic condition had discussed their SCD with a health care professional. Discussion and Implications: SCD and chronic conditions commonly co-occur. Having a chronic condition was associated with greater SCD-related functional limitations. SCD might complicate the management of chronic conditions, and patients and providers should be aware of increased risk for cognitive decline in the presence of chronic diseases.

      6. Breast and colorectal cancer recurrence and progression captured by five U.S. population-based registries: Findings from National Program of Cancer Registries patient-centered outcome researchexternal icon
        Thompson TD, Pollack LA, Johnson CJ, Wu XC, Rees JR, Hsieh MC, Rycroft R, Culp M, Wilson R, Wu M, Zhang K, Benard V.
        Cancer Epidemiol. 2020 Jan 6;64:101653.
        OBJECTIVES: Cancer recurrence is a meaningful patient outcome that is not captured in population-based cancer surveillance. This project supported National Program of Cancer Registries central cancer registries in five U.S. states to determine the disease course of all breast and colorectal cancer cases. The aims were to assess the feasibility of capturing disease-free (DF) status and subsequent cancer outcomes and to explore analytic approaches for future studies. METHODS: Data were obtained on 11,769 breast and 6033 colorectal cancer cancers diagnosed in 2011. Registry-trained abstractors reviewed medical records from multiple sources for up to 60 months to determine documented DF status, recurrence, progression and residual disease. We described the occurrence of these patient-centered outcomes along with analytic considerations when determining time-to-event outcomes and recurrence-free survival. RESULTS: Disease-free status was determined on all but 3.8 % of cancer cases. Among 14,458 cases that became DF, 6.1 % of breast and 13.0 % of colorectal cancer cases had a documented recurrence. Recurrence-free survival varied by stage; for stage II-III cancers at 48 months, 83.2 % of female breast and 69.2 % of colorectal cancer patients were alive without recurrence. The ability to distinguish between progression and residual disease among never disease-free patients limited our ability to examine progression as an outcome. CONCLUSIONS: This study demonstrated that population-based registries given intense support and resources can capture recurrence and offer a generalizable picture of cancer outcomes. Further work on refining definitions, sampling strategies, and novel approaches to capture recurrence could advance the ability of a national cancer surveillance system to contribute to patient-centered outcomes research.

      7. Should women with gestational diabetes be screened at delivery hospitalization for type 2 diabetes?external icon
        Waters TP, Kim SY, Werner E, Dinglas C, Carter EB, Patel R, Sharma AJ, Catalano P.
        Am J Obstet Gynecol. 2020 Jan;222(1):73.e1-73.e11.
        BACKGROUND: Less than one-half of women with gestational diabetes mellitus are screened for type 2 diabetes postpartum. Other approaches to postpartum screening need to be evaluated, including the role of screening during the delivery hospitalization. OBJECTIVE: To assess the performance of an oral glucose tolerance test administered during the delivery hospitalization compared with the oral glucose tolerance test administered at a 4- to 12-week postpartum visit. STUDY DESIGN: We conducted a combined analysis of patient-level data from 4 centers (6 clinical sites) assessing the utility of an immediate postpartum 75-g oral glucose tolerance test during the delivery hospitalization (PP1) for the diagnosis of type 2 diabetes compared with a routine 4- to 12-week postpartum oral glucose tolerance test (PP2). Eligible women underwent a 75-g oral glucose tolerance test at both PP1 and PP2. Sensitivity, specificity, and negative and positive predictive values of the PP1 test were estimated for diagnosis of type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. RESULTS: In total, 319 women completed a PP1 screening, with 152 (47.6%) lost to follow-up for the PP2 oral glucose tolerance test. None of the women with a normal PP1 oral glucose tolerance test (n=73) later tested as having type 2 diabetes at PP2. Overall, 12.6% of subjects (n=21) had a change from normal to impaired fasting glucose/impaired glucose tolerance or a change from impaired fasting glucose/impaired glucose tolerance to type 2 diabetes. The PP1 oral glucose tolerance test had 50% sensitivity (11.8-88.2), 95.7% specificity (91.3-98.2%) with a 98.1% (94.5-99.6%) negative predictive value and a 30% (95% confidence interval, 6.7-65.3) positive predictive value for type 2 diabetes vs normal/impaired fasting glucose/impaired glucose tolerance result. The negative predictive value of having type 2 diabetes at PP2 compared with a normal oral glucose tolerance test (excluding impaired fasting glucose/impaired glucose tolerance) at PP1 was 100% (95% confidence interval, 93.5-100) with a specificity of 96.5% (95% confidence interval, 87.9-99.6). CONCLUSION: A normal oral glucose tolerance test during the delivery hospitalization appears to exclude postpartum type 2 diabetes mellitus. However, the results of the immediate postpartum oral glucose tolerance test were mixed when including impaired fasting glucose or impaired glucose tolerance. As a majority of women do not return for postpartum diabetic screening, an oral glucose tolerance test during the delivery hospitalization may be of use in certain circumstances in which postpartum follow-up is challenging and resources could be focused on women with an abnormal screening immediately after the delivery hospitalization.

    • Communicable Diseases
      1. Paid leave and access to telework as work attendance determinants during acute respiratory illness, United States, 2017-2018external icon
        Ahmed F, Kim S, Nowalk MP, King JP, VanWormer JJ, Gaglani M, Zimmerman RK, Bear T, Jackson ML, Jackson LA, Martin E, Cheng C, Flannery B, Chung JR, Uzicanin A.
        Emerg Infect Dis. 2020 Jan;26(1).
        We assessed determinants of work attendance during the first 3 days after onset of acute respiratory illness (ARI) among workers 19-64 years of age who had medically attended ARI or influenza during the 2017-2018 influenza season. The total number of days worked included days worked at the usual workplace and days teleworked. Access to paid leave was associated with fewer days worked overall and at the usual workplace during illness. Participants who indicated that employees were discouraged from coming to work with influenza-like symptoms were less likely to attend their usual workplace. Compared with workers without a telework option, those with telework access worked more days during illness overall, but there was no difference in days worked at the usual workplace. Both paid leave benefits and business practices that actively encourage employees to stay home while sick are necessary to reduce the transmission of ARI and influenza in workplaces.

      2. Recommendations for providing quality sexually transmitted diseases clinical services, 2020external icon
        Barrow RY, Ahmed F, Bolan GA, Workowski KA.
        MMWR Recomm Rep. 2020 Jan 3;68(5):1-20.
        This report (hereafter referred to as STD QCS) provides CDC recommendations to U.S. health care providers regarding quality clinical services for sexually transmitted diseases (STDs) for primary care and STD specialty care settings. These recommendations complement CDC's Sexually Transmitted Diseases Treatment Guidelines, 2015 (hereafter referred to as the STD Guidelines), a comprehensive, evidence-based reference for prevention, diagnosis, and treatment of STDs. STD QCS differs from the STD Guidelines by specifying operational determinants of quality services in different types of clinical settings, describing on-site treatment and partner services, and indicating when STD-related conditions should be managed through consultation with or referral to a specialist. These recommendations might also help in the development of clinic-level policies (e.g., standing orders, express visits, specimen panels, and reflex testing) that can facilitate implementation of the STD Guidelines. CDC organized the recommendations for STD QCS into eight sections: 1) sexual history and physical examination, 2) prevention, 3) screening, 4) partner services, 5) evaluation of STD-related conditions, 6) laboratory, 7) treatment, and 8) referral to a specialist for complex STD or STD-related conditions.CDC developed the recommendations by synthesizing relevant, evidence-based guidelines and recommendations issued by other experts; reviewing current practice in the United States; soliciting Delphi ratings by subject matter experts on STD care in primary care and STD specialty care settings; discussing the scientific evidence supporting the proposed recommendations at a consultation meeting of experts and institutional stakeholders held November 20, 2015, in Atlanta, Georgia; conducting peer reviews of draft recommendations and supporting evidence; and discussing draft recommendations and supporting evidence during meetings of the CDC/Health Resources and Services Administration Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment STD Work Group. These recommendations are intended to help health care providers in primary care or STD specialty care settings offer STD services at their clinical settings and to help the persons seeking care live safer, healthier lives by preventing and treating STDs and related complications.

      3. Variation in E. coli concentrations in open drains across neighborhoods in Accra, Ghana: The influence of onsite sanitation coverage and interconnectedness of urban environmentsexternal icon
        Berendes DM, de Mondesert L, Kirby AE, Yakubu H, Adomako L, Michiel J, Raj S, Robb K, Wang Y, Doe B, Ampofo J, Moe CL.
        Int J Hyg Environ Health. 2020 ;224.
        Alongside efforts to improve safe management of feces along the entire sanitation chain, including after the toilet, global sanitation efforts are focusing on universal access ‘basic’ services: onsite facilities that safely contain excreta away from human contact. Although fecal sludge management is improving in urban areas, open drains remain a common fate for feces in these often densely-populated neighborhoods in low-income countries. To-date, it is unclear to what extent complete coverage of onsite sanitation reduces fecal contamination in the urban environment and how fecal contamination varies within urban drains across neighborhoods by sanitation status within a city. We assessed how neighborhood levels of environmental fecal contamination (via spatially-representative sampling of open drains for E. coli) varied across four neighborhoods with varying income, type and coverage of household sanitation facilities, and population density in Accra, Ghana. Neighborhoods with very high sanitation coverage (≥89%) still had high (&gt;4 log10 CFU/100 mL) E. coli concentrations in drains. Between-neighborhood variation in E. coli levels among the high coverage neighborhoods was significant: drain concentrations in neighborhoods with 93% and 89% coverage (4.7 (95% CI: 4.5, 4.9) &amp; 4.9 (95% CI: 4.5, 5.3) log10 CFU/100 mL, respectively) were higher than in the neighborhood with 97% coverage (4.1 log10 CFU/100 mL, 95% CI: 3.8, 4.4 log10 CFU/100 mL). Compared with the highest coverage neighborhood, the neighborhood with lowest coverage (48%) also had higher E. coli concentrations (5.6 log10 CFU/100 mL, 95% CI: 5.3, 5.9 log10 CFU/100 mL). Although fecal contamination in open drains appeared lower in neighborhoods with higher onsite sanitation coverage (and vice versa), other factors (e.g. fecal sludge management, animals, population density) may affect drain concentrations. These results underscore that neighborhood-level onsite sanitation improvements alone may not sufficiently reduce fecal hazards to public health from open drains. These findings supporting the need for integrated, city-level fecal sludge management alongside multifaceted interventions to reduce fecal contamination levels and human exposure.

      4. Primary care physician knowledge, attitudes, and diagnostic testing practices for norovirus and acute gastroenteritisexternal icon
        Cardemil CV, O'Leary ST, Beaty BL, Ivey K, Lindley MC, Kempe A, Crane LA, Hurley LP, Brtnikova M, Hall AJ.
        PLoS One. 2020 ;15(1):e0227890.
        BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE) across the age spectrum; candidate vaccines are in clinical trials. While norovirus diagnostic testing is increasingly available, stool testing may not be performed routinely, which can hamper surveillance and burden of disease estimates. Additionally, lack of knowledge of the burden of disease may inhibit provider vaccine recommendations, which could affect coverage rates and ultimately the impact of the vaccine. Our objectives were to understand physicians' stool testing practices in outpatients with AGE, and physician knowledge of norovirus, in order to improve surveillance and prepare for vaccine introduction. METHODS: Internet and mail survey on AGE, norovirus, and future norovirus vaccines conducted January to March 2018 among national networks of primary care pediatricians, family practice and general internal medicine physicians. RESULTS: The response rate was 59% (820/1383). During peak AGE season, physicians estimated they ordered stool tests for a median of 15% (interquartile range: 5-33%) of their outpatients with AGE. Stool tests were reported as more often available for ova and parasites, Clostridioides difficile, and bacterial culture (>95% for all specialties) than for norovirus (6-33% across specialties); even when available, norovirus-specific tests were infrequently ordered. Most providers were unaware that norovirus is a leading cause of AGE across all age groups (Pediatricians 80%, Family Practice 86%, General Internal Medicine 89%) or that alcohol-based hand sanitizers are ineffective against norovirus (Pediatricians 51%, Family Practice 66%, General Internal Medicine 62%). Concerns cited as major barriers to implementing a future norovirus vaccine included if the vaccine is not covered by insurance (General Internal Medicine 64%, Pediatricians 67%, Family Practice 74%) and lack of adequate reimbursement for vaccination (Pediatricians 43%, General Internal Medicine 46%, Family Practice 50%). Factors that providers believed were 'not at all a barrier' or 'minor barrier' to new vaccine introduction included the belief that "my patients won't need this vaccine" (General Internal Medicine 78%, Family Practice 86%, Pediatricians 90%) and "my patients already get too many vaccines" (Family Practice 89%, General Internal Medicine 92%, Pediatricians 95%). CONCLUSIONS: Primary care physicians had few concerns regarding future norovirus vaccine introduction, but have knowledge gaps on norovirus prevalence and hand hygiene for prevention. Also, physicians infrequently order stool tests for outpatients with AGE, which limits surveillance estimates that rely on physician-ordered stool diagnostics. Closing physician knowledge gaps on norovirus burden and transmission can help support norovirus vaccine introduction.

      5. Homotypic and heterotypic protection and risk of re-infection following natural norovirus infection in a highly endemic settingexternal icon
        Chhabra P, Rouhani S, Browne H, Yori PP, Salas MS, Olortegui MP, Moulton LH, Kosek MN, Vinje J.
        Clin Infect Dis. 2020 Jan 9.
        BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6,020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time RT-PCR followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HR) of infection among children with versus without prior exposure. RESULTS: Norovirus was detected in 1,288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR=0.35; p=0.015), GI.7 (HR=0.19; p=0.022), GII.4 (HR=0.39; p<0.001), and GII.6 (HR=0.52; p=0.006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR=0.52; p=0.005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to re-infection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.

      6. Household transmission of seasonal influenza from HIV-infected and HIV-uninfected individuals in South Africa, 2013-2014external icon
        Cohen C, Tshangela A, Valley-Omar Z, Iyengar P, Von Mollendorf C, Walaza S, Hellferscee O, Venter M, Martinson N, Mahlase G, McMorrow M, Cowling BJ, Treurnicht FK, Cohen AL, Tempia S.
        J Infect Dis. 2019 Apr 19;219(10):1605-1615.
        BACKGROUND: We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. METHODS: Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. RESULTS: We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio [OR] 0.2; 95% confidence interval [CI], 0.1-0.6; SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1-4 years (OR 3.6; 95% CI, 1.2-11.3) and 25-44 years (OR 8.0; 95% CI, 1.8-36.7), and contact age group 1-4 years (OR 3.5; 95% CI, 1.2-10.3) compared to 5-14 years, and sleeping with index case (OR 2.7; 95% CI, 1.3-5.5). HIV infection of index case was not associated with SI. CONCLUSIONS: HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.

      7. Hormonal contraception and HIV acquisition among women: an updated systematic reviewexternal icon
        Curtis KM, Hannaford PC, Rodriguez MI, Chipato T, Steyn PS, Kiarie JN.
        BMJ Sex Reprod Health. 2020 Jan;46(1):8-16.
        OBJECTIVE: To update a 2016 systematic review on hormonal contraception use and HIV acquisition. METHODS: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses. RESULTS: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk. CONCLUSIONS: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

      8. Mental and physical health status among chronic hepatitis B patientsexternal icon
        Daida YG, Boscarino JA, Moorman AC, Lu M, Rupp LB, Gordon SC, Teshale EH, Schmidt MA, Spradling PR.
        Qual Life Res. 2020 Jan 14.
        PURPOSE: Little is known about health-related quality of life (HRQoL) in patients with chronic hepatitis B virus (CHB) infection in the United States. Our goal is to understand factors associated with HRQoL in this population. METHODS: We conducted a survey to assess HRQoL and behavioral risks among patients with CHB infection from four large U.S. health care systems. Primary outcomes were generated from the SF-8 scale to assess HRQoL, as measured by the mental component scores (MCS) and physical component scores (PCS). The survey also measured socio-demographic information, hepatitis-related behavioral risk factors, treatment exposure/history, stress, and social support. We supplemented survey data with electronic health records data on patient income, insurance, disease severity, and comorbidities. Multivariate analysis was used to estimate and compare adjusted least square means of MCS and PCS, and examine which risk factors were associated with lower MCS and PCS. RESULTS: Nine hundred sixty-nine patients (44.6%) responded to the survey. Current life stressors and unemployment were associated with both lower MCS and PCS results in multivariate analyses. Lower MCS was also associated with White race and low social support, while lower PCS was also associated with Medicaid insurance. CONCLUSIONS: Stressful life events and unemployment were related to mental and physical health status of CHB patients. Those who have social support have better mental health; White and Medicaid patients are more likely to have poorer mental and physical health, respectively. Management of CHB patients should include stress management, social support, and financial or employment assistance.

      9. Trichomonas vaginalis virus among women with trichomoniasis and associations with demographics, clinical outcomes, and metronidazole resistanceexternal icon
        Graves KJ, Ghosh AP, Schmidt N, Augostini P, Secor WE, Schwebke JR, Martin DH, Kissinger PJ, Muzny CA.
        Clin Infect Dis. 2019 Nov 27;69(12):2170-2176.
        BACKGROUND: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kilo-base pair (kbp), double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine the TVV prevalence in US Trichomonas vaginalis isolates and TVV's associations with patient demographics, clinical outcomes, and metronidazole resistance. METHODS: Archived T. vaginalis isolates from the enrollment visits of 355 women participating in a T. vaginalis treatment trial in Birmingham, Alabama, were thawed and grown in culture. Their total RNA was extracted using a Trizol reagent. Contaminating, single-stranded RNA was precipitated using 4.0 M Lithium Chloride and centrifugation. The samples were analyzed by gel electrophoresis to visualize a 4.5 kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates obtained from the women's test of cure visits. RESULTS: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV-positive (TVV+) isolates were significantly older (P = .01), more likely to smoke (P = .04), and less likely to report a history of gonorrhea (P = .04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infections with TVV+ isolates (P = .14 and P = .44, respectively). Of 25 test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance, while 2/15 TVV-negative isolates demonstrated mild to moderate resistance (P = .23). CONCLUSIONS: Of 355 T. vaginalis isolates tested for TVV, T. vaginalis isolates tested for TVV, the prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be commensal to T. vaginalis.

      10. Copper intrauterine device use and HIV acquisition in women: a systematic reviewexternal icon
        Hannaford PC, Ti A, Chipato T, Curtis KM.
        BMJ Sex Reprod Health. 2020 Jan;46(1):17-25.
        OBJECTIVES: To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women. METHODS: We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings. RESULTS: From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users. CONCLUSION: The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.

      11. Risk and protective factors for cholera deaths during an urban outbreak - Lusaka, Zambia, 2017-2018external icon
        Mutale LS, Winstead AV, Sakubita P, Kapaya F, Nyimbili S, Mulambya NL, Nanzaluka FH, Gama A, Mwale V, Kim S, Ngosa W, Yard E, Sinyange N, Mintz E, Brunkard J, Mukonka V.
        Am J Trop Med Hyg. 2020 Jan 13.
        The Republic of Zambia declared a cholera outbreak in Lusaka, the capital, on October 6, 2017. By mid-December, 20 of 661 reported cases had died (case fatality rate 3%), prompting the CDC and the Zambian Ministry of Health through the Zambia National Public Health Institute to investigate risk factors for cholera mortality. We conducted a study of cases (cholera deaths from October 2017 to January 2018) matched by age-group and onset date to controls (persons admitted to a cholera treatment center [CTC] and discharged alive). A questionnaire was administered to each survivor (or relative) and to a family member of each decedent. We used univariable exact conditional logistic regression to calculate matched odds ratios (mORs) and 95% CIs. In the analysis, 38 decedents and 76 survivors were included. Median ages for decedents and survivors were 38 (range: 0.5-95) and 25 (range: 1-82) years, respectively. Patients aged > 55 years and those who did not complete primary school had higher odds of being decedents (matched odds ratio [mOR] 6.3, 95% CI: 1.2-63.0, P = 0.03; mOR 8.6, 95% CI: 1.8-81.7, P < 0.01, respectively). Patients who received immediate oral rehydration solution (ORS) at the CTC had lower odds of dying than those who did not receive immediate ORS (mOR 0.1, 95% CI: 0.0-0.6, P = 0.02). Cholera prevention and outbreak response should include efforts focused on ensuring access to timely, appropriate care for older adults and less educated populations at home and in health facilities.

      12. Early season pediatric influenza B/Victoria virus infections associated with a recently emerged virus subclade - Louisiana, 2019external icon
        Owusu D, Hand J, Tenforde MW, Feldstein LR, DaSilva J, Barnes J, Lee G, Tran J, Sokol T, Fry AM, Brammer L, Rolfes MA.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):40-43.
        Multiple genetically distinct influenza B/Victoria lineage viruses have cocirculated in the United States recently, circulating sporadically during the 2018-19 season and more frequently early during the 2019-20 season (1). The beginning of the 2019-20 influenza season in Louisiana was unusually early and intense, with infections primarily caused by influenza B/Victoria lineage viruses. One large pediatric health care facility in New Orleans (facility A) reported 1,268 laboratory-confirmed influenza B virus infections, including 23 hospitalizations from July 31 to November 21, 2019, a time when influenza activity is typically low. During this period, Louisiana also reported one pediatric death associated with influenza B virus infection. An investigation of the influenza B virus infections in Louisiana, including medical and vaccine record abstraction on 198 patients, primarily from facility A, with sporadic cases from other facilities in the state, found that none of the patients had received 2019-20 seasonal influenza vaccine, in part because influenza activity began before influenza vaccination typically occurs. Among 83 influenza B viruses sequenced from 198 patients in Louisiana, 81 (98%) belonged to the recently emerged B/Victoria V1A.3 genetic subclade. Nationally, to date, B/Victoria viruses are the most commonly reported influenza viruses among persons aged <25 years (2). Of the 198 patients in the investigation, 95% were aged <18 years. Although most illnesses were uncomplicated, the number of hospitalizations, clinical complications, and the reported pediatric death in Louisiana serve as a reminder that, even though influenza B viruses are less common than influenza A viruses in most seasons, influenza B virus infection can be severe in children. All persons aged >/=6 months should receive an annual influenza vaccination if they have not already received it (3). Antiviral treatment of influenza is recommended as soon as possible for all hospitalized patients and for outpatients at high risk for influenza complications (including children aged <2 years and persons with underlying medical conditions) (4).

      13. The HIV pre-exposure prophylaxis (PrEP) cascade at NYC sexual health clinics: navigation is the key to uptakeexternal icon
        Pathela P, Jamison K, Blank S, Daskalakis D, Hedberg T, Borges C.
        J Acquir Immune Defic Syndr. 2020 Jan 3.
        BACKGROUND: Clinics providing sexual health care pose unique opportunities to implement HIV pre-exposure prophylaxis (PrEP) programs. The PrEP program at New York City's Sexual Health Clinics provides intensive on-site navigation for linkage to PrEP care. We assessed uptake of this intervention. METHODS: We categorized men-who-have-sex-with-men (MSM) without HIV hierarchically as having had: 1) HIV post-exposure (PEP) use (past-year); or 2) selected sexually transmitted infections (STI) (past-year); or 3) HIV-diagnosed sex/needle-sharing partners (past 6 months); or 4) expressed interest in PrEP (day of clinic visit). We constructed PrEP cascades and used multivariable regression to examine acceptance of PrEP navigation, referral to a PrEP provider, linkage (<60 days), and PrEP prescription. RESULTS: 1,301 of 2,106 PrEP (62%) patients accepted navigation. Of those, 55% (718/1,301) were black or Hispanic MSM. STI and PEP patients had lowest navigation acceptance levels (35-46%). Of navigated patients, 56% (628/1,114) accepted referrals, 46% (288/628) linked to PrEP providers, and 82% (235/288) were prescribed PrEP; overall, 11% of those offered navigation (235/2,106) received prescriptions. Navigated MSM with PEP history (adjusted prevalence ratio (aPR) 1.34, 95% CI 1.16-1.56), prior STI (aPR 1.28, 95% CI 1.12-1.45), or HIV-diagnosed partners (aPR 1.18, 95% CI 1.01-1.37) were more likely than those with PrEP interest to accept referrals. Probability of linkage varied by insurance status; prescription did not vary by patient factors. CONCLUSIONS: Although MSM in key priority groups (e.g., prior STI) showed low navigation uptake, those who accepted navigation were likely to be referred for PrEP, suggesting a need for expanded up-front engagement.

      14. An evaluation of the Zambia influenza sentinel surveillance system, 2011-2017external icon
        Simusika P, Tempia S, Chentulo E, Polansky L, Mazaba ML, Ndumba I, Mbewe QK, Monze M.
        BMC Health Serv Res. 2020 Jan 13;20(1):35.
        BACKGROUND: Over the past decade, influenza surveillance has been established in several African countries including Zambia. However, information on the on data quality and reliability of established influenza surveillance systems in Africa are limited. Such information would enable countries to assess the performance of their surveillance systems, identify shortfalls for improvement and provide evidence of data reliability for policy making and public health interventions. METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza surveillance system (ISS) in Zambia during 2011-2017 using 9 attributes: (i) data quality and completeness, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability, (viii) utility, and (ix) sustainability. Each attribute was evaluated using pre-defined indicators. For each indicator we obtained the proportion (expressed as percentage) of the outcome of interest over the total. A scale from 1 to 3 was used to provide a score for each attribute as follows: < 60% (as obtained in the calculation above) scored 1 (weak performance); 60-79% scored 2 (moderate performance); >/=80% scored 3 (good performance). An overall score for each attribute and the ISS was obtained by averaging the scores of all evaluated attributes. RESULTS: The overall mean score for the ISS in Zambia was 2.6. Key strengths of the system were the quality of data generated (score: 2.9), its flexibility (score: 3.0) especially to monitor viral pathogens other than influenza viruses, its simplicity (score: 2.8), acceptability (score: 3.0) and stability (score: 2.6) over the review period and its relatively low cost ($310,000 per annum). Identified weaknesses related mainly to geographic representativeness (score: 2.0), timeliness (score: 2.5), especially in shipment of samples from remote sites, and sustainability (score: 1.0) in the absence of external funds. CONCLUSIONS: The system performed moderately well in our evaluation. Key improvements would include improvements in the timeliness of samples shipments and geographical coverage. However, these improvements would result in increased cost and logistical complexity. The ISSS in Zambia is largely reliant on external funds and the acceptability of maintaining the surveillance system through national funds would require evaluation.

      15. HIV partner service delivery among transgender women - United States, 2013-2017external icon
        Song W, Mulatu MS, Rao S, Wang G, Kudon HZ, O'Connor K.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):35-39.
        Transgender women* in the United States are disproportionately affected by human immunodeficiency virus (HIV) infection because of multiple factors, including stigma related to gender identity, unstable housing, limited employment options, and high-risk behaviors, such as sex work, unprotected receptive anal intercourse, and injection drug use, that tend to increase their vulnerability to becoming infected with HIV (1,2). In a recent meta-analysis of 88 U.S. studies conducted during 2006-2017, the mean estimated laboratory-confirmed prevalence of HIV infection among transgender women was 14.2%, and the mean self-reported prevalence estimate was 21.0% (3). The Ending the HIV Epidemic initiative calls for accelerating the implementation of evidence-based strategies in the right geographic areas targeted to the right persons to end the HIV epidemic in the United States (4). HIV partner services are effective strategies offered by public health workers to persons with a diagnosis of HIV infection (index persons) and their sex or needle-sharing partners (partners), who are notified of potential HIV exposure and offered HIV testing and related services. CDC analyzed HIV partner services data submitted by 61 health departments(dagger) during 2013-2017. Among 208,304 index persons, 1,727 (0.8%) were transgender women. Overall, 71.5% of index transgender women were interviewed for partner services, which was lower than that for all index persons combined (81.1%). Among 1,089 transgender women named as partners by index persons, 71.2% were notified of potential HIV exposure, which was lower than that for all partners combined (77.1%). Fewer than half (46.5%) of notified transgender women partners were tested for HIV, and approximately one in five (18.6%) of those who were tested received a new diagnosis of HIV infection, slightly higher than for all partners combined (17.6%). Additional efforts are needed to effectively implement partner services among transgender women and identify those whose infection with HIV is undiagnosed, provide timely prevention and care services, reduce HIV transmission, and contribute to ending the HIV epidemic.

      16. Treatment outcomes of patients with chronic hepatitis C receiving sofosbuvir-based combination therapy within national hepatitis C elimination program in the country of Georgiaexternal icon
        Tsertsvadze T, Gamkrelidze A, Nasrullah M, Sharvadze L, Morgan J, Shadaker S, Gvinjilia L, Butsashvili M, Metreveli D, Kerashvili V, Ezugbaia M, Chkhartishvili N, Abutidze A, Kvaratskhelia V, Averhoff F.
        BMC Infect Dis. 2020 Jan 10;20(1):30.
        BACKGROUND: Georgia has one of the highest HCV prevalence in the world and launched the world's first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. METHODS: Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. RESULTS: Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001). In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05-1.15]) and genotype 3 (RR = 1.14, CI [1.11-1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93-0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81-0.91]; RR = 0.86, CI [0.82-0.92]; RR = 0.88, CI [0.85-0.91] and RR = 0.92, CI [0.87-0.98], respectively) were less likely to achieve SVR. CONCLUSIONS: Georgia's real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.

    • Disaster Control and Emergency Services
      1. Estimation of external contamination and exposure rates due to fission product releaseexternal icon
        Dewji SA, Bales K, Asano E, Veinot K, Eckerman K, Hart S, Finklea L, Ansari A.
        Health Phys. 2020 Jan 7.
        In the event of a radiological incident, the release of fission products into the surrounding environment and the ensuing external contamination present a challenge for triage assessment by emergency response personnel. Reference exposure rate and skin dose rate calibration data for emergency response personnel are currently lacking for cases where receptors are externally contaminated with fission products. Simulations were conducted to compute reference exposure rate coefficients and skin dose rate coefficients from photon-emitting fission products of radiological concern. To accomplish this task, simplified mathematical skin phantoms were created using surface area and height specifications from International Commission on Radiological Protection Publication 89. Simulations were conducted using Monte Carlo radiation transport code using newborn, 1-y-old, 5-y-old, 10-y-old, 15-y-old, and adult phantoms for 22 photon-emitting radionuclides. Exposure rate coefficient data were employed in a case study simulating the radionuclide inventory for a 17 x 17 Westinghouse pressurized water reactor, following three burn-up cycles at 14,600 MWd per metric ton of uranium. The decay times following the final cycle represent the relative activity fractions over a period of 0.5-30 d. The resulting data can be used as calibration standards for triage efforts in emergency response protocols.

      2. To date more than 100 countries have carried out a Joint External Evaluation (JEE) as part of their Global Health Security programme. The JEE is a detailed effort to assess a country's capacity to prevent, detect and respond to population health threats in 19 programmatic areas. To date no attempt has been made to determine the validity of these measures. We compare scores and commentary from the JEE in three countries to the strengths and weaknesses identified in the response to a subsequent large-scale outbreak in each of those countries. Relevant indicators were compared qualitatively, and scored as low, medium or in a high level of agreement between the JEE and the outbreak review in each of these three countries. Three reviewers independently reviewed each of the three countries. A high level of correspondence existed between score and text in the JEE and strengths and weaknesses identified in the review of an outbreak. In general, countries responded somewhat better than JEE scores indicated, but this appears to be due in part to JEE-related identification of weaknesses in that area. The improved response in large measure was due to more rapid requests for international assistance in these areas. It thus appears that even before systematic improvements are made in public health infrastructure that the JEE process may assist in improving outcomes in response to major outbreaks.

    • Environmental Health
      1. The National Environmental Health Association is publishing a three-part series that highlights collaboration and partnerships with the Agency for Toxic Substances and Disease Registry (ATSDR) and redevelopment stakeholders to promote environmental health and land reuse as environmental and public health practices. This series will serve as a guide for identifying new and existing resources that can be adopted at the local environmental health level to safely reuse environmentally impacted land to improve community health outcomes. The conclusions in this series are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention and ATSDR.

      2. In utero exposure to endocrine-disrupting chemicals and telomere length at birthexternal icon
        Michels KB, De Vivo I, Calafat AM, Binder AM.
        Environ Res. 2019 Dec 17;182:109053.
        Telomere length correlates with morbidity and mortality. While telomere length appears to be influenced by hormone levels, the potential impact of exposure to endocrine-disrupting chemicals (EDCs) has not been studied. We examined the association between maternal gestational concentrations of biomarkers of EDC exposure and telomere length at birth in the Harvard Epigenetic Birth Cohort. EDC (phenols and phthalates) biomarker concentrations were measured in maternal spot urine samples during the first trimester and telomere length in maternal and cord blood collected at delivery among 181 mother-newborn singleton dyads. Maternal and newborn telomere length exhibited a positive correlation (Spearman rho = 0.20 (p-value< 0.01). Infant telomere length was associated with maternal biomarker concentrations of specific EDCs, and most of these associations were observed to be infant sex-specific. Prenatal exposure to triclosan, a non-paraben phenol with antimicrobial properties, was one of the most strongly associated EDCs with telomere length; telomere length was 20% (95% CI 5%-33%) shorter among boys in the highest quartile of maternal biomarker concentrations compared to the lowest quartile. In contrast, we observed longer telomere length associated with increased gestational concentrations of mono-isobutyl phthalate, and among boys, with increased concentrations of mono-2-ethylhexyl phthalate. In this birth cohort, we observed associations between maternal gestational exposure to select EDC biomarkers and telomere length, most of which were sex-specific. These findings need to be confirmed in future studies.

    • Epidemiology and Surveillance
      1. Strengthening timely detection and reporting of unusual respiratory events from health facilities in Yaounde, Cameroonexternal icon
        Alroy KA, Gwom LC, Ndongo CB, Kenmoe S, Monamele G, Clara A, Whitaker B, Manga H, Tayimetha CY, Tseuko D, Etogo B, Pasi O, Etoundi AG, Seukap E, Njouom R, Balajee A.
        Influenza Other Respir Viruses. 2020 Jan 10.
        BACKGROUND: The International Health Regulations state that early detection and immediate reporting of unusual health events is important for early warning and response systems. OBJECTIVE: To describe a pilot surveillance program established in health facilities in Yaounde, Cameroon in 2017 which aimed to enable detection and reporting of public health events. METHODS: Cameroon's Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, Cameroon Pasteur Center, and National Public Health Laboratory, implemented event-based surveillance (EBS) in nine Yaounde health facilities. Four signals were defined that could indicate possible public health events, and a reporting, triage, and verification system was established among partner organizations. A pre-defined laboratory algorithm was defined, and a series of workshops trained health facilities, laboratory, and public health staff for surveillance implementation. RESULTS: From May 2017 to January 2018, 30 signals were detected, corresponding to 15 unusual respiratory events. All health facilities reported a signal at least once, and more than three-quarters of health facilities reported >/=2 times. Among specimens tested, the pathogens detected included Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus, Pneumocystis jiroveci, influenza A (H1N1) virus, rhinovirus, and adenovirus. CONCLUSIONS: The events detected in this pilot were caused by routine respiratory bacteria and viruses, and no novel influenza viruses or other emerging respiratory threats were identified. The surveillance system, however, strengthened relationships and communication linkages between health facilities and public health authorities. Astute clinicians can play a critical role in early detection and EBS is one approach that may enable reporting of emerging outbreaks and public health events.

      2. Lessons from the first 6 years of an intervention-based field epidemiology training programme in Papua New Guinea, 2013-2018external icon
        Ropa B, Flint J, O'Reilly M, Pavlin BI, Dagina R, Peni B, Bauri M, Pukienei A, Merritt T, Terrell-Perica S, Yamba A, Prybylski D, Collins J, Durrheim DN, Henderson A, Bieb S.
        BMJ Glob Health. 2019 ;4(6):e001969.
        Papua New Guinea (PNG) faces a critical shortage of human resources to address pressing public health challenges arising from an increasing burden of communicable and non-communicable diseases. PNG is an independent State in the Pacific and home to 8.2 million people. Resource and infrastructure constraints due to the country's challenging geography have made it difficult and expensive to deliver health services and implement health programmes. The National Department of Health and its partners developed a field epidemiology training programme of Papua New Guinea (FETPNG) to strengthen the country's public health workforce. The training programme covers field epidemiology competencies and includes the design, implementation and evaluation of evidence-based interventions by Fellows. From 2013 to 2018, FETPNG graduated 81 field epidemiologists. Most FETPNG graduates (84%) were from provincial or district health departments or organisations. Many of their intervention projects resulted in successful public health outcomes with tangible local impacts. Health challenges addressed included reducing the burden of multi-drug resistant-tuberculosis (TB), increasing immunisation coverage, screening and treating HIV/TB patients, and improving reproductive health outcomes. FETPNG Fellows and graduates have also evaluated disease surveillance systems and investigated disease outbreaks. Early and unwavering national ownership of FETPNG created a sustainable programme fitting the needs of this low-resource country. A focus on designing and implementing effective public health interventions not only provides useful skills to Fellows but also contributes to real-time, tangible and meaningful improvements in the health of the population. The graduates of FETPNG now provide a critical mass of public health practitioners across the country. Their skills in responding to outbreaks and public health emergencies, in collecting, analysing and interpreting data, and in designing, implementing and evaluating public health interventions continues to advance public health in PNG.

    • Health Communication and Education
      1. Sexual and reproductive health web sites: An analysis of content for sexual and gender minority youthexternal icon
        Andrzejewski J, Rasberry CN, Mustanski B, Steiner RJ.
        Am J Health Promot. 2020 Jan 13:890117119899217.
        PURPOSE: Sexual and gender minority (SGM) youth face risks for negative sexual and reproductive health (SRH) outcomes; it is critical to provide these populations with health education that is both inclusive of and specific to their needs. We sought to characterize the strengths and weaknesses of SGM-related messages from web sites that address SRH for young people. We considered who is included, what topics are discussed, and how messages are framed. METHODS: A systematic Google search and screening process was used to identify health promotion web sites with SRH content for adolescents and young adults. Using MAXQDA, we thematically coded and analyzed SGM content qualitatively. RESULTS: Of 32 SRH web sites identified, 23 (71.9%) contained SGM content. Collectively, the sites included 318 unique SGM codes flagging this content. Approximately two-thirds of codes included messages that discussed SGM youth in aggregate (eg, lesbian, gay, bisexual, and transgender)-specific content about the diverse subpopulations within this umbrella term (eg, transgender youth) was more limited. In addition to SRH topics, most web sites had messages that addressed a broad array of other health issues including violence, mental health, and substance use (n = 17, 73.9%) and SGM-specific topics, for example coming out (n = 21, 91.3%). The former were often risk-framed, yet affirmational messages were common. Most web sites (n = 16; 69.6%) presented information for SGM youth both in stand-alone sections and integrated into broader content. Yet, integrated information was slightly more common (56.6% of all codes) than stand-alone content. CONCLUSIONS: Challenges of developing SRH content related to SGM youth include: (1) aggregate terms, which may not represent the nuances of sexual orientation and gender, (2) balancing risk versus affirmational messages, and (3) balancing stand-alone versus integrated content. However, SGM-related content also offers an opportunity to address diverse topics that can help meet the needs of these populations.

    • Health Disparities
      1. Poverty and health in Tennesseeexternal icon
        Beatty K, Egen O, Dreyzehner J, Wykoff R.
        South Med J. 2020 Jan;113(1):1-7.
        OBJECTIVES: Understanding the impact of poverty on health can inform efforts to target social programs and regional economic development. This study examined the effects of poverty on health among the 95 counties of Tennessee. METHODS: All of the counties of Tennessee were ranked by 5-year median household income, from the wealthiest to the poorest. The counties were divided into quintiles, from wealthiest to poorest, to reflect the general impact of wealth on health. Next, the five wealthiest counties and the five poorest counties were identified, allowing for examination of the extremes of poverty and wealth within Tennessee. Comparisons of quintiles and five wealthiest and poorest counties on key measures were performed using the independent t test. RESULTS: People living in the wealthiest quintile lived on average 2.5 to 4 years longer and had lower rates of all health behaviors and health outcomes investigated compared with those in the poorest quintile. This disparity was even more pronounced when comparing the wealthiest five counties to the poorest five. The five poorest counties, for example, had twice the years of potential life lost and were overwhelmingly rural in character, with similar accompanying disparities such as median income, high unemployment, and a more aged population. CONCLUSIONS: This study highlights the fact that lower income is associated with significantly worse health outcomes in Tennessee and reinforces the importance of economic development, specifically, and addresses the social determinants, more generally, in helping to improve Tennessee's overall health statistics.

      2. Addressing health equity in public health practice: Frameworks, promising strategies, and measurement considerationsexternal icon
        Liburd LC, Hall JE, Mpofu JJ, Marshall Williams S, Bouye K, Penman-Aguilar A.
        Annu Rev Public Health. 2020 Jan 3.
        This review describes the context of health equity and options for integrating equity into public health practice. We first discuss how the conceptualization of health equity and how equity considerations in US public health practice have been shaped by multidisciplinary engagements. We then discuss specific ways to address equity in core public health functions, provide examples of relevant frameworks and promising strategies, and discuss conceptual and measurement issues relevant to assessing progress in moving toward health equity. Challenges and opportunities and their implications for future directions are identified. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

      3. Mortgage discrimination and racial/ethnic concentration are associated with same-race/ethnicity partnering among people who inject drugs in 19 US citiesexternal icon
        Linton SL, Cooper HL, Chen YT, Khan MA, Wolfe ME, Ross Z, Des Jarlais DC, Friedman SR, Tempalski B, Broz D, Semaan S, Wejnert C, Paz-Bailey G.
        J Urban Health. 2020 Jan 13.
        Racial/ethnic homophily in sexual partnerships (partners share the same race/ethnicity) has been associated with racial/ethnic disparities in HIV. Structural racism may partly determine racial/ethnic homophily in sexual partnerships. This study estimated associations of racial/ethnic concentration and mortgage discrimination against Black and Latino residents with racial/ethnic homophily in sexual partnerships among 7847 people who inject drugs (PWID) recruited from 19 US cities to participate in CDC's National HIV Behavioral Surveillance. Racial/ethnic concentration was defined by two measures that respectively compared ZIP code-level concentrations of Black residents to White residents and Latino residents to White residents, using the Index of Concentration at the Extremes. Mortgage discrimination was defined by two measures that respectively compared county-level mortgage loan denial among Black applicants to White applicants and mortgage loan denial among Latino applicants to White applicants, with similar characteristics (e.g., income, loan amount). Multilevel logistic regression models were used to estimate associations. Interactions of race/ethnicity with measures of racial/ethnic concentration and mortgage discrimination were added to the final multivariable model and decomposed into race/ethnicity-specific estimates. In the final multivariable model, among Black PWID, living in ZIP codes with higher concentrations of Black vs. White residents and counties with higher mortgage discrimination against Black residents was associated with higher odds of homophily. Living in counties with higher mortgage discrimination against Latino residents was associated with lower odds of homophily among Black PWID. Among Latino PWID, living in ZIP codes with higher concentrations of Latino vs. White residents and counties with higher mortgage discrimination against Latino residents was associated with higher odds of homophily. Living in counties with higher mortgage discrimination against Black residents was associated with lower odds of homophily among Latino PWID. Among White PWID, living in ZIP codes with higher concentrations of Black or Latino residents vs. White residents was associated with lower odds of homophily, but living in counties with higher mortgage discrimination against Black residents was associated with higher odds of homophily. Racial/ethnic segregation may partly drive same race/ethnicity sexual partnering among PWID. Future empirical evidence linking these associations directly or indirectly (via place-level mediators) to HIV/STI transmission will determine how eliminating discriminatory housing policies impact HIV/STI transmission.

    • Health Economics
      1. A financial model for team-based opioid use disorder treatmentexternal icon
        Farrar M, White Z, Hulkower S, Fagan EB, Wilson CG.
        J Am Board Fam Med. 2020 Jan-Feb;33(1):124-128.
        INTRODUCTION: Opioid use disorder (OUD) affects 2 million Americans, yet many patients do not receive treatment. Lack of team-based care is a common barrier for office-based opioid treatment (OBOT). In 2015, we started OBOT in a family medicine practice. Based on our experiences, we developed a financial model for hiring a team member to provide nonbillable OBOT services through revenue from increased patient volume. METHODS: We completed a retrospective chart review from July 2015 to December 2016 to determine the average difference in medical visits per patient per month pre-OBOT versus post-OBOT. Secondary outcomes were the percentage of visits coded as a Level 3, Level 4, and Level 5, and the percentage of patients with Medicaid, private insurance, or self pay. With this information, we extrapolated to build a financial model to hire a team member to support OBOT. RESULTS: Twenty-three patients received OBOT during the study period. There was a net increase of 1.93 visits per patient per month (P < .001). Fourteen patients were insured by Medicaid, 7 had private insurance, and 2 were self pay. Twenty-three percent of OBOT visits were Level 3, 69% were Level 4, and 8% were Level 5. Assuming all visits were reimbursed by Medicaid and accounting for 20% cost of business, treating 1 existing patient for 1 year would generate $1,439. Treating 1 new patient would generate $1,677. CONCLUSIONS: In a fee-for-service model, the revenue generated from increased medical visits can offset the cost of hiring a team member to support nonbillable OBOT services.

    • Healthcare Associated Infections
      1. Sustaining outpatient antimicrobial stewardship: Do we need to think further outside the box?external icon
        Frost HM, Andersen LM, Fleming-Dutra KE, Norlin C, Czaja CA.
        Infect Control Hosp Epidemiol. 2020 Jan 10:1-3.

      2. Epidemiology of carbapenem-resistant Enterobacteriaceae in Egyptian intensive care units using National Healthcare-associated Infections Surveillance Data, 2011-2017external icon
        Kotb S, Lyman M, Ismail G, Abd El Fattah M, Girgis SA, Etman A, Hafez S, El-Kholy J, Zaki ME, Rashed HG, Khalil GM, Sayyouh O, Talaat M.
        Antimicrob Resist Infect Control. 2020 ;9:2.
        Objective: To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system. Methods: Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011-2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13. Results: There were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09). Conclusions: This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU's .

      3. Pathogens causing central-line-associated bloodstream infections in acute-care hospitals-United States, 2011-2017external icon
        Novosad SA, Fike L, Dudeck MA, Allen-Bridson K, Edwards JR, Edens C, Sinkowitz-Cochran R, Powell K, Kuhar D.
        Infect Control Hosp Epidemiol. 2020 Jan 9:1-7.
        OBJECTIVE: To describe pathogen distribution and rates for central-line-associated bloodstream infections (CLABSIs) from different acute-care locations during 2011-2017 to inform prevention efforts. METHODS: CLABSI data from the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) were analyzed. Percentages and pooled mean incidence density rates were calculated for a variety of pathogens and stratified by acute-care location groups (adult intensive care units [ICUs], pediatric ICUs [PICUs], adult wards, pediatric wards, and oncology wards). RESULTS: From 2011 to 2017, 136,264 CLABSIs were reported to the NHSN by adult and pediatric acute-care locations; adult ICUs and wards reported the most CLABSIs: 59,461 (44%) and 40,763 (30%), respectively. In 2017, the most common pathogens were Candida spp/yeast in adult ICUs (27%) and Enterobacteriaceae in adult wards, pediatric wards, oncology wards, and PICUs (23%-31%). Most pathogen-specific CLABSI rates decreased over time, excepting Candida spp/yeast in adult ICUs and Enterobacteriaceae in oncology wards, which increased, and Staphylococcus aureus rates in pediatric locations, which did not change. CONCLUSIONS: The pathogens associated with CLABSIs differ across acute-care location groups. Learning how pathogen-targeted prevention efforts could augment current prevention strategies, such as strategies aimed at preventing Candida spp/yeast and Enterobacteriaceae CLABSIs, might further reduce national rates.

      4. Implementation of the targeted assessment for prevention strategy in a healthcare system to reduce Clostridioides difficile infection ratesexternal icon
        White KA, Soe MM, Osborn A, Walling C, Fike LV, Gould CV, Kuhar DT, Edwards JR, Cochran RL.
        Infect Control Hosp Epidemiol. 2020 Jan 13:1-7.
        BACKGROUND: Prevention of Clostridioides difficile infection (CDI) is a national priority and may be facilitated by deployment of the Targeted Assessment for Prevention (TAP) Strategy, a quality improvement framework providing a focused approach to infection prevention. This article describes the process and outcomes of TAP Strategy implementation for CDI prevention in a healthcare system. METHODS: Hospital A was identified based on CDI surveillance data indicating an excess burden of infections above the national goal; hospitals B and C participated as part of systemwide deployment. TAP facility assessments were administered to staff to identify infection control gaps and inform CDI prevention interventions. Retrospective analysis was performed using negative-binomial, interrupted time series (ITS) regression to assess overall effect of targeted CDI prevention efforts. Analysis included hospital-onset, laboratory-identified C. difficile event data for 18 months before and after implementation of the TAP facility assessments. RESULTS: The systemwide monthly CDI rate significantly decreased at the intervention (beta2, -44%; P = .017), and the postintervention CDI rate trend showed a sustained decrease (beta1 + beta3; -12% per month; P = .008). At an individual hospital level, the CDI rate trend significantly decreased in the postintervention period at hospital A only (beta1 + beta3, -26% per month; P = .003). CONCLUSIONS: This project demonstrates TAP Strategy implementation in a healthcare system, yielding significant decrease in the laboratory-identified C. difficile rate trend in the postintervention period at the system level and in hospital A. This project highlights the potential benefit of directing prevention efforts to facilities with the highest burden of excess infections to more efficiently reduce CDI rates.

    • Informatics
      1. Acceptability of using geosocial networking applications for HIV/sexually transmitted disease partner notification and sexual health servicesexternal icon
        Contesse MG, Fredericksen RJ, Wohlfeiler D, Hecht J, Kachur R, Strona FV, Katz DA.
        Sex Transm Dis. 2020 Jan;47(1):41-47.
        BACKGROUND: Geosocial networking (GSN) app use among men who have sex with men (MSM) has presented new opportunities for increasing the reach and efficiency of sexual health interventions but also poses challenges to HIV/sexually transmitted disease partner notification. Understanding MSM's attitudes toward app-based preventive sexual health services can help inform their development and delivery. METHODS: We recruited US MSM who had met a sex partner on GSN apps in the last year to participate in an online survey assessing acceptability and preferences regarding app-based partner notification, health department presence, and sexual health services. Three app-based notification strategies were presented: sending notification messages through participant's/partner's app profile, health department app profile, or in-app anonymous messaging. RESULTS: Of 791 respondents, a majority (70%) preferred to be notified by their partner directly; however, most would get tested if notified by health department profile (95%) or anonymous in-app message (85%). Given the options provided, 50% preferred notifying a partner using their own profile, 26% with health department assistance, and 24% via in-app anonymous message. A majority (71%) were comfortable notifying a partner through a health department profile, and 74% were comfortable using in-app anonymous messaging. Most participants (82%) were comfortable with health departments having app profiles to provide sexual health services. CONCLUSIONS: Our results suggest that GSN app-based partner notification and sexual health services would be used by and are acceptable to US MSM. Partnering with app companies to integrate these services and increase access to public health programs has potential to improve MSM sexual health.

    • Injury and Violence
      1. Implementing a clinically based fall prevention programexternal icon
        Stevens JA, Smith ML, Parker EM, Jiang L, Floyd FD.
        Am J Lifestyle Med. 2020 Jan-Feb;14(1):71-77.
        Introduction. Among people aged 65 and older, falls are the leading cause of both fatal and nonfatal injuries. The burden of falls is expected to increase as the US population ages. The Centers for Disease Control and Prevention (CDC) developed the STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative to help primary care providers incorporate fall risk screening, assessment of patients' modifiable risk factors, and implementation of evidence-based treatment strategies. Methods. In 2010, CDC funded the New York State Department of Health to implement STEADI in primary care sites in selected communities. The Medical Director of United Health Services championed integrating fall prevention into clinical practice and oversaw staff training. Components of STEADI were integrated into the health system's electronic health record (EHR), and fall risk screening questions were added to the nursing staff's patient intake forms. Results. In the first 12 months, 14 practices saw 10 702 patients aged 65 and older. Of these, 8457 patients (79.0%) were screened for fall risk and 1534 (18.1%) screened positive. About 52% of positive patients completed the Timed Up and Go gait and balance assessment. Screening declined to 49% in the second 12 months, with 21% of the patients screening positive. Conclusions. Fall prevention can be successfully integrated into primary care when it is supported by a clinical champion, coupled with timely staff training/retraining, incorporated into the EHR, and adapted to fit into the practice workflow.

    • Laboratory Sciences
      1. Population-level human secretor status is associated with genogroup 2 type 4 norovirus predominanceexternal icon
        Arrouzet CJ, Ellis K, Kambhampati A, Chen Y, Steele M, Lopman B.
        J Infect Dis. 2020 Jan 4.
        BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis. Genogroup 2 type 4 (GII.4) has been the dominant norovirus genotype worldwide since its emergence in the mid-1990s. Individuals with a functional fucosyltransferase-2 gene, known as secretors, have increased susceptibility to GII.4 noroviruses. We hypothesized that this individual-level trait may drive GII.4 norovirus predominance at the human population level. METHODS: We conducted a systematic review for studies reporting norovirus outbreak or sporadic case genotypes and merged this with data on proportions of human secretor status in various countries from a separate systematic review. We used inverse variance-weighted linear regression to estimate magnitude of the population secretor-GII.4 proportion association. RESULTS: 219 genotype and 112 secretor studies with data from 38 countries were included in the analysis. Study-level GII.4 proportion among all noroviruses ranged from 0% to 100%. Country secretor proportion ranged from 43.8% to 93.9%. We observed a 0.69% (95% CI: 0.19, 1.18) increase in GII.4 proportion for each percent increase in human secretor proportion, controlling for Human Development Index. CONCLUSIONS: Norovirus evolution and diversity may be driven by local population human host genetics. Our results may have vaccine development implications including whether specific antigenic formulations would be required for different populations.

      2. Reverse transcription-polymerase chain reaction testing on filter paper-dried serum for laboratory-based dengue surveillance - American Samoa, 2018external icon
        Curren EJ, Tufa AJ, Hancock WT, Biggerstaff BJ, Vaifanua-Leo JS, Montalbo CA, Sharp TM, Fischer M, Hills SL, Gould CV.
        Am J Trop Med Hyg. 2020 Jan 13.
        Laboratory-based surveillance for arboviral diseases is challenging in resource-limited settings. We evaluated the use of filter paper-dried sera for detection of dengue virus (DENV) RNA during an outbreak in American Samoa. Matched liquid and filter paper-dried sera were collected from patients with suspected dengue and shipped to a reference laboratory for diagnostic testing. RNA was extracted from each sample and tested for DENV RNA by real-time reverse transcription-polymerase chain reaction (RT-PCR). Of 18 RT-PCR-positive liquid specimens, 14 matched filter paper-dried specimens were positive for a sensitivity of 78% (95% CI, 55-91%). Of 82 RT-PCR-negative liquid specimens, all filter paper-dried specimens were negative for a specificity of 100% (95% CI, 96-100%). Shipping of filter paper-dried specimens was similarly timely but less expensive than shipping liquid sera. Using filter paper-dried serum or blood can be a cost-effective and sustainable approach to surveillance of dengue and other arboviral diseases in resource-limited settings.

      3. Binding of the von Willebrand factor a domain of capillary morphogenesis protein 2 to anthrax protective antigen vaccine reduces immunogenicity in miceexternal icon
        de Oliveira FF, Mamillapalli S, Gonti S, Brey RN, Li H, Schiffer J, Casadevall A, Bann JG.
        mSphere. 2020 Jan 15;5(1).
        Protective antigen (PA) is a component of anthrax toxin that can elicit toxin-neutralizing antibody responses. PA is also the major antigen in the current vaccine to prevent anthrax, but stability problems with recombinant proteins have complicated the development of new vaccines containing recombinant PA. The relationship between antigen physical stability and immunogenicity is poorly understood, but there are theoretical reasons to think that this parameter can affect immune responses. We investigated the immunogenicity of anthrax PA, in the presence and absence of the soluble von Willebrand factor A domain of the human form of receptor capillary morphogenesis protein 2 (sCMG2), to elicit antibodies to PA in BALB/c mice. Prior studies showed that sCMG2 stabilizes the 83-kDa PA structure to pH, chemical denaturants, temperature, and proteolysis and slows the hydrogen-deuterium exchange rate of histidine residues far from the binding interface. In contrast to a vaccine containing PA without adjuvant, we found that mice immunized with PA in stable complex with sCMG2 showed markedly reduced antibody responses to PA, including toxin-neutralizing antibodies and antibodies to domain 4, which correlated with fewer toxin-neutralizing antibodies. In contrast, mice immunized with PA in concert with a nonbinding mutant of sCMG2 (D50A) showed anti-PA antibody responses similar to those observed with PA alone. Our results suggest that addition of sCMG2 to a PA vaccine formulation is likely to result in a significantly diminished immune response, but we discuss the multitude of factors that could contribute to reduced immunogenicity.IMPORTANCE The anthrax toxin PA is the major immunogen in the current anthrax vaccine (anthrax vaccine adsorbed). Improving the anthrax vaccine for avoidance of a cold chain necessitates improvements in the thermodynamic stability of PA. We address how stabilizing PA using sCMG2 affects PA immunogenicity in BALB/c mice. Although the stability of PA is increased by binding to sCMG2, PA immunogenicity is decreased. This study emphasizes that, while binding of a ligand retains or improves conformational stability without affecting the native sequence, epitope recognition or processing may be affected, abrogating an effective immune response.

      4. Alcohol consumption alters anti-Strongyloides stercoralis antibodies productionexternal icon
        De Souza JN, Cruz AD, Araujo WA, Sampaio LM, Allegretti SM, Teixeira MC, Handali S, Galvao-Castro B, Soares NM.
        Immunobiology. 2019 Dec 12:151898.
        Individuals infected with Strongyloides stercoralis have been reported to produce different immunoglobulins isotypes, yet few studies have evaluated their use in strongyloidiasis diagnosis. The aim of this work was to evaluate the immunoreactivity of different classes and subclasses of anti-S. stercoralis circulating antibodies in alcoholic patients by ELISA and to perform immunoblotting in samples with discordant results between parasitological and immunological methods. 345 male patients with a clinical diagnosis of alcoholism hospitalized at a reference center for alcoholics in Salvador, Bahia, Brazil, were included in this study. The fecal samples were examined by three different parasitological methods (spontaneous sedimentation, Baermann-Moraes and Agar Plate Culture methods). The ELISA was performed for the detection of IgG, IgG1, IgG4, IgE and IgA1 anti-S. stercoralis. Immunoblotting, for the detection of specific IgA1, was used to elucidate discordant results between parasitological and immunological methods. S. stercoralis infection frequency in alcoholic patients by parasitological methods was 21.4% (74/345). Although IgE-ELISA demonstrated a high sensitivity and specificity in non-alcoholic patients, about 30% (22/74) of alcoholics with larvae in feces were negative. IgG1-ELISA detected the lowest frequency of antibodies in alcoholic patients with larvae in feces, only 57% (42/74). IgG4-ELISA was the best assay for S. stercoralis infection immunodiagnosis. Immunoreactivity in the immunoblotting for IgA1 at 90, 75, 26 and/or 17kDa bands was observed in 92% (33/36) of alcoholics with larvae excretion and negative ELISA for one or more antibody isotypes. In conclusion, IgG4-ELISA showed the highest sensitivity and specificity, thus demonstrating its superiority for strongyloidiasis immunodiagnosis in alcoholic and non-alcoholic individuals. Both, IgE and IgG1-ELISA presented high sensitivities and specificities for S. stercoralis infection diagnosis in non-alcoholics, however there was low reactivity in alcoholic individuals. This can be associated with an increased susceptibility to severe strongyloidiasis in these patients. IgA1-immunoblotting can be used to confirm S. stercoralis infection when there are discordant results between parasitological methods and ELISA.

      5. In a companion paper, we requested the Judicial Commission to correct the type strain of Aeromonas punctata from ATCC 15468(T) to NCMB 74(T) (=ATCC 23309(T)). Correction of this error on the 1980 Approved Lists by an Opinion of the Judicial Commission will remove the status of the name Aeromonas caviae as a junior objective synonym of A. punctata. This is important because the scientific community continues to use the name A. caviae almost exclusively instead of A. punctata. However, the corrective action of this Opinion will cause a new problem. A. punctata and A. eucrenophila will then become objective synonyms because both species will have the same type strain NCMB 74(T), and A. punctata would have priority because it was published first (1890 vs. 1987). Thus, A. punctata rather than A. eucrenophila would become the correct name for DNA hybridization group 6. A. punctata has had a very confusing history since it was first described as Bacillus punctatus by Zimmermann in 1890. It was without a type strain for over 50 years, and unfortunately, has had an incorrect type strain for some 40 years. The name A. punctata as a bacterial species has been used incorrectly in the literature very frequently, either based on the wrong type strain or with the wrong definition or circumscription. The name A. punctata is not accepted or used by most specialists who study and publish scientific papers and reviews on Aeromonas. Under the heading 'Rejection of Names' Rule 56a of the Bacterial Code states reasons why the Judicial Commission can reject a name, the first is: '(1) An ambiguous name (nomen ambiguum), i.e., a name which has been used with different meanings and thus has become a source of error'. Rule 56a gives the Judicial Commission authority to place names on the list of rejected names. Our analysis of its history leads us to state unequivocally that A. punctata currently is, and has been throughout the vast majority of its history, an ambiguous name. After considering all the possible alternatives and their consequences we request the Judicial Commission to go against the rules of priority; to invoke case (1) of Rule 56a, and issue an Opinion conserving A. eucrenophila over A. punctata; and to place the name A. punctata on the list of rejected names. We argue that these actions will give instant stability to a complex and confusing situation by making A. eucrenophila rather than A. punctata the correct name for 'Aeromonas DNA hybridization group 6', an association that is almost universally accepted by the scientific community as reflected in the literature.

      6. Analysis of global collection of group A streptococcus genomes reveals that the majority encode a trio of M and M-like proteinsexternal icon
        Frost HR, Davies MR, Delforge V, Lakhloufi D, Sanderson-Smith M, Srinivasan V, Steer AC, Walker MJ, Beall B, Botteaux A, Smeesters PR.
        mSphere. 2020 Jan 8;5(1).
        The core Mga (multiple gene activator) regulon of group A Streptococcus (GAS) contains genes encoding proteins involved in adhesion and immune evasion. While all GAS genomes contain genes for Mga and C5a peptidase, the intervening genes encoding M and M-like proteins vary between strains. The genetic make-up of the Mga regulon of GAS was characterized by utilizing a collection of 1,688 GAS genomes that are representative of the global GAS population. Sequence variations were examined with multiple alignments, and the expression of all core Mga regulon genes was examined by quantitative reverse transcription-PCR in a representative strain collection. In 85.2% of the sampled genomes, the Mga locus contained genes encoding Mga, Mrp, M, Enn, and C5a peptidase proteins. These isolates account for 53% of global infections. Only 9.1% of genomes did not contain either an mrp or an enn gene. The pairwise identity within Enn (68.6%) and Mrp (83.2%) protein sequences was higher than within M proteins (44.7%). Gene expression varied between strains tested, but high expression was recorded for all genes in at least one strain. Previous nomenclature issues were clarified with molecular gene definitions. Our findings support a shift in focus in the GAS research field to further consider the role of Mrp and Enn in virulence and vaccine development.IMPORTANCE While the GAS M protein has been the leading vaccine target for decades, the bacteria encode many other virulence factors of interest for vaccine development. In this work, we show that emm-like genes are encoded in a remarkable majority of GAS genomes and expressed at a level similar to that for the emm gene. In collaboration with the U.S. Centers for Disease Control, we developed molecular definitions of the different emm and emm-like gene families. This clarification should abrogate mistyping of strains, especially in the area of whole-genome typing. We have also updated the emm-typing collection by removing emm-like gene sequences and provided in-depth analysis of Mrp and Enn protein sequence structure and diversity.

      7. OBJECTIVES: Syphilis morbidity is high among pregnant women in lower income countries with limited laboratory capacity. We evaluated a long-standing global Syphilis Serology Proficiency Programme (SSPP) that supports testing quality in national reference laboratories to determine if participation affects congenital syphilis elimination strategies. DESIGN: In this observational cross-sectional study, we calculated coverage on type, frequency and quality of syphilis testing reported by laboratories enrolled in the SSPP from 2008 to 2015. We used country-reported data to WHO on four congenital syphilis (CS) indicators and World Bank country economic data to compare coverage and completeness of reporting of indicators in lower income countries with and without an SSPP-enrolled laboratory. PARTICIPANTS: From 2008-2015, 78 laboratories from 51 countries participated in >1 SSPP evaluation; 56% were national reference laboratories, of which most (93%) participated for >3 years and 11 (22%) in all 24 cycles. RESULTS: Median proficiency performance score was >95% regardless of test conducted. Of the 51 countries with an SSPP-enrolled laboratory, 22 (43%) were lower-income countries, of which 21 reported CS data during 2008-2015. Comparing CS data from 87 (90% of total) lower income countries with and without an SSPP-enrolled laboratory, countries with an SSPP-laboratory had stronger reporting on antenatal syphilis testing (p=0.04). For 2015, an estimated 74% of prenatal syphilis tests and 63% of positive tests reported to WHO from countries with an SSPP-enrolled laboratory. CONCLUSION: The SSPP has focused well on national reference laboratories, but has been only partially successful in recruiting laboratories from lower income countries. The finding that over half of syphilis infections in pregnant women living in countries with SSPP-enrolled laboratories suggests wide reach of the current quality assurance programme. However, reach could expand with focussed recruitment of laboratories from lower income countries.

      8. The poly-gamma-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of D-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed D-, L-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-alpha, whereas B. licheniformis PGA elicited all those plus IL-1beta. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1beta, and TNF-alpha. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.

      9. Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell deathexternal icon
        Kagan VE, Tyurina YY, Sun WY, Vlasova , Dar H, Tyurin VA, Amoscato AA, Mallampalli R, van der Wel PC, He RR, Shvedova AA, Gabrilovich DI, Bayir H.
        Free Radic Biol Med. 2019 Dec 25;147:231-241.
        High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these "partial" intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented.

      10. Potent in vitro activity of beta-D-4'-chloromethyl-2'-deoxy-2'-fluorocytidine against Nipah virusexternal icon
        Lo MK, Amblard F, Flint M, Chatterjee P, Kasthuri M, Li C, Russell O, Verma K, Bassit L, Schinazi RF, Nichol ST, Spiropoulou CF.
        Antiviral Res. 2020 Jan 11:104712.
        Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that continues to cause outbreaks in humans characterized by high mortality and significant clinical sequelae in survivors. Currently, no therapeutics are approved for use in humans against NiV infection. Here, we report that 4'-chloromethyl-2'-deoxy-2'-fluorocytidine (ALS-8112) inhibits NiV. ALS-8112 is the parent nucleoside of lumicitabine, which has been evaluated in phase I and II clinical trials to treat pediatric and adult respiratory syncytial virus infection. In this study, we tested ALS-8112 against NiV and other major human respiratory pneumo- and paramyxoviruses in 2 human lung epithelial cell lines, and demonstrated the ability of ALS-8112 to reduce infectious wild-type NiV yield by over 6 orders of magnitude with no apparent cytotoxicity. However, further cytotoxicity testing in primary cells and bone marrow progenitor cells indicated cytotoxicity at higher concentrations of ALS-8112. Our results warrant the evaluation of lumicitabine against NiV infection in relevant animal models.

      11. Successful isolation of Treponema pallidum strains from patients' cryopreserved ulcer exudate using the rabbit modelexternal icon
        Pereira LE, Katz SS, Sun Y, Mills P, Taylor W, Atkins P, Thurlow CM, Chi KH, Danavall D, Cook N, Ahmed T, Debra A, Philip S, Cohen S, Workowski KA, Kersh E, Fakile Y, Chen CY, Pillay A.
        PLoS One. 2020 ;15(1):e0227769.
        Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

      12. Optimization and qualification of a functional anti-drug antibody assay for HIV-1 bnAbsexternal icon
        Seaman MS, Bilska M, Ghantous F, Eaton A, LaBranche CC, Greene K, Gao H, Weiner JA, Ackerman ME, Garber DA, Rosenberg YJ, Sarzotti-Kelsoe M, Montefiori DC.
        J Immunol Methods. 2020 Jan 6:112736.
        The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.

      13. Immunotoxicity and allergenic potential induced by topical application of perfluorooctanoic acid (PFOA) in a murine modelexternal icon
        Shane HL, Baur R, Lukomska E, Weatherly L, Anderson SE.
        Food Chem Toxicol. 2020 Jan 2:111114.
        Perfluorooctanoic acid (PFOA) is a per- and polyfluoroalkyl substance (PFAS) once used as a surfactant in the polymerization of chemicals. Because of its ubiquitous nature and long half-life, PFOA is commonly detected in the environment, wildlife, and humans. While skin exposure to PFOA is of concern, studies evaluating the immunotoxicity of dermal exposure are lacking. These studies evaluated the immunotoxicity of PFOA (0.5-2% w/v, or 12.5-50mg/kg/dose) following dermal exposure using a murine model. PFOA (0.5-2%) was not identified to be an irritant or sensitizer using the local lymph node assay. The IgM antibody response to sheep red blood cell. was significantly reduced in the spleen following 4-days of dermal exposure (2%). PFOA exposure produced a significant decrease in thymus (1 and 2%) and spleen (0.5-2%) weight along with an increase in liver weight (0.5-2%). Immune cell phenotyping identified a reduction in the frequency (1 and 2%) and number (0.5-2%) of splenic B-cells. To further define the mechanism of immunotoxicity, gene expression was also evaluated in the skin. The findings support a potential involvement of the nuclear receptor PPARalpha. These results demonstrate that dermal exposure to PFOA is immunotoxic and raise concern about potential adverse effects from dermal exposure.

      14. Inhalation of welding fumes reduced sperm counts and high fat diet reduced testosterone levels; differential effects in Sprague Dawley and Brown Norway ratsexternal icon
        Skovmand A, Erdely A, Antonini JM, Nurkiewicz TR, Shoeb M, Eye T, Kodali V, Loeschner K, Vidmar J, Agerholm JS, Goericke-Pesch S, Vogel U, Hougaard KS.
        Part Fibre Toxicol. 2020 Jan 10;17(1):2.
        BACKGROUND: Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m(3) of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7-12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24). RESULTS: At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFalpha). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet. CONCLUSION: Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.

      15. Seroreactivity against Marburg or related filoviruses in West and Central Africaexternal icon
        Steffen I, Lu K, Hoff NA, Mulembakani P, Okitolonda Wemakoy E, Muyembe-Tamfum JJ, Ndembi N, Brennan CA, Hackett J, Switzer WM, Saragosti S, Mbensa GO, Laperche S, Rimoin AW, Simmons G.
        Emerg Microbes Infect. 2020 Dec;9(1):124-128.
        A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary.

      16. Impacts of organomodified nanoclays and their incinerated byproducts on bronchial cell monolayer integrityexternal icon
        Stueckle TA, White A, Wagner A, Gupta RK, Rojanasakul Y, Dinu CZ.
        Chem Res Toxicol. 2019 Dec 16;32(12):2445-2458.
        Incorporation of engineered nanomaterials (ENMs) into nanocomposites using advanced manufacturing strategies is set to revolutionize diverse technologies. Of these, organomodified nanoclays (ONCs; i.e., smectite clays with different organic coatings) act as nanofillers in applications ranging from automotive to aerospace and biomedical systems. Recent toxicological evaluations increased awareness that exposure to ONC can occur along their entire life cycle, namely, during synthesis, handling, use, manipulation, and disposal. Compared to other ENMs, however, little information exists describing which physicochemical properties contribute to induced health risk. This study conducted high content screening on bronchial epithelial cell monolayers for coupled high-throughput in vitro assessment strategies aimed to evaluate acute toxicity of a library of ONCs (all of prevalent use) prior to and after simulated disposal by incineration. Coating-, incineration status-, and time-dependent effects were considered to determine changes in the pulmonary monolayer integrity, cell transepithelial resistance, apoptosis, and cell metabolism. Results showed that after exposure to each ONC at its half-maximal inhibitory concentration (IC50) there is a material-induced toxicity effect with pristine nanoclay, for instance, displaying acute loss of monolayer coverage, resistance, and metabolism, coupled with increased number of apoptotic cells. Conversely, the other three ONCs tested displayed little loss of monolayer integrity; however, they exhibited differential coating-dependent increased apoptosis and up to 40-45% initial reduction in cell metabolism. Moreover, incinerated byproducts of ONCs exhibited significant loss of monolayer coverage and integrity, increased necrosis, with little evidence of monolayer re-establishment. These findings indicate that characteristics of organic coating type largely determine the mechanism of cytotoxicity and the ability of the monolayer to recover. Use of high content screening coupled with traditional in vitro assays proves to serve as a rapid pulmonary toxicity assessment tool to help define prevention by targeted physicochemical material properties design strategies.

      17. The SOX9-aldehyde dehydrogenase axis determines resistance to chemotherapy in non-small-cell lung cancerexternal icon
        Voronkova MA, Rojanasakul LW, Kiratipaiboon C, Rojanasakul Y.
        Mol Cell Biol. 2020 Jan 3;40(2).
        Chemotherapy resistance and tumor relapse are the major contributors to low patient survival, and both have been largely attributed to cancer stem-like cells (CSCs) or tumor-initiating cells (TICs). Moreover, most conventional therapies are not effective against CSCs, which necessitates the discovery of CSC-specific biomarkers and drug targets. Here, we demonstrated that the embryonic transcription factor SOX9 is an important regulator of acquired chemoresistance in non-small-cell lung cancer (NSCLC). Our results show that SOX9 expression is elevated in NSCLC cells after treatment with the chemotherapeutic cisplatin and that overexpression of SOX9 correlates with worse overall survival in lung cancer patients. We further demonstrated that SOX9 knockdown increases cellular sensitivity to cisplatin, whereas its overexpression promotes drug resistance. Moreover, this transcription factor promotes the stem-like properties of NSCLC cells and increases their aldehyde dehydrogenase (ALDH) activity, which was identified to be the key mechanism of SOX9-induced chemoresistance. Finally, we showed that ALDH1A1 is a direct transcriptional target of SOX9, based on chromatin immunoprecipitation and luciferase reporter assays. Taken together, our novel findings on the role of the SOX9-ALDH axis support the use of this CSC regulator as a prognostic marker of cancer chemoresistance and as a potential drug target for CSC therapy.

      18. Evolutionary superscaffolding and chromosome anchoring to improve Anopheles genome assembliesexternal icon
        Waterhouse RM, Aganezov S, Anselmetti Y, Lee J, Ruzzante L, Reijnders M, Feron R, Berard S, George P, Hahn MW, Howell PI, Kamali M, Koren S, Lawson D, Maslen G, Peery A, Phillippy AM, Sharakhova MV, Tannier E, Unger MF, Zhang SV, Alekseyev MA, Besansky NJ, Chauve C, Emrich SJ, Sharakhov IV.
        BMC Biol. 2020 Jan 2;18(1):1.
        BACKGROUND: New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from 'finished'. Updating multi-scaffold drafts to chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) to predict scaffold neighbours (adjacencies) offers a potentially useful complementary method for improving draft assemblies. RESULTS: We evaluated and employed 3 gene synteny-based methods applied to 21 Anopheles mosquito assemblies to produce consensus sets of scaffold adjacencies. For subsets of the assemblies, we integrated these with additional supporting data to confirm and complement the synteny-based adjacencies: 6 with physical mapping data that anchor scaffolds to chromosome locations, 13 with paired-end RNA sequencing (RNAseq) data, and 3 with new assemblies based on re-scaffolding or long-read data. Our combined analyses produced 20 new superscaffolded assemblies with improved contiguities: 7 for which assignments of non-anchored scaffolds to chromosome arms span more than 75% of the assemblies, and a further 7 with chromosome anchoring including an 88% anchored Anopheles arabiensis assembly and, respectively, 73% and 84% anchored assemblies with comprehensively updated cytogenetic photomaps for Anopheles funestus and Anopheles stephensi. CONCLUSIONS: Experimental data from probe mapping, RNAseq, or long-read technologies, where available, all contribute to successful upgrading of draft assemblies. Our evaluations show that gene synteny-based computational methods represent a valuable alternative or complementary approach. Our improved Anopheles reference assemblies highlight the utility of applying comparative genomics approaches to improve community genomic resources.

      19. Hemagglutinin and neuraminidase antibodies are induced in an age- and subtype- dependent manner after influenza virus infectionexternal icon
        Wong SS, Waite B, Ralston J, Wood T, Reynolds GE, Seeds R, Newbern EC, Thompson MG, Huang QS, Webby RJ.
        J Virol. 2020 Jan 15.
        Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally-infected human cohorts in Auckland, New Zealand; a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases (n=50), and an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection (n=94). The induction of both HA and NA-antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those < 20 years old (yo) for influenza A (Serosurvey, p=0.01, Immunology, p=0.02), but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults >/= 20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% vs 14% [5 - 19 yo] and 0% [0 - 4 yo] respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 - 4 yo] and 75% [5 - 19 yo] vs 40% [ >/= 20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA-antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity.IMPORTANCE Data on the immunologic responses to neuraminidase (NA) is lacking when compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA-immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA-antibody after infection is influenced by age and subtypes. Such response dynamics suggests the influence of immunological memory and understanding how this process is regulated will be critical to any vaccine effort targeting NA-immunity.

    • Maternal and Child Health
      1. Infant mortality attributable to birth defects - United States, 2003-2017external icon
        Almli LM, Ely DM, Ailes EC, Abouk R, Grosse SD, Isenburg JL, Waldron DB, Reefhuis J.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):25-29.
        Birth defects are a leading cause of infant mortality in the United States, accounting for 20.6% of infant deaths in 2017 (1). Rates of infant mortality attributable to birth defects (IMBD) have generally declined since the 1970s (1-3). U.S. linked birth/infant death data from 2003-2017 were used to assess trends in IMBD. Overall, rates declined 10% during 2003-2017, but decreases varied by maternal and infant characteristics. During 2003-2017, IMBD rates decreased 4% for infants of Hispanic mothers, 11% for infants of non-Hispanic black (black) mothers, and 12% for infants of non-Hispanic white (white) mothers. In 2017, these rates were highest among infants of black mothers (13.3 per 10,000 live births) and were lowest among infants of white mothers (9.9). During 2003-2017, IMBD rates for infants who were born extremely preterm (20-27 completed gestational weeks), full term (39-40 weeks), and late term/postterm (41-44 weeks) declined 20%-29%; rates for moderate (32-33 weeks) and late preterm (34-36 weeks) infants increased 17%. Continued tracking of IMBD rates can help identify areas where efforts to reduce IMBD are needed, such as among infants born to black and Hispanic mothers and those born moderate and late preterm (32-36 weeks).

      2. Neural tube defects in pregnancies among women with diagnosed HIV infection - 15 jurisdictions, 2013-2017external icon
        Reefhuis J, FitzHarris LF, Gray KM, Nesheim S, Tinker SC, Isenburg J, Laffoon BT, Lowry J, Poschman K, Cragan JD, Stephens FK, Fornoff JE, Ward CA, Tran T, Hoover AE, Nestoridi E, Kersanske L, Piccardi M, Boyer M, Knapp MM, Ibrahim AR, Browne ML, Anderson BJ, Shah D, Forestieri NE, Maxwell J, Hauser KW, Obiri GU, Blumenfeld R, Higgins D, Espinet CP, Lopez B, Zielke K, Jackson LP, Shumate C, Russell K, Lampe MA.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 10;69(1):1-5.
        In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services(dagger) (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.( section sign) Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

      3. Evaluating data quality of newborn hearing screeningexternal icon
        Sanchez-Gomez MC, Dundon K, Deng X.
        J Early Hear Detect Interv. 2019 ;4(3):26-32.
        Scope: Jurisdictional-based Early Hearing Detection and Intervention Information Systems (EHDI-IS) collect data on the hearing screening and follow-up status of infants across the United States. These systems serve as tools that assist EHDI programs' staff and partners in their tracking activities and provide a variety of data reports to help ensure that all children who are deaf/hard of hearing (DHH) are identified early and receive recommended intervention services. The quality and timeliness of the data collected with these systems are crucial to effectively meeting these goals. Methodology: Forty-eight EHDI programs, funded by the Centers for Disease Control and Prevention (CDC), successfully evaluated the accuracy, completeness, uniqueness, and timeliness of the hearing screening data as well as the acceptability (i.e., willingness to report) of the EHDI-IS among data reporters (2013-2016). This article describes the evaluations conducted and presents the findings from these evaluation activities. Conclusions: Most state EHDI programs are receiving newborn hearing screening results from hospitals and birthing facilities in a consistent way and data reporters are willing to report according to established protocols. However, additional efforts are needed to improve the accuracy and completeness of reported demographic data, results from infants transferred from other hospitals, and results from infants admitted to the Neonatal Intensive Care Unit.

      4. Philosophy of care delivery for Spina Bifidaexternal icon
        Thibadeau J, Walker WO, Castillo J, Dicianno BE, Routh JC, Smith KA, Ouyang L.
        Disabil Health J. 2019 Dec 20:100883.
        The multidisciplinary model (MCM) is described as one that utilizes skills and experience from practitioners belonging to various disciplines, each treating patients from a specific clinical perspective.(1) The Spina Bifida Association (SBA) supports and recommends that clinical care for people with Spina Bifida (SB) be provided in specialty clinics of which the MCM is an example; that care be coordinated; and that there be a plan for transitional care.(2) This paper explores the challenges the MCM faces with a transitioning and aging population in a care system that calls for a positive patient experience, engaged health care professionals, desired outcomes, with consideration of cost.

      5. OBJECTIVE: To estimate the prevalence of health care transition components among youth with autism spectrum disorder (ASD) aged 12-17 using the 2016 National Survey of Children's Health (NSCH), compared to youth with other mental, behavioral, or developmental disorders (MBDDs) or youth without MBDDs. METHODS: The 2016 NSCH is a nationally and state representative survey that explores issues of health and well-being among children ages 0-17. Within the NSCH, parents of a subset of youth, ages 12-17, are asked a series of questions about their youth's eventual transition into the adult health care system. The current study explores components of this transition, comparing youth diagnosed with ASD, youth with other mental, behavioral, or developmental disorders (MBDDs), and youth without MBDDs. RESULTS: Approximately 1-in-4 youth with ASD had actively worked with their doctor to understand future changes to their health care, significantly less than youth with other MBDDs and youth without MBDDs. Fewer than 2-in-5 youth with ASD had met with their doctor privately or had a parent who knew how their youth would be insured when they reached adulthood. CONCLUSIONS: The current analysis of a nationally representative sample of youth reveals discrepancies in the proportion of youth with ASD receiving appropriate health care transition planning compared to youth with other MBDDs and youth without MBDDs. These findings suggest the potential for barriers among youth with ASD to effectively transitioning into the adult health care system.

    • Mining
      1. A new catalog of explosion source parameters in the Utah region with application to ML–MC-based depth discrimination at local distancesexternal icon
        Voyles JR, Holt MM, Hale JM, Koper KD, Burlacu R, Chambers DJ.
        Seismol Res Lett. 2019 ;91(1):222-236.
        A catalog of explosion source parameters is valuable for testing methods of source classification in seismically active regions. We develop a manually reviewed catalog of explosions in the Utah region for 1 October 2012 to 30 June 2018 and use it to assess a newly proposed, magnitude-based depth discriminant. Within the Utah region we define 26 event clusters that are primarily associated with mine blasts but also include explosions from weapons testing and disposal. The catalog refinement process consists of confirming the explosion source labels, revising the local (ML) and coda duration (MC) magnitudes, and relocating the hypocenters. The primary features used to determine source labels are waveform characteristics such as frequency content, the proximity of the preliminary epicenter to a permitted blast region, the time of day, and prior notification from mine operators. We reviewed 2199 seismic events of which 1545 are explosions, 459 are local earthquakes, and 195 are other event types. Of the reviewed events, 127 (5.8%) were reclassified with new labels. Over 74% of the reviewed explosions have both ML and MC, a sizable improvement over the unreviewed catalog (65%). The mean ML–MC value for the new explosion catalog is -0:196 +/- 0:017 (95% confidence interval) compared with a previously determined value of 0:048 +/- 0:008 for naturally occurring earthquakes in the Utah region. The shallow depths of the explosions lead to enhanced coda production, which in turn leads to anomalously large MC values. This finding confirms that ML-MC is a useful metric for discriminating explosions from deeper tectonic earthquakes in Utah. However, there is significant variation in ML–MC among the 26 explosion source regions, suggesting that ML–MC observations should be combined with other classification metrics to achieve the best performance in distinguishing explosions from earthquakes.

    • Occupational Safety and Health
      1. Identifying potentially risky phases leading to knee musculoskeletal disorders during shingle installation operationsexternal icon
        Dutta A, Breloff SP, Dai F, Sinsel EW, Warren CM, Wu JZ.
        J Constr Eng Manage. 2020 ;146(3).
        Repeated and prolonged awkward kneeling can result in musculoskeletal disorders (MSD) in construction roofers. However, a task-specific risk assessment for roofers' knee injuries is still missing in the literature. This study identified a ranking-based ergonomic method for suggesting potentially risky phases that may increase knee MSD risk during shingle installation operations. On a slope-adjustable wooden platform in a laboratory setting, nine subjects performed shingle installations that included seven phases: (1) reaching for shingles, (2) placing shingles, (3) grabbing nail gun, (4) moving to first nailing position, (5) nailing shingles, (6) replacing nail gun, and (7) returning to upright position. Flexion, abduction, adduction, and internal and external knee rotations were measured to assess relative risks of these phases by ranking them with a scoring model. The ranking results revealed that the phases of placing shingles and nailing shingles lead to the most knee MSD risk exposure, and awkward flexion, abduction, and adduction involved in these phases can significantly contribute to the potential knee MSD risk measurement. By using the ranking-based method, this study suggested that certain phases of the shingle installation process may increase knee MSD risk, which is useful for developing effective interventions to reduce knee injury risk exposures from roof shingle installation.

      2. Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an updateexternal icon
        Pinkerton L, Bertke SJ, Yiin J, Dahm M, Kubale T, Hales T, Purdue M, Beaumont JJ, Daniels R.
        Occup Environ Med. 2020 Jan 2.
        OBJECTIVES: To update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort. METHODS: Vital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration. RESULTS: Compared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD). CONCLUSIONS: This update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

    • Parasitic Diseases
      1. Anti-malarial drugs have long half-lives, so clinical trials to monitor their efficacy require long durations of follow-up to capture drug failure that may only become patent weeks after treatment. Reinfections often occur during follow-up so robust methods of distinguishing drug failures (recrudescence) from emerging new infections are needed to produce accurate failure rate estimates. "Molecular correction" aims to achieve this by comparing the genotypes between a patient's pre-treatment (initial) blood sample and any infection that occurs during follow-up, 'matching' genotypes indicating a drug failure. We use an in-silico approach to show that the widely used "match counting" method of molecular correction with microsatellite markers is likely to be highly unreliable and may lead to gross under- or over-estimates of true failure rates depending on the choice of matching criterion. A Bayesian algorithm for molecular correction has been previously developed and utilized for analysis of in vivo efficacy trials. We validated this algorithm using in silico data and showed it had high specificity and generated accurate failure rate estimates. This conclusion was robust for multiple drugs, different levels of drug failure rate, different levels of transmission intensity in the study sites, and microsatellite genetic diversity. The Bayesian algorithm was inherently unable to accurately identify low-density recrudescence that occurred in a small number of patients, but this did not appear to compromise its utility as a highly effective molecular correction method for analysing microsatellite genotypes. Strong consideration should be given to using Bayesian methodology for obtaining accurate failure rate estimates during routine monitoring trials of antimalarial efficacy that use microsatellite markers.

      2. Analysis of anti-Plasmodium IgG profiles among Fulani nomadic pastoralists in northern Senegal to assess malaria exposureexternal icon
        Seck MC, Thwing J, Badiane AS, Rogier E, Fall FB, Ndiaye PI, Diongue K, Mbow M, Ndiaye M, Diallo MA, Gomis JF, Mbaye A, Ndiaye T, Gaye A, Sy M, Deme AB, Ndiaye YD, Ndiaye D.
        Malar J. 2020 Jan 13;19(1):15.
        BACKGROUND: Northern Senegal is a zone of very low malaria transmission, with an annual incidence of < 5/1000 inhabitants. This area, where the Senegal National Malaria Control Programme has initiated elimination activities, hosts Fulani, nomadic, pastoralists that spend the dry season in the south where malaria incidence is higher (150-450/1000 inhabitants) and return to the north with the first rains. Previous research demonstrated parasite prevalence of < 1% in this Fulani population upon return from the south, similar to that documented in the north in cross-sectional surveys. METHODS: A modified snowball sampling survey of nomadic pastoralists was conducted in five districts in northern Senegal during September and October 2014. Demographic information and dried blood spots were collected. Multiplex bead-based assays were used to assess antibody responses to merozoite surface protein (MSP-119) antigen of the four primary Plasmodium species, as well as circumsporozoite protein (CSP) and liver stage antigen (LSA-1) of Plasmodium falciparum. RESULTS: In the five study districts, 1472 individuals were enrolled, with a median age of 22 years (range 1 to 80 years). Thirty-two percent of subjects were under 14 years and 57% were male. The overall seroprevalence of P. falciparum MSP-119, CSP and LSA-1 antibodies were 45, 12 and 5%, respectively. Plasmodium falciparum MSP-119 antibody responses increased significantly with age in all study areas, and were significantly higher among males. The highest seroprevalence to P. falciparum antigens was observed in the Kanel district (63%) and the lowest observed in Podor (28%). Low seroprevalence was observed for non-falciparum species in all the study sites: 0.4, 0.7 and 1.8%, respectively, for Plasmodium ovale, Plasmodium vivax and Plasmodium malariae MSP-1. Antibody responses to P. vivax were observed in all study sites except Kanel. CONCLUSION: Prevalence of P. falciparum MSP-119 antibodies and increases by study participant age provided data for low levels of exposure among this transient nomadic population. In addition, antibody responses to P. falciparum short half-life markers (CSP and LSA-1) and non-falciparum species were low. Further investigations are needed to understand the exposure of the Fulani population to P. vivax.

      3. The effectiveness of older insecticide-treated bed nets (ITNs) to prevent malaria infection in an area of moderate pyrethroid resistance: results from a cohort study in Malawiexternal icon
        Shah MP, Steinhardt LC, Mwandama D, Mzilahowa T, Gimnig JE, Bauleni A, Wong J, Wiegand R, Mathanga DP, Lindblade KA.
        Malar J. 2020 Jan 15;19(1):24.
        BACKGROUND: A previous cohort study in Malawi showed that users of new insecticide-treated bed nets (ITNs) were significantly protected against malaria compared to non-users, despite moderate levels of pyrethroid resistance among the primary mosquito vectors. The present study investigated whether ITNs that were 1-2 years old continued to protect users in the same area with moderate pyrethroid resistance. METHODS: One year following a baseline cross-sectional malaria parasitaemia prevalence survey and universal distribution of deltamethrin ITNs (May 2012), a fixed cohort of 1223 children aged 6-59 months was enrolled (April 2013). Children were tested for parasitaemia at monthly scheduled visits and at unscheduled sick visits from May to December 2013 using rapid diagnostic tests. ITN use the prior night and the condition of ITNs (based on presence of holes) was assessed by caregiver self-report. The incidence rate ratio (RR) comparing malaria infection among users and non-users of ITNs was modelled using generalized estimating equations adjusting for potential confounders and accounting for repeated measures on each child. The protective efficacy (PE) of ITN use was calculated as 1 - RR. RESULTS: In this cohort, self-reported ITN use remained consistently high (> 95%) over the study period. Although users of ITNs were slightly more protected compared to non-users of ITNs, the difference in incidence of infection was not statistically significant (RR 0.83, 95% confidence interval [CI] 0.54-1.27). Among ITN users, malaria incidence was significantly lower in users of ITNs with no holes (of any size) compared to users of ITNs with >/= 1 hole (RR 0.82, 95% CI 0.69-0.98). CONCLUSIONS: There was no significant PE of using 1-2 year-old ITNs on the incidence of malaria in children in an area of moderate pyrethroid resistance, but among ITN users, the authors found increased protection by ITNs with no holes compared to ITNs with holes. Given the moderate levels of pyrethroid resistance in the primary malaria vector and recent evidence of added benefits of ITNs with synergists or non-pyrethroid insecticides, next-generation ITNs may be a useful strategy to address pyrethroid resistance and should be further explored in Malawi.

      4. Fecal immunoglobulin A against a sporozoite antigen at 12 months is associated with delayed time to subsequent cryptosporidiosis in urban Bangladesh: A prospective cohort studyexternal icon
        Steiner KL, Kabir M, Priest JW, Hossain B, Gilchrist CA, Cook H, Ma JZ, Korpe PS, Ahmed T, Faruque AS, Haque R, Petri WA.
        Clin Infect Dis. 2020 Jan 2;70(2):323-326.
        In this prospective cohort study of Bangladeshi children, greater fecal immunoglobulin A, but not plasma immunoglobulin G, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.

    • Physical Activity
      1. Associations between neighborhood social cohesion and physical activity in the United States, National Health Interview Survey, 2017external icon
        Quinn TD, Wu F, Mody D, Bushover B, Mendez DD, Schiff M, Fabio A.
        Prev Chronic Dis. 2019 Dec 19;16:E163.
        BACKGROUND: Individual social support is positively related to physical activity participation. However, less is known about how neighborhood-level social structures relate to physical activity participation. METHODS: We analyzed 2017 National Health Interview Survey data for adult participants who completed all questions on physical activity and neighborhood cohesion (N = 23,006). Each cohesion question was binary coded (cohesion or not) and used as a predictor individually and for a composite score measuring total social cohesion. We used linear regression to estimate minutes of moderate aerobic activity, and we used logistic regression to estimate the odds of meeting aerobic guidelines (>/=150 min/wk), strength guidelines (>/=2 d/wk of muscle strengthening exercises), or both guidelines, predicted by the 5 definitions of cohesion (composite cohesion and the 4 questions separately). Models were adjusted for sex, age, race/ethnicity, family-income-to-poverty ratio, education, nativity, language, and neighborhood tenure. RESULTS: Respondents who reported having more social cohesion had 45.0 more minutes of aerobic activity and increased odds of meeting aerobic, strength, and combined guidelines (odds ratio [OR] = 1.22, OR = 1.13, and OR = 1.14, respectively; P < .01 for all). Reporting having availability of help when needed, neighbors to count on, trustworthy neighbors, and close-knit neighbors all resulted in increased odds of meeting aerobic guidelines but not increased odds for meeting strength guidelines in the latter 3 components or combined guidelines for the latter 2 components. CONCLUSIONS: Having neighborhood social cohesion or select individual components of neighborhood cohesion are positively related to meeting aerobic, strength, and combined guidelines.

    • Public Health Leadership and Management
      1. Proactive case detection of common childhood illnesses by community health workers: a systematic reviewexternal icon
        Whidden C, Thwing J, Gutman J, Wohl E, Leyrat C, Kayentao K, Johnson AD, Greenwood B, Chandramohan D.
        BMJ Glob Health. 2019 ;4(6):e001799.
        Introduction: Identifying design features and implementation strategies to optimise community health worker (CHW) programmes is important in the context of mixed results at scale. We systematically reviewed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries (LMICs) on mortality, morbidity and access to care for common childhood illnesses. Methods: Published studies were identified via electronic databases from 1978 to 2017. We included randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies, and assessed their quality for risk of bias. We reported measures of effect as study investigators reported them, and synthesised by outcomes of mortality, disease prevalence, hospitalisation and access to treatment. We calculated risk ratios (RRs) as a principal summary measure, with CIs adjusted for cluster design effect. Results: We identified 14 studies of 11 interventions from nine LMICs that met inclusion criteria. They showed considerable diversity in intervention design and implementation, comparison, outcomes and study quality, which precluded meta-analysis. Proactive case detection may reduce infant mortality (RR: 0.52-0.94) and increase access to effective treatment (RR: 1.59-4.64) compared with conventional community-based healthcare delivery (low certainty evidence). It is uncertain whether proactive case detection reduces mortality among children under 5 years (RR: 0.04-0.80), prevalence of infectious diseases (RR: 0.06-1.02), hospitalisation (RR: 0.38-1.26) or increases access to prompt treatment (RR: 1.00-2.39) because the certainty of this evidence is very low. Conclusion: Proactive case detection may provide promising benefits for child health, but evidence is insufficient to draw conclusions. More research is needed on proactive case detection with rigorous study designs that use standardised outcomes and measurement methods, and report more detail on complex intervention design and implementation. PROSPERO registration number: CRD42017074621.

    • Substance Use and Abuse
      1. Reducing negative consequences from use of methamphetamineexternal icon
        Compton WM, Jones CM, Underwood N.
        Addiction. 2020 Jan 11.

      2. Update: Product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020external icon
        Ellington S, Salvatore PP, Ko J, Danielson M, Kim L, Cyrus A, Wallace M, Board A, Krishnasamy V, King BA, Rose D, Jones CM, Pollack LA.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):44-49.
        CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged <18 years. While the investigation continues, CDC recommends that the best way for persons to ensure that they are not at risk is to consider refraining from the use of all e-cigarette, or vaping, products.

      3. Opiate and tobacco use and exposure to carcinogens and toxicants in Golestan Cohort Studyexternal icon
        Etemadi A, Poustchi H, Calafat AM, Blount BC, De Jesus VR, Wang L, Pourshams A, Shakeri R, Inoue-Choi M, Shiels MS, Roshandel G, Murphy G, Sosnoff CS, Bhandari D, Feng J, Xia B, Wang Y, Meng L, Kamangar F, Brennan P, Boffetta P, Dawsey SM, Abnet CC, Malekzadeh R, Freedman ND.
        Cancer Epidemiol Biomarkers Prev. 2020 Jan 8.
        BACKGROUND: There is little information on human exposure to carcinogens and toxicants related to opiate use, alone or combined with tobacco. METHODS: Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers: tobacco alkaloids, tobacco specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs) and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose. RESULTS: Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene ( summation operator2,3-phe) resulted almost completely from opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite, and a dimethylformamide metabolite were more strongly explained by opiate use. Acrylamide metabolites and summation operator2,3-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake. CONCLUSION: Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens. IMPACT: This high exposure, particularly among dual opiates and cigarette users can have substantial global public health impact.

      4. Cigarette and cigar sales in Hawaii before and after implementation of a Tobacco 21 Lawexternal icon
        Glover-Kudon R, Gammon DG, Rogers T, Coats EM, Loomis B, Johnson L, Welton M, Lavinghouze R.
        Tob Control. 2020 Jan 13.
        INTRODUCTION: On 1 January 2016, Hawaii raised the minimum legal age for tobacco access from 18 to 21 years ('Tobacco 21 (T21)') statewide, with no special population exemptions. We assessed the impact of Hawaii's T21 policy on sales of cigarettes and large cigars/cigarillos in civilian food stores, including menthol/flavoured product sales share. METHODS: Cigarette and large cigar/cigarillo sales and menthol/flavoured sales share were assessed in Hawaii, California (implemented T21 in June 2016 with a military exemption), and the US mainland using the only Nielsen data consistently available for each geographical area. Approximate monthly sales data from large-scale food stores with sales greater than US$2 million/year covered June 2012 to February 2017. Segmented regression analyses estimated changes in sales from prepolicy to postpolicy implementation periods. RESULTS: Following T21 in Hawaii, average monthly cigarette unit sales dropped significantly (-4.4%, p<0.01) coupled with a significant decrease in menthol market share (-0.8, p<0.01). This combination of effects was not observed in comparison areas. Unit sales of large cigars/cigarillos decreased significantly in each region following T21 implementation. T21 policies in Hawaii and California showed no association with flavoured/menthol cigar sales share, but there was a significant increase in flavoured/menthol cigar sales share in the USA (7.1%, p<0.01) relative to Hawaii's implementation date, suggesting T21 may have attenuated an otherwise upward trend. CONCLUSIONS: As part of a comprehensive approach to prevent or delay tobacco use initiation, T21 laws may help to reduce sales of cigarette and large cigar products most preferred by US youth and young adults.

      5. Trends in total binge drinks per adult who reported binge drinking - United States, 2011-2017external icon
        Kanny D, Naimi TS, Liu Y, Brewer RD.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):30-34.
        Each year, excessive drinking accounts for one in 10 deaths among U.S. adults aged 20-64 years (1), and approximately 90% of adults who report excessive drinking* binge drink (i.e., consume five or more drinks for men or four or more drinks for women on a single occasion) (2). In 2015, 17.1% of U.S. adults aged >/=18 years reported binge drinking approximately once a week and consumed an average of seven drinks per binge drinking episode, resulting in 17.5 billion total binge drinks, or 467 total binge drinks per adult who reported binge drinking (3). CDC analyzed 2011-2017 Behavioral Risk Factor Surveillance System (BRFSS) data to assess trends in total annual binge drinks per adult who reported binge drinking in the United States overall and in the individual states. The age-adjusted(dagger) total annual number of binge drinks per adult who reported binge drinking increased significantly from 472 in 2011 to 529 in 2017. Total annual binge drinks per adult who reported binge drinking also increased significantly from 2011 to 2017 among those aged 35-44 years (26.7%, from 468 to 593) and 45-64 years (23.1%, from 428 to 527). The largest percentage increases in total binge drinks per adult who reported binge drinking during this period were observed among those without a high school diploma (45.8%) and those with household incomes <$25,000 (23.9%). Strategies recommended by the Community Preventive Services Task Force( section sign) for reducing excessive drinking (e.g., regulating alcohol outlet density) might reduce binge drinking and related health risks.

      6. Chemical analysis of snus products from the United States and northern Europeexternal icon
        Lawler TS, Stanfill SB, Tran HT, Lee GE, Chen PX, Kimbrell JB, Lisko JG, Fernandez C, Caudill SP, deCastro BR, Watson CH.
        PLoS One. 2020 ;15(1):e0227837.
        INTRODUCTION: Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS: Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS: Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION: Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

      7. Bacterial infections associated with substance use disorders, large cohort of United States hospitals, 2012-2017external icon
        McCarthy NL, Baggs J, See I, Reddy SC, Jernigan JA, Gokhale RH, Fiore AE.
        Clin Infect Dis. 2020 Jan 7.
        BACKGROUND: Rises in incidence of bacterial infections such as endocarditis have been reported in conjunction with the opioid crisis, but recent trends for infective endocarditis (IE) and other serious infections among persons with substance use disorders (SUD) are unknown. METHODS: Using the Premier Healthcare Database, we identified hospitalizations among adults >/=18 years from 2012-2017 with primary discharge diagnoses of bacterial infections and secondary SUD diagnoses using ICD-9 and ICD-10 codes. We calculated annual rates of infections with SUD diagnoses and evaluated temporal trends. Blood and cardiac tissue specimens were identified from IE hospitalizations to describe microbiology distribution and temporal trends among hospitalizations with and without SUD. RESULTS: Among 72,481 weighted IE admissions recorded, SUD diagnoses increased from 19.9% in 2012 to 39.4% in 2017 (p<.0001). In adults, the rate of hospitalizations with SUD increased from 1.1 to 2.1 per 100,000 persons for IE, 1.4 to 2.4 per 100,000 persons for osteomyelitis, 0.5 to 0.9 per 100,000 persons for central nervous system abscesses, and 24.4 to 32.9 per 100,000 persons for skin and soft tissue infections. For those 18-44 years, IE-SUD hospitalizations more than doubled from 1.6 in 2012 to 3.6 in 2017 per 100,000 persons. Among all IE-SUD hospitalizations, 50.3% had a Staphylococcus aureus infection, compared to 19.4% of IE hospitalizations without SUD. CONCLUSIONS: Rates of hospitalizations for serious infections among persons with SUD are increasing, driven primarily by younger age groups. The differences in the microbiology of IE hospitalizations suggest SUD is changing the epidemiology of these infections.

      8. The detection of opioid misuse and heroin use from paramedic response documentation: Machine learning for improved surveillanceexternal icon
        Prieto JT, Scott K, McEwen D, Podewils LJ, Al-Tayyib A, Robinson J, Edwards D, Foldy S, Shlay JC, Davidson AJ.
        J Med Internet Res. 2020 Jan 3;22(1):e15645.
        BACKGROUND: Timely, precise, and localized surveillance of nonfatal events is needed to improve response and prevention of opioid-related problems in an evolving opioid crisis in the United States. Records of naloxone administration found in prehospital emergency medical services (EMS) data have helped estimate opioid overdose incidence, including nonhospital, field-treated cases. However, as naloxone is often used by EMS personnel in unconsciousness of unknown cause, attributing naloxone administration to opioid misuse and heroin use (OM) may misclassify events. Better methods are needed to identify OM. OBJECTIVE: This study aimed to develop and test a natural language processing method that would improve identification of potential OM from paramedic documentation. METHODS: First, we searched Denver Health paramedic trip reports from August 2017 to April 2018 for keywords naloxone, heroin, and both combined, and we reviewed narratives of identified reports to determine whether they constituted true cases of OM. Then, we used this human classification as reference standard and trained 4 machine learning models (random forest, k-nearest neighbors, support vector machines, and L1-regularized logistic regression). We selected the algorithm that produced the highest area under the receiver operating curve (AUC) for model assessment. Finally, we compared positive predictive value (PPV) of the highest performing machine learning algorithm with PPV of searches of keywords naloxone, heroin, and combination of both in the binary classification of OM in unseen September 2018 data. RESULTS: In total, 54,359 trip reports were filed from August 2017 to April 2018. Approximately 1.09% (594/54,359) indicated naloxone administration. Among trip reports with reviewer agreement regarding OM in the narrative, 57.6% (292/516) were considered to include information revealing OM. Approximately 1.63% (884/54,359) of all trip reports mentioned heroin in the narrative. Among trip reports with reviewer agreement, 95.5% (784/821) were considered to include information revealing OM. Combined results accounted for 2.39% (1298/54,359) of trip reports. Among trip reports with reviewer agreement, 77.79% (907/1166) were considered to include information consistent with OM. The reference standard used to train and test machine learning models included details of 1166 trip reports. L1-regularized logistic regression was the highest performing algorithm (AUC=0.94; 95% CI 0.91-0.97) in identifying OM. Tested on 5983 unseen reports from September 2018, the keyword naloxone inaccurately identified and underestimated probable OM trip report cases (63 cases; PPV=0.68). The keyword heroin yielded more cases with improved performance (129 cases; PPV=0.99). Combined keyword and L1-regularized logistic regression classifier further improved performance (146 cases; PPV=0.99). CONCLUSIONS: A machine learning application enhanced the effectiveness of finding OM among documented paramedic field responses. This approach to refining OM surveillance may lead to improved first-responder and public health responses toward prevention of overdoses and other opioid-related problems in US communities.

      9. BACKGROUND AND AIMS: Eleven U.S. states and the District of Columbia have legalized non-medical use of marijuana. Public marijuana smoking is generally prohibited, although some states have considered exemptions. This study assessed attitudes about public marijuana smoking, perceptions of harm from marijuana secondhand smoke (SHS), and self-reported marijuana SHS exposure. DESIGN: Internet panel survey fielded in June-July 2018. SETTING: USA PARTICIPANTS: U.S. adults aged >/=18 years (n=4,088). MEASUREMENTS: Current (past-30 day) tobacco product use, current marijuana use, opinions about public indoor marijuana smoking, perceptions of harm from marijuana SHS, and self-reported past-7 day exposure to marijuana SHS in public indoor or outdoor areas were assessed. Weighted prevalence estimates were computed and correlates were assessed using logistic and multinomial regression. FINDINGS: Overall, 27.4% (95% CI: 25.7, 29.1) of adults reported past-week marijuana SHS exposure in indoor and/or outdoor public areas; younger adults, blacks, Hispanics, those in the Northeast or West, and current marijuana and/or tobacco users were more commonly exposed (p<.0001). Over half of adults (52.4%; 95% CI: 50.7, 54.2) regarded marijuana SHS as harmful, and most (81.0%; 95% CI: 79.5, 82.4) opposed public marijuana smoking. Correlates of favoring public marijuana smoking included being male, younger (p<.01), black or Hispanic, past-month tobacco and/or marijuana users, and perceiving no/low harm from marijuana SHS (p<.0001). CONCLUSION: While one in four U.S. adults report recent marijuana secondhand smoke (SHS)exposure, a majority believe marijuana SHS is harmful and most oppose public marijuana smoking.

    • Zoonotic and Vectorborne Diseases
      1. Animal exposure and human plague, United States, 1970-2017external icon
        Campbell SB, Nelson CA, Hinckley AF, Kugeler KJ.
        Emerg Infect Dis. 2019 Dec;25(12):2270-2273.
        Since 1970, >50% of patients with plague in the United States had interactions with animals that might have led to infection. Among patients with pneumonic plague, nearly all had animal exposure. Improved understanding of the varied ways in which animal contact might increase risk for infection could enhance prevention messages.

      2. Risk factors for and seroprevalence of tickborne zoonotic diseases among livestock owners, Kazakhstanexternal icon
        Head JR, Bumburidi Y, Mirzabekova G, Rakhimov K, Dzhumankulov M, Salyer SJ, Knust B, Berezovskiy D, Kulatayeva M, Zhetibaev S, Shoemaker T, Nicholson WL, Moffett D.
        Emerg Infect Dis. 2020 Jan;26(1):70-80.
        Crimean-Congo hemorrhagic fever (CCHF), Q fever, and Lyme disease are endemic to southern Kazakhstan, but population-based serosurveys are lacking. We assessed risk factors and seroprevalence of these zoonoses and conducted surveys for CCHF-related knowledge, attitudes, and practices in the Zhambyl region of Kazakhstan. Weighted seroprevalence for CCHF among all participants was 1.2%, increasing to 3.4% in villages with a known history of CCHF circulation. Weighted seroprevalence was 2.4% for Lyme disease and 1.3% for Q fever. We found evidence of CCHF virus circulation in areas not known to harbor the virus. We noted that activities that put persons at high risk for zoonotic or tickborne disease also were risk factors for seropositivity. However, recognition of the role of livestock in disease transmission and use of personal protective equipment when performing high-risk activities were low among participants.


      3. Epidemiology and case-control study of Lassa fever outbreak in Nigeria from 2018 to 2019external icon
        Ipadeola O, Furuse Y, Ilori EA, Dan-Nwafor CC, Akabike KO, Ahumibe A, Ukponu W, Bakare L, Joseph G, Saleh M, Muwanguzi EN, Olayinka A, Namara G, Naidoo D, Iniobong A, Amedu M, Ugbogulu N, Makava F, Adeoye O, Uzoho C, Anueyiagu C, Okwor TJ, Mba NG, Akano A, Ogunniyi A, Mohammed A, Adeyemo A, Ugochukwu DK, Agogo E, Ihekweazu C.
        J Infect. 2020 Jan 8.

      4. Notes from the field: Multistate outbreak of Eastern equine encephalitis virus - United States, 2019external icon
        Lindsey NP, Martin SW, Staples JE, Fischer M.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):50-51.

      5. Case definitions used during the first 6 months of the 10th Ebola virus disease outbreak in the Democratic Republic of the Congo - four neighboring countries, August 2018-February 2019external icon
        Medley AM, Mavila O, Makumbi I, Nizeyemana F, Umutoni A, Balisanga H, Manoah YK, Geissler A, Bunga S, MacDonald G, Homsy J, Ojwang J, Ewetola R, Raghunathan PL, MacGurn A, Singler K, Ward S, Roohi S, Brown V, Shoemaker T, Lako R, Kabeja A, Muruta A, Lubula L, Merrill R.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 10;69(1):14-19.
        On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.

      6. Population movement patterns among the Democratic Republic of the Congo, Rwanda, and Uganda During an outbreak of Ebola virus disease: Results from community engagement in two districts - Uganda, March 2019external icon
        Nakiire L, Mwanja H, Pillai SK, Gasanani J, Ntungire D, Nsabiyumva S, Mafigiri R, Muneza N, Ward SE, Daffe Z, Ahabwe PB, Kyazze S, Ojwang J, Homsy J, McLntyre E, Lamorde M, Walwema R, Makumbi I, Muruta A, Merrill RD.
        MMWR Morb Mortal Wkly Rep. 2020 Jan 10;69(1):10-13.
        Tailoring communicable disease preparedness and response strategies to unique population movement patterns between an outbreak area and neighboring countries can help limit the international spread of disease. Global recognition of the value of addressing community connectivity in preparedness and response, through field work and visualizing the identified movement patterns, is reflected in the World Health Organization's declaration on July 17, 2019, that the 10th Ebola virus disease (Ebola) outbreak in the Democratic Republic of the Congo (DRC) was a Public Health Emergency of International Concern (1). In March 2019, the Infectious Diseases Institute (IDI), Uganda, in collaboration with the Ministry of Health (MOH) Uganda and CDC, had previously identified areas at increased risk for Ebola importation by facilitating community engagement with participatory mapping to characterize cross-border population connectivity patterns. Multisectoral participants identified 31 locations and associated movement pathways with high levels of connectivity to the Ebola outbreak areas. They described a major shift in the movement pattern between Goma (DRC) and Kisoro (Uganda), mainly through Rwanda, when Rwanda closed the Cyanika ground crossing with Uganda. This closure led some travelers to use a potentially less secure route within DRC. District and national leadership used these results to bolster preparedness at identified points of entry and health care facilities and prioritized locations at high risk further into Uganda, especially markets and transportation hubs, for enhanced preparedness. Strategies to forecast, identify, and rapidly respond to the international spread of disease require adapting to complex, dynamic, multisectoral cross-border population movement, which can be influenced by border control and public health measures of neighboring countries.


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CDC Science Clips Production Staff

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

Page last reviewed: January 27, 2020, 12:00 AM