Volume 12, Issue 20, June 22, 2020

CDC Science Clips: Volume 12, Issue 20, June 23, 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!

This week, CDC Science Clips is pleased to feature items related to the June CDC Public Health Grand Rounds: Smoking Cessation: Past, Present, and Future, which will present key findings on the recently released US Surgeon General’s report on Smoking Cessation. Smoking remains the leading preventable cause of death and disease in the United States. Although the percentage of adults who smoke is at an all-time low in the US, 34 million adults still smoke and therefore continue to be at risk of developing smoking-related diseases.

  1. CDC Public Health Grand Rounds
    • Substance Use and Abuse - Smoking Cessation
      1. Quitting smoking among adults - United States, 2000-2015external icon
        Babb S, Malarcher A, Schauer G, Asman K, Jamal A.
        MMWR Morb Mortal Wkly Rep. 2017 Jan 6;65(52):1457-1464.
        Quitting cigarette smoking benefits smokers at any age (1). Individual, group, and telephone counseling and seven Food and Drug Administration-approved medications increase quit rates (1-3). To assess progress toward the Healthy People 2020 objectives of increasing the proportion of U.S. adults who attempt to quit smoking cigarettes to ≥80.0% (TU-4.1), and increasing recent smoking cessation success to ≥8.0% (TU-5.1),* CDC assessed national estimates of cessation behaviors among adults aged ≥18 years using data from the 2000, 2005, 2010, and 2015 National Health Interview Surveys (NHIS). During 2015, 68.0% of adult smokers wanted to stop smoking, 55.4% made a past-year quit attempt, 7.4% recently quit smoking, 57.2% had been advised by a health professional to quit, and 31.2% used cessation counseling and/or medication when trying to quit. During 2000-2015, increases occurred in the proportion of smokers who reported a past-year quit attempt, recently quit smoking, were advised to quit by a health professional, and used cessation counseling and/or medication (p<0.05). Throughout this period, fewer than one third of persons used evidence-based cessation methods when trying to quit smoking. As of 2015, 59.1% of adults who had ever smoked had quit. To further increase cessation, health care providers can consistently identify smokers, advise them to quit, and offer them cessation treatments (2-4). In addition, health insurers can increase cessation by covering and promoting evidence-based cessation treatments and removing barriers to treatment access (2,4-6).

      2. Best practices for comprehensive tobacco control programs-2014
        Centers for Disease Control and Prevention .
        Atlanta, GA: US Department of Health and Human Services, CDC. 2014 .
        Best Practices for Comprehensive Tobacco Control Programs-2014 is an evidence-based guide to help states build and maintain effective tobacco control programs to prevent and reduce tobacco use. This document updates Best Practices for Comprehensive Tobacco Control Programs-2007. This updated edition describes an integrated approach to program development and provides recommended funding levels for effective state programs.

      3. Tobacco product use and cessation indicators among adults - United States, 2018external icon
        Creamer MR, Wang TW, Babb S, Cullen KA, Day H, Willis G, Jamal A, Neff L.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 15;68(45):1013-1019.
        Cigarette smoking is the leading cause of preventable disease and death in the United States (1). The prevalence of adult cigarette smoking has declined in recent years to 14.0% in 2017 (2). However, an array of new tobacco products, including e-cigarettes, has entered the U.S. market (3). To assess recent national estimates of tobacco product use among U.S. adults aged ≥18 years, CDC, the Food and Drug Administration (FDA), and the National Cancer Institute analyzed data from the 2018 National Health Interview Survey (NHIS). In 2018, an estimated 49.1 million U.S. adults (19.7%) reported currently using any tobacco product, including cigarettes (13.7%), cigars (3.9%), e-cigarettes (3.2%), smokeless tobacco (2.4%), and pipes* (1.0%). Most tobacco product users (83.8%) reported using combustible products (cigarettes, cigars, or pipes), and 18.8% reported using two or more tobacco products. The prevalence of any current tobacco product use was higher in males; adults aged ≤65 years; non-Hispanic American Indian/Alaska Natives; those with a General Educational Development certificate (GED); those with an annual household income <$35,000; lesbian, gay, or bisexual adults; uninsured adults; those with a disability or limitation; and those with serious psychological distress. The prevalence of e-cigarette and smokeless tobacco use increased during 2017-2018. During 2009-2018, there were significant increases in all three cigarette cessation indicators (quit attempts, recent cessation, and quit ratio). Implementing comprehensive population-based interventions in coordination with regulation of the manufacturing, marketing, and distribution of all tobacco products can reduce tobacco-related disease and death in the United States (1,4).

      4. State Medicaid coverage for tobacco cessation treatments and barriers to accessing treatments - United States, 2015-2017external icon
        DiGiulio A, Jump Z, Yu A, Babb S, Schecter A, Williams KS, Yembra D, Armour BS.
        MMWR Morb Mortal Wkly Rep. 2018 Apr 6;67(13):390-395.
        Cigarette smoking prevalence among Medicaid enrollees (25.3%) is approximately twice that of privately insured Americans (11.8%), placing Medicaid enrollees at increased risk for smoking-related disease and death (1). Medicaid spends approximately $39 billion annually on treating smoking-related diseases (2). Individual, group, and telephone counseling and seven Food and Drug Administration (FDA)-approved medications* are effective in helping tobacco users quit (3). Although state Medicaid coverage of tobacco cessation treatments improved during 2014-2015, coverage was still limited in most states (4). To monitor recent changes in state Medicaid cessation coverage for traditional (i.e., nonexpansion) Medicaid enrollees, the American Lung Association collected data on coverage of a total of nine cessation treatments: individual counseling, group counseling, and seven FDA-approved cessation medications(†) in state Medicaid programs during July 1, 2015-June 30, 2017. The American Lung Association also collected data on seven barriers to accessing covered treatments, such as copayments and prior authorization. As of June 30, 2017, 10 states covered all nine of these treatments for all enrollees, up from nine states as of June 30, 2015; of these 10 states, Missouri was the only state to have removed all seven barriers to accessing these cessation treatments. State Medicaid programs that cover all evidence-based cessation treatments, remove barriers to accessing these treatments, and promote covered treatments to Medicaid enrollees and health care providers would be expected to reduce smoking, smoking-related disease, and smoking-attributable federal and state health care expenditures (5-7).

      5. Treating tobacco use and dependence: 2008 updateexternal icon
        Fiore M, Jaen C, Bailey W, Benowitz N, Curry S, Dorfman S, et al .
        U.S. Public Health Service Clinical Practice Guideline. Rockville (MD): U.S. Department of Health and Human Services. 2008 .
        Includes new, effective clinical treatments for tobacco dependence that have become available since the 2000 Guideline was published.

      6. Relapse prevention interventions for smoking cessationexternal icon
        Hajek P, Stead LF, West R, Jarvis M, Hartmann-Boyce J, Lancaster T.
        Cochrane Database Syst Rev. 2013 Aug 20(8):Cd003999.
        BACKGROUND: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. MAIN RESULTS: Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted. AUTHORS' CONCLUSIONS: At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

      7. Surgeon General's Reports on Tobacco: A continued legacy of unbiased and rigorous synthesis of the scientific evidenceexternal icon
        King BA, Creamer MR, Harrell M, Kelder S, Norman L, Perry CL.
        Nicotine Tob Res. 2018 Jul 9;20(8):1033-1036.

      8. Internet-based programs incorporating behavior change techniques are associated with increased smoking cessation in the general population: A systematic review and meta-analysisexternal icon
        McCrabb S, Baker AL, Attia J, Skelton E, Twyman L, Palazzi K, McCarter K, Ku D, Bonevski B.
        Ann Behav Med. 2019 Feb 1;53(2):180-195.
        BACKGROUND AND AIMS: This study aims to (i) examine the effectiveness of internet-based smoking cessation programs; (ii) describe the number and type of behavior change techniques (BCTs) employed; and (iii) explore whether BCTs included in internet-based smoking cessation programs are related to program effectiveness. METHODS: MEDLINE, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched. Randomized controlled trials were included if they described the study of a smoking cessation program delivered via the internet; included current adult tobacco smokers from the general population; and were written in English. Random effects meta-analyses and meta-regressions were used to examine program effectiveness (pooled odds ratios, by outcome measure, i.e., 7 day point prevalence abstinence [PPA], 30 day PPA, other abstinence measure) in short- and long-term outcomes, and examine the associations between BCT number and type (individual BCTs and BCT domain) and program effectiveness. RESULTS: Results from 45 studies were included (n = 65,736). Intervention effectiveness was found in the short term for all outcome measures (OR = 1.29, 95% CI 1.12, 1.50, p = .001), for "prolonged abstinence" (OR = 1.43, 95% CI 1.09, 1.87, p = .009), and "30 day PPA" (OR = 1.75, 95% CI 1.13, 2.72, p = .013). Internet-based programs were effective in the long term for all outcome measures (OR = 1.19, 95% CI = 1.06, 1.35, p = .004) and for "prolonged abstinence" (OR = 1.40, 95% CI 1.19, 1.63, p < .001). On average, interventions used more BCTs than comparison groups (6.6 vs. 3.1, p = .0002). The impact of specific individual BCTs and BCT domains on effectiveness was examined and is reported. CONCLUSIONS: Internet-based smoking cessation interventions increased the odds of cessation by 29 per cent in the short term and by 19 per cent in the long term. Internet-based smoking cessation intervention development should incorporate BCTs to increase effectiveness. REGISTRATION: CRD42015014676.

      9. Public health consequences of e-cigarettesexternal icon
        National Academies of Sciences , Engineering , and Medicine .
        Washington (DC): The National Academies Press. 2018 .
        Millions of Americans use e-cigarettes. Despite their popularity, little is known about their health effects. Some suggest that e-cigarettes likely confer lower risk compared to combustible tobacco cigarettes, because they do not expose users to toxicants produced through combustion. Proponents of e-cigarette use also tout the potential benefits of e-cigarettes as devices that could help combustible tobacco cigarette smokers to quit and thereby reduce tobacco-related health risks. Others are concerned about the exposure to potentially toxic substances contained in e-cigarette emissions, especially in individuals who have never used tobacco products such as youth and young adults. Given their relatively recent introduction, there has been little time for a scientific body of evidence to develop on the health effects of e-cigarettes.

      10. A socioecological approach to addressing tobacco-related health disparitiesexternal icon
        National Cancer Institute .
        National Cancer Institute Tobacco Control Monograph 22. Bethesda (MD): U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. NIH Publication No. 17-CA-8035A. 2017 .
        Tobacco use remains the nation’s leading cause of preventable premature death, including death from cancer, and progress in reducing tobacco use and related disease and death has not been equally distributed across population groups. This monograph examines the current evidence surrounding tobacco-related health disparities (TRHD) across the tobacco use continuum - initiation, secondhand smoke exposure, current use, frequency and intensity, cessation, relapse, morbidity, and mortality - and the implications for future research and implementation of effective strategies. As this monograph demonstrates, a central challenge for cancer control is to ensure that all Americans benefit from advances in tobacco control research and practice.

      11. BACKGROUND: Tobacco use is the leading cause of preventable death in the United States. PURPOSE: To review the effectiveness and safety of pharmacotherapy and behavioral interventions for tobacco cessation. DATA SOURCES: 5 databases and 8 organizational Web sites were searched through 1 August 2014 for systematic reviews, and PubMed was searched through 1 March 2015 for trials on electronic nicotine delivery systems. STUDY SELECTION: Two reviewers examined 114 articles to identify English-language reviews that reported health, cessation, or adverse outcomes. DATA EXTRACTION: One reviewer abstracted data from good- and fair-quality reviews, and a second checked for accuracy. DATA SYNTHESIS: 54 reviews were included. Behavioral interventions increased smoking cessation at 6 months or more (physician advice had a pooled risk ratio [RR] of 1.76 [95% CI, 1.58 to 1.96]). Nicotine replacement therapy (RR, 1.60 [CI, 1.53 to 1.68]), bupropion (RR, 1.62 [CI, 1.49 to 1.76]), and varenicline (RR, 2.27 [CI, 2.02 to 2.55]) were also effective for smoking cessation. Combined behavioral and pharmacotherapy interventions increased cessation by 82% compared with minimal intervention or usual care (RR, 1.82 [CI, 1.66 to 2.00]). None of the drugs were associated with major cardiovascular adverse events. Only 2 trials addressed efficacy of electronic cigarettes for smoking cessation and found no benefit. Among pregnant women, behavioral interventions benefited cessation and perinatal health; effects of nicotine replacement therapy were not significant. LIMITATION: Evidence published after each review's last search date was not included. CONCLUSION: Behavioral and pharmacotherapy interventions improve rates of smoking cessation among the general adult population, alone or in combination. Data on the effectiveness and safety of electronic nicotine delivery systems are limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

      12. DESCRIPTION: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on counseling and interventions to prevent tobacco use and tobacco-related disease in adults, including pregnant women. METHODS: The USPSTF reviewed the evidence on interventions for tobacco smoking cessation that are relevant to primary care (behavioral interventions, pharmacotherapy, and complementary or alternative therapy) in adults, including pregnant women. POPULATION: This recommendation applies to adults aged 18 years or older, including pregnant women. RECOMMENDATIONS: The USPSTF recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide behavioral interventions and U.S. Food and Drug Administration-approved pharmacotherapy for cessation to adults who use tobacco. (A recommendation). The USPSTF recommends that clinicians ask all pregnant women about tobacco use, advise them to stop using tobacco, and provide behavioral interventions for cessation to pregnant women who use tobacco. (A recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of pharmacotherapy interventions for tobacco cessation in pregnant women. (I statement). The USPSTF concludes that the current evidence is insufficient to recommend electronic nicotine delivery systems for tobacco cessation in adults, including pregnant women. The USPSTF recommends that clinicians direct patients who smoke tobacco to other cessation interventions with established effectiveness and safety (previously stated). (I statement).

      13. The health benefits of smoking cessation: A report of the Surgeon General
        US Department of Health and Human Services .
        Rockville (MD): U.S. Department of Health and Human Services, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. DHHS Publication No. (CDC) 90-8416. 1990 .
        More than 38 million Americans have quit smoking, and almost half of all living adults in the United States who ever smoked have quit. Nevertheless, more than 50 million Americans continue to smoke. This Report reviews in detail the health consequences of smoking cessation for those who have quit and for those who will quit in the future.

      14. The health consequences of smoking - 50 years of progress: A report of the Surgeon Generalexternal icon
        US Department of Health and Human Services .
        Atlanta, GA: US Department of Health and Human Services, CDC. 2014 .
        Fifty years have passed since publication of the landmark report of the Surgeon General’s Advisory Committee on smoking and health. This report highlights both the dramatic progress our nation has made reducing tobacco use and the continuing burden of disease and death caused by smoking.

      15. Annual healthcare spending attributable to cigarette smoking: an updateexternal icon
        Xu X, Bishop EE, Kennedy SM, Simpson SA, Pechacek TF.
        Am J Prev Med. 2015 Mar;48(3):326-33.
        BACKGROUND: Fifty years after the first Surgeon General's report, tobacco use remains the nation's leading preventable cause of death and disease, despite declines in adult cigarette smoking prevalence. Smoking-attributable healthcare spending is an important part of overall smoking-attributable costs in the U.S. PURPOSE: To update annual smoking-attributable healthcare spending in the U.S. and provide smoking-attributable healthcare spending estimates by payer (e.g., Medicare, Medicaid, private insurance) or type of medical services. METHODS: Analyses used data from the 2006-2010 Medical Expenditure Panel Survey linked to the 2004-2009 National Health Interview Survey. Estimates from two-part models were combined to predict the share of annual healthcare spending that could be attributable to cigarette smoking. The analysis was conducted in 2013. RESULTS: By 2010, 8.7% (95% CI=6.8%, 11.2%) of annual healthcare spending in the U.S. could be attributed to cigarette smoking, amounting to as much as $170 billion per year. More than 60% of the attributable spending was paid by public programs, including Medicare, other federally sponsored programs, or Medicaid. CONCLUSIONS: These findings indicate that comprehensive tobacco control programs and policies are still needed to continue progress toward ending the tobacco epidemic in the U.S. 50 years after the release of the first Surgeon General's report on smoking and health.

  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. OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with systemic lupus erythematosus (SLE) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to analyze racial and ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: A total of 724 patients with SLE were retrospectively identified. Prevalence ratios (PRs) of SLE manifestations were calculated using Poisson regression models stratified by race/ethnicity and adjusted for sex, age at SLE diagnosis, and disease duration. We studied onset of severe SLE manifestations after SLE diagnosis using Kaplan-Meier methods to examine time-to-event and Cox proportional hazards regression models to estimate hazard ratios (HRs). White patients were the referent group in all analyses. RESULTS: African Americans, Asian/Pacific Islanders, and Hispanic patients had increased prevalence of renal manifestations (PR 1.74 [95% confidence interval (95% CI) 1.40-2.16], PR 1.68 [95% CI 1.38-2.05], and PR 1.35 [95% CI 1.05-1.74], respectively). Furthermore, African Americans had increased prevalence of neurologic manifestations (PR 1.49 [95% CI 1.12-1.98]), and both African Americans (PR 1.09 [95% CI 1.04-1.15]) and Asian/Pacific Islanders (PR 1.07 [95% CI 1.01-1.13]) had increased prevalence of hematologic manifestations. African Americans, Asian/Pacific Islanders, and Hispanic patients, respectively, had higher risk of developing lupus nephritis (HR 2.4 [95% CI 1.6-3.8], HR 4.3 [95% CI 2.9-6.4], and HR 2.3 [95% CI 1.4-3.8]) and thrombocytopenia (HR 2.3 [95% CI 1.1-4.4], HR 2.3 [95% CI 1.3-4.2], and HR 2.2 [95% CI 1.1-4.7]). Asian/Pacific Islander and Hispanic patients had higher risk of developing antiphospholipid syndrome (HR 2.5 [95% CI 1.4-4.4] and HR 2.6 [95% CI 1.3-5.1], respectively). CONCLUSION: This is the first epidemiologic study comparing lupus manifestations among 4 major racial and ethnic groups. We found substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups and discovered that African Americans, Asian/Pacific Islanders, and Hispanic patients are at increased risk of developing several severe manifestations following a diagnosis of SLE.

      2. PURPOSE: Rectal cancer is rarer than colon cancer and is a technically more difficult tumor for surgeons to remove, thus rectal cancer patients may travel longer for specialized treatment compared to colon cancer patients. The purpose of this study was to evaluate whether travel time for surgery was different for colon versus rectal cancer patients. METHODS: A secondary data analysis of colorectal cancer (CRC) incidence data from the Iowa Cancer Registry data was conducted. Travel times along a street network from all residential ZIP Codes to all cancer surgery facilities were calculated using a geographic information system. A new method for analyzing "time-to-place" data using the same type of survival analysis method commonly used to analyze "time-to-event" data is introduced. Cox proportional hazard model was used to analyze travel time differences for colon versus rectal cancer patients. RESULTS: A total of 5,844 CRC patients met inclusion criteria. Median travel time to the nearest surgical facility was 9 minutes, median travel time to the actual cancer surgery facilities was 22 minutes, and the median number of facilities bypassed was 3. Although travel times to the nearest surgery facilities were not significantly different for colon versus rectal cancer patients, rectal cancer patients on average traveled 15 minutes longer to their actual surgery facility and bypassed 2 more facilities to obtain surgery. DISCUSSION: In general, the survival analysis method used to analyze the time-to-place data as described here could be applied to a wide variety of health services and used to compare travel patterns among different groups.

      3. Continuous stakeholder engagement: Expanding the role of pharmacists in prevention of type 2 diabetes through the National Diabetes Prevention Programexternal icon
        Ross LW, Bana F, Blacher RJ, McDivitt J, Petty J, Beckner J, Montierth R.
        Prev Chronic Dis. 2020 Jun 4;17:E41.
        The pharmacy sector is a key partner in the National Diabetes Prevention Program (National DPP), as pharmacists frequently care for patients at high risk for type 2 diabetes. The Centers for Disease Control and Prevention aimed to increase pharmacist involvement in the program by leveraging partnerships with national pharmacy stakeholders. Continuous stakeholder engagement helped us to better understand the pharmacy sector and its needs. With stakeholders, we developed a guide and promotional campaign. By following a systematic process and including key stakeholders at every step of development, we successfully engaged these valuable partners in national type 2 diabetes prevention efforts. More pharmacy sites (n = 87) are now offering the National DPP lifestyle change program compared to before release of the guide (n = 27).

      4. Association of a province-wide intervention with salt intake and hypertension in Shandong Province, China, 2011-2016external icon
        Xu A, Ma J, Guo X, Wang L, Wu J, Zhang J, Bai Y, Xu J, Lu Z, Xu Z, Zhang X, Ding G, Hong Y, Du F, Wu Y, Yan L, Tang J, Cai X, Dong J, Xu C, Ren J, Chen X, Gao C, Zhang B, Yang Q, Moolenaar R, Cai Y, Jackson SL, Xie G, Yu S, Cui J, Wang Z, Zhao L, Ju L, Shen D, Yun S, Liang X, Bi Z, Wang Y.
        JAMA Intern Med. 2020 Apr 27;180(6):877-86.
        IMPORTANCE: High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. OBJECTIVE: To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. INTERVENTIONS: Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. MAIN OUTCOMES AND MEASURES: The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. RESULTS: Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. CONCLUSIONS AND RELEVANCE: The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide.

    • Communicable Diseases
      1. Building and sustaining optimized diagnostic networks to scale-up HIV viral load and early infant diagnosisexternal icon
        Alemnji G, Peter T, Vojnov L, Alexander H, Zeh C, Cohn J, Watts DH, de Lussigny S.
        J Acquir Immune Defic Syndr. 2020 Jul 1;84 Suppl 1:S56-s62.
        BACKGROUND: Progress toward meeting the UNAIDS 2014 HIV treatment (90-90-90) targets has been slow in some countries because of gaps in access to HIV diagnostic tests. Emerging point-of-care (POC) molecular diagnostic technologies for HIV viral load (VL) and early infant diagnosis (EID) may help reduce diagnostic gaps. However, these technologies need to be implemented in a complementary and strategic manner with laboratory-based instruments to ensure optimization. METHOD: Between May 2019 and February 2020, a systemic literature search was conducted in PubMed, the Cochrane Library, MEDLINE, conference abstracts, and other sources such as Unitaid, UNAIDS, WHO, and UNICEF websites to determine factors that would affect VL and EID scale-up. Data relevant to the search themes were reviewed for accuracy and were included. RESULTS: Collaborations among countries, implementing partners, and donors have identified a set of framework for the effective use of both POC-based and laboratory-based technologies in large-scale VL and EID testing programs. These frameworks include (1) updated testing policies on the operational utility of POC and laboratory-based technologies, (2) expanded integrated testing using multidisease diagnostic platforms, (3) laboratory network mapping, (4) use of more efficient procurement and supply chain approaches such as all-inclusive pricing and reagent rental, and (5) addressing systemic issues such as test turnaround time, sample referral, data management, and quality systems. CONCLUSIONS: Achieving and sustaining optimal VL and EID scale-up within tiered diagnostic networks would require better coordination among the ministries of health of countries, donors, implementing partners, diagnostic manufacturers, and strong national laboratory and clinical technical working groups.

      2. Cannabis use and fungal infections in a commercially insured population, United States, 2016external icon
        Benedict K, Thompson GR, Jackson BR.
        Emerg Infect Dis. 2020 Jun;26(6):1308-1310.
        Case reports have identified invasive fungal diseases in persons who use cannabis, and fungal contamination of cannabis has been described. In a large health insurance claims database, persons who used cannabis were 3.5 (95% CI 2.6-4.8) times more likely than persons who did not use cannabis to have a fungal infection in 2016.

      3. Measles outbreak amplified in a pediatric ward: Lyantonde District, Uganda, August 2017external icon
        Biribawa C, Atuhairwe JA, Bulage L, Okethwangu DO, Kwesiga B, Ario AR, Zhu BP.
        BMC Infect Dis. 2020 Jun 5;20(1):398.
        BACKGROUND: Measles is a highly infectious viral disease. In August 2017, Lyantonde District, Uganda reported a measles outbreak to Uganda Ministry of Health. We investigated the outbreak to assess the scope, factors facilitating transmission, and recommend control measures. METHODS: We defined a probable case as sudden onset of fever and generalized rash in a resident of Lyantonde, Lwengo, or Rakai Districts from 1 June-30 September 2017, plus >/=1 of the following: coryza, conjunctivitis, or cough. A confirmed case was a probable case with serum positivity of measles-specific IgM. We conducted a neighborhood- and age-matched case-control study to identified exposure factors, and used conditional logistic regression to analyze the data. We estimated vaccine effectiveness and vaccination coverage. RESULTS: We identified 81 cases (75 probable, 6 confirmed); 4 patients (4.9%) died. In the case-control study, 47% of case-patients and 2.3% of controls were hospitalized at Lyantonde Hospital pediatric department for non-measles conditions 7-21 days before case-patient's onset (ORadj = 34, 95%CI: 5.1-225). Estimated vaccine effectiveness was 95% (95%CI: 75-99%) and vaccination coverage was 76% (95%CI: 68-82%). During the outbreak, an "isolation" ward was established inside the general pediatric ward where there was mixing of both measles and non-measles patients. CONCLUSIONS: This outbreak was amplified by nosocomial transmission and facilitated by low vaccination coverage. We recommended moving the isolation ward outside of the building, supplemental vaccination, and vaccinating pediatric patients during measles outbreaks.

      4. Melioidosis in a resident of Texas with no recent travel history, United Statesexternal icon
        Cossaboom CM, Marinova-Petkova A, Strysko J, Rodriguez G, Maness T, Ocampo J, Gee JE, Elrod MG, Gulvik CA, Liu L, Bower WA, Hoffmaster AR, Blaney DD, Salzer JS, Yoder JS, Mattioli MC, Sidwa TJ, Ringsdorf L, Morrow G, Ledezma E, Kieffer A.
        Emerg Infect Dis. 2020 Jun;26(6):1295-1299.
        To our knowledge, environmental isolation of Burkholderia pseudomallei, the causative agent of melioidosis, from the continental United States has not been reported. We report a case of melioidosis in a Texas resident. Genomic analysis indicated that the isolate groups with B. pseudomallei isolates from patients in the same region, suggesting possible endemicity to this region.

      5. Public attitudes, behaviors, and beliefs related to COVID-19, stay-at-home orders, nonessential business closures, and public health guidance - United States, New York City, and Los Angeles, May 5-12, 2020external icon
        Czeisler ME, Tynan MA, Howard ME, Honeycutt S, Fulmer EB, Kidder DP, Robbins R, Barger LK, Facer-Childs ER, Baldwin G, Rajaratnam SM, Czeisler CA.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):751-758.
        SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to be transmitted mainly by person-to-person contact (1). Implementation of nationwide public health orders to limit person-to-person interaction and of guidance on personal protective practices can slow transmission (2,3). Such strategies can include stay-at-home orders, business closures, prohibitions against mass gatherings, use of cloth face coverings, and maintenance of a physical distance between persons (2,3). To assess and understand public attitudes, behaviors, and beliefs related to this guidance and COVID-19, representative panel surveys were conducted among adults aged >/=18 years in New York City (NYC) and Los Angeles, and broadly across the United States during May 5-12, 2020. Most respondents in the three cohorts supported stay-at-home orders and nonessential business closures* (United States, 79.5%; New York City, 86.7%; and Los Angeles, 81.5%), reported always or often wearing cloth face coverings in public areas (United States, 74.1%, New York City, 89.6%; and Los Angeles 89.8%), and believed that their state's restrictions were the right balance or not restrictive enough (United States, 84.3%; New York City, 89.7%; and Los Angeles, 79.7%). Periodic assessments of public attitudes, behaviors, and beliefs can guide evidence-based public health decision-making and related prevention messaging about mitigation strategies needed as the COVID-19 pandemic evolves.

      6. Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern Californiaexternal icon
        Deng X, Gu W, Federman S, du Plessis L, Pybus OG, Faria N, Wang C, Yu G, Bushnell B, Pan CY, Guevara H, Sotomayor-Gonzalez A, Zorn K, Gopez A, Servellita V, Hsu E, Miller S, Bedford T, Greninger AL, Roychoudhury P, Starita LM, Famulare M, Chu HY, Shendure J, Jerome KR, Anderson C, Gangavarapu K, Zeller M, Spencer E, Andersen KG, MacCannell D, Paden CR, Li Y, Zhang J, Tong S, Armstrong G, Morrow S, Willis M, Matyas BT, Mase S, Kasirye O, Park M, Masinde G, Chan C, Yu AT, Chai SJ, Villarino E, Bonin B, Wadford DA, Chiu CY.
        Science. 2020 Jun 8.
        The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, with >52,000 cases in California as of May 4, 2020. Here we investigate the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities. Lineages associated with outbreak clusters in 2 counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states.

      7. HIV outbreaks among people who inject drugs in Europe, North America, and Israelexternal icon
        Des Jarlais DC, Sypsa V, Feelemyer J, Abagiu AO, Arendt V, Broz D, Chemtob D, Seguin-Devaux C, Duwve JM, Fitzgerald M, Goldberg DJ, Hatzakis A, Jipa RE, Katchman E, Keenan E, Khan I, Konrad S, McAuley A, Skinner S, Wiessing L.
        Lancet HIV. 2020 Jun;7(6):e434-e442.
        During 2011-16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks.

      8. BACKGROUND: There is a high level of coinfection with HIV among persons diagnosed with syphilis in the United States. Public health workers at state and local health departments help inform exposed partners to STD/HIV infections to facilitate early testing and treatment (partner services). The federal initiative, Ending the HIV Epidemic (EHE), identifies four key strategies: diagnose, treat, prevent, and respond. This study describes the contributions of syphilis partner services to the EHE strategies in a county prioritized by the EHE plan. METHODS: A retrospective record review of reported early syphilis cases (less than one year's duration) between 2016 and 2018 in the Indianapolis area was conducted to determine the extent of new HIV diagnoses, retention in HIV care, and other evidence-based HIV prevention interventions occurring after provision of syphilis partner services. RESULTS: A total of 752 partners to early syphilis were attempted to be notified of exposure. 1,457 case patients and partners received STD/HIV prevention counseling; 400 partners received STD treatment; 352 partners learned their HIV status; and 22 received new HIV diagnoses, with 68% retained in medical care and 60% virally suppressed. Two-thirds of partner services were completed within 21 days. New HIV positivity among partners to HIV-negative syphilis case patients was 3.5%, and 14% among HIV-positive syphilis case patients. CONCLUSIONS: Partner services for syphilis was an effective method of addressing the EHE strategies, resulting in persons at risk tested, STD treatment provided, PrEP referrals, and new HIV cases identified, leading to retention in medical care and viral suppression.

      9. Decreased susceptibility to azithromycin in clinical Shigella isolates associated with HIV and sexually transmitted bacterial diseases, Minnesota, USA, 2012-2015external icon
        Eikmeier D, Talley P, Bowen A, Leano F, Dobbins G, Jawahir S, Gross A, Huspeni D, La Pointe A, Meyer S, Smith K.
        Emerg Infect Dis. 2020 Apr;26(4):667-674.
        Shigellosis outbreaks caused by Shigella with decreased susceptibility to azithromycin (DSA-Shigella) among men who have sex with men (MSM) have been reported worldwide. We describe sexual health indicators and antimicrobial drug resistance for shigellosis cases in Minnesota, USA. We analyzed a sample of isolates received during 2012-2015 and cross-referenced cases with the Minnesota Department of Health Sexually Transmitted Disease Database to ascertain patients' HIV status and recent chlamydia, gonorrhea, and syphilis infections. Of 691 Shigella isolates, 46 (7%) were DSA-Shigella; 91% of DSA-Shigella patients were men, of whom 60% were living with HIV. Among men, those with DSA-Shigella infection had greater odds of living with HIV, identifying as MSM, or having a recent diagnosis of a sexually transmitted disease. DSA-Shigella was associated with MSM, HIV infection, and recent sexually transmitted disease. To decrease spread of DSA-Shigella, interventions targeted at communities at high risk are needed.

      10. Validation of a SARS-CoV-2 spike protein ELISA for use in contact investigations and serosurveillanceexternal icon
        Freeman B, Lester S, Mills L, Rasheed MA, Moye S, Abiona O, Hutchinson GB, Morales-Betoulle M, Krapinunaya I, Gibbons A, Chiang CF, Cannon D, Klena J, Johnson JA, Owen SM, Graham BS, Corbett KS, Thornburg NJ.
        bioRxiv. 2020 Apr 25.
        Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed tohave had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population.

      11. Comparison of HIV incidence in the Zimbabwe Population-Based HIV Impact Assessment Survey (2015-2016), with modeled estimates: Progress toward epidemic controlexternal icon
        Gonese E, Musuka G, Ruangtragool L, Hakim A, Parekh B, Dobbs T, Duong YT, Patel H, Mhangara M, Mugurungi O, Mapingure M, Saito S, Herman-Roloff A, Gwanzura L, Tippett-Barr B, Kilmarx P, Justman J.
        AIDS Res Hum Retroviruses. 2020 Jun 5.
        BACKGROUND: Zimbabwe conducted a Population-Based HIV Impact Assessment (ZIMPHIA) cross-sectional survey, October 2015 and August 2016 to determine progress toward epidemic control. METHODS: Of 25,131 eligible adults 15-64 years, 20,577 (81.8%) consented to face-to-face questionnaire and biomarker testing in this nationally representative household survey. Home-based rapid HIV testing was performed using Determine, First Response and Stat-Pak as the tie-breaker. HIV-positive tests were confirmed in a laboratory using Geenius HIV-1/2, viral load (VL) was measured using Roche TaqMan and BioMerieux NucliSENS. Recency of infection was tested using Sedia HIV-1 Limiting Antigen-Avidity (LAg). Presence of antiretroviral (ARV) drugs was detected using HPLC/MS. The recent infection testing algorithm (RITA) included LAg-Avidity Enzyme-immuno-assay (EIA (normalised-optical density (ODn<=1.5), viral load>/=1000 copies/mL, and absence of antiretroviral drugs. Weighted annual HIV incidence was compared to UNAIDS Spectrum models estimates. RESULTS: Overall, 26 of 2,901 HIV-seropositive individuals had a recent infection (men, 8; women, 18). Overall weighted annual incidence among persons 15-64 years was 0.42% (95% confidence interval [CI]: 0.25-0.59) and 0.44% (95% CI: 0.25-0.62) for 15-49 years, similar to 2016 Spectrum model estimate (0.54%; 95% CI: 0.49-0.66) for this age group. Among persons aged 15-49 years, HIV prevalence was 13.35 % (95% CI: 12.71-14.02), estimated HIV-positive individuals were 968,951 (95% CI: 911,473-1,026,430), of these, 41,911 (95% CI: 37,412-44,787) were annual-new infections and this was similar to 2016 Spectrum estimates. CONCLUSION: The observed HIV incidence in ZIMPHIA 2015/16 validated the 2016 Spectrum estimates and Zimbabwe's progress toward epidemic control.

      12. Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patientexternal icon
        Harcourt J, Tamin A, Lu X, Kamili S, Sakthivel SK, Murray J, Queen K, Tao Y, Paden CR, Zhang J, Li Y, Uehara A, Wang H, Goldsmith C, Bullock HA, Wang L, Whitaker B, Lynch B, Gautam R, Schindewolf C, Lokugamage KG, Scharton D, Plante JA, Mirchandani D, Widen SG, Narayanan K, Makino S, Ksiazek TG, Plante KS, Weaver SC, Lindstrom S, Tong S, Menachery VD, Thornburg NJ.
        bioRxiv. 2020 Mar 7.
        The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures.

      13. Severe acute respiratory syndrome coronavirus 2 from patient with coronavirus disease, United Statesexternal icon
        Harcourt J, Tamin A, Lu X, Kamili S, Sakthivel SK, Murray J, Queen K, Tao Y, Paden CR, Zhang J, Li Y, Uehara A, Wang H, Goldsmith C, Bullock HA, Wang L, Whitaker B, Lynch B, Gautam R, Schindewolf C, Lokugamage KG, Scharton D, Plante JA, Mirchandani D, Widen SG, Narayanan K, Makino S, Ksiazek TG, Plante KS, Weaver SC, Lindstrom S, Tong S, Menachery VD, Thornburg NJ.
        Emerg Infect Dis. 2020 Jun;26(6):1266-1273.
        The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.

      14. Assessing the incidence of symptomatic respiratory syncytial virus illness within a prospective birth cohort in Managua, Nicaraguaexternal icon
        Kubale J, Kuan G, Gresh L, Ojeda S, Azziz-Baumgartner E, Sanchez N, Lopez R, Harris E, Balmaseda A, Gordon A.
        Clin Infect Dis. 2020 May 6;70(10):2029-2035.
        BACKGROUND: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among children worldwide, commonly through acute lower respiratory tract infections (ALRI). To assess the incidence rate of symptomatic RSV illness among young children, we conducted a prospective birth cohort study following children from 0-2 years of age in Managua, Nicaragua. METHODS: Children meeting the testing criteria (fever, history of fever, or severe respiratory symptoms [apnea, stridor, nasal flaring, wheezing, chest indrawing, and/or central cyanosis]) were tested for RSV infections using real-time reverse transcriptase-polymerase chain reaction. An acute lower respiratory infection was defined as a diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. The incidence rate was calculated, and 95% confidence intervals were estimated using a Poisson distribution. RESULTS: A total of 833 children participated in the cohort: 289 (34.7%) had at least 1 episode of laboratory-confirmed RSV, and 156 (18.7%) of had an episode of RSV-associated ALRI (RSV-ALRI). The incidence rate of symptomatic RSV was 248.1 cases per 1000 person-years (95% confidence interval [CI] 223.2-275.7). While infants aged 6-11 months had the highest incidence of symptomatic RSV (361.3/1000 person-years, 95% CI 304.4-428.8), infants <3 months had the highest incidence of severe RSV (RSV-associated hospitalizations and/or severe ALRI). RSV was also associated with 25.0-37.5% of deaths from medical causes (n = 8). CONCLUSIONS: A substantial burden of RSV exists among children aged <2 years in Nicaraguan communities. RSV was also a leading cause of infant mortality among study participants. The development and implementation of effective RSV prevention and treatment measures represent an opportunity to substantially reduce severe illness and death among children worldwide.

      15. Estimating neonatal herpes simplex virus incidence and mortality using capture-recapture, Floridaexternal icon
        Matthias J, du Bernard S, Schillinger JA, Hong J, Pearson V, Peterman TA.
        Clin Infect Dis. 2020 Jun 7.
        BACKGROUND: Neonatal herpes simplex virus infection (nHSV) leads to severe morbidity and mortality, but national incidence is uncertain. Florida regulations require that healthcare providers report cases, and clinical laboratories report test results when herpes simplex virus (HSV) is detected. We estimated nHSV incidence using laboratory-confirmed provider-reported cases and electronic laboratory reports (ELR) stored separately from provider-reported cases. Mortality was estimated using provider-reported cases, ELR, and vital statistics death records. METHODS: For 2011-2017, we reviewed: provider-reported cases (infants <60 days of age with HSV infection confirmed by culture or polymerase chain reaction (PCR)), ELR of HSV-positive culture or PCR results in the same age group, and death certificates containing International Classification of Disease, Tenth Revision, codes for herpes infection: P35.2, B00.0-B00.9, and A60.0-A60.9. Provider-reported cases were matched against ELR reports. Death certificates were matched with provider and ELR reports. Chapman's capture-recapture method was used to estimate nHSV incidence and mortality. Mortality from all three sources was estimated using log-linear modelling. RESULTS: Providers reported 114 nHSV cases and ELR identified 197 nHSV cases. Forty-six cases were common to both datasets, leaving 265 unique nHSV reports. Chapman's estimate suggests 483 (95% C.I. 383-634) nHSV cases occurred (31.5 infections per 100,000 live births). nHSV deaths were reported by providers (n=9), ELR (n=18), and vital statistics (n=31), totaling 34 unique reports. Log-linear modeling estimates 35.8 fatal cases occurred (95% CI 34-40). CONCLUSIONS: Chapman's estimates using data collected over 7 years in Florida, conclude nHSV infections occurred at a rate of 1 per 3000 live births.

      16. Healthcare-related stigma among men who have sex with men and transgender women in sub-Saharan Africa participating in HIV Prevention Trials Network (HPTN) 075 studyexternal icon
        Mbeda C, Ogendo A, Lando R, Schnabel D, Gust DA, Guo X, Akelo V, Dominguez K, Panchia R, Mbilizi Y, Chen Y, Chege W.
        AIDS Care. 2020 Jun 5:1-9.
        ABSTRACT The inability to access health services when needed is a critical barrier to HIV prevention, treatment and care among men who have sex with men (MSM) and transgender women (TGW). Using data collected in HPTN 075, we explored factors associated with any experienced healthcare-related stigma. HPTN 075 was a cohort study to assess the feasibility of recruiting and retaining MSM and TGW in clinical trials in sub-Saharan Africa. Of 401 MSM and TGW enrolled at four sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town, Soweto, South Africa) 397 contributed to the analysis (79.9% cis-gender and 20.1% TGW). Of these, (45.3%; 180/397) reported one or more of healthcare-related stigma experiences. Most frequently reported experiences included fear to seek healthcare services (36.3%) and avoiding seeking such services because of the discovery of MSM status (29.2%). Few men and TGW (2.5%) reported having been denied health services because of having sex with men. In multivariable analysis, more participants in Soweto [adjusted odds ratio (AOR) = 2.60] and fewer participants in Blantyre (AOR = 0.27) reported any healthcare-related stigma experiences, in comparison to participants in Kisumu. MSM and TGW that did not have a supportive gay community to rely on were more likely to report any healthcare-related stigma experiences (AOR = 1.46), whereas MSM and TGW who reported high social support and who never had engaged in transactional sex were less likely to report such experiences (AOR = 0.76 and AOR = 0.43, respectively). Our results suggest that encouraging support groups for MSM and TGW as well as training and sensitizing healthcare staff, and the general community, on MSM and TGW health issues and cultural competence may reduce stigma, improve access to healthcare, which could ultimately reduce HIV transmission.

      17. Carriage of Neisseria meningitidis in men who have sex with men presenting to public sexual health clinics, New York Cityexternal icon
        Ngai S, Weiss D, Bell JA, Majrud D, Zayas G, Crawley A, Kornblum J, Rodriguez-Rivera LD, Quinlan T, Halse TA, Retchless AC, MacNeil J, Pathela P.
        Sex Transm Dis. 2020 Jun 8.
        BACKGROUND: We conducted a N. meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission. METHODS: We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. Nm isolates were characterized by whole genome sequencing. RESULTS: Twenty-three percent (163/706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159/703), rectal 0.9% (6/695), and urethral 0.4% (3/696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: >3 men kissed (adjusted relative risk (aRR) 1.38; 95% confidence interval [CI] 1.03-1.86), performing oral sex (aRR 1.81; 95% CI 1.04-3.18), and antibiotic use (aRR 0.33; 95% CI 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages. CONCLUSIONS: Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM.

      18. BACKGROUND: Mobile HIV testing services (HTS) are effective at reaching undiagnosed people living with HIV. However, linkage to HIV care from mobile HTS is often poor, ranging from 10 to 60%. Point-of-care (POC) CD4 testing has shown to increase retention in health facilities, but little evidence exists about their use in mobile HTS. This study assessed the feasibility of POC CD4 test implementation and investigated linkage to HIV care among clients accepting a POC test at community-based mobile HTS. METHODS: This retrospective study used routinely collected data from clients who utilized community-based mobile HTS in the City of Cape Town Metropolitan district, South Africa between December 2014 and September 2016. A POC CD4 test was offered to all clients with an HIV positive diagnosis during this period, and a CD4 cell count was provided to clients accepting a POC CD4 test. Random effects logistic regression was used to assess factors associated with POC CD4 test uptake and self-reported linkage to care among clients accepting a POC test. Models were adjusted for sex, age, previous HIV test done, tuberculosis status and year of HIV diagnosis. RESULTS: One thousand three hundred twenty-five of Thirty-nine thousand seven hundred ninety clients utilizing mobile HTS tested HIV positive (3%). 51% (679/1325) accepted a POC test. The age group with the highest proportion accepting a POC test was 50+ years (60%). Females were less likely to accept a POC test than males (odds ratio = 0.7, 95%CI = 0.6-0.8). Median CD4 count was 429 cells/μl (interquartile range = 290-584). Among 679 clients who accepted a POC CD4 test, 491 (72%) linked to HIV care. CD4 cell count was not associated with linkage to care. CONCLUSION: Our findings suggest that mobile HTS can identify early HIV infection, and show that a high proportion of clients with a POC test result linked to care. Future research should assess factors associated with POC test acceptance and assess the impact of POC CD4 testing in comparison to alternative strategies to engage HIV positive people in care.

      19. Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020external icon
        Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S, Tie Y, Fullerton KE.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):759-765.
        The coronavirus disease 2019 (COVID-19) pandemic resulted in 5,817,385 reported cases and 362,705 deaths worldwide through May, 30, 2020,(dagger) including 1,761,503 aggregated reported cases and 103,700 deaths in the United States.( section sign) Previous analyses during February-early April 2020 indicated that age >/=65 years and underlying health conditions were associated with a higher risk for severe outcomes, which were less common among children aged <18 years (1-3). This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22-May 30, 2020. Cumulative incidence, 403.6 cases per 100,000 persons,( paragraph sign) was similar among males (401.1) and females (406.0) and highest among persons aged >/=80 years (902.0). Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race (Hispanic), 22% were non-Hispanic black (black), and 1.3% were non-Hispanic American Indian or Alaska Native (AI/AN). Among 287,320 (22%) cases with sufficient data on underlying health conditions, the most common were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%). The COVID-19 pandemic continues to be severe, particularly in certain population groups. These preliminary findings underscore the need to build on current efforts to collect and analyze case data, especially among those with underlying health conditions. These data are used to monitor trends in COVID-19 illness, identify and respond to localized incidence increase, and inform policies and practices designed to reduce transmission in the United States.

      20. Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra)external icon
        Taylor MM, Kara EO, Araujo MA, Silveira MF, Miranda AE, Branco Coelho IC, Bazzo ML, Mendes Pereira GF, Pereira Giozza S, Bermudez XP, Mello MB, Habib N, Nguyen MH, Thwin SS, Broutet N.
        BMC Infect Dis. 2020 Jun 10;20(1):405.
        BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer >/=1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier:, NCT03752112. Registration Date: November 22, 2018.

      21. A combination approach of behavioural and biomedical interventions for prevention of sexually transmitted infectionsexternal icon
        Toskin I, Bakunina N, Gerbase AC, Blondeel K, Stephenson R, Baggaley R, Mirandola M, Aral SO, Laga M, Holmes KK, Winkelmann C, Kiarie JN.
        Bull World Health Organ. 2020 Jun 1;98(6):431-434.

      22. Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trialexternal icon
        Wirth KE, Gaolathe T, Pretorius Holme M, Mmalane M, Kadima E, Chakalisa U, Manyake K, Matildah Mbikiwa A, Simon SV, Letlhogile R, Mukokomani K, van Widenfelt E, Moyo S, Bennett K, Leidner J, Powis KM, Lebelonyane R, Alwano MG, Jarvis J, Dryden-Peterson SL, Kgathi C, Moore J, Bachanas P, Raizes E, Abrams W, Block L, Sento B, Novitsky V, El-Halabi S, Marukutira T, Mills LA, Sexton C, Pals S, Shapiro RL, Wang R, Lei Q, DeGruttola V, Makhema J, Essex M, Lockman S, Tchetgen Tchetgen EJ.
        Lancet HIV. 2020 Jun;7(6):e422-e433.
        BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1.08 [95% CI 1.02-1.14], p=0.032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1.12 [95% CI 1.07-1.17], p=0.018; viral suppression 1.13 [1.09-1.17], p=0.017; male circumcision 1.26 [1.17-1.35], p=0.029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

    • Disaster Control and Emergency Services
      1. A social vulnerability index for disaster managementexternal icon
        Flanagan BE, Gregory EW, Hallisey EJ, Heitgerd JL, Lewis B.
        J Homel Secur Emerg Manag. 2020 ;8(1).
        Social vulnerability refers to the socioeconomic and demographic factors that affect the resilience of communities. Studies have shown that in disaster events the socially vulnerable are more likely to be adversely affected, i.e. they are less likely to recover and more likely to die. Effectively addressing social vulnerability decreases both human suffering and the economic loss related to providing social services and public assistance after a disaster. This paper describes the development of a social vulnerability index (SVI), from 15 census variables at the census tract level, for use in emergency management. It also examines the potential value of the SVI by exploring the impact of Hurricane Katrina on local populations.

    • Disease Reservoirs and Vectors
      1. Bartonella species in medically important mosquitoes, Central Europeexternal icon
        Rudolf I, Blazejova H, Mendel J, Strakova P, Sebesta O, Rettich F, Cabanova V, Miterpakova M, Betasova L, Pesko J, Barbusinova E, McKee C, Osikowicz L, Sikutova S, Hubalek Z, Kosoy M.
        Parasitol Res. 2020 Jun 6.
        Here, we provide the first mass molecular screening of medically important mosquitoes for Bartonella species using multiple genetic markers. We examined a total of 72,115 mosquito specimens, morphologically attributed to Aedes vexans (61,050 individuals), Culex pipiens (10,484 individuals) and species of the Anopheles maculipennis complex (581 individuals) for Bartonella spp. The initial screening yielded 63 Bartonella-positive A. vexans mosquitoes (mean prevalence 0.1%), 34 Bartonella-positive C. pipiens mosquitoes (mean prevalence 0.3%) and 158 Bartonella-positive A. maculipennis group mosquitoes (mean prevalence 27.2%). Several different Bartonella ITS sequences were recovered. This study highlights the need for molecular screening of mosquitoes, the most important vectors of arthropod-borne pathogens, for potential bacterial agents.

      2. Movement of St. Louis encephalitis virus in the Western United States, 2014- 2018external icon
        Swetnam DM, Stuart JB, Young K, Maharaj PD, Fang Y, Garcia S, Barker CM, Smith K, Godsey MS, Savage HM, Barton V, Bolling BG, Duggal N, Brault AC, Coffey LL.
        PLoS Negl Trop Dis. 2020 Jun 10;14(6):e0008343.
        St. Louis encephalitis virus (SLEV) is a flavivirus that circulates in an enzootic cycle between birds and mosquitoes and can also infect humans to cause febrile disease and sometimes encephalitis. Although SLEV is endemic to the United States, no activity was detected in California during the years 2004 through 2014, despite continuous surveillance in mosquitoes and sentinel chickens. In 2015, SLEV-positive mosquito pools were detected in Maricopa County, Arizona, concurrent with an outbreak of human SLEV disease. SLEV-positive mosquito pools were also detected in southeastern California and Nevada in summer 2015. From 2016 to 2018, SLEV was detected in mosquito pools throughout southern and central California, Oregon, Idaho, and Texas. To understand genetic relatedness and geographic dispersal of SLEV in the western United States since 2015, we sequenced four historical genomes (3 from California and 1 from Louisiana) and 26 contemporary SLEV genomes from mosquito pools from locations across the western US. Bayesian phylogeographic approaches were then applied to map the recent spread of SLEV. Three routes of SLEV dispersal in the western United States were identified: Arizona to southern California, Arizona to Central California, and Arizona to all locations east of the Sierra Nevada mountains. Given the topography of the Western United States, these routes may have been limited by mountain ranges that influence the movement of avian reservoirs and mosquito vectors, which probably represents the primary mechanism of SLEV dispersal. Our analysis detected repeated SLEV introductions from Arizona into southern California and limited evidence of year-to-year persistence of genomes of the same ancestry. By contrast, genetic tracing suggests that all SLEV activity since 2015 in central California is the result of a single persistent SLEV introduction. The identification of natural barriers that influence SLEV dispersal enhances our understanding of arbovirus ecology in the western United States and may also support regional public health agencies in implementing more targeted vector mitigation efforts to protect their communities more effectively.

    • Environmental Health
      1. Meta-analysis of animal studies applied to short-term inhalation exposure levels of hazardous chemicalsexternal icon
        Prussia AJ, Hill J, Cornwell CR, Siwakoti RC, Demchuk E.
        Regul Toxicol Pharmacol. 2020 Jun 3:104682.
        For short-term chemical inhalation exposures to hazardous chemicals, the incidence of a health effect in biological testing usually conforms to a general linear model with a probit link function dependent on inhalant concentration C and the duration of exposure t. The National Academy's Acute Exposure Guideline Levels (AEGLs) Committee relies on these models when establishing AEGLs. Threshold concentrations at AEGL durations are established by the toxic load equation C(n) x t=constant, which toxic load exponent n (TLE or n-value) directly follows from the bivariate probit model. When multiple probit datasets are available, the AEGL Committee routinely pools studies' incidence data. Such meta-analytical models are valid only when the pooled data are homogeneous, with similar sensitivities and equivalent responses to exposure concentrations and durations. In the present study, the homogeneity of datasets meta-analyzed by the AEGL Committee was examined, finding that 70% of datasets pooled by the AEGL Committee are heterogeneous. In these instances, data pooling leads to a statistically invalid model and TLE estimate, potentially resulting in under- or over-estimated inhalation guidance levels. When data pooling is inappropriate, other meta-analysis options include categorical regression, fixed and random effects models, or even designation of a key study based on scientific judgement. In the present work, options of TLE meta-analysis are summarized in a decision tree contingent on statistical testing.

      2. The article discusses the U.S. Centers for Disease Control and Prevention's (CDC) risk communication guidance for environmental health practitioners. Topics covered include the CDC's drinking water advisory communication toolbox and the CDC's crisis and emergency risk communication principles (CERC). Also discussed is the importance of understanding how someone receives a message.

      3. Urinary concentrations of phthalate metabolite mixtures in relation to serum biomarkers of thyroid function and autoimmunity among women from a fertility centerexternal icon
        Souter I, Bellavia A, Williams PL, Korevaar TI, Meeker JD, Braun JM, de Poortere RA, Broeren MA, Ford JB, Calafat AM, Chavarro JE, Hauser R, Minguez-Alarcon L.
        Environ Health Perspect. 2020 Jun;128(6):67007.
        BACKGROUND: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. OBJECTIVE: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. METHODS: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005-2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4) and triiodothyronine (fT3, TT3), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. RESULTS: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: -0.62; 95% confidence interval (CI): -0.12, -0.01; p=0.04; absolute difference: -8.31; 95% CI: -13.8, -2.85; p=0.003; absolute difference: -0.37; 95% CI: 0.54, -0.19; p<0.0001; and absolute difference: -0.21; 95% CI: -0.32, -0.10; p=0.003, respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb. CONCLUSIONS: Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women.

      4. PBPK model reporting template for chemical risk assessment applicationsexternal icon
        Tan YM, Chan M, Chukwudebe A, Domoradzki J, Fisher J, Hack CE, Hinderliter P, Hirasawa K, Leonard J, Lumen A, Paini A, Qian H, Ruiz P, Wambaugh J, Zhang F, Embry M.
        Regul Toxicol Pharmacol. 2020 Jun 2:104691.
        Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals. This harmonized reporting template can be adopted and customized by public health agencies receiving PBPK model submission, and it can also serve as general guidance for submitting PBPK-related studies for publication in journals or other modeling sharing purposes. The current effort represents one of several ongoing collaborations among the PBPK modeling and risk assessment communities to promote, when appropriate, incorporating PBPK modeling to characterize the influence of pharmacokinetics on safety decisions made by regulatory agencies.

      5. Heat-related deaths - United States, 2004-2018external icon
        Vaidyanathan A, Malilay J, Schramm P, Saha S.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):729-734.
        Deaths attributable to natural heat exposure, although generally considered preventable (1), represent a continuing public health concern in the United States. During 2004-2018, an average of 702 heat-related deaths occurred in the United States annually. To study patterns in heat-related deaths by age group, sex, race/ethnicity, and level of urbanization, and to explore comorbid conditions associated with deaths resulting from heat exposure, CDC analyzed nationally comprehensive mortality data from the National Vital Statistics System (NVSS).* The rate of heat-related mortality tended to be higher among males, persons aged >/=65 years, non-Hispanic American Indian/Alaska Natives, and persons living in noncore nonmetropolitan and large central metropolitan counties. Natural heat exposure was a contributing cause of deaths attributed to certain chronic medical conditions and other external causes. Preparedness and response initiatives directed toward extreme heat events, currently underway at local, state, and national levels, can contribute to reducing morbidity and mortality associated with natural heat exposure. Successful public health interventions(dagger) to mitigate heat-related deaths include conducting outreach to vulnerable communities to increase awareness of heat-related symptoms and provide guidance for staying cool and hydrated, particularly for susceptible groups at risk such as young athletes and persons who are older or socially isolated (2). Improved coordination across various health care sectors could inform local activities to protect health during periods of high heat. For instance, jurisdictions can monitor weather conditions and syndromic surveillance data to guide timing of risk communication and other measures (e.g., developing and implementing heat response plans, facilitating communication and education activities) to prevent heat-related mortality in the United States. CDC also recommends that federal, state, local, and tribal jurisdictions open cooling centers or provide access to public locations with air conditioning for persons in need of a safe, cool, environment during hot weather conditions. In light of the coronavirus disease 2019 (COVID-19) pandemic, CDC updated its guidance on the use of cooling centers to provide best practices (e.g., potential changes to staffing procedures, separate areas for persons with symptoms of COVID-19, and physical distancing) to reduce the risk for introducing and transmitting SARS COV-2, the virus that causes COVID-19, into cooling centers.( section sign).

      6. Prenatal exposure to a mixture of persistent organic pollutants (POPs) and child reading skills at school ageexternal icon
        Vuong AM, Xie C, Jandarov R, Dietrich KN, Zhang H, Sjodin A, Calafat AM, Lanphear BP, McCandless L, Braun JM, Yolton K, Chen A.
        Int J Hyg Environ Health. 2020 Jun 7;228:113527.
        BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined. METHODS: We estimated associations of prenatal serum concentrations of 17 POPs, namely 5 polybrominated diphenyl ethers (PBDEs), 6 polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and 4 per- and polyfluoroalkyl substances (PFAS), with Wide Range Achievement Test-4 reading composite scores at age 8 years in 161 children from a pregnancy and birth cohort (Health Outcomes and Measures of the Environment [HOME] Study, 2003-present) in Cincinnati, OH. We applied 6 statistical methods: least absolute shrinkage and selection operator (LASSO), elastic net (ENET), Sparse Principal Component Analysis (SPCA), Weighted Quantile Sum (WQS) regression, Bayesian Kernel Machine Regression (BKMR), and Bayesian Additive Regression Trees (BART), to estimate covariate-adjusted associations with individual and their mixtures in multi-pollutant models. RESULTS: Both LASSO and ENET models indicated inverse associations with reading scores for BDE-153 and BDE-28, and positive associations for CB-118, CB-180, perfluoroctanoate (PFOA), and perfluorononanoate (PFNA). The SPCA identified inverse associations for BDE-153 and BDE-100 and positive associations for perfluorooctane sulfonate (PFOS), PFOA, and PFNA, as parts of different principal component scores. The WQS regression showed the highest weights for BDE-100 (0.35) and BDE-28 (0.16) in the inverse association model and for PFNA (0.29) and CB-180 (0.21) in the positive association model. The BKMR model identified BDE-100 and BDE-153 for inverse associations and CB-118, CB-153, CB-180, PFOA, and PFNA for positive associations. The BART method found dose-response functions similar to the BKMR model. No interactions between POPs were identified. CONCLUSIONS: Despite some inconsistency among biomarkers, these analyses revealed inverse associations between prenatal PBDE concentrations and children's reading scores. Positive associations of PCB congeners and PFAS with reading skills were also found.

    • Epidemiology and Surveillance
      1. Mortality surveillance during the COVID-19 pandemicexternal icon
        Setel P, AbouZahr C, Atuheire EB, Bratschi M, Cercone E, Chinganya O, Clapham B, Clark SJ, Congdon C, de Savigny D, Karpati A, Nichols E, Jakob R, Mwanza J, Muhwava W, Nahmias P, Ortiz EM, Tshangela A.
        Bull World Health Organ. 2020 Jun 1;98(6):374.

    • Genetics and Genomics
      1. Addressing ethical challenges in US-based HIV phylogenetic researchexternal icon
        Dawson L, Benbow N, Fletcher FE, Kassaye S, Killelea A, Latham SR, Lee LM, Leitner T, Little SJ, Mehta SR, Martinez O, Minalga B, Poon A, Rennie S, Sugarman J, Sweeney P, Torian LV, Wertheim JO.
        J Infect Dis. 2020 Jun 11.
        In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials; in molecular epidemiology; and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in United States-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) community engagement; (4) legal issues; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

    • Health Economics
      1. Hepatitis A hospitalization costs, United States, 2017external icon
        Hofmeister MG, Yin S, Aslam MV, Teshale EH, Spradling PR.
        Emerg Infect Dis. 2020 May;26(5):1040-1041.
        The United States is in the midst of unprecedented person-to-person hepatitis A outbreaks. By using Healthcare Cost and Utilization Project data, we estimated the average costs per hepatitis A-related hospitalization in 2017. These estimates can guide investment in outbreak prevention efforts to stop the spread of this vaccine-preventable disease.

    • Healthcare Associated Infections
      1. Rhizopus microsporus infections associated with surgical procedures, Argentina, 2006-2014external icon
        Bowers JR, Monroy-Nieto J, Gade L, Travis J, Refojo N, Abrantes R, Santander J, French C, Dignani MC, Hevia AI, Roe CC, Lemmer D, Lockhart SR, Chiller T, Litvintseva AP, Clara L, Engelthaler DM.
        Emerg Infect Dis. 2020 May;26(5):937-944.
        Rhizopus spp. fungi are ubiquitous in the environment and a rare but substantial cause of infection in immunosuppressed persons and surgery patients. During 2005-2017, an abnormally high number of Rhizopus infections in surgery patients, with no apparent epidemiologic links, were reported in Argentina. To determine the likelihood of a common source of the cluster, we performed whole-genome sequencing on samples collected during 2006-2014. Most isolates were separated by >60 single-nucleotide polymorphisms, and we found no evidence for recombination or nonneutral mutation accumulation; these findings do not support common source or patient-to-patient transmission. Assembled genomes of most isolates were ≈25 Mbp, and multiple isolates had substantially larger assembled genomes (43-51 Mbp), indicative of infections with strain types that underwent genome expansion. Whole-genome sequencing has become an essential tool for studying epidemiology of fungal infections. Less discriminatory techniques may miss true relationships, possibly resulting in inappropriate attribution of point source.

      2. Prevalence of Candida auris in Canadian acute care hospitals among at-risk patients, 2018external icon
        Garcia-Jeldes HF, Mitchell R, McGeer A, Rudnick W, Amaratunga K, Vallabhaneni S, Lockhart SR, Bharat A.
        Antimicrob Resist Infect Control. 2020 Jun 10;9(1):82.
        To identify the prevalence of C. auris in Canadian patients who are potentially at risk for colonization, we screened 488 patients who were either hospitalized abroad, had a carbapenemase-producing organism (CPO), or were in units with high antifungal use. Two patients were colonized with C. auris; both had received healthcare in India and had a CPO. Among 35 patients who had recently received healthcare in the Indian subcontinent and were CPO colonized or infected, the prevalence of C. auris was 5.7%.

      3. Tuberculosis transmission across three states: the story of a solid organ donor born in an endemic country, 2018external icon
        Jones JM, Vikram HR, Lauzardo M, Hill A, Jones J, Haley C, Seaworth B, Oldham S, Brown M, Gutierrez F, Basavaraju SV.
        Transpl Infect Dis. 2020 Jun 8:e13357.
        Transmission of tuberculosis (TB) from a deceased solid organ donor to recipients can result in severe morbidity and mortality. In 2018, four solid organ transplant recipients residing in three states but sharing a common organ donor were diagnosed with TB disease. Two recipients were hospitalized and none died. The organ donor was born in a country with a high incidence of TB and experienced 8 weeks of headache and fever prior to death, but was not tested for TB during multiple hospitalizations or prior to organ procurement. TB isolates of two organ recipients and a close contact of the donor had identical TB genotypes and closely related whole-genome sequencing results. Donors with risk factors for TB, in particular birth or residence in countries with a higher TB incidence, should be carefully evaluated for TB.

      4. Antimicrobial use in US hospitals: Comparison of results from Emerging Infections Program Prevalence Surveys, 2015 and 2011external icon
        Magill SS, O'Leary E, Ray SM, Kainer MA, Evans C, Bamberg WM, Johnston H, Janelle SJ, Oyewumi T, Lynfield R, Rainbow J, Warnke L, Nadle J, Thompson DL, Sharmin S, Pierce R, Zhang AY, Ocampo V, Maloney M, Greissman S, Wilson LE, Dumyati G, Edwards JR.
        Clin Infect Dis. 2020 Jun 10.
        BACKGROUND: In the 2011 US hospital prevalence survey of healthcare-associated infections and antimicrobial use 50% of patients received antimicrobial medications on the survey date or day before. More hospitals have since established antimicrobial stewardship programs. We repeated the survey in 2015 to determine antimicrobial use prevalence and describe changes since 2011. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program sites in 10 states each recruited </=25 general and women's and children's hospitals. Hospitals selected a survey date from May-September 2015. Medical records for a random patient sample on the survey date were reviewed to collect data on antimicrobial medications administered on the survey date or day before. Percentages of patients on antimicrobial medications were compared; multivariable log-binomial regression modeling was used to evaluate factors associated with antimicrobial use. RESULTS: Of 12 299 patients in 199 hospitals, 6084 (49.5%; 95% CI, 48.6-50.4%) received antimicrobials. Among 148 hospitals in both surveys, overall antimicrobial use prevalence was similar in 2011 and 2015, although the percentage of neonatal critical care patients on antimicrobials was lower in 2015 (22.8% vs 32.0% [2011]; P = .006). Fluoroquinolone use was lower in 2015 (10.1% of patients vs 11.9% [2011]; P < .001). Third- or fourth-generation cephalosporin use was higher (12.2% vs 10.7% [2011]; P = .002), as was carbapenem use (3.7% vs 2.7% [2011]; P < .001). CONCLUSIONS: Overall hospital antimicrobial use prevalence was not different in 2011 and 2015; however, differences observed in selected patient or antimicrobial groups may provide evidence of stewardship impact.

      5. Detection of ciprofloxacin-resistant, beta-lactamase-producing Neisseria meningitidis serogroup Y isolates - United States, 2019-2020external icon
        McNamara LA, Potts C, Blain AE, Retchless AC, Reese N, Swint S, Lonsway D, Karlsson M, Lunquest K, Sweitzer JJ, Wang X, Hariri S, Fox LM.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):735-739.
        Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations.

      6. Modeling inpatient and outpatient antibiotic stewardship interventions to reduce the burden of Clostridioides difficile infection in a regional healthcare networkexternal icon
        Rhea S, Jones K, Endres-Dighe S, Munoz B, Weber DJ, Hilscher R, MacFarquhar J, Sickbert-Bennett E, DiBiase L, Marx A, Rineer J, Lewis J, Bobashev G.
        PLoS One. 2020 ;15(6):e0234031.
        Antibiotic exposure can lead to unintended outcomes, including drug-drug interactions, adverse drug events, and healthcare-associated infections like Clostridioides difficile infection (CDI). Improving antibiotic use is critical to reduce an individual's CDI risk. Antibiotic stewardship initiatives can reduce inappropriate antibiotic prescribing (e.g., unnecessary antibiotic prescribing, inappropriate antibiotic selection), impacting both hospital (healthcare)-onset (HO)-CDI and community-associated (CA)-CDI. Previous computational and mathematical modeling studies have demonstrated a reduction in CDI incidence associated with antibiotic stewardship initiatives in hospital settings. Although the impact of antibiotic stewardship initiatives in long-term care facilities (LTCFs), including nursing homes, and in outpatient settings have been documented, the effects of specific interventions on CDI incidence are not well understood. We examined the relative effectiveness of antibiotic stewardship interventions on CDI incidence using a geospatially explicit agent-based model of a regional healthcare network in North Carolina. We simulated reductions in unnecessary antibiotic prescribing and inappropriate antibiotic selection with intervention scenarios at individual and network healthcare facilities, including short-term acute care hospitals (STACHs), nursing homes, and outpatient locations. Modeled antibiotic prescription rates were calculated using patient-level data on antibiotic length of therapy for the 10 modeled network STACHs. By simulating a 30% reduction in antibiotics prescribed across all inpatient and outpatient locations, we found the greatest reductions on network CDI incidence among tested scenarios, namely a 17% decrease in HO-CDI incidence and 7% decrease in CA-CDI. Among intervention scenarios of reducing inappropriate antibiotic selection, we found a greater impact on network CDI incidence when modeling this reduction in nursing homes alone compared to the same intervention in STACHs alone. These results support the potential importance of LTCF and outpatient antibiotic stewardship efforts on network CDI burden and add to the evidence that a coordinated approach to antibiotic stewardship across multiple facilities, including inpatient and outpatient settings, within a regional healthcare network could be an effective strategy to reduce network CDI burden.

      7. Antibiotic stewardship in the intensive care unit. An Official American Thoracic Society Workshop Report in Collaboration with the AACN, CHEST, CDC, and SCCMexternal icon
        Wunderink RG, Srinivasan A, Barie PS, Chastre J, Dela Cruz CS, Douglas IS, Ecklund M, Evans SE, Evans SR, Gerlach AT, Hicks LA, Howell M, Hutchinson ML, Hyzy RC, Kane-Gill SL, Lease ED, Metersky ML, Munro N, Niederman MS, Restrepo MI, Sessler CN, Simpson SQ, Swoboda SM, Guillamet CV, Waterer GW, Weiss CH.
        Ann Am Thorac Soc. 2020 May;17(5):531-540.
        Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

    • Immunity and Immunization
      1. Modeling of rotavirus transmission dynamics and impact of vaccination in Ghanaexternal icon
        Asare EO, Al-Mamun MA, Armah GE, Lopman BA, Parashar UD, Binka F, Pitzer VE.
        Vaccine. 2020 Jun 5.
        BACKGROUND: Rotavirus incidence remains relatively high in low-income countries (LICs) compared to high-income countries (HICs) after vaccine introduction. Ghana introduced monovalent rotavirus vaccine in April 2012 and despite the high coverage, vaccine performance has been modest compared to developed countries. The predictors of low vaccine effectiveness in LICs are poorly understood, and the drivers of subnational heterogeneity in rotavirus vaccine impact are unknown. METHODS: We used mathematical models to investigate variations in rotavirus incidence in children <5 years old in Ghana. We fit models to surveillance and case-control data from three different hospitals: Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and War Memorial Hospital in Navrongo. The models were fitted to both pre- and post-vaccine data to estimate parameters describing the transmission rate, waning of maternal immunity, and vaccine response rate. RESULTS: The seasonal pattern and age distribution of rotavirus cases varied among the three study sites in Ghana. Our model was able to capture the spatio-temporal variations in rotavirus incidence across the three sites and showed good agreement with the age distribution of observed cases. The rotavirus transmission rate was highest in Accra and lowest in Navrongo, while the estimated duration of maternal immunity was longer (~5 months) in Accra and Kumasi and shorter (~3 months) in Navrongo. The proportion of infants who responded to the vaccine was estimated to be high in Accra and Kumasi and low in Navrongo. CONCLUSIONS: Rotavirus vaccine impact varies within Ghana. A low vaccine response rate was estimated for Navrongo, where rotavirus is highly seasonal and incidence limited to a few months of the year. Our findings highlight the need to further explore the relationship between rotavirus seasonality, maternal immunity, and vaccine response rate to determine how they influence vaccine effectiveness and to develop strategies to improve vaccine impact.

      2. Recent advances in human norovirus research and implications for candidate vaccinesexternal icon
        Cates J, Vinje J, Parashar U, Hall AJ.
        Expert Rev Vaccines. 2020 Jun 5.
        INTRODUCTION: Noroviruses are a leading cause of acute gastroenteritis worldwide. An estimated 21 million illnesses in the United States and upwards of 684 million illnesses worldwide are attributed to norovirus infection. There are no licensed vaccines to prevent norovirus, but several candidates are in development. Areas covered: We review recent advances in molecular epidemiology of noroviruses, immunology, and in-vitro cultivation of noroviruses using human intestinal enteroids. We also provide an update on the status of norovirus vaccine candidates. Expert opinion: Molecular epidemiological studies confirm the tremendous genetic diversity of noroviruses, the continuous emergence of new recombinant strains, and the predominance of GII.4 viruses worldwide. Duration of immunity, extent of cross protection between different genotypes, and differences in strain distribution for young children compared with adults remain key knowledge gaps. Recent discoveries regarding which epitopes are targeted by neutralizing antibodies using the novel in vitro culture of human noroviruses in human intestinal enteroids are enhancing our understanding of mechanisms of protection and providing guidance for vaccine development. A future norovirus vaccine has the potential to substantially reduce the burden of illnesses due to this ubiquitous virus.

      3. Access, demand, and utilization of childhood immunization services: A cross-sectional household survey in Western Area Urban district, Sierra Leone, 2019external icon
        Feldstein LR, Sutton R, Jalloh MF, Parmley L, Lahuerta M, Akinjeji A, Mansaray A, Eleeza O, Sesay T, Kulkarni S, Conklin L, Wallace AS.
        J Glob Health. 2020 Jun;10(1).
        Background: Urban childhood immunization programs face unique challenges in access, utilization, and demand due to frequent population movement between and within localities, sprawling informal settlements, and population heterogeneity. We conducted a cross-sectional household survey in the Western Area Urban district, Sierra Leone, stratified by slums and non-slums as defined by the United Nations Development Program. Methods: Based on data from child vaccination cards, weighted vaccination coverage was estimated from 450 children aged 12-36 months (household response rate = 83%). Interviews with 444 caregivers identified factors related to accessing routine immunization services. Factors associated with coverage in bivariate analyses were examined in multivariate models using backward stepwise procedure. Results: Coverage was similar in slums and non-slums for 3-doses of diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b (pentavalent) vaccine (86%, 92%) and second dose of measles vaccine (33%, 29%). In a multivariate logistic regression model, incomplete pentavalent vaccine coverage was associated with being second or later birth order (adjusted odds ratio (aOR) = 4.5 (95% confidence interval (CI) = 1.4-14.9), a household member not approving of childhood vaccinations (aOR = 7.55, 95% CI = 1.52-37.38), self-reported delay of child receiving recommended vaccinations (aOR = 4.8, 95% CI = 1.0-22.1), and living in a household made of natural or rudimentary materials (aOR = 3.5, 95% CI = 1.2-10.6). Overall, the majority (>70%) of caregivers reported occupation as petty trader and <50% reported receiving vaccination information via preferred communication sources. Conclusions: Although vaccination coverage in slums was similar to non-slums, study findings support the need for targeted interventions to improve coverage, especially for the second dose of measles vaccine to avoid large scale measles outbreaks. Strategies should focus on educating household members via preferred communication channels regarding the importance of receiving childhood vaccinations on time for all offspring, not just the first born. Vaccination coverage could be further improved by increasing accessibility through innovative strategies such as increasing the number of vaccination days and modifying hours.

      4. Effectiveness of 1, 2, and 3 doses of human papillomavirus vaccine against high-grade cervical lesions positive for human papillomavirus 16 or 18external icon
        Johnson Jones ML, Gargano JW, Powell M, Park IU, Niccolai LM, Bennett NM, Griffin MR, Querec T, Unger ER, Markowitz LE.
        Am J Epidemiol. 2020 Apr 2;189(4):265-276.
        Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008-2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received ≥24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18-positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.

      5. Effects of prior season vaccination on current season vaccine effectiveness in the US Flu VE Network, 2012-13 through 2017-18external icon
        Kim SS, Flannery B, Foppa IM, Chung JR, Nowalk MP, Zimmerman RK, Gaglani M, Monto AS, Martin ET, Belongia EA, McLean HQ, Jackson ML, Jackson LA, Patel M.
        Clin Infect Dis. 2020 Jun 7.
        BACKGROUND: We compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated. METHODS: Our analysis included data from the US Flu VE Network among participants >/=9 years old with acute respiratory illness from 2012-13 through 2017-18. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination compared to prior vaccinated. RESULTS: 31,819 participants were included. Vaccine protection against any influenza averaged 42% (38 to 47) among those vaccinated only the current season, 37% (33 to 40) among those vaccinated both seasons, and 26% (18 to 32) among those vaccinated only the prior season, compared to participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (37 to 46), including 57%, 27% and 55% against A(H1N1), A(H3N2) and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (7 to 23), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2). CONCLUSION: Our findings support ACIP recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.

      6. Progress toward rubella elimination - Western Pacific Region, 2000-2019external icon
        Knapp JK, Mariano KM, Pastore R, Grabovac V, Takashima Y, Alexander JP, Reef SE, Hagan JE.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):744-750.
        Rubella is the leading vaccine-preventable cause of birth defects. Rubella typically manifests as a mild febrile rash illness; however, infection during pregnancy, particularly during the first trimester, can result in miscarriage, fetal death, or a constellation of malformations known as congenital rubella syndrome (CRS), commonly including one or more visual, auditory, or cardiac defects (1). In 2012, the Regional Committee of the World Health Organization (WHO) Western Pacific Region (WPR)* committed to accelerate rubella control, and in 2017, resolved that all countries or areas (countries) in WPR should aim for rubella elimination(dagger) as soon as possible (2,3). WPR countries are capitalizing on measles elimination activities, using a combined measles and rubella vaccine, case-based surveillance for febrile rash illness, and integrated diagnostic testing for measles and rubella. This report summarizes progress toward rubella elimination and CRS prevention in WPR during 2000-2019. Coverage with a first dose of rubella-containing vaccine (RCV1) increased from 11% in 2000 to 96% in 2019. During 1970-2019, approximately 84 million persons were vaccinated through 62 supplementary immunization activities (SIAs) conducted in 27 countries. Reported rubella incidence increased from 35.5 to 71.3 cases per million population among reporting countries during 2000-2008, decreased to 2.1 in 2017, and then increased to 18.4 in 2019 as a result of outbreaks in China and Japan. Strong sustainable immunization programs, closing of existing immunity gaps, and maintenance of high-quality surveillance to respond rapidly to and contain outbreaks are needed in every WPR country to achieve rubella elimination in the region.

      7. Estimating population immunity to poliovirus in Lebanon: Results from a seroprevalence survey, 2016external icon
        Mansour Z, Said R, Wannemuehler K, Weldon W, Estephan J, Khachan J, Warrak R, Hendley W, Ehrhardt D, Farag NH.
        Vaccine. 2020 Jun 1.
        INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. RESULTS: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. CONCLUSION: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status.

      8. Vaccine effectiveness on DNA prevalence of human papillomavirus infection in anal and oral specimens from men who have sex with men- United States, 2016-2018external icon
        Meites E, Winer RL, Newcomb ME, Gorbach PM, Querec TD, Rudd J, Collins T, Lin J, Moore J, Remble T, Swanson F, Franz J, Bolan RK, Golden MR, Mustanski B, Crosby RA, Unger ER, Markowitz LE.
        J Infect Dis. 2020 Jun 6.
        BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended for young adult men who have sex with men (MSM) since 2011. METHODS: The Vaccine Impact in Men (VIM) study surveyed MSM and transgender women aged 18-26 years in 3 U.S. cities during 2016-2018. Self-collected anal swab and oral rinse specimens were assessed for 37 types of HPV DNA. We compared HPV prevalence among vaccinated and unvaccinated participants and determined adjusted prevalence ratios (aPR) and confidence intervals (CI). RESULTS: Among 1,767 participants, 704 (39.8%) self-reported receiving HPV vaccine. Median age at vaccination (18.7 years) was older than age at first sex (15.7 years). Quadrivalent vaccine-type HPV was detected in anal or oral specimens from 475 (26.9%) participants. Vaccine-type HPV prevalence was lower among vaccinated (22.9%) compared with unvaccinated (31.6%) participants; aPR for those who initiated vaccination at </=18 years was 0.41 (95% CI: 0.24-0.57) and at >18 years was 0.82 (95% CI: 0.67-0.98). Vaccine effectiveness for at least one HPV vaccine dose at age >/=18 years or >18 years was 59% and 18%, respectively. CONCLUSIONS: Findings suggest real-world effectiveness of HPV vaccination among young adult MSM. This effect was stronger with younger age at vaccination.

    • Injury and Violence
      1. Objective: To estimate frequency and type of older adult fall-related injuries treated in emergency departments (EDs). Methods: We used the 2015 National Electronic Injury Surveillance System: All Injury Program. Patient data were abstracted from the narratives describing the circumstance of injury. Data for community-dwelling older adults (n = 34,336) were analyzed to explore differences in injury diagnosis by demographic characteristics, location of fall, and disposition. Results: 70% of head-related injuries were internal injuries, suggestive of a traumatic brain injury. Most hip injuries were fractures or dislocations (73.3%). Women had higher percentages of fractures/dislocations but lower percentages of internal injuries than men. About a third of fall-related ED visits required hospitalization or transfer. Discussion: Falls in older adults result in array of injuries and pose a burden on the healthcare system. Understanding how fall injuries vary by different characteristics can help inform targeted prevention strategies.

      2. Sexual violence in sport: American Medical Society for Sports Medicine Position Statementexternal icon
        Koontz JS, Mountjoy M, Abbott KE, Aron CM, Basile KC, Carlson CT, Chang CJ, Diamond AB, Dugan SA, Hainline B, Herring SA, Hopkins E, Joy EA, Judge JP, LaBotz M, Matuszak J, McDavis CJ, Myers RA, Nattiv A, Tanji JL, Wagner J, Roberts WO.
        Clin J Sport Med. 2020 Jun 8.
        The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a Position Statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the task force used an iterative process and expert consensus to finalize the Position Statement. The objective of this Position Statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

      3. Characteristics of concussion in elementary school-aged children: Implications for clinical managementexternal icon
        Master CL, Curry AE, Pfeiffer MR, Metzger KB, Kessler RS, Haarbauer-Krupa J, DePadilla L, Greenspan A, Breiding MJ, Arbogast KB.
        J Pediatr. 2020 May 29.
        OBJECTIVE: To comprehensively characterize the clinical presentation and course of care for concussion among 5- to 11-year-old children, identifying preinjury and injury factors potentially influencing clinical outcomes. STUDY DESIGN: A single-institution retrospective cohort study using electronic health record data from children ages 5- to 11 years with a concussion from July 1, 2014, through June 30, 2015. Electronic health record data were abstracted for a 20% random sample of 292 patients. RESULTS: Three-fourths of patients (74.3%) presenting for concussion care had a standardized visiovestibular assessment performed. Almost all of those who eventually sought specialty care (92.9%) also had such an assessment, and only 42.9% patients initially seen in the emergency department or urgent care were examined in this manner. Of those assessed, 62.7% (n = 136) demonstrated deficits, with children ages 9-11 years more frequently exhibiting deficits than their younger counterparts (67.9% vs 53.2%; P = .03). Almost all patients (95.9%) reported at least 1 somatic symptom (eg, headache, dizziness), and one-half to two-thirds reported problems with sleep (54.1%) and visiovestibular symptoms (66.1%). Only 11.6% of children were referred for rehabilitation therapies and less than one-half of concussed patients (43.8%) were provided with a letter recommending school accommodations. CONCLUSIONS: Somatic symptoms, sleep problems, and visiovestibular deficits are common in elementary school-aged children with concussion, but specific visiovestibular clinical assessments are often not performed, particularly in the emergency department setting. Recommendations for school accommodations are often not provided at the time of concussion diagnosis. Incorporating a standardized visiovestibular assessment into practice could facilitate early targeted school accommodations and thereby improve return to learning for elementary school-aged children with concussion.

    • Laboratory Sciences
      1. The current context of malaria elimination requires urgent development and implementation of highly sensitive and specific methods for prompt detection and treatment of malaria parasites. Such methods should overcome current delays in diagnosis, allow the detection of low-density infections and address the difficulties in accessing remote endemic communities. In this study, we assessed the performance of the RealAmp and malachite-green loop mediated isothermal amplification (MG-LAMP) methodologies, using microscopy and conventional nested-PCR as reference techniques. Both LAMP techniques were performed for Plasmodium genus, P. falciparum, and P. vivax identification using 136 whole blood samples collected from three communities located in the Peruvian Amazon basin. Turnaround time and costs of performing the LAMP assays were estimated and compared to that of microscopy and nested-PCR. Using nested-PCR as reference standard, we calculated the sensitivity, specificity and 95% confidence interval (CI) for all methods. RealAmp had a sensitivity of 92% (95% CI: 85-96.5%) and specificity of 100% (95% CI: 89.1-100%) for species detection; sensitivity and specificity of MG-LAMP were 94% (95% CI: 87.5-97.8%) and 100% (89.1-100%), respectively. Whereas microscopy showed 88.1% sensitivity (95% CI: 80.2-93.7%) and 100% specificity (95%: 89.1-100%). The turnaround time and costs of performing the LAMP assays were lower compared to those associated with nested-PCR but higher than those associated with microscopy. The two LAMP assays were shown to be more sensitive and simple to implement than microscopy. Both LAMP methodologies could be used as large-scale screening tests, but the MG-LAMP assay uses a simple, portable heat-block while the RealAmp requires a RealAmp machine or a real-time PCR machine. This makes the MG-LAMP an appropriate choice for malaria surveillance studies in endemic sites. Use of LAMP tests in active case detection of Plasmodium parasites could help to detect positive malaria cases early.

      2. The effect of various cell phone related activities on gait kinematicsexternal icon
        Brennan AC, Breloff SP.
        J Musculoskelet Res. 2019 ;22(3-4).
        Background: With cell phone use and ownership on the rise, daily circumstances often require individuals to divide attentional resources between walking and a cell phone-related task. This division of attention has been found to detrimentally effect task performance, making pedestrian cell phone usage an increasing safety concern. However, most studies have investigated the impact of dual-Tasks on situational awareness and few have focused on tasks other than texting. Therefore, this study aimed to investigate the effect of various cell phone-related tasks on lower limb kinematics during walking. Methods: Fourteen healthy, college-Aged subjects completed gait analysis trials in five walking conditions, one single-Task walking condition and four dual task conditions: Walk+Converse, Walk+Read (Simple), Walk+Read (Difficult), and Walk+Text. Subjects' movements were recorded with a motion capture system and peak sagittal plane lower extremity joint angles, gait velocity, and stride length were calculated. Results: Of the eight kinematic outcome measures analyzed, all but one revealed some significant (p < 0.05) differences between dual-Task walking conditions. Gait velocity and stride length both decreased due to the addition of the dual tasking, with the magnitude of the reduction becoming more apparent with the increased difficulty of the cell phone-based task. Conclusion: This study supports a fundamental change to gait kinematics in response to cell phone use while walking, with the magnitude of impact being directly related to the complexity of the secondary task. The significant changes to gait kinematics in complex dual-Task situations could present a threat to balance.

      3. Characterization of a Borrelia miyamotoi membrane antigen (BmaA) for serodiagnosis of Borrelia miyamotoi diseaseexternal icon
        Harris EK, Brandt KS, Van Gundy TJ, Goodrich I, Wormser GP, Armstrong BA, Gilmore RD.
        Ticks and Tick-borne Diseases. 2020 ;11(5).
        Borrelia miyamotoi is a tick-borne pathogen that causes Borrelia miyamotoi disease (BMD), an emerging infectious disease of increasing public health significance. B. miyamotoi is transmitted by the same tick vector (Ixodes spp.) as B. burgdorferi sensu lato (s.l.), the causative agent of Lyme disease, therefore laboratory assays to differentiate BMD from Lyme disease are needed to avoid misdiagnoses and for disease confirmation. We previously performed a global immunoproteomic analysis of the murine host antibody response against B. miyamotoi infection to discover antigens that could serologically distinguish the two infections. An initial assessment identified a putative lipoprotein antigen, here termed BmaA, as a promising candidate to augment current research-based serological assays. In this study, we show that BmaA is an outer surface-associated protein by its susceptibility to protease digestion. Synthesis of BmaA in culture was independent of temperature at either 23 °C or 34 °C. The BmaA gene is present in two identical loci harbored on separate plasmids in North American strains LB-2001 and CT13-2396. bmaA-like sequences are present in other B. miyamotoi strains and relapsing fever borrelia as multicopy genes and as paralogous or orthologous gene families. IgM and IgG antibodies in pooled serum from BMD patients reacted with native BmaA fractionated by 2-dimensional gel electrophoresis and identified by mass spectrometry. IgG against recombinant BmaA was detected in 4 of 5 BMD patient serum samples as compared with 1 of 23 serum samples collected from patients with various stages of Lyme disease. Human anti-B. turicatae serum did not seroreact with recombinant BmaA suggesting a role as a species-specific diagnostic antigen. These results demonstrated that BmaA elicits a human host antibody response during B. miyamotoi infection but not in a tested group of B. burgdorferi-infected Lyme disease patients, thereby providing a potentially useful addition for developing BMD serodiagnostic tests.

      4. Assessing the performance of dried-blood-spot DNA extraction methods in next generation sequencingexternal icon
        Hendrix MM, Cuthbert CD, Cordovado SK.
        Int J Neonatal Screen. 2020 Apr 30;6(2):1-15.
        An increasing number of newborn screening laboratories in the United States and abroad are moving towards incorporating next-generation sequencing technology, or NGS, into routine screening, particularly for cystic fibrosis. As more programs utilize this technology for both cystic fibrosis and beyond, it is critical to identify appropriate DNA extraction methods that can be used with dried blood spots that will result in consistent, high-quality sequencing results. To provide comprehensive quality assurance and technical assistance to newborn screening laboratories wishing to incorporate NGS assays, CDC's Newborn Screening and Molecular Biology Branch designed a study to evaluate the performance of nine commercial or laboratory-developed DNA extraction methods that range from a highly purified column extraction to a crude detergent-based no-wash boil prep. The DNA from these nine methods was used in two NGS library preparations that interrogate the CFTR gene. All DNA extraction methods including the cruder preps performed reasonably well with both library preps. One lower-concentration, older sample was excluded from one of the assay evaluations due to poor performance across all DNA extraction methods. When 84 samples, versus eight, were run on a flow cell, the DNA quality and quantity were more significant variables.

      5. Characterization of horizontally acquired ribotoxin encoding genes and their transcripts in Aedes aegyptiexternal icon
        Lapadula WJ, Marcet PL, Taracena M, Lenhart A, Juri Ayub M.
        Gene. 2020 Jun 5:144857.
        Ribosome Inactivating Proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine residue in the conserved sarcin/ricin loop of the 28S rRNA. The occurrence of RIP genes has been described in a wide range of plant taxa, as well as in several species of bacteria and fungi. A remarkable case is the presence of these genes in metazoans belonging to the Culicinae subfamily. We reported that these genes are derived from a single horizontal gene transfer event, most likely from a bacterial donor species. Moreover, we have shown evidence that mosquito RIP genes are evolving under purifying selection, suggesting that these toxins have acquired a functional role in these organisms. In the present work, we characterized the intra-specific sequence variability of Aedes aegypti RIP genes (RIPAe1, RIPAe2, and RIPAe3) and tested their expression at the mRNA level. Our results show that RIPAe2 and RIPAe3 are transcribed and polyadenylated, and their expression levels are modulated across the developmental stages. Varibility among genes was observed, including the existence of null alleles for RIPAe1 and RIPAe2, with variants showing partial deletions. These results further support the existence of a physiological function for these foreign genes in mosquitoes. The possible nature of this functionality is discussed.

      6. A number of errors with potentially significant consequences may be introduced at various points in the analytical process which result in skewed, erroneous analytical results. Precautionary procedures such as contamination control, following established sample collection protocols, and having a complete understanding of the long-term stability of the elements of interest can minimize or eliminate these errors. Contamination control is critical in quantification of Cr and Co in human whole blood. Cr and Co levels in most biological samples are low, but these elements occur naturally in the environment and are often found in commercial and consumer products, which increases the risk of contamination. In this paper, we demonstrated that lot screening process in which we pre-screen a sub-set of manufactured lots used in collecting, analyzing, and storing blood samples is a critical step in controlling Cr and Co contamination. Stainless steel needles are often utilized in blood collection but are considered a potential source of introducing metal contamination to the patient sample. We conducted two studies to determine if there is a possibility of Cr or Co leaching into the human whole blood from the needles during blood collection. We analyzed blood collected from 100 donors and blood collected in-vitro in the laboratory from designated vessel containing spiked blood with higher levels of Cr and Co. Two blood tubes were consecutively collected through one needle. In both studies, Cr and Co concentration levels in the two consecutively collected tubes were compared. Based on the results from donor and in-vitro blood collection studies, we concluded there was no Cr and Co leaching from the limited sets of stainless steel needles used in these studies. Further, we demonstrated that Cr and Co human whole blood samples are stable for one year stored at temperatures of -70 degrees C, -20 degrees C, and 4 degrees C, and six months at room temperature.

      7. Lipidomics is a rapidly growing field, fueled by developments in analytical instrumentation and bioinformatics. To date, most researchers and industries have employed their own lipidomics workflows without a consensus on best practices. Without a community-wide consensus on best practices for the prevention of lipid degradation and transformations through sample collection and analysis, it is difficult to assess the quality of lipidomics data and hence trust results. Clinical studies often rely on samples being stored for weeks or months until they are analyzed, but inappropriate sampling techniques, storage temperatures, and analytical protocols can result in the degradation of complex lipids and the generation of oxidized or hydrolyzed metabolite artifacts. While best practices for lipid stability are sample dependent, it is generally recommended that strategies during sample preparation capable of quenching enzymatic activity and preventing oxidation should be considered. In addition, after sample preparation, lipid extracts should be stored in organic solvents with antioxidants at -20 degrees C or lower in an airtight container without exposure to light or oxygen. This will reduce or eliminate sublimation, and chemically and physically induced molecular transformations such as oxidation, enzymatic transformation, and photon/heat-induced degradation. This review explores the available literature on lipid stability, with a particular focus on human health and/or clinical lipidomic applications. Specifically, this includes a description of known mechanisms of lipid degradation, strategies, and considerations for lipid storage, as well as current efforts for standardization and quality insurance of protocols.

      8. Of the eighteen hemagglutinin (HA) subtypes (H1-H18) that have been identified in bats and aquatic birds, many HA subtypes have been structurally characterized. However, several subtypes (H8, H11 and H12) still require characterization. To better understand all of these HA subtypes at the molecular level, HA structures from an A(H4N6) (A/swine/Missouri/A01727926/2015), an A(H8N4) (A/turkey/Ontario/6118/1968), an A(H11N9) (A/duck/Memphis/546/1974), an A(H14N5) A/mallard/Gurjev/263/1982, and an A(H15N9) (A/wedge-tailed shearwater/Western Australia/2576/1979 were determined by X-ray crystallography at 2.2Å, 2.3Å, 2.8Å, 3.0Å and 2.5Å resolution, respectively. The interactions between these viruses and host receptors were studied utilizing glycan-binding analyses with their recombinant HA. The data show that all avian HAs retain their strict binding preference to avian receptors, whereas swine H4 has a weak human receptor binding. The molecular characterization and structural analyses of the HA from these zoonotic influenza viruses not only provide a deeper appreciation and understanding of the structure of all HA subtypes, but also re-iterate why continuous global surveillance is needed.

    • Maternal and Child Health
      1. Indicators of social competence and social participation among US children with Tourette syndromeexternal icon
        Bitsko RH, Danielson ML, Leeb RT, Bergland B, Fuoco MJ, Ghandour RM, Lewin AB.
        J Child Neurol. 2020 Jun 9.
        Children with Tourette syndrome often have behavioral and social difficulties, which may be associated with co-occurring mental, emotional, or behavioral disorders. This study investigated social competence, including behavioral problems and social skills, and social activities between children with and without Tourette syndrome using a nationally representative sample. In the 2007 National Survey of Children's Health, parents reported on health care provider diagnosis of Tourette syndrome, co-occurring mental, emotional, or behavioral disorders, and indicators of social competence. Children aged 6-17 years with and without Tourette syndrome were compared. Most (78.7%) children with Tourette syndrome had a co-occurring mental, emotional, or behavioral disorder. Children with Tourette syndrome had significantly lower social competence, exhibited by higher levels of behavior problems (mean score 11.6 for Tourette syndrome and 9.0 for no Tourette syndrome) and lower levels of social skills (mean 15.3) than children without a Tourette syndrome diagnosis (mean 17.1); however, these associations were no longer significant after controlling for co-occurring mental, emotional, or behavioral disorders. Moderate to severe Tourette syndrome was associated with the highest ratings of behavioral problems and the lowest ratings of social skills. Children with and without Tourette syndrome were equally likely to participate in social activities; the difference for children with moderate to severe Tourette syndrome being less likely to participate in activities compared to children with mild Tourette syndrome had a chi-square test P value of .05. In conclusion, Tourette syndrome was associated with lower social competence, particularly for children with moderate to severe Tourette syndrome. Monitoring social functioning and co-occurring conditions among children with Tourette syndrome, and referral for evidence-based interventions when needed, may benefit overall health and functioning.

      2. ADHD and psychiatric comorbidity: Functional outcomes in a school-based sample of childrenexternal icon
        Cuffe SP, Visser SN, Holbrook JR, Danielson ML, Geryk LL, Wolraich ML, McKeown RE.
        J Atten Disord. 2020 Jul;24(9):1345-1354.
        Objective: Investigate the prevalence and impact of psychiatric comorbidities in community-based samples of schoolchildren with/without ADHD. Method: Teachers and parents screened children in South Carolina (SC; n = 4,604) and Oklahoma (OK; n = 12,626) for ADHD. Parents of high-screen and selected low-screen children received diagnostic interviews (SC: n = 479; OK: n = 577). Results: Psychiatric disorders were increased among children with ADHD and were associated with low academic performance. Conduct disorder/oppositional defiant disorder (CD/ODD) were associated with grade retention (ODD/CD + ADHD: odds ratio [OR] = 3.0; confidence interval [CI] = [1.5, 5.9]; ODD/CD without ADHD: OR = 4.0; CI = [1.7, 9.7]). School discipline/police involvement was associated with ADHD alone (OR = 3.2; CI = [1.5, 6.8]), ADHD + CD/ODD (OR = 14.1, CI = [7.3, 27.1]), ADHD + anxiety/depression (OR = 4.8, CI = [1.6, 14.8]), and CD/ODD alone (OR = 2.8, CI = [1.2, 6.4]). Children with ADHD + anxiety/depression had tenfold risk for poor academic performance (OR = 10.8; CI = [2.4, 49.1]) compared to children with ADHD alone. This should be interpreted with caution due to the wide confidence interval. Conclusion: Most children with ADHD have psychiatric comorbidities, which worsens functional outcomes. The pattern of outcomes varies by type of comorbidity.

      3. Health care transition perceptions among parents of adolescents with congenital heart defects in Georgia and New Yorkexternal icon
        Gaydos LM, Sommerhalter K, Raskind-Hood C, Fapo O, Lui G, Hsu D, Van Zutphen A, Glidewell J, Farr S, Rodriguez FH, Hoffman T, Book W.
        Pediatr Cardiol. 2020 Jun 4.
        With increasing survival trends for children and adolescents with congenital heart defects (CHD), there is a growing need to focus on transition from pediatric to adult specialty cardiac care. To better understand parental perspectives on the transition process, a survey was distributed to 451 parents of adolescents with CHD who had recent contact with the healthcare system in Georgia (GA) and New York (NY). Among respondents, 90.7% reported excellent, very good or good health-related quality of life (HRQoL) for their adolescent. While the majority of parents (77.8%) had been told by a provider about their adolescent's need to transition to adult specialty cardiac care, most reported concerns about transitioning to adult care. Parents were most commonly concerned with replacing the strong relationship with pediatric providers (60.7%), locating an appropriate adult provider (48.7%), and accessing adult health insurance coverage (43.6%). These findings may offer insights into transition planning for adolescents with CHD.

    • Nutritional Sciences
      1. Objective: To explore whether the association between bottle-feeding during the first year and childhood obesity at age 6 years is mediated by change in weight-for-age z-score (DeltaWAZ) during infancy. Methods: Participants were 1062 mother-child pairs who participated in the Infant Feeding Practices Study II and Year 6 Follow-Up. Mothers completed 1 prenatal questionnaire, 10 postpartum questionnaires during the first year, and 1 follow-up questionnaire at 6 years. Child weights were reported by mothers and used to determine DeltaWAZ from birth to later infancy. Causal mediation analysis was used to determine the average direct effect of bottle-feeding on obesity at age 6 years and the average causal mediation effect of bottle-feeding through DeltaWAZ. Results: Infants who experienced rapid increases in bottle-feeding frequency during the first 6 months had significantly greater DeltaWAZ compared with infants who had consistently low bottle-feeding frequency until 12 months of age [beta = 0.45, 95% confidence interval (CI) 0.11-0.80]. Significant predictors of obesity at age 6 years were larger birth weight [adjusted odds ratio (AOR) = 4.27, 95% CI 2.42-7.64] and larger DeltaWAZ (AOR = 1.59, 95% CI 1.29-1.98). An indirect effect of bottle-feeding, mediated via DeltaWAZ, accounted for 59% of the total effect of bottle-feeding on obesity at age 6 years. Conclusions: Rapid increases in bottle use during the first 6 months postpartum predicted greater risk for obesity at age 6 years via an indirect mediation effect of larger DeltaWAZ from birth to later infancy.

    • Occupational Safety and Health

      1. Spirometric abnormalities and lung function decline in current and former microwave popcorn and current flavoring manufacturing workersexternal icon
        Cox-Ganser JM, White SK, Fedan KB, Bailey RL, Fechter-Leggett E, Cummings KJ.
        J Occup Environ Med. 2020 Jun;62(6):412-419.
        OBJECTIVE: The aim of this study was to compare spirometry results in microwave popcorn and flavoring manufacturing workers. METHODS: We used NIOSH data on current and former microwave popcorn workers (MPWs) and surveillance data on flavoring manufacturing workers (FMWs). RESULTS: Former MPW had higher prevalence of mixed and high severity abnormalities, some had excessive lung function drops. Current MPW had lowest occurrence of excessive lung function drops. FMW with excessive drops and spirometric abnormalities at last test had developed a restrictive pattern. Spirometric abnormalities and excessive drops were associated with work-related factors. CONCLUSION: There was evidence of a healthy worker survivor effect in MPW. Importantly, removal from exposure did not always stabilize lung function decline indicating a need for continued monitoring. The development of a restrictive pattern should raise the level of suspicion for possible work-related disease in flavoring-exposed workers.

      2. Job complexity and hazardous working conditions: How do they explain educational gradient in mortality?external icon
        Fujishiro K, MacDonald LA, Howard VJ.
        J Occup Health Psychol. 2020 Jun;25(3):176-186.
        Although education's protective effects on health have been well recognized, specific mechanisms through which higher education is associated with better health are still debated. Occupation, although strongly shaped by education, has rarely been examined as a mediating mechanism. Education attainment is patterned by race in the United States, and the same education does not lead to similar occupations for members of different racial/ethnic groups. Therefore, examining the link from education to jobs to mortality can illuminate potential mechanisms that create racial health disparities. Using a large U.S. national cohort of Black and White men and women, we examined if 2 occupational characteristics, substantive complexity of work and hazardous working conditions, mediate the effect of education on mortality. Data on occupation were collected between 2011 and 2013, and mortality follow-up data up to March 2018 were included in this analysis. The race- and gender-stratified analyses showed that among White men, the association between higher education and lower mortality was mediated by lower hazard on the job. Among Black men and White women, higher complexity of work explained the association between higher education and lower mortality. Among Black women, neither job characteristic mediated the association. These results suggest that occupational characteristics help explain health inequalities not only by education but also by race and gender. Investigating occupation explicitly in the causal chain of health disparities will help us better understand the mechanism of and potential solutions for health inequalities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

      3. Bioactivity of circulatory factors after pulmonary exposure to mild- and stainless-steel welding fumesexternal icon
        Kodali V, Shoeb M, Meighan TG, Eye T, Friend SA, Hubczak J, Kashon ML, Zeidler-Erdely PC, Antonini JM, Erdely A.
        Toxicol Sci. 2020 Jun 8.
        Studies suggest that alterations in circulating factors are a driver of pulmonary-induced cardiovascular dysfunction. To evaluate if circulating factors effect endothelial function after a pulmonary exposure to welding fumes, an exposure known to induce cardiovascular dysfunction, serum collected from Sprague-Dawley rats 24 h after an intratracheal instillation exposure to 2 mg/rat of two compositionally distinct metal-rich welding fume particulates [manual metal arc welding using stainless steel electrodes (MMA-SS) or gas metal arc welding using mild steel electrodes (GMA-MS)] or saline was used to test molecular and functional effects of in vitro cultures of primary cardiac microvascular endothelial cells (PCME) or ex vivo organ cultures. The welding fumes elicited significant pulmonary injury and inflammation with only minor changes in measured serum antioxidant and cytokine levels. PCME cells were challenged for 4 h with serum collected from exposed rats, and 84 genes related to endothelial function were analyzed. Changes in relative mRNA patterns indicated that serum from rats exposed to MMA-SS, and not GMA-MS or PBS, could influence several functional aspects related to endothelial cells, including cell migration, angiogenesis, inflammation, and vascular function. The predictions were confirmed using a functional in vitro assay (scratch assay) as well as an ex vivo multicellular environment (aortic ring angiogenesis assay), validating the concept that endothelial cells can be used as an effective screening tool of exposed workers for determining bioactivity of altered circulatory factors. Overall, the results indicate that pulmonary MMA-SS fume exposure can cause altered endothelial function systemically via altered circulating factors.

      4. Characterization of aerosolized particles from nanoclay-enabled composites during manipulation processesexternal icon
        Lee EG, Cena L, Kwon J, Afshari A, Park H, Casuccio G, Bunker K, Lersch T, Gall A, Pham H, Wagner A, Agarwal S, Dinu CZ, Gupta R, Friend SA, Stueckle TA.
        Environmental Science: Nano. 2020 ;7(5):1539-1553.
        Manufacturing, processing, use, and disposal of nanoclay-enabled composites potentially lead to the release of nanoclay particles from the polymer matrix in which they are embedded; however, exposures to airborne particles are poorly understood. The present study was conducted to characterize airborne particles released during sanding of nanoclay-enabled thermoplastic composites. Two types of nanoclay, Cloisite® 25A and Cloisite® 93A, were dispersed in polypropylene at 0%, 1%, and 4% loading by weight. Zirconium aluminum oxide (P100/P180 grits) and silicon carbide (P120/P320 grits) sandpapers were used to abrade composites in controlled experiments followed by real-time and offline particle analyses. Overall, sanding the virgin polypropylene with zirconium aluminum oxide sandpaper released more particles compared to silicon carbide sandpaper, with the later exhibiting similar or lower concentrations than that of polypropylene. Thus, a further investigation was performed for the samples collected using the zirconium aluminum oxide sandpaper. The 1% 25A, 1% 93A, and 4% 93A composites generated substantially higher particle number concentrations (1.3-2.6 times) and respirable mass concentrations (1.2-2.3 times) relative to the virgin polypropylene, while the 4% 25A composite produced comparable results, regardless of sandpaper type. It was observed that the majority of the inhalable particles were originated from composite materials with a significant number of protrusions of nanoclay (18-59%). These findings indicate that the percent loading and dispersion of nanoclay in the polypropylene modified the mechanical properties and thus, along with sandpaper type, affected the number of particles released during sanding, implicating the cause of potential adverse health effects.

      5. OBJECTIVE: The study sought to develop an information model of data describing a person's work for use by health information technology (IT) systems to support clinical care, population health, and public health. MATERIALS AND METHODS: Researchers from the National Institute for Occupational Safety and Health worked with stakeholders to define relationships and structure, vocabulary, and interoperability standards that would be useful and collectable in health IT systems. RESULTS: The Occupational Data for Health (ODH) information model illustrates relationships and attributes for a person's employment status, retirement dates, past and present jobs, usual work, and combat zone periods. Key data about the work of a household member that could be relevant to the health of a minor were also modeled. Existing occupation and industry classification systems were extended to create more detailed value sets that enable self-reporting and support patient care. An ODH code system, available in the Public Health Information Network Vocabulary Access and Distribution System, was established to identify the remaining value sets. ODH templates were prepared in all 3 Health Level 7 Internationalinteroperability standard formats. DISCUSSION: The ODH information model suggests data elements ready for use by health IT systems in the United States. As new data elements and values are better defined and refined by stakeholders and feedback is obtained through experience using ODH in clinical settings, the model will be updated. CONCLUSION: The ODH information model suggests standardized work information for trial use in health IT systems to support patient care, population health, and public health.

      6. The effectiveness of ergonomic interventions in material handling operationsexternal icon
        Wurzelbacher SJ, Lampl MP, Bertke SJ, Tseng CY.
        Appl Ergon. 2020 Sep;87:103139.
        This study evaluated the effectiveness of ergonomic interventions in material handling operations involving 33 employers and 535 employees from 2012 to 2017. Outcomes included employee-reported low back/upper extremity pain and safety incidents at baseline, every three months, and annually for up to two years. A total of 32.5% of employees completed at least one survey, while 13.6% completed all nine surveys over two years. Among highly exposed employees (who reported handling >= 50 lbs. > 33% of the time), upper extremity pain frequency and severity were lower among those who reported using the intervention routinely versus those that reported using their body strength alone to handle objects >= 50 lbs. After excluding from analyses one employer that used anti-fatigue mats, low back pain frequency was also significantly lower among highly exposed intervention users. In conclusion, there was some evidence that the interventions were effective in reducing employee-reported pain for highly exposed employees.

      7. During a public health emergency, respirator shortages can have a profound impact on the national response, such as for the current coronavirus disease 2019 (COVID-19) pandemic. Due to a severe shortage of respirators (particularly filtering facepiece respirators [FFRs]), there may be contexts in which understanding the performance of FFRs that are approved for use as part of a crisis capacity strategy is desired. This includes FFRs that are not covered under the National Institute for Occupational Safety and Health (NIOSH) Respirator Approval Program because they have been stored past their designated shelf life, have been decontaminated, or are approved by international certification bodies other than NIOSH. The purpose of this document is to provide a general framework to assess the performance of FFRs that are only being used as a crisis capacity strategy. The intended audience are those who are responsible for managing large amounts of FFRs. This framework includes a four-step process consisting of: 1) defining the population of FFRs to be sampled; 2) providing sampling strategy options; 3) inspecting and testing the sampled units; and 4) evaluating the results. In addition to the four-step process, we provide an example of how NIOSH recently evaluated the quality of FFRs sampled from ten U.S. stockpiles.

    • Parasitic Diseases
      1. Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community studyexternal icon
        Dubray CL, Sircar AD, Beau de Rochars VM, Bogus J, Direny AN, Ernest JR, Fayette CR, Goss CW, Hast M, O'Brian K, Pavilus GE, Sabin DF, Wiegand RE, Weil GJ, Lemoine JF.
        PLoS Negl Trop Dis. 2020 Jun 8;14(6):e0008298.
        In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

      2. Nationwide monitoring for Plasmodium falciparum drug-resistance alleles to chloroquine, sulfadoxine, and pyrimethamine, Haiti, 2016-2017external icon
        Rogier E, Herman C, Huber CS, Hamre KE, Pierre B, Mace KE, Presumé J, Mondélus G, Romilus I, Elismé T, Eisele TP, Druetz T, Existe A, Boncy J, Lemoine JF, Udhayakumar V, Chang MA.
        Emerg Infect Dis. 2020 May;26(5):902-909.
        Haiti is striving for zero local malaria transmission by the year 2025. Chloroquine remains the first-line treatment, and sulfadoxine/pyrimethamine (SP) has been used for mass drug-administration pilot programs. In March 2016, nationwide molecular surveillance was initiated to assess molecular resistance signatures for chloroquine and SP. For 778 samples collected through December 2017, we used Sanger sequencing to investigate putative resistance markers to chloroquine (Pfcrt codons 72, 74, 75, and 76), sulfadoxine (Pfdhps codons 436, 437, 540, 581, 613), and pyrimethamine (Pfdhfr codons 50, 51, 59, 108, 164). No parasites harbored Pfcrt point mutations. Prevalence of the Pfdhfr S108N single mutation was 47%, and we found the triple mutant Pfdhfr haplotype (108N, 51I, and 59R) in a single isolate. We observed no Pfdhps variants except in 1 isolate (A437G mutation). These data confirm the lack of highly resistant chloroquine and SP alleles in Haiti and support the continued use of chloroquine and SP.

      3. Selection of antibody responses associated with Plasmodium falciparum infections in the context of malaria eliminationexternal icon
        van den Hoogen LL, Stresman G, Presume J, Romilus I, Mondelus G, Elisme T, Existe A, Hamre KE, Ashton RA, Druetz T, Joseph V, Beeson JG, Singh SK, Boncy J, Eisele TP, Chang MA, Lemoine JF, Tetteh KK, Rogier E, Drakeley C.
        Front Immunol. 2020 ;11:928.
        In our aim to eliminate malaria, more sensitive tools to detect residual transmission are quickly becoming essential. Antimalarial antibody responses persist in the blood after a malaria infection and provide a wider window to detect exposure to infection compared to parasite detection metrics. Here, we aimed to select antibody responses associated with recent and cumulative exposure to malaria using cross-sectional survey data from Haiti, an elimination setting. Using a multiplex bead assay, we generated data for antibody responses (immunoglobulin G) to 23 Plasmodium falciparum targets in 29,481 participants across three surveys. This included one community-based survey in which participants were enrolled during household visits and two sentinel group surveys in which participants were enrolled at schools and health facilities. First, we correlated continuous antibody responses with age (Spearman) to determine which showed strong age-related associations indicating accumulation over time with limited loss. AMA-1 and MSP-119 antibody levels showed the strongest correlation with age (0.47 and 0.43, p < 0.001) in the community-based survey, which was most representative of the underlying age structure of the population, thus seropositivity to either of these antibodies was considered representative of cumulative exposure to malaria. Next, in the absence of a gold standard for recent exposure, we included antibody responses to the remaining targets to predict highly sensitive rapid diagnostic test (hsRDT) status using receiver operating characteristic curves. For this, only data from the survey with the highest hsRDT prevalence was used (7.2%; 348/4,849). The performance of the top two antigens in the training dataset (two-thirds of the dataset; n = 3,204)-Etramp 5 ag 1 and GLURP-R0 (area-under-the-curve, AUC, 0.892 and 0.825, respectively)-was confirmed in the test dataset (remaining one-third of the dataset; n = 1,652, AUC 0.903 and 0.848, respectively). As no further improvement was seen by combining seropositivity to GLURP-R0 and Etramp 5 ag 1 (p = 0.266), seropositivity to Etramp 5 ag 1 alone was selected as representative of current or recent exposure to malaria. The validation of antibody responses associated with these exposure histories simplifies analyses and interpretation of antibody data and facilitates the application of results to evaluate programs.

    • Reproductive Health
      1. Adverse pregnancy conditions among privately insured women with and without congenital heart defectsexternal icon
        Downing KF, Tepper NK, Simeone RM, Ailes EC, Gurvitz M, Boulet SL, Honein MA, Howards PP, Valente AM, Farr SL.
        Circ Cardiovasc Qual Outcomes. 2020 Jun 8:Circoutcomes119006311.
        Background In women with congenital heart defects (CHD), changes in blood volume, heart rate, respiration, and edema during pregnancy may lead to increased risk of adverse outcomes and conditions. The American Heart Association recommends providers of pregnant women with CHD assess cardiac health and discuss risks and benefits of cardiac-related medications. We described receipt of American Heart Association-recommended cardiac evaluations, filled potentially teratogenic or fetotoxic (Food and Drug Administration pregnancy category D/X) cardiac-related prescriptions, and adverse conditions among pregnant women with CHD compared with those without CHD. Methods and Results Using 2007 to 2014 US healthcare claims data, we ascertained a retrospective cohort of women with and without CHD aged 15 to 44 years with private insurance covering prescriptions during pregnancy. CHD was defined as >/=1 inpatient code or >/=2 outpatient CHD diagnosis codes >30 days apart documented outside of pregnancy and categorized as severe or nonsevere. Log-linear regression, accounting for multiple pregnancies per woman, generated adjusted prevalence ratios (aPRs) for associations between the presence/severity of CHD and stillbirth, preterm birth, and adverse conditions from the last menstrual period to 90 days postpartum. We identified 2056 women with CHD (2334 pregnancies) and 1 374 982 women without (1 524 077 pregnancies). During the last menstrual period to 90 days postpartum, 56% of women with CHD had comprehensive echocardiograms and, during pregnancy, 4% filled potentially teratogenic or fetotoxic cardiac-related prescriptions. Women with CHD, compared with those without, experienced more adverse conditions overall (aPR, 1.9 [95% CI, 1.7-2.1]) and, specifically, obstetric (aPR, 1.3 [95% CI, 1.2-1.4]) and cardiac conditions (aPR, 10.2 [95% CI, 9.1-11.4]), stillbirth (aPR, 1.6 [95% CI, 1.1-2.4]), and preterm delivery (aPR, 1.6 [95% CI, 1.4-1.8]). More women with severe CHD, compared with nonsevere, experienced adverse conditions overall (aPR, 1.5 [95% CI, 1.2-1.9]). Conclusions Women with CHD have elevated prevalence of adverse cardiac and obstetric conditions during pregnancy; 4 in 100 used potentially teratogenic or fetotoxic medications, and only half received an American Heart Association-recommended comprehensive echocardiogram.

    • Substance Use and Abuse
      1. Data quality considerations when using county-level opioid overdose death rates to inform policy and practiceexternal icon
        Jones CM, Warner M, Hedegaard H, Compton W.
        Drug Alcohol Depend. 2019 Nov 1;204:107549.

      2. BACKGROUND: Expansion of buprenorphine for opioid use disorder treatment is a core component of the opioid overdose epidemic response. The Comprehensive Addiction and Recovery Act (CARA) of 2016 authorized nurse practitioners (NPs) and physician assistants (PAs) to obtain a DATA-waiver to prescribe buprenorphine. The objectives of this study are to examine national- and county-level buprenorphine prescription dispensing, patterns by patient demographics and clinician specialty, and county-level characteristics associated with buprenorphine dispensing. METHODS: Retrospective analysis of buprenorphine prescriptions dispensed from approximately 92% of all retail prescriptions in the US (2017-2018). Analyses include rates of buprenorphine prescriptions dispensed, by patient demographics and prescriber specialty, changes in buprenorphine prescriptions dispensed at the national- and county-level, and county-level characteristics associated with buprenorphine dispensing. RESULTS: Buprenorphine prescriptions dispensed increased by 9.1% nationally, from 40.7-44.4 per 1000 residents. From 2017 to 2018, NPs (351.9%) and PAs (257.3%) had the largest percent increases in dispensed buprenorphine prescriptions, accounting for 79.6% of the total increase. In 2018, county-level characteristics associated with high buprenorphine dispensing included. among others: greater potential buprenorphine treatment capacity, higher drug overdose death rates, and higher rates of Medicaid enrollment. Rural counties were associated with low buprenorphine dispensing. CONCLUSION: Buprenorphine dispensing rates increased in the US from 2017 to 2018, suggesting the addition of NPs and PAs by CARA has contributed to an increase in dispensed buprenorphine prescriptions.

    • Veterinary Medicine
      1. Oral bait preferences and feasibility of oral rabies vaccination in Bangladeshi dogsexternal icon
        Bonwitt J, Bonaparte S, Blanton J, Gibson AD, Hoque M, Kennedy E, Islam K, Siddiqi UR, Wallace RM, Azam S.
        Vaccine. 2020 Jun 5.
        Oral rabies vaccination (ORV) can increase rabies vaccination coverage among dogs that are inaccessible to parenteral vaccination (i.e., inaccessible dogs). Because bait uptake can differ according to the bait attractant used and dog characteristics, we evaluated proportion of bait uptake and time to bait uptake using three bait formulations. We looked for associations between bait uptake and dog characteristics (temperament, age, and body condition) and assessed the efficiency of using these bait formulations, as measured by number of dogs vaccinated per hour. A total of 356 baits were offered to free roaming dogs in urban and peri-urban districts of Bangladesh. Fish baits were ignored by 86% (n = 122; 95% CI: 79-91%) of dogs, whereas 60% (n = 45; 95% CI: 49-70%) consumed egg baits and 89% (n = 124; 95% CI: 83-93%) consumed intestine baits. Among the consumed baits, dogs fully consumed 56% (n = 10; 95% CI: 34-75%) of fish baits, 84% (n = 38; 95% CI: 71-92%) of egg baits, and 98% (n = 122; 95% CI: 94-100%) of intestine baits. Among inaccessible dogs, no associations were found between bait uptake and dog characteristics in either bivariate or multivariate analyses. Bait consumption averaged 2 dogs per hour for fish baits, 10 dogs per hour for egg baits, and 18 dogs per hour for intestine baits. The absence of association between bait type preference and individual dog characteristics simplifies the process of choosing attractants for oral rabies vaccines. While intestine attractants achieved highest uptake, egg baits may prove a suitable compromise when considering biological and operational constraints. The efficiency of ORV was demonstrated when compared to parenteral vaccination of free-roaming dogs previously described.

    • Vital Statistics
      1. Background: The cause of death (COD) statement is a vital statistic that refers to the disease(s) and process(es) that lead to death. Obtaining accurate COD is valuable for mortality prevention priorities. The statements are formulated using International Classification of Diseases and related health problems, version 10 (ICD-10) system. However, physicians may be unfamiliar with these standards or fail to use them and instead refer to mechanisms or manner of death when stating COD. We present results of an of assessment of quality of COD statements in decedent cases reviewed during a one-month mortuary-based surveillance at Kenyatta National Hospital (KNH) and the City mortuaries in Nairobi, Kenya in 2015. Methods: Quality elements reviewed were completeness, correctness and order of stating the immediate (ICOD), antecedent, underlying (UCOD), and other significant causes (OSCs) as per the ICD 10 standards, in all deaths reported among adolescents and adults aged 15 years or older at the two mortuaries. COD were assessed for correct sequencing from immediate, antecedent, to underlying compared with autopsy pathology and clinical findings where available. Errors in COD statements were classified as missing or containing incomplete information such as: lack of underlying cause of an injury; incorrect words or statements; presence of more than one competing COD; use of the mechanism of death or anatomic and physiologic processes or signs and symptoms, and or laboratory results as CODs. Pearson's χ-squared test was used to compare proportions. Results: Out of 810, 610 (75.3%) deaths having HIV statuses were abstracted and 356 had at least one COD documented; 114 (32%) females and 242 (68%) males; 239 (67.1%) from KNH and 117 (32.9%) City mortuary. The cases from City mortuary had higher rates of correct statements on 116 (99.1%) ICOD, 90 (89.1%) UCOD, and 40 (81.6%) OSCs, compared to KNH Mortuary; 50 (20.9%), 200 (90.1%) and 62 (76.5%) respectively, p < 0.001. The most common type of errors was incomplete information and citing mechanisms of death as the COD. Conclusions: In addition to revising national forms to conform to ICD-10, there is a need for periodic training of individuals responsible for completing death certificates. This will improve correctness and completeness of COD in order to provide reliable mortality data in Kenya.

    • Zoonotic and Vectorborne Diseases
      1. Ticks and tickborne diseases are increasingly problematic. There have been positive developments that should result in improved strategies and better tools to suppress ticks, reduce human tick bites, and roll back tickborne diseases. However, we equally need to address the question of who is responsible for implementing the solutions. The current model of individual responsibility for tick control evolved from a scenario in the 1990s focusing strongly on exposure to blacklegged ticks and Lyme disease spirochetes in peridomestic settings of the northeastern United States. Today, the threat posed by human-biting ticks is more widespread across the eastern United States, increasingly complex (multiple tick species and >10 notable tickborne pathogens), and, across tick species, more spatially diffuse (including backyards, neighborhood green spaces, and public recreation areas). To mitigate tick-associated negative societal effects, we must consider shifting the responsibility for tick control to include both individual persons and professionally staffed tick-management programs.

      2. Epidemiology of rabies cases among international travellers, 2013-2019: A retrospective analysis of published reportsexternal icon
        Gautret P, Diaz-Menendez M, Goorhuis A, Wallace RM, Msimang V, Blanton J, Dacheux L, Parize P, Blumberg L, Bourhy H, Grobusch MP.
        Travel Med Infect Dis. 2020 Jun 7:101766.
        BACKGROUND: Sixty cases of rabies in international travellers from 1990 to 2012 were previously reviewed. We present here an update of rabies cases in international travellers from 2013 to 2019. METHODS: We systematically reviewed the existing literature and collected 23 cases of rabies in individuals who crossed an international border between the time of infection and diagnosis, or who were infected following expatriation or migration. RESULTS: Most cases were in male adult travellers and diagnosed in Europe and the Middle East, with most exposures in Asia or in Africa. Migrants originating from rabies-endemic low-and-middle income countries and their descendants accounted for two thirds of cases. Other cases were in tourists, business travellers and expatriates. Median travel duration (excluding migration trip) was 60 days (range 7-240 days). Most cases were due to dog bites and most common clinical presentation was furious rabies. In most patients (74%), no rabies post-exposure prophylaxis (RPEP) was administered before rabies symptoms appeared. Other patients received incomplete RPEP series. CONCLUSION: Rabies should be suspected in any patient with encephalitis or paralysis who travelled to, or migrated from a rabies-endemic country. Comprehensive information about a rabies risk should be given to travellers to rabies endemic countries, notably migrants visiting friends and relatives.

      3. Quality of age data in the Sierra Leone Ebola databaseexternal icon
        Womack LS, Alpren C, Martineau F, Jambai A, Singh T, Kaiser R, Redd JT.
        Pan African Medical Journal. 2020 ;35 .
        Introduction: while it is suspected that some ages were misreported during the 2014-2016 West African Ebola outbreak, an analysis examining age data quality has not been conducted. The study objective was to examine age heaping and terminal digit preference as indicators for quality of age data collected in the Sierra Leone Ebola Database (SLED). Method(s): age data quality for adult patients was analyzed within SLED for the Viral Hemorrhagic Fever (VHF) database and the laboratory testing dataset by calculating Whipple's index and Myers's blended index, stratified by sex and region. Result(s): age data quality was low in both the VHF database (Whipple's index for the 5-year range, 229.2) and the laboratory testing dataset (Whipple's index for the 5-year range, 236.4). Age was reported more accurately in the Western Area and least accurately in the Eastern Province. Age data for females were less accurate than for males. Conclusion(s): age data quality was low in adult patients during the 2014-2016 Ebola outbreak in Sierra Leone, which may reduce its use as an identifying or stratifying variable. These findings inform future analyses using this database and describe a phenomenon that has relevance in data collection methods and analyses for future outbreaks in developing countries.

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  • Kathy Tucker, Librarian
  • William (Bill) Thomas, MLIS, Librarian
  • Jarvis Sims, MIT, MLIS, Librarian


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: June 26, 2020, 12:00 AM