Volume 11, Issue 25 June 25, 2019

CDC Science Clips: Volume 11, Issue 25, June 25, 2019

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

  1. Top Articles of the Week

    Selected weekly by a senior CDC scientist from the standard sections listed below.

    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Effectiveness and cost of organized outreach for colorectal cancer screening: A randomized controlled trialexternal icon
        Somsouk M, Rachocki C, Mannalithara A, Garcia D, Laleau V, Grimes B, Issaka RB, Chen E, Vittinghoff E, Shapiro JA, Ladabaum U.
        J Natl Cancer Inst. 2019 Jun 12.
        BACKGROUND: Colorectal cancer (CRC) screening remains underutilized especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FIT) compared with usual care. METHODS: Patients aged 50-75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomized to outreach intervention with usual care versus usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at one year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided. RESULTS: 5,386 patients were randomized to the intervention group and 5,434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs. 37.4%, P < 0.001; difference 20.5%, 95% CI 18.6-22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT versus those who had not (71.9% vs. 35.7%, P < 0.001). There was evidence of effect modification of the intervention by race/ethnicity, marital status, language, and clinic. Outreach cost approximately $23/patient and $112/additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9,200/quality-adjusted life-year gained vs. usual care. CONCLUSION: Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remains to be determined.

    • Communicable Diseases
      • Impact of the 1918 influenza pandemic in coastal Kenyaexternal icon
        Andayi F, Chaves SS, Widdowson MA.
        Trop Med Infect Dis. 2019 Jun 8;4(2).
        The 1918 influenza pandemic was the most significant pandemic recorded in human history. Worldwide, an estimated half billion persons were infected and 20 to 100 million people died in three waves during 1918 to 1919. Yet the impact of this pandemic has been poorly documented in many countries especially those in Africa. We used colonial-era records to describe the impact of 1918 influenza pandemic in the Coast Province of Kenya. We gathered quantitative data on facility use and all-cause mortality from 1912 to 1925, and pandemic-specific data from active reporting from September 1918 to March 1919. We also extracted quotes from correspondence to complement the quantitative data and describe the societal impact of the pandemic. We found that crude mortality rates and healthcare utilization increased six- and three-fold, respectively, in 1918, and estimated a pandemic mortality rate of 25.3 deaths/1000 people/year. Impact to society and the health care system was dramatic as evidenced by correspondence. In conclusion, the 1918 pandemic profoundly affected Coastal Kenya. Preparation for the next pandemic requires continued improvement in surveillance, education about influenza vaccines, and efforts to prevent, detect and respond to novel influenza outbreaks.

      • Factors affecting pre-exposure prophylaxis implementation for women in the United States: A systematic reviewexternal icon
        Bradley E, Forsberg K, Betts JE, DeLuca JB, Kamitami E, Porter SE, Sipe TA, Hoover KW.
        J Womens Health (Larchmt). 2019 Jun 10.
        Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective pill that HIV-negative individuals can take once daily to prevent HIV infection. Although PrEP is a private, user-controlled method that empowers women to protect themselves without relying on a partner’s behavior, women’s PrEP use has been extremely low. We systematically reviewed the literature to identify and summarize factors that may be affecting PrEP implementation for women in the United States. We conducted a search of the Centers for Disease Control and Prevention HIV/AIDS Prevention Research Synthesis Project database (MEDLINE, EMBASE, and CINAHL) and PubMed to identify peer-reviewed studies published between January 2000 and April 2018 that reported U.S. women’s or health care providers’ PrEP knowledge or awareness, willingness to use or prescribe, attitudes, barriers and facilitators to use or prescription, or PrEP adherence and discontinuation influences. Thirty-nine studies (26 women, 13 providers) met the eligibility criteria. In these studies, 0%-33% of women had heard of PrEP. Between 51% and 97% of women were willing to try PrEP, and 60%-92% of providers were willing to prescribe PrEP to women. Implementation barriers included access, cost, stigma, and medical distrust. Three studies addressed adherence or discontinuation. PrEP knowledge is low among women and providers. However, women and providers generally have positive views when aware of PrEP, including a willingness to use or prescribe PrEP to women. Most of the implementation barriers highlighted in studies were social or structural factors (e.g., access). Additional studies are needed to address research gaps, including studies of PrEP adherence and discontinuation.

      • The development and approval of tecoviromat (TPOXX((R))), the first antiviral against smallpoxexternal icon
        Merchlinsky M, Albright A, Olson V, Schiltz H, Merkeley T, Hughes C, Petersen B, Challberg M.
        Antiviral Res. 2019 Jun 7.
        The classification of smallpox by the U.S. Centers for Disease Control and Prevention (CDC) as a Category A Bioterrorism threat agent has resulted in the U.S. Government investing significant funds to develop and stockpile a suite of medical countermeasures to ameliorate the consequences of a smallpox epidemic. This stockpile includes both vaccines for prophylaxis and antivirals to treat symptomatic patients. In this manuscript, we describe the path to approval for the first therapeutic against smallpox, identified during its development as ST-246, now known as tecovirimat and TPOXX((R)), a small-molecule antiviral compound sponsored by SIGA Technologies to treat symptomatic smallpox. Because the disease is no longer endemic, the development and approval of TPOXX((R)) was only possible under the U.S. Food and Drug and Administration Animal Rule (FDA 2002). In this article, we describe the combination of animal model studies and clinical trials that were used to satisfy the FDA requirements for the approval of TPOXX ((R)) under the Animal Rule.

      • Performance of a dual human immunodeficiency virus/syphilis rapid test compared to conventional serological testing for syphilis and HIV in a laboratory setting – results of the Zimbabwe STI Etiology Studyexternal icon
        Rietmeijer CA, Mungati M, Kilmarx PH, Barr BT, Gonese E, Kularatne RS, Lewis DA, Klausner JD, Rodgers L, Handsfield HH.
        Sex Transm Dis. 2019 Jun 7.
        BACKGROUND: Dual human immunodeficiency virus (HIV)/syphilis rapid, point-of-care testing may enhance syphilis screening among high risk populations, increase case finding, reduce time to treatment and prevent complications. We assessed the laboratory-based performance of a rapid dual HIV/syphilis test using serum collected from patients enrolled in the Zimbabwe Sexually Transmitted Infections (STI) Etiology study. METHODS: Blood specimens were collected from patients presenting with STI syndromes in six, predominantly urban STI clinics in different regions of Zimbabwe. All specimens were tested at a central research laboratory using the Standard Diagnostics Bioline HIV/Syphilis Duo test. The treponemal syphilis component of the dual rapid test was compared to the Treponema pallidum haemagglutination assay (TPHA) as a gold standard comparator, both alone or in combination with a non-treponemal test, the rapid plasma reagin (RPR) test. The HIV component of the dual test was compared to a combination of HIV rapid tests conducted at the research laboratory following the Zimbabwe national HIV testing algorithm. RESULTS: Of 600 men and women enrolled in the study, 436 consented to serological syphilis and HIV testing and had specimens successfully tested by all assays. The treponemal component of the dual test had a sensitivity of 66.2% (95% C.I.: 55.2% – 77.2%) and a specificity of 96.4% (95% C.I.: 94.5% – 98.3%) when compared to TPHA; the sensitivity increased to 91.7% (95% C.I.: 82.6% – 99.9%) when both TPHA and RPR were positive. The HIV component of the dual test had a sensitivity of 99.4% (95% C.I.: 98.4% – 99.9%) and a specificity of 100% (95% C.I. 99.9% – 100%) when compared to the HIV testing algorithm. CONCLUSION: Laboratory performance of the SD Bioline HIV/Syphilis Duo test was high for the HIV component of the test. Sensitivity of the treponemal component was lower than reported from most laboratory-based evaluations in the literature. However, sensitivity of the test increased substantially among patients more likely to have active syphilis for which results of both standard treponemal and non-treponemal tests were positive.

    • Food Safety
      • Use of whole-genome sequencing for food safety and public health in the United Statesexternal icon
        Brown E, Dessai U, McGarry S, Gerner-Smidt P.
        Foodborne Pathog Dis. 2019 Jun 13.
        Whole-genome sequencing (WGS) is increasingly used by food regulatory and public health agencies in the United States to facilitate the detection, investigation, and control of foodborne bacterial outbreaks, and food regulatory and other activities in support of food safety. WGS has added a level of precision to the surveillance leading to faster and more efficient decision making in the preparedness and response to foodborne infections. In this review, we report the history of WGS technology at the Centers for Disease Control & Prevention (CDC), the Food and Drug Administration (FDA), and the United States Department of Agriculture’s Food Safety and Inspection Service (USDA/FSIS) as it applies to food safety. The basic principle of the method, the analysis, and interpretation of the data are explained as is its major strengths and limitations. We also describe the benefits and possibilities of the WGS technology to the food industry throughout the farm-to-fork continuum and the prospects of metagenomic sequencing applied directly to the sample specimen with or without pre-enrichment culture.

    • Injury and Violence
      • OBJECTIVE: Intimate partner (IP) problems are risk factors for suicide among men. However, there is little understanding of why some male suicide decedents who had such problems killed their partners before death (i.e., “IP homicide-suicide”), while most of these decedents did not. To inform prevention efforts, this study identified correlates of IP homicide among male suicide decedents with known IP problems. METHODS: We examined IP homicide correlates among male suicide decedents aged 18+ years who had known IP problems using 2003-2015 National Violent Death Reporting System data. Prevalence odds ratios and 95% confidence intervals were estimated for demographic, incident, and circumstance variables. IP homicide-suicide narratives were examined to identify additional prevention opportunities. RESULTS: An estimated 1,504 (5.0%) of 30,259 male suicide decedents who had IP problems killed their partner. IP homicide-suicide perpetration was positively correlated with suicide by firearm and precipitating civil legal problems but negatively correlated with mental health/substance abuse treatment. An estimated 33.7% of IP homicide-suicides occurred during a breakup; 21.9% of IP homicide-suicide perpetrators had domestic violence histories. CONCLUSIONS: Connections between the criminal justice and mental health systems as well as stronger enforcement of laws prohibiting firearm possession among domestic violence offenders may prevent IP homicide-suicides.

    • Reproductive Health
      • Prevalence and maternal characteristics associated with receipt of prenatal care provider counseling about medications safe to take during pregnancyexternal icon
        D’Angelo DV, Bauman BL, Broussard CS, Tong VT, Ko JY, Kapaya M, Harrison L, Ahluwalia IB.
        Prev Med. 2019 Jun 4.
        Use of some medications during pregnancy can be harmful to the developing fetus, and discussion of the risks and benefits with prenatal care providers can provide guidance to pregnant women. We used Pregnancy Risk Assessment Monitoring System data collected for 2015 births aggregated from 34 US states (n=40,480 women) to estimate the prevalence of self-reported receipt of prenatal care provider counseling about medications safe to take during pregnancy. We examined associations between counseling and maternal characteristics using adjusted prevalence ratios (aPR). The prevalence of counseling on medications safe to take during pregnancy was 89.2% (95% confidence interval [CI]: 88.7-89.7). Women who were nulliparous versus multiparous (aPR 1.03; 95% CI: 1.02-1.04), who used prescription medications before pregnancy versus those who did not, (aPR 1.03; 95% CI: 1.02-1.05), and who reported having asthma before pregnancy versus those who did not, (aPR 1.05; 95% CI: 1.01-1.08) were more likely to report receipt of counseling. There was no difference in counseling for women with pre-pregnancy diabetes, hypertension, and/or depression compared to those without. Women who entered prenatal care after the first trimester were less likely to report receipt of counseling (aPR 0.93; 95% CI: 0.91-0.96). Overall, self-reported receipt of counseling was high, with some differences by maternal characteristics. Although effect estimates were small, it is important to ensure that information is available to prenatal care providers about medication safety during pregnancy, and that messages are communicated to women who are or might become pregnant.

    • Substance Use and Abuse
      • INTRODUCTION: Widely marketed flavored tobacco products might appeal to nonusers and could be contributing to recent increases in tobacco product use. We assessed flavored product use among current tobacco users; and measured associations between flavored product use and dependence among US adults. METHODS: Data were from the 2014-2015 Tobacco Use Supplement to the Current Population Survey, a cross-sectional household-based survey of U.S. adults >/=18 years (n=163,920). Current users of cigarettes, cigars, pipes, hookahs, smokeless tobacco, and electronic cigarettes (e-cigarettes) were asked whether their usual product was menthol or came in any characterizing flavors. Proportions of flavored product users were computed nationally and by state and demographic characteristics. Tobacco dependence was assessed with two proxy measures: daily use and use </=30 minutes after waking. Associations between flavored product use and tobacco dependence were examined using logistic regression adjusted for sex, age, race/ethnicity, and multi tobacco product use. RESULTS: An estimated 41.0% of current users of any tobacco product usually used a flavored product during 2014-2015. The proportion ranged from 22.5% (Maine) to 62.1% (D.C.). By product, the proportion ranged from 28.3% (cigars) to 87.2% (hookah). Flavored product use was associated with: daily tobacco product use among current e-cigarette users (adjusted odds ratio [AOR]=1.71), cigar smokers (AOR=1.42), and cigarette smokers (AOR=1.13); and tobacco product use </=30 minutes after waking among current cigar smokers (AOR=1.80), and cigarette smokers (AOR=1.11). CONCLUSIONS: Restricting sales of flavored tobacco products and implementation of proven population-level tobacco control interventions could help reduce tobacco product use among U.S. adults. IMPLICATIONS: During 2014-2015, flavored tobacco products were widely used by U.S. adults with variations across states and demographic characteristics. Use of flavored e-cigarettes, flavored cigars, and menthol cigarettes were associated with daily tobacco use: use of flavored cigars and menthol cigarettes were associated with tobacco use within 30 minutes after waking. These findings suggest associations between flavor use and increased tobacco dependence. Prohibiting sale of flavored products can reduce access to those products, and could help reduce tobacco dependence and promote cessation behaviors among current tobacco product users.

    • Zoonotic and Vectorborne Diseases

  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. New directions in incidence and prevalence of diagnosed diabetes in the USAexternal icon
        Benoit SR, Hora I, Albright AL, Gregg EW.
        BMJ Open Diabetes Res Care. 2019 ;7(1).
        Objective: To determine whether diabetes prevalence and incidence has remained flat or changed direction during the past 5 years. Research design and methods: We calculated annual prevalence and incidence of diagnosed diabetes (type 1 and type 2 combined) for civilian, non-institutionalized adults aged 18-79 years using annual, nationally representative cross-sectional survey data from the National Health Interview Survey from 1980 to 2017. Trends in rates by age group, sex, race/ethnicity, and education were calculated using annual percentage change (APC). Results: Overall, the prevalence of age-adjusted, diagnosed diabetes did not change significantly from 1980 to 1990, but increased significantly (APC 4.4%) from 1990 to 2009 to a peak of 8.2 per 100 adults (95% CI 7.8 to 8.6), and then plateaued through 2017. The incidence of age-adjusted, diagnosed diabetes did not change significantly from 1980 to 1990, but increased significantly (APC 4.8%) from 1990 to 2007 to 7.8 per 1000 adults (95% CI 6.7 to 9.0), and then decreased significantly (APC -3.1%) to 6.0 (95% CI 4.9 to 7.3) in 2017. The decrease in incidence appears to be driven by non-Hispanic whites with an APC of -5.1% (p=0.002) after 2008. Conclusions: After an almost 20-year increase in the national prevalence and incidence of diagnosed diabetes, an 8-year period of stable prevalence and a decrease in incidence has occurred. Causes of the plateauing and decrease are unclear but the overall burden of diabetes remains high and deserves continued monitoring and intervention.

      2. Endometriosis as a comorbid condition in chronic fatigue syndrome (CFS): Secondary analysis of data from a CFS case-control studyexternal icon
        Boneva RS, Lin JS, Wieser F, Nater UM, Ditzen B, Taylor RN, Unger ER.
        Front Pediatr. 2019 ;7:195.
        Background: Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only). Methods: This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided). Results: The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 +/- 0.3 vs. 5.5 +/- 0.3, p = 0.02), younger mean age at menopause onset (36.4 +/- 3.0 vs. 47.0 +/- 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups. Conclusions: We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.

      3. Diabetes care editors’ expert forum 2018: Managing big data for diabetes research and careexternal icon
        Riddle MC, Blonde L, Gerstein HC, Gregg EW, Holman RR, Lachin JM, Nichols GA, Turchin A, Cefalu WT.
        Diabetes Care. 2019 ;42(6):1136-1146.
        Technological progress in the past half century has greatly increased our ability to collect, store, and transmit vast quantities of information, giving rise to the term “big data.” This term refers to very large data sets that can be analyzed to identify patterns, trends, and associations. In medicinedincluding diabetes care and researchdbig data come from three main sources: electronic medical records (EMRs), surveys and registries, and randomized controlled trials (RCTs). These systems have evolved in different ways, each with strengths and limitations. EMRs continuously accumulate information about patients and make it readily accessible but are limited by missing data or data that are not quality assured. Because EMRs vary in structure and management, comparisons of data between health systems may be difficult. Registries and surveys provide data that are consistently collected andrepresentativeof broadpopulationsbutare limited in scopeandmaybeupdated only intermittently. RCT databases excel in the specificity, completeness, and accuracy of their data, but rarely include a fully representative sample of the general population. Also, they are costly to build and seldommaintained after a trial’s end. To consider these issues, and the challenges andopportunities they present, the editors of Diabetes Care convened a group of experts in management of diabetes related data on 21 June 2018, in conjunction with the American Diabetes Association’s 78th Scientific Sessions in Orlando, FL. This article summarizes the discussion and conclusions of that forum, offering a vision of benefits that might be realized from prospectively designed and unified data-management systems to support the collective needs of clinical, surveillance, and research activities related to diabetes.

      4. PURPOSE: We estimated the costs and effectiveness of state programs in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) based on the type of delivery structure. METHODS: Programs were classified into three delivery structures: (1) centralized, (2) decentralized, and (3) mixed. Centralized programs offer clinical services in satellite offices, but all other program activities are performed centrally. Decentralized programs contract with other entities to fully manage and provide screening and diagnostic services and other program activities. Programs with mixed service delivery structures have both centralized and decentralized features. Programmatic costs were averaged over a 3 year period (2006-2007, 2008-2009, and 2009-2010). Effectiveness was defined in terms of the average number of women served over the 3 years. We report costs per woman served by program activity and delivery structure and incremental cost effectiveness by program structure and by breast/cervical services. RESULTS: Average costs per woman served were lowest for mixed program structures (breast = $225, cervical = $216) compared to decentralized (breast = cervical = $276) and centralized program structures (breast = $259, cervical = $251). Compared with decentralized programs, for each additional woman served, centralized programs saved costs of $281 (breast) and $284 (cervical). Compared with decentralized programs, for each additional woman served, mixed programs added an additional $109 cost for breast but saved $1,777 for cervical cancer. CONCLUSIONS: Mixed program structures were associated with the lowest screening and diagnostic costs per woman served and had generally favorable incremental costs relative to the other program structures.

      5. INTRODUCTION: Racial and socioeconomic disparities exist in cervical cancer screening, incidence, and mortality. The purpose of this study was to investigate how cervical cancer stage at diagnosis is associated with rurality and race/ethnicity. METHODS: We analyzed 2010 through 2014 data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. We compared cervical cancer frequency and age-adjusted incidence for each stage by county-level rurality and race/ethnicity. RESULTS: There were 59,432 incident cases of cervical cancer reported from 2010 through 2014. The most common stage at diagnosis was localized (urban, 43.3%; rural 41.3%). Rural counties had higher incidence than urban counties for localized (rate ratio [RR] = 1.11; 95% confidence interval [CI], 1.07-1.15), regional (RR = 1.14; 95% CI, 1.10-1.19), and distant (RR = 1.12; 95% CI, 1.05-1.19) stage cervical cancer. Hispanic and non-Hispanic black women had higher incidence of regional and distant cervical cancer than non-Hispanic white women. Non-Hispanic white women in rural counties had higher incidence than those in urban counties at every stage. However, incidence for non-Hispanic white women was lower than for non-Hispanic black or Hispanic women. CONCLUSION: Rural counties had higher incidence of cervical cancer than urban counties at every stage. However, the association of rural residence with incidence varied by race/ethnicity.

    • Communicable Diseases
      1. Trends in number and composition of sex partners among men who have sex with men in the United States, National HIV Behavioral Surveillance, 2008-2014external icon
        Chapin-Bardales J, Rosenberg ES, Sullivan PS, Jenness SM, Paz-Bailey G.
        J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):257-265.
        BACKGROUND: Social and legal acceptance of long-term same-sex partnerships in the United States has increased over the past decade which may impact sexual partnering among men who have sex with men (MSM). Identifying whether and how partnering trends have evolved at a national level could improve understanding of HIV transmission and prevention among MSM partnerships. METHODS: We used Centers for Disease Control and Prevention’s National HIV Behavioral Surveillance data (2008, 2011, and 2014) to study trends in the number and partner type composition (main/casual) of male sex partners among US MSM. Changes over time were assessed in Poisson regression models with the link function tailored to the count and binary outcomes. RESULTS: The mean total number of partners in the past year increased, while the mean number of main partners remained stable. The percentage of MSM with both main and casual partners increased, and we observed a shift from having >/=1 main and 0 casual partners to having >/=1 main and >/=2 casual partners. Condomless anal sex in the past year increased regardless of partner composition. DISCUSSION: Findings suggest casual partnering among MSM has increased in recent years, including among those with >/=1 main partners. Both partner-based and individual prevention programs remain critical to reaching MSM.

      2. Influenza virus-related critical illness: prevention, diagnosis, treatmentexternal icon
        Chow EJ, Doyle JD, Uyeki TM.
        Crit Care. 2019 Jun 12;23(1):214.
        Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses.Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit. Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients. Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock. A number of pharmaceutical agents are in development for treatment of severe influenza.

      3. Text or e-mail messages can provide timely notification of sexually transmitted disease (STD) results to patients. We assessed STD clinic patient opinions about text/e-mail notification via a service called Chexout. Among 113 patients who opted in, the majority found results notification via texts/e-mails to be satisfactory (99.0%) and easy (92.9%).

      4. BACKGROUND: Current guidelines recommend that sexually active men who have sex with men (MSM) be screened at least annually for bacterial sexually transmitted infections (STIs) at sites of sexual contact regardless of condom use. Extragenital (rectal and pharyngeal) STI are common in MSM and associated with an increased risk of HIV. We describe the prevalence of MSM who reported any STI test and an extragenital STI test in the past 12 months (p12m) in the United States. METHODS: Data were obtained from the 2017 American Men’s Internet Survey (AMIS), an annual cross-sectional behavioral internet survey of MSM in the United States. We examined the prevalence of MSM who reported any STI test and an extragenital STI test in the p12m and compared the prevalence across demographic, clinical, and behavioral factors. RESULTS: Of 10, 049 sexually-active MSM who participated in AMIS 2017, 42% reported any STI test in the p12m and 16% reported an extragenital (rectal or pharyngeal) STI test in the p12m. Among those who reported getting an extragenital STI test in the p12m, 19% reported providing a throat swab only, 14% reported providing a rectal swab only, and 68% reported providing both a rectal and throat swab for STI testing. CONCLUSION: In a large sample of internet-using MSM in the United States, levels of STI screening were sub-optimal, with fewer than half (42%) of MSM reporting any STI test and even fewer reporting an extragenital STI test in the p12m. Increased efforts are needed to ensure annual STI screening guidelines among MSM are implemented.

      5. Brief report: Durability of the effect of financial incentives on HIV viral load suppression and continuity in care: HPTN 065 Studyexternal icon
        El-Sadr WM, Beauchamp G, Hall HI, Torian LV, Zingman BS, Lum G, Elion RA, Buchacz K, Burns D, Zerbe A, Gamble T, Donnell DJ.
        J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):300-303.
        BACKGROUND: Results from the HPTN 065 study showed that financial incentives (FI) were associated with significantly higher viral load suppression and higher levels of engagement in care among patients at HIV care sites randomized to FI versus sites randomized to standard of care (SOC). We assessed HIV viral suppression and continuity in care after intervention withdrawal to determine the durability of FI on these outcomes. SETTING: A total of 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, participated in the study. METHODS: Laboratory data reported to the US National HIV Surveillance System were used to determine site-level viral suppression and continuity in care outcomes. Postintervention effects were assessed for the 3 quarters after discontinuation of FI. Generalized estimation equations were used to compare FI and SOC site-level outcomes after intervention withdrawal. RESULTS: After FI withdrawal, a trend remained for an increase in viral suppression by 2.7% (-0.3%, 5.6%, P = 0.076) at FI versus SOC sites, decreasing from the 3.8% increase noted during implementation of the intervention. The significant increase in continuity in care during the FI intervention was sustained after intervention with 7.5% (P = 0.007) higher continuity in care at FI versus SOC sites. CONCLUSIONS: After the withdrawal of FI, findings at the 9-months postintervention withdrawal from this large study showed evidence of durable effects of FI on continuity in care, with trend for continued higher viral suppression. These findings are promising for adoption of such interventions to enhance key HIV-related care outcomes.

      6. Nationally representative data comparing demographic, risk, and clinical information among bisexual men with other MSM or heterosexuals are lacking. We described differences in demographic characteristics, behaviors, and clinical outcomes among self-identified HIV-positive bisexual, gay, and heterosexual men receiving HIV medical care in the United States. We analyzed data from the 2009-2013 cycles of the Medical Monitoring Project (MMP), a surveillance system that provides nationally representative estimates of behavioral and clinical characteristics of adults with diagnosed HIV in medical care. Altogether, 10% (95% confidence interval [CI] 9-11) of men self-identified as bisexual, 56% (CI 51-61) as gay, and 32% (CI 28-37) as heterosexual. We observed significant differences in demographic factors, clinical outcomes, drug use, and sexual behavior among bisexual men compared with gay and heterosexual men. Providers should consider sexual identities as well as sexual behaviors when developing and implementing prevention programs.

      7. Considerable distance to reach 90-90-90 targets among female sex workers, men who have sex with men and transgender women in Port Moresby, Papua New Guinea: findings from a cross-sectional respondent-driven sampling surveyexternal icon
        Hakim AJ, Badman SG, Weikum D, Amos A, Willie B, Narokobi R, Gabuzzi J, Pekon S, Kupul M, Hou P, Aeno H, Neo Boli R, Nembari J, Ase S, Kaldor JM, Vallely AJ, Kelly-Hanku A.
        Sex Transm Infect. 2019 Jun 10.
        OBJECTIVE: To characterise the Joint United Nations Programme on HIV/AIDS 90-90-90 cascade among female sex workers (FSW) and men who have sex with men (MSM)/transgender women (TGW) in Port Moresby, Papua New Guinea (PNG). METHODS: We conducted respondent-driven sampling surveys among FSW and MSM/TGW in Port Moresby, PNG from June to October 2016. All participants spoke English or Tok Pisin and were aged >12 years. FSW had to be born female and sell/exchange sex with a male in the past 6 months. MSM/TGW had to be born male and have oral/anal sex with another male-born person in the past 6 months. Participants were interviewed and offered rapid HIV diagnostic and viral load testing. HIV viral suppression (VS) was defined as <1000 copies/mL. RESULTS: We recruited 674 FSW and 400 MSM/TGW; HIV prevalence was 15.2% (95% CI 11.7 to 18.8) and 8.5% (95% CI 5.0 to 11.9), respectively. Among FSW living with HIV, 39.0% (95% CI 26.6 to 51.4) self-reported having been diagnosed; of them 79.6% (95% CI 62.7 to 96.5) self-reported being on antiretroviral therapy (ART), and 54.1% (95% CI 31.8 to 76.4) achieved VS. Among MSM/TGW living with HIV, 24.4% (95% CI 4.7 to 44.1) self-reported having been diagnosed; of them 43.9% (95% CI 33.6 to 54.8) self-reported being on ART, and 86.1% (95% CI 71.1 to 93.9) achieved VS. CONCLUSIONS: ART use among those aware of their HIV status is encouraging. However, the generally low awareness of infection status among FSW and MSM/TGW with HIV and the low VS among FSW on ART indicate an urgent need for innovative strategies to increase testing uptake and ART adherence among these populations. Monitoring drug resistance may be warranted.

      8. Low detectable postpartum viral load is associated with HIV transmission in Malawi’s prevention of mother-to-child transmission programmeexternal icon
        Landes M, van Lettow M, Nkhoma E, Tippett Barr B, Truwah Z, Shouten E, Jahn A, Auld A, Kalua T, van Oosterhout JJ.
        J Int AIDS Soc. 2019 Jun;22(6):e25290.
        INTRODUCTION: In 2011, Malawi implemented “Option B+,” a test-and-treat strategy for the prevention of maternal to child transmission of HIV (PMTCT); however limited data on viral load (VL) suppression exist. We describe VL suppression in HIV-infected women at four to twenty-six weeks postpartum, factors associated with VL suppression and the impact of VL suppression levels on MTCT. METHODS: HIV-positive mothers at four to twenty-six weeks postpartum were enrolled in a nested cross-sectional study within the “National Evaluation of Malawi’s PMTCT Programme” cohort study between October 2014 and May 2016. HIV-exposed infants received HIV-1 DNA testing and venous samples determined maternal VL, classified as unsuppressed (>1000 copies/mL), low-detectable (40 to 1000 copies/mL) or undetectable (<40 copies/mL). Socio-demographic and PMTCT indicators were collected. Suboptimal adherence was defined as self-reported >/=2 days missed ART in the month prior to visit. RESULTS: Of the 1274 women, 1191 (93.5%) knew their HIV status and 1154/1191 (96.9%) were on ART. VL was available for 1124/1154 (97.4%) of women on ART: 988/1124 (87.9%) had VL suppression of whom 86 (8.7%) had low-detectable and 902 (91.3%) undetectable VL. Suboptimal adherence was associated with unsuppressed VL (vs. suppressed VL; aOR 3.1, 95% CI 2.0 to 4.9; p < 0.001). Women with low-detectable VL were more likely to be adolescent (vs. undetectable VL; aOR 3.0, 95% CI 1.4 to 6.6), on ART <6 months (aOR 4.4, 95% CI 2.3 to 8.6), report suboptimal adherence (aOR 2.1, 95% CI 1.1 to 3.8; p = 0.02), and less likely to have primary or secondary education (vs. none; aOR 0.3, 95% CI 0.2 to 0.7 or aOR 0.3, 95% 0.1 to 0.6). MTCT ratios among women on ART who had undetectable VL, low-detectable VL and unsuppressed VL were 0.9% (8/902; 95% CI 0.3 to 1.5), 7.0% (6/86; 95% CI 1.5 to 12.5) and 14.0% (19/136; 95% CI 8.1 to 20.0). Unsuppressed VL and low-detectable VL (vs. undetectable VL) increased the risk of MTCT 17-fold (aOR 17.4, 95% CI 7.4 to 41.1; p = 0.002) and ninefold (aOR 8.5, 95% CI 2.9 to 25.2; p < 0.001). CONCLUSIONS: Unsuppressed and low-detectable VL was strongly predictive of MTCT among women on ART and associated with suboptimal adherence. This urges further consideration of optimal VL monitoring and target levels to reach elimination of paediatric infection.

      9. Use of lotteries for the promotion of voluntary medical male circumcision service: A discrete-choice experiment among adult men in Tanzaniaexternal icon
        Ong JJ, Neke N, Wambura M, Kuringe E, Grund JM, Plotkin M, d’Elbee M, Torres-Rueda S, Mahler HR, Weiss HA, Terris-Prestholt F.
        Med Decis Making. 2019 Jun 10:272989×19852095.
        Voluntary medical male circumcision (VMMC) is effective in reducing the risk of human immunodeficiency virus (HIV). However, countries like Tanzania have high HIV prevalence but low uptake of VMMC. We conducted a discrete-choice experiment to evaluate the preferences for VMMC service attributes in a random sample of 325 men aged 18 years or older from the general population in 2 Tanzanian districts, Njombe and Tabora. We examined the preference for financial incentives in the form of a lottery ticket or receiving a guaranteed transport voucher for attendance at a VMMC service. We created a random-parameters logit model to account for individual preference heterogeneity and a latent class analysis model for identifying groups of men with similar preferences to test the hypothesis that men who reported sexually risky behaviors (i.e., multiple partners and any condomless sex in the past 12 months) may have a preference for participation in a lottery-based incentive. Most men preferred a transport voucher (84%) over a lottery ticket. We also found that offering a lottery-based financial incentive may not differentially attract those with greater sexual risk. Our study highlights the importance of gathering local data to understand preference heterogeneity, particularly regarding assumptions around risk behaviors.

    • Disease Reservoirs and Vectors
      1. Rickettsia parkeri is a recently recognized human pathogen transmitted in the southeastern United States by Amblyomma maculatum, the Gulf Coast tick. Since R. parkeri was conclusively identified as a human pathogen in 2004, over 40 cases of R. parkeri rickettsiosis have been identified in the United States, most of which occur in the southeastern states. During 2012-2014, five of these cases were identified by a single urgent care practice in Coweta County, a Georgia county within the Atlanta metropolitan area. To investigate the occurrence of R. parkeri-infected A. maculatum in the Atlanta metropolitan area, ticks were collected from 6 counties around the city of Atlanta and evaluated for infection with a Rickettsia species. A total of 263 questing adult A. maculatum were collected during 2015 and 2016. Of these, 93 (35%) were PCR-positive for DNA of R. parkeri and an additional 46 (17%) were PCR-positive for DNA of “Candidatus Rickettsia andeanae,” a spotted fever group Rickettsia species of unknown pathogenicity. No co-infections of these two rickettsiae were detected; however four of the six counties sampled showed presence of both rickettsial organisms. The high frequency of R. parkeri in these tick populations indicates a potential risk for those living, working, or recreating in A. maculatum-infested habitats within these six counties in the Atlanta metropolitan area.

      2. Detection of highly pathogenic avian influenza A(H5N6) viruses in waterfowl in Bangladeshexternal icon
        Yang G, Chowdury S, Hodges E, Rahman MZ, Jang Y, Hossain ME, Jones J, Stark TJ, Di H, Cook PW, Ghosh S, Azziz-Baumgartner E, Barnes JR, Wentworth DE, Kennedy E, Davis CT.
        Virology. 2019 May 28;534:36-44.
        Bangladesh has reported repeated outbreaks of highly pathogenic avian influenza (HPAI) A(H5) viruses in poultry since 2007. Because of the large number of live poultry markets (LPM) relative to the population density of poultry throughout the country, these markets can serve as sentinel sites for HPAI A(H5) detection. Through active LPM surveillance during June 2016-June 2017, HPAI A(H5N6) viruses along with 14 other subtypes of influenza A viruses were detected. The HPAI A(H5N6) viruses belonged to clade and were likely introduced into Bangladesh around March 2016. Human infections with influenza clade viruses in Bangladesh have not been identified, but the viruses had several molecular markers associated with potential human infection. Vigilant surveillance at the animal-human interface is essential to identify emerging avian influenza viruses with the potential to threaten public and animal health.

    • Drug Safety
      1. Assessment of ICD-10-CM code assignment validity for case finding of outpatient anticoagulant-related bleeding among Medicare beneficiariesexternal icon
        Shehab N, Ziemba R, Campbell KN, Geller AI, Moro RN, Gage BF, Budnitz DS, Yang TH.
        Pharmacoepidemiol Drug Saf. 2019 May 29.
        PURPOSE: To assess performance of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code assignments for identifying bleeding events resulting in emergency department visits and hospitalizations among outpatient Medicare beneficiaries prescribed anticoagulants. METHODS: Performance of 206 ICD-10-CM code assignments indicative of bleeding, five anticoagulant adverse effect/poisoning codes, and five coagulopathy codes (according to Medicare Parts A and B claims) as assessed among Medicare fee-for-service beneficiaries prescribed anticoagulants between October 1, 2015 and September 30, 2016 (according to Part D claims). Structured medical record review was the gold standard for validating the presence of anticoagulant-related bleeding. Sensitivity was adjusted to correct for partial verification bias due to sampling design. RESULTS: Based on the study sample of 1166 records (583 cases, 583 controls), 57 of 206 codes yielded the optimal performance for anticoagulant-related bleeding (diagnostic odds ratio, 51; positive predictive value (PPV), 75.7% [95% CI, 72.0%-79.1%]; adjusted sensitivity, 70.0% [95% CI, 63.2%-77.7%]). Codes for intracranial bleeding demonstrated the highest PPV (85.0%) and adjusted sensitivity (91.0%). Bleeding codes in the primary position demonstrated high PPV (86.9%), but low adjusted sensitivity (36.0%). The adjusted sensitivity improved to 69.5% when codes in a secondary position were added. Only one adverse effect/poisoning code was used, appearing in 7.8% of cases and controls (PPV, 71.4% and adjusted sensitivity, 6.8%). CONCLUSIONS: Performance of ICD-10-CM code assignments for bleeding among patients prescribed anticoagulants varied by bleed type and code position. Adverse effect/poisoning codes were not commonly used and would have missed over 90% of anticoagulant-related bleeding cases.

    • Environmental Health
      1. Polybrominated biphenyl exposure and menstrual cycle functionexternal icon
        Howards PP, Terrell ML, Jacobson MH, Taylor KC, Kesner JS, Meadows JW, Spencer JB, Manatunga AK, Marcus M.
        Epidemiology. 2019 Jun 6.
        BACKGROUND: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function. METHODS: In 2004-06, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine for up to 6 months. We assayed urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-74 (n=70). RESULTS: We observed that high (>3.0 parts per billion (ppb)) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (</=1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure. CONCLUSIONS: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

      2. Characterizing environmental asthma triggers and healthcare use patterns in Puerto Ricoexternal icon
        Lewis LM, Mirabelli MC, Beavers SF, Kennedy CM, Shriber J, Stearns D, Morales Gonzalez JJ, Santiago MS, Felix IM, Ruiz-Serrano K, Dirlikov E, Lozier MJ, Sircar K, Flanders WD, Rivera-Garcia B, Irizarry-Ramos J, Bolanos-Rosero B.
        J Asthma. 2019 Jun 12:1-12.
        Objective: Asthma carries a high burden of disease for residents of Puerto Rico. We conducted this study to better understand asthma-related healthcare use and to examine potential asthma triggers. Methods: We characterized asthma-related healthcare use in 2013 by demographics, region, and date using outpatient, hospital, and emergency department (ED) insurance claims with a primary diagnostic ICD-9-CM code of 493.XX. We examined environmental asthma triggers, including outdoor allergens (i.e., mold and pollen), particulate pollution, and influenza-like illness. Analyses included descriptive statistics and Poisson time-series regression. Results: During 2013, there were 550,655 medical asthma claims reported to the Puerto Rico Healthcare Utilization database, representing 148 asthma claims/1,000 persons; 71% of asthma claims were outpatient visits, 19% were hospitalizations, and 10% were ED visits. Females (63%), children aged </=9 years (77% among children), and adults aged >/=45 years (80% among adults) had the majority of asthma claims. Among health regions, Caguas had the highest asthma claim-rate at 142/1,000 persons (overall health region claim-rate = 108). Environmental exposures varied across the year and demonstrated seasonal patterns. Metro health region regression models showed positive associations between increases in mold and particulate matter <10 microns in diameter (PM10) and outpatient asthma claims. Conclusions: This study provides information about patterns of asthma-related healthcare use across Puerto Rico. Increases in mold and PM10 were associated with increases in asthma claims. Targeting educational interventions on exposure awareness and reduction techniques, especially to persons with higher asthma-related healthcare use, can support asthma control activities in public health and clinical settings.

    • Epidemiology and Surveillance
      1. Multistate analysis of prospective Legionnaires’ disease cluster detection using SaTScan, 2011-2015external icon
        Edens C, Alden NB, Danila RN, Fill MA, Gacek P, Muse A, Parker E, Poissant T, Ryan PA, Smelser C, Tobin-D’Angelo M, Schrag SJ.
        PLoS One. 2019 ;14(5):e0217632.
        Detection of clusters of Legionnaires’ disease, a leading waterborne cause of pneumonia, is challenging. Clusters vary in size and scope, are associated with a diverse range of aerosol-producing devices, including exposures such as whirlpool spas and hotel water systems typically associated with travel, and can occur without an easily identified exposure source. Recently, jurisdictions have begun to use SaTScan spatio-temporal analysis software prospectively as part of routine cluster surveillance. We used data collected by the Active Bacterial Core surveillance platform to assess the ability of SaTScan to detect Legionnaires’ disease clusters. We found that SaTScan analysis using traditional surveillance data and geocoded residential addresses was unable to detect many common Legionnaires’ disease cluster types, such as those associated with travel or a prolonged time between cases. Additionally, signals from an analysis designed to simulate a real-time search for clusters did not align with clusters identified by traditional surveillance methods or a retrospective SaTScan analysis. A geospatial analysis platform better tailored to the unique characteristics of Legionnaires’ disease epidemiology would improve cluster detection and decrease time to public health action.

    • Health Economics
      1. Expenditures on screening promotion activities in CDC’s Colorectal Cancer Control Program, 2009-2014external icon
        Tangka FK, Subramanian S, Hoover S, Cole-Beebe M, DeGroff A, Joseph D, Chattopadhyay S.
        Prev Chronic Dis. 2019 Jun 6;16:E72.
        INTRODUCTION: The Centers for Disease Control and Prevention (CDC) established the Colorectal Cancer Control Program (CRCCP) in 2009 to reduce disparities in colorectal cancer screening and increase screening and follow-up as recommended. We estimate the cost for evidence-based intervention and non-evidence-based intervention screening promotion activities and examine expenditures on screening promotion activities. We also identify factors associated with the costs of these activities. METHODS: By using cost and resource use data collected from 25 state grantees over multiple years (July 2009 to June 2014), we analyzed the total cost for each screening promotion activity. Multivariate analysis was used to assess the factors associated with screening promotion costs reported by grantees. RESULTS: The promotion activities with the largest allocation of funding across the years and grantees were mass media, patient navigation, outreach and education, and small media. Across all years of the program and across grantees, the amount spent on specific promotion activities varied widely. The factor significantly associated with promotion costs was region in which the grantee was located. CONCLUSION: CDC’s CRCCP grantees spent the largest amount of the screening promotion funds on mass media, which is not recommended by the Community Preventive Services Task Force. Given the large variation across grantees in the use of and expenditures on screening promotion interventions, a systematic assessment of the yield from investment in specific promotion activities could better guide optimal resource allocation.

      2. Health and economic burden of influenza-associated illness in South Africa, 2013-2015external icon
        Tempia S, Moyes J, Cohen AL, Walaza S, Edoka I, McMorrow ML, Treurnicht FK, Hellferscee O, Wolter N, von Gottberg A, Nguweneza A, McAnerney JM, Dawood H, Variava E, Cohen C.
        Influenza Other Respir Viruses. 2019 Jun 11.
        BACKGROUND: Economic burden estimates are essential to guide policy-making for influenza vaccination, especially in resource-limited settings. METHODS: We estimated the cost, absenteeism, and years of life lost (YLL) of medically and non-medically attended influenza-associated mild and severe respiratory, circulatory and non-respiratory/non-circulatory illness in South Africa during 2013-2015 using a modified version of the World Health Organization (WHO) worksheet based tool for estimating the economic burden of seasonal influenza. Additionally, we restricted the analysis to influenza-associated severe acute respiratory illness (SARI) and influenza-like illness (ILI; subsets of all-respiratory illnesses) as suggested in the WHO manual. RESULTS: The estimated mean annual cost of influenza-associated illness was $270.5 million, of which $111.3 million (41%) were government-incurred costs, 40.7 million (15%) were out-of-pocket expenses, and $118.4 million (44%) were indirect costs. The cost of influenza-associated medically attended mild illness ($107.9 million) was 2.3 times higher than that of severe illness ($47.1 million). Influenza-associated respiratory illness costs ($251.4 million) accounted for 93% of the total cost. Estimated absenteeism and YLL were 13.2 million days and 304 867 years, respectively. Among patients with influenza-associated WHO-defined ILI or SARI, the costs ($95.3 million), absenteeism (4.5 million days), and YLL (65 697) were 35%, 34%, and 21% of the total economic and health burden of influenza. CONCLUSION: The economic burden of influenza-associated illness was substantial from both a government and a societal perspective. Models that limit estimates to those obtained from patients with WHO-defined ILI or SARI substantially underestimated the total economic and health burden of influenza-associated illness.

    • Immune System Disorders
      1. Contribution of antimicrobials to the development of allergic diseaseexternal icon
        Anderson SE, Weatherly L, Shane HL.
        Curr Opin Immunol. 2019 Jun 8;60:91-95.
        Antimicrobials represent a broad class of chemicals with the intended purpose of eliminating or controlling the growth of harmful microorganisms. Exposure can occur occupationally or through the use or consumption of consumer products. The use of antimicrobial agents has been associated with an increased incidence of allergic diseases, including asthma, atopic dermatitis, and less commonly, anaphylaxis. Very diverse immunological mechanisms and mediators have been identified in the sensitization response to antimicrobial chemicals and the importance of the local microenviroment in the response is increasingly being recognized. A complete understanding of the mechanisms of allergic diseases resulting from antimicrobial exposure will help to ensure safe environments and exposure limits.

    • Immunity and Immunization
      1. Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trialsexternal icon
        Clark A, van Zandvoort K, Flasche S, Sanderson C, Bines J, Tate J, Parashar U, Jit M.
        Lancet Infect Dis. 2019 Jun 6.
        BACKGROUND: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. METHODS: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). FINDINGS: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93-100) 2 weeks following the final dose of vaccination and 94% (87-98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74-92) after 2 weeks and 77% (67-84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48-81) after 2 weeks of follow-up and 44% (27-59) after 12 months. INTERPRETATION: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. FUNDING: Bill & Melinda Gates Foundation.

      2. Estimation of the incidence of Guillain-Barre syndrome during pregnancy in the United Statesexternal icon
        Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB.
        Open Forum Infect Dis. 2019 ;6(3).
        Guillain-Barr? syndrome (GBS) is an adverse event of interest after vaccination, yet few data are available for background rates during pregnancy. We confirmed 2 cases of incident GBS and estimated an incidence of 2.8 confirmed GBS cases per million person-years (95% confidence interval, 0.5-9.3), indicating rare occurrence. Our findings will help inform safety assessments of Zika vaccines in pregnant populations.

      3. Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonisation and Invasive Disease in Cambodian Childrenexternal icon
        Turner P, Leab P, Ly S, Sao S, Miliya T, Heffelfinger JD, Batmunkh N, Lessa FC, Walldorf JA, Hyde TB, Ork V, Hossain MS, Gould KA, Hinds J, Cooper BS, Ngoun C, Turner C, Day NP.
        Clin Infect Dis. 2019 Jun 7.
        BACKGROUND: Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3+0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonisation and invasive disease in children aged <5 years. METHODS: Six colonisation surveys were done between January 2014 and January 2018 in children attending the outpatient department of a non-governmental paediatric hospital in Siem Reap. Nasopharyngeal swabs were analysed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012 – December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonisation data were modelled to estimate vaccine effectiveness (VE). RESULTS: Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, vaccine effectiveness (VE) estimates for colonisation were 16.6% (95% CI 10.6-21.8) for all pneumococci and 39.2% (26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (17.7-33.0) decrease in multi-drug resistant pneumococcal colonisation. IPD incidence was estimated to have declined by 26.4% (14.4-35.8) by 2018, with a decrease of 36.3% (23.8-46.9) for VT IPD and an increase of 101.4% (62.0-145.4) for non-vaccine serotype IPD. CONCLUSIONS: Following PCV13 introduction into the Cambodian immunisation schedule there have been declines in VT pneumococcal colonisation and disease in children aged <5 years. Modelling of dominant serotype colonisation data produced plausible vaccine effectiveness estimates.

      4. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 studyexternal icon
        Van Damme P, De Coster I, Bandyopadhyay AS, Revets H, Withanage K, De Smedt P, Suykens L, Oberste MS, Weldon WC, Costa-Clemens SA, Clemens R, Modlin J, Weiner AJ, Macadam AJ, Andino R, Kew OM, Konopka-Anstadt JL, Burns CC, Konz J, Wahid R, Gast C.
        Lancet. 2019 Jun 4.
        BACKGROUND: Use of oral live-attenuated polio vaccines (OPV), and injected inactivated polio vaccines (IPV) has almost achieved global eradication of wild polio viruses. To address the goals of achieving and maintaining global eradication and minimising the risk of outbreaks of vaccine-derived polioviruses, we tested novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates that are genetically more stable than existing OPVs, with a lower risk of reversion to neurovirulence. Our study represents the first in-human testing of these two novel OPV2 candidates. We aimed to evaluate the safety and immunogenicity of these vaccines, the presence and extent of faecal shedding, and the neurovirulence of shed virus. METHODS: In this double-blind, single-centre phase 1 trial, we isolated participants in a purpose-built containment facility at the University of Antwerp Hospital (Antwerp, Belgium), to minimise the risk of environmental release of the novel OPV2 candidates. Participants, who were recruited by local advertising, were adults (aged 18-50 years) in good health who had previously been vaccinated with IPV, and who would not have any contact with immunosuppressed or unvaccinated people for the duration of faecal shedding at the end of the study. The first participant randomly chose an envelope containing the name of a vaccine candidate, and this determined their allocation; the next 14 participants to be enrolled in the study were sequentially allocated to this group and received the same vaccine. The subsequent 15 participants enrolled after this group were allocated to receive the other vaccine. Participants and the study staff were masked to vaccine groups until the end of the study period. Participants each received a single dose of one vaccine candidate (candidate 1, S2/cre5/S15domV/rec1/hifi3; or candidate 2, S2/S15domV/CpG40), and they were monitored for adverse events, immune responses, and faecal shedding of the vaccine virus for 28 days. Shed virus isolates were tested for the genetic stability of attenuation. The primary outcomes were the incidence and type of serious and severe adverse events, the proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools, and a combined index of the prevalence, duration, and quantity of viral shedding in all participants. This study is registered with EudraCT, number 2017-000908-21 and, number NCT03430349. FINDINGS: Between May 22 and Aug 22, 2017, 48 volunteers were screened, of whom 15 (31%) volunteers were excluded for reasons relating to the inclusion or exclusion criteria, three (6%) volunteers were not treated because of restrictions to the number of participants in each group, and 30 (63%) volunteers were sequentially allocated to groups (15 participants per group). Both novel OPV2 candidates were immunogenic and increased the median blood titre of serum neutralising antibodies; all participants were seroprotected after vaccination. Both candidates had acceptable tolerability, and no serious adverse events occurred during the study. However, severe events were reported in six (40%) participants receiving candidate 1 (eight events) and nine (60%) participants receiving candidate 2 (12 events); most of these events were increased blood creatinine phosphokinase but were not accompanied by clinical signs or symptoms. Vaccine virus was detected in the stools of 15 (100%) participants receiving vaccine candidate 1 and 13 (87%) participants receiving vaccine candidate 2. Vaccine poliovirus shedding stopped at a median of 23 days (IQR 15-36) after candidate 1 administration and 12 days (1-23) after candidate 2 administration. Total shedding, described by the estimated median shedding index (50% cell culture infective dose/g), was observed to be greater with candidate 1 than candidate 2 across all participants (2.8 [95% CI 1.8-3.5] vs 1.0 [0.7-1.6]). Reversion to neurovirulence, assessed as paralysis of transgenic mice, was low in isolates from those vaccinated with both candidates, and sequencing of shed virus indicated that there was no loss of attenuation in domain V of the 5′-untranslated region, the primary site of reversion in Sabin OPV. INTERPRETATION: We found that the novel OPV2 candidates were safe and immunogenic in IPV-immunised adults, and our data support the further development of these vaccines to potentially be used for maintaining global eradication of neurovirulent type-2 polioviruses. FUNDING: Bill & Melinda Gates Foundation.

      5. Incidence of herpes zoster among children: 2003-2014external icon
        Weinmann S, Naleway AL, Koppolu P, Baxter R, Belongia EA, Hambidge SJ, Irving SA, Jackson ML, Klein NP, Lewin B, Liles E, Marin M, Smith N, Weintraub E, Chun C.
        Pediatrics. 2019 Jun 10.
        BACKGROUND AND OBJECTIVES: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. METHODS: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. RESULTS: The study included 6 372 067 children with >/=1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. CONCLUSIONS: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.

    • Injury and Violence
      1. Workplace interventions for intimate partner violence: A systematic reviewexternal icon
        Adhia A, Gelaye B, Friedman LE, Marlow LY, Mercy JA, Williams MA.
        J Workplace Behav Health. 2019 .
        Workplace interventions represent important opportunities to increase awareness of and adherence to disease prevention and health promotion initiatives. However, research on workplace interventions for intimate partner violence (IPV) has not been systematically evaluated. This systematic review summarizes existing studies evaluating workplace interventions for IPV. PubMed, PsycINFO, Business Source Complete, Web of Science, and Social Services Abstracts were systematically searched for English-language studies published before November 2017. Six studies evaluating five interventions were included. Only one study used a randomized design, and only two studies measured whether outcomes were sustained over time. None of the interventions addressed perpetrators of IPV. Interventions focused on recognizing signs of abuse, responding to victims, and providing referrals to community-based resources. Methodological rigor of included studies varied, but all reported at least one intervention-related benefit. Findings included improved awareness of IPV, increased provision of information to victims, and greater willingness to intervene if an employee may be experiencing IPV. Although sparse, available evidence suggests there are potential benefits of workplace interventions for IPV. It is important for future interventions to focus on primary and secondary prevention of IPV and address perpetration, and for investigators to use rigorous study designs and measure whether effects are sustained.

      2. Considerations for neurosurgeons: recommendations from the CDC Pediatric Mild Traumatic Brain Injury Guidelineexternal icon
        Timmons SD, Waltzman D, Duhaime AC, Spinks TJ, Sarmiento K.
        J Neurosurg. 2019 Jun 7:1-5.

        [No abstract]

    • Laboratory Sciences
      1. Emerging novel GII.P16 noroviruses associated with multiple capsid genotypesexternal icon
        Barclay L, Cannon JL, Wikswo ME, Phillips AR, Browne H, Montmayeur AM, Tatusov RL, Burke RM, Hall AJ, Vinje J.
        Viruses. 2019 Jun 8;11(6).
        Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation.

      2. [No abstract]

      3. Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts’ consensus recommendationsexternal icon
        Bongomin F, Govender NP, Chakrabarti A, Robert-Gangneux F, Boulware DR, Zafar A, Oladele RO, Richardson MD, Gangneux JP, Alastruey-Izquierdo A, Bazira J, Boyles TH, Sarcarlal J, Nacher M, Obayashi T, Worodria W, Pasqualotto AC, Meya DB, Cheng B, Sriruttan C, Muzoora C, Kambugu A, Rodriguez Tudela JL, Jordan A, Chiller TM, Denning DW.
        Eur J Clin Microbiol Infect Dis. 2019 Jun 7.

        [No abstract]

      4. A growing number of carbon nanotubes and nanofibers (CNT/F) exposure and epidemiologic studies have utilized 25- and 37-mm open-faced cassettes (OFCs) to assess the inhalable aerosol fraction. It has been previously established that the 37-mm OFC undersamples particles >20 ?m in diameter, but the size-selective characteristics of the 25-mm OFC have not yet been fully evaluated. This article describes an experimental study conducted to determine if the 25- and 37-mm OFCs performed with relative equivalence to a reference inhalable aerosol sampler when challenged with CNT/F particles. Side-by-side paired samples were collected within a small Venturi chamber using a 25-mm styrene OFC, 37-mm styrene OFC, 25-mm aluminum OFC, and button inhalable aerosol sampler. Three types of CNT/F materials and an Arizona road dust were used as challenge aerosols for the various sampler configurations. Repeated experiments were conducted for each sampler configuration and material. The OFC samplers operated at flow rates of 2 and 5 L/min. Results showed that the 25-mm OFC performed comparably to the button sampler when challenged with CNT/F aerosols, which was demonstrated in five of the six experimental scenarios with an average error of 21%. Overall, the results of this study indicate that the sampling efficiency of the 25- and 37-mm OFCs adequately followed the ISO/ACGIH/CEN inhalable sampling convention when challenged with CNT/F aerosols. Past exposure and epidemiologic studies that used these OFC samplers can directly compare their results to studies that have used other validated inhalable aerosol samplers. ?, This work was authored as part of the Contributor?s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

      5. Detection of oseltamivir-resistant zoonotic and animal influenza A viruses using the rapid influenza antiviral resistance testexternal icon
        Hodges EN, Mishin VP, De la Cruz J, Guo Z, Nguyen HT, Fallows E, Stevens J, Wentworth DE, Davis CT, Gubareva LV.
        Influenza Other Respir Viruses. 2019 Jun 11.
        Mutations in the influenza virus neuraminidase (NA) that cause reduced susceptibility to the NA inhibitor (NAI) oseltamivir may occur naturally or following antiviral treatment. Currently, detection uses either a traditional NA inhibition assay or gene sequencing to identify known markers associated with reduced inhibition by oseltamivir. Both methods are laborious and require trained personnel. The influenza antiviral resistance test (iART), a prototype system developed by Becton, Dickinson and Company for research use only, offers a rapid and simple method to identify such viruses. This study investigated application of iART to influenza A viruses isolated from non-human hosts with a variety of NA subtypes (N1-N9).

      6. Concurrent with rising production of carbon-based engineered nanomaterials is a potential increase in respiratory and cardiovascular diseases due to exposure to nanomaterials in the workplace atmosphere. While single-cell models of pulmonary exposure are often used to determine the potential toxicity of nanomaterials in vitro, previous studies have shown that coculture cell models better represent the cellular response and crosstalk that occurs in vivo. This study identified differential gene regulation in human small airway epithelial cells (SAECs) grown either in monoculture or in coculture with human microvascular endothelial cells following exposure of the SAECs to multiwalled carbon nanotubes (MWCNTs). SAEC genes that either changed their regulation direction from upregulated in monoculture to downregulated in coculture (or vice versa) or had a more than a two-fold changed in the same regulation direction were identified. Genes that changed regulation direction were most often involved in the processes of cellular growth and proliferation and cellular immune response and inflammation. Genes that had a more than a two-fold change in regulation in the same direction were most often involved in the inflammatory response. The direction and fold-change of this differential gene regulation suggests that toxicity testing in monoculture may exaggerate cellular responses to MWCNTs, and coculture of cells may provide a more in-depth assessment of toxicological responses.

      7. Duplex real-time RT-PCR assay for detection and subgroup-specific identification of human respiratory syncytial virusexternal icon
        Wang L, Piedra P, Avadhanula V, Durigon EL, Machablishvili A, Lopez MR, Thornburg N, Peret TC.
        J Virol Methods. 2019 Jun 7:113676.
        Human respiratory syncytial virus (HRSV) is a leading cause of acute respiratory illness in young children worldwide. Reliable detection and identification of HRSV subgroup A and B infections are essential for accurate disease burden estimates in anticipation of licensure of novel HRSV vaccines and immunotherapies. To ensure continued reliability, molecular assays must remain current with evolving virus strains. We have developed a HRSV subgroup-specific real-time RT-PCR (rRT-PCR) assay for detection and subgroup identification using primers and subgroup-specific probes targeting a conserved region of the nucleoprotein gene combined in a single duplex reaction using all genome sequence data currently available in GenBank. The assay was validated for analytical sensitivity, specificity, reproducibility and clinical performance with a geographically diverse collection of viral isolates and respiratory specimens in direct comparison with an established pan-HRSV rRT-PCR reference test. The assay was sensitive, reproducibly detecting as few as 5 to 10 copies/reaction of target RNA. The assay was specific, showing no amplification with a panel of 16 other common respiratory pathogens or predicted by in silico primer/probe analysis. The duplex rRT-PCR assay based on the most current available genome sequence data permits rapid, sensitive and specific detection and subgroup identification of HRSV.

    • Maternal and Child Health
      1. In 1998 a Tolerable Upper Intake Level (UL) for folic acid was established based on case reports from the 1940s suggesting that high-dosage folic acid intake, used to treat patients with pernicious anemia, had the potential to precipitate or speed-up the development of neurological problems. This UL has been employed in the decision-making process used by more than 80 countries to establish programs to fortify staple foods with folic acid to prevent neural tube birth defects. Some have claimed that this UL is flawed and has become an obstacle to the wider adoption of neural tube defect prevention programs and have called for re-evaluation of the scientific validity of this UL. Case reports cannot establish causality, but they can reveal patterns in the timing of the onset and treatment of patients with pernicious anemia. These patterns can be compared with secular trends of usual medical practice for the treatment of pernicious anemia and with the changes in usage of folic acid preparations, including recommended therapeutic dosage and precautions for its usage surrounding the synthesis of folic acid in 1945 and vitamin B12 in 1948. Folic acid package inserts, early editions of hematology textbooks, and international expert reports provide valuable historical information. The recommended therapeutic daily dosage for folic acid of 5-20 mg was unchanged from 1946 through to 1971. The likely cause of the neurological problems encountered is the development of vitamin B12 neuropathy when pernicious anemia was treated with high-dosage folic acid before vitamin B12 was widely available in the early 1950s. Thus, the historical record does not provide compelling evidence that folic acid can potentially cause neurologic complications among those with low vitamin B12 status and lends support for reconsidering the basis for the UL of folic acid.

    • Nutritional Sciences
      1. BACKGROUND: Excess sodium intake can increase blood pressure, and high blood pressure is a major risk factor for cardiovascular disease. Accurate population sodium intake estimates are essential for monitoring progress toward reduction, but data are limited on the amount of sodium consumed from discretionary salt. OBJECTIVES: The aim of this study was to compare measured sodium intake from salt added at the table with that estimated according to the Healthy People 2020 (HP 2020) methodology. METHODS: Data were analyzed from the 2014 Salt Sources Study, a cross-sectional convenience sample of 450 white, black, Asian, and Hispanic adults living in Alabama, Minnesota, and California. Sodium intake from foods and beverages was assessed for each participant through the use of 24-h dietary recalls. Estimated sodium intake from salt used at the table was assessed from self-reported frequency and estimated amounts from a previous study (HP 2020 methodology). Measured intake was assessed through the use of duplicate salt samples collected on recall days. RESULTS: Among all study participants, estimated and measured mean sodium intakes from salt added at the table were similar, with a nonsignificant difference of 8.9 mg/d (95% CI: -36.6, 54.4 mg/d). Among participants who were non-Hispanic Asian, Hispanic, had a bachelor’s degree or higher education, lived in California or Minnesota, did not report hypertension, or had normal BMI, estimated mean sodium intake was 77-153 mg/d greater than measured intake (P < 0.05). The estimated mean sodium intake was 186-300 mg/d lower than measured intake among participants who were non-Hispanic black, had a high school degree or less, or reported hypertension (P < 0.05). CONCLUSIONS: The HP 2020 methodology for estimating sodium consumed from salt added at the table may be appropriate for the general US adult population; however, it underestimates intake in certain population subgroups, particularly non-Hispanic black, those with a high school degree or less, or those with self-reported hypertension. This study was registered at as NCT02474693.

    • Occupational Safety and Health
      1. Firefighters’ absorption of PAHs and VOCs during controlled residential fires by job assignment and fire attack tacticexternal icon
        Fent KW, Toennis C, Sammons D, Robertson S, Bertke S, Calafat AM, Pleil JD, Wallace MA, Kerber S, Smith D, Horn GP.
        J Expo Sci Environ Epidemiol. 2019 Jun 7.
        To better understand the absorption of combustion byproducts during firefighting, we performed biological monitoring (breath and urine) on firefighters who responded to controlled residential fires and examined the results by job assignment and fire attack tactic. Urine was analyzed for metabolites of polycyclic aromatic hydrocarbons (PAHs) and breath was analyzed for volatile organic compounds (VOCs) including benzene. Median concentrations of PAH metabolites in urine increased from pre-firefighting to 3-h post firefighting for all job assignments. This change was greatest for firefighters assigned to attack and search with 2.3, 5.6, 3.9, and 1.4-fold median increases in pyrene, phenanthrene, naphthalene, and fluorene metabolites. Median exhaled breath concentrations of benzene increased 2-fold for attack and search firefighters (p < 0.01) and 1.4-fold for outside vent firefighters (p = 0.02). Compared to interior attack, transitional attack resulted in 50% less uptake of pyrene (p = 0.09), 36% less uptake phenanthrene (p = 0.052), and 20% less uptake of fluorene (p < 0.01). Dermal absorption likely contributed to firefighters’ exposures in this study. Firefighters’ exposures will vary by job assignment and can be reduced by employing a transitional fire attack when feasible.

      2. Evaluation of emissions and exposures at workplaces using desktop 3-dimensional printersexternal icon
        Stefaniak AB, Johnson AR, du Preez S, Hammond DR, Wells JR, Ham JE, LeBouf RF, Menchaca KW, Martin SB, Duling MG, Bowers LN, Knepp AK, Su FC, de Beer DJ, du Plessis JL.
        J Chem Health Saf. 2019 Mar-Apr;26(2):19-30.
        There is a paucity of data on additive manufacturing process emissions and personal exposures in real-world workplaces. Hence, we evaluated atmospheres in four workplaces utilizing desktop &quot;3-dimensional&quot; (3-d) printers [fused filament fabrication (FFF) and sheer] for production, prototyping, or research. Airborne particle diameter and number concentration and total volatile organic compound concentrations were measured using real-time instruments. Airborne particles and volatile organic compounds were collected using time-integrated sampling techniques for off-line analysis. Personal exposures for metals and volatile organic compounds were measured in the breathing zone of operators. All 3-d printers that were monitored released ultrafine and fine particles and organic vapors into workplace air. Particle number-based emission rates (#/min) ranged from 9.4 times 109 to 4.4 times 1011 (n = 9 samples) for FFF 3-d printers and from 1.9 to 3.8 times 109 (n = 2 samples) for a sheer 3-d printer. The large variability in emission rate values reflected variability from the printers as well as differences in printer design, operating conditions, and feedstock materials among printers. A custom-built ventilated enclosure evaluated at one facility was capable of reducing particle number and total organic chemical concentrations by 99.7% and 53.2%, respectively. Carbonyl compounds were detected in room air; however, none were specifically attributed to the 3-d printing process. Personal exposure to metals (aluminum, iron) and 12 different organic chemicals were all below applicable NIOSH Recommended Exposure Limit values, but results are not reflective of all possible exposure scenarios. More research is needed to understand 3- d printer emissions, exposures, and efficacy of engineering controls in occupational settings.

    • Occupational Safety and Health – Mining
      1. Evaluation of post-blast re-entry times based on gas monitoring of return airexternal icon
        Bahrami D, Yuan L, Rowland JH, Zhou L, Thomas R.
        Min Metall Explor. 2019 Jun;36(3):513-521.
        Blasting is the main method of production in many non-coal underground mining operations and produces multiple toxic gases as a result. The Mine Safety and Health Administration (MSHA) requires mine operators to measure the level of toxic gases in mines as frequently as necessary to ensure they are below regulatory safety limits. The current practice uses portable gas monitors to check the concentrations of toxic gases after a fixed post-blast time. This paper studies the application of a gas monitoring system in the return entry of a limestone mine to determine a safe re-entry time. The National Institute for Occupational Safety and Health (NIOSH) conducted such a monitoring program in a limestone mine from September 2016 through May 2018. NIOSH/PMRD (Pittsburgh Mining Research Division) is endeavoring to develop workplace solutions to improve detection of and reduce the risk of hazardous conditions. This study showed that the use of gas monitoring in the return air can be a useful tool at the mine operator’s disposal to detect and reduce the risk of hazardous conditions and also to reliably estimate the re-entry time.

      2. Comparing the implementation of two dust control technologies from a sociotechnical systems perspectiveexternal icon
        Haas EJ, Cecala AB, Colinet JF.
        Min Metall Explor. 2019 Apr:[Epub ahead of print].
        A sociotechnical system (STS) creates a framework that allows an examination of how social and technical factors affect organizational outcomes within a specific environmental context. STS has been rigorously studied with a primary research focus addressing worker-technology interactions. Although these interactions are important, the social processes and interactions that occur whenever any technical or environmental change is introduced into the system have been undervalued. If social processes are better understood, mining organizations could efficiently prepare and stabilize for such changes. With this goal in mind, we sought to extend STS theory through applying principles of meta-design to analyze the results of two case study interventions. Specifically, we studied the impact of an unregulated dust control technology (the Helmet-CAM) and a regulated dust control technology (the Continuous Personal Dust Monitor) on factors within an STS including employees’ knowledge of, communication about, and use of technology to mitigate respirable dust sources. The results are presented in a way that first, addresses the overarching principles of meta-design STS including organizational participation, flexibility, and communication and second, examines how technology implementation processes differ when the organization is complying with a formal, higher-level requirement. Results show that a prominent focus on the social factors within an STS framework could help reduce unpredictability on the technical side and may improve communication within the system to help reduce adoption time, especially if and when accompanying a new, formal work process.

      3. Magnetic proximity detection systems (PDSs) are used with continuous mining machines (CMMs) to protect miners from striking and pinning accidents. Generators are used in a PDS to create magnetic fields covering the space around a CMM. The PDS determines the proximity of a miner relative to the CMM based on the magnetic flux density detected by a miner-wearable component (MWC) and simultaneously alerts the miner and stops the motion of the CMM if the miner is within a proximity that creates a striking hazard. A stable magnetic field is essential to the accuracy of the proximity calculations performed by the PDS. This paper presents the results of a systematic study of the magnetic influence of two types of steel structures found near a CMM – the body of the CMM itself and the wire mesh used for roof and rib control. The results show that the steel of the CMM body can change the magnetic field distribution and also alter electrical parameters of a PDS by changing its generator current. The study also shows that, depending on the distance between the wire mesh and a generator, the magnetic field can also be altered.

      4. Leveraging IIoT to improve machine safety in the mining industryexternal icon
        McNinch M, Parks D, Jacksha R, Miller A.
        Min Metall Explor. 2019 May:[Epub ahead of print].
        Each year, hundreds of mine workers are involved in machinery-related accidents. Many of these accidents involve inadequate or improper use of lockout/tagout (LOTO) procedures. To mitigate the occurrence of these accidents, new safety methods are needed to monitor access to hazardous areas around operating machinery, improve documentation/monitoring of maintenance that requires shutdown of the machinery, and prevent unexpected startup or movement during machine maintenance activities. The National Institute for Occupational Safety and Health (NIOSH) is currently researching the application of Internet of Things (IoT) technologies to provide intelligent machine monitoring as part of a comprehensive LOTO program. This paper introduces NIOSH’s two phase implementation of an IoT-based intelligent machine monitoring system. Phase one is the installation of a proof-of-concept system at a concrete batch plant, while phase two involves scaling up the system to include additional sensors, more detailed safety/performance metrics, proximity detection, and predictive failure analysis.

      5. Evaluation of different carbon monoxide sensors for battery charging stationsexternal icon
        Rowland JH, Yuan L, Thomas RA, Zhou L.
        Min Metall Explor. 2019 Apr;36(2):245-255.
        Hydrogen (H2) gas released during battery charging can result in cross-interference for carbon monoxide (CO) sensors used for early fire detection and compromise the integrity of the mine atmospheric monitoring system (AMS). In this study, a series of laboratory-scale and full-scale experiments were conducted to evaluate the responses of different CO sensors to H2 gas. In the laboratory-scale experiments, constant H2concentrations in the airflow, from 100 to 500 ppm, pass through sensors. While in the full-scale experiments, increasing H2concentrations generated as a byproduct from charging the batteries at the battery charging station rise to the sensors under different ventilation scenarios. The H2 concentrations at the CO sensor location were measured using H2 sensors and were correlated with the CO sensor response. The effects of ventilation and sensor location on the CO sensors responses were also analyzed. The results of this study can help mining companies to select appropriate CO sensors and improve the deployment of these sensors to ensure the safeguard of underground miners.

      6. Face ventilation on a bleederless longwall panelexternal icon
        Schatzel SJ, Gangrade V, Addis JD, Hollerich CA, Chasko LL.
        Min Metall Explor. 2019 Jun;36(3):531-539.
        A ventilation study using tracer gas was conducted at a western US coal mine. The objective of the study was to evaluate the movement of longwall face air exchanges between the face and worked-out area and to document the presence or absence of face airflow pathways between these locations. The mine operator uses a bleederless longwall ventilation system with a back return and a blowing mine ventilation system. The study was conducted on an active panel and included both underground and surface monitoring sites. The study used sulfur hexafluoride (SF6) released as a slug on the longwall face and in the front of the gob inby the face. The velocity of the tracer gas movement in the gob was 0.019 m/s (3.7 fpm). The rate of movement for the overall tracer gas slug averaged about 0.0091 m/s (1.8 fpm). A separate tracer gas test initiated with the release of SF6 into the legs of the first shield showed the existence of more than one pathway of face air in the general direction from the headgate towards the tailgate corner. Maintaining adequate ventilation air on longwall faces is important for worker safety and for the dilution of methane emitted from the face and caved gob. A more detailed characterization of longwall system air and gas movement allows a mine to better assess its ventilation design for controlling gas on the face and in the gob.

      7. Overview of current US longwall gateroad support practicesexternal icon
        Sears MM, Esterhuizen GS, Tulu IB.
        Min Metall Explor. 2019 May.
        In 2015, 40 longwall mines provided nearly 60% of the US coal production from underground mining methods. This represents a substantial, yet gradual increase from just under 50% over the last 5 years. As a result of this increased production share, the percentage of ground fall related fatalities in longwall mines has also increased when compared to all US underground coal mines. Additionally, about 80% of ground fall related fatalities have occurred in areas where the roof was supported. In an attempt to better understand the status quo of current US longwall support practices, a sample of 21 longwall mines were visited, representing about 40% of the currently active longwall mines in 4 of the 5 major US longwall producing regions. The resulting data was obtained from a wide variety of overburden depths, geologic conditions, mining heights, ground conditions, support practices, and gateroad configurations. The data collected is reported using both qualitative and quantitative methods. The results from the research update previous efforts in classifying mining accidents and injuries as well as current support practices. This data provides a necessary background for future research aimed at further reduction of ground fall accidents and injuries.

      8. Proximity detection systems (PDSs) for mobile machines have the potential to decrease injuries and fatalities. Early adopters of the technology have identified some challenges, which present an opportunity to explore and improve the integration of mobile PDSs in underground coal mines. The current research study applied the task-technology fit framework to investigate the fit between mobile PDS technology and mining relative to health and safety, from the perspective of leaders at two coal mines. Quantitative results from the study show that mine leaders evaluated mobile PDS favorably for training and ease of use, system feedback, user authorization and experience, and less favorably for safety, compatibility, task completion, and reliability. Qualitative results reveal specific task, mine, and system characteristics that may have influenced leaders’ evaluations. The study includes considerations and suggestions for safe technology integration.

      9. Roof bolter operators may be exposed to high respirable dust concentrations on continuous miner sections with blowing face ventilation when bolting is performed downwind of the continuous miner. One solution to reduce the high respirable dust concentrations is to use a canopy air curtain (CAC) to deliver clean air from a filtered blower fan directly to the bolter operators under the canopies. The influence of CAC installation in the airflow and dust dispersion around the location of the roof bolter operator can be evaluated by using computational fluid dynamics (CFD). This study, performed by the National Institute for Occupational Safety and Health (NIOSH), considers two scenarios: (1) a roof bolting machine in the center of the entry for installation of the fifth row of bolts from the face, and (2) a roof bolting machine positioned close to the face for the installation of the last row of bolts. In both scenarios, the bolting machine is placed in an environment which contains 6.0 mg/m3 of respirable dust and is ventilated by a blowing curtain with 3000 cfm (1.42 m3/s) of air. This environment is used to simulate the roof bolter machine operating downstream of a continuous mining machine. Two operation positions are simulated at the same bolting location: dual drill heads in the inward position for two inside bolts and dual drill heads in the outward position for two outside bolts. The influence of the CAC on airflows and dust dispersion is evaluated with the CAC operating at 250 cfm (0.12 m3/s).

      10. Influence of trailing cables on magnetic proximity detection systemsexternal icon
        Zhou C, Li J, Damiano N, DuCarme J, Noll J.
        Min Metall Explor. 2019 Apr;36(2):277-284.
        Preventing machine-related injuries is one of the major safety concerns in underground coal mines. Severe injuries and fatalities occur when a miner is struck, crushed, or pinned by mining equipment such as a continuous mining machine (CMM), shuttle car, or a scoop. Proximity detection systems (PDSs) have been applied in mining to reduce these types of injuries and fatalities. All of the PDSs that are currently approved by the Mine Safety and Health Administration (MSHA) for use in underground coal mines are magnetic-field based and could be affected by metallic objects such as trailing cables. Researchers from the National Institute for Occupational Safety and Health (NIOSH) investigated the influence of trailing cables on the performance of PDSs. In particular, the magnetic field coupled from proximity system generators to a de-energized trailing cable were characterized. The results show that significant energy can be coupled from the proximity system generators to a trailing cable when there is a closed loop in the cable. The effect on PDS performance from the magnetic field radiated around an energized trailing cable was also quantified for different current amplitudes in the cable. It is shown that the magnetic field caused by the electric current in the trailing cable mainly consists of a 60-Hz signal and its harmonics which cause little interference to the PDS. The results presented in this paper can help PDS manufacturers to design better systems that are more immune to these effects.

    • Parasitic Diseases
      1. Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infectionexternal icon
        Plucinski MM, McElroy PD, Dimbu PR, Fortes F, Nace D, Halsey ES, Rogier E.
        Parasit Vectors. 2019 Jun 10;12(1):293.
        BACKGROUND: Lingering post-treatment parasite antigen in blood complicates malaria diagnosis through antigen detection. Characterization of antigen clearance dynamics is important for interpretation of positive antigen detection tests. RESULTS: We used a bead-based serological assay to measure lactate dehydrogenase (LDH), aldolase (Aldo), and histidine-rich protein 2 (HRP2) levels in 196 children with Plasmodium falciparum malaria treated with effective antimalarials and followed for 28 to 42 days as part of therapeutic efficacy studies in Angola. Compared to pre-treatment levels, antigen concentrations two days after treatment declined by 99.7% for LDH, 96.3% for Aldo, and 54.6% for HRP2. After Day 2, assuming a first-order kinetics clearance model, half-lives of the antigens were 1.8 days (95% CI: 1.5-2.3) for LDH, 3.2 days (95% CI: 3.0-3.4) for Aldo, and 4.8 days (95% CI: 4.7-4.9) for HRP2. CONCLUSIONS: LDH and Aldo show substantially different clearance rates than HRP2, and their presence is largely indicative of active infection.

    • Substance Use and Abuse
      1. Private settings are major sources of secondhand smoke (SHS) exposure among youth. We measured prevalence and correlates of youth exposures to home and vehicle SHS. The 2016 National Youth Tobacco Survey of U.S. 6th-12th graders was analyzed (n=20,675). Past-7-day home or vehicle SHS exposures were self-reported. Descriptive and multivariable analyses were performed on weighted data. Among all students, past-7-day SHS exposures were: vehicle (21.4%, 5.56 million); home (21.7%, 5.64 million); home or vehicle (29.0%, 7.50 million); vehicle and home (14.0%, 3.63 million). By household tobacco-use status, home or vehicle SHS exposure was: tobacco-free households, 8.4%; households with combustible-only tobacco users, 59.8%; households with smokeless tobacco/e-cigarette-only users, 21.8%; and households with combined tobacco products usage, 73.9%. Where only the youth respondent but no other household member(s) used tobacco, the measure of association (vs. tobacco-free households) was ~two-fold higher for vehicle SHS exposures (Adjusted Odds Ratio [AOR]=6.09; 95% Confidence Interval [CI]=4.93-7.54 than for home SHS exposures (AOR=3.16; 95%CI=2.35-4.25). Conversely, where only household member(s) but not the youth respondent used tobacco, the measure of association was over two-fold higher for home SHS exposures (AOR=22.15; 95%CI=19.12-25.67) than for vehicle SHS exposure (AOR=7.91; 95%CI=6.96-8.98). In summary, nearly one-third of U.S. youth (7.50 million) were exposed to either home or vehicle SHS. Among non-tobacco-using youth with tobacco-using household member(s), the home was a dominant SHS exposure source; among tobacco-using youth with non-tobacco-using household member(s), a vehicle was a dominant exposure source, possibly peers’. Smoke-free environments, including homes and cars, can reduce youth SHS exposure.

      2. Social and physical environmental characteristics associated with adult current cigarette smokingexternal icon
        Caraballo RS, Rice KL, Neff LJ, Garrett BE.
        Prev Chronic Dis. 2019 Jun 6;16:E71.
        INTRODUCTION: Our objective was to identify social and physical environmental factors associated with current cigarette smoking among adults by metropolitan county in the United States. METHODS: We linked cigarette smoking data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) Selected Metropolitan Area Risk Trends (SMART) data set to 7 social and physical environmental characteristics: county type (metropolitan designation), primary care physician density, income inequality, percentage of the population that was a racial/ethnic minority, violent crime rate, education, and percentage of county residents with low income and no health insurance, all obtained from several county data sets. Spatial regression and hierarchical logistic regression modeling were performed. RESULTS: Results showed that metropolitan counties with a high proportion of non-Hispanic white adults (P < .001), lower education levels (high school graduate or less) (P < .001), and high violent crime rates (P < .001) had a higher adult cigarette smoking prevalence than other metropolitan counties. Spatial models showed 63.3% of the variability in county cigarette smoking prevalence was explained by these 3 factors as well as county type (based on population size of the of metropolitan area), primary care physician density, and percentage of county residents with low income and no health insurance. At an individual level, results showed that as the density (population) of primary care physicians increased in a county, the odds of being a current smoker decreased (OR, 0.980; P = .02). CONCLUSION: We found a significant association between adult cigarette smoking and county social and physical environmental factors. These place-based factors, especially social environmental characteristics, may reveal tobacco-related disparities to be considered when developing strategies to reduce tobacco use.

    • Veterinary Medicine
      1. [No abstract]

    • Vital Statistics
      1. A systematic review of vital events tracking by community health agentsexternal icon
        Nichols EK, Ragunanthan NW, Ragunanthan B, Gebrehiwet H, Kamara K.
        Glob Health Action. 2019 ;12(1):1597452.
        Background: Efforts to improve national civil registration and vital statistics (CRVS) systems are focusing on transforming traditionally passive systems into active systems that have the ability to reach the household level. While community health agents remain at the core of many birth and death reporting efforts, previous literature has not explored elements for their successful integration into CRVS efforts. Objective: To inform future efforts to improve CRVS systems, we conducted a systematic review of literature to understand and describe the design features, resulting data quality, and factors impacting the performance of community health agents involved in tracking vital events. Methods: We reviewed 393 articles; reviewers extracted key information from 58 articles meeting the eligibility criteria: collection of birth and/or death information outside of a clinic environment by a community agent. Reviewers recorded information in an Excel database on various program aspects, and results were summarized into key themes and topic areas. Results: The majority of articles described work in rural areas of Africa or South-East Asia. Nearly all articles (86%) cited some form of household visitation by community health agents. Only one article described a process in which vital events tracking activities were linked to official vital events registers. Other factors commonly described included program costs, relationship of community agents to community, and use of mobile devices. About 1/3 of articles reported quantitative information on performance and quality of vital events data tracked; various methods were described for measuring completeness of reporting, which varied greatly across articles. Conclusions: The multitude of articles on this topic attests to the availability of community health agents to track vital events. Creating a programmatic norm of integrating with CRVS systems the vital events information collected from existing community health programs has the potential to provide governments with information essential for public health decision-making.

    • Zoonotic and Vectorborne Diseases
      1. Quality of life reported by survivors after hospitalization for Middle East respiratory syndrome (MERS)external icon
        Batawi S, Tarazan N, Al-Raddadi R, Al Qasim E, Sindi A, Al Johni S, Al-Hameed FM, Arabi YM, Uyeki TM, Alraddadi BM.
        Health Qual Life Outcomes. 2019 Jun 11;17(1):101.
        INTRODUCTION: Data are lacking on impact of Middle East Respiratory Syndrome (MERS) on health-related quality of life (HRQoL) among survivors. METHODS: We conducted a cross-sectional survey of MERS survivors who required hospitalization in Saudi Arabia during 2016-2017, approximately 1 year after diagnosis. The Short-Form General Health Survey 36 (SF-36) was administered by telephone interview to assess 8 quality of life domains for MERS survivors and a sample of survivors of severe acute respiratory infection (SARI) without MERS. We compared mean SF-36 scores of MERS and non-MERS SARI survivors using independent t-test, and compared categorical variables using chi-square test. Adjusted analyses were performed using multiple linear regression. RESULTS: Of 355 MERS survivors, 83 were eligible and 78 agreed to participate. MERS survivors were younger than non-MERS SARI survivors (mean +/- SD): (44.9 years +/-12.9) vs (50.0 years +/-13.6), p = 0.031. Intensive care unit (ICU) admissions were similar for MERS and non-MERS SARI survivors (46.2% vs. 57.1%), p = 0.20. After adjusting for potential confounders, there were no significant differences between MERS and non-MERS SARI survivors in physical component or mental component summary scores. MERS ICU survivors scored lower than MERS survivors not admitted to an ICU for physical function (p = 0.05), general health (p = 0.01), vitality (p = 0.03), emotional role (p = 0.03) and physical component summary (p < 0.02). CONCLUSIONS: Functional scores were similar for MERS and non-MERS SARI survivors. However, MERS survivors of critical illness reported lower quality of life than survivors of less severe illness. Efforts are needed to address the long-term medical and psychological needs of MERS survivors.

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