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Volume 12, Issue 11, April 10, 2020

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CDC Science Clips: Volume 12, Issue 11, April 10, 2020

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

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on Hepatitis C Screening. The items marked with an asterisk may be of particular interest to clinicians and public health professionals seeking background information in this area.

The report consists of these components:

  1. CDC Vital Signs
    • Hepatitis C Screening
      1. *Viral hepatitis surveillance - United States, 2017
        Centers for Disease Control and Prevention .
        Atlanta, GA: US Department of Health and Human Services, CDC. 2019 .

      2. *Hepatitis C
        Centers for Disease Control and Prevention , National Center for HIV/AIDS , Viral Hepatitis , STD , and TB Prevention .
        Atlanta, GA: US Department of Health and Human Services, CDC. 2019 .

      3. Estimating prevalence of hepatitis C virus infection in the United States, 2013-2016external icon
        Hofmeister MG, Rosenthal EM, Barker LK, Rosenberg ES, Barranco MA, Hall EW, Edlin BR, Mermin J, Ward JW, Ryerson AB.
        Hepatology. 2019 Mar;69(3):1020-1031.
        Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the United States, causing substantial morbidity and mortality and costing billions of dollars annually. To update the estimated HCV prevalence among all adults aged >/=18 years in the United States, we analyzed 2013-2016 data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of HCV in the noninstitutionalized civilian population and used a combination of literature reviews and population size estimation approaches to estimate the HCV prevalence and population sizes for four additional populations: incarcerated people, unsheltered homeless people, active-duty military personnel, and nursing home residents. We estimated that during 2013-2016 1.7% (95% confidence interval [CI], 1.4-2.0%) of all adults in the United States, approximately 4.1 (3.4-4.9) million persons, were HCV antibody-positive (indicating past or current infection) and that 1.0% (95% CI, 0.8-1.1%) of all adults, approximately 2.4 (2.0-2.8) million persons, were HCV RNA-positive (indicating current infection). This includes 3.7 million noninstitutionalized civilian adults in the United States with HCV antibodies and 2.1 million with HCV RNA and an estimated 0.38 million HCV antibody-positive persons and 0.25 million HCV RNA-positive persons not part of the 2013-2016 NHANES sampling frame. Conclusion: Over 2 million people in the United States had current HCV infection during 2013-2016; compared to past estimates based on similar methodology, HCV antibody prevalence may have increased, while RNA prevalence may have decreased, likely reflecting the combination of the opioid crisis, curative treatment for HCV infection, and mortality among the HCV-infected population; efforts on multiple fronts are needed to combat the evolving HCV epidemic, including increasing capacity for and access to HCV testing, linkage to care, and cure.

      4. Hepatitis C virus (HCV) is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood (e.g., via injection drug use, needle stick injuries) (1). In the last 10 years, increases in HCV infection in the general U.S. population (1) and among pregnant women (2) are attributed to a surge in injection drug use associated with the opioid crisis. Opioid use disorders among pregnant women have increased (3), and approximately 68% of pregnant women with HCV infection have opioid use disorder (4). National trends in HCV infection among pregnant women by opioid use disorder status have not been reported to date. CDC analyzed hospital discharge data from the 2000-2015 Healthcare Cost and Utilization Project (HCUP) to determine whether HCV infection trends differ by opioid use disorder status at delivery. During this period, the national rate of HCV infection among women giving birth increased >400%, from 0.8 to 4.1 per 1,000 deliveries. Among women with opioid use disorder, rates of HCV infection increased 148%, from 87.4 to 216.9 per 1,000 deliveries, and among those without opioid use disorder, rates increased 271%, although the rates in this group were much lower, increasing from 0.7 to 2.6 per 1,000 deliveries. These findings align with prior ecological data linking hepatitis C increases with the opioid crisis (2). Treatment of opioid use disorder should include screening and referral for related conditions such as HCV infection.

      5. Prevalence of hepatitis C virus infection in US states and the District of Columbia, 2013 to 2016external icon
        Rosenberg ES, Rosenthal EM, Hall EW, Barker L, Hofmeister MG, Sullivan PS, Dietz P, Mermin J, Ryerson AB.
        JAMA Netw Open. 2018 Dec 7;1(8):e186371.
        Importance: Infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in the United States, and incidence has increased rapidly in recent years, likely owing to increased injection drug use. Current estimates of prevalence at the state level are needed to guide prevention and care efforts but are not available through existing disease surveillance systems. Objective: To estimate the prevalence of current HCV infection among adults in each US state and the District of Columbia during the years 2013 to 2016. Design, Setting, and Participants: This survey study used a statistical model to allocate nationally representative HCV prevalence from the National Health and Nutrition Examination Survey (NHANES) according to the spatial demographics and distributions of HCV mortality and narcotic overdose mortality in all National Vital Statistics System death records from 1999 to 2016. Additional literature review and analyses estimated state-level HCV infections among populations not included in the National Health and Nutrition Examination Survey sampling frame. Exposures: State, accounting for birth cohort, biological sex, race/ethnicity, federal poverty level, and year. Main Outcomes and Measures: State-level prevalence estimates of current HCV RNA. Results: In this study, the estimated national prevalence of HCV from 2013 to 2016 was 0.84% (95% CI, 0.75%-0.96%) among adults in the noninstitutionalized US population represented in the NHANES sampling frame, corresponding to 2035100 (95% CI, 1803600-2318000) persons with current infection; accounting for populations not included in NHANES, there were 231600 additional persons with HCV, adjusting prevalence to 0.93%. Nine states contained 51.9% of all persons living with HCV infection (California [318900], Texas [202500], Florida [151000], New York [116000], Pennsylvania [93900], Ohio [89600], Michigan [69100], Tennessee [69100], and North Carolina [66400]); 5 of these states were in Appalachia. Jurisdiction-level median (range) HCV RNA prevalence was 0.88% (0.45%-2.34%). Of 13 states in the western United States, 10 were above this median. Three of 10 states with the highest HCV prevalence were in Appalachia. Conclusions and Relevance: Using extensive national survey and vital statistics data from an 18-year period, this study found higher prevalence of HCV in the West and Appalachian states for 2013 to 2016 compared with other areas. These estimates can guide state prevention and treatment efforts.

      6. CDC recommendations for hepatitis C screening among adults - United States, 2020
        Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson A.
        MMWR Recomm Rep. 2020 ;69(No. RR–2):1-20.

      7. Hepatitis C virus in women of childbearing age, pregnant women, and childrenexternal icon
        Schillie SF, Canary L, Koneru A, Nelson NP, Tanico W, Kaufman HW, Hariri S, Vellozzi CJ.
        Am J Prev Med. 2018 Nov;55(5):633-641.
        INTRODUCTION: Perinatal transmission is an increasingly important mode of hepatitis C virus transmission. The authors characterized U.S. births among hepatitis C virus-infected women and evaluated trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5years. METHODS: In 2017, National Center for Health Statistics birth certificate data (48 states and District of Columbia) were analyzed to assess the number of hepatitis C virus-infected women delivering live births in 2015, and commercial laboratory data were analyzed to assess hepatitis C virus testing and positivity among women of childbearing age, pregnant women, and children aged <5years from 2011 to 2016. RESULTS: In 2015, a total of 0.38% (n=14,417) of live births were delivered by hepatitis C virus-infected women. Births delivered by hepatitis C virus-infected women, compared with births overall, occurred more often in women who were aged 20-29years (60.7% vs 50.9%); white, non-Hispanic (80.2% vs 52.8%); covered by Medicaid or other government insurance (79.2% vs 43.9%); and had rural residence (26.0% vs 14.0%). From 2011 to 2016 laboratory data, among women of childbearing age, hepatitis C virus testing increased by 39%, from 6.1% to 8.4%, and positivity increased by 36%, from 4.4% to 6.0%. Among pregnant women, hepatitis C virus testing increased by 135%, from 5.7% to 13.4%, and positivity increased by 39%, from 2.6% to 3.6%. Among children, hepatitis C virus testing increased by 25%, from 0.47% to 0.59%, and positivity increased by 13%, from 3.6% to 4.0%. CONCLUSIONS: The potential for perinatal hepatitis C virus transmission exists. Expanded hepatitis C virus testing guidelines may address the burden of disease in this population.

      8. Prevalence of spontaneous clearance of hepatitis C virus infection doubled from 1998 to 2017external icon
        Seo S, Silverberg MJ, Hurley LB, Ready J, Saxena V, Witt D, Hare CB, Champsi JH, Korn DG, Pauly MP, Chamberland S, Lai JB, Marcus JL.
        Clin Gastroenterol Hepatol. 2020 Feb;18(2):511-513.
        Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.(1-3) We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.

      9. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virusexternal icon
        US Public Health Service , Infectious Diseases Society of America .
        MMWR Recomm Rep. 1999 Aug 20;48(Rr-10):1-59, 61-6.


  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. BACKGROUND: Rates of intra-arterial revascularization treatments (IAT) for acute ischemic stroke (AIS) are increasing in the USA. Using a multi-state stroke registry, we studied the trend in IAT use among patients with AIS over a period spanning 11 years. We examined the impact of IAT rates on hospital procedure volumes and patient outcome after stroke. METHODS: We used data from the Paul Coverdell National Acute Stroke Program (PCNASP) and explored trends in IAT between 2008 and 2018. Patient outcomes were examined by rates of IAT procedures across hospitals. Specifically, outcomes were compared across low-volume (<15 IAT per year), medium-volume (15-30 IAT per year), and high-volume hospitals (>30 IAT per year). Favorable outcome was defined as discharge to home. RESULTS: There were 612 958 patients admitted with AIS to 687 participating hospitals within the PCNASP during this study. Only 2.9% of patients (mean age 68.5 years, 49.3% women) received IAT. The percent of patients with AIS receiving IAT increased from 1% in 2008 to 5.3% in 2018 (p<0.001). The proportion of low-volume hospitals decreased over time (p<0.001), and the proportions of medium-volume (p=0.007) and high-volume hospitals (p<0.001) increased between 2008 and 2018. When compared with medium-volume hospitals, high-volume hospitals had a higher (p<0.0001) and low-volume hospitals had a lower (p<0.0001) percent of patients discharged to home. CONCLUSION: High-volume hospitals were associated with a higher rate of favorable outcome. With the increased use of IAT among patients with AIS, the proportion of low-volume hospitals performing IAT significantly decreased.

      2. The YSI 2300 Analyzer Replacement Meeting Reportexternal icon
        Han J, Heinemann L, Ginsberg BH, Alva S, Appel M, Bess S, Chen KY, Freckmann G, Harris DR, Hartwig M, Hinzmann R, Kerr D, Krouwer J, Morrow L, Nichols J, Pfutzner A, Pleus S, Rice M, Sacks DB, Schlueter K, Vesper HW, Klonoff DC.
        J Diabetes Sci Technol. 2020 Mar 16.
        This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.

      3. Comparing hemoglobin distributions between population-based surveys matched by country and timeexternal icon
        Hruschka DJ, Williams AM, Mei Z, Leidman E, Suchdev PS, Young MF, Namaste S.
        BMC Public Health. 2020 Mar 30;20(1):422.
        BACKGROUND: Valid measurement of hemoglobin is important for tracking and targeting interventions. This study compares hemoglobin distributions between surveys matched by country and time from The Demographic and Health Survey (DHS) Program and the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. METHODS: Four pairs of nationally representative surveys measuring hemoglobin using HemoCue(R) with capillary (DHS) or venous (BRINDA) blood were matched by country and time. Data included 17,719 children (6-59 months) and 21,594 non-pregnant women (15-49 y). Across paired surveys, we compared distributional statistics and anemia prevalence. RESULTS: Surveys from three of the four countries showed substantial differences in anemia estimates (9 to 31 percentage point differences) which were consistently lower in BRINDA compared to DHS (2 to 31 points for children, 1 to 16 points for women). CONCLUSION: We identify substantial differences in anemia estimates from surveys of similar populations. Further work is needed to identify the cause of these differences to improve the robustness of anemia estimates for comparing populations and tracking improvements over time.

      4. The High Obesity Program: A collaboration between public health and Cooperative Extension Services to address obesityexternal icon
        Kahin SA, Murriel AL, Pejavara A, O'Toole T, Petersen R.
        Prev Chronic Dis. 2020 Mar 19;17:E26.

      5. Young-onset type 2 diabetes mellitus - implications for morbidity and mortalityexternal icon
        Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE.
        Nat Rev Endocrinol. 2020 Mar 20.
        Accumulating data suggest that type 2 diabetes mellitus (T2DM) in younger people (aged <40 years), referred to as young-onset T2DM, has a more rapid deterioration of beta-cell function than is seen in later-onset T2DM. Furthermore, individuals with young-onset T2DM seem to have a higher risk of complications than those with type 1 diabetes mellitus. As the number of younger adults with T2DM increases, young-onset T2DM is predicted to become a more frequent feature of the broader diabetes mellitus population in both developing and developed nations, particularly in certain ethnicities. However, the magnitude of excess risk of premature death and incident complications remains incompletely understood; likewise, the potential reasons for this excess risk are unclear. Here, we review the evidence pertaining to young-onset T2DM and its current and future burden of disease in terms of incidence and prevalence in both developed and developing nations. In addition, we highlight the associations of young-onset T2DM with premature mortality and morbidity.

      6. Multiple chronic conditions (MCC) reduce quality of life and are associated with high per capita health care spending. One potential way to reduce Medicare spending for MCC is to identify counties whose populations have high levels of spending compared to level of disease burden. Using a nationally representative sample of Medicare Fee-for-Service beneficiaries, this paper presents a method to measure the collective burden of several chronic conditions in a population, which the authors have termed the concentration of chronic conditions (CCC). The authors observed a significantly positive linear relationship between the CCC measure and county-level per capita Medicare spending. This area-level measure can be operationalized to identify counties that might benefit from targeted efforts designed to optimally manage and prevent chronic illness.

      7. The burden of obesity and other chronic diseases negatively affects the nation's health, businesses, economy, and military readiness. The prevalence is higher in certain geographic locations. Beginning in 2014, the Centers for Disease Control and Prevention's Division of Nutrition, Physical Activity, and Obesity awarded funding to 11 land-grant universities through the High Obesity Program. This program implemented evidence- and practice-based strategies with a goal to increase access to nutritious foods and places to be physically active in counties in which the prevalence of obesity among adults was more than 40%. In these counties, funded land-grant universities developed partnerships and collaborations to work with community organizations, public health agencies, and other stakeholders to promote policy and environmental changes that address obesity. Data were collected by the Cooperative Extension Service in each selected county with technical assistance from land-grand universities and the Centers for Disease Control and Prevention. More than 2 million people were reached by the nutrition and physical activity policy, systems, and environmental interventions implemented.

      8. Combating gastric cancer in Alaska Native people: An expert and community symposiumexternal icon
        Nolen LD, Vindigni SM, Parsonnet J.
        Gastroenterology. 2020 Apr;158(5):1197-1201.

      9. Terms and measures of cognitive health associated with dementia and Alzheimer's disease: A scoping reviewexternal icon
        Quinn K, Miyawaki CE, Croff R, Vogel MT, Belza B, Souza AM, Liu M, Edwards VJ, Friedman DB.
        Res Aging. 2020 Mar 20.
        The Healthy Brain Initiative: National Public Health Road Map to Maintaining Cognitive Health (2007) called on the research community to disseminate its work on cognitive aging and cognitive health. The purpose of this scoping review was to (1) identify terminology that cognitive, social, and behavioral scientists use to describe cognitive aging and cognitive health, in association with dementia and Alzheimer's disease, among older adults; (2) demonstrate how such terms are defined; and (3) illustrate how these constructs are measured in research settings. Empirical studies published 2007-2018 were examined for terminology, definitions, disciplinary orientation, and measurement mechanisms. Analysis of the corpus and a detailed review of the terms "cognitive impairment" and "mild cognitive impairment" reveal that formal definitions are provided infrequently and measurement of constructs ranges widely. Overall, the variability in terminology, definitions, and measures reflects a need for greater specificity in research communication, such that cross-disciplinary collaboration can be facilitated.

    • Communicable Diseases
      1. Extragenital gonorrhea and chlamydia positivity and the potential for missed extragenital gonorrhea with concurrent urethral chlamydia among men who have sex with men attending STD clinics - STD Surveillance Network, 2015-2019external icon
        Abara WE, Llata EL, Schumacher C, Carlos-Henderson J, Peralta AM, Huspeni D, Kerani RP, Elder H, Toevs K, Pathela P, Asbel L, Nguyen TQ, Bernstein KT, Torrone EA, Kirkcaldy RD.
        Sex Transm Dis. 2020 Mar 16.
        BACKGROUND: Extragenital gonorrhea (GC) and chlamydia (CT) are usually asymptomatic and only detected through screening. Ceftriaxone plus azithromycin is the recommended GC treatment; monotherapy (azithromycin or doxycycline) is recommended for CT. In urethral CT-positive/urethral GC-negative persons who are not screened extragenitally, CT monotherapy can lead to GC undertreatment and may foster the development of gonococcal antimicrobial resistance. We assessed urethral and extragenital GC and CT positivity among men who have sex with men (MSM) attending sexually transmitted disease (STD) clinics. METHODS: We included visit data for MSM tested for GC and CT at 30 STD clinics in 10 jurisdictions during 1/1/2015-6/30/2019. Using an inverse-variance random effects model to account for heterogeneity between jurisdictions, we calculated weighted test visit positivity estimates and 95% confidence intervals (CI) for GC and CT at urethral and extragenital sites, and extragenital GC among urethral CT-positive/GC-negative test visits. RESULTS: Of 139,718 GC and CT test visits, we calculated overall positivity (GC=16.7% [95% CI=14.4-19.1]; CT=13.3% [95% CI=12.7-13.9]); urethral positivity (GC=7.5% [95% CI=5.7-9.3]; CT=5.2% [95% CI=4.6-5.8]); rectal positivity (GC=11.8% [95% CI=10.4-13.2]; CT=12.6% [95% CI=11.8-13.4]); and pharyngeal positivity (GC=9.1% [95% CI=7.9-10.3]; CT=1.8% [95% CI=1.6-2.0]). Of 4,566 urethral CT-positive/GC-negative test visits with extragenital testing, extragenital GC positivity was 12.5% (95% CI=10.9-14.1). CONCLUSION: Extragenital GC and CT were common among MSM. Without extragenital screening of MSM with urethral CT, extragenital GC would have been undetected and undertreated in ~13% of these men. Undertreatment could potentially select for antimicrobial resistance. These findings underscore the importance of extragenital screening in MSM.

      2. Typhoid outbreaks, 1989-2018: Implications for prevention and controlexternal icon
        Appiah GD, Chung A, Bentsi-Enchill AD, Kim S, Crump JA, Mogasale V, Pellegrino R, Slayton RB, Mintz ED.
        Am J Trop Med Hyg. 2020 Mar 30.
        Typhoid fever remains an important public health problem in low- and middle-income countries, with large outbreaks reported from Africa and Asia. Although the WHO recommends typhoid vaccination for control of confirmed outbreaks, there are limited data on the epidemiologic characteristics of outbreaks to inform vaccine use in outbreak settings. We conducted a literature review for typhoid outbreaks published since 1990. We found 47 publications describing 45,215 cases in outbreaks occurring in 25 countries from 1989 through 2018. Outbreak characteristics varied considerably by WHO region, with median outbreak size ranging from 12 to 1,101 cases, median duration from 23 to 140 days, and median case fatality ratio from 0% to 1%. The largest number of outbreaks occurred in WHO Southeast Asia, 13 (28%), and African regions, 12 (26%). Among 43 outbreaks reporting a mode of disease transmission, 24 (56%) were waterborne, 17 (40%) were foodborne, and two (5%) were by direct contact transmission. Among the 34 outbreaks with antimicrobial resistance data, 11 (32%) reported Typhi non-susceptible to ciprofloxacin, 16 (47%) reported multidrug-resistant (MDR) strains, and one reported extensively drug-resistant strains. Our review showed a longer median duration of outbreaks caused by MDR strains (148 days versus 34 days for susceptible strains), although this difference was not statistically significant. Control strategies focused on water, sanitation, and food safety, with vaccine use described in only six (13%) outbreaks. As typhoid conjugate vaccines become more widely used, their potential role and impact in outbreak control warrant further evaluation.

      3. Prevalence of Mycoplasma genitalium infection, antimicrobial resistance mutations and symptom resolution following treatment of urethritisexternal icon
        Bachmann LH, Kirkcaldy RD, Geisler WM, Wiesenfeld HC, Manhart LE, Taylor SN, Sena AC, McNeil CJ, Newman L, Myler N, Fuchs R, Bowden KE.
        Clin Infect Dis. 2020 Mar 18.
        BACKGROUND: Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the U.S. or associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and post-treatment symptom persistence. METHODS: We enrolled men presenting with urethritis symptoms to 6 U.S. sexually transmitted disease (STD) clinics during June 2017-July 2018; men with urethritis were eligible for follow-up contact and (if persistent symptoms or MG) chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S rRNA loci (macrolide-associated mutations [MRMs]) and parC and gyrA (quinolone-associated mutations [QRMs]) were detected by targeted amplification/Sanger sequencing. RESULTS: Among 914 evaluable participants, 28.7% (95% CI 23.8-33.6) had MG. Men with MG were more often black (79.8% vs 66%), <30 years (72.9% vs 56.1%), and reported only female partners (83.7% vs 74.2%) than men without MG. Among MG-positive participants, 64.4% (95% CI 58.2%-70.3%) had MRM, 11.5% (95% CI 7.9-16.0%) had parC mutations, and 0% had gyrA mutations. Among participants treated with azithromycin-based therapy at enrollment and who completed the follow-up survey, persistent symptoms were reported by 25.8% of MG-positive/MRM-positive men, 13% of MG-positive/MRM-negative men, and 17.2% of MG-negative men. CONCLUSIONS: MG infection was common among men with urethritis; MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men with and without MG.

      4. Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient dataexternal icon
        Barr DA, Lewis JM, Feasey N, Schutz C, Kerkhoff AD, Jacob ST, Andrews B, Kelly P, Lakhi S, Muchemwa L, Bacha HA, Hadad DJ, Bedell R, van Lettow M, Zachariah R, Crump JA, Alland D, Corbett EL, Gopinath K, Singh S, Griesel R, Maartens G, Mendelson M, Ward AM, Parry CM, Talbot EA, Munseri P, Dorman SE, Martinson N, Shah M, Cain K, Heilig CM, Varma JK, Gottberg AV, Sacks L, Wilson D, Squire SB, Lalloo DG, Davies G, Meintjes G.
        Lancet Infect Dis. 2020 Mar 13.
        BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96.2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per muL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2.48, 95% CI 2.05-3.08) but not after 30 days (1.25, 0.84-2.49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3.15, 95% CI 1.16-8.84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.

      5. OBJECTIVE: To estimate the proportion of U.S. HIV-positive men who report a male HIV-negative/unknown status (HIV-discordant) sexual partner taking PrEP, and the use of multiple HIV prevention strategies within partnerships. DESIGN: The Medical Monitoring Project is a complex sample survey of U.S. adults with diagnosed HIV. METHODS: We used data collected during June 2016-May 2018 among sexually-active HIV-positive men who had >/=1 HIV-discordant male partner (N = 1,871) to estimate the weighted prevalence of reporting >/=1 partner taking PrEP. Among HIV-discordant partnerships (N = 4,029), we estimated PrEP use, viral suppression among HIV-positive partners, and condomless anal sex. We evaluated significant (p < 0.05) differences between groups using prevalence ratios with predicted marginal means. RESULTS: Twenty-eight percent of sexually-active HIV-positive MSM reported >/= 1 HIV-discordant male partner taking PrEP. Twenty percent of HIV-discordant partners were reported to be taking PrEP; 73% were taking PrEP or the HIV-positive partner was virally suppressed. PrEP use was lower among black and Hispanic partners compared with white partners (12% and 19% vs. 27%). Fewer black than white MSM were in partnerships in which PrEP was used or the HIV-positive partner had sustained viral suppression (69% vs. 77%). Condomless anal intercourse was more prevalent in partnerships involving PrEP use and in partnerships involving either PrEP use or sustained viral suppression among the HIV-positive partner. CONCLUSIONS: PrEP use was reported among 1 in 5 partners, with disparities between black and white partners. Increasing PrEP use and decreasing racial/ethnic disparities could reduce disparities in HIV incidence and help end the U.S. HIV epidemic.

      6. Presumed ocular histoplasmosis syndrome in a commercially insured population, United Statesexternal icon
        Benedict K, Shantha JG, Yeh S, Beer KD, Jackson BR.
        PLoS One. 2020 ;15(3):e0230305.
        PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM(R) MarketScan(R) Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.

      7. Notes from the field: Nationwide hepatitis E outbreak concentrated in informal settlements - Namibia, 2017-2020external icon
        Bustamante ND, Matyenyika SR, Miller LA, Goers M, Katjiuanjo P, Ndiitodino K, Ndevaetela EE, Kaura U, Nyarko KM, Kahuika-Crentsil L, Haufiku B, Handzel T, Teshale EH, Dziuban EJ, Nangombe BT, Hofmeister MG.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):355-357.

      8. Respiratory and nonrespiratory diagnoses associated with influenza in hospitalized adultsexternal icon
        Chow EJ, Rolfes MA, O'Halloran A, Alden NB, Anderson EJ, Bennett NM, Billing L, Dufort E, Kirley PD, George A, Irizarry L, Kim S, Lynfield R, Ryan P, Schaffner W, Talbot HK, Thomas A, Yousey-Hindes K, Reed C, Garg S.
        JAMA Netw Open. 2020 Mar 2;3(3):e201323.
        Importance: Seasonal influenza virus infection is a major cause of morbidity and mortality and may be associated with respiratory and nonrespiratory diagnoses. Objective: To examine the respiratory and nonrespiratory diagnoses reported for adults hospitalized with laboratory-confirmed influenza between 2010 and 2018 in the United States. Design, Setting, and Participants: This cross-sectional study used data from the US Influenza Hospitalization Surveillance Network (FluSurv-NET) from October 1 through April 30 of the 2010-2011 through 2017-2018 influenza seasons. FluSurv-NET is a population-based, multicenter surveillance network with a catchment area that represents approximately 9% of the US population. Patients are identified by practitioner-ordered influenza testing. Adults (aged >/=18 years) hospitalized with laboratory-confirmed influenza were included in the study. Exposures: FluSurv-NET defines laboratory-confirmed influenza as a positive influenza test result by rapid antigen assay, reverse transcription-polymerase chain reaction, direct or indirect fluorescent staining, or viral culture. Main Outcomes and Measures: Acute respiratory or nonrespiratory diagnoses were defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) discharge diagnosis codes. The analysis included calculation of the frequency of acute respiratory and nonrespiratory diagnoses with a descriptive analysis of patient demographic characteristics, underlying medical conditions, and in-hospital outcomes by respiratory and nonrespiratory diagnoses. Results: Of 89 999 adult patients hospitalized with laboratory-confirmed influenza, 76 649 (median age, 69 years; interquartile range, 55-82 years; 55% female) had full medical record abstraction and at least 1 ICD code for an acute diagnosis. In this study, 94.9% of patients had a respiratory diagnosis and 46.5% had a nonrespiratory diagnosis, including 5.1% with only nonrespiratory diagnoses. Pneumonia (36.3%), sepsis (23.3%), and acute kidney injury (20.2%) were the most common acute diagnoses. Fewer patients with only nonrespiratory diagnoses received antiviral therapy for influenza compared with those with respiratory diagnoses (81.4% vs 88.9%; P < .001). Conclusions and Relevance: Nonrespiratory diagnoses occurred frequently among adults hospitalized with influenza, further contributing to the burden of infection in the United States. The findings suggest that during the influenza season, practitioners should consider influenza in their differential diagnosis for patients who present to the hospital with less frequently recognized manifestations and initiate early antiviral treatment for patients with suspected or confirmed infection.

      9. Perceptions of patient HIV risk by primary care providers in high-HIV prevalence areas in the southern United Statesexternal icon
        Drumhiller K, Geter A, Elmore K, Gaul Z, Sutton MY.
        AIDS Patient Care STDS. 2020 Mar;34(3):102-110.
        The southern United States accounted for 52% of new HIV diagnoses in 2015. Visits to primary care providers (PCPs) offer opportunities for routine HIV screening. However, of at-risk persons in the United States who visited a health care provider within the previous year, >75% were not offered a test for HIV. Perceptions of patient population risk by PCPs could offer insight into these missed opportunities, and inform development of HIV testing interventions for PCPs to increase routine screening. During April-October 2017, we conducted online surveys regarding PCP's perceptions of patient HIV risk in six areas of the South with high-HIV prevalence. Surveys queried HIV-related knowledge, beliefs, attitudes, and practices. Free-text responses to the question "Are there any unique or special risk factors relating to HIV infection in your patient population?" were analyzed using NVivo for applied thematic analysis. Of 526 respondents, the mean age was 47 years with 65% white, 13% Asian/other, 13% black, 6% Hispanic/Latino; 71% female; 93% straight/heterosexual; and 35% offered HIV screening correctly based on standard of care. Main themes revealed were as follows: (1) provider perceptions of patient risk factors (e.g., "injection drug use is rampant"), (2) provider perceptions of patient barriers to access and care (e.g., "concern for parental notification and cost for treatment"), and (3) provider misconceptions of HIV risk and patient stigmatization (e.g., "I have a low-risk population"). Our findings suggest that PCPs in the South may warrant education regarding local HIV prevalence and routine HIV screening and prevention practices.

      10. Transgender youth experiences and perspectives related to HIV preventive servicesexternal icon
        Fontenot HB, Cahill SR, Wang T, Geffen S, White BP, Reisner S, Conron K, Harper CR, Johns MM, Avripas SA, Michaels S, Dunville R.
        Pediatrics. 2020 Mar 17.
        BACKGROUND: In the United States, transgender youth are at especially high risk for HIV infection. Literature regarding HIV prevention strategies for this vulnerable, often-hidden population is scant. Before effective, population-based HIV prevention strategies may be adequately developed, it is necessary to first enhance the contextual understanding of transgender youth HIV risk and experiences with HIV preventive services. METHODS: Two 3-day, online, asynchronous focus groups were conducted with transgender youth from across the United States to better understand participant HIV risk and experiences with HIV preventive services. Participants were recruited by using online advertisements posted via youth organizations. Qualitative data were analyzed by using content analysis. RESULTS: A total of 30 transgender youth participated. The average age was 18.6 years, and youth reported a wide range of gender identities (eg, 27% were transgender male, 17% were transgender female, and 27% used >/=1 term) and sexual orientations. Four themes emerged: (1) barriers to self-efficacy in sexual decision-making; (2) safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; (3) need for support and education; and (4) desire for affirmative and culturally competent experiences and interactions (eg, home, school, and health care). CONCLUSIONS: Youth discussed experiences and perspectives related to their gender identities, sexual health education, and HIV preventive services. Findings should inform intervention development to improve support and/or services, including the following: (1) increasing provider knowledge and skills to provide gender-affirming care, (2) addressing barriers to services (eg, accessibility and affordability as well as stigma and discrimination), and (3) expanding sexual health education to be inclusive of all gender identities, sexual orientations, and definitions of sex and sexual activity.

      11. The predictive performance of a pneumonia severity score in human immunodeficiency virus-negative children presenting to hospital in 7 low- and middle-income countriesexternal icon
        Gallagher KE, Knoll MD, Prosperi C, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, O'Brien KL, Thea DM, Awori JO, Baillie VL, Ebruke BE, Goswami D, Kamau A, Maloney SA, Moore DP, Mwananyanda L, Olutunde EO, Seidenberg P, Sissoko S, Sylla M, Thamthitiwat S, Zaman K, Scott JA.
        Clin Infect Dis. 2020 Mar 3;70(6):1050-1057.
        BACKGROUND: In 2015, pneumonia remained the leading cause of mortality in children aged 1-59 months. METHODS: Data from 1802 human immunodeficiency virus (HIV)-negative children aged 1-59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study with severe or very severe pneumonia during 2011-2014 were used to build a parsimonious multivariable model predicting mortality using backwards stepwise logistic regression. The PERCH severity score, derived from model coefficients, was validated on a second, temporally discrete dataset of a further 1819 cases and compared to other available scores using the C statistic. RESULTS: Predictors of mortality, across 7 low- and middle-income countries, were age <1 year, female sex, >/=3 days of illness prior to presentation to hospital, low weight for height, unresponsiveness, deep breathing, hypoxemia, grunting, and the absence of cough. The model discriminated well between those who died and those who survived (C statistic = 0.84), but the predictive capacity of the PERCH 5-stratum score derived from the coefficients was moderate (C statistic = 0.76). The performance of the Respiratory Index of Severity in Children score was similar (C statistic = 0.76). The number of World Health Organization (WHO) danger signs demonstrated the highest discrimination (C statistic = 0.82; 1.5% died if no danger signs, 10% if 1 danger sign, and 33% if >/=2 danger signs). CONCLUSIONS: The PERCH severity score could be used to interpret geographic variations in pneumonia mortality and etiology. The number of WHO danger signs on presentation to hospital could be the most useful of the currently available tools to aid clinical management of pneumonia.

      12. BACKGROUD: PrEP use among populations most vulnerable to HIV as identified in national HIV prevention goals is not fully known. This systematic review assessed trends of lifetime self-reported PrEP use and disparities among key populations. METHODS: We used CDC HIV/AIDS Prevention Research Synthesis cumulative database of electronic and manual searches in MEDLINE, CINAHL, EMBASE, and PsycINFO from 2000-2019 to identify English-language primary studies reporting PrEP use. Two reviewers independently screened citations, extracted data, and assessed risk of bias with modified Newcastle-Ottawa Scale. We estimated pooled proportions and crude/adjusted odds ratios (OR). RESULTS: We identified 95 eligible studies including 95,854 US-based survey respondents. A few studies (6.3%) focused on people who inject drugs (PWID). In 2015-2017, men who have sex with men (MSM) had highest proportion of individuals who used PrEP over their lifetime (13.9%[95%CI:8.8-21.1],k[number of surveys]=49) followed by Hispanic/Latinos (11.5[7.1-18.1],12), transgender women (11.2[5.8-20.6],5), and blacks (9.9[8.3-11.8],18). Odds of PrEP use increased by 34%/year (OR=1.34/year[95%CI:1.09-1.64]) and significantly increased over time among MSM (1.53/year[1.21-1.93]) and blacks (1.44[1.13-1.83]). People in the Southern US (9.9[4.7-19.7],8) and youth (7.3[4.7-11.2],8) had lower rates and did not demonstrate growth (0.94[0.29-3.18];0.82[0.43-1.55]). Odds of reporting lifetime PrEP use was twice (2.07[1.27-3.38]) as great among MSM than non-MSM. CONCLUSIONS: Proportions of PrEP use in published surveys have been growing, but remain low for people in the Southern US and youth, and understudied in PWID. Limitations include few studies in certain years while strengths include large number of respondents. Culturally-tailored approaches targeting vulnerable populations are essential to increase PrEP use to reduce disparities in HIV acquisition.

      13. The Spectrum-STI Groups model: syphilis prevalence trends across high-risk and lower-risk populations in Yunnan, Chinaexternal icon
        Korenromp EL, Zhang W, Zhang X, Ma Y, Jia M, Luo H, Guo Y, Zhang X, Gong X, Chen F, Li J, Nishijima T, Chen Z, Taylor MM, Hecht K, Mahiane G, Rowley J, Chen XS.
        Sci Rep. 2020 Mar 25;10(1):5472.
        The Spectrum-STI model, structured by sub-groups within a population, was used in a workshop in Yunnan, China, to estimate provincial trends in active syphilis in 15 to 49-year-old adults. Syphilis prevalence data from female sex workers (FSW), men who have sex with men (MSM), and lower-risk women and men in Yunnan were identified through literature searches and local experts. Sources included antenatal care clinic screening, blood donor screening, HIV/STI bio-behavioural surveys, sentinel surveillance, and epidemiology studies. The 2017 provincial syphilis prevalence estimates were 0.26% (95% confidence interval 0.17-0.34%) in women and 0.28% (0.20-0.36%) in men. Estimated prevalence was 6.8-fold higher in FSW (1.69% (0.68-3.97%) than in lower-risk women (0.25% (0.18-0.35%)), and 22.7-fold higher in MSM (5.35% (2.74-12.47%) than in lower-risk men (0.24% (0.17-0.31%). For all populations, the 2017 estimates were below the 2005 estimates, but differences were not significant. In 2017 FSW and MSM together accounted for 9.3% of prevalent cases. These estimates suggest Yunnan's STI programs have kept the overall prevalence of syphilis low, but prevalence remains high in FSW and MSM. Strengthening efforts targeting FSW and MSM, and identification of other risk populations e.g. among heterosexual men, are critical to reduce syphilis.

      14. Gonorrhea prevalence among young women and men entering the National Job Training Program, 2000-2017external icon
        Learner ER, Kreisel K, Kirkcaldy RD, Schlanger K, Torrone EA.
        Am J Public Health. 2020 Mar 19:e1-e8.
        Objectives. To examine long-term gonorrhea prevalence trends from a sentinel surveillance population of young people at elevated risk for gonorrhea.Methods. We analyzed annual cross-sectional urogenital gonorrhea screening data from 191 991 women (2000-2017) and 224 348 men (2003-2017) 16 to 24 years of age entering the National Job Training Program, a US vocational training program. We estimated prevalence among women using an expectation-maximization algorithm incorporated into a logistic regression to account for increases in screening test sensitivity; log-binomial regression was used to estimate prevalence among men.Results. The adjusted gonorrhea prevalence among women followed a U-shaped curve, falling from 2.9% to 1.6% from 2000 through 2011 before rising to 2.7% in 2017. The prevalence among men declined from 1.4% to 0.8% from 2003 through 2017. In the case of both women and men, the prevalence was highest across all study years among those who were Black or American Indian/Alaska Native and those who resided in the South or Midwest.Conclusions. Trends among National Job Training Program enrollees suggest that gonorrhea prevalence is rising among young women while remaining low and steady among young men. (Am J Public Health. Published online ahead of print March 19, 2020: e1-e8. doi:10.2105/AJPH.2019.305559).

      15. Communicable disease among people experiencing homelessness in Californiaexternal icon
        Liu CY, Chai SJ, Watt JP.
        Epidemiol Infect. 2020 Mar 30:1-37.

      16. Global epidemiology of tuberculosis and progress toward meeting global targets - worldwide, 2018external icon
        MacNeil A, Glaziou P, Sismanidis C, Date A, Maloney S, Floyd K.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):281-285.
        Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1), including among persons living with human immunodeficiency virus (HIV) infection (2). A World Health Organization (WHO) initiative, The End Tuberculosis Strategy, set ambitious targets for 2020-2035, including 20% reduction in TB incidence and 35% reduction in the absolute number of TB deaths by 2020 and 90% reduction in TB incidence and 95% reduction in TB deaths by 2035, compared with 2015 (3). This report evaluated global progress toward these targets based on data reported by WHO (1). Annual TB data routinely reported to WHO by 194 member states were used to estimate TB incidence and mortality overall and among persons with HIV infection, TB-preventive treatment (TPT) initiation, and drug-resistant TB for 2018 (1). In 2018, an estimated 10 million persons had incident TB, and 1.5 million TB-related deaths occurred, representing 2% and 5% declines from 2017, respectively. The number of persons with both incident and prevalent TB remained highest in the WHO South-East Asia and African regions. Decreases in the European region were on track to meet 2020 targets. Globally, among persons living with HIV, 862,000 incident TB cases occurred, and 1.8 million persons initiated TPT. Rifampicin-resistant or multidrug-resistant TB occurred among 3.4% of persons with new TB and 18% among persons who were previously treated for TB (overall, among 4.8% of persons with TB). The modest decreases in the number of persons with TB and the number of TB-related deaths were consistent with recent trends, and new and substantial progress was observed in increased TPT initiation among persons living with HIV. However, to meet the global targets for 2035, more intensive efforts are needed by public health partners to decrease TB incidence and deaths and increase the number of persons receiving TB curative and preventive treatment. Innovative approaches to case finding, scale-up of TB preventive treatment, use of newer TB treatment regimens, and prevention and control of HIV will contribute to decreasing TB.

      17. Genetic characterization of mumps viruses associated with the resurgence of mumps in the United States: 2015-2017external icon
        McNall RJ, Wharton AK, Anderson R, Clemmons N, Lopareva EN, Gonzalez C, Espinosa A, Probert WS, Hacker JK, Liu G, Garfin J, Strain A, Boxrud D, Bryant PW, George KS, Davis T, Griesser RH, Shult P, Bankamp B, Hickman CJ, Wroblewski K, Rota PA.
        Virus Res. 2020 Mar 16:197935.
        Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8% of the sequences were identified as genotypes C, H, J, or K, and 0.5% were identified as vaccine strains in genotypes A or N, while most sequences (98.7%) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks.

      18. Tuberculosis preventive treatment scale-up among antiretroviral therapy patients - 16 countries supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019external icon
        Melgar M, Nichols C, Cavanaugh JS, Kirking HL, Surie D, Date A, Ahmedov S, Maloney S, Fukunaga R.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):329-334.
        Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS(dagger) Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality.

      19. Long-term immunological responses to treatment among HIV-2 patients in Cote d'Ivoireexternal icon
        Minchella PA, Adje-Toure C, Zhang G, Tehe A, Hedje J, Rottinghaus ER, Kohemun N, Aka M, Diallo K, Ouedraogo GL, De Cock KM, Nkengasong JN.
        BMC Infect Dis. 2020 Mar 12;20(1):213.
        BACKGROUND: Studies indicate that responses to HIV-2 treatment regimens are worse than responses to HIV-1 regimens during the first 12 months of treatment, but longer-term treatment responses are poorly described. We utilized data from Cote d'Ivoire's RETRO-CI laboratory to examine long-term responses to HIV-2 treatment. METHODS: Adult (>/=15 years) patients with baseline CD4 counts < 500 cells/mul that initiated treatment at one of two HIV treatment centers in Abidjan, Cote d'Ivoire between 1998 and 2004 were included in this retrospective cohort study. Patients were stratified by baseline CD4 counts and survival analyses were employed to examine the relationship between HIV type and time to achieving CD4 >/= 500 cells/mul during follow up. RESULTS: Among 3487 patients, median follow-up time was 4 years and 57% had documented ART regimens for > 75% of their recorded visits. Kaplan-Meier estimates for achievement of CD4 >/= 500 cells/mul after 6 years of follow-up for patients in the lower CD4 strata (< 200 cells/mul) were 40% (HIV-1), 31% (HIV-dual), and 17% (HIV-2) (log-rank p < 0.001). Cox Regression indicated that HIV-1 was significantly associated with achievement of CD4 >/= 500 cells/mul during follow-up, compared to HIV-2. CONCLUSIONS: Sub-optimal responses to long-term HIV-2 treatment underscore the need for more research into improved and/or new treatment options for patients with HIV-2. In many West African countries, effective treatment of both HIV-1 and HIV-2 will be essential in the effort to reach epidemic control.

      20. Notes from the field: Ongoing cluster of highly related disseminated gonococcal infections - southwest Michigan, 2019external icon
        Nettleton WD, Kent JB, Macomber K, Brandt MG, Jones K, Ridpath AD, Raphael BH, Wells EV.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):353-354.

      21. Repeat symptomatic Neisseria gonorrhoeae infections among men who have sex with men in Bangkok, Thailand, 2006-2016external icon
        Pattanasin S, Holtz TH, Ungsedhapand C, Tongtoyai J, Chonwattana W, Sukwicha W, Sirivongrangson P, Mock PA, Chitwarakorn A, Dunne EF.
        Int J STD AIDS. 2020 Mar 30.

      22. Hepatitis C virus antibody screening in a cohort of pregnant women: Identifying seroprevalence and risk factorsexternal icon
        Prasad M, Saade GR, Sandoval G, Hughes BL, Reddy UM, Mele L, Salazar A, Varner MW, Gyamfi-Bannerman C, Thorp JM, Tita AT, Swamy GK, Chien EK, Casey BM, Peaceman AM, El-Sayed YY, Iams JD, Gibbs RS, Sibai B, Wiese N, Kamili S, Macones GA.
        Obstet Gynecol. 2020 Mar 10.
        OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015. METHODS: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody-positive, two women at similar gestational age who were HCV antibody-negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group. RESULTS: Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1-2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case-control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2-64.0), blood transfusion (aOR 3.7, 95% CI 1.3-10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8-22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4-19.8), and smoking (aOR 2.4, 95% CI 1.2-4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%). CONCLUSION: In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959321.

      23. Second nationwide anti-tuberculosis drug resistance survey in Namibiaexternal icon
        Ruswa N, Mavhunga F, Roscoe JC, Beukes A, Shipiki E, van Gorkom J, Sawadogo S, Agolory S, Menzies H, Tiruneh D, Makumbi B, Bayer B, Zezai A, Campbell P, Alexander H, Kalisvaart N, Forster N.
        Int J Tuberc Lung Dis. 2019 Jul 1;23(7):858-864.
        SETTING: Namibia ranks among the 30 high TB burden countries worldwide. Here, we report results of the second nationwide anti-TB drug resistance survey.OBJECTIVE: To assess the prevalence and trends of multidrug-resistant TB (MDR-TB) in Namibia.METHODS: From 2014 to 2015, patients with presumptive TB in all regions of Namibia had sputum subjected to mycobacterial culture and phenotypic drug susceptibility testing (DST) for rifampicin, isoniazid, ethambutol and streptomycin if positive on smear microscopy and/or Xpert MTB/RIF.RESULTS: Of the 4124 eligible for culture, 3279 (79.5%) had Mycobacterium tuberculosis isolated. 3126 (95%) had a first-line DST completed (2392 new patients, 699 previously treated patients, 35 with unknown treatment history). MDR-TB was detected in 4.5% (95%CI 3.7-5.4) of new patients, and 7.9% (95%CI 6.0-10.1) of individuals treated previously. MDR-TB was significantly associated with previous treatment (OR 1.8, 95%CI 1.3-2.5) but not with HIV infection, sex, age or other demographic factors. Prior treatment failure demonstrated the strongest association with MDR-TB (OR 17.6, 95%CI 5.3-58.7).CONCLUSION: The prevalence of MDR-TB among new TB patients in Namibia is high and, compared with the first drug resistance survey, has decreased significantly among those treated previously. Namibia should implement routine screening of drug resistance among all TB patients.

      24. We analyzed data from 2012-2016 for patients who were hospitalized or who died after >/=1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment.

      25. Tuberculosis - United States, 2019external icon
        Schwartz NG, Price SF, Pratt RH, Langer AJ.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):286-289.
        Since 1989, the United States has pursued a goal of eliminating tuberculosis (TB) through a strategy of rapidly identifying and treating cases and evaluating exposed contacts to limit secondary cases resulting from recent TB transmission (1). This strategy has been highly effective in reducing U.S. TB incidence (2), but the pace of decline has significantly slowed in recent years (2.2% average annual decline during 2012-2017 compared with 6.7% during 2007-2012) (3). For this report, provisional 2019 data reported to CDC's National Tuberculosis Surveillance System were analyzed to determine TB incidence overall and for selected subpopulations and these results were compared with those from previous years. During 2019, a total of 8,920 new cases were provisionally reported in the United States, representing a 1.1% decrease from 2018.* TB incidence decreased to 2.7 cases per 100,000 persons, a 1.6% decrease from 2018. Non-U.S.-born persons had a TB rate 15.5 times greater than the rate among U.S.-born persons. The U.S. TB case count and rate are the lowest ever reported, but the pace of decline remains slow. In recent years, approximately 80% of U.S. TB cases have been attributed to reactivation of latent TB infection (LTBI) acquired years in the past, often outside the United States (2). An expanded TB elimination strategy for this new decade should leverage existing health care resources, including primary care providers, to identify and treat persons with LTBI, without diverting public health resources from the continued need to limit TB transmission within the United States. Partnerships with health care providers, including private providers, are essential for this strategy's success.

      26. Using an established outbreak response plan and molecular epidemiology methods in an HIV transmission cluster investigation, Tennessee, January-June 2017external icon
        Sizemore L, Fill MM, Mathieson SA, Black J, Brantley M, Cooper K, Garrett J, Switzer WM, Peters PJ, Wester C.
        Public Health Rep. 2020 Mar 30:33354920915445.
        INTRODUCTION: In April 2017, the Tennessee Department of Health (TDH) was notified of an increase in the number of persons newly diagnosed with HIV in eastern Tennessee in the same month. Two were identified as persons with a history of injection drug use (IDU) and named each other as syringe-sharing partners, prompting an investigation into a possible HIV cluster among persons with a history of IDU. MATERIALS AND METHODS: TDH and public health staff members in eastern Tennessee collaborated to implement procedures outlined in TDH's HIV/hepatitis C virus (HCV) Outbreak Response Plan, including conducting enhanced interviewing and using a preestablished database for data collection and management. To complement contact tracing and enhanced interviewing, TDH partnered with the Centers for Disease Control and Prevention to conduct molecular HIV analyses. RESULTS: By June 27, 2017, the investigation had identified 31 persons newly diagnosed with HIV infection; 8 (26%) self-reported IDU, 4 of whom were also men who have sex with men (MSM). Of the remaining 23 persons newly diagnosed with HIV infection, 10 were MSM who did not report IDU, 9 reported high-risk heterosexual contact, and 4 had other or unknown risk factors. Molecular analysis of the 14 HIV-1 polymerase genes (including 7 of the 8 persons self-reporting IDU) revealed 3 distinct molecular clusters, one of which included 3 persons self-reporting IDU. PRACTICE IMPLICATIONS: This investigation highlights the importance of implementing an established Outbreak Response Plan and using HIV molecular analyses in the event of a transmission cluster or outbreak investigations. Future HIV outbreak surveillance will include using Global Hepatitis Outbreak Surveillance Technology to identify HCV gene sequences as a potential harbinger for HIV transmission networks.


      28. Tuberculosis disease and infection among household contacts of bacteriologically confirmed and non-confirmed tuberculosis patientsexternal icon
        Warria K, Nyamthimba P, Chweya A, Agaya J, Achola M, Reichler M, Cowden J, Heilig CM, Borgdorff MW, Cain KP, Yuen C.
        Trop Med Int Health. 2020 Mar 14.
        OBJECTIVE: To compare the prevalence of tuberculosis infection and disease in household contacts of patients with bacteriologically confirmed tuberculosis disease and contacts of non-bacteriologically confirmed disease in western Kenya. METHODS: We enrolled newly diagnosed index patients and their household contacts from March 2014 to June 2016. All contacts were evaluated with a symptom questionnaire, tuberculin skin test (TST), and HIV test. Clinical evaluation and sputum testing were performed for those with symptoms, positive TST result, or HIV infection. RESULTS: We enrolled 1155 contacts of 330 index patients with bacteriologically confirmed tuberculosis and 192 contacts of 55 index patients with non-bacteriologically confirmed tuberculosis. 3.5% of contacts of patients with bacteriologically confirmed tuberculosis were diagnosed with tuberculosis, whereas no contacts of index patients with non-bacteriologically confirmed tuberculosis were. Of those diagnosed with tuberculosis disease, 58.5% reported symptoms, 34.1% reported no symptoms but had positive TST results, and 7.3% had neither symptoms nor positive TST but were HIV-positive. Among 872 contacts with a TST result, 50.9% of contacts of index patients with bacteriologically confirmed tuberculosis and 41.0% of contacts of index patients with non-bacteriologically confirmed tuberculosis had a positive result (prevalence ratio = 1.16, 95% confidence interval 0.92-1.48). CONCLUSION: In a high-burden setting, tuberculosis disease was more prevalent among contacts of patients with bacteriologically confirmed tuberculosis than contacts of patients with non-bacteriologically confirmed disease. TST was feasible to perform and helped to detect cases that would have been missed had only symptomatic contacts been evaluated.

      29. Factors associated with 36-month loss to follow-up and mortality outcomes among HIV-infected adults on antiretroviral therapy in Central Kenyaexternal icon
        Wekesa P, McLigeyo A, Owuor K, Mwangi J, Nganga E, Masamaro K.
        BMC Public Health. 2020 Mar 14;20(1):328.
        BACKGROUND: The scale-up of HIV treatment programs has resulted in a reduction in HIV-related morbidity and mortality. However, retention of patients in these programs remains a challenge in sub-Saharan Africa. Understanding factors associated with loss to follow-up (LTFU) and mortality outcomes is therefore important to inform targeted program interventions. METHODS: A retrospective multi-cohort analysis of 23,890 adult patients on ART over 36 months of follow-up in Kenya was done. Multivariate logistic regression analysis was done to assess for factors associated with LTFU and mortality at 6, 12, 24, and 36 months of follow-up. RESULTS: Majority, 67.7%, were female. At 36 months, 27.2% were LTFU and 13.5% had died. Factors associated with mortality at 36 months included older age (51 years and above) using 20-35 years as reference [(adjusted odds ratio [aOR], 1.51, 95% confidence interval (CI) 1.23-1.86, p < 0.001], being male (aOR, 1.59, 95% CI 1.39-1.83, p < 0.001), divorced using married as reference (aOR, 1.86, 95% CI 1.56-2.22, p < 0.001), having a body mass index (BMI) score of less than 18.5 kg/m(2) using 18.5-24.9 kg/m(2) as reference (aOR = 1.79, 95% CI 1.52-2.11, p < 0.001), and, World Health Organization stage III and IV using stage I as the reference (aOR, 1.94, 95% CI 1.43-2.63 and aOR, 4.24, 95% CI 3.06-5.87, p < 0.001 respectively). Factors associated with LTFU at 36 months included being young between 20 and 35 years (aOR, 1.49, 95% CI 1.40-1.59, p < 0.001) using 36-50 years as reference, being male (aOR, 1.19, 95% CI 1.12-1.27, p < 0.001), and being single or divorced using married as reference (aOR, 1.34, 95% CI 1.23-1.45 and aOR, 1.25, 95% CI 1.15-1.36, p < 0.001 respectively). Patients with baseline BMI of less than 18.5 kg/m(2) using normal BMI as reference (aOR, 1.68, 95% CI 1.39-2.02, p < 0.001) were also likely to be LTFU. CONCLUSIONS: Factors associated with LTFU and mortality were generally similar over time. Implementation of programs in similar settings should be tailored to gender, age profiles, nutritional, and, marital status of patients to address LTFU. In addition, programs should focus on the care of older patients to reduce the risk of mortality.

      30. Prevalence of HPV infection among sexually active adolescents and young adults in Brazil: The POP-Brazil Studyexternal icon
        Wendland EM, Villa LL, Unger ER, Domingues CM, Benzaken AS.
        Sci Rep. 2020 Mar 18;10(1):4920.
        For Brazil, there are no nationwide data on HPV prevalence against which the impact of the HPV immunization program can be measured in the future. Therefore, we aim to evaluate the prevalence of genital HPV infection among adolescents and young adults in Brazil. A cross-sectional, multicentric, nationwide survey was conducted between September 2016 and November 2017. Sexually active unvaccinated women and men aged 16 to 25 years old were recruited from 119 public primary care units, including all 26 state capitals and the Federal District. All participants answered a face-to-face interview and provided biological samples for genital HPV analysis. We used an automated DNA extraction method and HPV genotyping was performed using the Linear Array genotyping test (Roche). Of 7,694 participants, 53.6% (95% CI 51.4-55.8) were positive for any HPV type. The prevalence of high-risk HPV types was significantly higher in women (38.6% vs. 29.2%, P < 0.001). The HPV types included in the quadrivalent vaccine were detected in 1002 (14.8%) specimens, with a different pattern of HPV infection between sexes. Characteristics associated with overall HPV detection included female gender, self-declaration of race as brown/pardo, lower socioeconomic class, single or dating, current smoking and having 2 or more sex partners in the past year. We found a high prevalence of HPV, with significant differences between regions. Our data provide information that may be considered when developing HPV prevention policies and constitute a baseline against which the impact of the HPV immunization program in Brazil can be measured in future years.

      31. Children and their families are entitled to the benefits of differentiated ART deliveryexternal icon
        Wilkinson L, Siberry GK, Golin R, Phelps BR, Wolf HT, Modi S, Grimsrud A.
        J Int AIDS Soc. 2020 Apr;23(4):e25482.

      32. Awareness of HIV-positive status and linkage to treatment prior to pregnancy in the "test and treat" era: A national antenatal sentinel survey, 2017, South Africaexternal icon
        Woldesenbet S, Kufa T, Cheyip M, Ayalew K, Lombard C, Manda S, Nadol P, Barron P, Chirombo B, Igumbor E, Pillay Y, Puren A.
        PLoS One. 2020 ;15(3):e0229874.
        INTRODUCTION: Knowledge of HIV status in South Africa (SA) is reported to be 90% among people living with HIV. National level estimates could mask population-specific levels, which are critical to monitor program coverage and potential impact. Using data from the 2017 national antenatal sentinel survey, we assessed knowledge of HIV-positive status, initiation of antiretroviral therapy (ART), and socio-demographic characteristics associated with knowledge of HIV-positive status prior to the current pregnancy among women attending antenatal care. METHODS: Between 1 October and 15 November 2017, a nationally representative sample of 32,716 pregnant women were enrolled from 1,595 public health facilities selected from all districts of SA. Data on age, gravidity, knowledge of HIV-positive status and ART initiation prior to pregnancy were extracted from medical records. A blood sample was collected from each woman regardless of prior knowledge of HIV status or ART history, and tested for HIV in the laboratory. All HIV-positive pregnant women enrolled in the survey were eligible for inclusion in the analysis. Multivariable survey logistic regression was used to examine factors associated with knowledge of HIV-positive status prior to the current pregnancy. RESULTS: Of 10,065 eligible HIV-positive women, 60.8% (95% confidence interval (CI):59.9%-61.7%) knew their HIV status prior to the current pregnancy, of whom 91.1% (95% CI: 90.4%-91.7%) initiated ART prior to the current pregnancy. Knowledge of HIV-positive status was lower among adolescent girls and young women (15-24 years) (38.9%) and primigravid women (40.5%) compared with older women (35-49 years) (75.5%) and multigravid women (64.7%). In a multivariable analysis, significant effect modification was found between gravidity and age (P value = 0.047). Being in the age group 15-24 years compared to the age group 35-49 years decreased the odds of knowing HIV-positive status by 80% (adjusted odds ratio (AOR): 0.2, 95% CI:0.1-0.4) among primigravid women and by 60%(AOR: 0.4, 95% CI:0.3-0.4) among multigravid women. CONCLUSION: Knowledge of HIV-positive status prior to the current pregnancy fell short of the target of 90% among pregnant women living with HIV. This was especially low among adolescent girls and young women, highlighting the gap in youth friendly reproductive health and HIV testing services.

      33. Susceptibility to hepatitis A virus infection in the United States, 2007-2016external icon
        Yin S, Barker L, Ly KN, Kilmer G, Foster MA, Drobeniuc J, Jiles RB.
        Clin Infect Dis. 2020 Mar 20.
        BACKGROUND: Despite national immunization efforts, including universal childhood hepatitis A (HepA) vaccination recommendations in 2006, hepatitis A virus (HAV)-associated outbreaks have increased in the United States. Unvaccinated or previously uninfected persons are susceptible to HAV infection, yet the susceptibility in the U.S. population is not well known. METHODS: Using National Health and Nutrition Examination Survey 2007-2016 data, we estimated HAV susceptibility prevalence (total HAV antibody negative) among persons aged >/=2 years. Among U.S.-born adults aged >/=20 years, we examined prevalence, predictors, and age-adjusted trends of HAV susceptibility by sociodemographic characteristics. We assessed HAV susceptibility and self-reported non-vaccination to HepA among risk groups and the "immunization cohort" (those born in or after 2004). RESULTS: Among U.S.-born adults aged >/=20 years, HAV susceptibility prevalence was 74.1% (95% CI: 72.9-75.3%) during 2007-2016. Predictors of HAV susceptibility were age group 30-49 years, non-Hispanic white/black, 130% above the poverty level, and no health insurance. Prevalences of HAV susceptibility and non-vaccination to HepA, respectively, were 72.9% and 73.1% among persons who reported injection drug use, 67.5% and 65.2% among men who had sex with men, 55.2% and 75.1% among persons with hepatitis B or hepatitis C, and 22.6% and 25.9% among the immunization cohort. Susceptibility and non-vaccination decreased over time among the immunization cohort, but remained stable among risk groups. CONCLUSION: During 2007-2016, approximately three-fourths of U.S.-born adults remained HAV susceptible. Enhanced vaccination efforts are critically needed, particularly targeting adults at highest risk for HAV infection, to mitigate the current outbreaks.

      34. Influenza-associated hospitalization in children younger than 5 years of age in Suzhou, China, 2011-2016external icon
        Yu J, Zhang X, Shan W, Gao J, Hua J, Tian J, Ding Y, Zhang J, Chen L, Song Y, Zhou S, Iuliano AD, Greene CM, Zhang T, Zhao G.
        Pediatr Infect Dis J. 2019 May;38(5):445-452.
        BACKGROUND: Studying the burden and risk factors associated with severe illness from influenza infection in young children in eastern China will contribute to future cost-effectiveness analyses of local influenza vaccine programs. METHODS: We conducted prospective, severe acute respiratory infection (SARI) surveillance at Suzhou University-Affiliated Children's Hospital to estimate influenza-associated hospitalizations in Suzhou University-Affiliated Children's Hospital by month in children younger than 5 years of age from October 2011 to September 2016. SARI was defined as fever (measured axillary temperature >/= 38 degrees C) and cough or sore throat or inflamed/red pharynx in the 7 days preceding hospitalization. We combined SARI surveillance data with healthcare utilization survey data to estimate and characterize the burden of influenza-associated SARI hospitalizations in Suzhou within this age group in the 5-year period. RESULTS: Of the 36,313 SARI cases identified, 2,297 from respiratory wards were systematically sampled; of these, 259 (11%) were influenza positive. Estimated annual influenza-associated SARI hospitalization rates per 1,000 children younger than 5 years of age ranged from 4 (95% confidence interval [CI], 2-5) in the 2012-2013 season to 16 (95% CI, 14-19) in the 2011-2012 season. The predominant viruses were A/H3N2 (59%) in 2011-12, both A/H1N1pdm09 (42%) and B (46%) in 2012-13, A/H3N2 (71%) in 2013-14, A/H3N2 (55%) in 2014-15 and both A/H1N1pdm09 (50%) and B (50%) in 2015-16. The age-specific influenza-associated SARI hospitalization rates for the 5-year period were 11 (95% CI, 8-15) per 1,000 children 0-5 months of age; 8 (95% CI, 7-10) per 1,000 children 6-23 months of age and 5 (95% CI, 4-5) per 1,000 children 24-59 months of age, respectively. CONCLUSIONS: From 2011 to 2016, influenza-associated SARI hospitalization rates in children aged younger than 5 years of age in Suzhou, China, were high, particularly among children 0-5 months of age. Higher hospitalization rates were observed in years where the predominant circulating virus was influenza A/H3N2. Immunization for children > 6 months, and maternal and caregiver immunization for those < 6 months, could reduce influenza-associated hospitalizations in young children in Suzhou.

    • Disaster Control and Emergency Services
      1. Trends and characteristics of CDC Global Rapid Response Team deployments - a 6-month report, October 2018-March 2019external icon
        Ben Hamida A, Bugli D, Hoffman A, Greiner AL, Harley D, Saindon JM, Walsh J, Bierman E, Mallory J, Blaylock K, Shetty S, Bensyl DM, Wheeler BD.
        Public Health Rep. 2020 Mar 30:33354920914662.
        The Centers for Disease Control and Prevention (CDC) Global Rapid Response Team (GRRT) was launched in June 2015 to strengthen the capacity for international response and to provide an agency-wide roster of qualified surge-staff members who can deploy on short notice and for long durations. To assess GRRT performance and inform future needs for CDC and partners using rapid response teams, we analyzed trends and characteristics of GRRT responses and responders, for deployments of at least 1 day during October 1, 2018, through March 31, 2019. One hundred twenty deployments occurred during the study period, corresponding to 2645 person-days. The median deployment duration was 19 days (interquartile range, 5-30 days). Most deployments were related to emergency response (n = 2367 person-days, 90%); outbreaks of disease accounted for almost all deployment time (n = 2419 person-days, 99%). Most deployments were to Africa (n = 1417 person-days, 54%), and epidemiologists were the most commonly deployed technical advisors (n = 1217 person-days, 46%). This case study provides useful information for assessing program performance, prioritizing resource allocation, informing future needs, and sharing lessons learned with other programs managing rapid response teams. GRRT has an important role in advancing the global health security agenda and should continuously be assessed and adjusted to new needs.

      2. During a severe pandemic, especially one causing respiratory illness, many people may require mechanical ventilation. Depending on the extent of the outbreak, there may be insufficient capacity to provide ventilator support to all of those in need. As part of a larger conceptual framework for determining need for and allocation of ventilators during a public health emergency, this article focuses on the strategies to assist state and local planners to allocate stockpiled ventilators to healthcare facilities during a pandemic, accounting for critical factors in facilities' ability to make use of additional ventilators. These strategies include actions both in the pre-pandemic and intra-pandemic stages. As a part of pandemic preparedness, public health officials should identify and query healthcare facilities in their jurisdiction that currently care for critically ill patients on mechanical ventilation to determine existing inventory of these devices and facilities' ability to absorb additional ventilators. Facilities must have sufficient staff, space, equipment, and supplies to utilize allocated ventilators adequately. At the time of an event, jurisdictions will need to verify and update information on facilities' capacity prior to making allocation decisions. Allocation of scarce life-saving resources during a pandemic should consider ethical principles to inform state and local plans for allocation of ventilators. In addition to ethical principles, decisions should be informed by assessment of need, determination of facilities' ability to use additional ventilators, and facilities' capacity to ensure access to ventilators for vulnerable populations (eg, rural, inner city, and uninsured and underinsured individuals) or high-risk populations that may be more susceptible to illness.

      3. Training and fit testing of health care personnel for reusable elastomeric half-mask respirators compared with disposable N95 respiratorsexternal icon
        Pompeii LA, Kraft CS, Brownsword EA, Lane MA, Benavides E, Rios J, Radonovich LJ.
        Jama. 2020 Mar 25.

    • Disease Reservoirs and Vectors
      1. An assessment of adult mosquito collection techniques for studying species abundance and diversity in Maferinyah, Guineaexternal icon
        Cansado-Utrilla C, Jeffries CL, Kristan M, Brugman VA, Heard P, Camara G, Sylla M, Beavogui AH, Messenger LA, Irish SR, Walker T.
        Parasit Vectors. 2020 Mar 24;13(1):150.
        BACKGROUND: Several mosquito collection methods are routinely used in vector control programmes. However, they target different behaviours causing bias in estimation of species diversity and abundance. Given the paucity of mosquito trap data in West Africa, we compared the performance of five trap-lure combinations and Human Landing Catches (HLCs) in Guinea. METHODS: CDC light traps (LT), BG sentinel 2 traps (BG2T), gravid traps (GT) and Stealth traps (ST) were compared in a 5 x 5 Latin Square design in three villages in Guinea between June and July 2018. The ST, a portable trap which performs similarly to a LT but incorporates LEDs and incandescent light, was included since it has not been widely tested. BG2T were used with BG and MB5 lures instead of CO2 to test the efficacy of these attractants. HLCs were performed for 5 nights, but not as part of the Latin Square. A Generalised Linear Mixed Model was applied to compare the effect of the traps, sites and collection times on mosquito abundance. Species identification was confirmed using PCR-based analysis and Sanger sequencing. RESULTS: A total of 10,610 mosquitoes were captured across five traps. ST collected significantly more mosquitoes (7096) than the rest of the traps, but resulted in a higher number of damaged specimens. ST and BG2T collected the highest numbers of Anopheles gambiae (s.l.) and Aedes aegypti mosquitoes, respectively. HLCs captured predominantly An. coluzzii (41%) and hybrids of An. gambiae and An. coluzzii (36%) in contrast to the five traps, which captured predominantly An. melas (83%). The rural site (Senguelen) presented the highest abundance of mosquitoes and overall diversity in comparison with Fandie (semi-rural) and Maferinyah Centre I (semi-urban). Our results confirm the presence of four species for the first time in Guinea. CONCLUSIONS: ST collected the highest number of mosquitoes suggesting this trap may play an important role for mosquito surveillance in Guinea and similar sites in West Africa. We recommend the incorporation of molecular tools in entomological studies since they have helped to identify 25 mosquito species in this area.

      2. Clonal spread of Yersinia enterocolitica 1B/O:8 in multiple zoo speciesexternal icon
        Hicks CL, Napier JE, Armstrong DL, Gladney LM, Tarr CL, Freeman MM, Iwen PC.
        J Zoo Wildl Med. 2020 Mar 17;51(1):170-176.
        Yersinia enterocolitica (YE) bioserotype 1B/O:8 (YE 1B/O:8) was identified in routine culture of a variety of zoo species housed at Omaha's Henry Doorly Zoo and Aquarium (OHDZA) from April to July 2011. Animal cases representing 12 species had YE detected from 34 cases during routine fecal monitoring and/or during postmortem examination: Coquerel's sifakas (Propithecus coquereli, two cases), black & white (BW) ruffed lemurs (Varecia variegata variegata, six cases), red ruffed lemurs (Varecia rubra, seven cases), white handed gibbon (Hylobates lar albimana, one case), black lemurs (Eulemur macaco, three cases), mongoose lemurs (Eulemur mongoz, two cases), African hunting dogs (Lycaon pictus, five cases), agile gibbons (Hylobates agilis, three cases), siamangs (Hylobates syndactylus, two cases), colobus monkey (Colobus angolensis palliates, one case), argus pheasant (Argusianus argus, one case), and orangutan (Pongo pygmaeus, one case). Most species were not symptomatic; however, three symptomatic cases in Coquerel's sifakas (two) and a white handed gibbon (one) showed clinical signs of diarrhea and lethargy that resulted in death for the Coquerel's sifakas. One unexpected death also occurred in a BW ruffed lemur. To the authors' knowledge, this is the first report of YE 1B/O:8 in such a large variety of zoo species. The source of the YE could not be identified, prompting the initiation of a diseases surveillance program to prevent further cases for the species that are sensitive to YE. To date, no additional cases have been identified, thus suggesting a single introduction of the YE 1B/O:8 strain into the zoo environment.

      3. The distributions of the Afrotropical Anopheles mosquitoes were first summarized in 1938. In 2017, an extensive geo-coded inventory was published for 48 sub-Saharan African countries, including information such as sampling methods, collection dates, geographic co-ordinates and the literature consulted to produce the database. Using the information from the 2017 inventory, earlier distribution lists, museum collections and publications since 2016, this paper presents an updated, simplified list of Anopheles species by mainland countries and associated Afrotropical islands, with comments where applicable. It is intended as a supplement to the 2017 geo-coded inventory.

    • Drug Safety
      1. Prescribers and naloxone pharmacy claimsexternal icon
        Smart R, Geiger CK, Jones CM, Stein BD.
        J Gen Intern Med. 2020 Mar 24.

    • Environmental Health
      1. Gestational and childhood urinary triclosan concentrations and academic achievement among 8-year-old childrenexternal icon
        Jackson-Browne MS, Papandonatos GD, Chen A, Calafat AM, Yolton K, Lanphear BP, Braun JM.
        Neurotoxicology. 2020 Mar 19.
        BACKGROUND: Early life exposure to triclosan, an antimicrobial chemical and suspected endocrine disruptor, may adversely affect neurodevelopment. No studies have examined gestational and early childhood exposure to triclosan and children's academic achievement. METHODS: Using data from 195 mother-child pairs from the HOME Study, we quantified triclosan in maternal and child urine samples up to nine times between the second trimester of gestation (16-weeks) and age 8 years. At age 8 years, we administered the reading and math components of the Wide Range Achievement Test-4 (WRAT-4) to children. Using multiple informants models, we estimated covariate-adjusted associations of triclosan concentrations during each time period with WRAT-4 scores. We also tested whether associations differed by exposure period and child sex. RESULTS: There was evidence that timing of exposure modified the associations between triclosan and reading composite scores (triclosan-exposure period interaction p-value = 0.20), but not math scores (interaction p-value = 0.72). Each 10-fold increase in triclosan concentrations at delivery was associated with lower reading composite scores (beta:-2.6; 95% CI:-5.0, -0.1). Additionally, we observed weaker and less precise inverse association of math scores with triclosan concentrations at delivery (beta:-1.9; 95% CI:-4.6, 0.8) and at age 1 year (beta:-2.0; 95% CI:-6.0, 2.1). There was not strong evidence that child sex modified the pattern of associations between repeated triclosan measures and WRAT-4 reading composite or math scores (sex-triclosan-exposure period interaction p-values>0.20). CONCLUSION: Urinary triclosan concentrations at delivery and at age 1 year, but not other times during gestation or childhood, were associated with lower reading composite and to a lesser extent math test scores at age 8 years in this cohort of U.S. children.

      2. Advancing global health through environmental and public health trackingexternal icon
        Lauriola P, Crabbe H, Behbod B, Yip F, Medina S, Semenza JC, Vardoulakis S, Kass D, Zeka A, Khonelidze I, Ashworth M, de Hoogh K, Shi X, Staatsen B, Knudsen LE, Fletcher T, Houthuijs D, Leonardi GS.
        Int J Environ Res Public Health. 2020 Mar 17;17(6).
        Global environmental change has degraded ecosystems. Challenges such as climate change, resource depletion (with its huge implications for human health and wellbeing), and persistent social inequalities in health have been identified as global public health issues with implications for both communicable and noncommunicable diseases. This contributes to pressure on healthcare systems, as well as societal systems that affect health. A novel strategy to tackle these multiple, interacting and interdependent drivers of change is required to protect the population's health. Public health professionals have found that building strong, enduring interdisciplinary partnerships across disciplines can address environment and health complexities, and that developing Environmental and Public Health Tracking (EPHT) systems has been an effective tool. EPHT aims to merge, integrate, analyse and interpret environmental hazards, exposure and health data. In this article, we explain that public health decision-makers can use EPHT insights to drive public health actions, reduce exposure and prevent the occurrence of disease more precisely in efficient and cost-effective ways. An international network exists for practitioners and researchers to monitor and use environmental health intelligence, and to support countries and local areas toward sustainable and healthy development. A global network of EPHT programs and professionals has the potential to advance global health by implementing and sharing experience, to magnify the impact of local efforts and to pursue data knowledge improvement strategies, aiming to recognise and support best practices. EPHT can help increase the understanding of environmental public health and global health, improve comparability of risks between different areas of the world including Low and Middle-Income Countries (LMICs), enable transparency and trust among citizens, institutions and the private sector, and inform preventive decision making consistent with sustainable and healthy development. This shows how EPHT advances global health efforts by sharing recent global EPHT activities and resources with those working in this field. Experiences from the US, Europe, Asia and Australasia are outlined for operating successful tracking systems to advance global health.

      3. Maternal serum perfluoroalkyl substance mixtures and thyroid hormone concentrations in maternal and cord sera: The HOME Studyexternal icon
        Lebeaux RM, Doherty BT, Gallagher LG, Zoeller RT, Hoofnagle AN, Calafat AM, Karagas MR, Yolton K, Chen A, Lanphear BP, Braun JM, Romano ME.
        Environ Res. 2020 Mar 16;185:109395.
        BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture. METHODS: We collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers. RESULTS: PFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (beta = 0.09; 95% CrI: -0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT4 suggesting modification by maternal TPOAb status. CONCLUSIONS: These findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings.

      4. Effect of environmental temperature and humidity on permethrin biomarkers of exposure in U.S. soldiers wearing permethrin-treated uniformsexternal icon
        Maule AL, Heaton KJ, Cadarette B, Taylor KM, Guerriere KI, Haven CC, Scarpaci MM, Kenefick RW, Ospina M, Calafat AM, Proctor SP.
        Am J Trop Med Hyg. 2020 Mar 30.
        Environmental factors, including high temperature and humidity, can influence dermal absorption of chemicals. Soldiers can be dermally exposed to permethrin while wearing permethrin-treated uniforms. This study aimed at examining the effects of high temperature and a combined high temperature and humid environment on permethrin absorption compared with ambient conditions when wearing a permethrin-treated uniform. Twenty-seven male enlisted soldiers wore study-issued permethrin-treated army uniforms for 33 consecutive hours in three different environments: 1) simulated high temperature (35 degrees C, 40% relative humidity [rh]) (n = 10), 2) simulated high temperature and humidity (30 degrees C, 70% rh) (n = 10), and 3) ambient conditions (13 degrees C, 60% rh) (n = 7). Spot urine samples, collected at 21 scheduled time points before, during, and after wearing the study uniforms, were analyzed for permethrin exposure biomarkers (3-phenoxybenzoic acid, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid) and creatinine. Biomarker concentrations were 60-90% higher in the heat and combined heat/humidity groups (P < 0.001-0.022) than the ambient group. Also, the average daily permethrin dose, calculated 12 hours after removing the treated uniforms, was significantly higher in the heat (P = 0.01) and the heat/humidity (P = 0.03) groups than the ambient group. There were no significant differences in biomarker concentrations or computed average daily dose between the heat and the heat/humidity groups. Both hot and combined hot and humid environmental conditions significantly increased permethrin absorption in soldiers wearing permethrin-treated uniforms.

      5. National Toxic Substances Incidents Program - nine states, 2010-2014external icon
        Melnikova N, Wu J, Ruiz P, Orr MF.
        MMWR Surveill Summ. 2020 Mar 20;69(2):1-10.
        PROBLEM/CONDITION: Every year in the United States, thousands of toxic substance incidents harm workers, first responders, and the public with the potential for catastrophic consequences. Surveillance data enable public health and safety professionals to understand the patterns and causes of these incidents, which can improve prevention efforts and preparation for future incidents. PERIOD COVERED: 2010-2014. DESCRIPTION OF SYSTEM: In 2010, the Agency for Toxic Substances and Disease Registry (ATSDR) initiated the National Toxic Substance Incidents Program (NTSIP), and it was retired in 2014. Nine state health departments participated in NTSIP surveillance: California, Louisiana, North Carolina, New York, Missouri, Oregon, Tennessee, Utah, and Wisconsin. The states conducted surveillance on acute toxic substance incidents, defined as an uncontrolled or illegal acute (lasting <72 hours) release of any toxic substance including chemical, biologic, radiologic, and medical materials. Surveillance focused on associated morbidity and mortality and public health actions. This report presents an overview of NTSIP and summarizes incidents and injuries from the nine participating states during 2010-2014. RESULTS: During 2010-2014, participating state health departments reported 22,342 incidents, of which 13,529 (60.6%) met the case definition for acute toxic substance incidents, and included 6,635 injuries among 5,134 injured persons, of whom 190 died. A trend analysis of the three states participating the entire time showed a decrease in the number of incidents with injuries. NTSIP incidents were 1.8 times more likely and injured persons were 10 times more likely to be associated with fixed facilities than transportation. Natural gas, carbon monoxide, ammonia, and chemicals used in illegal methamphetamine production were the most frequent substances in fixed-facility incidents. Sodium and potassium hydroxide, hydrochloric acid, natural gas, and sulfuric acid were the most frequent substances in transportation-related incidents. Carbon monoxide was the most frequent substance in incidents with a large number of injured persons, and chemicals used in illegal methamphetamine production were the most frequent substance in incidents involving decontamination. Incidents most frequently occurred during normal business days (Monday through Friday) and hours (6:00 a.m.-5:59 p.m.) and warmer months (March-August). The transportation and warehousing industry sector had the largest number of incidents (4,476); however, most injured persons were injured in their private residences (1,141) or in the industry sectors of manufacturing (668), educational services (606), and real estate rental and leasing (425). The most frequently injured persons were members of the public (43.6%), including students. Injured first responders, particularly police, frequently were not wearing any chemically protective equipment. Respiratory system problems (23.9%) were the most frequently reported symptoms among injured persons and, in a related finding, volatilization was the most frequent type of release in incidents with injured persons. INTERPRETATION: Industrial and transportation incidents occur frequently and have the potential for catastrophic outcomes. However, exposures to toxic substances occur frequently in other settings. Carbon monoxide, natural gas, and chemicals used in illegal methamphetamine production are commonly found in places where persons live, work, attend school, and recreate and are large contributors to incidents affecting the public. Having active NTSIP state surveillance programs did appear to improve the incidents with morbidity and/or mortality, but these programs have ended. PUBLIC HEALTH ACTION: Archived NTSIP public use data are available to download from the website for analysis. There are also many publications and reports on the website to help understand chemical risks. In addition, jurisdictions might choose to collect surveillance data themselves in a similar manner to what NTSIP states did. Chemical incident surveillance data can be used by public health and safety practitioners, worker representatives, emergency planners, preparedness coordinators, industries, and emergency responders to prepare for and prevent chemical incidents and injuries. As noted by the U.S. Chemical Safety Board, more action needs to be taken to prevent large industrial incidents. Although preventing such incidents might not be in the realm of public health, describing the public health implications and preparing for them is. Another important finding of NTSIP is that industrial incidents are only part of the problem. For example, a large number of persons were injured in a private residence or vehicle (22.2%) and an educational facility (11.8%). Public health professionals must resourcefully target prevention and preparedness to protect vulnerable populations in locations where they might spend time (e.g., schools, daycares, nursing homes, recreational areas, jails, prisons, and hospitals). Reducing the threat of chemical incidents and injuries in the United States will require a concerted effort with a variety of stakeholders including industry and labor, responder groups, policymakers, academia, and citizen advocacy groups.

      6. Morphology and quantification of fungal growth in residential dust and carpetsexternal icon
        Nastasi N, Haines SR, Xu L, da Silva H, Divjan A, Barnes MA, Rappleye CA, Perzanowski MS, Green BJ, Dannemiller KC.
        Build Environ. 2020 ;174.
        Mold growth indoors is associated with negative human health effects, and this growth is limited by moisture availability. Dust deposited in carpet is an important source of human exposure due to potential elevated resuspension compared to hard floors. However, we need an improved understanding of fungal growth in dust and carpet to better estimate human exposure. The goal of this study was to compare fungal growth quantity and morphology in residential carpet under different environmental conditions, including equilibrium relative humidity (ERH) (50%, 85%, 90%, 95%, 100%), carpet fiber material (nylon, olefin, wool) and presence/absence of dust. We analyzed incubated carpet and dust samples from three Ohio homes for total fungal DNA, fungal allergen Alt a 1, and fungal morphology. Dust presence and elevated ERH (≥85%) were the most important variables that increased fungal growth. Elevated ERH increased mean fungal DNA concentration (P < 0.0001), for instance by approximately 1000 times at 100% compared to 50% ERH after two weeks. Microscopy also revealed more fungal growth at higher ERH. Fungal concentrations were up to 100 times higher in samples containing house dust compared to no dust. For fiber type, olefin had the least total fungal growth, and nylon had the most total fungi and A. alternata growth in unaltered dust. Increased ERH conditions were associated with increased Alt a 1 allergen concentration. The results of this study demonstrate that ERH, presence/absence of house dust, and carpet fiber type influence fungal growth and allergen production in residential carpet, which has implications for human exposure.

      7. Correlates of organochlorine pesticide plasma concentrations among reproductive-aged black womenexternal icon
        Orta OR, Wesselink AK, Bethea TN, Henn BC, Sjodin A, Wegienka G, Baird DD, Wise LA.
        Environ Res. 2020 Mar 7;184:109352.
        BACKGROUND: Organochlorine pesticides (OCPs) are lipophilic persistent organic pollutants associated with adverse health outcomes. Black women have higher body burdens compared with other U.S. populations and research on their correlates is limited. METHODS: Using baseline data from a prospective cohort study of Black women aged 23-35 years from the Detroit, Michigan metropolitan area (enrolled 2010-2012), we examined correlates of plasma concentrations of the following OCPs: dichlorodiphenyltrichloroethane (p,p'-DDE), hexachlorobenzene (HCB), oxychlordane, and trans-nonachlor. At enrollment, we collected non-fasting blood samples from 742 participants. We also collected data on demographic, behavioral, dietary, occupational, and medical history factors via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent (%) differences across categories of each correlate and 95% confidence intervals (CIs). RESULTS: In models adjusted for all other correlates, a 5-year increase in age was associated with 24% higher oxychlordane (95% CI: 12%, 38%) and 26% higher trans-nonachlor (95% CI: 12%, 42%) plasma concentrations. Heavy alcohol use was associated with 7-9% higher plasma concentrations of p,p'-DDE, oxychlordane, and trans-nonachlor. Current smoking was associated with 10-19% higher plasma concentrations of all four OCPs, and was highest for current smokers of >/=10 cigarettes/day (% differences ranged from 22 to 29%). Compared with having never been breastfed during infancy, having been breastfed for >/=3 months was associated with 15% higher concentrations of p,p'-DDE (95% CI: 6%, 25%), 14% higher oxychlordane (95% CI: 5%, 24%), and 15% higher trans-nonachlor (95% CI: 5%, 27%). Consumption of >/=5 vs. </=2 glasses/day of tap or bottled water was associated with 8-15% higher plasma concentrations of all four OCPs, and was highest for trans-nonachlor (% difference: 15%; 95% CI: 6%, 26%). No other dietary predictors were appreciably associated with plasma OCP concentrations. Obesity, parity, higher birth order, and longer lactation duration were inversely associated with plasma OCP concentrations. CONCLUSIONS: In Black U.S. women of reproductive age, older age was an important correlate of plasma OCP concentrations. Exposure to OCPs earlier in life appears to contribute to current blood concentrations. In addition, tobacco, alcohol, and drinking water may be important sources of exposure.

      8. Dust in homes can contain phthalates that may adversely affect child development, but whether residential interventions and dust removal can prevent children's exposure to phthalates is unknown. We quantified the influence of a residential lead hazard intervention and dust control on children's urinary phthalate metabolite concentrations. Between 2003 and 2006, The Health Outcomes and Measures of the Environment (HOME) Study randomized 355 pregnant women to receive an intervention to reduce either residential lead or injury hazards before delivery. We quantified eight urinary phthalate metabolites from 288 children at ages 1, 2, or 3 years (680 observations). During yearly home visits, we assessed dust accumulation in housing units. Children in the lead intervention group had 11-12% lower concentrations of the sum of di(2-ethylhexyl) phthalate metabolites, monocarboxyoctyl phthalate, and monocarboxynonyl phthalate compared to the injury intervention group. Monoethyl phthalate concentrations did not differ by group. In observational analyses, children living in housing units that appeared clean had 12-17% lower concentrations of these phthalate metabolites and monobenzyl phthalate, compared to children living in housing units with more dust accumulation. Features of this lead hazard intervention and measures to control dust may reduce children's exposure to phthalates found in building materials and household furnishings.

    • Epidemiology and Surveillance
      1. Previous research has shown that increasing the size of incentives can increase response rates for probability-based, cross-sectional surveys. However, the effects of incentives on web panels have not been extensively studied. We sought to answer the question: What is the effect of larger, postpaid incentives on (1) response, (2) data quality, and (3) nonresponse bias for individuals in a web panel? We analyzed data from the 2015 and 2016 National Internet Flu Survey, a survey that uses the GfK KnowledgePanel as its sampling frame. We compare panel members who received a postpaid, standard 1,000-point (the equivalent of US$1) incentive in 2015 to panelists who received a larger, 5,000-point (the equivalent of US$5) incentive in 2016. We found that larger incentives were associated with increased interview completion rates with minimal impact on data quality or bias.

      2. The Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program created standardized sub-county geographies that are comparable over time, place, and outcomes. Expected census tract-level counts were calculated for asthma emergency department visits and lung cancer. Census tracts were aggregated for various total population and sub-population thresholds, then suppression and stability were examined. A total of 5,000 persons was recommended for the more common outcome scheme and a total of 20,000 persons was recommended for the rare outcome scheme. Health outcomes with a median case count of 17.0 cases or higher should produce stable estimates at the census tract level. This project generated recommendations for three sub-county geographies that will be useful for surveillance purposes: census tract, a more common outcome aggregation scheme, and a rare outcome aggregation scheme. This methodology can be applied anywhere to aggregate geographic units and produce stable rates at a finer resolution.

    • Global Health
      1. Health of Special Immigrant Visa holders from Iraq and Afghanistan after arrival into the United States using Domestic Medical Examination data, 2014-2016: A cross-sectional analysisexternal icon
        Kumar GS, Pezzi C, Wien S, Mamo B, Scott K, Payton C, Urban K, Hughes S, Kennedy L, Cabanting N, Montour J, Titus M, Aguirre J, Kawasaki B, Ford R, Jentes ES.
        PLoS Med. 2020 Mar;17(3):e1003083.
        BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (>/=5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage.

      2. Health screenings administered during the domestic medical examination of refugees and other eligible immigrants in nine US states, 2014-2016: A cross-sectional analysisexternal icon
        Pezzi C, Lee D, Kumar GS, Kawasaki B, Kennedy L, Aguirre J, Titus M, Ford R, Mamo B, Urban K, Hughes S, Payton C, Scott K, Montour J, Jentes ES.
        PLoS Med. 2020 Mar;17(3):e1003065.
        BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program's potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination's impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research.

      3. BACKGROUND: The United States has admitted over 80,000 Special Immigrant Visa holders (SIVH), which include children. Despite the increase in the proportion of SIVH admissions to the US over recent years, little is known about health conditions in SIV children. We report the frequency of selected diseases identified overseas and assess differences in selected conditions between SIV children from Iraq and Afghanistan. METHODS AND FINDINGS: We analyzed 15,729 overseas medical exam data in Centers for Disease Control and Prevention's Electronic Disease Notification system (EDN) for children less than 18 years of age from Iraq (29.1%) and Afghanistan (70.9%) who were admitted to the US from April 2009 through December 2017 in a cross-sectional analysis. Variables included age, sex, native language, measured height and weight, and results of the overseas medical examination. From our analysis, less than 1% of SIV children (Iraqi: 0.1%; Afghan: 0.12%) were reported to have abnormal tuberculosis test findings, less than 1% (Iraqi: 0.3%; Afghan: 0.7%) had hearing abnormalities, and about 4% (Iraqi: 6.0% Afghan: 2.9%) had vision abnormalities, with a greater prevalence of vision abnormalities noted in Iraqis (OR: 1.9, 95% CI 1.6-2.2, p <0.001). Seizure disorders were noted in 46 (0.3%) children, with Iraqis more likely to have a seizure disorder (OR: 7.6, 95% CI 3.8-15.0, p < 0.001). On average, children from Afghanistan had a lower mean height-for-age z-score (Iraqi: -0.28; Afghan: -0.68). Only the data quality assessment for height for age for children >/=5 years fell within WHO recommendations. Limitations included the inability to obtain all SIVH records and self-reported medical history of noncommunicable diseases. CONCLUSION: In this investigation, we found that less than 1% of SIV children were reported to have abnormal tuberculosis test findings and 4% of SIV children had reported vision abnormalities. Domestic providers caring for SIVH should follow the US Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees, including an evaluation for malnutrition. Measurement techniques and anthropometric equipment used in panel site clinics should be assessed, and additional training in measurement techniques should be considered. Future analyses could further explore the health of SIV children after resettlement in the US.

    • Health Behavior and Risk

    • Health Economics
      1. Cost-effectiveness and budgetary impact of hepatitis C virus testing, treatment, and linkage to care in US prisonsexternal icon
        Assoumou SA, Tasillo A, Vellozzi C, Eftekhari Yazdi G, Wang J, Nolen S, Hagan L, Thompson W, Randall LM, Strick L, Salomon JA, Linas BP.
        Clin Infect Dis. 2020 Mar 17;70(7):1388-1396.
        BACKGROUND: Hepatitis C virus (HCV) testing and treatment uptake in prisons remains low. We aimed to estimate clinical outcomes, cost-effectiveness (CE), and budgetary impact (BI) of HCV testing and treatment in United States (US) prisons or linkage to care at release. METHODS: We used individual-based simulation modeling with healthcare and Department of Corrections (DOC) perspectives for CE and BI analyses, respectively. We simulated a US prison cohort at entry using published data and Washington State DOC individual-level data. We considered permutations of testing (risk factor based, routine at entry or at release, no testing), treatment (if liver fibrosis stage >/=F3, for all HCV infected or no treatment), and linkage to care (at release or no linkage). Outcomes included quality-adjusted life-years (QALY); cases identified, treated, and cured; cirrhosis cases avoided; incremental cost-effectiveness ratios; DOC costs (2016 US dollars); and BI (healthcare cost/prison entrant) to generalize to other states. RESULTS: Compared to "no testing, no treatment, and no linkage to care," the "test all, treat all, and linkage to care at release" model increased the lifetime sustained virologic response by 23%, reduced cirrhosis cases by 54% at a DOC annual additional cost of $1440 per prison entrant, and would be cost-effective. At current drug prices, targeted testing and liver fibrosis-based treatment provided worse outcomes at higher cost or worse outcomes at higher cost per QALY gained. In sensitivity analysis, fibrosis-based treatment restrictions were cost-effective at previous higher drug costs. CONCLUSIONS: Although costly, widespread testing and treatment in prisons is considered to be of good value at current drug prices.

      2. Comparative economic analysis of strategies for Japanese encephalitis vaccination of U.S. travelersexternal icon
        Carias C, Hills SL, Kahn EB, Adhikari BB, Fischer M, Meltzer MI.
        Vaccine. 2020 Mar 10.
        BACKGROUND: Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories. METHODS: We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend >/=1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending >/=20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs. RESULTS: The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios. CONCLUSION: Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios.

      3. Currently, the Advisory Committee on Immunization Practices recommends one-time tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination for all adults 19 years and older. This study is designed to evaluate the cost-effectiveness of Tdap vaccination for Tdap-eligible adults aged 19 through 85 in the United States. A cost-effectiveness model was developed to compute costs and health outcomes associated with pertussis among 100,000 Tdap-eligible persons of each age cohort. From the societal perspective, the cost per quality-adjusted life-year (QALY) saved was evaluated under the vaccination scenarios. Sensitivity analyses were also conducted to evaluate the impacts of changes in key variables. All costs were adjusted to 2018 US$ with an annual discount rate of 3% applied to costs and outcomes. The incremental cost-effectiveness ratios (ICERs) for vaccinating US adults aged 19 to 85 with Tdap ranged from $248,000/QALY to $900,000/QALY. The lowest cost per QALY was found to be $248,000 for the age 65 cohort, followed by $332,000 for the cohort of age 19, and followed by $477,000 for the age 50 cohort. Sensitivity analysis showed the most dramatic changes in ICER occurred when changing the underreporting factor, vaccine effectiveness and vaccination costs. While Tdap vaccination may not be as cost effective as predicted earlier, it remains the best available preventive measure against pertussis. Further investigation of the true burden of pertussis disease among adults and the effectiveness of Tdap vaccination in this population is needed to better estimate the impact of Tdap vaccination.

      4. Out-of-pocket costs and HIV pre-exposure prophylaxis persistence in a US multicity demonstration projectexternal icon
        Furukawa NW, Schneider JA, Coleman ME, Wiener JB, Shrestha RK, Smith DK.
        Health Serv Res. 2020 Mar 20.
        OBJECTIVE: To evaluate whether out-of-pocket (OOP) costs reduced HIV pre-exposure prophylaxis (PrEP) persistence. DATA SOURCE: Participants from five urban community health centers (CHCs) in four US cities enrolled in a PrEP demonstration project from September 2014 to August 2017. STUDY DESIGN: Patients initiating PrEP were followed quarterly until they withdrew from PrEP care or the study ended. Self-reported OOP medication and clinic visit costs were assessed by semiannual questionnaires. Persistence was defined as the time from study enrollment to the last visit after which two subsequent 3-month visits were missed. Multivariable Cox proportional hazard regression was used to assess the effect of demographics, insurance, and OOP costs on PrEP persistence. PRINCIPAL FINDINGS: Among 918 participants with OOP cost data, the average quarterly OOP cost was $34 (median: $5, IQR: $0-$25). Participants who were men, White, employed, completed college, and had commercial insurance had higher OOP costs. Higher OOP costs were not associated with lower PrEP persistence by Cox proportional hazards regression (adjusted hazard ratio = 1.00 per $50 increase, 95% CI = 0.97, 1.02). CONCLUSION: Among patients receiving care from these urban CHCs, OOP costs were low and did not undermine PrEP persistence.


    • Healthcare Associated Infections
      1. Quantifying the roles of vomiting, diarrhea, and residents vs. staff in norovirus transmission in U.S. nursing home outbreaksexternal icon
        Adams C, Young D, Gastanaduy PA, Paul P, Marsh Z, Hall AJ, Lopman BA.
        PLoS Comput Biol. 2020 Mar 25;16(3):e1007271.
        The role of individual case characteristics, such as symptoms or demographics, in norovirus transmissibility is poorly understood. Six nursing home norovirus outbreaks occurring in South Carolina, U.S. from 2014 to 2016 were examined. We aimed to quantify the contribution of symptoms and other case characteristics in norovirus transmission using the reproduction number (REi) as an estimate of individual case infectivity and to examine how transmission changes over the course of an outbreak. Individual estimates of REi were calculated using a maximum likelihood procedure to infer the average number of secondary cases generated by each case. The associations between case characteristics and REi were estimated using a weighted multivariate mixed linear model. Outbreaks began with one to three index case(s) with large estimated REi's (range: 1.48 to 8.70) relative to subsequent cases. Of the 209 cases, 155 (75%) vomited, 164 (79%) had diarrhea, and 158 (76%) were nursing home residents (vs. staff). Cases who vomited infected 2.12 (95% CI: 1.68, 2.68) times the number of individuals as non-vomiters, cases with diarrhea infected 1.39 (95% CI: 1.03, 1.87) times the number of individuals as cases without diarrhea, and resident-cases infected 1.53 (95% CI: 1.15, 2.02) times the number of individuals as staff-cases. Index cases tended to be residents (vs. staff) who vomited and infected considerably more secondary cases compared to non-index cases. Results suggest that individuals, particularly residents, who vomit are more infectious and tend to drive norovirus transmission in U.S. nursing home norovirus outbreaks. While diarrhea also plays a role in norovirus transmission, it is to a lesser degree than vomiting in these settings. Results lend support for prevention and control measures that focus on cases who vomit, particularly if those cases are residents.

      2. Evaluation of clinicians' knowledge, attitudes, and planned behaviors related to an intervention to improve acute respiratory infection managementexternal icon
        Hruza HR, Velasquez T, Madaras-Kelly KJ, Fleming-Dutra KE, Samore MH, Butler JM.
        Infect Control Hosp Epidemiol. 2020 Mar 17:1-8.
        BACKGROUND: Acute respiratory tract infections (ARIs) are commonly diagnosed and major drivers of antibiotic prescribing. Clinician-focused interventions can reduce unnecessary antibiotic prescribing for ARIs. We elicited clinician feedback to design sustainable interventions to improve ARI management by understanding the mental framework of clinicians surrounding antibiotic prescribing within Veterans' Health Administration clinics. METHODS: We conducted one-on-one interviews with clinicians (n = 20) from clinics targeted for intervention at 5 facilities. The theory of planned behavior guided interview questions. Interviews were audio recorded and transcribed for qualitative analysis. An iterative coding approach identified 6 themes. RESULTS: Emergent themes: (1) barriers to appropriate prescribing are multifactorial and include challenges of behavior change; (2) antibiotic prescribing decisions are perceived as autonomous yet, diagnostic uncertainty and perceptions of patient demand can make prescribing decisions difficult; (3) clinicians perceive variation in peer prescribing practices and influences; (4) clinician-focused interventions are valuable if delivered with sensitivity; (5) communication strategies for educating patients are preferred to a shared decisions process; and (6) team standardization of practice and communication are key to facilitate appropriate prescribing. Clinicians perceived audit-and-feedback with peer comparison, academic detailing, and enhanced patient communication strategies as viable approaches to improving appropriate prescribing. CONCLUSION: Implementation strategies that enable clinicians to overcome diagnostic uncertainty, perceived patient demand, and improve patient education are desired. Implementation strategies were welcomed, and some were more readily accepted (eg, audit feedback) than others (eg, shared decision making). Implementation strategies should address clinicians' perceptions of antibiotic prescribing practices and should enhance their patient communication skills.

      3. Acrophialophora levis brain abscess in a kidney transplant patient: A case report and review of the literatureexternal icon
        Modlin CE, Collins LF, Burd EM, Lockhart SR, Marshall Lyon G.
        Med Mycol Case Rep. 2020 ;28:12-15.
        We report the first case of Acrophialophora levis causing cerebral phaeohyphomycosis in a solid organ transplantation recipient. A. levis is a rare cause of invasive dematiaceous fungal infection among immunocompromised persons. We describe the clinical course of a kidney transplant patient who presented with acute hemiplegia due to a brain abscess from which A. levis was isolated. We review published clinical cases attributed to Acrophialophora species infection and discuss current limitations in its identification, diagnosis and management.

      4. National Healthcare Safety Network Standardized Antimicrobial Administration Ratios (SAARs): A progress report and risk modeling update using 2017 dataexternal icon
        O'Leary EN, Edwards JR, Srinivasan A, Neuhauser MM, Webb AK, Soe MM, Hicks LA, Wise W, Wu H, Pollock DA.
        Clin Infect Dis. 2020 Mar 26.
        BACKGROUND: The Standardized Antimicrobial Administration Ratio (SAAR) is a risk-adjusted metric of antimicrobial use (AU) developed by the CDC in 2015 as a tool for hospital antimicrobial stewardship programs (ASPs) to track and compare AU to a national benchmark. In 2018, CDC updated the SAAR by expanding the locations and antimicrobial categories for which SAARs can be calculated and by modeling adult and pediatric locations separately. METHODS: We identified eligible patient care locations and defined SAAR antimicrobial categories. Predictive models were developed for eligible adult and pediatric patient care locations using negative binomial regression applied to nationally aggregated AU data from locations reporting >/=9 months of 2017 data to the National Healthcare Safety Network (NHSN). RESULTS: 2017 baseline SAAR models were developed for seven adult and eight pediatric SAAR antimicrobial categories using data reported from 2,156 adult and 170 pediatric locations across 457 hospitals. The inclusion of step-down units and general hematology-oncology units in adult 2017 baseline SAAR models and the addition of SAARs for narrow-spectrum beta-lactam agents, antifungals predominantly used for invasive candidiasis, antibacterial agents posing the highest risk for Clostridioides difficile infection, and azithromycin (pediatrics only) expand the role SAARs can play in ASP efforts. Final risk-adjusted models are used to calculate predicted antimicrobial days, the denominator of the SAAR, for 40 SAAR types displayed in NHSN. CONCLUSIONS: SAARs can be used as a metric to prompt investigation into potential overuse or underuse of antimicrobials and to evaluate the effectiveness of ASP interventions.

      5. The p-traps of hospital handwashing sinks represent a potential reservoir for antimicrobial-resistant organisms of major public health concern, such as carbapenemase-producing KPC+ Klebsiella pneumoniae (CPKP). Bacteriophages have reemerged as potential biocontrol agents, particularly against biofilm-associated, drug-resistant microorganisms. The primary objective of our study was to formulate a phage cocktail capable of targeting a CPKP strain (CAV1016) at different stages of colonization within polymicrobial drinking water biofilms using a CDC biofilm reactor (CBR) p-trap model. A cocktail of four CAV1016 phages, all exhibiting depolymerase activity, were isolated from untreated wastewater using standard methods. Biofilms containing Pseudomonas aeruginosa, Micrococcus luteus, Stenotrophomonas maltophilia, Elizabethkingia anophelis, Cupriavidus metallidurans, and Methylobacterium fujisawaense were established in the CBR p-trap model for a period of 28 d. Subsequently, CAV1016 was inoculated into the p-trap model and monitored over a period of 21 d. Biofilms were treated for 2 h at either 25 °C or 37 °C with the phage cocktail (109 PFU/ml) at 7, 14, and 21 d post-inoculation. The effect of phage treatment on the viability of biofilm-associated CAV1016 was determined by plate count on m-Endo LES agar. Biofilm heterotrophic plate counts (HPC) were determined using R2A agar. Phage titers were determined by plaque assay. Phage treatment reduced biofilm-associated CAV1016 viability by 1 log10 CFU/cm2 (p &lt; 0.05) at 7 and 14 d (37 ℃) and 1.4 log10 and 1.6 log10 CFU/cm2 (p &lt; 0.05) at 7 and 14 d, respectively (25 ℃). No significant reduction was observed at 21 d post-inoculation. Phage treatment had no significant effect on the biofilm HPCs (p &gt; 0.05) at any time point or temperature. Supplementation with a non-ionic surfactant appears to enhance phage association within biofilms. The results of this study suggest the potential of phages to control CPKP and other carbapenemase-producing organisms associated with microbial biofilms in the healthcare environment.

      6. Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as 'reference standard.'

    • Immunity and Immunization
      1. The potential role of using vaccine patches to induce immunity: platform and pathways to innovation and commercializationexternal icon
        Badizadegan K, Goodson JL, Rota PA, Thompson KM.
        Expert Rev Vaccines. 2020 Feb;19(2):175-194.
        Introduction: In the last two decades, the evidence related to using vaccine patches with multiple short projections (</=1 mm) to deliver vaccines through the skin increased significantly and demonstrated their potential as an innovative delivery platform.Areas covered: We review the vaccine patch literature published in English as of 1 March 2019, as well as available information from key stakeholders related to vaccine patches as a platform. We identify key research topics related to basic and translational science on skin physical properties and immunobiology, patch development, and vaccine manufacturing.Expert opinion: Currently, vaccine patch developers continue to address some basic science and other platform issues in the context of developing a potential vaccine patch presentation for an existing or new vaccine. Additional clinical data and manufacturing experience could shift the balance toward incentivizing existing vaccine manufactures to further explore the use of vaccine patches to deliver their products. Incentives for innovation of vaccine patches differ for developed and developing countries, which will necessitate different strategies (e.g. public-private partnerships, push, or pull mechanisms) to support the basic and applied research needed to ensure a strong evidence base and to overcome translational barriers for vaccine patches as a delivery platform.

      2. Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic dataexternal icon
        Chaguza C, Heinsbroek E, Gladstone RA, Tafatatha T, Alaerts M, Peno C, Cornick JE, Musicha P, Bar-Zeev N, Kamng'ona A, Kadioglu A, McGee L, Hanage WP, Breiman RF, Heyderman RS, French N, Everett DB, Bentley SD.
        Clin Infect Dis. 2020 Mar 17;70(7):1294-1303.
        BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden. METHODS: We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes. RESULTS: In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons >/=5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs)-namely 7C, 15B/C, and 23A-in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV. CONCLUSIONS: We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV.

      3. Assessment of immunity to polio among Rohingya children in Cox's Bazar, Bangladesh, 2018: A cross-sectional surveyexternal icon
        Estivariz CF, Bennett SD, Lickness JS, Feldstein LR, Weldon WC, Leidman E, Ehlman DC, Khan MF, Adhikari JM, Hasan M, Billah MM, Oberste MS, Alamgir AS, Flora MD.
        PLoS Med. 2020 Mar;17(3):e1003070.
        BACKGROUND: We performed a cross-sectional survey in April-May 2018 among Rohingya in Cox's Bazar, Bangladesh, to assess polio immunity and inform vaccination strategies. METHODS AND FINDINGS: Rohingya children aged 1-6 years (younger group) and 7-14 years (older group) were selected using multi-stage cluster sampling in makeshift settlements and simple random sampling in Nayapara registered camp. Surveyors asked parents/caregivers if the child received any oral poliovirus vaccine (OPV) in Myanmar and, for younger children, if the child received vaccine in any of the 5 campaigns delivering bivalent OPV (serotypes 1 and 3) conducted during September 2017-April 2018 in Cox's Bazar. Dried blood spot (DBS) specimens were tested for neutralizing antibodies to poliovirus types 1, 2, and 3 in 580 younger and 297 older children. Titers >/= 1:8 were considered protective. Among 632 children (335 aged 1-6 years, 297 aged 7-14 years) enrolled in the study in makeshift settlements, 51% were male and 89% had arrived after August 9, 2017. Among 245 children (all aged 1-6 years) enrolled in the study in Nayapara, 54% were male and 10% had arrived after August 9, 2017. Among younger children, 74% in makeshift settlements and 92% in Nayapara received >3 bivalent OPV doses in campaigns. Type 1 seroprevalence was 85% (95% CI 80%-89%) among younger children and 91% (95% CI 86%-95%) among older children in makeshift settlements, and 92% (88%-95%) among younger children in Nayapara. Type 2 seroprevalence was lower among younger children than older children in makeshift settlements (74% [95% CI 68%-79%] versus 97% [95% CI 94%-99%], p < 0.001), and was 69% (95% CI 63%-74%) among younger children in Nayapara. Type 3 seroprevalence was below 75% for both age groups and areas. The limitations of this study are unknown routine immunization history and poor retention of vaccination cards. CONCLUSIONS: Younger Rohingya children had immunity gaps to all 3 polio serotypes and should be targeted by future campaigns and catch-up routine immunization. DBS collection can enhance the reliability of assessments of outbreak risk and vaccination strategy impact in emergency settings.

      4. Vaccination coverage survey and seroprevalence among forcibly displaced Rohingya children, Cox's Bazar, Bangladesh, 2018: A cross-sectional studyexternal icon
        Feldstein LR, Bennett SD, Estivariz CF, Cooley GM, Weil L, Billah MM, Uzzaman MS, Bohara R, Vandenent M, Adhikari JM, Leidman E, Hasan M, Akhtar S, Hasman A, Conklin L, Ehlman D, Alamgir A, Flora MS.
        PLoS Med. 2020 Mar;17(3):e1003071.
        BACKGROUND: During August 2017-January 2018, more than 700,000 forcibly displaced Rohingyas crossed into Cox's Bazar, Bangladesh. In response to measles and diphtheria cases, first documented in September and November 2017, respectively, vaccination campaigns targeting children <15 years old were mobilized during September 2017-March 2018. However, in a rapidly evolving emergency situation, poor sanitation, malnutrition, overcrowding, and lack of access to safe water and healthcare can increase susceptibility to infectious diseases, particularly among children. We aimed to estimate population immunity to vaccine-preventable diseases (VPDs) after vaccination activities in the camps to identify any remaining immunity gaps among Rohingya children. METHODS AND FINDINGS: We conducted a cross-sectional serologic and vaccination coverage survey in Nayapara Registered Refugee Camp ("Nayapara") and makeshift settlements (MSs) April 28, 2018 to May 31, 2018, among 930 children aged 6 months to 14 years. MSs are informal, self-settled areas with a population of more than 850,000, the majority of whom arrived after August 2017, whereas Nayapara is a registered camp and has better infrastructure than MSs, including provision of routine immunization services. Households were identified using simple random sampling (SRS) in Nayapara and multistage cluster sampling in MSs (because household lists were unavailable). Dried blood spots (DBSs) were collected to estimate seroprotection against measles, rubella, diphtheria, and tetanus, using Luminex multiplex bead assay (MBA). Caregiver interviews assessed vaccination campaign participation using vaccination card or recall. In Nayapara, 273 children aged 1 to 6 years participated; 46% were female and 88% were registered refugees. In MSs, 358 children aged 1 to 6 years and 299 children aged 7 to 14 years participated; 48% of all children in MSs were female, and none were registered refugees. In Nayapara, estimated seroprotection among 1- to 6-year-olds was high for measles, rubella, diphtheria, and tetanus (91%-98%; 95% confidence interval [CI] 87%-99%); children >6 years were not assessed. In MSs, measles seroprotection was similarly high among 1- to 6-year-olds and 7- to 14-year-olds (91% [95% CI 86%-94%] and 99% [95% CI 96%-100%], respectively, p < 0.001). Rubella and diphtheria seroprotection in MSs were significantly lower among 1- to 6-year-olds (84% [95% CI 79%-88%] and 63% [95% CI 56%-70%]) compared to 7- to 14-year-olds (96% [95% CI 90%-98%] and 77% [95% CI 69%-84%]) (p < 0.001). Tetanus seroprevalence was similar among 1- to 6-year-olds and 7- to 14-year-olds (76% [95% CI 69%-81%] and 84% [95% CI 77%-89%], respectively; p = 0.07). Vaccination campaign coverage was consistent with seroprotection in both camps. However, nonresponse, the main limitation of the study, may have biased the seroprotection and campaign coverage results. CONCLUSIONS: In this study, we observed that despite multiple vaccination campaigns, immunity gaps exist among children in MSs, particularly for diphtheria, which requires serial vaccinations to achieve maximum protection. Therefore, an additional tetanus-diphtheria campaign may be warranted in MSs to address these remaining immunity gaps. Rapid scale-up and strengthening of routine immunization services to reach children and to deliver missed doses to older children is also critically needed to close immunity gaps and prevent future outbreaks.

      5. Background We conducted a matched case-control study in China during the 2013/14-2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years.Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of >/=1 dose of influenza vaccine during the immediate prior season.Results In total, 4,185 case-control pairs were analyzed. Among children 6-35 months, VE for current season dose(s) across the three seasons during 2013/14-2015/16 were 59% (95% Confidence Interval: 44-71%), 12% (-11%,30%), 54% (32-69%); among unprimed children 6-35 months, VE for 1 vs 2 current season doses were 45% (8-67%) vs 65% (46-78%), -2% (-53%,32%) vs 19% (-11%,40%), and 37% (-24%,68%) vs 61% (32-78%). Among children aged 3-8 years, VE for current season dose(s) across study seasons were 62% (36-78%), 43% (22-58%), 32% (1-53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children.Conclusion Findings support utility of providing second dose ("booster dose") of seasonal influenza vaccine to unprimed children aged 6-35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3-8 years in China.

      6. Association between vaccine exemption policy change in California and adverse event reportingexternal icon
        Hause AM, Hesse EM, Ng C, Marquez P, McNeil MM, Omer SB.
        Pediatr Infect Dis J. 2020 Mar 5.
        BACKGROUND: California Senate Bill 277 (SB277) eliminated non-medical immunization exemptions. Since its introduction on February 19, 2015, the rate of medical exemptions in the state has increased. Filing a report to Vaccine Adverse Event Reporting System (VAERS) may be perceived as helpful in applying for a medical exemption. Our objective was to describe trends in reporting to VAERS from California coincident with introduction of SB277. METHODS: This was a retrospective study of Californian children <18 years for whom a VAERS report was submitted between June 1, 2011 and July 31, 2018. VAERS is a national, passive, vaccine safety surveillance program co-managed by Centers for Disease Control and Prevention and FDA. The main outcomes were the proportion of VAERS reports submitted by parents (vs. other reporter types), time from immunization to VAERS report (reporting time), and adverse event type. We also performed spatial analysis, mapping reports pre- and post-mandate by county. RESULTS: We identified 6703 VAERS reports from California during the study period. The proportion of reports received from parents increased after implementation of SB277, from 14% to 23%. The median reporting time by parents increased from 9 days in 2013-2014 to 31 days in 2016-2017. After the introduction of SB277, we observed an increase in reports describing behavioral and developmental symptoms among reports submitted >6 months after immunization. CONCLUSIONS: These recent changes in reporting patterns coincident with the introduction of SB277 may indicate that more parents are using VAERS to assist in applying for a medical exemption for their child.

      7. Development of a new oral poliovirus vaccine for the eradication end game using codon deoptimizationexternal icon
        Konopka-Anstadt JL, Campagnoli R, Vincent A, Shaw J, Wei L, Wynn NT, Smithee SE, Bujaki E, Te Yeh M, Laassri M, Zagorodnyaya T, Weiner AJ, Chumakov K, Andino R, Macadam A, Kew O, Burns CC.
        NPJ Vaccines. 2020 ;5:26.
        Enormous progress has been made in global efforts to eradicate poliovirus, using live-attenuated Sabin oral poliovirus vaccine (OPV). However, as the incidence of disease due to wild poliovirus has declined, vaccine-derived poliovirus (VDPV) has emerged in areas of low-vaccine coverage. Coordinated global cessation of routine, type 2 Sabin OPV (OPV2) use has not resulted in fewer VDPV outbreaks, and continued OPV use in outbreak-response campaigns has seeded new emergences in low-coverage areas. The limitations of existing vaccines and current eradication challenges warranted development of more genetically stable OPV strains, most urgently for OPV2. Here, we report using codon deoptimization to further attenuate Sabin OPV2 by changing preferred codons across the capsid to non-preferred, synonymous codons. Additional modifications to the 5' untranslated region stabilized known virulence determinants. Testing of this codon-deoptimized new OPV2 candidate (nOPV2-CD) in cell and animal models demonstrated that nOPV2-CD is highly attenuated, grows sufficiently for vaccine manufacture, is antigenically indistinguishable from Sabin OPV2, induces neutralizing antibodies as effectively as Sabin OPV2, and unlike Sabin OPV2 is genetically stable and maintains an attenuation phenotype. In-human clinical trials of nOPV2-CD are ongoing, with potential for nOPV strains to serve as critical vaccine tools for achieving and maintaining polio eradication.

      8. Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective reviewexternal icon
        Lai J, Nguyen C, Tabwaia B, Nikuata A, Baueri N, Timeon E, Diaaldeen M, Iuta T, Ozturk MH, Moore A, Hall A, Nyambat B, Davis S, Rahman A, Erasmus W, Fox K, Russell F.
        BMC Infect Dis. 2020 Mar 12;20(1):207.
        BACKGROUND: Kiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken. METHODS: Inpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010-December 2013 (pre-rotavirus vaccine) and January 2016-September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction. RESULTS: The incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12.8% vs. 7.2%, p < 0.001) and all-cause under-five mortality (15.9% vs. 5.7%, p = 0.006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction. CONCLUSIONS: AGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.

      9. Qualitative variation among commercial immunoassays to detect measles-specific IgGexternal icon
        Latner DR, Sowers SB, Anthony K, Colley H, Badeau C, Coates J, Wong P, Fakile Y, Interiano C, Pannell KB, Leung-Pineda V, Patel MM, Rota PA, Limbago BM, Hickman CJ.
        J Clin Microbiol. 2020 Apr 1.
        Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary re-vaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization (PRN), the gold standard method and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG negative sera and for samples with intermediate to high levels of IgG. False negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody.

      10. Evaluation of non-continuous temperature-monitoring practices for vaccine storage units: a Monte Carlo simulation studyexternal icon
        Leidner AJ, Lee CE, Tippins A, Messonnier ML, Stevenson JM.
        Journal of Public Health. 2020 .
        Objectives: Evaluate different non-continuous temperature-monitoring practices for detection of out-of-range temperatures (above or below the recommended temperature range of 2-8 degreeC for refrigeration units), which are called excursions, within vaccine storage units. Method(s): Simulations based on temperature data collected by 243 digital data loggers operated in vaccine storage units at health-care providers who participated in a CDC-sponsored continuous temperature monitoring pilot project, from 2012 to 2015. In the primary analysis, we evaluate: (1) twice-daily current temperature readings without minimum and maximum readings (min/max), (2) twice-daily current temperature readings with once-daily min/max, and (3) twice-daily current temperature readings with twice-daily min/max. Result(s): Recording current temperature twice daily without min/max resulted in the detection of 4.8-6.4% of the total number of temperature excursions. When min/max readings were introduced, the percentage of detected temperature excursions increased to 27.8-96.6% with once-daily min/max and to 34.8-96.7% with twice-daily min/max. Conclusion(s): Including min/max readings improves the ability of a temperature monitoring practice to detect temperature excursions. No combination of the non-continuous temperature monitoring practices were able to consistently detect all simulated temperature excursions.

      11. Qualitative insights into reasons for missed opportunities for vaccination in Kenyan health facilitiesexternal icon
        Li AJ, Tabu C, Shendale S, Okoth PO, Sergon K, Maree E, Mugoya IK, Machekanyanga Z, Onuekwusi IU, Ogbuanu IU.
        PLoS One. 2020 ;15(3):e0230783.
        BACKGROUND: In 2016, Kenya conducted a study of missed opportunities for vaccination (MOV)-when eligible children have contact with the health system but are not fully vaccinated-to explore some of the reasons for persistent low vaccination coverage. This paper details the qualitative findings from that assessment. METHODS: Using the World Health Organization MOV methodology, teams conducted focus group discussions among caregivers and health workers and in-depth interviews of key informants in 10 counties in Kenya. Caregivers of children <24 months of age visiting the selected health facilities on the day of the assessment were requested to participate in focus group discussions. Health workers were purposively sampled to capture a broad range of perspectives. Key informants were selected based on their perceived insight on immunization services at the county, sub-county, or health facility level. RESULTS: Six focus group discussions with caregivers, eight focus group discussions with health workers, and 35 in-depth interviews with key informants were completed. In general, caregivers had positive attitudes toward healthcare and vaccination services, but expressed a desire for increased education surrounding vaccination. In order to standardize vaccination checks at all health facility visits, health workers and key informants emphasized the need for additional trainings for all staff members on immunization. Health workers and key informants also highlighted the negative impact of significant understaffing in health facilities, and the persistent challenge of stock-outs of vaccines and vaccination-related supplies. CONCLUSIONS: Identified factors that could contribute to MOV include a lack of knowledge surrounding vaccination among caregivers and health workers, inadequate number of health workers, and stock-outs of vaccines or vaccination-related materials. In addition, vaccination checks outside of vaccination visits lacked consistency, leading to MOV in non-vaccinating departments. Qualitative assessments could provide a starting point for understanding and developing interventions to address MOV in other countries.

      12. Evolving epidemiology of poliovirus serotype 2 following withdrawal of the type 2 oral poliovirus vaccineexternal icon
        Macklin GR, O'Reilly KM, Grassly NC, Edmunds WJ, Mach O, Santhana Gopala Krishnan R, Voorman A, Vertefeuille JF, Abdelwahab J, Gumede N, Goel A, Sosler S, Sever J, Bandyopadhyay AS, Pallansch MA, Nandy R, Mkanda P, Diop OM, Sutter RW.
        Science. 2020 Mar 19.
        While there have been no cases of type-2 wild poliovirus for over 20 years, transmission of type-2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the type-2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all poliovirus type 2. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimate the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet, our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. The novel OPV2 is urgently required, alongside a contingency strategy if this vaccine does not materialize or perform as anticipated.

      13. Impact of media reports regarding influenza vaccine on obstetricians' vaccination practicesexternal icon
        O'Leary ST, Cataldi JR, Lindley MC, Hurley LP, Riley LE, Brtnikova M, Crane LA, Beaty B, Stokley S, Fisher A, Kempe A.
        Vaccine. 2020 Mar 21.
        BACKGROUND: In 2017, three media stories regarding influenza vaccine may have impacted obstetricians' (OB) influenza vaccination practices: reports of reduced influenza vaccine effectiveness, a severe influenza season, and a possible increased risk of miscarriage among pregnant women receiving 2009 H1N1 vaccine in the 1st trimester who had received H1N1 vaccine the previous season (later disproven). OBJECTIVE: Describe OB's: (1) awareness of; (2) attitudes and experiences related to; and (3) reported alterations in practice as a result of these reports. METHODS: A survey among a nationally representative sample of OBs April to June 2018. RESULTS: Response rate was 65% (302/468). 88% of OBs were "very aware" of the severe season, 74% of lower effectiveness, and 25% of the miscarriage study (47% "completely unaware" of miscarriage study). Among those aware, 58%, 57%, and 16% reported >/=10% of pregnant patients initiated discussions about the severe season, lower effectiveness, and miscarriage study, respectively. Most (83%) agreed reports about increased severity increased their enthusiasm for recommending influenza vaccine; fewer agreed reports about the miscarriage study (18%) and lower vaccine effectiveness (12%) decreased their enthusiasm for recommending influenza vaccine. Providers were more likely to initiate discussion with patients about increased severity of the season than the other reports. However, 35% agreed the miscarriage study reports increased their concerns about influenza vaccine safety; 18% (n = 48) reported changing the way they recommended influenza vaccine. Of those, 17 (6% of all respondents) reported not recommending influenza vaccine to women during the 1st trimester and 26 (10% of all respondents) recommended it but were willing to delay until the 2nd trimester. CONCLUSIONS: During a season in which media stories could have influenced OB influenza vaccination behaviors in different directions, reports underscoring importance of influenza vaccine may have had more impact on OBs' recommendations than reports questioning vaccine safety or effectiveness.

      14. Drivers and barriers of vaccine acceptance among pregnant women in Kenyaexternal icon
        Otieno NA, Otiato F, Nyawanda B, Adero M, Wairimu WN, Ouma D, Atito R, Wilson A, Gonzalez-Casanova I, Malik FA, Widdowson MA, Omer SB, Chaves SS, Verani JR.
        Hum Vaccin Immunother. 2020 Mar 25:1-9.
        Maternal vaccination coverage remains suboptimal globally and is lowest in low- and middle-income countries. Attitudes toward maternal vaccines have been characterized in middle-high income settings, however data from African countries are limited. We assessed drivers and barriers of vaccine acceptance among pregnant women in Kenya. We conducted a cross-sectional survey among pregnant women aged 15-49 y. We enrolled a convenience sample of women presenting for antenatal care at seven health-care facilities in four diverse counties (Nairobi, Mombasa, Marsabit, Siaya) of Kenya and from the community in two counties (Nairobi, Siaya). We described frequencies of socio-demographic characteristics of participants and their knowledge, attitudes, and beliefs regarding maternal vaccination. We enrolled 604 pregnant women with a median age of 26.5 y, of whom 48.2% had primary education or less. More than 95% agreed that maternal vaccines are "important for my health" and that getting vaccinated is "a good way to protect myself from disease". The most commonly cited reason in favor of maternal vaccination was disease prevention (53.2%). Fear of side effects to mother/baby (15.1%) was the most frequently reported potential barrier. Influenza vaccine is not in routine use in Kenya; however, 77.8% reported willingness to accept influenza vaccination during pregnancy. Maternal vaccination is well accepted among Kenyan pregnant women. We identified the provision of adequate vaccine information and addressing safety concerns as opportunities to improve maternal vaccine uptake. The expressed willingness to receive a vaccine not currently in routine use bodes well for implementation of new maternal vaccines in Kenya.

      15. In March 2019, a group of global health leaders with expertise in influenza, vaccinology and pandemic preparedness was convened for a meeting titled "Shaping Meeting to explore the value of a coordinated work plan for epidemic and pandemic influenza vaccine preparedness." Influenza epidemics occur annually in every country in the world, resulting in significant global burden of illness and deaths. While every country is effected, most deaths and severe disease occur in low- and lower middle-income countries (LIC and LMIC). Influenza immunization programs that limit the burden of disease, deaths, and reduce economic impact are a fundamental public health intervention for seasonal epidemics. In addition, they provide the experience, systems and infrastructure for the timely and efficient use of vaccines and other medical countermeasures critical for effective pandemic responses. Pandemic influenza response activities, including vaccination efforts, will be most effective if used and practiced regularly. Consequently, countries with seasonal influenza prevention and control programs should be better prepared for, and have more effective pandemic responses than countries without such programs. A decade after the 2009 pandemic, despite ongoing prevention efforts, most LICs and LMICs still lack access to robust seasonal influenza immunization programs. Given this current state, meeting participants concluded that there is critical need to advance the expansion and strengthening of seasonal influenza immunization programs in LICs and LMICs not only to reduce the economic and public health effects of annual influenza epidemics, but also to increase preparedness to mitigate the threat of future pandemics and improve global heath security. Many government and private sectors, in a whole of government approach, need to be working together to support and advance countries' epidemic and pandemic influenza capacities preparedness objectives. Accomplishment of these objectives can be achieved with a coordinated work plan developed and guided by an alliance of international stakeholders, to include, among others, government, and nongovernment organization representation, civil society representatives, vaccine manufacturers, international organizations, and health security and influenza experts.

      16. Waning of measured influenza vaccine effectiveness over time: the potential contribution of leaky vaccine effectexternal icon
        Tokars JI, Patel MM, Foppa IM, Reed C, Fry AM, Ferdinands JM.
        Clin Infect Dis. 2020 Mar 28.
        INTRODUCTION: Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6%-11% per month during the 2011-12 to 2014-15 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees ("leaky") rather than complete protection in a subset of vaccinees. Since it is not known whether influenza vaccine is leaky, we simulated the 2011-12 to 2014-15 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE. METHODS: We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2 and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates. RESULTS: For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses. CONCLUSIONS: The leaky vaccine bias could account for some, but probably not all of the observed intra-seasonal decreases in mVE. These results underscore the need for strategies to deal with intra-seasonal vaccine effectiveness decline.

      17. New analytic approaches for analyzing and presenting polio surveillance data to supplement standard performance indicatorsexternal icon
        VanderEnde K, Voorman A, Khan S, Anand A, Snider CJ, Goel A, Wassilak S.
        Vaccine X. 2020 Apr 9;4:100059.
        Background: Sensitive surveillance for acute flaccid paralysis (AFP) allows for rapid detection of polio outbreaks and provides essential evidence to support certification of the eradication of polio. However, accurately assessing the sensitivity of surveillance systems can be difficult due to limitations in the reliability of available performance indicators, including the rate of detection of non-polio AFP and the proportion of adequate stool sample collection. Recent field reviews have found evidence of surveillance gaps despite indicators meeting expected targets. Methods: We propose two simple new approaches for AFP surveillance performance indicator analysis to supplement standard indicator analysis approaches commonly used by the Global Polio Eradication Initiative (GPEI): (1) using alternative groupings of low population districts in the country (spatial binning) and (2) flagging unusual patterns in surveillance data (surveillance flags analysis). Using GPEI data, we systematically compare AFP surveillance performance using standard indicator analysis and these new approaches. Results: Applying spatial binning highlights areas meeting surveillance indicator targets that do not when analyzing performance of low population districts. Applying the surveillance flags we find several countries with unusual data patterns, in particular age groups which are not well-covered by the surveillance system, and countries with implausible rates of adequate stool specimen collection. Conclusions: Analyzing alternate groupings of administrative units is a simple method to find areas where traditional AFP surveillance indicator targets are not reliably met. For areas where AFP surveillance indicator targets are met, systematic assessment of unusual patterns ('flags') can be a useful prompt for further investigation and field review.

    • Informatics
      1. Use of electronic medical records to conduct surveillance of malaria among Peace Corps volunteersexternal icon
        Davlantes E, Henderson S, Ferguson RW, Lewis L, Tan KR.
        JAMIA Open. 2019 01 Dec;2(4):498-504.
        Objective: The Peace Corps' disease surveillance for Peace Corps Volunteers (PCVs) was incorporated into an electronic medical records (EMR) system in 2015. We evaluated this EMR-based surveillance system, focusing particularly on malaria as it is deadly but preventable. Material(s) and Method(s): In 2016, we administered a survey to Peace Corps Medical Officers (PCMOs), who manage PCVs' medical care, and semistructured phone interviews to headquarters staff. We assessed the structure of the surveillance system and its utility to stakeholders, evaluated surveillance case definitions for malaria, and compared clinical information in the EMR for malaria cases captured by surveillance during the first half of 2016. Result(s): Of 131 PCMOs, 77 (59%) completed the survey. Of 53 respondents in malaria-endemic nations, 98% believed most PCVs contact them about possible malaria. Of 134 cases with a malaria clinical diagnosis in the EMR between January and August 2016, 58 (43% sensitivity) were reported to the surveillance system by PCMOs. The remaining cases in the surveillance system were added during data cleaning, which is time-intensive. Among the 48 malaria cases identified by surveillance between January and June 2016, positive predictive value was 67%. Discussion(s): Areas for improvement include streamlining PCMO documentation, refining case definitions, and improving data quality. With such improvements, surveillance data can be used to inform epidemiological analysis, clinical care, health education, and policy. Conclusion(s): The EMR is an important tool for malaria surveillance among PCVs and, with the refinements mentioned, could serve as a framework for other multinational organizations to monitor their staff.

    • Injury and Violence
      1. Tailored activation of middle-aged men to promote discussion of recent active suicide thoughts: A randomized controlled trialexternal icon
        Jerant A, Duberstein P, Kravitz RL, Stone DM, Cipri C, Franks P.
        J Gen Intern Med. 2020 Mar 17.
        PURPOSE: Middle-aged men are at high risk of suicide. While about half of those who kill themselves visit a primary care clinician (PCC) shortly before death, in current practice, few spontaneously disclose their thoughts of suicide during the visits, and PCCs seldom inquire about such thoughts. In a randomized controlled trial, we examined the effect of a tailored interactive computer program designed to encourage middle-aged men's discussion of suicide with PCCs. METHODS: We recruited men 35-74 years old reporting recent (within 4 weeks) active suicide thoughts from the panels of 42 PCCs (the unit of randomization) in eight offices within a single California health system. In the office before a visit, men viewed the intervention corresponding to their PCC's random group assignment: Men and Providers Preventing Suicide (MAPS) (20 PCCs), providing tailored multimedia promoting discussion of suicide thoughts, or control (22 PCCs), composed of a sleep hygiene video plus brief non-tailored text encouraging discussion of suicide thoughts. Logistic regressions, adjusting for patient nesting within physicians, examined MAPS' effect on patient-reported suicide discussion in the subsequent office visit. RESULTS: Sixteen of the randomized PCCs had no patients enroll in the trial. From the panels of the remaining 26 PCCs (12 MAPS, 14 control), 48 men (MAPS 21, control 27) were enrolled (a mean of 1.8 (range 1-5) per PCC), with a mean age of 55.9 years (SD 11.4). Suicide discussion was more likely among MAPS patients (15/21 [65%]) than controls (8/27 [35%]). Logistic regression showed men viewing MAPS were more likely than controls to discuss suicide with their PCC (OR 5.91, 95% CI 1.59-21.94; P = 0.008; nesting-adjusted predicted effect 71% vs. 30%). CONCLUSIONS: In addressing barriers to discussing suicide, the tailored MAPS program activated middle-aged men with active suicide thoughts to engage with PCCs around this customarily taboo topic.

      2. Introduction: Despite 49 states and the District of Columbia having seat belt laws that permit either primary or secondary enforcement, nearly half of persons who die in passenger vehicle crashes in the United States are unbelted. Monitoring seat belt use is important for measuring the effectiveness of strategies to increase belt use. Objective: Document self-reported seat belt use by state seat belt enforcement type and compare 2016 self-reported belt use with observed use and use among passenger vehicle occupant (PVO) fatalities. Methods: We analyzed the Behavioral Risk Factor Surveillance System (BRFSS) self-reported seat belt use data during 2011–2016. The Pearson correlation coefficient (r) was used to compare the 2016 BRFSS state estimates with observed seat belt use from state-based surveys and with unrestrained PVO fatalities from the Fatality Analysis Reporting System. Results: During 2011–2016, national self-reported seat belt use ranged from 86–88%. In 2016, national self-reported use (87%) lagged observed use (90%) by 3 percentage points. By state, the 2016 self-reported use ranged from 64% in South Dakota to 93% in California, Hawaii, and Oregon. Seat belt use averaged 7 percentage points higher in primary enforcement states (89%) than in secondary states (82%). Self-reported state estimates were strongly positively correlated with state observational estimates (r = 0.80) and strongly negatively correlated with the proportion of unrestrained PVO fatalities (r = −0.77). Conclusion: National self-reported seat belt use remained essentially stable during 2011–2016 at around 87%, but large variations existed across states. Practical Applications: If seat belt use in secondary enforcement states matched use in primary enforcement states for 2016, an additional 3.98 million adults would have been belted. Renewed attention to increasing seat belt use will be needed to reduce motor-vehicle fatalities. Self-reported and observational seat belt data complement one another and can aid in designing targeted and multifaceted interventions.

    • Laboratory Sciences
      1. Carbon nanotube (CNT)-induced pulmonary inflammation and fibrosis have been intensively observed and characterized in numerous animal studies in the past decade. Remarkably, CNT-induced fibrotic lesions highly resemble some human fibrotic lung diseases, such as IPF and pneumoconiosis, regarding disease development and pathological features. This notion leads to a serious concern over the health impact of CNTs in exposed human populations, considering the rapidly expanding production of CNT materials for diverse industrial and commercial applications, and meanwhile provides the rationale for exploring CNT-induced pathologic effects in the lung. Accumulating mechanistic understanding of CNT lung pathology at the systemic, cellular, and molecular levels has demonstrated the potential of using CNT-exposed animals as a new disease model for the studies on inflammation, fibrosis, and the interactions between these two disease states. Tissue microenvironment plays critical roles in maintaining homeostasis and physiological functions of organ systems. When aberrant microenvironment forms under intrinsic or extrinsic stimulation, tissue abnormality, organ dysfunction, and pathological outcomes are induced, resulting in disease development. In this article, the cellular and molecular alterations that are induced in tissue microenvironment and implicated in the initiation and progression of inflammation and fibrosis in CNT-exposed lungs, including effector cells, soluble mediators, and functional events exemplified by cell differentiation and extracellular matrix (ECM) modification, are summarized and discussed. This analysis would provide new insights into the mechanistic understanding of lung inflammation and fibrosis induced by CNTs, as well as the development of CNT-exposed animals as a new model for human lung diseases.

      2. The virulence of Escherichia coli O157:H7 isolates in mice depends on Shiga toxin type 2a (Stx2a)-induction and high levels of Stx2a in stoolexternal icon
        Hauser JR, Atitkar RR, Petro CD, Lindsey RL, Strockbine N, O'Brien AD, Melton-Celsa AR.
        Front Cell Infect Microbiol. 2020 ;10:62.
        In this study we compared nine Shiga toxin (Stx)-producing Escherichia coli O157:H7 patient isolates for Stx levels, stx-phage insertion site(s), and pathogenicity in a streptomycin (Str)-treated mouse model. The strains encoded stx 2a, stx 1a and stx 2a, or stx 2a and stx 2c. All of the strains elaborated 10(5)-10(6) cytotoxic doses 50% (CD50) into the supernatant after growth in vitro as measured on Vero cells, and showed variable levels of increased toxin production after growth with sub-inhibitory levels of ciprofloxacin (Cip). The stx 2a+stx 2c+ isolates were 90-100% lethal for Str-treated BALB/c mice, though one isolate, JH2013, had a delayed time-to-death. The stx 2a+ isolate was avirulent. Both an stx 2a and a recA deletion mutant of one of the stx 2a+stx 2c+ strains, JH2010, exhibited at least a three-log decrease in cytotoxicity in vitro and both were avirulent in the mice. Stool from Str-treated mice infected with the highly virulent isolates were 10- to 100-fold more cytotoxic than feces from mice infected with the clinical isolate, JH2012, that made only Stx2a. Taken together these findings demonstrate that the stx 2a-phage from JH2010 induces to higher levels in vivo than does the phage from JH2012. The stx 1a+stx 2a+ clinical isolates were avirulent and neutralization of Stx1 in stool from mice infected with those strains indicated that the toxin produced in vivo was primarily Stx1a. Treatment of mice infected with Stx1a+Stx2a+ isolates with Cip resulted in an increase in Stx2a production in vivo and lethality in the mice. Our data suggest that high levels of Stx2a in stool are predictive of virulence in mice.

      3. Epidermal growth factor receptor and transforming growth factor beta signaling pathways cooperate to mediate Chlamydia pathogenesisexternal icon
        Igietseme JU, Partin J, George Z, Omosun Y, Goldstein J, Joseph K, Ellerson D, Eko FO, Pohl J, Bandea C, Black CM.
        Infect Immun. 2020 Mar 23;88(4).
        Human genital Chlamydia infection is a major public health concern due to the serious reproductive system complications. Chlamydia binds several receptor tyrosine kinases (RTKs) on host cells, including the epidermal growth factor receptor (EGFR), and activates cellular signaling cascades for host invasion, cytoskeletal remodeling, optimal inclusion development, and induction of pathogenic epithelial-mesenchyme transition (EMT). Chlamydia also upregulates transforming growth factor beta (TGF-beta) expression, whose signaling pathway synergizes with the EGFR cascade, but its role in infectivity, inclusions, and EMT induction is unknown. We hypothesized that the EGFR and TGF-beta signaling pathways cooperate during chlamydial infection for optimal inclusion development and stable EMT induction. The results revealed that Chlamydia upregulated TGF-beta expression as early as 6 h postinfection of epithelial cells and stimulated both the EGFR and TGF-beta signaling pathways. Inhibition of either the EGFR or TGF-betaR1 signaling substantially reduced inclusion development; however, the combined inhibition of both EGFR and TGF-betaR1 signaling reduced inclusions by over 90% and prevented EMT induction. Importantly, EGFR inhibition suppressed TGF-beta expression, and an inhibitory thrombospondin-1 (Tsp1)-based peptide inhibited chlamydia-induced EMT, revealing a major source of active TGF-beta during infection. Finally, TGF-betaR signaling inhibition suppressed the expression of transforming acidic coiled-coil protein-3 (TACC3), which stabilizes EGFR signaling, suggesting reciprocal regulation between TGF-beta and EGFR signaling during chlamydial infection. Thus, RTK-mediated host invasion by chlamydia upregulated TGF-beta expression and signaling, which cooperated with other cellular signaling cascades and cytoskeletal remodeling to support optimal inclusion development and EMT induction. This finding may provide new targets for chlamydial disease biomarkers and prevention.

      4. Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serologyexternal icon
        Kamath K, Reifert J, Johnston T, Gable C, Pantazes RJ, Rivera HN, McAuliffe I, Handali S, Daugherty PS.
        Sci Rep. 2020 Mar 24;10(1):5294.
        The detection of pathogen-specific antibodies remains a cornerstone of clinical diagnostics. Yet, many test exhibit undesirable performance or are completely lacking. Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. Antibody binding peptide motifs were identified from 28 Chagas repertoires using a bacterial display random 12-mer peptide library and next-generation sequencing (NGS). Thirty-three motifs were selected and mapped to candidate Chagas antigens. In a blinded validation set (n = 72), 30/30 Chagas were positive, 30/30 non-Chagas were negative, and 1/12 Leishmania sp. was positive. After unblinding, a Leishmania cross-reactive epitope was identified and removed from the panel. The Chagas assay exhibited 100% sensitivity (30/30) and specificity (90/90) in a second blinded validation set including individuals with other parasitic infections. Amongst additional epitope repertoires with unknown Chagas serostatus, assay specificity was 99.8% (998/1000). Thus, the Chagas assay achieved a combined sensitivity and specificity equivalent or superior to diagnostic algorithms that rely on three separate tests to achieve high specificity. NGS-based serology via SERA provides an effective approach to discover antigenic epitopes and develop high performance multiplex serological assays.

      5. Genotyping and subtyping Cryptosporidium to identify risk factors and transmission patterns - Nebraska, 2015-2017external icon
        Loeck BK, Pedati C, Iwen PC, McCutchen E, Roellig DM, Hlavsa MC, Fullerton K, Safranek T, Carlson AV.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):335-338.
        Cryptosporidium is an enteric pathogen that is transmitted through animal-to-person or person-to-person contact or through ingestion of contaminated water or food. In the United States, Cryptosporidium affects an estimated 750,000 persons each year; however, only approximately 11,000 cases are reported nationally (1,2). Persons infected with Cryptosporidium typically develop symptoms within 2 to 10 days after exposure. Common symptoms include watery diarrhea, abdominal cramps, nausea, vomiting, or fever, which can last 1 to 2 weeks. Cryptosporidiosis is a nationally notifiable disease in the United States. Nebraska presents a unique setting for the evaluation of this pathogen because, compared with other states, Nebraska has a greater reliance on agriculture and a higher proportion of the population residing and working in rural communities. Cryptosporidium species and subtypes are generally indistinguishable using conventional diagnostic methods. Using molecular characterization, Nebraska evaluated the genetic diversity of Cryptosporidium and found a dichotomy in the distribution of cases of cryptosporidiosis caused by Cryptosporidium parvum and Cryptosporidium hominis among rural and urban settings. Characterizing clusters of C. hominis cases revealed that several child care facilities were affected by the same subtype, suggesting community-wide transmission and indicating a need for effective exclusion policies. Several cases of cryptosporidiosis caused by non-C. parvum or non-C. hominis species and genotypes indicated unique animal exposures that were previously unidentified. This study enhanced epidemiologic data by validating known Cryptosporidium sources, confirming outbreaks, and, through repeat interviews, providing additional information to inform cryptosporidiosis prevention and control efforts.

      6. Sequencing and characterization of five extensively drug-resistant Salmonella enterica serotype Typhi isolates implicated in human infections from Punjab, Pakistanexternal icon
        Tagg KA, Amir A, Ikram A, Chen JC, Kim JY, Meservey E, Joung YJ, Halpin JL, Batra D, Leeper MM, Katz LS, Saeed A, Freeman M, Watkins LF, Salman M, Folster JP.
        Microbiol Resour Announc. 2020 Mar 26;9(13).
        A large outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi infections is ongoing in Pakistan, predominantly in Sindh Province. Here, we report the sequencing and characterization of five XDR Salmonella Typhi isolates from the Punjab province of Pakistan that are closely related to the outbreak strain and carry the same IncY plasmid.

      7. Joint toxicity of a multi-heavy metal mixture and chemoprevention in Sprague Dawley ratsexternal icon
        Wang Y, Tang Y, Li Z, Hua Q, Wang L, Song X, Zou B, Ding M, Zhao J, Tang C.
        Int J Environ Res Public Health. 2020 Feb 24;17(4).
        To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg*bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg*bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg*bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.

      8. Urushiol compounds detected in Toxicodendron-labeled consumer products using mass spectrometryexternal icon
        Zhang AJ, Aschenbeck KA, Law BF, B'Hymer C, Siegel PD, Hylwa SA.
        Dermatitis. 2020 Mar/Apr;31(2):134-139.
        BACKGROUND: Urushiol, the culprit allergen in Toxicodendron plants such as poison ivy, is an oily mixture of 15 and 17 carbon side chain alk-(en)-yl catechols. Recently, consumer products have been identified that contain Toxicodendron as an ingredient on their label; however, no studies have assessed whether urushiol is indeed present within these products. OBJECTIVE: The aim of the study was to determine whether urushiol compounds are present in consumer products labeled as containing Toxicodendron species. METHODS: Gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry were performed on 9 consumer products labeled as containing Toxicodendron species, including topical homeopathic remedies. Single ion monitoring gas chromatography-mass spectrometry was programmed in selective ion mode to detect 3-methylcatechol characteristic fragment ions of alk-(en)-yl catechols after silanization. Similarly, single ion monitoring liquid chromatography-tandem mass spectrometry was programmed to detect 4 urushiol pentadecylcatechols and 5 urushiol heptadecylcatechols using previously reported mass-to-charge ratios. RESULTS: Gas chromatography-mass spectrometry detected alk-(en)-yl catechols in 67% (6/9) of the products tested. Liquid chromatography-tandem mass spectrometry detected multiple urushiol pentadecylcatechols and heptadecylcatechols in 44% (4/9) of the products tested. CONCLUSIONS: Alk-(en)-yl catechols and multiple urushiols were detected in consumer products listing Toxicodendron species as an ingredient. Clinicians should be aware of these known allergenic ingredients in consumer products.

    • Maternal and Child Health
      1. Implementing a learning collaborative framework for states working to improve outcomes for vulnerable populations: The Opioid Use Disorder, Maternal Outcomes, and Neonatal Abstinence Syndrome Initiative Learning Communityexternal icon
        Kroelinger CD, Addison D, Rodriguez M, Rice ME, Frey MT, Hickner HR, Weber MK, Mueller T, Velonis A, Uesugi K, Romero L, Akbarali S, Foster N, Ko JY, Pliska E, Mackie C, Cox S, Fehrenbach SN, Barfield WD.
        J Womens Health (Larchmt). 2020 Mar 13.
        The opioid crisis has impacted vulnerable populations, specifically pregnant and postpartum women, and infants prenatally exposed to substances, including infants with Neonatal Abstinence Syndrome. Lack of access to clinical and social services; potential stigma or discrimination; and lack of resources for provision of services, including screening and treatment, have impacted the health of these populations. In 2018, using a systems change approach, the Association of State and Territorial Health Officials (ASTHO) and the Centers for Disease Control and Prevention (CDC) convened an Opioid use disorder, Maternal outcomes, Neonatal abstinence syndrome Initiative Learning Community (OMNI LC) that included other federal agencies, national clinical and nonclinical organizations, and 12 state leadership groups. The purpose of the OMNI LC was to determine areas of focus and identify strategies and best practices for implementing systems change to improve maternal and infant outcomes associated with opioid use disorder (OUD) during the perinatal period. Activities included in-person convenings with policy goal action plan development, virtual learning sessions, intensive technical assistance (TA), and temporary field placements. The OMNI LC partnering agencies and state teams met bimonthly for the first year of the initiative. At the in-person convening, state teams identified barriers to developing and implementing systems change in activity-specific action plans within five areas of focus: financing and coverage; access to and coordination of quality services; provider training and awareness; ethical, legal, and social considerations; and data, monitoring, and evaluation. State teams also identified stakeholder partnerships as a necessary component of strategy development in all areas of focus. Four virtual learning sessions were conducted on the areas of focus identified by state teams, and ASTHO conducted three intensive TA opportunities, and five states were identified for temporary field placement. To successfully address the impact of the opioid crisis on pregnant and postpartum women and infants, states developed innovative strategies focused on increasing support, services, and resources. Moving forward, state teams will participate in two additional in-person meetings, continue to identify barriers to the work, refine and customize action plans, and set new goals, to effect broad-ranging systems change for these vulnerable populations.

      2. Prevalence of autism spectrum disorder among children aged 8 years - Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2016external icon
        Maenner MJ, Shaw KA, Baio J, Washington A, Patrick M, DiRienzo M, Christensen DL, Wiggins LD, Pettygrove S, Andrews JG, Lopez M, Hudson A, Baroud T, Schwenk Y, White T, Rosenberg CR, Lee LC, Harrington RA, Huston M, Hewitt A, Esler A, Hall-Lande J, Poynter JN, Hallas-Muchow L, Constantino JN, Fitzgerald RT, Zahorodny W, Shenouda J, Daniels JL, Warren Z, Vehorn A, Salinas A, Durkin MS, Dietz PM.
        MMWR Surveill Summ. 2020 Mar 27;69(4):1-12.
        PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] </=70); this percentage was higher among girls than boys (40% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively). Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ </=70 had a later median age at ASD diagnosis than white children with IQ </=70 (48 months versus 42 months). INTERPRETATION: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. PUBLIC HEALTH ACTION: These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.

      3. Early identification of autism spectrum disorder among children aged 4 years - Early Autism and Developmental Disabilities Monitoring Network, six sites, United States, 2016external icon
        Shaw KA, Maenner MJ, Baio J, Washington A, Christensen DL, Wiggins LD, Pettygrove S, Andrews JG, White T, Rosenberg CR, Constantino JN, Fitzgerald RT, Zahorodny W, Shenouda J, Daniels JL, Salinas A, Durkin MS, Dietz PM.
        MMWR Surveill Summ. 2020 Mar 27;69(3):1-11.
        PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network, a subset of the overall ADDM Network, is an active surveillance program that estimates ASD prevalence and monitors early identification of ASD among children aged 4 years. Children included in surveillance year 2016 were born in 2012 and had a parent or guardian who lived in the surveillance area in Arizona, Colorado, Missouri, New Jersey, North Carolina, or Wisconsin, at any time during 2016. Children were identified from records of community sources including general pediatric health clinics, special education programs, and early intervention programs. Data from comprehensive evaluations performed by community professionals were abstracted and reviewed by trained clinicians using a standardized ASD surveillance case definition with criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). RESULTS: In 2016, the overall ASD prevalence was 15.6 per 1,000 (one in 64) children aged 4 years for Early ADDM Network sites. Prevalence varied from 8.8 per 1,000 in Missouri to 25.3 per 1,000 in New Jersey. At every site, prevalence was higher among boys than among girls, with an overall male-to-female prevalence ratio of 3.5 (95% confidence interval [CI] = 3.1-4.1). Prevalence of ASD between non-Hispanic white (white) and non-Hispanic black (black) children was similar at each site (overall prevalence ratio: 0.9; 95% CI = 0.8-1.1). The prevalence of ASD using DSM-5 criteria was lower than the prevalence using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria at one of four sites that used criteria from both editions. Among sites where >/=60% of children aged 4 years had information about intellectual disability (intelligence quotient </=70 or examiner's statement of intellectual disability documented in an evaluation), 53% of children with ASD had co-occurring intellectual disability. Of all children aged 4 years with ASD, 84% had a first evaluation at age </=36 months and 71% of children who met the surveillance case definition had a previous ASD diagnosis from a community provider. Median age at first evaluation and diagnosis for this age group was 26 months and 33 months, respectively. Cumulative incidence of autism diagnoses received by age 48 months was higher for children aged 4 years than for those aged 8 years identified in Early ADDM Network surveillance areas in 2016. INTERPRETATION: In 2016, the overall prevalence of ASD in the Early ADDM Network using DSM-5 criteria (15.6 per 1,000 children aged 4 years) was higher than the 2014 estimate using DSM-5 criteria (14.1 per 1,000). Children born in 2012 had a higher cumulative incidence of ASD diagnoses by age 48 months compared with children born in 2008, which indicates more early identification of ASD in the younger group. The disparity in ASD prevalence has decreased between white and black children. Prevalence of co-occurring intellectual disability was higher than in 2014, suggesting children with intellectual disability continue to be identified at younger ages. More children received evaluations by age 36 months in 2016 than in 2014, which is consistent with Healthy People 2020 goals. Median age at earliest ASD diagnosis has not changed considerably since 2014. PUBLIC HEALTH ACTION: More children aged 4 years with ASD are being evaluated by age 36 months and diagnosed by age 48 months, but there is still room for improvement in early identification. Timely evaluation of children by community providers as soon as developmental concerns have been identified might result in earlier ASD diagnoses, earlier receipt of evidence-based interventions, and improved developmental outcomes.

      4. Obstetrician-gynecologist views of pregnancy-related medication safetyexternal icon
        SteelFisher GK, Hero JO, Caporello HL, Blendon RJ, Walker W, Broussard CS, Gilboa SM, Polen KN, Ben-Porath EN.
        J Womens Health (Larchmt). 2020 Apr 1.
        Background: Medication use among pregnant women is widespread, despite limited evidence about the teratogenicity of most medications. Improved physician-patient communication about pregnancy-related medication safety has been identified as a strategy to address this critical issue; however, little is known about physicians' knowledge, attitudes, and practices that could inform tools for information access and sharing to support such communication. The primary objective of this study is to address gaps in what is known about obstetrician-gynecologist views, practices, and needs related to accessing and sharing pregnancy-related medication safety information with patients. Materials and Methods: The basis for this study is a nationally representative, randomized survey of 506 practicing obstetrician-gynecologists. The survey was completed by mail or online between October 26, 2015 and May 8, 2016 with a 52% response rate. Data were weighted to population parameters to reduce the risk of potential nonresponse biases. Analyses included univariate distributions and comparisons between physicians in different residency cohorts using all-pairs dependent t-tests. Results: Findings point to critical features of obstetrician-gynecologist access and sharing of medication safety information. Obstetrician-gynecologists often retrieve medication safety information during a clinical visit. There is widespread provision of potentially problematic "safe lists" to patients, particularly by younger cohorts, and limited counseling for reproductive-aged patients not actively planning a pregnancy. Conclusions: To improve clinical care, physician-patient communication may be enhanced with technical and policy solutions, including improved digital information tools for retrieving and discussing information in the clinical setting; evidence-based, written information for physicians to share with patients; and encouragement for counseling all women of reproductive age receiving teratogenic medications.

    • Medicine
      1. Patient exposure from radiologic and nuclear medicine procedures in the United States: Procedure volume and effective dose for the period 2006-2016external icon
        Mettler FA, Mahesh M, Bhargavan-Chatfield M, Chambers CE, Elee JG, Frush DP, Miller DL, Royal HD, Milano MT, Spelic DC, Ansari AJ, Bolch WE, Guebert GM, Sherrier RH, Smith JM, Vetter RJ.
        Radiology. 2020 Mar 17:192256.
        Background Comprehensive assessments of the frequency and associated doses from radiologic and nuclear medicine procedures are rarely conducted. The use of these procedures and the population-based radiation dose increased remarkably from 1980 to 2006. Purpose To determine the change in per capita radiation exposure in the United States from 2006 to 2016. Materials and Methods The U.S. National Council on Radiation Protection and Measurements conducted a retrospective assessment for 2016 and compared the results to previously published data for the year 2006. Effective dose values for procedures were obtained from the literature, and frequency data were obtained from commercial, governmental, and professional society data. Results In the United States in 2006, an estimated 377 million diagnostic and interventional radiologic examinations were performed. This value remained essentially the same for 2016 even though the U.S. population had increased by about 24 million people. The number of CT scans performed increased from 67 million to 84 million, but the number of other procedures (eg, diagnostic fluoroscopy) and nuclear medicine procedures decreased from 17 million to 13.5 million. The number of dental radiographic and dental CT examinations performed was estimated to be about 320 million in 2016. Using the tissue-weighting factors from Publication 60 of the International Commission on Radiological Protection, the U.S. annual individual (per capita) effective dose from diagnostic and interventional medical procedures was estimated to have been 2.9 mSv in 2006 and 2.3 mSv in 2016, with the collective doses being 885 000 and 755 000 person-sievert, respectively. Conclusion The trend from 1980 to 2006 of increasing dose from medical radiation has reversed. Estimated 2016 total collective effective dose and radiation dose per capita dose are lower than in 2006. (c) RSNA, 2020 See also the editorial by Einstein in this issue.

    • Nutritional Sciences
      1. Carbonating the household diet: a Pakistani taleexternal icon
        Datta BK, Husain MJ.
        Public Health Nutr. 2020 Mar 20:1-9.
        OBJECTIVE: Carbonated beverage consumption is associated with various adverse health conditions such as obesity, type 2 diabetes and CVD. Pakistan has a high burden of these health conditions. At the same time, the carbonated beverage industry is rapidly growing in Pakistan. In this context, we analyse the trends and socioeconomic factors associated with carbonated beverage consumption in Pakistan. DESIGN: We use six waves of the cross-sectional household surveys from 2005-2006 to 2015-2016 to analyse carbonated beverage consumption. We examine the trends in carbonated beverage consumption-prevalence for different economic groups categorised by per capita household consumption quintiles. We estimate the expenditure elasticity of carbonated beverages for these groups using a two-stage budgeting system framework. We also construct concentration curves of carbonated beverage expenditure share to analyse the burden of expenditure across households of different economic status. SETTING: Pakistan. PARTICIPANTS: Nationally representative sample of households in respective survey waves. RESULTS: We find that the wealthier the household, the higher is the prevalence of carbonated beverage consumption, and the prevalence has increased for all household groups over time. From the expenditure elasticity analysis, we observe that carbonated beverages are becoming an essential part of food consumption particularly for wealthier households. And, lastly, poorer households are bearing a larger share of carbonated beverage expenditure in 2014-2016 than that in 2006-2008. CONCLUSION: Carbonated beverages are becoming an increasingly essential part of household food consumption in Pakistan. Concerns about added sugar intake can prompt consideration of public health approaches to reduce dietary causes of the disease burden in Pakistan.

      2. BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery. METHODS: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted. RESULTS: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Delta0.2 kg/m(2); 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m(2) higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Delta0.22 cm; p = 0.25) and higher FFM (Delta0.11 kg; p = 0.078) in the reduced dose group. CONCLUSIONS: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

      3. Malnutrition trends in Rohingya children aged 6-59 months residing in informal settlements in Cox's Bazar District, Bangladesh: An analysis of cross-sectional, population-representative surveysexternal icon
        Leidman E, Miah ML, Humphreys A, Toroitich-van Mil L, Wilkinson C, Chelang'at Koech M, Sebuliba H, Abu Bakr Siddique M, Bilukha O.
        PLoS Med. 2020 Mar;17(3):e1003060.
        BACKGROUND: More than 700,000 ethnic Rohingya have crossed the border from Rakhine State, Myanmar to Cox's Bazar District, Bangladesh, following escalated violence by Myanmar security forces. The majority of these displaced Rohingya settled in informal sites on previously forested land, in areas without basic infrastructure or access to services. METHODS AND FINDINGS: Three cross-sectional population-representative cluster surveys were conducted, including all informal settlements of Rohingya refugees in the Ukhia and Teknaf Upazilas of Cox's Bazar District. The first survey was conducted during the acute phase of the humanitarian response (October-November 2017), and the second and third surveys were conducted 6 (April-May 2018) and 12 (October-November 2018) months later. Anthropometric indices (weight, height, mid-upper arm circumference [MUAC], oedema) and haemoglobin (Hb) were measured in children aged 6-59 months following standard procedures. Final samples for survey rounds 1, 2, and 3 (R1, R2, and R3) included 1,113, 628, and 683 children, respectively, of which approximately half were male (50.7%-53.5% per round) and a third were 6-23 months of age (32.4%-33.3% per round). Prevalence of global acute malnutrition (GAM) as assessed by weight for height in R2 (12.1%, 95% CI: 9.6-15.1) and R3 (11.0%, 95% CI: 8.4-14.2) represent a significant decline from the observed prevalence in R1 (19.4%, 95% CI: 16.8-22.3) (p < 0.001 for both comparisons). Overall, the prevalence of anaemia significantly declined (p < 0.001) between the first 2 rounds (47.9%, 95% CI: 44.1-51.7 and 32.3%, 95% CI: 27.8-37.1, respectively); prevalence increased significantly (p = 0.04) to 39.8% (95% CI, 34.1-45.4) during R3 but remained below R1 levels. Reported receipt of both fortified blended foods (12.8%) and micronutrient powders (10.3%) were low during R1 but increased significantly (p < 0.001 for both) within the first 6 months to 49.8% and 29.9%, respectively. Although findings demonstrate improvement in anthropometric indicators during a period in which nutrition programme coverage increased, causation cannot be determined from the cross-sectional design. CONCLUSIONS: These data document significant improvements in both acute and micronutrient malnutrition among Rohingya children in makeshift settlements. These declines coincide with a scaleup of services aimed at prevention and treatment of malnutrition. Ongoing activities to improve access to nutritional services may facilitate further reductions in malnutrition levels to sustained below-crisis levels.

      4. Correlates of infrequent plain water intake among US high school students: National Youth Risk Behavior Survey, 2017external icon
        Park S, Onufrak S, Cradock A, Patel A, Hecht C, Merlo C, Blanck HM.
        Am J Health Promot. 2020 Mar 18:890117120911885.
        PURPOSE: To examine factors associated with frequency of plain water (ie, tap, bottled, and unflavored sparkling water) intake among US high school students. DESIGN: Quantitative, cross-sectional study. SETTING: The 2017 national Youth Risk Behavior Survey data. SUBJECTS: US high school students with plain water intake data (N = 10 698). MEASURES: The outcome was plain water intake. Exposure variables were demographics, academic grades, and behavioral characteristics. ANALYSIS: We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for factors associated with infrequent plain water intake (<3 vs >/=3 times/day). RESULTS: Overall, 48.7% of high school students reported drinking plain water <3 times/day. Factors associated with infrequent plain water intake were younger age (</=15 years; aOR = 1.20, CI = 1.05-1.37); earning mostly D/F grades (aOR = 1.37, CI = 1.07-1.77); consuming regular soda 1 to 6 times/week (aOR = 1.92, CI = 1.67-2.20) or >/=1 time/day (aOR = 3.23, CI = 2.65-3.94), sports drinks 1 to 6 times/week (aOR = 1.30, CI = 1.14-1.49), milk <2 glasses/day (aOR = 1.51, CI = 1.31-1.73), fruits <2 times/day (aOR = 1.92, CI = 1.66-2.22), and vegetables <3 times/day (aOR = 2.42, CI = 2.04-2.89); and being physically active >/=60 minutes/day on <5 days/week (aOR = 1.83, CI = 1.60-2.08). Students with obesity were less likely to have infrequent water intake (aOR = 0.63, CI = 0.53-0.74). CONCLUSIONS: Infrequent plain water intake was associated with younger age, poor academic grades, poor dietary behaviors, and physical inactivity. These findings can inform intervention efforts to increase water intake to promote healthy lifestyles among adolescents.

      5. Updated population minimal eliciting dose distributions for use in risk assessment of 14 priority food allergensexternal icon
        Remington BC, Westerhout J, Meima MY, Blom WM, Kruizinga AG, Wheeler MW, Taylor SL, Houben GF, Baumert JL.
        Food Chem Toxicol. 2020 Mar 13:111259.
        Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011-2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03mg for walnut protein and 26.2mg for shrimp protein. ED05 estimates ranged between 0.4mg for mustard protein and 280mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods.

      6. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of ageexternal icon
        Suchdev PS, Jefferds ME, Ota E, da Silva Lopes K, De-Regil LM.
        Cochrane Database Syst Rev. 2020 Feb 28;2:Cd008959.
        BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin A, and zinc, affect more than two billion people worldwide. Young children are highly vulnerable because of rapid growth and inadequate dietary practices. Multiple micronutrient powders (MNPs) are single-dose packets containing multiple vitamins and minerals in powder form, which are mixed into any semi-solid food for children six months of age or older. The use of MNPs for home or point-of-use fortification of complementary foods has been proposed as an intervention for improving micronutrient intake in children under two years of age. In 2014, MNP interventions were implemented in 43 countries and reached over three million children. This review updates a previous Cochrane Review, which has become out-of-date. OBJECTIVES: To assess the effects and safety of home (point-of-use) fortification of foods with MNPs on nutrition, health, and developmental outcomes in children under two years of age. For the purposes of this review, home fortification with MNP refers to the addition of powders containing vitamins and minerals to semi-solid foods immediately before consumption. This can be done at home or at any other place that meals are consumed (e.g. schools, refugee camps). For this reason, MNPs are also referred to as point-of-use fortification. SEARCH METHODS: We searched the following databases up to July 2019: CENTRAL, MEDLINE, Embase, and eight other databases. We also searched four trials registers, contacted relevant organisations and authors of included studies to identify any ongoing or unpublished studies, and searched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with individual randomisation or cluster-randomisation. Participants were infants and young children aged 6 to 23 months at the time of intervention, with no identified specific health problems. The intervention consisted of consumption of food fortified at the point of use with MNP formulated with at least iron, zinc, and vitamin A, compared with placebo, no intervention, or use of iron-containing supplements, which is standard practice. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, and assessed the risk of bias of included studies. We reported categorical outcomes as risk ratios (RRs) or odds ratios (ORs), with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) and 95% CIs. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry. Home fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 mug/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI -0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity. In comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD -2.81 g/L, 95% CI -10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously. Reporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce. It appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. AUTHORS' CONCLUSIONS: Home fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.

    • Occupational Safety and Health
      1. Effect of electrocautery settings on particulate concentrations in surgical plume during tonsillectomyexternal icon
        Carr MM, Patel VA, Soo JC, Friend S, Lee EG.
        Otolaryngol Head Neck Surg. 2020 Mar 31:194599820914275.
        OBJECTIVES: To describe the effect of monopolar electrocautery (EC) settings on surgical plume particulate concentration during pediatric tonsillectomy. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: During total tonsillectomy exclusively performed with EC, air was sampled with a surgeon-worn portable particle counter. The airborne mean and maximum particle concentrations were compared for tonsillectomy performed with EC at 12 W vs 20 W, with smoke evacuation system (SES) and no smoke evacuation (NS). RESULTS: A total of 36 children were included in this analysis: 9 cases with EC at 12 W and SES (12SES), 9 cases with EC at 20 W and SES (20SES), 9 cases with EC at 12 W without SES (12NS), and 9 cases with EC at 20 W without SES (20NS). Mean particle number concentration in the breathing zone during tonsillectomy was 1661 particles/cm(3) for 12SES, 5515 particles/cm(3) for 20SES, 8208 particles/cm(3) for 12NS, and 78,506 particles/cm(3) for 20NS. There was a statistically significant difference in the particle number concentrations among the 4 groups. The correlation between the particle number concentration and EC time was either moderate (for 12SES) or negative (for remaining groups). CONCLUSION: Airborne particle concentrations during tonsillectomy are over 9.5 times higher when EC is set at 20 W vs 12 W with NS, which is mitigated to 3.3 times with SES. Applying lower EC settings with SES during pediatric tonsillectomy significantly reduces surgical plume exposure for patients, surgeons, and operating room personnel, which is a well-known occupational health hazard.

      2. The objective of this study is to identify effective engineering methods for controlling handheld workpiece vibration during grinding processes. Prolonged and intensive exposures to such vibration can cause hand-arm vibration syndrome among workers performing workpiece grinding, but how to effectively control these exposures remains an important issue. This study developed a methodology for performing their analyses and evaluations based on a model of the entire grinding machine-workpiece-hand-arm system. The model can simulate the vibration responses of a workpiece held in the worker's hands and pressed against a grinding wheel in order to shape the workpiece in the major frequency range of concern (6.3-1600 Hz). The methodology was evaluated using available experimental data. The results suggest that the methodology is acceptable for these analyses and evaluations. The results also suggest that the workpiece vibration resulting from the machine vibration generally depends on two mechanisms or pathways: (1) the direct vibration transmission from the grinding machine; and (2) the indirect transmission that depends on both the machine vibration transmission to the workpiece and the interface excitation transformation to the workpiece vibration. The methodology was applied to explore and/or analyze various engineering methods for controlling workpiece vibrations. The modeling results suggest that while these intervention methods have different advantages and limitations, some of their combinations can effectively reduce the vibration exposures of grinding workers. These findings can be used as guidance for selecting and developing more effective technologies to control handheld workpiece vibration exposures.

      3. Lifetime prevalence of self-reported work-related health problems among U.S. workers - United States, 2018external icon
        Free H, Groenewold MR, Luckhaupt SE.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):361-365.
        Approximately 2.8 million nonfatal workplace illnesses and injuries were reported in the United States in 2018 (1). Current surveillance methods might underestimate the prevalence of occupational injuries and illnesses (2,3). One way to obtain more information on occupational morbidity is to assess workers' perceptions about whether they have ever experienced health problems related to work (4). Occupational exposures might directly cause, contribute to, exacerbate, or predispose workers to various health problems (work-related health problems). CDC's National Institute for Occupational Safety and Health estimated the lifetime prevalence of self-reported, work-related health problems for the currently employed population overall and stratified by various demographic and job characteristics using data from the 2018 version of the SummerStyles survey. Overall, 35.1% of employed respondents had ever experienced a work-related health problem (95% confidence interval [CI] = 33.0%-37.3%). The most commonly reported work-related health problem was back pain (19.4%, 95% CI = 17.6%-21.2%). Among industries, construction (48.6%, 95% CI = 36.54%-60.58%) had the highest prevalence of any work-related health problems. Workplace injury and illness prevention programs are needed to reduce the prevalence of work-related health problems, especially in higher-risk industries.

      4. Advancing safe and healthy work for all agesexternal icon
        Grosch JW.
        Ind Health. 2020 ;58(2):89-90.

      5. Nonphysical workplace violence in a state-based cohort of education workersexternal icon
        Konda S, Tiesman HM, Hendricks S, Grubb PL.
        J Sch Health. 2020 Mar 29.
        BACKGROUND: The purpose of this study was to estimate the prevalence, identify risk factors, and assess the impact of nonphysical workplace violence (WPV) events among education workers (teachers, professionals, and support personnel). METHODS: A cross-sectional survey was mailed to a random sample of 6450 education workers, stratified by sex, occupation, and school location in Pennsylvania. Multivariable logistic regression was performed to assess risk factors. RESULTS: Of the 2514 participants, 859 (34%) reported experiencing at least one nonphysical WPV event during the 2009-2010 school year. Coworkers were the most common source of bullying. Most education workers responded that they did not receive an adequate response from their administration after reporting a nonphysical WPV event. Risks of nonphysical assaults increased for education workers who were female, those working in an urban school, and those in their first 3 years of working in their current school. Those assaulted were significantly likely to have low job satisfaction, find work more stressful, and have poor mental health compared to those were not assaulted. CONCLUSIONS: Administration support for specific prevention efforts and post-event responses that address the risk factors for nonphysical WPV are essential for creating a positive, safe work environment in schools.

      6. Using workers' compensation claims data to describe nonfatal injuries among workers in Alaskaexternal icon
        Lucas DL, Lee JR, Moller KM, O'Connor MB, Syron LN, Watson JR.
        Saf Health Work. 2020 .
        Background: To gain a better understanding of nonfatal injuries in Alaska, underutilized data sources such as workers’ compensation claims must be analyzed. The purpose of the current study was to utilize workers’ compensation claims data to estimate the risk of nonfatal, work-related injuries among occupations in Alaska, characterize injury patterns, and prioritize future research. Methods: A dataset with information on all submitted claims during 2014–2015 was provided for analysis. Claims were manually reviewed and coded. For inclusion in this study, claims had to represent incidents that resulted in a nonfatal acute traumatic injury, occurred in Alaska during 2014–2015, and were approved for compensation. Results: Construction workers had the highest number of injuries (2,220), but a rate lower than the overall rate (34 per 1,000 construction workers, compared to 40 per 1,000 workers overall). Fire fighters had the highest rate of injuries on the job, with 162 injuries per 1,000 workers, followed by law enforcement officers with 121 injuries per 1,000 workers. The most common types of injuries across all occupations were sprains/strains/tears, contusions, and lacerations. Conclusion: The successful use of Alaska workers’ compensation data demonstrates that the information provided in the claims dataset is meaningful for epidemiologic research. The predominance of sprains, strains, and tears among all occupations in Alaska indicates that ergonomic interventions to prevent overexertion are needed. These findings will be used to promote and guide future injury prevention research and interventions.

      7. Nonfatal violent workplace crime characteristics and rates by occupation - United States, 2007-2015external icon
        Siegel M, Johnson CY, Lawson CC, Ridenour M, Hartley D.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):324-328.
        Workplace violence can lead to adverse physical and psychological outcomes and affect work function (1). According to the U.S. Bureau of Labor Statistics, intentional injury by another person is a leading cause of nonfatal injury requiring missed workdays (2). Most estimates of workplace violence include only crimes reported to employers or police, which are known underestimates (3,4). Using 2007-2015 data from the National Crime Victimization Survey (NCVS), characteristics of self-reported nonfatal violent workplace crimes, whether reported to authorities or not, and rates by occupation were examined. Estimates of crime prevalence were stratified by crime characteristics and 22 occupational groups. Overall, approximately eight violent workplace crimes were reported per 1,000 workers. During 2007-2010, workers in Protective services reported the highest rates of violent workplace crimes (101 per 1,000 workers), followed by Community and social services (19 per 1,000). Rates were higher among men (nine per 1,000) than among women (six per 1,000). Fifty-eight percent of crimes were not reported to police. More crimes against women than against men involved offenders known from the workplace (34% versus 19%). High-risk occupations appear to be those involving interpersonal contact with persons who might be violent, upset, or vulnerable. Training and controls should emphasize how employers and employees can recognize and manage specific risk factors in prevention programs. In addition, workplace violence-reduction interventions might benefit from curricula developed for men and women in specific occupational groups.

      8. Purpose: Law enforcement is a dangerous profession not only due to assaults, accidents and homicides but also due to health risks. This study examined trends in the national frequency and rate of law enforcement job-related illness deaths in the United States over a 22-year period (1997–2018). Design/methodology/approach: Data were obtained from the National Law Enforcement Officers Memorial Fund (NLEOMF) on death frequencies related to health issues at work. Death rates were based on the total number of police officers in the United States [rate = (frequency/population at risk) × 100,000]. Trends were examined using standardized regression. Findings: A total of 646 deaths were attributed to job-related illness. There was a significant upward trend in overall job-related illness deaths (frequency analyses: β = 0.88, p < 0.0001; rate analyses: β = 0.82, p ≤ 0.0001) mainly driven by a significant increase in 911 cancer deaths (frequency analyses: β = 0.88, p < 0.0001; rate analyses: β = 0.88, p ≤ 0.0001). Nearly 82 percent of circulatory deaths were from a heart attack, with an average death age of 46.5 years. Research limitations/implications: Deaths were not included if they failed to meet medical requirements of the NLEOMF. The data are descriptive, do not estimate risk and should be interpreted cautiously. Practical implications: Police wellness programs may help to reduce the danger of deaths associated with job-related illness. Originality/value: This is among the first studies to examine frequency and rate of police health–related deaths due to job exposures.

      9. Occupational exposure to secondhand cannabis smoke among law enforcement officers providing security at outdoor concert eventsexternal icon
        Wiegand DM, Methner MM, Grimes GR, Couch JR, Wang L, Zhang L, Blount BC.
        Ann Work Expo Health. 2020 Mar 27.
        OBJECTIVES: Numerous states within the USA have legalized cannabis for medical or non-medical (adult/recreational) use. With the increased availability and use of cannabis, occupational and environmental exposures to secondhand cannabis smoke (SHCS) raise concerns over whether non-users may be at risk for a 'contact high', impaired neurocognitive function, harm from irritants and carcinogens in smoke, or potentially failing a cannabis screening test. The extent of health effects from potential occupational exposure to SHCS is unknown. This is a study of occupational exposures to SHCS among law enforcement officers (LEOs) providing security at outdoor concerts on a college campus in a state where adult use of cannabis is legal. METHODS: Investigators evaluated a convenience sample of LEOs' potential exposure to SHCS and symptoms experienced while providing security during two open-air stadium rock-n-roll concerts on consecutive days in July 2018. During each event, full-shift area and LEO personal air samples were collected for Delta9-tetrahydrocannabinol (Delta9-THC), the psychoactive component of cannabis. Urine (pre- and postevent; n = 58) and blood (postevent; n = 29) were also collected and analyzed for Delta9-THC and two of its metabolites [11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and 11-nor-hydroxy-delta-9-tetrahydrocannabinol (OH-THC)]. Urine samples were analyzed using ultrahigh performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry and results were compared with the Department of Transportation guidelines for urine screening for cannabis. Blood (postevent) samples were also collected and the plasma fraction was tested for Delta9-THC, THC-COOH, and OH-THC using high-performance liquid chromatography coupled with mass spectrometry. LEOs also completed a medical questionnaire asking about symptoms experienced during the concerts. RESULTS: Twenty-nine LEOs participated in the evaluation. Measurable amounts of Delta9-THC were found in area (concentrations ranged from non-detectable to 330 ng m-3) and personal air samples (53-480 ng m-3). Small amounts (<1.0 ng ml-1) of a Delta9-THC metabolite (THC-COOH) were found in the postevent urine of 34% of LEOs. Neither Delta9-THC nor its metabolites were detected in any blood sample. LEOs reported experiencing non-specific symptoms during the concerts, such as burning, itchy, or red eyes (31%); dry mouth (21%); headache (21%); and coughing (21%). CONCLUSIONS: Identification of Delta9-THC in the breathing zone for some LEOs indicates the potential for airborne exposure to the psychoactive component of cannabis. However, the magnitude of these exposures was small compared with those that would result in a dose of Delta9-THC associated with psychotropic effects. Similarly, THC-COOH was found in the postevent urine of some LEOs at concentrations that were orders of magnitude below active use cut-points used during a cannabis screening test (50 ng ml-1). Exposure to SHCS was not high enough to detect concentrations of THC, THC-COOH, to OH-THC in the blood, which could be due to differences between the limits of detection for the tests employed. The ocular and respiratory symptoms reported by LEOs may be related to irritants in SHCS. However, the health effects of SHCS remain unclear, and further research concerning occupational and environmental exposures is warranted.

    • Occupational Safety and Health - Mining
      1. OBJECTIVES: Pneumoconiosis prevalence and severity among US coal miners has been increasing for the past 20 years. An examination of the current approaches to primary and secondary prevention efforts is warranted. One method of secondary prevention is the Mine Safety and Health Administration-administered part 90 option programme where US coal miners with radiographic evidence of pneumoconiosis can exercise their right to be placed in a less dusty area of the mine. This study focuses on characterising the progression of disease among US coal miners who participated in the National Institute for Occupational Safety and Health-administered Coal Workers' Health Surveillance Programme (CWHSP) and exercised their part 90 job transfer option. METHODS: Chest radiograph classifications of working underground coal miners who exercised their part 90 job transfer option during 1 January 1986 to 21 November 2016 and participated in the CWHSP during 1 January 1981 to 19 March 2019 were analysed. RESULTS: 513 miners exercised their part 90 option and participated in the CWHSP at least once during this time period. Of the 149 miners with >/=2 radiographs available, 48 (32%) showed progression after exercising part 90 and had more severe disease prior to exercising, compared with miners who did not progress (severity score of 2.8 vs 1.7, p=0.0002). CONCLUSION: The part 90 job transfer option programme is not routinely used as intended to prevent progression of pneumoconiosis among US coal miners. The one-third of miners who participated in part 90 and continued to progress, exercised their part 90 option at a later stage of disease compared with non-progressors.


      3. Cryogenic air supply for cooling built-in-place refuge alternatives in hot mineexternal icon
        Yan L, Yantek D, Reyes M, Whisner B, Bickson J, Srednicki J, Damiano N, Bauer E.
        Min Metall Explor. 2020 .
        Built-in-place (BIP) refuge alternatives (RAs) are designed to provide a secure space for miners who cannot escape during a mine emergency. Heat and humidity buildup within RAs may expose miners to physiological hazards such as heat stress. To minimize the risk of heat stress, Title 30 Code of Federal Regulations (CFR), or 30 CFR, mandates a maximum allowable apparent temperature (AT) for an occupied RA of 35 °C (95 °F) (MSHA 2008 [1]). The National Institute for Occupational Safety and Health (NIOSH) has conducted extensive research on the thermal environment of occupied RAs intended for use in underground coal mines. NIOSH research has demonstrated that a fully occupied BIP RA can exceed the AT limit by > 5.6 °C (10 °F) in mines with elevated mine strata and air temperatures (Bissert et al. 2017 [2]). In this circumstance, an RA cooling system could provide a solution. This paper provides an overview of test methodology and findings as well as guidance on improving the performance of a cryogenic air system prototype by optimizing the flow rate, increasing the tank storage capacity, and improving the efficiency of the heat exchanger of the cryogenic system. This may enable BIP RAs to meet the 35 °C (95 °F) AT limit in mines with elevated temperatures. The information in this paper is useful for RA manufacturers and mines that may choose to implement a cryogenic air system as a heat mitigation strategy.

      4. Influence of steel mesh on magnetic proximity detection systems: An experimental studyexternal icon
        Zhou C, Whisner BG, Carr JL, Srednicki J.
        Prog Electromagn Res M Pier M. 2020 ;90:89-97.
        Proximity Detection Systems (PDSs) are used in the mining industry for protecting mine workers from striking, pinning, and crushing injuries when they work in close proximity to heavy machines such as continuous mining machines (CMMs). Currently all PDSs approved by the Mine Safety and Health Administration (MSHA) are magnetic field based systems which can be influenced by the presence of steel wire mesh that is commonly used for supporting roof and ribs in underground coal mines. In this paper, researchers at the National Institute for Occupational Safety and Health (NIOSH) characterized the influence of the mesh on the performance of magnetic PDSs by measuring the magnetic field difference around a CMM caused by the presence of the mesh. The results show that the magnetic fields are generally enhanced by the mesh which causes PDS detection zones to be increased correspondingly. It was discovered that the fields around the joints of two mesh sections have the greatest enhancement and thus deserve more attention. In addition, it was found that the presence of mesh can also cause a variation in the generator current. The experimental results show that the generator current variation and thus the magnetic field change caused by the mesh can be significant (on the order of ten) when the mesh is extremely close to the generator (e.g., less than 1 cm) and is negligible when mesh is relatively far (greater than 0.15 m). The findings in this paper can be used to develop guidelines and best practices to mitigate the influence of mesh on PDSs.

    • Parasitic Diseases
      1. WHO malaria nucleic acid amplification test external quality assessment scheme: results of distribution programmes one to threeexternal icon
        Cunningham JA, Thomson RM, Murphy SC, de la Paz Ade M, Ding XC, Incardona S, Legrand E, Lucchi NW, Menard D, Nsobya SL, Saez AC, Chiodini PL, Shrivastava J.
        Malar J. 2020 Mar 30;19(1):129.
        BACKGROUND: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria. In recent years, there has been surge in the use of various kinds of nucleic-acid amplification based tests (NAATs) for detection and identification of Plasmodium spp. to support clinical care in high-resource settings and clinical and epidemiological research worldwide. However, these tests are not without challenges, including lack (or limited use) of standards and lack of reproducibility, due in part to variation in protocols amongst laboratories. Therefore, there is a need for rigorous quality control, including a robust external quality assessment (EQA) scheme targeted towards malaria NAATs. To this effect, the WHO Global Malaria Programme worked with the UK National External Quality Assessment Scheme (UK NEQAS) Parasitology and with technical experts to launch a global NAAT EQA scheme in January 2017. METHODS: Panels of NAAT EQA specimens containing five major species of human-infecting Plasmodium at various parasite concentrations and negative samples were created in lyophilized blood (LB) and dried blood spot (DBS) formats. Two distributions per year were sent, containing five LB and five DBS specimens. Samples were tested and validated by six expert referee laboratories prior to distribution. Between 37 and 45 laboratories participated in each distribution and submitted results using the online submission portal of UK NEQAS. Participants were scored based on their laboratory's stated capacity to identify Plasmodium species, and individual laboratory reports were sent which included performance comparison with anonymized peers. RESULTS: Analysis of the first three distributions revealed that the factors that most significantly affected performance were sample format (DBS vs LB), species and parasite density, while laboratory location and the reported methodology used (type of nucleic acid extraction, amplification, or DNA vs RNA target) did not significantly affect performance. Referee laboratories performed better than non-referee laboratories. CONCLUSIONS: Globally, malaria NAAT assays now inform a range of clinical, epidemiological and research investigations. EQA schemes offer a way for laboratories to assess and improve their performance, which is critical to safeguarding the reliability of data and diagnoses especially in situations where various NAAT methodologies and protocols are in use.

      2. "We have this, with my husband, we live in harmony": exploring the gendered decision-making matrix for malaria prevention and treatment in Nampula Province, Mozambiqueexternal icon
        Hildon ZJ, Escorcio-Ymayo M, Zulliger R, Arias de Aramburu R, Lewicky N, Harig H, Chidassicua JB, Underwood C, Pinto L, Figueroa ME.
        Malar J. 2020 Mar 30;19(1):133.
        BACKGROUND: Conceptualizing gender dynamics and ways of bridging entrenched gender roles will contribute to better health promotion, policy and planning. Such processes are explored in relation to malaria in Mozambique. METHODS: A multi-method, qualitative study using focus group discussions (FGDs) and in-depth interviews (IDIs) explored the perspectives of community members, leaders and stakeholders on malaria. The study was conducted in Nampula Province, in an intervention district for the Tchova Tchova Stop Malaria (TTSM) gender-sensitive community dialogues, and in a non-intervention district. RESULTS: Participants (n = 106) took part in six FGDs and five IDIs in each district. Those exposed to TTSM commonly stated that the programme influenced more equalitarian gender roles, attitudes and uptake of protective malaria-related practices. These positive changes occurred within the context of an observed, gendered decision-making matrix, which aligns inward- or outward-facing decisions with malaria prevention or treatment. Decisions more dependent on male or elder sanctioning at community level are outward-facing decisions, while decisions falling within women's domain at household level are inward-facing decisions. Related to prevention, using bed nets was largely an inward-facing prevention decision for women, who were generally tasked with hanging, washing and making nets usable. Net purchase and appropriation for malaria prevention (rather than for instance for fishing) was men's prerogative. Regular net use was associated with sleeping together more regularly, bringing couples closer. Attending antenatal care to access intermittent preventive treatment during pregnancy was often an outward-facing prevention decision, under the purview of older, influential women and ultimately needing sanctioning by men. With respect to seeking care for malaria symptoms, women typically sought help from traditional healers first. This inward-facing treatment decision was within their control, in contrast to the frequently transport-dependent, outward-facing decision to attend a health facility. Sharing decisions was described as a feature of a "harmonious household," something that was said to be encouraged by the TTSM intervention and that was both lived and aspirational. CONCLUSIONS: TTSM community dialogues helped communication on both interpersonal (couple) and community levels, ultimately encouraging malaria-related behaviours. Leveraging ways of bringing men and women together to share decision making will improve malaria intervention success.

      3. Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocolexternal icon
        L'Episcopia M, Kelley J, Patel D, Schmedes S, Ravishankar S, Menegon M, Perrotti E, Nurahmed AM, Talha AA, Nour BY, Lucchi N, Severini C, Talundzic E.
        Parasit Vectors. 2020 Mar 14;13(1):137.
        BACKGROUND: Routine molecular surveillance for imported drug-resistant malaria parasites to the USA and European Union is an important public health activity. The obtained molecular data are used to help keep chemoprophylaxis and treatment guidelines up to date for persons traveling to malaria endemic countries. Recent advances in next-generation sequencing (NGS) technologies provide a new and effective way of tracking malaria drug-resistant parasites. METHODS: As part of a technology transfer arrangement between the CDC Malaria Branch and the Istituto Superiore di Sanita (ISS), Rome, Italy, the recently described Malaria Resistance Surveillance (MaRS) protocol was used to genotype 148 Plasmodium falciparum isolates from Eritrea for kelch 13 (k13) and cytochrome b (cytb) genes, molecular markers associated with resistance to artemisinin (ART) and atovaquone/proguanil (AP), respectively. RESULTS: Spanning the full-length k13 gene, seven non-synonymous single nucleotide polymorphisms (SNPs) were found (K189N, K189T, E208K, D281V, E401Q, R622I and T535M), of which none have been associated with artemisinin resistance. No mutations were found in cytochrome b. CONCLUSION: All patients successfully genotyped carried parasites susceptible to ART and AP treatment. Future studies between CDC Malaria Branch and ISS are planned to expand the MaRS system, including data sharing, in an effort to maintain up to date treatment guidelines for travelers to malaria endemic countries.

      4. Screening for malaria antigen and anti-malarial IgG antibody in forcibly-displaced Myanmar nationals: Cox's Bazar district, Bangladesh, 2018external icon
        Lu A, Cote O, Dimitrova SD, Cooley G, Alamgir A, Uzzaman MS, Flora MS, Widiati Y, Akhtar MS, Vandenent M, Ehlman DC, Bennett SD, Feldstein LR, Rogier E.
        Malar J. 2020 Mar 30;19(1):130.
        BACKGROUND: Several refugee settlements in Bangladesh have provided housing and medical care for the forcibly-displaced Myanmar nationals (FDMN, also known as Rohingya) population. The identification of malaria infection status in the refugee settlements is useful in treating infected persons and in developing malaria prevention recommendations. Assays for Plasmodium antigens and human IgG against Plasmodium parasites can be used as indicators to determine malaria infection status and exposure. METHODS: Dried blood spot (DBS) samples (N = 1239) from a household survey performed April-May 2018 in three settlements in Cox's Bazar district, Bangladesh were utilized for a sample population of children from ages 1-14 years of age. The samples were tested using a bead-based multiplex antigen assay for presence of the pan-Plasmodium antigen aldolase as well as Plasmodium falciparum histidine rich protein 2 (HRP2). A bead-based multiplex assay was also used to measure human IgG antibody response to P. falciparum, Plasmodium malariae, and Plasmodium vivax merozoite surface protein 1 antigen (MSP1) isoforms, and P. falciparum antigens LSA1, CSP, and GLURP-R0. RESULTS: There were no detectable Plasmodium antigens in any samples, suggesting no active malaria parasite infections in the tested children. IgG seroprevalence was highest to P. vivax (3.1%), but this was not significantly different from the percentages of children antibody responses to P. falciparum (2.1%) and P. malariae (1.8%). The likelihood of an anti-Plasmodium IgG response increased with age for all three malaria species. Evidence of exposure to any malaria species was highest for children residing 8-10 months in the settlements, and was lower for children arriving before and after this period of time. CONCLUSIONS: Absence of Plasmodium antigen in this population provides evidence that children in these three Bangladeshi refugee settlements did not have malaria at time of sampling. Higher rates of anti-malarial IgG carriage from children who were leaving Myanmar during the malaria high-transmission season indicate these migrant populations were likely at increased risk of malaria exposure during their transit.

      5. Monitoring the physical and insecticidal durability of the long-lasting insecticidal net DawaPlus((R)) 2.0 in three States in Nigeriaexternal icon
        Obi E, Okoh F, Blaufuss S, Olapeju B, Akilah J, Okoko OO, Okechukwu A, Maire M, Popoola K, Yahaya MA, Uneke CJ, Awolola S, Pigeon O, Babalola S, Koenker H, Kilian A.
        Malar J. 2020 Mar 30;19(1):124.
        BACKGROUND: Following guidance from the US President's Malaria Initiative, durability monitoring of DawaPlus((R)) 2.0 brand of long-lasting insecticidal net (LLIN) distributed during the 2015/16 mass campaign was set up in three ecologically different states: Zamfara, Ebonyi and Oyo. METHODS: This was a prospective cohort study of representative samples of households from each location, recruited at baseline, 1 to 6 months after the mass campaign. All campaign nets in the households were labelled and followed up over a period of 36 months in Zamfara and Ebonyi and 24 months in Oyo. Primary outcome was the "proportion of nets surviving in serviceable condition" based on attrition and integrity measures and the median survival in years. The outcome for insecticidal durability was determined by bio-assay from sub-samples of campaign nets. RESULTS: A total of 439 households (98% of target) and 1096 campaign nets (106%) were included in the study. Definite outcomes could be determined for 92% of the cohort nets in Zamfara, 88% in Ebonyi and 75% in Oyo. All-cause attrition was highest in Oyo with 47% no longer present after 24 months, 53% in Ebonyi and 28% in Zamfara after 36 months. Overall only 1% of all campaign nets were used for other purposes. Estimated survival in serviceable condition of the campaign nets was 80% in Zamfara, 55% in Ebonyi (36 months follow-up) and 75% in Oyo (24 months follow-up) corresponding to median survival of 5.3, 3.3, 3.2 years, respectively. Factors associated with better survival were exposure to social messaging combined with a positive net-care attitude and only adult users. Failing to fold the net when hanging and having children under 5 years of age in the household negatively impacted net survival. Insecticidal effectiveness testing at final survey showed knock-down rates of 50-69%, but 24-h mortality above 95% resulting in 100% optimal performance in Ebonyi and Oyo and 97% in Zamfara. CONCLUSIONS: Results confirm the strong influence of net-use environment and behavioural factors in the physical survival of the same LLIN brand, which can increase the time until 50% of nets are no longer serviceable by up to 2 years.

      6. Conventional and high-sensitivity malaria rapid diagnostic test performance in 2 transmission settings: Haiti 2017external icon
        Rogier E, Hamre KE, Joseph V, Plucinski MM, Presume J, Romilus I, Mondelus G, Elisme T, van den Hoogen L, Lemoine JF, Drakeley C, Ashton RA, Chang MA, Existe A, Boncy J, Stresman G, Druetz T, Eisele TP.
        J Infect Dis. 2020 Feb 18;221(5):786-795.
        Accurate malaria diagnosis is foundational for control and elimination, and Haiti relies on histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) identifying Plasmodium falciparum in clinical and community settings. In 2017, 1 household and 2 easy-access group surveys tested all participants (N = 32 506) by conventional and high-sensitivity RDTs. A subset of blood samples (n = 1154) was laboratory tested for HRP2 by bead-based immunoassay and for P. falciparum 18S rDNA by photo-induced electron transfer polymerase chain reaction. Both RDT types detected low concentrations of HRP2 with sensitivity estimates between 2.6 ng/mL and 14.6 ng/mL. Compared to the predicate HRP2 laboratory assay, RDT sensitivity ranged from 86.3% to 96.0% between tests and settings, and specificity from 90.0% to 99.6%. In the household survey, the high-sensitivity RDT provided a significantly higher number of positive tests, but this represented a very small proportion (<0.2%) of all participants. These data show that a high-sensitivity RDT may have limited utility in a malaria elimination setting like Haiti.

    • Physical Activity
      1. People with disabilities are at increased risk of chronic diseases, many of which physical activity can help prevent and manage. Certain environmental features can support or hinder participation in important activities like walking, particularly for people with disabilities. The purpose of this study is to examine differences in the prevalence of perceived neighborhood environmental supports and barriers for walking, by disability status, among US adults. Participants in the 2015 National Health Interview Survey Cancer Control Supplement (N=15,280) reported their disability status (mobility disability, non-mobility disability, or no disability) and perceptions of neighborhood environmental supports (walkable roads, sidewalks, paths, trails; sidewalks on most streets; and walkable shops; transit; movies, libraries, churches; relaxing places) and barriers (traffic, crime, animals) for walking. Adjusted models conducted in 2019 included demographic characteristics. Prevalence of most supports was lower among adults with mobility or non-mobility disabilities versus no disability. For example, 54.9% and 57.5% of adults with mobility and non-mobility disabilities respectively reported sidewalks on most streets, compared to 64.1% of adults with no disability. After adjustment, significant differences remained when comparing adults with a mobility disability versus no disability for two supports (roads, sidewalks, paths, trails; relaxing places). All perceived barriers were significantly more common among adults with any disability versus no disability, regardless of adjustment. In the United States, adults with disabilities perceive fewer neighborhood environmental supports and more barriers for walking than their counterparts. Strategies that increase supports and address barriers for walking may help promote physical activity among adults with disabilities.

      2. Association of daily step count and step intensity with mortality among US adultsexternal icon
        Saint-Maurice PF, Troiano RP, Bassett DR, Graubard BI, Carlson SA, Shiroma EJ, Fulton JE, Matthews CE.
        Jama. 2020 Mar 24;323(12):1151-1160.
        Importance: It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality. Objective: Describe the dose-response relationship between step count and intensity and mortality. Design, Setting, and Participants: Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015. Exposures: Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema. Results: A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34). Conclusions and Relevance: Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day.

    • Public Health Leadership and Management
      1. The US Public Health Service and the American Medical Association House of Delegates: Informing policy at the intersection of public health and medical careexternal icon
        Iskander J, Thomas D, Vora NM, Davlantes E, Lewis B, Griffiths S, Toye S, Puddy RW.
        Public Health Rep. 2020 Mar 30:33354920915438.

    • Reproductive Health
      1. Disability and pregnancy: A cross-federal agency collaboration to collect population-based data about experiences around the time of pregnancyexternal icon
        D'Angelo DV, Cernich A, Harrison L, Kortsmit K, Thierry JM, Folger S, Warner L.
        J Womens Health (Larchmt). 2020 Mar;29(3):291-296.
        Many reproductive-aged women with a disability can achieve successful healthy pregnancies; however, they may face challenges accessing prenatal and postpartum care and finding providers who are knowledgeable about their specific condition. Depending on the nature of the disability, some women may also be at increased risk for adverse maternal and infant outcomes such as pre-eclampsia, infection, anemia, primary cesarean delivery, or preterm birth. Population-based data are needed to better understand the pregnancy and postpartum experiences of women living with disability. The National Institutes of Health and the Centers for Disease Control and Prevention (CDC) collaborated to address these data gaps by leveraging CDC's Pregnancy Risk Assessment Monitoring System (PRAMS) to gather information about disability among women who have had a recent live birth. Data collection began in 2019. Information gathered through PRAMS can be used to guide the development of clinical practices guidelines, intervention programs, and other initiatives of federal, state, and local agencies to improve services and the health of women of reproductive age living with disability.

      2. Assessment of contraceptive use in Puerto Rico during the 2016 Zika virus outbreakexternal icon
        Ellington SR, Serrano Rodriguez R, Goldberg H, Bertolli J, Simeone R, Soto Mercado A, Pazol K, Jamieson DJ, Honein MA, Swartzendruber A, Miles T, Cordero J, Shapiro-Mendoza C.
        Contraception. 2020 Mar 16.
        OBJECTIVES: The objectives of this analysis were to 1) estimate prevalence of contraceptive use among women at risk for unintended pregnancy and 2) identify correlates of contraceptive use among women with ongoing or potential need for contraceptive services in Puerto Rico during the 2016 Zika virus (ZIKV) outbreak. Study Design We conducted a cell-phone survey July-November, 2016. Women aged 18-49 years living in Puerto Rico were eligible. We completed 3,059 interviews; the overall response rate was 69.2%. After weighting, the data provide population-based estimates. For this analysis, we included women at risk for unintended pregnancy, and assessed ongoing or potential need for contraceptive services in this group, excluding women using permanent contraceptive methods. RESULTS: Most women reported using contraception (82.8%), and use increased with age. Female sterilization and male condoms were most frequently reported (40.8% and 17.1%, respectively). Among women with ongoing or potential need for contraceptive services, 24.7% talked to a healthcare provider about ZIKV, and 31.2% reported a change in childbearing intentions due to ZIKV. Most women were at least a little worried about getting infected with ZIKV (74.3%) or having a baby with a birth defect (80.9%). Being very worried about getting infected with ZIKV and already having Zika were significantly associated with use of any contraception (adjusted prevalence ratio: 1.19, 95% CI: 1.03-1.38 and 1.32, 95% CI: 1.01-1.72, respectively). CONCLUSIONS: These findings underscore the need for regular contraceptive prevalence studies to inform programs about contraceptive needs, especially during public health emergencies. IMPLICATIONS: When the 2016 Zika virus outbreak began in Puerto Rico there were no recent population-based data available on contraceptive prevalence. To fill this information gap, we conducted a population-based survey. Our findings provided baseline contraceptive prevalence estimates to support response planning and allocation of health resources.

      3. Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and bloodexternal icon
        Haddad LB, Swaims-Kohlmeier A, Mehta CC, Haaland RE, Brown NL, Sheth AN, Chien H, Titanji K, Achilles SL, Lupo D, Hart CE, Ofotokun I.
        PLoS One. 2020 ;15(3):e0230473.
        BACKGROUND: While prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman's risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk. OBJECTIVE: Evaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant. METHODS: We prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18-45, with normal menses (22-35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated for markers of activation (CD38, HLA-DR), retention (CD103) and trafficking (CCR7) on HIV target cells (CCR5+CD4+ T cells) using multicolor flow cytometry. Cytokines and chemokines in the CVL supernatant and blood plasma were measured in a Luminex assay. We estimated and compared study endpoints among the samples collected before and after contraception initiation with repeated-measures analyses using linear mixed models. RESULTS: Fifteen of 18 women who received an Eng-Implant completed all 4 study visits. The percentage of CD4+ T cells in CVL was not increased after implant placement but the percentage of CD4+ T cells expressing the HIV co-receptor CCR5 did increase after implant placement (p = 0.02). In addition, the percentage of central memory CD4+ T-cells (CCR7+) in CVL increased after implant placement (p = 0.004). The percentage of CVL CD4+, CCR5+ HIV target cells expressing activation markers after implant placement was either reduced (HLA-DR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not significantly different after implant placement except for a higher level of the soluble lymphocyte activation marker (sCD40L; p = 0.04) and lower levels of IL12p70 (p = 0.02) and G-CSF (p<0.001). In systemic blood, none of the changes noted in CVL after implant placement occurred except for decreases in the percentage CD4 T-cells expressing HLA-DR+ T cells (p = 0.006) and G-CSF (p = 0.02). CONCLUSIONS: Eng-Implant use was associated with a moderate increase in the availability of HIV target cells in the genital tract, however the percentage of these cells that were activated did not increase and there were minimal shifts in the overall immune environment. Given the mixed nature of these findings, it is unclear if these implant-induced changes alter HIV risk.

    • Social and Behavioral Sciences
      1. Conversational topics of social media messages associated with state-level mental distress ratesexternal icon
        Bowen DA, Wang J, Holland K, Bartholow B, Sumner SA.
        J Ment Health. 2020 Mar 30:1-8.
        Background: Upstream public health indicators of poor mental health in the United States (U.S.) are currently measured by national telephone-based surveys; however, results are delayed by 1-2 years, limiting real-time assessment of trends.Aim: The aim of this study was to evaluate associations between conversational topics on Twitter from 2018 to 2019 and mental distress rates from 2017 to 2018 for the 50 U.S. states and capital.Method: We used a novel lexicon, Empath, to examine conversational topics from aggregate social media messages from Twitter that correlated most strongly with official U.S. state-level rates of mental distress from the Behavioral Risk Factor Surveillance System.Results: The ten lexical categories most positively correlated with rates of frequent mental distress at the state-level included categories about death, illness, or injury. Lexical categories most inversely correlated with mental distress included categories that serve as proxies for economic prosperity and industry. Using the prevalence of the 10 most positively and 10 most negatively correlated lexical categories to predict state-level rates of mental distress via a linear regression model on an independent sample of data yielded estimates that were moderately similar to actual rates (mean difference = 0.52%; Pearson correlation = 0.45, p < 0.001).Conclusion: This work informs efforts to use social media to measure population-level trends in mental health.

    • Substance Use and Abuse
      1. Gas chromatography-tandem mass spectrometry method for selective detection of 2-nitropropane in mainstream cigarette smokeexternal icon
        Chapman GM, Junco JG, Cardenas RB, Watson CH, Valentin-Blasini L.
        Beitrage zur Tabakforschung International/ Contributions to Tobacco Research. 2019 ;28(7):300-309.
        Although 2-nitropropane is a potentially harmful compound present in cigarette smoke, there are few fully-validated, modern methods to quantitate it in mainstream cigarette smoke. We developed an isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method for the detection of 2-nitropropane in mainstream cigarette smoke. The vapor fraction of mainstream cigarette smoke was collected in inert polyvinyl fluoride gas sampling bags and extracted with hexanes containing isotopically labeled internal standard, then purified and concentrated via solid-phase extraction using a normal phase silica adsorbent and a 100% dichloromethane eluant. This method is sensitive enough to measure vapor phase 2-nitro-propane concentrations in the nanogram range, with a 19 ng per cigarette method limit of detection. Product variability estimated from the analysis of 15 cigarette products yielded relative standard deviations ranging from 5.4% to 15.7%, and estimates of precision from two quality control products yielded relative standard deviations of 9.49% and 14.9%. Under the Health Canada Intense smoking regimen, 2-nitropropane in machine-generated mainstream smoke from 15 cigarette products ranged from 98.3 to 363 ng per cigarette.

      2. Patterns and characteristics of methamphetamine use among adults - United States, 2015-2018external icon
        Jones CM, Compton WM, Mustaquim D.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):317-323.
        Methamphetamine is a highly addictive central nervous system stimulant. Methamphetamine use is associated with a range of health harms, including psychosis and other mental disorders, cardiovascular and renal dysfunction, infectious disease transmission, and overdose (1,2). Although overall population rates of methamphetamine use have remained relatively stable in recent years (3), methamphetamine availability and methamphetamine-related harms (e.g., methamphetamine involvement in overdose deaths and number of treatment admissions) have increased in the United States* (4,5); however, analyses examining methamphetamine use patterns and characteristics associated with its use are limited. This report uses data from the 2015-2018 National Surveys on Drug Use and Health (NSDUHs) to estimate methamphetamine use rates in the United States and to identify characteristics associated with past-year methamphetamine use. Rates (per 1,000 adults aged >/=18 years) for past-year methamphetamine use were estimated overall, by demographic group, and by state. Frequency of past-year use and prevalence of other substance use and mental illness among adults reporting past-year use were assessed. Multivariable logistic regression examined characteristics associated with past-year use. During 2015-2018, the estimated rate of past-year methamphetamine use among adults was 6.6 per 1,000. Among adults reporting past-year methamphetamine use, an estimated 27.3% reported using on >/=200 days, 52.9% had a methamphetamine use disorder, and 22.3% injected methamphetamine. Controlling for other factors, higher adjusted odds ratios for past-year use were found among men; persons aged 26-34, 35-49, and >/=50 years; and those with lower educational attainment, annual household income <$50,000, Medicaid only or no insurance, those living in small metro and nonmetro counties,(dagger) and those with co-occurring substance use and co-occurring mental illness. Additional efforts to build state and local prevention and response capacity, expand linkages to care, and enhance public health and public safety collaborations are needed to combat increasing methamphetamine harms.

      3. IntroductionThe duration of incoming quitline calls may serve as a crude proxy for the potential amount of reactive counseling provided.AimsTo explore whether call duration may be useful for monitoring quitline capacity and service delivery.MethodsUsing data on the duration of incoming quitline calls to 1-800-QUIT-NOW from 2012 through 2015, we examined national trends and state-level variation in average call duration. We estimated a regression model of average call duration as a function of total incoming calls, nationally and by state, controlling for confounders.ResultsFrom 2012 through 2015, average call duration was 11.4 min, nationally, and was 10 min or longer in 33 states. Average call duration was significantly correlated with quitline service provider. Higher incoming call volume was significantly associated with lower average call duration in 32 states and higher average call duration in five states (P-value <0.05). The relationship between call volume and call duration was not correlated with quitline service provider.ConclusionsVariation in average call duration across states likely reflects different service delivery models. Average call duration was associated with call volume in many states. Significant changes in call duration may highlight potential quitline capacity issues that warrant further investigation.

      4. We used data from the 2016 and 2017 SummerStyles survey (N = 4,186 and 4,066, respectively) to assess US adults' perceptions about the harms of nicotine in electronic vapor products (EVP) to the developing adolescent brain. Of respondents in 2016, 68.5% agreed exposure to nicotine in EVP was harmful, and of respondents in 2017, 62.6% agreed (P < .001). This agreement varied by several covariates. Continued efforts are warranted to educate the public about the risks of EVP use among youth, including the harmful effects of nicotine exposure on the developing adolescent brain.

      5. Prevalence of and risk factors associated with nonfatal overdose among veterans who have experienced homelessnessexternal icon
        Riggs KR, Hoge AE, DeRussy AJ, Montgomery AE, Holmes SK, Austin EL, Pollio DE, Kim YI, Varley AL, Gelberg L, Gabrielian SE, Blosnich JR, Merlin J, Gundlapalli AV, Jones AL, Gordon AJ, Kertesz SG.
        JAMA Netw Open. 2020 Mar 2;3(3):e201190.
        Importance: Individuals with a history of homelessness are at increased risk for drug or alcohol overdose, although the proportion who have had recent nonfatal overdose is unknown. Understanding risk factors associated with nonfatal overdose could guide efforts to prevent fatal overdose. Objectives: To determine the prevalence of recent overdose and the individual contributions of drugs and alcohol to overdose and to identify characteristics associated with overdose among veterans who have experienced homelessness. Design, Setting, and Participants: This survey study was conducted from November 15, 2017, to October 1, 2018, via mailed surveys with telephone follow-up for nonrespondents. Eligible participants were selected from the records of 26 US Department of Veterans Affairs medical centers and included veterans who had received primary care at 1 of these Veterans Affairs medical centers and had a history of experiencing homelessness according to administrative data. Preliminary analyses were conducted in October 2018, and final analyses were conducted in January 2020. Main Outcomes and Measures: Self-report of overdose (such that emergent medical care was obtained) in the previous 3 years and substances used during the most recent overdose. All percentages are weighted according to propensity to respond to the survey, modeled from clinical characteristics obtained in electronic health records. Results: A total of 5766 veterans completed the survey (completion rate, 40.2%), and data on overdose were available for 5694 veterans. After adjusting for the propensity to respond to the survey, the mean (SD) age was 56.4 (18.3) years; 5100 veterans (91.6%) were men, 2225 veterans (38.1%) were black, and 2345 veterans (40.7%) were white. A total of 379 veterans (7.4%) reported any overdose during the past 3 years; 228 veterans (4.6%) reported overdose involving drugs, including 83 veterans (1.7%) who reported overdose involving opioids. Overdose involving alcohol was reported by 192 veterans (3.7%). In multivariable analyses, white race (odds ratio, 2.44 [95% CI, 2.00-2.98]), self-reporting a drug problem (odds ratio, 1.66 [95% CI, 1.39-1.98]) or alcohol problem (odds ratio, 2.54 [95% CI, 2.16-2.99]), and having witnessed someone else overdose (odds ratio, 2.34 [95% CI, 1.98-2.76]) were associated with increased risk of overdose. Conclusions and Relevance: These findings suggest that nonfatal overdose is relatively common among veterans who have experienced homelessness. While overdose involving alcohol was more common than any specific drug, 1.7% of veterans reported overdose involving opioids. Improving access to addiction treatment for veterans who are experiencing homelessness or who are recently housed, especially for those who have experienced or witnessed overdose, could help to protect this population.

      6. Variation in adult outpatient opioid prescription dispensing by age and sex - United States, 2008-2018external icon
        Schieber LZ, Guy GP, Seth P, Losby JL.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):298-302.
        In 2017, prescription opioids were involved in 36% of opioid-involved overdose deaths in the United States (1). Prescription opioids can be obtained by prescription or through diversion (the channeling of regulated drugs from legal to illegal sources) (2). Among new heroin users, 66%-83% reported that their opioid use began with the misuse of a prescription opioid (3). "Misuse" is generally defined as drugs taken for a purpose other than that directed by the prescribing physician, in greater amounts, more often, or for a longer duration than prescribed (2). Exposure to prescription opioids can be lessened by ensuring recommended prescribing, thereby potentially reducing the risk for misuse, opioid use disorder, and overdose (4). Sex and age groups with high exposure to prescription opioids are not well defined. Using a retail pharmaceutical database from IQVIA,* nationwide trends in opioid prescription fill rates for adult outpatients by age and sex were examined during 2008-2018. Opioid prescription fill rates were disproportionately higher among men and women aged >/=65 years and women of all ages. For reasons not well understood, these disparities persisted over 11 years even as the opioid fill rate declined for each age group and sex. Interventions to improve prescribing practices by following evidence-based guidelines that include weighing the benefits and risks for using prescription opioids for each patient and adopting a multimodal approach to pain management could improve patient safety while ameliorating pain. These efforts might need to consider the unique needs of women and older adults, who have the highest opioid prescription fill rates.

      7. Nonfatal drug overdoses treated in emergency departments - United States, 2016-2017external icon
        Vivolo-Kantor AM, Hoots BE, Scholl L, Pickens C, Roehler DR, Board A, Mustaquim D, Smith Ht, Snodgrass S, Liu S.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):371-376.
        In 2017, drug overdoses caused 70,237 deaths in the United States, a 9.6% rate increase from 2016 (1). Monitoring nonfatal drug overdoses treated in emergency departments (EDs) is also important to inform community prevention and response activities. Analysis of discharge data provides insights into the prevalence and trends of nonfatal drug overdoses, highlighting opportunities for public health action to prevent overdoses. Using discharge data from the Healthcare Cost and Utilization Project's (HCUP) Nationwide Emergency Department Sample (NEDS), CDC identified nonfatal overdoses for all drugs, all opioids, nonheroin opioids, heroin, benzodiazepines, and cocaine and examined changes from 2016 to 2017, stratified by drug type and by patient, facility, and visit characteristics. In 2017, the most recent year for which population-level estimates of nonfatal overdoses can be generated, a total of 967,615 nonfatal drug overdoses were treated in EDs, an increase of 4.3% from 2016, which included 305,623 opioid-involved overdoses, a 3.1% increase from 2016. From 2016 to 2017, the nonfatal overdose rates for all drug types increased significantly except for those involving benzodiazepines. These findings highlight the importance of continued surveillance of nonfatal drug overdoses treated in EDs to inform public health actions and, working collaboratively with clinical and public safety partners, to link patients to needed recovery and treatment resources (e.g., medication-assisted treatment).

      8. Drug and opioid-involved overdose deaths - United States, 2017-2018external icon
        Wilson N, Kariisa M, Seth P, Smith H, Davis NL.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):290-297.
        Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.

    • Veterinary Medicine
      1. Acute human orthopneumovirus infection in a captive white-handed gibbonexternal icon
        Sojka PA, Ploog CL, Garner MM, Kiupel M, Kuypers J, Huynh T.
        J Vet Diagn Invest. 2020 Mar 13.
        We report herein a fatal case of acute human orthopneumovirus (formerly respiratory syncytial virus) infection in a captive white-handed gibbon (Hylobates lar). Other members of the housing group had mild respiratory signs. Gross examination revealed bilateral pulmonary congestion and froth in the bronchi. Microscopically, the lungs had lymphocytic, neutrophilic infiltration of the interstitium and alveolar walls. There was necrosis of terminal bronchiolar epithelium and terminal bronchioles, and surrounding alveoli contained necrotic and exfoliated epithelial cells admixed with histiocytes and syncytial cells. Additional lesions included nonsuppurative meningoencephalitis, and epidermal hyperkeratosis and hyperplasia with syncytial cell formation. PCR screening for 12 human respiratory viruses was positive for orthopneumovirus in multiple tissues, including lung, and immunohistochemical staining for human orthopneumovirus detected viral antigen within bronchial epithelial cells. IHC and PCR for measles virus on preserved sections were negative. White-handed gibbons have not been previously reported as hosts for human orthopneumovirus, an important respiratory pathogen of both primates and humans.

      2. Entamoeba histolytica infections in wild and semi-wild orangutans in Sumatra and Kalimantanexternal icon
        Stuart P, Yalcindag E, Ali IK, Peckova R, Nurcahyo W, Morrogh-Bernard H, Foitova I.
        Am J Primatol. 2020 Mar 16:e23124.
        Key to the success of orangutan conservation management practices is the prevention of the introduction of infectious diseases to the remaining populations. Previous reports of Entamoeba spp. positive orangutans are of concern as Entamoeba spp. infection has been linked to morbidity and mortality in primates. It remains to be determined if the Entamoeba species infecting orangutans is the pathogenic Entamoeba histolytica. Orangutan fecal samples have been collected from orangutans from sites in Sumatra (Bukit Lawang, Ketambe, and Suaq, 241 samples from 64 individuals), and two sites in Kalimantan (Sebangau and Tuanan, 129 samples from 39 individuals). All samples were from wild orangutans except for a proportion from Sumatra which were from semi-wild (108 samples, 10 individuals). E. histolytica-specific nested PCR assays were carried out on the fecal samples. A total of 36 samples from 17 individuals tested positive for E. histolytica. When compared with published sequences using NCBI BLAST the E. histolytica positive samples showed a 98-99% concordance. The majority (76%, n = 36) of the positive isolates came from semi-wild orangutans in Bukit Lawang. This study supports the growing body of evidence that contact with humans is an important risk factor for infection of wild primates with E. histolytica.

    • Zoonotic and Vectorborne Diseases
      1. Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019external icon
        Aceng JR, Ario AR, Muruta AN, Makumbi I, Nanyunja M, Komakech I, Bakainaga AN, Talisuna AO, Mwesigye C, Mpairwe AM, Tusiime JB, Lali WZ, Katushabe E, Ocom F, Kaggwa M, Bongomin B, Kasule H, Mwoga JN, Sensasi B, Mwebembezi E, Katureebe C, Sentumbwe O, Nalwadda R, Mbaka P, Fatunmbi BS, Nakiire L, Lamorde M, Walwema R, Kambugu A, Nanyondo J, Okware S, Ahabwe PB, Nabukenya I, Kayiwa J, Wetaka MM, Kyazze S, Kwesiga B, Kadobera D, Bulage L, Nanziri C, Monje F, Aliddeki DM, Ntono V, Gonahasa D, Nabatanzi S, Nsereko G, Nakinsige A, Mabumba E, Lubwama B, Sekamatte M, Kibuule M, Muwanguzi D, Amone J, Upenytho GD, Driwale A, Seru M, Sebisubi F, Akello H, Kabanda R, Mutengeki DK, Bakyaita T, Serwanjja VN, Okwi R, Okiria J, Ainebyoona E, Opar BT, Mimbe D, Kyabaggu D, Ayebazibwe C, Sentumbwe J, Mwanja M, Ndumu DB, Bwogi J, Balinandi S, Nyakarahuka L, Tumusiime A, Kyondo J, Mulei S, Lutwama J, Kaleebu P, Kagirita A, Nabadda S, Oumo P, Lukwago R, Kasozi J, Masylukov O, Kyobe HB, Berdaga V, Lwanga M, Opio JC, Matseketse D, Eyul J, Oteba MO, Bukirwa H, Bulya N, Masiira B, Kihembo C, Ohuabunwo C, Antara SN, Owembabazi W, Okot PB, Okwera J, Amoros I, Kajja V, Mukunda BS, Sorela I, Adams G, Shoemaker T, Klena JD, Taboy CH, Ward SE, Merrill RD, Carter RJ, Harris JR, Banage F, Nsibambi T, Ojwang J, Kasule JN, Stowell DF, Brown VR, Zhu BP, Homsy J, Nelson LJ, Tusiime PK, Olaro C, Mwebesa HG, Woldemariam YT.
        Global Health. 2020 Mar 19;16(1):24.
        BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies.

      2. COVID-19: towards controlling of a pandemicexternal icon
        Bedford J, Enria D, Giesecke J, Heymann DL, Ihekweazu C, Kobinger G, Lane HC, Memish Z, Oh MD, Sall AA, Schuchat A, Ungchusak K, Wieler LH.
        Lancet. 2020 Mar 17.

      3. Functional outcomes among a cohort of children in northeastern Brazil meeting criteria for follow-up of congenital Zika virus infectionexternal icon
        Bertolli J, Attell JE, Rose C, Moore CA, Melo F, Staples JE, Kotzky K, Krishna N, Satterfield-Nash A, Pereira IO, Pessoa A, Smith DC, Faria e Silva Santelli AC, Boyle CA, Peacock G.
        Am J Trop Med Hyg. 2020 Mar 30.
        Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraiba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.

      4. Pediatric Q Feverexternal icon
        Cherry CC, Kersh GJ.
        Curr Infect Dis Rep. 2020 ;22(4).
        Purpose of Review: The non-specific presentation of acute Q fever makes it difficult to diagnose in children, but untreated Q fever can result in chronic infections that have severe complications. Recent Findings: Pediatric Q fever cases continue to be infrequently reported in the literature, and primarily document cases of persistent infections with Coxiella burnetii. Standardized treatment protocols for chronic Q fever in children still do not exist. Doxycycline and hydroxychloroquine are the treatment combination most utilized by healthcare providers to treat Q fever endocarditis or osteomyelitis in children, but a variety of other antibiotic combinations have been reported with varying results. The use of adjunctive therapies, such as such as interferon gamma, has produced mixed outcomes. Summary: The true impact of Coxiella burnetii on the health of children remains unknown; long-term longitudinal follow-up of children with acute or chronic Q fever has not been reported. Both the acute and chronic forms of Q fever are underreported and underdiagnosed. Healthcare providers should consider Q fever in pediatric patients with culture-negative endocarditis or osteomyelitis.

      5. Parenting in a time of COVID-19external icon
        Cluver L, Lachman JM, Sherr L, Wessels I, Krug E, Rakotomalala S, Blight S, Hillis S, Bachman G, Green O, Butchart A, Tomlinson M, Ward CL, Doubt J, McDonald K.
        Lancet. 2020 Mar 25.

      6. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USAexternal icon
        Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K, Rubin R, Morales-Estrada S, Black SR, Pacilli M, Fricchione MJ, Chugh RK, Walblay KA, Ahmed NS, Stoecker WC, Hasan NF, Burdsall DP, Reese HE, Wallace M, Wang C, Moeller D, Korpics J, Novosad SA, Benowitz I, Jacobs MW, Dasari VS, Patel MT, Kauerauf J, Charles EM, Ezike NO, Chu V, Midgley CM, Rolfes MA, Gerber SI, Lu X, Lindstrom S, Verani JR, Layden JE.
        Lancet. 2020 Mar 13.
        BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

      7. Reviewing solutions of scale for canine rabies elimination in Indiaexternal icon
        Gibson AD, Wallace RM, Rahman A, Bharti OK, Isloor S, Lohr F, Gamble L, Mellanby RJ, King A, Day MJ.
        Trop Med Infect Dis. 2020 Mar 23;5(1).
        Canine rabies elimination can be achieved through mass vaccination of the dog population, as advocated by the WHO, OIE and FAO under the 'United Against Rabies' initiative. Many countries in which canine rabies is endemic are exploring methods to access dogs for vaccination, campaign structures and approaches to resource mobilization. Reviewing aspects that fostered success in rabies elimination campaigns elsewhere, as well as examples of largescale resource mobilization, such as that seen in the global initiative to eliminate poliomyelitis, may help to guide the planning of sustainable, scalable methods for mass dog vaccination. Elimination of rabies from the majority of Latin America took over 30 years, with years of operational trial and error before a particular approach gained the broad support of decision makers, governments and funders to enable widespread implementation. The endeavour to eliminate polio now enters its final stages; however, there are many transferrable lessons to adopt from the past 32 years of global scale-up. Additionally, there is a need to support operational research, which explores the practicalities of mass dog vaccination roll-out and what are likely to be feasible solutions at scale. This article reviews the processes that supported the scale-up of these interventions, discusses pragmatic considerations of campaign duration and work-force size and finally provides an examples hypothetical resource requirements for implementing mass dog vaccination at scale in Indian cities, with a view to supporting the planning of pilot campaigns from which expanded efforts can grow.

      8. Zika virus infection and Guillain-Barre syndrome in northeastern Mexico: A case-control studyexternal icon
        Gongora-Rivera F, Grijalva I, Infante-Valenzuela A, Camara-Lemarroy C, Garza-Gonzalez E, Paredes-Cruz M, Grajales-Muniz C, Guerrero-Cantera J, Vargas-Ramos I, Soares J, Abrams JY, Styczynski AR, Camacho-Ortiz A, Villarino ME, Belay ED, Schonberger LB, Sejvar JJ.
        PLoS One. 2020 ;15(3):e0230132.
        BACKGROUND: Beginning August 2017, we conducted a prospective case-control investigation in Monterrey, Mexico to assess the association between Zika virus (ZIKV) and Guillain-Barre syndrome (GBS). METHODS: For each of 50 GBS case-patients, we enrolled 2-3 afebrile controls (141 controls in total) matched by sex, age group, and presentation to same hospital within 7 days. RESULTS: PCR results for ZIKV in blood and/or urine were available on all subjects; serum ZIKV IgM antibody for 52% of case-patients and 80% of controls. Subjects were asked about antecedent illness in the two months prior to neurological onset (for case-patients) or interview (for controls). Laboratory evidence of ZIKV infection alone (PCR+ or IgM+) was not significantly different between case-patients and controls (OR: 1.26, 95% CI: 0.45-3.54) but antecedent symptomatic ZIKV infection [a typical ZIKV symptom (rash, joint pain, or conjunctivitis) plus laboratory evidence of ZIKV infection] was higher among case-patients (OR: 12.45, 95% CI: 1.45-106.64). GBS case-patients with laboratory evidence of ZIKV infection were significantly more likely to have had typical ZIKV symptoms than controls with laboratory evidence of ZIKV infection (OR: 17.5, 95% CI: 3.2-96.6). This association remained significant even when only GBS case-patients who were afebrile for 5 days before onset were included in the analysis, (OR 9.57 (95% CI: 1.07 to 85.35). CONCLUSIONS: During ZIKV epidemics, this study indicates that increases in GBS will occur primarily among those with antecedent symptomatic ZIKV.

      9. From H5N1 to HxNy: An epidemiologic overview of human infections with avian influenza in the Western Pacific Region, 2003-2017external icon
        Hamid S, Arima Y, Dueger E, Konings F, Bell L, Lee CK, Luo D, Otsu S, Olowokure B, Li A.
        Western Pac Surveill Response J. 2018;9(5 Suppl 1):53-67.

      10. Notes from the field: First evidence of locally acquired dengue since 1944 - Guam, 2019external icon
        Kern-Allely S, Pobutsky A, Hancock WT.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):387-388.

      11. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - King County, Washington, March 2020external icon
        Kimball A, Hatfield KM, Arons M, James A, Taylor J, Spicer K, Bardossy AC, Oakley LP, Tanwar S, Chisty Z, Bell JM, Methner M, Harney J, Jacobs JR, Carlson CM, McLaughlin HP, Stone N, Clark S, Brostrom-Smith C, Page LC, Kay M, Lewis J, Russell D, Hiatt B, Gant J, Duchin JS, Clark TA, Honein MA, Reddy SC, Jernigan JA.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):377-381.
        Older adults are susceptible to severe coronavirus disease 2019 (COVID-19) outcomes as a consequence of their age and, in some cases, underlying health conditions (1). A COVID-19 outbreak in a long-term care skilled nursing facility (SNF) in King County, Washington that was first identified on February 28, 2020, highlighted the potential for rapid spread among residents of these types of facilities (2). On March 1, a health care provider at a second long-term care skilled nursing facility (facility A) in King County, Washington, had a positive test result for SARS-CoV-2, the novel coronavirus that causes COVID-19, after working while symptomatic on February 26 and 28. By March 6, seven residents of this second facility were symptomatic and had positive test results for SARS-CoV-2. On March 13, CDC performed symptom assessments and SARS-CoV-2 testing for 76 (93%) of the 82 facility A residents to evaluate the utility of symptom screening for identification of COVID-19 in SNF residents. Residents were categorized as asymptomatic or symptomatic at the time of testing, based on the absence or presence of fever, cough, shortness of breath, or other symptoms on the day of testing or during the preceding 14 days. Among 23 (30%) residents with positive test results, 10 (43%) had symptoms on the date of testing, and 13 (57%) were asymptomatic. Seven days after testing, 10 of these 13 previously asymptomatic residents had developed symptoms and were recategorized as presymptomatic at the time of testing. The reverse transcription-polymerase chain reaction (RT-PCR) testing cycle threshold (Ct) values indicated large quantities of viral RNA in asymptomatic, presymptomatic, and symptomatic residents, suggesting the potential for transmission regardless of symptoms. Symptom-based screening in SNFs could fail to identify approximately half of residents with COVID-19. Long-term care facilities should take proactive steps to prevent introduction of SARS-CoV-2 (3). Once a confirmed case is identified in an SNF, all residents should be placed on isolation precautions if possible (3), with considerations for extended use or reuse of personal protective equipment (PPE) as needed (4).

      12. COVID-19 in a long-term care facility - King County, Washington, February 27-March 9, 2020external icon
        McMichael TM, Clark S, Pogosjans S, Kay M, Lewis J, Baer A, Kawakami V, Lukoff MD, Ferro J, Brostrom-Smith C, Riedo FX, Russell D, Hiatt B, Montgomery P, Rao AK, Currie DW, Chow EJ, Tobolowsky F, Bardossy AC, Oakley LP, Jacobs JR, Schwartz NG, Stone N, Reddy SC, Jernigan JA, Honein MA, Clark TA, Duchin JS.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):339-342.
        On February 28, 2020, a case of coronavirus disease (COVID-19) was identified in a woman resident of a long-term care skilled nursing facility (facility A) in King County, Washington.* Epidemiologic investigation of facility A identified 129 cases of COVID-19 associated with facility A, including 81 of the residents, 34 staff members, and 14 visitors; 23 persons died. Limitations in effective infection control and prevention and staff members working in multiple facilities contributed to intra- and interfacility spread. COVID-19 can spread rapidly in long-term residential care facilities, and persons with chronic underlying medical conditions are at greater risk for COVID-19-associated severe disease and death. Long-term care facilities should take proactive steps to protect the health of residents and preserve the health care workforce by identifying and excluding potentially infected staff members and visitors, ensuring early recognition of potentially infected patients, and implementing appropriate infection control measures.

      13. Epidemiology of Covid-19 in a long-term care facility in King County, Washingtonexternal icon
        McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, Lewis J, Baer A, Kawakami V, Lukoff MD, Ferro J, Brostrom-Smith C, Rea TD, Sayre MR, Riedo FX, Russell D, Hiatt B, Montgomery P, Rao AK, Chow EJ, Tobolowsky F, Hughes MJ, Bardossy AC, Oakley LP, Jacobs JR, Stone ND, Reddy SC, Jernigan JA, Honein MA, Clark TA, Duchin JS.
        N Engl J Med. 2020 Mar 27.
        BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health-Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.

      14. Public health responses to COVID-19 outbreaks on cruise ships - worldwide, February-March 2020external icon
        Moriarty LF, Plucinski MM, Marston BJ, Kurbatova EV, Knust B, Murray EL, Pesik N, Rose D, Fitter D, Kobayashi M, Toda M, Canty PT, Scheuer T, Halsey ES, Cohen NJ, Stockman L, Wadford DA, Medley AM, Green G, Regan JJ, Tardivel K, White S, Brown C, Morales C, Yen C, Wittry B, Freeland A, Naramore S, Novak RT, Daigle D, Weinberg M, Acosta A, Herzig C, Kapella BK, Jacobson KR, Lamba K, Ishizumi A, Sarisky J, Svendsen E, Blocher T, Wu C, Charles J, Wagner R, Stewart A, Mead PS, Kurylo E, Campbell S, Murray R, Weidle P, Cetron M, Friedman CR.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):347-352.
        An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged >/=65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.

      15. First mildly ill, non-hospitalized case of coronavirus disease 2019 (COVID-19) without viral transmission in the United States - Maricopa County, Arizona, 2020external icon
        Scott SE, Zabel K, Collins J, Hobbs KC, Kretschmer MJ, Lach M, Turnbow K, Speck L, White JR, Maldonado K, Howard B, Fowler J, Singh S, Robinson S, Pompa AP, Chatham-Stephens K, Xie A, Cates J, Lindstrom S, Lu X, Rolfes MA, Flanagan M, Sunenshine R.
        Clin Infect Dis. 2020 Apr 2.
        BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, non-hospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on January 22, 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (>/=10 minutes within 2 meters). Medium-risk contacts wore all U.S. Centers for Disease Control and Prevention (CDC)-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), >/=1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

      16. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1external icon
        van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, de Wit E, Munster VJ.
        N Engl J Med. 2020 Mar 17.


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