Volume 12, Issue 21, June 30, 2020

CDC Science Clips: Volume 12, Issue 21, June 30, 2020

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Employment outcomes among cancer survivors in the United States: Implications for cancer care deliveryexternal icon
        de Moor JS, Kent EE, McNeel TS, Virgo KS, Swanberg J, Tracy JK, Banegas MP, Han X, Qin J, Yabroff KR.
        J Natl Cancer Inst. 2020 Jun 13.
        The national prevalence of employment changes after a cancer diagnosis has not been fully documented. Cancer survivors who worked for pay at or since diagnosis (n = 1,490) were identified from the 2011, 2016 and 2017 Medical Expenditure Panel Survey and Experiences with Cancer Supplements. Analyses characterized employment changes due to cancer and identified correlates of those employment changes. Employment changes were made by 41.3% (95% CI = 38.0% to 44.6%) of cancer survivors, representing over 3.5 million adults in the United States. Of these, 75.4% (95% CI = 71.3 to 79.2%) took extended paid time-off and 46.1% (95% CI = 41.6 to 50.7%) made other changes, including switching to part-time or to a less demanding job. Cancer survivors who were younger, female, non-white or multiple races/ethnicities, and <20 years since last cancer treatment were more likely to make employment changes. Findings highlight the need for patient-provider communication about the effects of cancer and its treatment on employment.

    • Communicable Diseases
      • Severe coronavirus infections in pregnancy: A systematic reviewexternal icon
        Galang RR, Chang K, Strid P, Snead MC, Woodworth KR, House LD, Perez M, Barfield WD, Meaney-Delman D, Jamieson DJ, Shapiro-Mendoza CK, Ellington SR.
        Obstet Gynecol. 2020 Jun 16.
        OBJECTIVE: To inform the current coronavirus disease 2019 (COVID-19) outbreak, we conducted a systematic literature review of case reports of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, during pregnancy and summarized clinical presentation, course of illness, and pregnancy and neonatal outcomes. DATA SOURCES: We searched MEDLINE and from inception to April 23, 2020. METHODS OF STUDY SELECTION: We included articles reporting case-level data on MERS-CoV, SARS-CoV, and SARS-CoV-2 infection in pregnant women. Course of illness, indicators of severe illness, maternal health outcomes, and pregnancy outcomes were abstracted from included articles. TABULATION, INTEGRATION, AND RESULTS: We identified 1,328 unique articles, and 1,253 articles were excluded by title and abstract review. We completed full-text review on 75, and 29 articles were excluded by full-text review. Among 46 publications reporting case-level data, eight described 12 cases of MERS-CoV infection, seven described 17 cases of SARS-CoV infection, and 31 described 98 cases of SARS-CoV-2 infection. Clinical presentation and course of illness ranged from asymptomatic to severe fatal disease, similar to the general population of patients. Severe morbidity and mortality among women with MERS-CoV, SARS-CoV, or SARS-CoV-2 infection in pregnancy and adverse pregnancy outcomes, including pregnancy loss, preterm delivery, and laboratory evidence of vertical transmission, were reported. CONCLUSION: Understanding whether pregnant women may be at risk for adverse maternal and neonatal outcomes from severe coronavirus infections is imperative. Data from case reports of SARS-CoV, MERS-CoV, and SAR-CoV-2 infections during pregnancy are limited, but they may guide early public health actions and clinical decision-making for COVID-19 until more rigorous and systematically collected data are available. The capture of critical data is needed to better define how this infection affects pregnant women and neonates. This review was not registered with PROSPERO.

      • Respiratory syncytial virus-associated hospitalizations among young children: 2015-2016external icon
        Rha B, Curns AT, Lively JY, Campbell AP, Englund JA, Boom JA, Azimi PH, Weinberg GA, Staat MA, Selvarangan R, Halasa NB, McNeal MM, Klein EJ, Harrison CJ, Williams JV, Szilagyi PG, Singer MN, Sahni LC, Figueroa-Downing D, McDaniel D, Prill MM, Whitaker BL, Stewart LS, Schuster JE, Pahud BA, Weddle G, Avadhanula V, Munoz FM, Piedra PA, Payne DC, Langley G, Gerber SI.
        Pediatrics. 2020 Jun 16.
        BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden. METHODS: Children <5 years old hospitalized for ARI were enrolled through active, prospective, population-based surveillance from November 1, 2015, to June 30, 2016, at 7 US pediatric hospital sites. Clinical information was obtained from parent interviews and medical records. Midturbinate nasal and throat flocked swabs were collected and tested for RSV by using molecular diagnostic assays at each site. We conducted descriptive analyses and calculated population-based rates of RSV-associated hospitalizations. RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were <2 years old, and 526 (50%) were <6 months old. RSV-associated hospitalization rates were 2.9 per 1000 children <5 years old and 14.7 per 1000 children <6 months old; the highest age-specific rate was observed in 1-month-old infants (25.1 per 1000). Most children who were infected with RSV (67%) had no underlying comorbid conditions and no history of preterm birth. CONCLUSIONS: During the 2015-2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants <6 months. Most children who were RSV-positive had no history of prematurity or underlying medical conditions, suggesting that all young children could benefit from targeted interventions against RSV.

    • Disease Reservoirs and Vectors
      • Methods and indicators for measuring patterns of human exposure to malaria vectorsexternal icon
        Monroe A, Moore S, Okumu F, Kiware S, Lobo NF, Koenker H, Sherrard-Smith E, Gimnig J, Killeen GF.
        Malar J. 2020 Jun 16;19(1):207.
        BACKGROUND: Effective targeting and evaluation of interventions that protect against adult malaria vectors requires an understanding of how gaps in personal protection arise. An improved understanding of human and mosquito behaviour, and how they overlap in time and space, is critical to estimating the impact of insecticide-treated nets (ITNs) and determining when and where supplemental personal protection tools are needed. Methods for weighting estimates of human exposure to biting Anopheles mosquitoes according to where people spend their time were first developed over half a century ago. However, crude indoor and outdoor biting rates are still commonly interpreted as indicative of human-vector contact patterns without any adjustment for human behaviour or the personal protection effects of ITNs. MAIN TEXT: A small number of human behavioural variables capturing the distribution of human populations indoors and outdoors, whether they are awake or asleep, and if and when they use an ITN over the course of the night, can enable a more accurate representation of human biting exposure patterns. However, to date no clear guidance is available on what data should be collected, what indicators should be reported, or how they should be calculated. This article presents an integrated perspective on relevant indicators of human-vector interactions, the critical entomological and human behavioural data elements required to quantify human-vector interactions, and recommendations for collecting and analysing such data. CONCLUSIONS: If collected and used consistently, this information can contribute to an improved understanding of how malaria transmission persists in the context of current intervention tools, how exposure patterns may change as new vector control tools are introduced, and the potential impact and limitations of these tools. This article is intended to consolidate understanding around work on this topic to date and provide a consistent framework for building upon it. Additional work is needed to address remaining questions, including further development and validation of methods for entomological and human behavioural data collection and analysis.

    • Genetics and Genomics
      • Ten recommendations for supporting open pathogen genomic analysis in public healthexternal icon
        Black A, MacCannell DR, Sibley TR, Bedford T.
        Nat Med. 2020 Jun 11.
        Increasingly, public-health agencies are using pathogen genomic sequence data to support surveillance and epidemiological investigations. As access to whole-genome sequencing has grown, greater amounts of molecular data have helped improve the ability to detect and track outbreaks of diseases such as COVID-19, investigate transmission chains and explore large-scale population dynamics, such as the spread of antibiotic resistance. However, the wide adoption of whole-genome sequencing also poses new challenges for public-health agencies that must adapt to support a new set of expertise, which means that the capacity to perform genomic data assembly and analysis has not expanded as widely as the adoption of sequencing itself. In this Perspective, we make recommendations for developing an accessible, unified informatic ecosystem to support pathogen genomic analysis in public-health agencies across income settings. We hope that the creation of this ecosystem will allow agencies to effectively and efficiently share data, workflows and analyses and thereby increase the reproducibility, accessibility and auditability of pathogen genomic analysis while also supporting agency autonomy.

    • Healthcare Associated Infections
      • Long-term outcomes of patients with fungal infections associated with contaminated methylprednisolone injectionsexternal icon
        Malani AN, Kauffman CA, Latham R, Peglow S, Ledtke CS, Kerkering TM, Kaufman DH, Triplett PF, Wright PW, Bloch KC, McCotter O, Toda M, Jackson BR, Pappas PG, Chiller TM.
        Open Forum Infect Dis. 2020 Jun;7(6):ofaa164.
        Background: The largest health care-associated infection outbreak in the United States occurred during 2012-2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. Methods: This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. Results: Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. Conclusions: Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections.

    • Immunity and Immunization
      • An overview of rotavirus vaccination programs in developing countriesexternal icon
        Hallowell BD, Tate J, Parashar U.
        Expert Rev Vaccines. 2020 Jun 16:1-9.
        INTRODUCTION: Rotavirus is the leading cause of acute diarrhea among children <5 years worldwide. As all children are equally susceptible to infection and disease development, rotavirus vaccination programs are the best upstream approach to preventing rotavirus disease, and the subsequent risk of hospitalization or death. AREAS COVERED: We provide an overview of global rotavirus vaccine policy, summarize the burden of rotavirus disease in developing countries, review data on the effectiveness, impact, safety, and the cost-effectiveness of rotavirus vaccination programs, and identify areas for further research and improvement. EXPERT OPINION: Rotavirus vaccines continue to be an effective, safe, and cost-effective solution to preventing rotavirus disease. As two new rotavirus vaccines enter the market (Rotasiil and Rotavac) and Asian countries continue to introduce rotavirus vaccines into their national immunization programs, documenting vaccine safety, effectiveness, and impact in these settings will be paramount.

    • Nutritional Sciences
      • Health and budgetary impact of achieving 10-year U.S. sodium reduction targetsexternal icon
        Dehmer SP, Cogswell ME, Ritchey MD, Hong Y, Maciosek MV, LaFrance AB, Roy K.
        Am J Prev Med. 2020 Jun 4.
        INTRODUCTION: This study estimates the health, economic, and budgetary impact resulting from graduated sodium reductions in the commercially produced food supply of the U.S., which are consistent with draft U.S. Food and Drug Administration voluntary guidance and correspond to Healthy People 2020 objectives and the 2015-2020 Dietary Guidelines for Americans. METHODS: Reduction in mean U.S. dietary sodium consumption to 2,300 mg/day was implemented in a microsimulation model designed to evaluate prospective cardiovascular disease-related policies in the U.S. POPULATION: The analysis was conducted in 2018-2020, and the microsimulation model was constructed using various data sources from 1948 to 2018. Modeled outcomes over 10 years included prevalence of systolic blood pressure >/=140 mmHg; incident myocardial infarction, stroke, cardiovascular disease events, and cardiovascular disease-related mortality; averted medical costs by payer in 2017 U.S. dollars; and productivity. RESULTS: Reducing sodium consumption is expected to reduce the number of people with systolic blood pressure >/=140 mmHg by about 22% and prevent approximately 895.2 thousand cardiovascular disease events (including 218.9 thousand myocardial infarctions and 284.5 thousand strokes) and 252.5 thousand cardiovascular disease-related deaths over 10 years in the U.S. Savings from averted disease costs are expected to total almost $37 billion-most of which would be attributed to Medicare ($18.4 billion) and private insurers ($13.4 billion)-and increased productivity from reduced disease burden and premature mortality would account for another $18.2 billion in gains. CONCLUSIONS: Systemic sodium reductions in the U.S. food supply can be expected to produce substantial health and economic benefits over a 10-year period, particularly for Medicare and private insurers.

    • Occupational Safety and Health
    • Parasitic Diseases
      • First international external quality assessment scheme of nucleic acid amplification tests for the detection of Schistosoma and soil-transmitted helminths, including Strongyloides: A pilot studyexternal icon
        Cools P, van Lieshout L, Koelewijn R, Addiss D, Ajjampur SS, Ayana M, Bradbury RS, Cantera JL, Dana D, Fischer K, Imtiaz R, Kabagenyi J, Lok J, McCarthy J, Mejia R, Mekonnen Z, Njenga SM, Othman N, Shao H, Traub R, Van Esbroeck M, Vercruysse J, Vlaminck J, Williams SA, Verweij JJ, van Hellemond JJ, Levecke B.
        PLoS Negl Trop Dis. 2020 Jun 16;14(6):e0008231.
        BACKGROUND: Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used. METHODS AND PRINCIPAL FINDINGS: A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing. CONCLUSIONS/SIGNIFICANCE: We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs.

    • Public Health Leadership and Management
      • Employee turnover is a major challenge facing the federal workforce, which has lost more employees to voluntary turnover than any other form of turnover. This study determined the associations between engagement, demographic factors, and voluntary turnover intention by analyzing 2015 Federal Employee Viewpoint Survey data. The findings indicate that employees with higher engagement levels are less likely to report an intention to leave their jobs than those with lower engagement levels. All engagement factors—perceptions of supervisors, leaders, and intrinsic work experience—are independently associated with turnover intention. Demographics also influenced turnover intention; being younger, male, and in a supervisory role and having a higher education level and shorter tenure were more likely to indicate turnover intention. Increasing employee engagement can have a positive effect on retaining a productive federal workforce. To retain an effective federal workforce, human capital management practices are needed to optimize factors that reduce turnover intention.

    • Substance Use and Abuse
      • Transitioning from pharmaceutical opioids: A discrete-time survival analysis of heroin initiation in suburban/exurban communitiesexternal icon
        Gaines TL, Wagner KD, Mittal ML, Bowles JM, Copulsky E, Faul M, Harding RW, Davidson PJ.
        Drug Alcohol Depend. 2020 May 28;213:108084.
        INTRODUCTION: Research identifying pathways to heroin use has typically been conducted among urban populations. This study examined heroin initiation following pharmaceutical opioid use in three suburban/exurban Southern California counties. METHODS: Interviewer-administered surveys collected data among 330 participants (65.9 % male; 63.9 % non-Hispanic white) whose initial use of any opioid was a pharmaceutical opioid. Retrospective discrete-time survival analysis identified predictors of heroin initiation, measured as self-reported age of first heroin use. RESULTS: Median age of first pharmaceutical opioid use was 17 years; 50.6 % initially acquired pharmaceutical opioids from an illicit source, 56.7 % first used pharmaceutical opioids for recreational purposes, and 86 % initiated heroin use. Average time from first pharmaceutical opioid use to first heroin use was 8.2 years. Drug/alcohol treatment (adjusted Hazard Ratio [aHR]: 0.67, 95 % CI: 0.50, 0.88) was associated with delayed time to heroin initiation. Obtaining opioids from non-medical sources (aHR: 2.21, 95 % CI: 1.55, 3.14) was associated with accelerated time to heroin initiation. Reporting supply problems with obtaining pharmaceutical opioids (e.g., unable to acquire pharmaceutical opioids) was associated with accelerated time to heroin initiation, but the magnitude of this effect was dependent on one's history of methamphetamine use (p < 0.05). CONCLUSIONS: Time to heroin initiation following pharmaceutical opioid use was accelerated among those reporting supply problems and delayed among those with exposure to substance use treatment. Interventions interrupting supply of opioids might benefit from coordination with evidence-based medication-assisted treatment to minimize the risk of transitioning to heroin use, particularly among those with a long history of non-prescribed pharmaceutical opioid use.

  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. Relative survival after diagnosis with a primary brain or other central nervous system tumor in the National Program of Cancer Registries, 2004 to 2014external icon
        Ostrom QT, Truitt G, Gittleman H, Brat DJ, Kruchko C, Wilson R, Barnholtz-Sloan JS.
        Neurooncol Pract. 2020 Jun;7(3):306-312.
        Background: The majority of reported cancer survival statistics in the United States are generated using the National Cancer Institute's publicly available Surveillance, Epidemiology, and End Results (SEER) data, which prior to 2019 represented 28% of the US population (now 37%). In the case of rare cancers or special subpopulations, data sets based on a larger portion of the US population may contribute new insights into these low-incidence cancers. The purpose of this study is to characterize the histology-specific survival patterns for all primary malignant and nonmalignant primary brain tumors in the United States using the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Methods: Survival data were obtained from the NPCR (includes data from 39 state cancer registries, representing 81% of the US population). Relative survival rates (RS) with 95% CI were generated using SEER*Stat 8.3.5 from 2004 to 2014 by behavior, histology, sex, race/ethnicity, and age at diagnosis. Results: Overall, there were 488 314 cases from 2004 to 2014. Overall 5-year RS was 69.8% (95% CI = 69.6%-69.9%). Five-year RS was 35.9% (95% CI = 35.6%-36.1%) for malignant and 90.2% (95% CI = 90.1%-90.4%) for nonmalignant tumors. Pilocytic astrocytoma had the longest 5-year RS (94.2%, 95% CI = 93.6%-94.6%) of all glioma subtypes, whereas glioblastoma had the shortest 5-year RS (6.1%, 95% CI = 6.0%-6.3%). Nonmalignant nerve sheath tumors had the longest 5-year RS (99.3%, 95% CI = 99.1%-99.4%). Younger age and female sex were associated with increased survival for many histologies. Conclusions: Survival after diagnosis with primary brain tumor varies by behavior, histology, and age. Using such a database that includes more than 80% of the US population may represent national survival patterns.

      2. BACKGROUND: Among U.S. adults, over 4 million report a history of epilepsy, and more than 15 million report a history of chronic obstructive pulmonary disease (COPD); Chronic obstructive pulmonary disease, which includes chronic bronchitis and emphysema, is a common somatic comorbidity of epilepsy. This study assessed the relationship between self-reported physician-diagnosed epilepsy and COPD in a large representative sample of the U.S. adult population and explored possible mechanisms. METHODS: Cross-sectional National Health Interview Surveys for 2013, 2015, and 2017 were aggregated to compare the prevalence of COPD between U.S. respondents aged >/=18years with a history of physician-diagnosed epilepsy (n=1783) and without epilepsy (n=93,126). We calculated prevalence of COPD by age-standardized adjustment and prevalence ratios of COPD overall adjusted for sociodemographic and risk factors, by using multivariable logistic regression analyses. A Z-test was conducted to compare the prevalence between people with and without epilepsy at the statistical significance level of 0.05. Prevalence ratios whose 95% confidence intervals did not overlap 1.00 were considered statistically significant. RESULTS: The overall age-standardized prevalence was 5.7% for COPD and 1.8% for epilepsy. Age-standardized prevalence of COPD among respondents with epilepsy (15.4%) exceeded that among those without epilepsy (5.5%). The association remained significantly different among all sociodemographic and risk factor subgroups (p<.05). In the adjusted analyses, epilepsy was also significantly associated with COPD, overall (adjusted prevalence ratio=1.8, 95% confidence interval=1.6-2.1) and in nearly all subgroups defined by selected characteristics. CONCLUSIONS: Epilepsy is associated with a higher prevalence of COPD in U.S. adults. Public health interventions targeting modifiable behavioral and socioeconomic risk factors among people with epilepsy may help prevent COPD and related premature death.

    • Communicable Diseases
      1. Outcomes of HIV-positive patients with non-tuberculous mycobacteria positive culture who received anti-tuberculous treatment in Botswana: Implications of using diagnostic algorithms without non-tuberculous mycobacteriaexternal icon
        Agizew T, Boyd R, Mathebula U, Mathoma A, Basotli J, Serumola C, Pals S, Finlay A, Lekone P, Rankgoane-Pono G, Tlhakanelo T, Chihota V, Auld AF.
        PLoS One. 2020 ;15(6):e0234646.
        BACKGROUND: Patients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert(R) MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures. METHODS: PLHIV attending one of the 22 participating HIV clinics, who screened positive for >/=1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment. RESULTS: Among 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated 'no MTB'. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher's exact test p = 1.00. CONCLUSIONS: While the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential.

      2. Sexual mixing patterns and anal human papillomavirus among young gay, bisexual, and other men who have sex with men and transgender women in 2 cities in the United States, 2012-2014external icon
        Assaf RD, Javanbakht M, Meites E, Gratzer B, Steinau M, Crosby RA, Markowitz LE, Unger ER, Gorbach PM.
        Sex Transm Dis. 2020 Jul;47(7):473-480.
        BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection. Men who have sex with men (MSM) and transgender women (TGW) are at high risk for anal HPV infection and subsequent anal cancer. This study assessed the association of partner discordances with prevalent high-risk anal HPV (HRAHPV) among MSM and TGW. METHODS: Participants were enrolled in the cross-sectional young men's HPV study of gay, bisexual, and other MSM, and TGW, aged 18 to 26 years, from 2 cities. Participants completed a confidential standardized computer-assisted interview and provided self-collected anal swabs for type-specific HPV DNA testing. Multivariate analyses were conducted for 3 discordances of interest (i.e., partner age, race/ethnicity, and concurrent partner) to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Eight hundred sixty-two participants were included for partner race/ethnicity discordance, 601 for partner age discordance, and 581 for concurrent partner analysis. Most reported being older than 21 years, cisgender male, and gay. Adjusted odds of HRAHPV were not significantly increased among participants reporting partner age discrepancy >10 years (aOR, 0.89; 95% CI, 0.51-1.56), partner race/ethnicity discordance (aOR, 0.88; CI, 0.62-1.24), or partner with concurrent partners (aOR, 0.85; 95% CI, 0.50-1.42), compared with those who did not. CONCLUSIONS: This analysis did not identify any partner discordances associated with HRAHPV. Because HPV infection can persist for years, sexual mixing patterns with early partners might be more relevant than the most recent sex partner. Prevalence of HRAHPV was high and could be preventable by preexposure vaccination, as recommended for everyone through age 26 years including MSM and TGW.

      3. Sex differences in the treatment of HIVexternal icon
        Cohn J, Ake J, Moorhouse M, Godfrey C.
        Curr HIV/AIDS Rep. 2020 Jun 11.
        PURPOSE OF REVIEW: Biological and societal influences are different for men and women leading to different HIV outcomes and related infectious and non-infectious complications. This review evaluates sex differences in the epidemiology and immunological response to HIV and looks at major complications and coinfections, as well as care delivery systems focusing on low- and middle-income countries (LMICs) where most people with HIV live. RECENT FINDINGS: More women than men access testing and treatment services in LMIC; women are more likely to be virologically suppressed in that environment. There is a growing recognition that the enhanced immunological response to several pathogens including HIV may result in improved outcomes for infectious comorbidities but may result in a greater burden of non-communicable diseases. Men and women have different requirements for HIV care. Attention to these differences may improve outcomes for all.

      4. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020external icon
        Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, Nahabedian J, Anderson K, Gilboa SM.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):769-775.
        As of June 16, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in 2,104,346 cases and 116,140 deaths in the United States.* During pregnancy, women experience immunologic and physiologic changes that could increase their risk for more severe illness from respiratory infections (1,2). To date, data to assess the prevalence and severity of COVID-19 among pregnant U.S. women and determine whether signs and symptoms differ among pregnant and nonpregnant women are limited. During January 22-June 7, as part of COVID-19 surveillance, CDC received reports of 326,335 women of reproductive age (15-44 years) who had positive test results for SARS-CoV-2, the virus that causes COVID-19. Data on pregnancy status were available for 91,412 (28.0%) women with laboratory-confirmed infections; among these, 8,207 (9.0%) were pregnant. Symptomatic pregnant and nonpregnant women with COVID-19 reported similar frequencies of cough (>50%) and shortness of breath (30%), but pregnant women less frequently reported headache, muscle aches, fever, chills, and diarrhea. Chronic lung disease, diabetes mellitus, and cardiovascular disease were more commonly reported among pregnant women than among nonpregnant women. Among women with COVID-19, approximately one third (31.5%) of pregnant women were reported to have been hospitalized compared with 5.8% of nonpregnant women. After adjusting for age, presence of underlying medical conditions, and race/ethnicity, pregnant women were significantly more likely to be admitted to the intensive care unit (ICU) (aRR = 1.5, 95% confidence interval [CI] = 1.2-1.8) and receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2-2.4). Sixteen (0.2%) COVID-19-related deaths were reported among pregnant women aged 15-44 years, and 208 (0.2%) such deaths were reported among nonpregnant women (aRR = 0.9, 95% CI = 0.5-1.5). These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar. To reduce occurrence of severe illness from COVID-19, pregnant women should be counseled about the potential risk for severe illness from COVID-19, and measures to prevent infection with SARS-CoV-2 should be emphasized for pregnant women and their families.

      5. HIV testing trends at visits to physician offices, community health centers, and emergency departments - United States, 2009-2017external icon
        Hoover KW, Huang YA, Tanner ML, Zhu W, Gathua NW, Pitasi MA, DiNenno EA, Nair S, Delaney KP.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):776-780.
        In 2019, the U.S. Department of Health and Human Services launched the Ending the HIV Epidemic: A Plan for America (EHE) initiative to end the U.S. human immunodeficiency virus (HIV) epidemic by 2030. A critical component of the EHE initiative involves early diagnosis of HIV infection, along with prevention of new transmissions, treatment of infections, and response to HIV outbreaks (1). HIV testing is the first step in identifying persons with HIV infection who need to be engaged in treatment and care as well as persons with a negative HIV test result and who are at high risk for infection and can benefit from HIV preexposure prophylaxis (PrEP) and other prevention services. These opportunities are often missed for persons receiving clinical services in ambulatory care settings (2). Data from the 2009-2016 National Ambulatory Medical Care Survey (NAMCS) and 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed to estimate trends in HIV testing at visits by males and nonpregnant females to physician offices, community health centers (CHCs), and emergency departments (EDs) in the United States. HIV tests were performed at 0.63% of 516 million visits to physician offices, 2.65% of 37 million visits to CHCs, and 0.55% of 87 million visits to EDs. The percentage of visits with an HIV test did not increase at visits to physician offices during 2009-2016, increased at visits to CHC physicians during 2009-2014, and increased slightly at visits to EDs during 2009-2017. All adolescents and adults should have at least one HIV test in their lifetime (3). Strategies that reduce clinical barriers to HIV testing (e.g., clinical decision supports that use information in electronic health records [EHRs] to order an HIV test for persons who require one or standing orders for routine opt-out testing) are needed to increase HIV testing at ambulatory care visits.

      6. Household illness and associated water and sanitation factors in peri-urban Lusaka, Zambia, 2016–2017external icon
        Hubbard SC, Meltzer MI, Kim S, Malambo W, Thornton AT, Shankar MB, Adhikari BB, Jeon S, Bampoe VD, Cunningham LC, Murphy JL, Derado G, Mintz ED, Mwale FK, Chizema-Kawesha E, Brunkard JM.
        npj Clean Water. 2020 ;3(1).
        In Zambia limited access to adequate water and sanitation is a key developmental challenge, particularly for rapidly expanding peri-urban areas. During 2016–2017, a cross-sectional household survey was conducted among 12,500 households representing ~60,000 individuals to assess the burden of household diarrheal and respiratory disease and to measure water, sanitation, and hygiene (WASH) characteristics in Lusaka, Zambia. We found that socio-economic factors, including having an additional household member, having children <5 years old in the household, living in a rental home, and higher annual household expenditure were associated with diarrhea and respiratory illness. We also found an increased risk for diarrhea associated with a number of WASH-related factors–such as not covering all water storage containers, not using soap for handwashing, having an unimproved sanitation facility, and utilizing a heavily shared toilet (≥18 people). Detectable free chlorine residual in household stored water and more hours of water availability per day were associated with reduced odds of waterborne illness. In all, 75% of household stored water was contaminated with E. coli and households consuming less water (<20 L/day per person) for all purposes had lower odds of diarrhea than households consuming more water—these findings highlight the need for enhanced WASH services within densely populated peri-urban areas and the importance of achieving universal access to safely managed water and sanitation services.

      7. Men and women of color have had low pre-exposure prophylaxis (PrEP) uptake. How one's preferred source of health information shapes attitudes toward PrEP is unclear. We conducted cross-sectional surveys to assess changes in PrEP awareness, knowledge, and attitudes, trusted sources for PrEP information, and associations between trusted source of information and PrEP knowledge and attitudes. Participants were recruited from six areas served by community health centers in Chicago, IL (two health centers); Jackson, MS; Newark, NJ; Philadelphia, PA; and Washington, D.C. during June-September 2015 (n = 160) and June-September 2016 (n = 200). Participants were Black (74%), heterosexual (81%), and largely unaware of PrEP (72%). Participants who trusted health experts and community organizations for PrEP information had lower percentages of agreeing with statements indicative of negative PrEP attitudes. Interventions that increase PrEP awareness as well as knowledge and favorable attitudes might help increase PrEP use in communities with high HIV prevalence.

      8. Characteristics associated with hospitalization among patients with COVID-19 - metropolitan Atlanta, Georgia, March-April 2020external icon
        Killerby ME, Link-Gelles R, Haight SC, Schrodt CA, England L, Gomes DJ, Shamout M, Pettrone K, O'Laughlin K, Kimball A, Blau EF, Burnett E, Ladva CN, Szablewski CM, Tobin-D'Angelo M, Oosmanally N, Drenzek C, Murphy DJ, Blum JM, Hollberg J, Lefkove B, Brown FW, Shimabukuro T, Midgley CM, Tate JE, CDC COVID-19 Response Clinical Team .
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):790-794.
        The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged >/=18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age >/=65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.

      9. Partner notification approaches for sex partners and children of human immunodeficiency virus index cases in Cote d'Ivoireexternal icon
        Kingbo MK, Isaakidis P, Lasry A, Takarinda KC, Manzi M, Pringle J, Konan FA, N'Draman J, Danho NK, Abokon AK, Doumatey NI.
        Sex Transm Dis. 2020 Jul;47(7):450-457.
        BACKGROUND: Four partner notification approaches were introduced in health facilities in Cote d'Ivoire to increase human immunodeficiency virus (HIV) testing uptake among the type of contacts (sex partners and biological children younger than 15 years). The study assessed the 4 approaches: client referral (index cases refer the contacts for HIV testing), provider referral (health care providers refer the contacts), contract referral (index case-provider hybrid approach), and dual referral (both the index and their partner are tested simultaneously). METHODS: Program data were collected at 4 facilities from October 2018 to March 2019 from index case files and HIV testing register. We compared uptake of the approaches, uptake of HIV testing, and HIV positivity percentages, stratified by contact type and gender. RESULTS: There were 1089 sex partners and 469 children from 1089 newly diagnosed index cases. About 90% of children were contacted through client referral: 85.2% of those were tested and 1.4% was positive. Ninety percent of the children came from female index cases. The provider referral brought in 56.3% of sex partners, of whom 97.2% were HIV-tested. The client referral brought in 30% of sex partners, of whom only 81.5% were HIV-tested. The HIV positivity percentages were 75.5% and 72.7%, respectively, for the 2 approaches. Male index cases helped to reach twice as many HIV-positive sexual contacts outside the household (115) than female index cases (53). The contract and dual referrals were not preferred by index cases. CONCLUSIONS: Provider referral is a successful and acceptable strategy for bringing in sex partners for testing. Client referral is preferred for children.

      10. Potential indirect effects of the COVID-19 pandemic on use of emergency departments for acute life-threatening conditions - United States, January-May 2020external icon
        Lange SJ, Ritchey MD, Goodman AB, Dias T, Twentyman E, Fuld J, Schieve LA, Imperatore G, Benoit SR, Kite-Powell A, Stein Z, Peacock G, Dowling NF, Briss PA, Hacker K, Gundlapalli AV, Yang Q.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):795-800.
        On March 13, 2020, the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, states enacted stay-at-home orders to slow the spread of SARS-CoV-2, the virus that causes COVID-19, and reduce the burden on the U.S. health care system. CDC* and the Centers for Medicare & Medicaid Services (CMS)(dagger) recommended that health care systems prioritize urgent visits and delay elective care to mitigate the spread of COVID-19 in health care settings. By May 2020, national syndromic surveillance data found that emergency department (ED) visits had declined 42% during the early months of the pandemic (1). This report describes trends in ED visits for three acute life-threatening health conditions (myocardial infarction [MI, also known as heart attack], stroke, and hyperglycemic crisis), immediately before and after declaration of the COVID-19 pandemic as a national emergency. These conditions represent acute events that always necessitate immediate emergency care, even during a public health emergency such as the COVID-19 pandemic. In the 10 weeks following the emergency declaration (March 15-May 23, 2020), ED visits declined 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis, compared with the preceding 10-week period (January 5-March 14, 2020). EDs play a critical role in diagnosing and treating life-threatening conditions that might result in serious disability or death. Persons experiencing signs or symptoms of serious illness, such as severe chest pain, sudden or partial loss of motor function, altered mental state, signs of extreme hyperglycemia, or other life-threatening issues, should seek immediate emergency care, regardless of the pandemic. Clear, frequent, highly visible communication from public health and health care professionals is needed to reinforce the importance of timely care for medical emergencies and to assure the public that EDs are implementing infection prevention and control guidelines that help ensure the safety of their patients and health care personnel.

      11. Notes from the field: Measles outbreak associated with international air travel - California, March-April 2017external icon
        Lu L, Roland E, Shearer E, Zahn M, Djuric M, McDonald E, Redd S, Tardivel K.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):803-804.

      12. Haemophilus influenzae serotype a (Hia) carriage in a small Alaska community after a cluster of invasive Hia disease, 2018external icon
        Nolen LD, Tiffany A, DeByle C, Bruden D, Thompson G, Reasonover A, Hurlburt D, Mosites E, Simons BC, Klejka J, Castrodale L, McLaughlin J, Bruce MG.
        Clin Infect Dis. 2020 Jun 12.
        BACKGROUND: Between May and July 2018, four invasive Haemophilus influenzae serotype a (iHia) infections occurred in a remote Alaska community. We performed a public health response to prevent further illness and understand Hia carriage in the community. METHODS: We collected oropharyngeal (OP) samples community-wide from untreated individuals to evaluate baseline carriage. Risk factor data was collected by interview. To prevent additional illness, we offered prophylactic rifampin to individuals in contact with iHia patients (contacts) and to all children aged <10 years. OP samples were collected again eight weeks post-rifampin distribution. Samples were tested using real-time PCR and culture. RESULTS: At baseline, Hia was carried by 4/27 (14.8%) contacts and 7/364 (1.9%) non-contacts (p<0.01). Contacts aged <10 years were more likely to carry Hia at any timepoint (11/18, 61%) than contacts aged >/=10 years (3/34, 8.8%) or non-contacts aged <10 years (2/139, 1.4%) and >/=10 years (6/276, 2.2%)(p<0.001 for all). Hia carriers were clustered in nine households (7% of total households). At the household level, carriage was associated with households with >/=1 contact (PR=5.6, CI:1.3-21.6), crowding (PR=7.7, CI:1.1-199.5) and >/=3 tobacco users (PR=5.0, CI:1.2-19.6). Sixty-six percent (40/61) of contacts and 90% (111/124) of non-contacts aged <10 years received rifampin. Elevated carriage prevalence persisted in contacts when retested eight weeks after rifampin distribution (contacts 6/25 (24%), non-contacts 2/114 (1.8%), p<0.001). CONCLUSIONS: Hia carriage prevalence was significantly higher among people who had contact with iHia patients than the general community. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community.

      13. Prion propagation estimated from brain diffusion MRI is subtype dependent in sporadic Creutzfeldt-Jakob diseaseexternal icon
        Pascuzzo R, Oxtoby NP, Young AL, Blevins J, Castelli G, Garbarino S, Cohen ML, Schonberger LB, Gambetti P, Appleby BS, Alexander DC, Bizzi A.
        Acta Neuropathol. 2020 Jun 13.
        Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible brain proteinopathy. Five main clinicopathological subtypes (sCJD-MM(V)1, -MM(V)2C, -MV2K, -VV1, and -VV2) are currently distinguished. Histopathological evidence suggests that the localisation of prion aggregates and spongiform lesions varies among subtypes. Establishing whether there is an initial site with detectable imaging abnormalities (epicentre) and an order of lesion propagation would be informative for disease early diagnosis, patient staging, management and recruitment in clinical trials. Diffusion magnetic resonance imaging (MRI) is the most-used and most-sensitive test to detect spongiform degeneration. This study was designed to identify, in vivo and for the first time, subtype-dependent epicentre and lesion propagation in the brain using diffusion-weighted images (DWI), in the largest known cross-sectional dataset of autopsy-proven subjects with sCJD. We estimate lesion propagation by cross-sectional DWI using event-based modelling, a well-established data-driven technique. DWI abnormalities of 594 autopsy-diagnosed subjects (448 patients with sCJD) were scored in 12 brain regions by 1 neuroradiologist blind to the diagnosis. We used the event-based model to reconstruct sequential orderings of lesion propagation in each of five pure subtypes. Follow-up data from 151 patients validated the estimated sequences. Results showed that epicentre and ordering of lesion propagation are subtype specific. The two most common subtypes (-MM1 and -VV2) showed opposite ordering of DWI abnormality appearance: from the neocortex to subcortical regions, and vice versa, respectively. The precuneus was the most likely epicentre also in -MM2 and -VV1 although at variance with -MM1, abnormal signal was also detected early in cingulate and insular cortices. The caudal-rostral sequence of lesion propagation that characterises -VV2 was replicated in -MV2K. Combined, these data-driven models provide unprecedented dynamic insights into subtype-specific epicentre at onset and propagation of the pathologic process, which may also enhance early diagnosis and enable disease staging in sCJD.

      14. Performance of oropharyngeal swab testing compared to nasopharyngeal swab testing for diagnosis of COVID-19 -United States, January-February 2020external icon
        Patel MR, Carroll D, Ussery E, Whitham H, Elkins CA, Noble-Wang J, Rasheed JK, Lu X, Lindstrom S, Bowen V, Waller J, Armstrong G, Gerber S, Brooks JT.
        Clin Infect Dis. 2020 Jun 16.
        Among 146 nasopharyngeal (NP) and oropharyngeal (OP) swab pairs collected </=7 days since illness onset, CDC real-time RT-PCR SARS-CoV-2 assay diagnostic results were 95.2% concordant. However, NP swab Ct values were lower (indicating more virus) in 66.7% of concordant-positive pairs, suggesting NP swabs may more accurately detect amount of SARS-CoV-2.

      15. Social media recruitment is no longer an uncharted avenue for survey research. The results thus far provide evidence of an engaging means of recruiting hard-to-reach populations. Questions remain, however, regarding whether the data collected using this method of recruitment produce quality data. This article assesses one aspect that may influence the quality of data gathered through nonprobability sampling using social media advertisements for a hard-to-reach sexual and gender minority youth population: recruitment design formats. The data come from the Survey of Today’s Adolescent Relationships and Transitions, which used a variety of forms of advertisements as survey recruitment tools on Facebook, Instagram, and Snapchat. Results demonstrate that design decisions such as the format of the advertisement (e.g., video or static) and the use of eligibility language on the advertisements impact the quality of the data as measured by break-off rates and the use of nonsubstantive responses. Additionally, the type of device used affected the measures of data quality.

      16. Number of people who inject drugs in Son La, Vietnam: Population size estimation based on official recordsexternal icon
        Tuan LA, Thi Thanh Ha N, Nguyen QD, Tong Le G, Thanh DC, Morgan M, Abdul-Quader AS.
        J Epidemiol Glob Health. 2020 Jun;10(2):131-134.
        AIMS: Estimated population sizes of key populations are critical for resource allocation as well as for monitoring program performance to prevent HIV infection. In 2018, using official records we recruited and conducted a brief survey among People Who Use Drugs (PWUD) to estimate the population size of People Who Inject Drugs (PWID) in Son La Province, Vietnam. METHODS: In Son La, the authorities develop and maintain a master list of individuals who are suspected of using drugs. The list is updated quarterly and is used to monitor the drug use situation in the province. The list, however, does not distinguish injecting from non-injecting drug users. Individual lists from six districts, 24 communes, and 96 hamlets were selected from among those from 12 districts, 204 communes, and 3335 hamlets in the whole province. After reviewing the lists with the hamlet health workers, based on the length of the lists, a minimum of 20% of the total or five drug users in any hamlet with fewer than 25 PWUD were randomly selected for a brief assessment. In addition to basic demographics, the assessment included any drug use in the last 3 months, injection drug use in the last 3 months, and the last time injected. RESULTS: A total of 250 PWUD were interviewed by hamlet health workers. The total number of PWID across all 12 districts in Son La was estimated at 4475 [95% Confidence Interval (CI): 3379-5570] and the corresponding proportion of PWID among PWUD was 48.4% (95% CI: 36.6-60.4). CONCLUSION: The exercise provided an estimated number of PWID in Son La. For planning HIV prevention and care service needs among PWID, additional studies using different methods are needed to validate and improve the population size of PWID in the province of Son La.

      17. Outbreaks associated with untreated recreational water - California, Maine, and Minnesota, 2018-2019external icon
        Vanden Esschert KL, Mattioli MC, Hilborn ED, Roberts VA, Yu AT, Lamba K, Arzaga G, Zahn M, Marsh Z, Combes SM, Smith ES, Robinson TJ, Gretsch SR, Laco JP, Wikswo ME, Miller AD, Tack DM, Wade TJ, Hlavsa MC.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):781-783.
        Outbreaks associated with fresh or marine (i.e., untreated) recreational water can be caused by pathogens or chemicals, including toxins. Voluntary reporting of these outbreaks to CDC's National Outbreak Reporting System (NORS) began in 2009. NORS data for 2009-2017 are finalized, and data for 2018-2019 are provisional. During 2009-2019 (as of May 13, 2020), public health officials from 31 states voluntarily reported 119 untreated recreational water-associated outbreaks, resulting at least 5,240 cases; 103 of the outbreaks (87%) started during June-August. Among the 119 outbreaks, 88 (74%) had confirmed etiologies. The leading etiologies were enteric pathogens: norovirus (19 [22%] outbreaks; 1,858 cases); Shiga toxin-producing Escherichia coli (STEC) (19 [22%]; 240), Cryptosporidium (17 [19%]; 237), and Shigella (14 [16%]; 713). This report highlights three examples of outbreaks that occurred during 2018-2019, were caused by leading etiologies (Shigella, norovirus, or STEC), and demonstrate the wide geographic distribution of such outbreaks across the United States. Detection and investigation of untreated recreational water-associated outbreaks are challenging, and the sources of these outbreaks often are not identified. Tools for controlling and preventing transmission of enteric pathogens through untreated recreational water include epidemiologic investigations, regular monitoring of water quality (i.e., testing for fecal indicator bacteria), microbial source tracking, and health policy and communications (e.g., observing beach closure signs and not swimming while ill with diarrhea).

      18. Factors associated with vaginal detection of prostate-specific antigen among participants in a clinical trial in Malawiexternal icon
        Zia Y, Davis N, Wiener J, Hobbs MM, Lapple D, Chinula L, Tegha G, Msika A, Tang J, Kourtis AP.
        Sex Transm Infect. 2020 Jun 11.

    • Environmental Health
      1. Reduction in drinking water arsenic exposure and health risk through arsenic treatment among private well households in Maine and New Jersey, USAexternal icon
        Yang Q, Flanagan SV, Chillrud S, Ross J, Zeng W, Culbertson C, Spayd S, Backer L, Smith AE, Zheng Y.
        Sci Total Environ. 2020 May 25;738:139683.
        Over 2 million mostly rural Americans are at risk of drinking water from private wells that contain arsenic (As) exceeding the U.S. Environmental Protection Agency (USEPA) Maximum Contaminant Level (MCL) of 10 micrograms per liter (mug/L). How well existing treatment technologies perform in real world situations, and to what extent they reduce health risks, are not well understood. This study evaluates the effectiveness of household As treatment systems in southern-central Maine (ME, n = 156) and northern New Jersey (NJ, n = 94) and ascertains how untreated well water chemistry and other factors influence As removal. Untreated and treated water samples, as well as a treatment questionnaire, were collected. Most ME households had point-of-use reverse-osmosis systems (POU RO), while in NJ, dual-tank point-of-entry (POE) whole house systems were popular. Arsenic treatment systems reduced well water arsenic concentrations ([As]) by up to two orders of magnitude, i.e. from a median of 71.7 to 0.8 mug/L and from a mean of 105 to 14.3 mug/L in ME, and from a median of 8.6 to 0.2 mug/L and a mean of 15.8 to 2.1 mug/L in NJ. More than half (53%) of the systems in ME reduced water [As] to below 1 mug/L, compared to 69% in NJ. The treatment system failure rates were 19% in ME (>USEPA MCL of 10 mug/L) and 16% in NJ (>NJ MCL of 5 mug/L). In both states, the higher the untreated well water [As] and the As(III)/As ratio, the higher the rate of treatment failure. POE systems failed less than POU systems, as did the treatment systems installed and maintained by vendors than those by homeowners. The 7-fold reduction of [As] in the treated water reduced skin cancer risk alone from 3765 to 514 in 1 million in ME, and from 568 to 75 in 1 million in NJ.

    • Genetics and Genomics
      1. A Vibrio cholerae core genome multilocus sequence typing scheme to facilitate the epidemiological study of choleraexternal icon
        Liang KY, Orata FD, Islam MT, Nasreen T, Alam M, Tarr CL, Boucher YF.
        J Bacteriol. 2020 Jun 15.
        Core genome multilocus sequence typing (cgMLST) has gained popularity in recent years in epidemiological research and subspecies level classification. cgMLST retains the intuitive nature of traditional MLST but offers much greater resolution by utilizing significantly larger portions of the genome. Here, we introduce a cgMLST scheme for Vibrio cholerae, a bacterium abundant in marine and freshwater environments and the etiologic agent of cholera. A set of 2,443 core genes ubiquitous in V. cholerae were used to analyze a comprehensive dataset of 1,262 clinical and environmental strains collected from 52 countries, including 65 newly sequenced genomes in this study. We established a sublineage threshold based on 133 allelic differences that creates clusters nearly identical to traditional MLST types, providing backwards compatibility to new cgMLST classifications. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying strains from the same outbreak and closely related isolates which could give clues on outbreak origin. Using cgMLST, we confirmed the South Asian origin of modern epidemics and identified clustering affinity among sublineages of environmental isolates from the same geographic origin. Advantages of this method are highlighted by direct comparison with existing classification methods, such as MLST and single nucleotide polymorphism-based methods. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease-of-use. We anticipate this scheme will serve as a basis for a universally applicable and standardized classification system for V. cholerae research and epidemiological surveillance in the future. This cgMLST scheme is publicly available on PubMLST ( Vibrio cholerae of the O1 and O139 serogroups are the causative agents of cholera, an acute diarrheal disease that plagued the world for centuries, if not millennia. Here, we introduce a core genome multilocus sequence typing scheme for V. cholerae Using this scheme, we have standardized the definition for subspecies-level classification, facilitating global collaboration in the surveillance of V. cholerae In addition, this typing scheme allows for quick identification of outbreak-related isolates that can guide subsequent analyses, serving as an important first step in epidemiological research. This scheme is also easily scalable to analyze thousands of isolates at various levels of resolution making it an invaluable tool for large-scale ecological and evolutionary analyses.

      2. Redundant meta-analyses are common in genetic epidemiologyexternal icon
        Sigurdson M, Khoury MJ, Ioannidis JP.
        J Clin Epidemiol. 2020 Jun 12.
        OBJECTIVE: The massive growth in the publication of meta-analyses may cause redundancy and wasted efforts. We performed a meta-epidemiologic study to evaluate the extent of potential redundancy in published meta-analyses in genetic epidemiology. STUDY DESIGN: Using a sample of 38 index meta-analyses of genetic associations published in 2010, we retrieved additional meta-analyses that evaluated identical associations (same genetic variant and phenotype) using the HuGE (Human Genome Epidemiology) Navigator and PubMed databases. We analyzed the frequency of potential duplication and examined whether subsequent meta-analyses cited previous meta-analyses on the exact same association. RESULTS: Based on 38 index meta-analyses, we retrieved a total of 99 duplicate meta-analyses. Only 12 of the index meta-analyses (32%) were unambiguously unique. We found a mean of 2.6 duplicates and median of 2 duplicates per meta-analysis. In case studies, only 29-54% of previously published meta-analyses were cited by subsequent ones. CONCLUSIONS: These results suggest that duplication is common in meta-analyses of genetic associations.

    • Health Disparities
      1. Good Health and Wellness: Reflections on implementing health promotion in Indian Countryexternal icon
        Gerber C, Locklear S, Stewart K, Marshall L, Colleen G, James R.
        Health Promot Pract. 2020 Jun 16:1524839920934811.
        In 2014, the Centers for Disease Control and Prevention (CDC) launched "A Comprehensive Approach to Good Health and Wellness in Indian County" (GHWIC) to promote health and chronic disease prevention in tribal communities while facilitating cross-cultural learning and relationship-building. Through GHWIC, CDC aimed to work with American Indian and Alaska Native communities to identify effective health promotion strategies to address chronic disease disparities. Tribal sovereignty, community context, and consideration of tribal histories (e.g., oppression, genocide, and cultural erasure) are key to health improvement efforts and work with tribes. These elements center experience, knowledge, and self-determination to reclaim good health and wellness as Indigenous peoples see it. The Implementation Reflection Project was a qualitative inquiry composed of one-on-one discussions and small group sessions conducted to explore experiences of CDC staff, national partners, and tribal recipients as they implemented GHWIC program activities. The Project documented observations and recommendations for future tribal health funding efforts and identified best practices for effective partnerships with tribes and tribal organizations. Findings centered around tribal experiences with GHWIC, improved program processes, the importance of relationships, and the effects of internal capacity on implementation. Key suggestions for future work with tribal entities included simplifying and clarifying roles, expectations, and administration requirements, and establishing clear and consistent communication between program partners. The approach CDC used with GHWIC recipients was effective and respectful, but room for growth remains. Potential future collaborators in Indian Country should consider these findings when planning health promotion initiatives.

    • Healthcare Associated Infections
      1. Assessing solid organ donors and monitoring transplant recipients for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection - U.S. Public Health Service Guideline, 2020external icon
        Jones JM, Kracalik I, Levi ME, Bowman JS, Berger JJ, Bixler D, Buchacz K, Moorman A, Brooks JT, Basavaraju SV.
        MMWR Recomm Rep. 2020 Jun 26;69(4):1-16.
        The recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013;128:247-343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.

      2. Antibiotic susceptibility of NDM-producing enterobacterales collected in the United States, 2017-2018external icon
        Lutgring JD, Balbuena R, Reese N, Gilbert SE, Ansari U, Bhatnagar A, Boyd S, Campbell D, Cochran J, Haynie J, Ilutsik J, Longo C, Swint S, Rasheed JK, Brown AC, Karlsson M.
        Antimicrob Agents Chemother. 2020 Jun 15.
        The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-beta-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase-producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention's Antibiotic Resistance Laboratory Network. The aim of the study was to determine the susceptibility of these isolates against 32 currently available antibiotics using reference broth microdilution and explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretative criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretative criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible) 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug-resistant, and 116 isolates were extensively drug-resistant (42.2%) 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.

      3. Powassan virus infection likely acquired through blood transfusion presenting as encephalitis in a kidney transplant recipientexternal icon
        Taylor L, Stevens T, Destrampe EM, Brown JA, McGavic J, Gould CV, Chambers TV, Kosoy OI, Burkhalter KL, Annambhotla P, Basavaraju SV, Groves J, Osborn RA, Weiss J, Stramer SL, Misch EA.
        Clin Infect Dis. 2020 Jun 15.
        A kidney transplant patient without known tick exposure developed encephalitis three weeks after transplantation. During the transplant hospitalization, the patient had received a blood transfusion from an asymptomatic donor later discovered to have been infected with Powassan virus. This report describes a probable instance of transfusion-transmitted Powassan virus infection.

      4. Candida auris outbreak involving liver transplant recipients in a Surgical Intensive Care Unitexternal icon
        Theodoropoulos NM, Bolstorff B, Bozorgzadeh A, Brandeburg C, Cumming M, Daly JS, Ellison RT, Forsberg K, Gade L, Gibson L, Greenough T, Litvintseva AP, Mack DA, Madoff L, Martins PN, McHale E, Melvin Z, Movahedi B, Stiles T, Vallabhaneni S, Levitz SM.
        Am J Transplant. 2020 Jun 12.
        Candida auris is a difficult to eradicate yeast that has caused outbreaks in healthcare facilities. We report a cluster of five patients in one intensive care unit who were colonized or infected in 2017. The initial two patients were recipients of liver transplants who had cultures that grew C. auris within three days of each other in June 2017 (days 43 and 30 post-transplant). Subsequent screening cultures identified two additional patients with C. auris colonization. Respiratory and urine cultures from a fifth patient yielded C. auris. All isolates were fluconazole-resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from NY/NJ strains, consistent with a separate introduction. However, no source or contact was found. Two of the five patients died. C. auris infection likely contributed to one patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that while severe disease from C. auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C. auris to date.

    • Immunity and Immunization
      1. Progress toward polio eradication - worldwide, January 2018-March 2020external icon
        Chard AN, Datta SD, Tallis G, Burns CC, Wassilak SG, Vertefeuille JF, Zaffran M.
        MMWR Morb Mortal Wkly Rep. 2020 Jun 26;69(25):784-789.
        Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.

      2. Improving staff experience with vaccine data entry with 2D barcode scanningexternal icon
        Evanson HV, Reed JH, Cox R, Clinthorne AD, Williams WW, Vallero J, Rodgers L, Greene M, Koeppl P, Gerlach K.
        J Nurs Care Qual. 2020 Jun 12.
        BACKGROUND: Small fonts on vaccine labels make manually recording vaccine data in patient records time-consuming and challenging. Vaccine 2-dimensional (2D) barcode scanning is a promising alternative to manually recording these data. PROBLEM: While vaccine 2D barcode scanning assists in data entry, adoption of scanning technology is still low. APPROACH: Pilot sites (n = 27) within a health system scanned 2D barcodes to record vaccine data for 6 months. The time to record through scanning and nonscanning methods was measured for 13 vaccinators at 9 sites. A survey was administered to participants across all sites about their experience. OUTCOMES: On average, 22 seconds were saved per vaccine scanned versus entered manually (7 vs 29 seconds, respectively). Participants reported preference for scanning over other vaccine entry options and identified benefits of scanning. CONCLUSION: Expanded use of 2D barcode scanning can meaningfully improve clinical practices by improving efficiency and staff satisfaction during vaccine data entry.

      3. Immunogenicity of the hepatitis A vaccine 20 years after infant immunizationexternal icon
        Mosites E, Seeman S, Negus S, Homan C, Morris J, Nelson NP, Spradling PR, Bruce M, McMahon B.
        Vaccine. 2020 Jun 10.
        To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer >/= 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.

    • Injury and Violence
      1. Elder mistreatment is an important public health problem that can be prevented. By investing in upstream prevention and taking a multigenerational approach, the U.S. can help create communities where older adults are safe, thriving, and living out the remainder of their lives free from abuse and exploitation. The need to do so has never been more pressing as the U.S. is on the precipice of historic population changes that could place a substantial burden on families, communities, and systems of care and protection for older adults. This article describes these changes and how public health efforts can make a difference.

      2. Background: Sports- and recreation-related concussions are a common injury among children. Sports officials (SOs) and athletic trainers (ATs) are integral to setting the stage for safe play and managing concussions when they occur, and significant numbers of both groups have completed the Centers for Disease Control and Prevention's HEADS UP online concussion training course. However, the utility of the course for these audiences has not been assessed. We hypothesized that sports officials’ and athletic trainers’ concussion-related knowledge, attitudes, and behavioral intentions will improve from pre- and post-test after completing CDC's HEADS UP online concussion training course. Method: Respondents’ concussion-related knowledge, attitudes, and behavioral intentions were assessed both before and after taking the training course. Differences between pre- and post-test scores were calculated based on the Wilcoxon Signed Rank Test Z-score or McNemar's test. Effect sizes were interpreted. Results: The SOs and ATs who participated in the HEADS UP online training had a high level of concussion knowledge before taking the course: 90% or more of respondents could identify the correct response for at least seven of the 13 knowledge questions in the pre-test. Still, the course was effective at improving the respondents’ knowledge about return-to-play protocols and concussion reporting. Further, SOs and ATs demonstrated improvement in their concussion-related attitudes and behavioral intentions between the pre- and post-test. Conclusion: SOs’ and ATs’ concussion knowledge, attitudes, and behavioral intentions improved immediately following completion of the CDC HEADS UP online training. Future research could also focus on the long-term retention of this type of training. Practical Applications: This study provides insight into how to better focus concussion-related educational programs to fit SOs’ and ATs’ needs.

      3. A process for identifying indicators with public data: An example from sexual violence preventionexternal icon
        McKool M, Freire K, Basile KC, Jones KM, Klevens J, DeGue S, Smith SG.
        Am J Eval. 2020 .
        Despite advances in the sexual violence (SV) prevention field, practitioners still face challenges with identifying indicators to measure the impact of their prevention strategies. Public data, such as existing administrative and surveillance system data, may be a good option for organizations to examine trends in indicators for the purpose of program evaluation. In this article, we describe a framework and a process for identifying indicators with public data. Specifically, we present the SV Indicator Framework and a five-step indicator review process, which we used to identify indicators for a national SV prevention program. We present the findings of the indicator review and explain how the process could be used by evaluators and program planners within other developing topic areas. Tracking indicators with public data, in conjunction with other evaluation methods, may be a viable option for state-level program evaluations. We discuss limitations and implications for practice and research.

    • Laboratory Sciences
      1. Innovative approaches for Histoplasma detectionexternal icon
        Caceres DH, Fernandez NB, Lockhart SR.
        Curr Fungal Infect Rep. 2020 .
        Purpose of Review: This review highlights innovative approaches for histoplasmosis detection using laboratory technologies published in the past 6 years. Recent Findings: Microscopy and culture are the gold standards for confirming the diagnosis of histoplasmosis, but these can be slow, and their sensitivity and specificity can vary. It is well known that rapid diagnosis is necessary to save lives. Newer technologies based on detection of antibodies, antigens, and DNA can enable rapid and accurate clinical diagnosis. Summary: Based on a systematic review of the literature and evaluation of methodologies in five areas, assay accuracy, rapid testing, point of care testing, commercial availability, and use in animal diagnosis and environmental detection, we describe innovative approaches for detection of Histoplasma/histoplasmosis.

      2. Virus-host interactions between nonsecretors and human norovirusexternal icon
        Lindesmith LC, Brewer-Jensen PD, Mallory ML, Jensen K, Yount BL, Costantini V, Collins MH, Edwards CE, Sheahan TP, Vinje J, Baric RS.
        Cell Mol Gastroenterol Hepatol. 2020 Apr 11;10(2):245-267.
        BACKGROUND & AIMS: Human norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by the FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set of fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2(-/-)) express a limited array of HBGAs. Thus, nonsecretors have less diverse norovirus strain infections, including resistance to the epidemiologically dominant GII.4 strains. Because future human norovirus vaccines will comprise GII.4 antigen and because secretor phenotype impacts GII.4 infection and immunity, nonsecretors may mimic young children immunologically in response to GII.4 vaccination, providing a needed model to study cross-protection in the context of limited pre-exposure. METHODS: By using specimens collected from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus, we evaluated the breadth of serologic immunity by surrogate neutralization assays, and cellular activation and cytokine production by flow cytometry. RESULTS: GII.2 infection resulted in broad antibody and cellular immunity activation that persisted for at least 30 days for T cells, monocytes, and dendritic cells, and for 180 days for blocking antibody. Multiple cellular lineages expressing interferon-γ and tumor necrosis factor-α dominated the response. Both T-cell and B-cell responses were cross-reactive with other GII strains, but not GI strains. To promote entry mechanisms, inclusion of bile acids was essential for GII.2 binding to nonsecretor HBGAs. CONCLUSIONS: These data support development of within-genogroup, cross-reactive antibody and T-cell immunity, key outcomes that may provide the foundation for eliciting broad immune responses after GII.4 vaccination in individuals with limited GII.4 immunity, including young children.

      3. Performance evaluation of the Aptima HIV-1 RNA Quant assay on the Panther system using the standard and dilution protocolsexternal icon
        Rossetti R, Smith T, Luo W, Taussig J, Valentine-Graves M, Sullivan P, Ingersoll JM, Kraft CS, Ethridge S, Wesolowski L, Delaney KP, Owen SM, Johnson JA, Masciotra S.
        J Clin Virol. 2020 Jun 1;129:104479.
        BACKGROUND: Currently, FDA-approved HIV-1 viral load (VL) assays use venipuncture-derived plasma. The Hologic Panther system uses 0.7mL total volume for the Aptima HIV-1 Quant Assay standard (APT-Quant-std) and dilution (APT-Quant-dil) protocols. However, smaller plasma volumes from fingerstick whole blood (FSB) collected in EDTA-microtainer tubes (MCT) could provide an easier sample collection method for HIV-1 VL testing. OBJECTIVES: To evaluate the performance of the APT-Quant-std compared to the Roche CAP/CTM and Abbott m2000RT VL assays and an alternative APTQuant 1:7 dilution protocol, the latter using 100muL of MCT-derived plasma from FSB. STUDY DESIGN: Linearity was determined using commercial HIV-1 RNA plasma controls. Dilutions ranging 1.56-2.95 log10 copies/mL were prepared to determine the APT-Quant-dil Limit of Quantitation (LOQ) using Probit analysis. Specificity of APT-Quant-std was calculated using 326 HIVnegative samples. To evaluate agreement, 329 plasma specimens were tested with APT-Quant-std, CAP/CTM, and m2000RT. Forty-seven matched venipuncture and MCT-derived plasma specimens were tested with APT-Quant-std and APT-Quant-dil. RESULTS: Among the RNA controls, specificity was 99.69 % for APT-Quant-std. The R2 values were 0.988 (APT-Quant-std/CAP/CTM), 0.980 (APT-Quant-std/ m2000RT), and 0.997 (APT-Quant-std/APT-Quant-dil). The APT-Quant-dil LOQ was estimated at 2.7 log10 copies/mL (500 copies/mL) (95 %CI 2.62-2.87). At 2.3 log10 copies/mL (200 copies/mL), the overall agreement was 91.0 % for APT-Quant-std/CAP/CTM, 85.7 % for APT-Quant-std/m2000RT, and 82.9 % for APT-Quant-std/APT-Quant-dil. Quantified APT-Quant-std results were on average 0.2 log10 copies/mL higher than CAP/CTM and m2000RT and 0.14 log10 copies/mL higher than APT-Quant-dil. CONCLUSION: APT-Quant showed similar performance compared to the CAP/CTM and m2000RT assays and remains sensitive and accurate using the dilution protocol.

    • Parasitic Diseases

      1. Malaria infection prevalence and sensitivity of reactive case detection in zanzibarexternal icon
        Stuck L, Fakih BS, Al-Mafazy AH, Hofmann NE, Holzschuh A, Grossenbacher B, Bennett A, Cotter C, Reaves E, Ali A, der Horst TV, Felger I, Hetzel MW, Yukich J.
        Int J Infect Dis. 2020 Jun 10.
        BACKGROUND: Reactive case detection (RCD) is a commonly used strategy for malaria surveillance and response in elimination settings. Many approaches to RCD assume detectable infections are clustered within and around homes of passively detected cases (index households), which has been evaluated in a number of settings with disparate results. METHODS: Household questionnaires and diagnostic testing were conducted following RCD investigations in Zanzibar, Tanzania, including the index household and up to 9 additional neighboring households. RESULTS: Of 12,487 participants tested by malaria rapid diagnostic test (RDT), 3.2% of those residing in index households and 0.4% of those residing in non-index households tested positive (OR = 8.4; 95%CI: 5.7, 12.5). Of 6,281 participants tested by quantitative polymerase chain reaction (qPCR), 8.4% of those residing in index households and 1.3% of those residing in non-index households tested positive (OR = 7.1; 95%CI: 6.1, 10.9). Within households of index cases defined as imported, odds of qPCR-positivity amongst members reporting recent travel were 1.4 times higher than among those without travel history (95%CI: 0.2, 4.4). Amongst non-index households, odds of qPCR-detectable infection were no different between households located within 50 m of the index household as compared with those located farther away (OR = 0.8, 95%CI: 0.5, 1.4). Sensitivity of RDT to detect qPCR-detectable infections was 34% (95%CI: 26.4, 42.3). CONCLUSIONS: Malaria prevalence in index households in Zanzibar is much higher than in non-index households, in which prevalence is very low. Travelers represent a high-risk population. Low sensitivity of RDTs due to a high prevalence of low-density infections results in an RCD system missing a large proportion of the parasite reservoir.

    • Reproductive Health
      1. Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trialexternal icon
        Tang JH, Davis NL, Corbett AH, Chinula L, Cottrell ML, Zia Y, Tegha G, Stanczyk FZ, Hurst S, Hosseinipour MC, Haddad LB, Kourtis AP.
        Contraception: X. 2020 ;2.
        Objectives: Our primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study design: We performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. Results: The geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations < 180 pg/mL (the previously suggested minimum threshold concentration for efficacy). Conclusions: Efavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations < 180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. Implications: Among 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up.

    • Substance Use and Abuse

    • Zoonotic and Vectorborne Diseases
      1. Investigation of Japanese encephalitis virus as a cause of acute encephalitis in southern Pakistan, April 2015-January 2018external icon
        Fatima T, Rais A, Khan E, Hills SL, Chambers TV, Hotwani A, Qureshi S, Shafquat S, Malik S, Qamar F, Mir F, Marfin AA, Zaidi A, Khowaja AR, Shakoor S.
        PLoS One. 2020 ;15(6):e0234584.
        BACKGROUND: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan. METHODS: Persons aged >/=1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples had confirmatory testing using plaque reduction neutralization tests. RESULTS: Among 227 patients, testing was performed on CSF in 174 (77%) and on serum in 53 (23%) patients. Six of eight patient samples positive or equivocal for JEV IgM had sufficient volume for confirmatory testing. One patient had evidence of recent West Nile virus (WNV) neurologic infection based on CSF testing. One patient each had recent dengue virus (DENV) infection and WNV infection based on serum results. Recent flavivirus infections were identified in two persons, one each based on CSF and serum results. Specific flaviviruses could not be identified due to serologic cross-reactivity. For the sixth person, JEV neutralizing antibodies were confirmed in CSF but there was insufficient volume for further testing. CONCLUSIONS: Hospital-based JE surveillance in Karachi, Pakistan could not confirm or exclude local JEV transmission. Nonetheless, Pakistan remains at risk for JE due to presence of the mosquito vector, amplifying hosts, and rice irrigation. Laboratory surveillance for JE should continue among persons with acute encephalitis. However, in view of serological cross-reactivity, confirmatory testing of JE IgM positive samples at a reference laboratory is essential.

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

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