Volume 12, Issue, 7 March 3, 2020

CDC Science Clips: Volume 12, Issue 7, March 3, 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!

NOTE: For current information on COVID-19, please consult the following resources:

CDC: Coronavirus Disease 2019
NIH: National Library of Medicine Coronavirus Disease 2019 (COVID-19) Resources and Informationexternal icon
WHO Information and Guidance: Coronavirus disease (COVID-19) outbreakexternal icon
WHO: Global Research on COVID-19external icon

  1. 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. Cancer Informatics for Cancer Centers (CI4CC): Building a community focused on sharing ideas and best practices to improve cancer care and patient outcomesexternal icon
        Barnholtz-Sloan JS, Rollison DE, Basu A, Borowsky AD, Bui A, DiGiovanna J, Garcia-Closas M, Genkinger JM, Gerke T, Induni M, Lacey JV, Mirel L, Permuth JB, Saltz J, Shenkman EA, Ulrich CM, Zheng WJ, Nadaf S, Kibbe WA.
        JCO Clin Cancer Inform. 2020 Feb;4:108-116.
        Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings. These meetings are a place to review our priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues we, as informatics leaders, individually face at our respective institutions and cancer centers. Here we provide a brief history of the CI4CC organization and meeting highlights from the latest CI4CC meeting that took place in Napa, California from October 14-16, 2019. The focus of this meeting was "intersections between informatics, data science, and population science." We conclude with a discussion on "hot topics" on the horizon for cancer informatics.

      2. Characteristics and health status of informal unpaid caregivers - 44 states, District of Columbia, and Puerto Rico, 2015-2017external icon
        Edwards VJ, Bouldin ED, Taylor CA, Olivari BS, McGuire LC.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 21;69(7):183-188.
        In 2015, an estimated 17.7 million U.S. persons were informal caregivers who provided substantial services through in-home, unpaid assistance to their family members and friends (1). Caregiving can have many benefits, such as enhancing the bond between caregiver and recipient, but it can also place an emotional and physical strain on caregivers, leading to higher rates of depression, lower quality of life, and poorer overall health (2). As the U.S. population continues to age (3), the need for informal caregivers will likely increase. However, little nationally representative information on prevalence of caregivers is available. This study examined demographic characteristics and health status of informal caregivers from 44 states,* the District of Columbia (DC), and Puerto Rico, based on data from the Behavioral Risk Factor Surveillance System (BRFSS) collected during 2015-2017. Overall, approximately one in five adults reported that they had provided care to a family member or friend in the preceding 30 days. Fifty-eight percent of caregivers were women, and a majority were non-Hispanic white, with at least some college education, and married or living with a partner. Across all states, 19.2% of caregivers reported being in fair or poor health, although significant state-to-state variation occurred. Caregivers provide important support to family members, friends, and the health care system and might compromise their own health to provide this support (1,2). Better understanding of caregivers and the challenges they face could inform implementation of improvements in support systems that could enhance not only the health of the caregiver, but that of the care recipient as well. For example, additional data regarding demographics at the state level might aid in more effective planning and support of caregivers with evidence-based programs and assistance (

      3. Background and Objective: As obesity among children and adolescents is associated with major health risks, including the persistence of obesity into adulthood, there has been interest in targeting prevention efforts at children and adolescent. The longitudinal tracking of BMI and obesity, as well as the effects of initial age and duration of follow-up on this tracking, were examined in a large electronic health record (EHR) database. Method(s): The data consisted of 2.04 million children who were examined from 2006 through 2018. These children were initially examined between ages 2 and 9 years and had a final examination, on average, 4 years later. Result(s): Overall, children with obesity at one examination were 7.7 times more likely to have obesity at a subsequent examination than children with a BMI <= 95<sup>th</sup> percentile. Further, 71% of children with obesity at one examination continued to have obesity at re-examination. Although 2-year-olds had a relative risk of 5.5 and a positive predictive value of 54%, then sensitivity of obesity at younger ages was low. Of the children who were re-examined after age 10 y and found to have obesity, only 22% had a BMI >= 95<sup>th</sup> percentile at age 2 years. Conclusion(s): Despite the tracking of obesity at all ages, these results agree with previous reports that have found that an elevated BMI at a very young age will identify only a small proportion of older children with obesity. Copyright Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd

      4. Association of indoor tanning regulations with health and economic outcomes in North America and Europeexternal icon
        Gordon LG, Rodriguez-Acevedo AJ, Koster B, Guy GP, Sinclair C, Van Deventer E, Green AC.
        JAMA Dermatol. 2020 Feb 19.
        Importance: UV radiation emissions from indoor tanning devices are carcinogenic. Regulatory actions may be associated with reduced exposure of UV radiation at a population level. Objective: To estimate the long-term health and economic consequences of banning indoor tanning devices or prohibiting their use by minors only in North America and Europe compared with ongoing current levels of use. Design, Setting, and Participants: This economic analysis modeled data for individuals 12 to 35 years old in North America and Europe, who commonly engage in indoor tanning. A Markov cohort model was used with outcomes projected during the cohort's remaining life-years. Models were populated by extracting data from high-quality systematic reviews and meta-analyses, epidemiologic reports, and cancer registrations. Main Outcomes and Measures: Main outcomes were numbers of melanomas and deaths from melanoma, numbers of keratinocyte carcinomas, life-years, and health care and productivity costs. Extensive sensitivity analyses were performed to assess the stability of results. Results: In an estimated population of 110932523 in the United States and Canada and 141970492 in Europe, for the next generation of youths and young adults during their remaining lifespans, regulatory actions that ban indoor tanning devices could be expected to gain 423000 life-years, avert 240000 melanomas (-8.2%), and avert 7.3 million keratinocyte carcinomas (-7.8%) in North America and gain 460000 life-years, avert 204000 melanomas (-4.9%), and avert 2.4 million keratinocyte carcinomas (-4.4%) in Europe compared with ongoing current levels of use. Economic cost savings of US $31.1 billion in North America and euro21.1 billion (US $15.9 billion) in Europe could occur. Skin cancers averted and cost savings after prohibiting indoor tanning by minors may be associated with one-third of the corresponding benefits of a total ban. Conclusions and Relevance: Banning indoor tanning may be associated with reduced skin cancer burden and health care costs. Corresponding gains from prohibiting indoor tanning by minors only may be smaller.

      5. Characterizing the weight-glycemia phenotypes of type 1 diabetes in youth and young adulthoodexternal icon
        Kahkoska AR, Nguyen CT, Jiang X, Adair LA, Agarwal S, Aiello AE, Burger KS, Buse JB, Dabelea D, Dolan LM, Imperatore G, Lawrence JM, Marcovina S, Pihoker C, Reboussin BA, Sauder KA, Kosorok MR, Mayer-Davis EJ.
        BMJ Open Diabetes Res Care. 2020 Jan;8(1).
        INTRODUCTION: Individuals with type 1 diabetes (T1D) present with diverse body weight status and degrees of glycemic control, which may warrant different treatment approaches. We sought to identify subgroups sharing phenotypes based on both weight and glycemia and compare characteristics across subgroups. RESEARCH DESIGN AND METHODS: Participants with T1D in the SEARCH study cohort (n=1817, 6.0-30.4 years) were seen at a follow-up visit >5 years after diagnosis. Hierarchical agglomerative clustering was used to group participants based on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c) which were estimated by reinforcement learning tree predictions from 28 covariates. Interpretation of cluster weight status and glycemic control was based on mean BMIz and HbA1c, respectively. RESULTS: The sample was 49.5% female and 55.5% non-Hispanic white (NHW); mean+/-SD age=17.6+/-4.5 years, T1D duration=7.8+/-1.9 years, BMIz=0.61+/-0.94, and HbA1c=76+/-21 mmol/mol (9.1+/-1.9)%. Six weight-glycemia clusters were identified, including four normal weight, one overweight, and one subgroup with obesity. No cluster had a mean HbA1c <58 mmol/mol (7.5%). Cluster 1 (34.0%) was normal weight with the lowest HbA1c and comprised 85% NHW participants with the highest socioeconomic position, insulin pump use, dietary quality, and physical activity. Subgroups with very poor glycemic control (ie, >/=108 mmol/mol (>/=12.0%); cluster 4, 4.4%, and cluster 5, 7.5%) and obesity (cluster 6, 15.4%) had a lower proportion of NHW youth, lower socioeconomic position, and reported decreased pump use and poorer health behaviors (overall p<0.01). The overweight subgroup with very poor glycemic control (cluster 5) showed the highest lipids and blood pressure (p<0.01). CONCLUSIONS: There are distinct subgroups of youth and young adults with T1D that share weight-glycemia phenotypes. Subgroups may benefit from tailored interventions addressing differences in clinical care, health behaviors, and underlying health inequity.

      6. Trends in diabetes incidence worldwide: Are the findings real?external icon
        Magliano DJ, Chen L, Pavkov ME, Gregg EW, Shaw JE.
        Maturitas. 2020 Feb 1.

      7. Notes from the Field: Characteristics of Million Hearts hypertension control champions, 2012-2019external icon
        Ritchey MD, Hannan J, Wall HK, George MG, Sperling LS.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 21;69(7):196-197.

      8. Effects of comorbid cardiovascular disease and diabetes mellitus on hand osteoarthritis, pain, and functional state transitionsexternal icon
        Scherzer ZA, Alvarez C, Renner JB, Murphy LB, Schwartz TA, Jordan JM, Golightly YM, Nelson AE.
        J Rheumatol. 2020 Feb 15.
        OBJECTIVE: The purpose of this study is to examine the course of hand osteoarthritis (HOA) and its relationship with cardiovascular disease (CVD) and diabetes (DM). METHODS: Data were collected at 3 time points from 845 Johnston County Osteoarthritis Project participants (2/3 women, 1/3 African-Americans, mean age 60 years) with and without HOA, CVD, or DM. A diagnosis of radiographic hand osteoarthritis (rHOA) required a Kellgren-Lawrence severity grade of >/=2 in at least 3 joints in each hand. A four-state progressive model included transitions based on rHOA and pain or function as defined using the AUStralian CANadian Osteoarthritis Hand Index (AUSCAN). Markov multi-state models estimated hazard ratios and 95% confidence intervals (aHR [95%]) for associations between DM or CVD and specific state transitions, adjusting for baseline and time-varying covariates. RESULTS: Participants with DM (vs those without DM) were more likely to experience worsening pain with rHOA. Individuals who had or developed CVD (vs those who did not) were significantly less likely to experience symptomatic improvement, regardless of rHOA status. Those with DM or CVD (vs those without these comorbidities) were less likely to experience improvement in function, although this was statistically significant only for those with DM and no rHOA. CONCLUSION: Overall, having or developing DM and/or CVD reduced the likelihood of symptomatic and functional improvement over time, suggesting an impact of comorbid CVD and DM on the clinical and radiographic course of HOA. Additional studies are needed to confirm these findings.

      9. Impact of rurality on stage IV ovarian cancer at diagnosis: A Midwest Cancer Registry Cohort Studyexternal icon
        Weeks KS, Lynch CF, West M, McDonald M, Carnahan R, Stewart SL, Charlton M.
        J Rural Health. 2020 Feb 20.
        PURPOSE: We aim to understand if rurality impacts patients' odds of presenting with stage IV ovarian cancer at diagnosis independent of distance to primary care provider and the socioeconomic status of a patient's residential census tract. METHODS: A cohort of 1,000 women with ovarian cancer in Iowa, Kansas, and Missouri were sampled and analyzed from the cancer registries' statewide population data. The sample contained those with a histologically confirmed primary ovarian cancer diagnosis in 2011-2012. All variables were captured through an extension of standard registry protocol using standardized definitions and abstraction manuals. Chi-square tests and a multivariable logistic regression model were used. FINDINGS: At diagnosis, 111 women in our sample had stage IV cancer and 889 had stage I-III. Compared to patients with stage I-III cancer, patients with stage IV disease had a higher average age, more comorbidities, and were more often living in rural areas. Multivariate analysis showed that rural women (vs metropolitan) had a greater odds of having stage IV ovarian cancer at diagnosis (odds ratio = 2.41 and 95% confidence interval = 1.33-4.39). CONCLUSION: Rural ovarian cancer patients have greater odds of having stage IV cancer at diagnosis in Midwestern states independent of the distance they lived from their primary care physician and the socioeconomic status of their residential census tract. Rural women's greater odds of stage IV cancer at diagnosis could affect treatment options and mortality. Further investigation is needed into reasons for these findings.

    • Communicable Diseases
      1. Adherence and viral suppression among participants of the patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A collaboration between community-based pharmacists and HIV clinical providersexternal icon
        Byrd KK, Hou JG, Bush T, Hazen R, Kirkham H, Delpino A, Weidle PJ, Shankle MD, Camp NM, Suzuki S, Clay PG.
        Clin Infect Dis. 2020 Feb 14;70(5):789-797.
        BACKGROUND: Human immunodeficiency virus (HIV) viral suppression (VS) decreases morbidity, mortality, and transmission risk. METHODS: The Patient-centered HIV Care Model integrated community-based pharmacists with HIV medical providers and required them to share patient clinical information, identify therapy-related problems, and develop therapy-related action plans.Proportions adherent to antiretroviral therapy (proportion of days covered [PDC] >/=90%) and virally suppressed (HIV RNA <200 copies/mL), before and after model implementation, were compared. Factors associated with postimplementation VS were determined using multivariable logistic regression; participant demographics, baseline viral load, and PDC were explanatory variables. PDC was modified to account for time to last viral load in the year postimplementation, and stratified as <50%, 50% to <80%, 80% to <90%, and >/=90%. RESULTS: The 765 enrolled participants were 43% non-Hispanic black, 73% male, with a median age of 48 years; 421 and 649 were included in the adherence and VS analyses, respectively. Overall, proportions adherent to therapy remained unchanged. However, VS improved a relative 15% (75% to 86%, P < .001). Higher PDC (adjusted odds ratio [AOR], 1.74 per 1-level increase in PDC category [95% confidence interval {CI}, 1.30-2.34]) and baseline VS (AOR, 7.69 [95% CI, 3.96-15.7]) were associated with postimplementation VS. Although non-Hispanic black persons (AOR, 0.29 [95% CI, .12-.62]) had lower odds of suppression, VS improved a relative 23% (63% to 78%, P < .001). CONCLUSIONS: Integrated care models between community-based pharmacists and primary medical providers may identify and address HIV therapy-related problems and improve VS among persons with HIV.

      2. Emerging priorities for HIV service deliveryexternal icon
        Ford N, Geng E, Ellman T, Orrell C, Ehrenkranz P, Sikazwe I, Jahn A, Rabkin M, Ayisi Addo S, Grimsrud A, Rosen S, Zulu I, Reidy W, Lejone T, Apollo T, Holmes C, Kolling AF, Phate Lesihla R, Nguyen HH, Bakashaba B, Chitembo L, Tiriste G, Doherty M, Bygrave H.
        PLoS Med. 2020 Feb;17(2):e1003028.
        Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

      3. Primary healthcare centers engagement in tuberculosis treatment in Ukraineexternal icon
        Geliukh E, Nabirova D, Davtyan K, Yesypenko S, Zachariah R.
        J Infect Dev Ctries. 2019 Jul 31;13(7.1):83s-88s.
        INTRODUCTION: We assessed the influence of a result-based financing (RBF) model, which included incentives for Primary Healthcare facilities on TB treatment outcomes. METHODOLOGY: We compared TB patients > 17 years and their treatment outcomes among those who did and did not benefit from RBF-model in 14 districts of Odeska oblast, Ukraine in 2017. Log-binomial regression was used to examine factors associated with being included in RBF-model. RESULTS: Of 2,269 reported TB patients, 308 (14%) were included in RBF-model. Most patients in the RBF-model were from rural areas 229 (74%), unemployed 218 (71%), and HIV-infected 131 (43%). Individuals from urban areas (Adjusted risk ratio, ARR =0.9, 95% Confidence Interval, CI:0.89-0.94), having drug-resistant TB (ARR = 0.3, 95% CI: 0.18-0.45), and relapse TB (ARR = 0.6, 95% CI:0.40-0.83) were less likely to be included in RBF-model. Favorable outcomes in new/relapse cases with RBF-model was 89% compared with 41% (p < 0.001) without RBF. Similarly, for other retreatment this was 83% versus 40% (p < 0.001). Failures in the no-RBF group was 29% for new and relapse cases while for other retreatment cases, it was 26% (significantly higher than in the RBF-model). CONCLUSION: RBF-model is effective in achieving high levels of favorable TB treatment outcomes. Almost three-in-ten TB patients in non-RBF category failed TB treatment despite having drug-susceptible TB. Efforts are now needed to include it within ongoing public health reforms and assess the feasibility of scaling-up this intervention through implementation research and dedicated funding.

      4. Tuberculosis infection among people with diabetes: United States population differences by race/ethnicityexternal icon
        Haddad MB, Lash TL, Castro KG, Hill AN, Navin TR, Gandhi NR, Magee MJ.
        Am J Prev Med. 2020 Feb 13.
        INTRODUCTION: Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity. METHODS: This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011-2012 data sets and was conducted in 2018-2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group. RESULTS: Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection. CONCLUSIONS: Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection.

      5. HIV prevention research on men who have sex with men: A scoping review of systematic reviews, 1988-2017external icon
        Higa DH, Crepaz N, McDonald CM, Adegbite-Johnson A, DeLuca JB, Kamitani E, Sipe TA.
        AIDS Educ Prev. 2020 Feb 19:1-24.
        In the United States, men who have sex with men (MSM) are disproportionately affected by HIV. To identify research gaps and inform HIV prevention for MSM, we conducted a scoping review of systematic reviews using CDC's Prevention Research Synthesis database. Eligibility criteria comprised English-language systematic reviews focused on HIV prevention for MSM, published during 1988-2017, and included at least one U.S. primary study. We coded data type, subpopulations, topics, and key findings. To assess study quality, we used the Assessment of Multiple Systematic Reviews (AMSTAR). Among 129 relevant systematic reviews, study quality was high or moderate for 63%. Most common topics were sexual behavior and disease vulnerability. The most frequently mentioned MSM subgroups were HIV-positive, Black or African American, and young. Research gaps include Hispanic/Latino MSM, pre-exposure prophylaxis (PrEP), treatment as prevention, social determinants of health, health disparities, syndemics, and protective factors for sexual health.

      6. Strategies for active detection of tuberculosis in Ukraine: Comparative effectiveness amongst key populations (2014-2018)external icon
        Kamenska N, Nabirova D, Davtyan K, Davtyan H, Zachariah R, Aslanyan G.
        J Infect Dev Ctries. 2019 Jul 31;13(7.1):89s-94s.
        INTRODUCTION: Ukraine has gaps in Tuberculosis (TB) service coverage, especially in key populations (KPs). We compared effectiveness of three different strategies for active TB detection among KPs and their linkage to TB treatment during three time periods. METHODOLOGY: The KPs included people who inject drugs (PWID), sex workers (SW), men who have sex with men (MSM) and groups at-risk of TB (ex-prisoners, Roma and homeless). The active case finding included decentralized symptom screening and specimen collection (2014, strategy-1), decentralized screening with patient referred for specimen collection (2015-2017, strategy-2) and strategy-2 plus GeneXpert (2018, strategy-3). RESULTS: In total 680,760 KPs were screened, of whom 68% were PWID. TB case detection per 100,000 populations was 1,191 in strategy-1, 302 in strategy-2, and 235 in strategy-3. The number needed to screen (NNS) to identify one case was respectively 84, 332, and 425. TB detection was highest among homeless (range: 1,839-2,297 per 100,000 population). The lowest detection was among the MSM and SW. Between 2014 and 2018, 82-94% of all diagnosed TB patients in KPs started TB treatment. CONCLUSIONS: The active case finding in KPs increased detection of TB cases in Ukraine, and the majority of diagnosed KPs initiated TB treatment. Centralization of diagnosis reduced the effectiveness of TB screening. Each region in Ukraine should assess the composition and the needs of KPs which will allow for adoption of specific strategies to detect TB among KPs with high TB prevalence.

      7. A community-wide acute diarrheal disease outbreak associated with drinking contaminated water from shallow bore-wells in a tribal village, India, 2017external icon
        Maramraj KK, Subbalakshmi G, Ali MS, Dikid T, Yadav R, Sodha SV, Jain SK, Singh SK.
        BMC Public Health. 2020 Feb 14;20(1):231.
        BACKGROUND: In 2016, India reported 709 acute diarrheal disease (ADD) outbreaks (> 25% of all outbreaks). Tribal populations are at higher risk with 27% not having accessibility to safe drinking water and 75% households not having toilets. On June 26, 2017 Pedda-Gujjul-Thanda, a tribal village reported an acute diarrheal disease (ADD) outbreak. We investigated to describe the epidemiology, identify risk factors, and provide evidence-based recommendations. METHODS: We defined a case as >/=3 loose stools within 24 h in Pedda-Gujjul-Thanda residents from June 24-30, 2017. We identified cases by reviewing hospital records and house-to-house survey. We conducted a retrospective cohort study and collected stool samples for culture. We assessed drinking water supply and sanitation practices and tested water samples for faecal-contamination. RESULTS: We identified 191 cases (65% females) with median age 36 years (range 4-80 years) and no deaths. The attack-rate (AR) was 37% (191/512). Downhill colonies (located on slope of hilly terrains of the village) reported higher ARs (56%[136/243], p < 0.001) than others (20%[55/269]). Symptoms included diarrhea (100%), fever (17%), vomiting (16%) and abdominal pain (13%). Drinking water from five shallow bore-wells located in downhill colonies was significantly associated with illness (RR = 4.6, 95%CI = 3.4-6.1 and population attributable fraction 61%). In multi-variate analysis, drinking water from the shallow bore-wells located in downhill colonies (aOR = 7.9, [95% CI =4.7-13.2]), illiteracy (aOR =6, [95% CI = 3.6-10.1]), good hand-washing practice (aOR = 0.4, [95%CI = 0.2-0.7]) and household water treatment (aOR = 0.3, [95%CI = 0.2-0.5]) were significantly associated with illness. Two stool cultures were negative for Vibrio cholerae. Heavy rainfall was reported from June 22-24. Five of six water samples collected from shallow bore-wells located in downhill colonies were positive for faecal contamination. CONCLUSION: An ADD outbreak with high attack rate in a remote tribal village was associated with drinking water from shallow downhill bore-wells, likely contaminated via runoff from open defecation areas after heavy rains. Based on our recommendations, immediate public health actions including repair of leakages at contaminated water sources and alternative supply of purified canned drinking water to families, and as long-term public health measures construction of house-hold latrines and piped-water supply initiated.

      8. Community water service and incidence of respiratory, skin, and gastrointestinal infections in rural Alaska, 2013-2015external icon
        Mosites E, Lefferts B, Seeman S, January G, Dobson J, Fuente D, Bruce M, Thomas T, Hennessy T.
        Int J Hyg Environ Health. 2020 Feb 11;225:113475.
        BACKGROUND: Communities in rural Alaska have access to multiple types of water service (piped, vehicle-hauled, and self-hauled) and experience varying levels of water service coverage. We assessed the incidence rate of inpatient and outpatient infectious disease visits among communities with different water service types and coverage levels. METHODS: We classified ICD-9 codes for inpatient and outpatient visits to the Yukon-Kuskokwim Health Corporation facilities between 2013 and 2015 into six infectious disease categories. Using Poisson models, we compared the incidence of visits in each category across communities with differing water service coverage levels as defined by water service billing data for the same years. Using census data, we adjusted for community median household income, median age, crowding, and health aide staffing. RESULTS: We included 48 communities in this analysis. After adjusting for possible confounders, each 10% increase in piped water coverage was associated with a 4% lower incidence of pneumonia/influenza visits (adjusted incidence rate ratio [IRR] 0.96, 95% CI 0.93-0.98), a 2% lower incidence of other respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.99), an 8% lower incidence of methicillin-resistant Staphylococcus visits (adjusted IRR 0.92, 95% CI 0.87-0.97), and a 4% lower incidence of other skin infections visits (adjusted IRR 0.96, 95% CI 0.95-0.98). Each 10% increase in vehicle-hauled water coverage was associated with a 2% lower incidence of respiratory infection visits (adjusted IRR 0.98, 95% CI 0.97-0.996) and a 3% lower incidence of skin infection visits (adjusted IRR 0.97, 95% CI 0.95-0.99), also after adjustment. CONCLUSIONS: Higher levels of water service coverage were associated with lower incidence rates of visits for several infectious disease categories. These associations were more pronounced for communities with piped water service compared to vehicle-hauled water service.

      9. Impact of abstinence and of reducing illicit drug use without abstinence on human immunodeficiency virus viral loadexternal icon
        Nance RM, Trejo ME, Whitney BM, Delaney JA, Altice FL, Beckwith CG, Chander G, Chandler R, Christopoulous K, Cunningham C, Cunningham WE, Del Rio C, Donovan D, Eron JJ, Fredericksen RJ, Kahana S, Kitahata MM, Kronmal R, Kuo I, Kurth A, Mathews WC, Mayer KH, Moore RD, Mugavero MJ, Ouellet LJ, Quan VM, Saag MS, Simoni JM, Springer S, Strand L, Taxman F, Young JD, Crane HM.
        Clin Infect Dis. 2020 Feb 14;70(5):867-874.
        BACKGROUND: Substance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. METHODS: This was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. RESULTS: The number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4-2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively). CONCLUSIONS: Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions.

      10. What's PrEP?: peer navigator acceptability among minority MSM in Washingtonexternal icon
        Pagkas-Bather J, Jaramillo J, Henry J, Grandberry V, Ramirez LF, Cervantes L, Stekler JD, Andrasik MP, Graham SM.
        BMC Public Health. 2020 Feb 18;20(1):248.
        BACKGROUND: Peer navigation is a promising strategy to link at-risk minority men who have sex with men (MSM) to HIV prevention services including pre-exposure prophylaxis (PrEP). METHODS: Thirty-two Black and 63 Latinx HIV-negative MSM living in western Washington completed a survey examining attitudes towards peer navigation and PrEP. Factor analysis derived a score for peer navigator acceptability, and linear regression identified associations with this outcome. RESULTS: Forty-eight percent were interested in peer navigation. Being insured, higher sexual stigma, and higher PHQ-9 score were associated with higher acceptability, while higher income and having a regular medical provider were associated with lower acceptability. In multivariable analysis, higher sexual stigma predicted higher acceptability, while higher income predicted lower acceptability. Men preferred that peers be matched on sexual orientation, race, age and culture. CONCLUSION: Peer navigation interventions to reach minority men should address stigma, focus on lower-income men, and try to match peers to clients to the extent possible.

      11. First case of high-level azithromycin resistant Neisseria gonorrhoeae in North Carolinaexternal icon
        Palavecino EL, Kilic A, Schmerer MW, Dobre-Buonya O, Toler C, McNeil CJ.
        Sex Transm Dis. 2020 Feb 18.
        We report on the first high-level azithromycin resistant Neisseria gonorrhoeae isolate (MIC >/= 256 mug/ml) in North Carolina isolated from a pharyngeal swab of a 33-year-old HIV-negative man who has sex with men. In addition, the isolate was found to be susceptible to cefixime, ceftriaxone, and penicillin and resistant to tetracycline. By whole genome sequencing, the strain was assigned as MLST ST9363, NG-MAST ST5035 and a novel NG-STAR sequence type, ST1993.

      12. Tuberculosis transmission or mortality among persons living with HIV, USA, 2011-2016external icon
        Schmit KM, Shah N, Kammerer S, Bamrah Morris S, Marks SM.
        J Racial Ethn Health Disparities. 2020 Feb 14.
        BACKGROUND: Persons living with HIV are more likely to have tuberculosis (TB) disease attributed to recent transmission (RT) and to die during TB treatment than persons without HIV. We examined factors associated with RT or mortality among TB/HIV patients. METHODS: Using National TB Surveillance System data from 2011 to 2016, we calculated multivariable adjusted odds ratios (aOR) with 99% confidence intervals (CI) to estimate associations between patient characteristics and RT or mortality. Mortality analyses were restricted to 2011-2014 to allow sufficient time for reporting outcomes. RESULTS: TB disease was attributed to RT in 491 (20%) of 2415 TB/HIV patients. RT was more likely among those reporting homelessness (aOR, 2.6; CI, 2.0, 3.5) or substance use (aOR,1.6; CI, 1.2, 2.1) and among blacks (aOR,1.8; CI, 1.2, 2.8) and Hispanics (aOR, 1.8; CI, 1.1, 2.9); RT was less likely among non-US-born persons (aOR, 0.2; CI, 0.2, 0.3). The proportion who died during TB treatment was higher among persons with HIV than without (8.6% versus 5.2%; p < 0.0001). Among 2273 TB/HIV patients, 195 died during TB treatment. Age >/= 65 years (aOR, 5.3; CI, 2.4, 11.6), 45-64 years (aOR, 2.2; CI, 1.4, 3.4), and having another medical risk factor for TB (aOR, 3.3; CI, 1.8, 6.2) were associated with death; directly observed treatment (DOT) for TB was protective (aOR, 0.5; CI, 0.2, 1.0). CONCLUSIONS: Among TB/HIV patients, blacks, Hispanics, and those reporting homelessness or substance use should be prioritized for interventions that decrease TB transmission. Improved adherence to treatment through DOT was associated with decreased mortality, but additional interventions are needed to reduce mortality among older patients and those TB/HIV patients with another medical risk factor for TB.

      13. Epidemiology, clinical features, and resource utilization associated with respiratory syncytial virus in the community and hospitalexternal icon
        Smithgall M, Maykowski P, Zachariah P, Oberhardt M, Vargas CY, Reed C, LaRussa P, Saiman L, Stockwell MS.
        Influenza Other Respir Viruses. 2020 Feb 20.
        BACKGROUND: The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized. METHODS: We identified individuals of all ages with laboratory-confirmed RSV from two sources, a community cohort undergoing surveillance for acute respiratory infections (ARIs) and hospitalized patients from the same geographic area of New York City between 2013 and 15. The epidemiology, clinical features, and resource utilization (antibiotic/steroid/ribavirin usage, chest X-rays, respiratory-support (continuous positive airway pressure [CPAP], mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and indicators of disease severity (respiratory-support, and/or ICU admission or death)) were compared among age groups using univariate and bivariate analyses. RESULTS: In the community cohort (1777 people with 1805 ARIs), 66(3.7%) tested RSV-positive (3.8% of <1-year-olds; 3.8% of adults >/=65); 40.9% were medically attended, and 23.1% reported antibiotic usage. Among 40,461 tests performed on hospital patients, 2.7% were RSV-positive within +/- 2 days of admission (37.3% <1 year old; 17.4% >/=65 years old). Among RSV-positive hospitalized adults >/=65%, 92.7%, 89.6% and 78.1% received a chest X-ray, antibiotics and/or steroids respectively, compared with 48.9%, 45.7%, and 48.7% of children <1. Severe illness occurred in 27.0% RSV-positive hospitalized <1-year-olds and 19.8% >/=65-year-olds. CONCLUSIONS: Respiratory syncytial virus had a demonstrated impact in the community and hospital. Only 40% of RSV community cases were medically attended. In the hospitalized-cohort, <1- and >/= 65-year-olds accounted for the majority of patients and had similar rates of severe illness. In addition, resource utilization was high in older adults, making both young children and older adults important potential RSV vaccine targets.

    • Disaster Control and Emergency Services
      1. Did internal displacement from the 2010 earthquake in Haiti lead to long-term violence against children? A matched pairs study designexternal icon
        Cerna-Turoff I, Kane JC, Devries K, Mercy J, Massetti G, Baiocchi M.
        Child Abuse Negl. 2020 Feb 12;102:104393.
        BACKGROUND: Empirical evidence is limited and contradictory on violence against children after internal displacement from natural disasters. Understanding how internal displacement affects violence is key in structuring effective prevention and response. OBJECTIVE: We examined the effect of internal displacement from the 2010 Haitian earthquake on long-term physical, emotional, and sexual violence against children and outlined a methodological framework to improve future evidence quality. PARTICIPANTS AND SETTING: We analyzed violence against adolescent girls and boys within the nationally representative, Haiti Violence Against Children Survey. METHODS: We pre-processed data by matching on pre-earthquake characteristics for displaced and non-displaced children and applied 95 % confidence intervals from McNemar's exact test, with sensitivity analyses, to evaluate differences in violence outcomes between matched pairs after the earthquake. RESULTS: Internal displacement was not associated with past 12-month physical, emotional, and sexual violence two years after the earthquake for girls and boys. Most violence outcomes were robust to potential unmeasured confounding. Odds ratios for any form of violence against girls were 0.84 (95 % CI: 0.52-1.33, p = 0.500) and against boys were 1.03 (95 % CI: 0.61-1.73, p = 1.000). CONCLUSIONS: Internal displacement was not a driver of long-term violence against children in Haiti. Current global protocols in disaster settings may initiate services after the optimal window of time to protect children from violence, and the post-displacement setting may be central in determining violence outcomes. The combination of specific data structures and matching methodologies is promising to increase evidence quality after rapid-onset natural disasters, especially in low-resource settings.

      2. Nigeria's Joint External Evaluation and National Action Plan for Health Securityexternal icon
        Ojo OE, Dalhat M, Garfield R, Lee C, Oyebanji O, Oyetunji A, Ihekweazu C.
        Health Secur. 2020 Jan/Feb;18(1):16-20.
        Nigeria is working to protect against and respond more effectively to disease outbreaks. Quick mobilization and control of the Ebola epidemic in 2014, at least 4 major domestic outbreaks each year, and significant progress toward polio eradication led to adoption of the World Health Organization's Global Health Security Joint External Evaluation (JEE) and National Action Plan for Health Security (NAPHS). The process required joint assessment and planning among many agencies, ministries, and sectors over the past 2 years. We carried out a JEE of 19 core programs in 2017 and launched a detailed NAPHS to improve prevention, detection, and response in December 2018, which required us to create topic-specific groups to document work to date and propose JEE scores. We then met with an international team for 5 days to review and revise scoring and recommendations, created a 5-year implementation plan, developed a management team to oversee implementation, drafted legislation to manage outbreaks, trained professionals at state and local levels of government, and set priorities among the many possible activities recommended. Management software and leadership skills were developed to monitor global health security programs. We learned to use international assistance strategically to strengthen planning and mentor national staff. Finally, a review of every major disease outbreak was used to prepare for the next challenge. Review and adaptation of this plan each year will be critical to ensure sustained momentum and progress. Many low-income countries are skilled at managing vertical disease control programs. Balancing and combining the 19 core activities of a country's public health system is a more demanding challenge.

    • Disease Reservoirs and Vectors
      1. Use of emerging technology allowing for identification of genetic material from pathogens and endosymbionts in ticks collected from humans, domestic animals, wildlife, or the environment has resulted in an avalanche of new data on tick-microorganism associations. This rapidly growing stream of new information is a tremendous resource but also presents challenges, including how detection of pathogen genetic material in ticks should best be interpreted. There is a tendency in the more recent published literature to incorrectly use the term "vector" based on detection of pathogen genetic material from tick species not experimentally confirmed to serve as vectors of the pathogen in question. To serve as a vector of a horizontally maintained pathogen, such as a Borrelia burgdorferi sensu lato (s.l.) Lyme borreliosis spirochete, the tick species in question must be capable of acquiring the pathogen while feeding in the larval or nymphal stage on an infectious host, maintaining it transstadially through the molt, and then transmitting the pathogen to a naive host while feeding in the subsequent nymphal or adult stage. This review examines the experimental evidence for and against species of hard (ixodid) ticks from different genera to serve as vectors of B. burgdorferi s.l. spirochetes. Of the 18 Ixodes species ticks evaluated to date, 13 were experimentally confirmed as vectors of B. burgdorferi s.l. spirochetes. These studies focused primarily on the three major Lyme borreliosis agents: Borrelia burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii. In striking contrast, none of 8 tick species from other genera (1 Amblyomma species, 5 Dermacentor species, and 2 Haemaphysalis species) evaluated to date were unequivocally experimentally confirmed as vectors of B. burgdorferi s.l. spirochetes. The strength of the evidence for or against each tick species to serve as a vector of B. burgdorferi s.l. spirochetes is discussed together with key knowledge gaps and research challenges.

      2. Preliminary evaluation of human personal protective measures against the nymphal stage of the Asian longhorned Tick (Acari: Ixodidae)external icon
        Foster E, Fleshman AC, Ford SL, Levin ML, Delorey MJ, Eisen RJ, Eisen L.
        J Med Entomol. 2020 Feb 19.
        The invasive, human-biting Asian longhorned tick, Haemaphysalis longicornis Neumann, is establishing in the United States. This tick is a threat to public health in its native range in Asia, serving as a vector of severe fever with thrombocytopenia syndrome virus and Rickettsia japonica, the agent of Japanese spotted fever. However, there is a lack of published information specifically for H. longicornis concerning the efficacy of generally recommended personal tick bite prevention measures. We, therefore, evaluated permethrin-treated clothing and formulated human skin repellent products, representing the six repellent active ingredients generally recommended for tick bite prevention by the Centers for Disease Control and Prevention (CDC), against H. longicornis nymphs from a colony established with adult ticks collected in New York state. Reluctance of H. longicornis nymphs to stay in contact with nontreated human skin precluded the use of a human skin bioassay to optimally evaluate repellency. In a Petri dish choice bioassay, all tested product formulations were highly effective with estimated repellencies ranging from 93 to 97%. In addition, we observed strong contact irritancy of a summer-weight permethrin-treated garment against H. longicornis nymphs, with 96% of introduced ticks dislodging from the vertically oriented textile within 3 min. These preliminary studies indicate that personal tick bite prevention measures currently recommended by the CDC are effective against the invasive H. longicornis. However, additional studies are needed to explore the efficacy of the evaluated products against different life stages of H. longicornis, as well as ticks collected in the field rather than reared in the laboratory.

    • Environmental Health
      1. Spatial exploration of the CDC's Social Vulnerability Index and heat-related health outcomes in Georgiaexternal icon
        Lehnert EA, Wilt G, Flanagan B, Hallisey E.
        Int J Disaster Risk Reduct. 2020 ;46.
        Heat-related illness, an environmental exposure-related outcome commonly treated in U.S. hospital emergency departments (ED), is likely to rise with increased incidence of heat events related to climate change. Few studies demonstrate the spatial and statistical relationship of social vulnerability and heat-related health outcomes. We explore relationships of Georgia county-level heat-related ED visits and mortality rates (2002–2008), with CDC's Social Vulnerability Index (CDC SVI). Bivariate Moran's I analysis revealed significant clustering of high SVI rank and high heat-related ED visit rates (0.211, p < 0.001) and high smoothed mortality rates (0.210, p < 0.001). Regression revealed that for each 10% increase in SVI ranking, ED visit rates significantly increased by a factor of 1.18 (95% CI = 1.17–1.19), and mortality rates significantly increased by a factor of 1.31 (95% CI = 1.16–1.47). CDC SVI values are spatially linked and significantly associated with heat-related ED visit, and mortality rates in Georgia.

      2. Characterization of trace elements exposure in pregnant women in the United States, NHANES 1999-2016external icon
        Watson CV, Lewin M, Ragin-Wilson A, Jones R, Jarrett JM, Wallon K, Ward C, Hilliard N, Irvin-Barnwell E.
        Environ Res. 2020 Jan 31;183:109208.
        OBJECTIVE: The objective of the current study is to report on urine, blood and serum metal concentrations to characterize exposures to trace elements and micronutrient levels in both pregnant women and women of child-bearing age in the U.S. National Health and Nutrition Examination Survey (NHANES) years 1999-2016. METHODS: Urine and blood samples taken from NHANES participants were analyzed for thirteen urine metals, three blood metals, three serum metals, speciated mercury in blood and speciated arsenic in urine. Adjusted and unadjusted least squares geometric means and 95% confidence intervals were calculated for all participants among women aged 15-44 years. Changes in exposure levels over time were also examined. Serum cotinine levels were used to adjust for smoke exposure, as smoking is a source of metal exposure. RESULTS: Detection rates for four urine metals from the ATSDR Substance Priority List: arsenic, lead, mercury and cadmium were ~83-99% for both pregnant and non-pregnant women of child bearing age. A majority of metal concentrations were higher in pregnant women compared to non-pregnant women. Pregnant women had higher mean urine total arsenic, urine mercury, and urine lead; however, blood lead and mercury were higher in non-pregnant women. Blood lead, cadmium, mercury, as well as urine antimony, cadmium and lead in women of childbearing age decreased over time, while urine cobalt increased over time. CONCLUSIONS: Pregnant women in the US have been exposed to several trace metals, with observed concentrations for some trace elements decreasing since 1999.

      3. Trends and patterns of phthalates and phthalate alternatives exposure in pregnant women from Mexico City during 2007-2010external icon
        Wu H, Kupsco AJ, Deierlein AL, Just AC, Calafat AM, Oken E, Braun JM, Mercado-Garcia A, Cantoral A, Tellez-Rojo MM, Wright RO, Baccarelli AA.
        Environ Sci Technol. 2020 Feb 4;54(3):1740-1749.
        Phthalates are associated with several adverse health outcomes, but few studies have evaluated phthalate exposures in Mexican populations, particularly pregnant women. Between 2007 and 2011, 948 pregnant women from Mexico City were recruited as part of the PROGRESS cohort. We quantified 17 metabolites of phthalates and phthalate alternatives in urine samples collected during the second and third trimesters and examined temporal trends of metabolite concentrations, within-person reproducibility, and relations of individual metabolites with sociodemographic, lifestyle, and occupational factors. Concentrations of mono-2-ethyl-5-carboxypentyl terephthalate, a metabolite of the alternative phthalate di-2-ethylhexyl terephthalate, increased monotonically from 2007 to 2010 (31% per year; 95% confidence interval = 23 and 39%). We observed moderate to high correlations among metabolites collected at the same visit, but there was high variability between second and third trimester phthalate metabolite concentrations (intraclass correlation coefficients = 0.17-0.35). In general, higher socioeconomic status was associated with higher phthalate concentrations. Some metabolites were associated with maternal age and education, but no consistent patterns were observed. Women working in the home and those who worked in administration had higher concentrations of several phthalate metabolites relative to students, professionals, and those in customer service. Biomonitoring efforts are warranted to investigate present and future exposure trends and patterns.

    • Health Economics
      1. Global and regional estimates and projections of diabetes-related health expenditure: results from the International Diabetes Federation Diabetes Atlas, 9(th) editionexternal icon
        Williams R, Karuranga S, Malanda B, Saeedi P, Basit A, Besancon S, Bommer C, Esteghamati A, Ogurtsova K, Zhang P, Collagiuri S.
        Diabetes Res Clin Pract. 2020 Feb 13:108072.
        AIMS: Diabetes and its complications have a significant economic impact on individuals and their families, health systems and national economies. METHODS: The direct health expenditure of diabetes was calculated relying on the following inputs: diagnosed and undiagnosed diabetes prevalence estimates, United Nations population estimates, World Health Organization health expenditure per capita and ratios of health expenditure for people with diabetes compared to people without diabetes. RESULTS: The estimated global direct health expenditure on diabetes in 2019 is USD 760 billion and is expected to grow to a projected USD 825 billion by 2030 and USD 845 billion by 2045.There is a wide variation in annual health expenditures on diabetes. The United States of America has the highest estimated expenditure with USD 294.6 billion, followed by China and Brazil, with USD 109.0 billion and USD 52.3 billion, respectively. The age group with the largest annual diabetes-related health expenditure is 60-69 years with USD 177.7 billion, followed by 50-59 years, and 70-79 years with USD 173.0 billion and USD 171.5 billion, respectively Slightly higher diabetes-related health expenditure is seen in women than in men (USD 382.6 billion vs. USD 377.6 billion, respectively). The same difference is expected to be present in 2030 and 2045. CONCLUSIONS: There were large disparities between high-, middle- and low-income countries with total health expenditures in high-income countries being over 400 times those in low-income countries, with the ratio for annual direct health expenditure per person between these groups of countries is more than 39-fold.

    • Healthcare Associated Infections
      1. Molecular characterization and clinical outcomes of Candida auris infection: Single-center experience in Saudi Arabiaexternal icon
        Almaghrabi RS, Albalawi R, Mutabagani M, Atienza E, Aljumaah S, Gade L, Forsberg K, Litvintseva A, Althawadi S.
        Mycoses. 2020 Feb 18.
        BACKGROUND: Candida auris is a difficult-to-diagnose multidrug-resistant yeast that can cause invasive infections with high mortality. Since emerging in 2009, this pathogen has been associated with numerous outbreaks around the world. Whole genome sequencing (WGS) is instrumental for understanding the emergence and local transmission of this pathogen. OBJECTIVES: To describe the clinical, molecular characteristics of Candida auris infection and clinical outcome in our center. PATIENTS AND METHODS: Patients with positive cultures for Candida auris were identified in a microbiology database. Clinical characteristics and antifungal susceptibility were obtained. Isolates were sent to the US CDC for whole genome sequencing. RESULTS: Seven unique patients with eight different isolates were identified. Seven isolates were sent to the US CDC for whole genome sequencing. None of the patients had blood stream infection. 30-day mortality was higher in infected patients compared with those who were colonized. Seven of the eight isolates were resistant to both fluconazole and five were resistant to amphotericin B. WGS analysis demonstrated that the seven isolates belonged to the South Asian clade but formed two distinct subclades suggesting two independent introductions and ongoing transmission within the facility. CONCLUSIONS: Candida auris is associated with a high mortality rate in infected patients. Strict infection control measures and surveillance for asymptomatic cases are warranted to halt ongoing transmission.

      2. Faces of resistance: Using real-world patients and their advocates to teach medical students about antimicrobial stewardshipexternal icon
        Nori P, Cowman K, Jezek A, Nosanchuk JD, Slosar-Cheah M, Sarwar U, Bartash R, Ostrowsky B.
        Open Forum Infect Dis. 2019 ;6(12).
        We engaged medical students with antimicrobial stewardship (AS) and antimicrobial resistance (AMR) through patient stories and a panel on AMR advocacy with experts from the Centers for Disease Control and Prevention and the Infectious Diseases Society of America. Students were surveyed on their perceptions about AS and AMR (response rate = 139 of 166, 84%).

      3. An innovative quality improvement approach for rapid improvement of infection prevention and control at health facilities in Sierra Leoneexternal icon
        Rondinelli I, Dougherty G, Madevu-Matson CA, Toure M, Akinjeji A, Ogongo I, Kolwaite A, Weiss J, Gleason B, Lyman MM, Benya H, Rabkin M.
        Int J Qual Health Care. 2020 Feb 13.
        QUALITY CHALLENGE: The Sierra Leone (SL) Ministry of Health and Sanitation's National Infection Prevention and Control Unit (NIPCU) launched National Infection and Prevention Control (IPC) Policy and Guidelines in 2015, but a 2017 assessment found suboptimal compliance with standards on environmental cleanliness (EC), waste disposal (WD) and personal protective equipment (PPE) use. METHODS: ICAP at Columbia University (ICAP), NIPCU and the Centers for Disease Control and Prevention (CDC) designed and implemented a Rapid Improvement Model (RIM) quality improvement (QI) initiative with a compressed timeframe of 6 months to improve EC, WD and PPE at eight purposively selected health facilities (HFs). Targets were collaboratively developed, and a 37-item checklist was designed to monitor performance. HF teams received QI training and weekly coaching and convened monthly to review progress and exchange best practices. At the final learning session, a "harvest package" of the most effective ideas and tools was developed for use at additional HFs. RESULTS: The RIM resulted in marked improvement in WD and EC performance and modest improvement in PPE. Aggregate compliance for the 37 indicators increased from 67 to 96% over the course of 4 months, with all HFs showing improvement. Average PPE compliance improved from 85 to 89%, WD from 63 to 99% and EC from 51 to 99%. LESSONS LEARNED: The RIM QIC approach is feasible and effective in SL's austere health system and led to marked improvement in IPC performance. The best practices are being scaled up and the RIM QIC methodology is being applied to other domains.

      4. Genomic characterization of Neisseria gonorrhoeae Strains from 2016 United States Sentinel Surveillance Displaying Reduced Susceptibility to Azithromycinexternal icon
        Schmerer MW, Abrams AJ, Seby S, Thomas JC, Cartee J, Lucking S, Vidyaprakash E, Pham CD, Sharpe S, Pettus K, St Cyr SB, Torrone EA, Kersh EN, Gernert KM.
        Antimicrob Agents Chemother. 2020 Feb 18.
        In 2016, the proportion of Neisseria gonorrhoeae isolates with reduced susceptibility to azithromycin rose to 3.6%. A phylogenetic analysis of 334 N. gonorrhoeae isolates collected in 2016 revealed a single, geographically diverse lineage of isolates with MICs of 2-16 mug/mL that carried a mosaic-like mtr locus, whereas the majority of isolates with MICs >/= 16 mug/mL appeared sporadically and carried 23S rRNA mutations. Continued molecular surveillance of N. gonorrheae will identify new resistance mechanisms.

    • Immunity and Immunization
      1. Pneumococcal conjugate vaccine breakthrough infections: 2001-2016external icon
        Adebanjo TA, Pondo T, Yankey D, Hill HA, Gierke R, Apostol M, Barnes M, Petit S, Farley M, Harrison LH, Holtzman C, Baumbach J, Bennett N, McGuire S, Thomas A, Schaffner W, Beall B, Whitney CG, Pilishvili T.
        Pediatrics. 2020 Feb 13.
        BACKGROUND: Most countries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the invasive pneumococcal disease (IPD) breakthrough infection incidence in children receiving 2 vs 3 primary PCV doses with and without booster doses (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0). METHODS: We used 2001-2016 Active Bacterial Core surveillance data to identify breakthrough infections (vaccine-type IPD in children receiving >/=1 7-valent pneumococcal conjugate vaccine [PCV7] or 13-valent pneumococcal conjugate vaccine [PCV13] dose) among children aged <5 years. We estimated schedule-specific IPD incidence rates (IRs) per 100 000 person-years and compared incidence by schedule (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0) using rate differences (RDs) and incidence rate ratios. RESULTS: We identified 71 PCV7 and 49 PCV13 breakthrough infections among children receiving a schedule of interest. PCV13 breakthrough infection rates were higher in children aged <1 year receiving the 2 + 0 (IR: 7.8) vs 3 + 0 (IR: 0.6) schedule (incidence rate ratio: 12.9; 95% confidence interval: 4.1-40.4); PCV7 results were similar. Differences in PCV13 breakthrough infection rates by schedule in children aged <1 year were larger in 2010-2011 (2 + 0 IR: 18.6; 3 + 0 IR: 1.4; RD: 16.6) vs 2012-2016 (2 + 0 IR: 3.6; 3 + 0 IR: 0.2; RD: 3.4). No differences between schedules were detected in children aged >/=1 year for PCV13 breakthrough infections. CONCLUSIONS: Fewer PCV breakthrough infections occurred in the first year of life with 3 primary doses. Differences in breakthrough infection rates by schedule decreased as vaccine serotypes decreased in circulation.

      2. BACKGROUND: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of post-vaccine serum anti-rotavirus immunoglobulin A (IgA) that serves as an individual-level immune correlate of protection against rotavirus gastroenteritis. METHODS: Individual-level data on 5,074 infants enrolled in nine GlaxoSmithKline Rotarix Phase II/III clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis. RESULTS: Seroconversion (IgA >/=20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis up to 1 year of age. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR=0.04, 95% confidence interval (CI)=0.01-0.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (0.46, 0.25-0.86). As the IgA threshold increased, the risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. DISCUSSION: Post-vaccination anti-rotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis up to 1 year of age. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance.

      3. Interim estimates of 2019-20 seasonal influenza vaccine effectiveness - United States, February 2020external icon
        Dawood FS, Chung JR, Kim SS, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Belongia EA, McLean HQ, Gaglani M, Dunnigan K, Foust A, Sessions W, DaSilva J, Le S, Stark T, Kondor RJ, Barnes JR, Wentworth DE, Brammer L, Fry AM, Patel MM, Flannery B.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 21;69(7):177-182.
        During the 2019-20 influenza season, influenza-like illness (ILI)* activity first exceeded the national baseline during the week ending November 9, 2019, signaling the earliest start to the influenza season since the 2009 influenza A(H1N1) pandemic. Activity remains elevated as of mid-February 2020. In the United States, annual vaccination against seasonal influenza is recommended for all persons aged >/=6 months (1). During each influenza season, CDC estimates seasonal influenza vaccine effectiveness in preventing laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report used data from 4,112 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during October 23, 2019-January 25, 2020. Overall, vaccine effectiveness (VE) against any influenza virus associated with medically attended ARI was 45% (95% confidence interval [CI] = 36%-53%). VE was estimated to be 50% (95% CI = 39%-59%) against influenza B/Victoria viruses and 37% (95% CI = 19%-52%) against influenza A(H1N1)pdm09, indicating that vaccine has significantly reduced medical visits associated with influenza so far this season. Notably, vaccination provided substantial protection (VE = 55%; 95% CI = 42%-65%) among children and adolescents aged 6 months-17 years. Interim VE estimates are consistent with those from previous seasons, ranging from 40%-60% when influenza vaccines were antigenically matched to circulating viruses. CDC recommends that health care providers continue to administer influenza vaccine to persons aged >/=6 months because influenza activity is ongoing, and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses as well as other influenza viruses that might circulate later in the season.

      4. Relative and absolute effectiveness of high-dose and standard-dose influenza vaccine against influenza-related hospitalization among older adults - United States, 2015-2017external icon
        Doyle JD, Beacham L, Martin ET, Talbot HK, Monto A, Gaglani M, Middleton DB, Silveira FP, Zimmerman RK, Alyanak E, Smith ER, Flannery BL, Rolfes M, Ferdinands JM.
        Clin Infect Dis. 2020 Feb 18.
        BACKGROUND: Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged >/=65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. METHODS: Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at eight hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015-2016 and 2016-2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. RESULTS: Among 1487 enrolled patients aged >/=65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] -42%, 38%) and that of HD-IIV was 32% (95%CI -3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95%CI -1%, 48%). CONCLUSIONS: During two U.S. influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged >/=65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

      5. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurologyexternal icon
        Farez MF, Correale J, Armstrong MJ, Rae-Grant A, Gloss D, Donley D, Holler-Managan Y, Kachuck NJ, Jeffery D, Beilman M, Gronseth G, Michelson D, Lee E, Cox J, Getchius T, Sejvar J, Narayanaswami P.
        Neurology. 2019 Sep 24;93(13):584-594.
        OBJECTIVE: To update the 2002 American Academy of Neurology (AAN) guideline regarding immunization and multiple sclerosis (MS). METHODS: The panel performed a systematic review and classified articles using the AAN system. Recommendations were based on evidence, related evidence, principles of care, and inferences according to the AAN 2011 process manual, as amended. MAJOR RECOMMENDATIONS LEVEL B EXCEPT WHERE INDICATED: Clinicians should discuss the evidence regarding immunizations in MS with their patients and explore patients' opinions, preferences, and questions. Clinicians should recommend that patients with MS follow all local vaccine standards, unless there are specific contraindications and weigh local vaccine-preventable disease risks when counseling patients. Clinicians should recommend that patients with MS receive the influenza vaccination annually. Clinicians should counsel patients with MS about infection risks associated with specific immunosuppressive/immunomodulating (ISIM) medications and treatment-specific vaccination guidance according to prescribing information (PI) and vaccinate patients with MS as needed at least 4-6 weeks before initiating patients' ISIM therapy. Clinicians must screen for infections according to PI before initiating ISIM medications (Level A) and should treat patients testing positive for latent infections. In high-risk populations, clinicians must screen for latent infections before starting ISIM therapy even when not specifically mentioned in PI (Level A) and should consult specialists regarding treating patients who screen positive for latent infection. Clinicians should recommend against using live-attenuated vaccines in people with MS receiving ISIM therapies. Clinicians should delay vaccinating people with MS who are experiencing a relapse.

      6. Identifying vaccine-associated rash illness amidst a large measles outbreak - Minnesota, 2017external icon
        Martin KG, Banerjee E, McMahon M, Kenyon C, Strain A, Muscoplat MH, Gastanaduy PA, Rota PA, Mody RK, Ehresmann K.
        Clin Infect Dis. 2020 Feb 18.
        Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, having a measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles.

      7. Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive Group B Streptococci within the US: 2015-2017external icon
        McGee L, Chochua S, Li Z, Mathis S, Rivers J, Metcalf B, Ryan A, Alden N, Farley MM, Harrison LH, Snippes Vagnone P, Lynfield R, Smelser C, Muse A, Thomas AR, Schrag S, Beall BW.
        Clin Infect Dis. 2020 Feb 15.
        BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS: Using whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states. RESULTS: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more beta-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2microg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS: This first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

      8. Health workers' perceptions and challenges in implementing meningococcal serogroup a conjugate vaccine in the routine childhood immunization schedule in Burkina Fasoexternal icon
        Nkwenkeu SF, Jalloh MF, Walldorf JA, Zoma RL, Tarbangdo F, Fall S, Hien S, Combassere R, Ky C, Kambou L, Diallo AO, Krishnaswamy A, Ake FH, Hatcher C, Patel JC, Medah I, Novak RT, Hyde TB, Soeters HM, Mirza I.
        BMC Public Health. 2020 Feb 19;20(1):254.
        BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in 2017 into the routine childhood immunization schedule (at 15-18 months of age) in Burkina Faso to help reduce meningococcal meningitis burden. MACV was scheduled to be co-administered with the second dose of measles-containing vaccine (MCV2), a vaccine already in the national schedule. One year following the introduction of MACV, an assessment was conducted to qualitatively examine health workers' perceptions of MACV introduction, identify barriers to uptake, and explore opportunities to improve coverage. METHODS: Twelve in-depth interviews were conducted with different cadres of health workers in four purposively selected districts in Burkina Faso. Districts were selected to include urban and rural areas as well as high and low MCV2 coverage areas. Respondents included health workers at the following levels: regional health managers (n = 4), district health managers (n = 4), and frontline healthcare providers (n = 4). All interviews were recorded, transcribed, and thematically analyzed using qualitative content analysis. RESULTS: Four themes emerged around supply and health systems barriers, demand-related barriers, specific challenges related to MACV and MCV2 co-administration, and motivations and efforts to improve vaccination coverage. Supply and health systems barriers included aging cold chain equipment, staff shortages, overworked and poorly trained staff, insufficient supplies and financial resources, and challenges with implementing community outreach activities. Health workers largely viewed MACV introduction as a source of motivation for caregivers to bring their children for the 15- to 18-month visit. However, they also pointed to demand barriers, including cultural practices that sometimes discourage vaccination, misconceptions about vaccines, and religious beliefs. Challenges in co-administering MACV and MCV2 were mainly related to reluctance among health workers to open multi-dose vials unless enough children were present to avoid wastage. CONCLUSIONS: To improve effective administration of vaccines in the second-year of life, adequate operational and programmatic planning, training, communication, and monitoring are necessary. Moreover, clear policy communication is needed to help ensure that health workers do not refrain from opening multi-dose vials for small numbers of children.

      9. Principles of vaccine licensure, approval, and recommendations for useexternal icon
        Pickering LK, Meissner HC, Orenstein WA, Cohn AC.
        Mayo Clin Proc. 2020 Feb 13.
        The licensure and recommendation processes for vaccines are complex. In the United States, vaccines are licensed for the civilian and military populations on the basis of review of Biologics License Applications submitted to the Food and Drug Administration (FDA) by vaccine manufacturers. For FDA-licensed vaccines, the product label includes indications, contraindications, and precautions for each vaccine. Package inserts do not include recommendations for vaccine use from the Advisory Committee on Immunization Practices (ACIP). The ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the director of the Centers for Disease Control and Prevention on the use of vaccines and related agents for control of vaccine preventable diseases in the civilian and military populations of the United States. As an external advisory committee to the Centers for Disease Control and Prevention, the ACIP has no regulatory authority but the committee does have responsibility for approving vaccines to be covered under the Vaccines for Children program. To implement ACIP vaccine recommendations in the public and private sectors, a collaboration of federal, state, and local governments as well as private organizations dealing with public health, vaccine supply, vaccine administration, vaccine finance, outcomes monitoring, public perception, and public trust and support must work together. Issues including vaccine misinformation, declining community immunity (herd protection), and need for risk communication add stress to this complex and fragile system. This study describes the functions of and interactions between FDA and ACIP.

      10. Continued evidence of the impact of rotavirus vaccine in children less than 3 years of age from the US New Vaccine Surveillance Network- a multi-site active surveillance program, 2006-2016external icon
        Staat MA, Payne DC, Halasa N, Weinberg GA, Donauer S, Wikswo M, McNeal M, Edwards KM, Szilagyi PG, Bernstein DI, Curns AT, Sulemana I, Esona MD, Bowen MD, Parashar UD.
        Clin Infect Dis. 2020 Feb 15.
        BACKGROUND: Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in three US counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006-2016. METHODS: Children <3 years of age hospitalized or visiting the ED with AGE, were enrolled from January 2006-June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as pre-vaccine and 2008-2016 as post-vaccine periods. Rotavirus genotype trends were compared over time. RESULTS: Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and post-vaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the post-vaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the pre-vaccine period with a significantly lower proportion (7%) in the post-vaccine period (p<.001). G2P[4] remained stable (8% to 14%) in both periods, while G3P[8] and G12P[8] increased in proportion from pre-to post-vaccine periods (1% to 25% and 17% to 40%) respectively. CONCLUSIONS: The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children <3 years of age and a shift in the residual genotypes from G1P[8] to other genotypes.

    • Injury and Violence
      1. Microfinance programs provide access to small amounts of capital in the form of credit, savings, or financial incentives. There is evidence that microfinance reduces financial strain and reduces violence making it a promising public health approach. However, most of this evidence was generated internationally in low-resource countries; thus, it is likely that adaptations are necessary for microfinance to be effective at preventing violence in the U.S. This article reviews the evidence base for microfinance interventions on violence outcomes; outlines the potential of microfinance to prevent violence in the U.S.; and offers some possible adaptations in order to increase the likelihood that microfinance will prevent violence in the U.S. Programs might consider providing matched savings instead of small loans to individuals and providing job skills training. Furthermore, it is important for U.S. microfinance programs to engage multiple sectors and to consider additional content, such as a gender equity component and safety planning to protect those who might be in violent relationships. It is also important that these adaptations be rigorously evaluated for impacts on multiple forms of violence.

    • Laboratory Sciences
      1. Brucella exposure risk events in 10 clinical laboratories, New York City, USA, 2015 to 2017external icon
        Ackelsberg J, Liddicoat A, Burke T, Szymczak WA, Levi MH, Ostrowsky B, Hamula C, Patel G, Kopetz V, Saverimuttu J, Sordillo EM, D'Souza D, Mitchell EA, Lowe W, Khare R, Tang YW, Bianchi AL, Egan C, Perry MJ, Hughes S, Rakeman JL, Adams E, Kharod GA, Tiller R, Saile E, Lee S, Gonzalez E, Hoppe B, Leviton IM, Hacker S, Ni KF, Orsini RL, Jhaveri S, Mazariegos I, Dingle T, Koll B, Stoddard RA, Galloway R, Hoffmaster A, Fine A, Lee E, Dentinger C, Harrison E, Layton M.
        J Clin Microbiol. 2020 Jan 28;58(2).
        From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

      2. Clinical-laboratory interface interventions to improve impact of viral load and early infant diagnosis testing scale-upexternal icon
        Alemnji GA, Pati R, Chun H, Zeh C, Mosha F, Siberry G, Ondoa P.
        AIDS Res Hum Retroviruses. 2020 Feb 19.
        Despite tremendous improvements in viral load (VL) monitoring and early infant diagnosis (EID) in many countries, low VL and EID testing rates and low VL suppression rates persist in specific regions and among certain subpopulations. The VL/EID cascade includes patient and provider demand creation, sample collection and transportation, laboratory testing, results transmission back to the clinic, and patient management. Gaps in communication and coordination between clinical and laboratory counterparts can lead to suboptimal outcomes, such as delay or inability to collect and transport samples to the laboratory for testing and failure of test results to reach providers and patients in an efficient, timely, and effective manner. To bridge these gaps and optimize the impact of VL/EID scale-up, we reviewed the components of the cascade and their inter-relationships to identify barriers and facilitators. As part of this process, people living with HIV must be engaged in creating demand for VL/EID testing. In addition, there should be strong communication and collaboration between the clinical and laboratory teams throughout the cascade, along with joint performance review, site visits, and continuous quality improvement activities. Strengthening the clinical-laboratory interface requires innovative solutions and implementation of best practices, including the use of point-of-care diagnostics, simplified data systems, and an efficient supply chain system to minimize interface gaps.

      3. Rapid, sensitive, and accurate point-of-care detection of lethal amatoxins in urineexternal icon
        Bever CS, Swanson KD, Hamelin EI, Filigenzi M, Poppenga RH, Kaae J, Cheng LW, Stanker LH.
        Toxins (Basel). 2020 Feb 15;12(2).
        Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of alpha-amanitin (alpha-AMA) or gamma-AMA, and 100 ng/mL of beta-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography-mass spectrometry (LC-MS) methods.

      4. Implementation of a three-tiered approach to identify and characterize anti-drug antibodies raised against HIV-specific broadly neutralizing antibodiesexternal icon
        Bharadwaj P, Riekofski C, Lin S, Seaman MS, Garber DA, Montefiori D, Sarzotti-Kelsoe M, Ackerman ME, Weiner JA.
        J Immunol Methods. 2020 Feb 15:112764.
        The ability to detect, quantify, and interrogate the properties of immune responses raised against biological therapeutics is not only important to our understanding of these molecules, but also to their success in the clinic. A tiered assay approach to identify the presence, specificity, and titer of anti-drug antibody (ADA) responses has been adopted as a gold standard by industry leaders, the FDA, and the EMA. In order to support pre-clinical and clinical trials, these assays must be standardized, and their performance sufficiently characterized to ensure the accuracy and reproducibility of results under relevant testing conditions. Here we present implementation of electrochemiluminiscence assays that fit into the tiered paradigm of ADA testing for five HIV broadly neutralizing antibodies (3NC117, 3BNC117-LS, 10-1074, PGT121, and PGDM1400) in compliance with Good Clinical Laboratory practices. Assay sensitivities and matrix effects were evaluated and used to inform the development of positivity cut points. Once cut points were established, assay precision, specificity, free-drug tolerance, and robustness were defined. In all cases, assay characteristics met or surpassed recommendations set forth by the FDA. To further evaluate the performance of these assays and the tiered approach, samples from non-human primates that had received a subset of the five therapeutics were evaluated. In sum, this study reports qualification of a set of ADA assays available to the scientific community as pre-clinical and clinical trials of broadly HIV-neutralizing antibodies proceed, and a framework that is easily adapted as new drug products are advanced in the clinic.

      5. CoMPARA: Collaborative modeling project for androgen receptor activityexternal icon
        Mansouri K, Kleinstreuer N, Abdelaziz AM, Alberga D, Alves VM, Andersson PL, Andrade CH, Bai F, Balabin I, Ballabio D, Benfenati E, Bhhatarai B, Boyer S, Chen J, Consonni V, Farag S, Fourches D, Garcia-Sosa AT, Gramatica P, Grisoni F, Grulke CM, Hong H, Horvath D, Hu X, Huang R, Jeliazkova N, Li J, Li X, Liu H, Manganelli S, Mangiatordi GF, Maran U, Marcou G, Martin T, Muratov E, Nguyen DT, Nicolotti O, Nikolov NG, Norinder U, Papa E, Petitjean M, Piir G, Pogodin P, Poroikov V, Qiao X, Richard AM, Roncaglioni A, Ruiz P, Rupakheti C, Sakkiah S, Sangion A, Schramm KW, Selvaraj C, Shah I, Sild S, Sun L, Taboureau O, Tang Y, Tetko IV, Todeschini R, Tong W, Trisciuzzi D, Tropsha A, Van Den Driessche G, Varnek A, Wang Z, Wedebye EB, Williams AJ, Xie H, Zakharov AV, Zheng Z, Judson RS.
        Environ Health Perspect. 2020 Feb;128(2):27002.
        BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of approximately 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.

    • Maternal and Child Health
      1. Fragile X syndrome-associated emergency department visits in the United States, 2006-2011external icon
        Do TQ, Riley C, Paramsothy P, Ouyang L, Bolen J, Grosse SD.
        Am J Intellect Dev Disabil. 2020 Mar;125(2):103-108.
        Using national data, we examined emergency department (ED) encounters during 2006-2011 for which a diagnosis code for fragile X syndrome (FXS) was present (n = 7,217). Almost half of ED visits coded for FXS resulted in hospitalization, which is much higher than for ED visits not coded for FXS. ED visits among females coded for FXS were slightly more likely to result in hospitalization. These findings underscore the importance of surveillance systems that could accurately identify individuals with FXS, track healthcare utilization and co-occurring conditions, and monitor quality of care in order to improve care and reduce FXS-associated morbidity.

    • Mining
      1. Evaluation of stress-control layout at the Subtropolis Mine, Petersburg, Ohioexternal icon
        Iannacchione A, Miller T, Esterhuizen G, Slaker B, Murphy M, Cope N, Thayer S.
        Int J Min Sci Technol. 2020 .
        The Subtropolis room-and-pillar mine extracts the Vanport Limestone (Allegheny Formation, Pennsylvanian System) near Petersburg, Ohio. Strata instability problems associated with excessive concentrations of lateral stress caused the mine operator to implement a change in layout design. This mining method has been identified as a stress control layout and has been used by other underground stone mines in the past with varying degrees of success. Practical experience has shown that entry headings advance in the direction of the principal lateral stress, producing lower stress concentrations with better mining conditions. It is important to minimize stress concentrations along the mining front, so an arrow-shaped advance is recommended. This technique advances more developments (headings) in a “good” direction and reduces developments (crosscuts) in the “bad direction.” As is expected, the stress control layout enhances the potential for shear failures in crosscuts. It is, therefore, important to focus crosscut engineering interventions that either: (a) lower stress concentrations (for example, an arched roof) or (b) enhance strength of the strata containing the shears (for example, rock reinforcement). This study focuses on observing strata conditions on a regular basis and monitoring the response of these strata to changing geologic and mining conditions through 3D Dynamic LiDAR scans.

    • Occupational Safety and Health
      1. Recent studies have reported emission rates of up to 10<sup>12</sup> ultrafine particles/min from fused filament fabrication three-dimensional printers when operated in unventilated or minimally ventilated test chambers. However, in these studies, there are no data to relate this rate to airborne concentrations in a manufacturing environment. An assessment of particle exposures of workers was conducted at a three-dimensional printing shop using multiple fused filament printers with unfilled and carbon nanotube and/or carbon nanofiber-infused polyetheletherketone filaments. The study simultaneously evaluated emissions in two environments: (1) in a field portable test chamber with one three-dimensional printer and (2) in the manufacturing area with multiple printers in use. Emission rates were calculated for a variety of filaments and ranged from 1.21 to 33.5 x 10<sup>11</sup> particles/min, with geometric mean diameters ranging from 11.4 to 33.3 nm. The emission rates estimated by a scanning mobility particle sizer were much lower than from the fast mobility particle sizer due to differences in the lower size resolution. Samples collected in the chamber and manufacturing area by thermophoretic sampling included free (no polymer) carbon nanotubes and nanofibers and their bundles. The company reportedly never handled free carbon nanotubes or nanofibers, and prior research has indicated that the release of free nanomaterials through three-dimensional printing or mechanical action is highly unlikely. This presents the possibility that these materials are being released from the matrix during use or that these materials were brought into the facility through the supply chain, or by other means.

      2. The CDC Worksite Health ScoreCard: An assessment tool to promote employee health and well-beingexternal icon
        Lang JE, Mummert A, Roemer EC, Kent KB, Koffman DM, Goetzel RZ.
        Am J Health Promot. 2020 Mar;34(3):319-321.

      3. Prevalence of workplace health practices and policies in hospitals: Results from the Workplace Health in America Studyexternal icon
        Mulder L, Belay B, Mukhtar Q, Lang JE, Harris D, Onufrak S.
        Am J Health Promot. 2020 Feb 20:890117120905232.
        PURPOSE: To provide a nationally representative description on the prevalences of policies, practices, programs, and supports relating to worksite wellness in US hospitals. DESIGN: Cross-sectional, self-report of hospitals participating in Workplace Health in America (WHA) survey from November 2016 through September 2017. SETTING: Hospitals across the United States. PARTICIPANTS: Random sample of 338 eligible hospitals participating in the WHA survey. MEASURES: We used previous items from the 2004 National Worksite Health Promotion survey. Key measures included presence of Worksite Health Promotion programs, evidence-based strategies, health screenings, disease management programs, incentives, work-life policies, barriers to health promotion program implementation, and occupational safety and health. ANALYSIS: Independent variables included hospital characteristics (eg, size). Dependent characteristics included worksite health promotion components. Descriptive statistics and chi(2) analyses were used. RESULTS: Eighty-two percent of hospitals offered a wellness programs during the previous year with larger hospitals more likely than smaller hospitals to offer programs (P < .01). Among hospitals with wellness programs, 69% offered nutrition programs, 74% offered physical activity (PA) programs, and 84% had a policy to restrict all tobacco use. Among those with cafeterias or vending machines, 40% had a policy for healthier foods. Only 47% and 25% of hospitals offered lactation support or healthy sleep programs, respectively. CONCLUSION: Most hospitals offer wellness programs. However, there remain hospitals that do not offer wellness programs. Among those that have wellness programs, most offer supports for nutrition, PA, and tobacco control. Few hospitals offered programs on healthy sleep or lactation support.

    • Parasitic Diseases
      1. Given that the C580Y polymorphism in the Plasmodium falciparum propeller domain of the kelch 13 gene (pfk13) was documented in Guyana, monitoring for mutations associated with antimalarial resistance was undertaken in neighboring Roraima state in Brazil. Polymorphisms in the pfmdr1 and pfk13 genes were investigated in 275 P. falciparum samples. No pfk13 mutations were observed. Triple mutants 184F, 1042D, and 1246Y were observed in 100% of the samples successfully sequenced for the pfmdr1 gene, with 20.1% of these having an additional mutation at codon 1034C. Among them, 2.5% of samples harbored two copies of the pfmdr1 gene. We found no evidence of the spread of C580Y parasites to Roraima state, Brazil. As previously observed, the 184F, 1042D, and 1246Y mutations in the pfmdr1 gene appear to be fixed in this region. Continued molecular surveillance is essential to detect any potential migration or local emergence of artemisinin-resistant mutation.

      2. Autochthonous Chagas disease - Missouri, 2018external icon
        Turabelidze G, Vasudevan A, Rojas-Moreno C, Montgomery SP, Baker M, Pratt D, Enyeart S.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 21;69(7):193-195.
        On December 13, 2017, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected case of Chagas disease in a Missouri woman. The patient had donated blood, and laboratory screening revealed antibodies to Trypanosoma cruzi, the parasite that causes Chagas disease. Evaluation by physicians found no clinical symptoms consistent with Chagas disease. The patient had no travel history that would have suggested a significant risk for Chagas disease risk and had no occupational exposure to the disease agent. She had never received a blood transfusion or organ transplant. Confirmatory testing of the patient's serum at CDC for T. cruzi antibody was consistent with infection. These findings raise the possibility that the exposure to T. cruzi occurred locally (autochthonously) in Missouri. Although the insect vector for the parasite T. cruzi, triatomines (commonly known as "kissing bugs"), has been identified previously in Missouri, no locally acquired human cases of Chagas disease have been identified in the state. Health care providers and public health professionals should be aware of the possibility of locally acquired Chagas disease in the southern United States.

    • Physical Activity
      1. Physical activity types among US adults with mobility disability, Behavioral Risk Factor Surveillance System, 2017external icon
        Hollis ND, Zhang QC, Cyrus AC, Courtney-Long E, Watson K, Carroll DD.
        Disabil Health J. 2020 Feb 3:100888.
        BACKGROUND: The Physical Activity Guidelines for Americans, second edition, recommend that all adults participate in moderate-intensity equivalent aerobic physical activity at least 150-300 min/week for substantial health benefits and muscle-strengthening activities involving all major muscle groups 2 or more days a week. The prevalence of the general population meeting the Guidelines and the types of physical activity in which they engage have been described elsewhere. Similar descriptions are lacking for individuals with mobility disability whose physical activity profiles may differ from the general population. OBJECTIVE: This study examined patterns of aerobic and muscle-strengthening physical activity among US adults with mobility disability. METHODS: We used 2017 Behavioral Risk Factor Surveillance System data from 66,635 adults with mobility disability. We estimated the percentage who engaged in any aerobic physical activity, met the aerobic and/or muscle-strengthening guidelines, and who participated in specific activities. RESULTS: Less than half (45.2%) of US adults with mobility disability reported engaging in aerobic physical activity, and 39.5% met one or both components of the physical activity guidelines. Walking was the most commonly reported activity type (34.0%). CONCLUSIONS: Walking is a common activity type among adults with mobility disability. Efforts to make walking or wheelchair rolling a safe, viable option are important to helping decrease barriers that may limit the ability of those with mobility disability to engage in walking or other physical activity types.

    • Public Health Law
      1. State and territorial laws prohibiting sales of tobacco products to persons aged <21 years - United States, December 20, 2019external icon
        Marynak K, Mahoney M, Williams KS, Tynan MA, Reimels E, King BA.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 21;69(7):189-192.
        Raising the minimum legal sales age (MLSA) for tobacco products to 21 years (T21) is a strategy to help prevent and delay the initiation of tobacco product use (1). On December 20, 2019, Congress raised the federal MLSA for tobacco products from 18 to 21 years. Before enactment of the federal T21 law, localities, states, and territories were increasingly adopting their own T21 laws as part of a comprehensive approach to prevent youth initiation of tobacco products, particularly in response to recent increases in use of e-cigarettes among youths (2). Nearly all tobacco product use begins during adolescence, and minors have cited social sources such as older peers and siblings as a common source of access to tobacco products (1,3). State and territorial T21 laws vary widely and can include provisions that might not benefit the public's health, including penalties to youths for purchase, use, or possession of tobacco products; exemptions for military populations; phase-in periods; and preemption of local laws. To understand the landscape of U.S. state and territorial T21 laws before enactment of the federal law, CDC assessed state and territorial laws prohibiting sales of all tobacco products to persons aged <21 years. As of December 20, 2019, 19 states, the District of Columbia (DC), Guam, and Palau had enacted T21 laws, including 13 enacted in 2019. Compared with T21 laws enacted during 2013-2018, more laws enacted in 2019 have purchase, use, or possession penalties; military exemptions; phase-in periods of 1 year or more; and preemption of local laws related to tobacco product sales. T21 laws could help prevent and reduce youth tobacco product use when implemented as part of a comprehensive approach that includes evidence-based, population-based tobacco control strategies such as smoke-free laws and pricing strategies (1,4).

    • Public Health Leadership and Management
      1. OBJECTIVE: To examine the associations between Medicaid expansion and nurse staffing ratios and hospital-wide readmission rates. DATA SOURCES: Secondary data from the 2011-2016 Healthcare Cost Report Information System, the American Hospital Association Annual Survey, and the Hospital Compare data. STUDY DESIGN: Difference-in-difference models are used to compare outcomes in hospitals located in states that expanded Medicaid with those located in nonexpansion states. The changes in nurse staffing ratios and hospital-wide readmission rates are calculated in each one of the postexpansion years (2014, 2015, and 2016), compared to pre-expansion. PRINCIPAL FINDINGS: Results indicate that nurse staffing ratios increased, whereas hospital-wide readmission rates declined in expansion states relative to nonexpansion states. Nurse staffing ratios increased by 0.33, 0.42, and 0.46 registered nurses hours per adjusted patient days in 2014, 2015, and 2016 in hospitals located in expansion states, compared with hospitals in nonexpansion states after expansion. This increase was statistically significant (P < .001) in 2015 and 2016, but marginally significant (P = .016) in 2014. Hospital-wide readmission rates statistically significantly decreased by 9, 16, and 18 per 10 000 patients (P < .001) in 2014, 2015, and 2016, respectively, in expansion vs nonexpansion states hospitals after expansion. CONCLUSIONS: Medicaid expansion was associated with gradually improved hospitals' nurse staffing ratios and hospital-wide readmission rates from 2014 through 2016. The continued monitoring of quality measures of hospitals can help assess the impact of Medicaid expansion over a longer period of time.

    • Substance Use and Abuse
      1. Resurgent methamphetamine use at treatment admission in the United States, 2008-2017external icon
        Jones CM, Olsen EO, O'Donnell J, Mustaquim D.
        Am J Public Health. 2020 Feb 20:e1-e8.
        Objectives. To evaluate trends and correlates of methamphetamine use in the United States.Methods. Data are from 15 747 334 drug-related treatment admissions among persons aged 12 years or older in the 2008-2017 Treatment Episode Data Set. We analyzed trends and used multivariable logistic regression.Results. Methamphetamine-related admissions increased from 15.1% of drug-related treatment admissions in 2008 to 23.6% in 2017. Increases occurred among nearly all demographic groups. Methamphetamine injection increased from 17.5% of admissions in 2008 to 28.4% in 2017. Among methamphetamine-related admissions, heroin use increased from 5.3% of admissions in 2008 to 23.6% in 2017. Characteristics associated with increased odds of reporting methamphetamine use at admission included female sex; admissions aged 35 to 44 years; admissions in the Midwest, South, and West; unemployment; not in labor force; living dependent; living homeless; and having a referral from criminal justice, a health care provider, or other community treatment source.Conclusions. Treatment admissions involving methamphetamine use increased significantly over the past decade and appear to be linked to the ongoing opioid crisis in the United States. Efforts to mobilize public health prevention, treatment, and response strategies to address rising methamphetamine use and overdose are needed. (Am J Public Health. Published online ahead of print February 20, 2020: e1-e8. doi:10.2105/AJPH.2019.305527).

      2. Modes of marijuana use - smoking, vaping, eating, and dabbing: Results from the 2016 BRFSS in 12 Statesexternal icon
        Schauer GL, Njai R, Grant-Lenzy AM.
        Drug Alcohol Depend. 2020 Feb 6;209:107900.
        BACKGROUND: The prevalence of modes of marijuana use (e.g., smoked, vaped, eaten, dabbed, etc.), and of multi-modal use has not been assessed across multiple states, and can inform marijuana prevention and education work, given that certain modes of use are associated with specific public health risks. This study aimed to assess the prevalence of different modalities of reported marijuana use among adults in 12 states. METHODS: Data came from 6174 adult marijuana users age 18 and older who responded to questions about past month and mode of marijuana use on the 2016 BRFSS surveys in 12 states with varied state marijuana policies. We used weighted frequencies for descriptive analyses, and logistic regression to identify correlates of multi-modal use. RESULTS: The prevalence of past month (current) marijuana use among adults in these states was 9.1 % (males = 12.0 %, females= 6.3 %). Among current marijuana users, 33.7 % reported multiple methods of marijuana use, 90.1 % reported any marijuana smoking (e.g., joints, blunts, bongs, bowls), 58.3 % reported only smoking (no other modes of consumption), 24.5 % reported any edible use, 4.5 % reported using only edibles, 19.4 % reported any marijuana vaping, 2.1 % reported only vaping, 14.5 % reported any dabbing (flash vaporization/inhalation of highly concentrated marijuana), and 0.4 % reported only dabbing. Correlates of multimodal use are also examined. CONCLUSION: Multi-modal use of marijuana is common, and use of non-smoked marijuana (edibles, vaping, dabbing) often occurs in conjunction with other modes of marijuana use. Ongoing surveillance of marijuana modes of use and multi-modal use is warranted to inform public education and prevention.

    • Zoonotic and Vectorborne Diseases
      1. Rickettsia felis identified in two fatal cases of acute meningoencephalitisexternal icon
        Mawuntu AH, Johar E, Anggraeni R, Feliana F, Bernadus JB, Safari D, Yudhaputri FA, Dhenni R, Dewi YP, Kato C, Powers AM, Rosenberg R, Soebandrio A, Myint KS.
        PLoS Negl Trop Dis. 2020 Feb 18;14(2):e0007893.
        BACKGROUND: Rickettsia felis has recently emerged worldwide as a cause of human illness. Typically causing mild, undifferentiated fever, it has been implicated in several cases of non-fatal neurological disease in Mexico and Sweden. Its distribution and pathogenicity in Southeast Asia is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We retroactively tested cerebrospinal fluid (CSF) or sera from 64 adult patients admitted to hospital in North Sulawesi, Indonesia with acute neurological disease. Rickettsia felis DNA was identified in the CSF of two fatal cases of meningoencephalitis using multi-locus sequence typing semi-nested PCR followed by Sanger sequencing. DNA from both cases had 100% sequence homologies to the R. felis reference strain URRWXCal2 for the 17-kDa and ompB genes, and 99.91% to gltA. CONCLUSION/SIGNIFICANCE: The identification of R. felis in the CSF of two fatal cases of meningoencephalitis in Indonesia suggests the distribution and pathogenicity of this emerging vector-borne bacteria might be greater than generally recognized. Typically Rickettsia are susceptible to the tetracyclines and greater knowledge of R. felis endemicity in Indonesia should lead to better management of some acute neurological cases.

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