Volume 11, Issue 28 July 16, 2019

CDC Science Clips: Volume 11, Issue 28, July 16, 2019

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

This week Science Clips is pleased to feature the winners of the 2019 CDC Charles C. Shepard Science Awards as well as citations related to the keynote address by Jon Duke MD MS, Georgia Institute of Technology – “Unlocking Big Data for Public Health.”

  1. CDC Charles C. Shepard Science Awards
    • Assessment
      1. Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort studyexternal icon
        Saha SK, Schrag SJ, El Arifeen S, Mullany LC, Shahidul Islam M, Shang N, Qazi SA, Zaidi AK, Bhutta ZA, Bose A, Panigrahi P, Soofi SB, Connor NE, Mitra DK, Isaac R, Winchell JM, Arvay ML, Islam M, Shafiq Y, Nisar I, Baloch B, Kabir F, Ali M, Diaz MH, Satpathy R, Nanda P, Padhi BK, Parida S, Hotwani A, Hasanuzzaman M, Ahmed S, Belal Hossain M, Ariff S, Ahmed I, Ibne Moin SM, Mahmud A, Waller JL, Rafiqullah I, Quaiyum MA, Begum N, Balaji V, Halen J, Nawshad Uddin Ahmed AS, Weber MW, Hamer DH, Hibberd PL, Sadeq-Ur Rahman Q, Mogan VR, Hossain T, McGee L, Anandan S, Liu A, Panigrahi K, Abraham AM, Baqui AH.
        Lancet. 2018 Jul 14;392(10142):145-159.
        BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95.4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI] 11.2-15.6) per 1000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5.4, 95% CrI 4.8-6.3 episodes per 1000 livebirths), followed by Ureaplasma spp (2.4, 1.6-3.2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation.

    • Data Methods and Study Design
      1. Hierarchical Bayes models have been used in disease mapping to examine small scale geographic variation. State level geographic variation for less common causes of mortality outcomes have been reported however county level variation is rarely examined. Due to concerns about statistical reliability and confidentiality, county-level mortality rates based on fewer than 20 deaths are suppressed based on Division of Vital Statistics, National Center for Health Statistics (NCHS) statistical reliability criteria, precluding an examination of spatio-temporal variation in less common causes of mortality outcomes such as suicide rates (SRs) at the county level using direct estimates. Existing Bayesian spatio-temporal modeling strategies can be applied via Integrated Nested Laplace Approximation (INLA) in R to a large number of rare causes of mortality outcomes to enable examination of spatio-temporal variations on smaller geographic scales such as counties. This method allows examination of spatiotemporal variation across the entire U.S., even where the data are sparse. We used mortality data from 2005-2015 to explore spatiotemporal variation in SRs, as one particular application of the Bayesian spatio-temporal modeling strategy in R-INLA to predict year and county-specific SRs. Specifically, hierarchical Bayesian spatio-temporal models were implemented with spatially structured and unstructured random effects, correlated time effects, time varying confounders and space-time interaction terms in the software R-INLA, borrowing strength across both counties and years to produce smoothed county level SRs. Model-based estimates of SRs were mapped to explore geographic variation.

    • Laboratory Science
      1. Use of a Scalable Replicon-Particle Vaccine to Protect Against Lethal Lassa Virus Infection in the Guinea Pig Modelexternal icon
        Kainulainen MH, Spengler JR, Welch SR, Coleman-McCray JD, Harmon JR, Klena JD, Nichol ST, Albarino CG, Spiropoulou CF.
        J Infect Dis. 2018 May 25;217(12):1957-1966.
        Lassa fever is a viral zoonosis that can be transmitted from person to person, especially in the hospital setting. The disease is endemic to several countries in West Africa and can be a major contributor to morbidity and mortality in affected areas. There are no approved vaccines to prevent Lassa virus infection. In this work, we present a vaccine candidate that combines the scalability and efficacy benefits of a live vaccine with the safety benefits of single-cycle replication. The system consists of Lassa virus replicon particles devoid of the virus essential glycoprotein gene, and a cell line that expresses the glycoprotein products, enabling efficient vaccine propagation. Guinea pigs vaccinated with these particles showed no clinical reaction to the inoculum and were protected against fever, weight loss, and lethality after infection with Lassa virus.

    • Prevention and Control
      1. Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trialexternal icon
        Zaman K, Estivariz CF, Morales M, Yunus M, Snider CJ, Gary HE, Weldon WC, Oberste MS, Wassilak SG, Pallansch MA, Anand A.
        Lancet Infect Dis. 2018 Jun;18(6):657-665.
        BACKGROUND: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. METHODS: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0.1 mL in total] of about 10(5) 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0.5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0.05 (one-tailed) was used. This trial is registered at, number NCT02643368, and is closed to accrual. FINDINGS: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4.2% [90% CI -7.9 to -0.4] in the 1 week group and -1.8% [-5.0 to 1.5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1.0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines. INTERPRETATION: Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response. FUNDING: US Centers for Disease Control and Prevention.

    • Shepard Awards Keynote Speaker: Jon Duke MD MS, Georgia Institute of Technology, “Unlocking Big Data for Public Health”
      1. Bridging islands of information to establish an integrated knowledge base of drugs and health outcomes of interestexternal icon
        Boyce RD, Ryan PB, Noren GN, Schuemie MJ, Reich C, Duke J, Tatonetti NP, Trifiro G, Harpaz R, Overhage JM, Hartzema AG, Khayter M, Voss EA, Lambert CG, Huser V, Dumontier M.
        Drug Saf. 2014 Aug;37(8):557-67.
        The entire drug safety enterprise has a need to search, retrieve, evaluate, and synthesize scientific evidence more efficiently. This discovery and synthesis process would be greatly accelerated through access to a common framework that brings all relevant information sources together within a standardized structure. This presents an opportunity to establish an open-source community effort to develop a global knowledge base, one that brings together and standardizes all available information for all drugs and all health outcomes of interest (HOIs) from all electronic sources pertinent to drug safety. To make this vision a reality, we have established a workgroup within the Observational Health Data Sciences and Informatics (OHDSI, collaborative. The workgroup’s mission is to develop an open-source standardized knowledge base for the effects of medical products and an efficient procedure for maintaining and expanding it. The knowledge base will make it simpler for practitioners to access, retrieve, and synthesize evidence so that they can reach a rigorous and accurate assessment of causal relationships between a given drug and HOI. Development of the knowledge base will proceed with the measureable goal of supporting an efficient and thorough evidence-based assessment of the effects of 1,000 active ingredients across 100 HOIs. This non-trivial task will result in a high-quality and generally applicable drug safety knowledge base. It will also yield a reference standard of drug-HOI pairs that will enable more advanced methodological research that empirically evaluates the performance of drug safety analysis methods.

      2. A few useful things to know about machine learningexternal icon
        Domingos P.
        Communications of the ACM. 2012 ;55(10):78-87.
        MACHINE LEARNING SYSTEMS automatically learn programs from data. This is often a very attractive alternative to manually constructing them, and in the last decade the use of machine learning has spread rapidly throughout computer science and beyond. Machine learning is used in Web search, spam filters, recommender systems, ad placement, credit scoring, fraud detection, stock trading, drug design, and many other applications. A recent report from the McKinsey Global Institute asserts that machine learning (a.k.a. data mining or predictive analytics) will be the driver of the next big wave of innovation. 15 Several fine textbooks are available to interested practitioners and researchers (for example, Mitchell 16 and Witten et al. 24). However, much of the “folk knowledge” that is needed to successfully develop machine learning applications is not readily available in them. As a result, many machine learning projects take much longer than necessary or wind up producing less-than-ideal results. Yet much of this folk knowledge is fairly easy to communicate. This is the purpose of this article. ? 2012 ACM.

      3. Patients on multiple medications are at increased risk for adverse drug events. While physicians can reduce this risk by regularly reviewing the side-effect profiles of their patients’ medications, this process can be time-consuming. We created a decision support system designed to expedite reviewing potential adverse reactions through information visualization. The system includes a database containing 16,340 unique drug and side-effect pairs, representing 250 common medications. A numeric score is assigned to each pair reflecting the strength of association between drug and effect. Based on these scores, the system generates graphical adverse reaction maps for any user-selected combination of drugs. A study comparing speed and accuracy of retrieving side-effect data using this tool versus UpToDate demonstrated a 60% reduction in time to complete a query (61 s vs. 155 s, p < 0.0001) with no decrease in accuracy. These findings suggest that information visualization can significantly expedite review of potential adverse drug events.

      4. Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research networkexternal icon
        Duke JD, Ryan PB, Suchard MA, Hripcsak G, Jin P, Reich C, Schwalm MS, Khoma Y, Wu Y, Xu H, Shah NH, Banda JM, Schuemie MJ.
        Epilepsia. 2017 Aug;58(8):e101-e106.
        Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

      5. Electronic medical billing records and public health surveillance: comparison of two systems used during the 1996 Atlanta Olympic Gamesexternal icon
        Duke JD, Tindol GA, Toomey KE, Pitts SR, Dean AG.
        J Public Health Manag Pract. 2002 May;8(3):18-29.
        For selected diagnoses of public health interest during the 1996 Olympic Games, the authors compared data concurrently obtained on the same patient population by two separate surveillance systems: (1) an existing hospital electronic medical billing records system and (2) a system based on manual record abstraction. Counts of total patient visits closely agreed, though the two systems differed considerably in some diagnostic categories, especially injuries. The authors concluded that while causation, risk factors, and illness severity are not reflected directly in standard International Classification of Diseases (ICD) codes, and “E” codes to indicate causation may not be used, special-purpose surveillance systems based on existing computerized medical records may be as effective as manual data abstracting.

      6. Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchersexternal icon
        Hripcsak G, Duke JD, Shah NH, Reich CG, Huser V, Schuemie MJ, Suchard MA, Park RW, Wong IC, Rijnbeek PR, van der Lei J, Pratt N, Noren GN, Li YC, Stang PE, Madigan D, Ryan PB.
        Stud Health Technol Inform. 2015 ;216:574-8.
        The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world.

      7. Characterizing treatment pathways at scale using the OHDSI networkexternal icon
        Hripcsak G, Ryan PB, Duke JD, Shah NH, Park RW, Huser V, Suchard MA, Schuemie MJ, DeFalco FJ, Perotte A, Banda JM, Reich CG, Schilling LM, Matheny ME, Meeker D, Pratt N, Madigan D.
        Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7329-36.
        Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.

      8. Medicine. Big data meets public healthexternal icon
        Khoury MJ, Ioannidis JP.
        Science. 2014 Nov 28;346(6213):1054-5.

        [No abstract]

      9. No small change for the health information economyexternal icon
        Mandl KD, Kohane IS.
        N Engl J Med. 2009 Mar 26;360(13):1278-81.

        [No abstract]

      10. Finding the missing link for big biomedical dataexternal icon
        Weber GM, Mandl KD, Kohane IS.
        Jama. 2014 Jun 25;311(24):2479-80.

        [No abstract]

      11. A free and open-source software library originally developed by Google, TensorFlow makes it easy for beginners and experts to create machine learning models for desktop, mobile, web, and cloud with a collection of workflows to develop and train models using Python, JavaScript, or Swift.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Knee osteoarthritis and the risk of medically treated injurious falls among older adults: A community-based US cohort studyexternal icon
        Barbour KE, Sagawa N, Boudreau RM, Winger ME, Cauley JA, Nevitt MC, Fujii T, Patel KV, Strotmeyer ES.
        Arthritis Care Res (Hoboken). 2019 Jul;71(7):865-874.
        OBJECTIVE: The risk of falls among adults with knee osteoarthritis (OA) has been documented, yet, to our knowledge no studies have examined knee OA and the risk of medically treated injurious falls (overall and by sex), which is an outcome of substantial clinical and public health relevance. METHODS: Using data from the Health Aging and Body Composition Knee Osteoarthritis Substudy, a community-based study of white and African American older adults, we tested associations between knee OA status and the risk of injurious falls among 734 participants with a mean +/- SD age of 74.7 +/- 2.9 years. Knee radiographic OA (ROA) was defined as having a Kellgren-Lawrence grade of >/=2 in at least 1 knee. Knee symptomatic ROA (sROA) was defined as having both ROA and pain symptoms in the same knee. Injurious falls were defined using a validated diagnosis code algorithm from linked Medicare fee-for-service claims. Cox regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: The mean +/- SD follow-up time was 6.59 +/- 3.12 years. Of the 734 participants, 255 (34.7%) had an incident injurious fall over the entire study period. In the multivariate model, compared with those without ROA or pain, individuals with sROA (HR 1.09 [95% CI 0.73-1.65]) did not have a significantly increased risk of injurious falls. Compared with men without ROA or pain, men with sROA (HR 2.57 [95% CI 1.12-5.91]) had a significantly higher risk of injurious falls. No associations were found for women or by injurious fall type. CONCLUSION: Knee sROA was independently associated with an increased risk of injurious falls in older men, but not in older women.

      2. Overview of Centers for Disease Control and Prevention’s Case Investigation of Cervical Cancer Studyexternal icon
        Benard VB, Greek A, Jackson JE, Senkomago V, Hsieh MC, Crosbie A, Alverson G, Stroup AM, Richardson LC, Thomas CC.
        J Womens Health (Larchmt). 2019 Jul 2.
        Background: Despite advances in cervical cancer screening, a significant number of women in the United States have not received adequate screening. Studies have suggested that approximately half of the women who developed cervical cancer were not adequately screened. The Centers for Disease Control and Prevention (CDC) Case Investigation of Cervical Cancer (CICC) Study took a unique approach to reconstruct the time before a woman’s cervical cancer diagnosis and understand the facilitators and barriers to screening and care. This article provides an overview of the study. Methods: This study included all cervical cancer survivors diagnosed with invasive cervical cancer aged 21 years and older in three U.S. states from 2014-2016. The study design consisted of three different data collection methods, including comprehensive registry data, a mailed survey, and medical chart abstraction. This overview compares the characteristics of cervical cancer survivors in the three states by study participation and eligibility status. Results: Registries identified 2,748 women diagnosed with invasive cervical cancer. Of these, 1,730 participants were eligible for participation, 28% (n = 481) enrolled in the study and 23% (n = 400) consented to the medical chart abstraction. Conclusion: The CICC Study is unique in that it addresses, with medical record verification, the medical history of woman 5 years before their cervical cancer diagnosis as well as provides information from the woman on her health care behaviors. This study provides data on a general population of cervical cancer survivors in three states that could be used to guide interventions to increase cervical cancer screening.

      3. Epilepsy is more common among children and adults living in households at lowest incomes. Like those living with any complex chronic condition, people with epilepsy need quality healthcare to improve their health and social outcomes. The purpose of this study was to use the latest national data to provide updated estimates of the percentages of adults aged 18-64years with active epilepsy who were uninsured in 2010, 2013, 2015, and 2017 and to examine changes in health insurance coverage during these years. We analyzed nationally representative samples of adults (aged 18-64years) from the 2010, 2013, 2015, and 2017 National Health Interview Survey (NHIS). We used a validated epilepsy surveillance case definition to classify adults as having active epilepsy during 2010 and 2013 (n=507) and during 2015 and 2017 (n=582). We used the NHIS recode variables available in each year that account for a series of questions posed to respondents to confirm coverage and that ultimately classify respondents with different healthcare coverage types. Overall, the percentage of uninsured adults among respondents aged 18-64years with active epilepsy decreased by more than half (59%), from 17.7% (95% confidence interval [CI]=13.6%-22.7%) in 2010 and 2013 to 7.3% (95% CI=4.8%-10.7%) in 2015 and 2017. The decrease in the percentage of uninsured adults with active epilepsy after 2010 and 2013 was balanced by a similar increase in public insurance coverage and private insurance coverage in 2015 and 2017. Epilepsy stakeholders can ensure that all uninsured adults with epilepsy obtain access to health insurance coverage. National Health Interview Survey data on epilepsy, when available, can be used to monitor trends in insurance status in the new decade.

      4. Impact of making dental care affordable on quality of life in adults aged 45 years and olderexternal icon
        Naavaal S, Griffin SO, Jones JA.
        J Aging Health. 2019 Jul 1:898264319857967.
        Objective: The objective of this study was to examine the associations between self-reported ability to afford dental care and quality of life in adults aged 45 years and older. Method: We used publicly available cross-sectional data from the 2008 National Health Interview Survey and its oral health supplement for 11,760 adults aged 45+ years. The increased probabilities of reporting dental problems attributable to an inability to afford dental care were estimated from multivariate models and combined with respective dental problem disability weights from the Global Burden of Disease to measure loss in quality of life. Results: Prevalence of reported inability to afford dental care, severe tooth loss, severe periodontitis, and untreated caries were 11.9%, 8.5%, 14.3%, and 37.9%, respectively. Inability to afford dental care was associated with an increase of 0.017 disability-adjusted life-years (DALYs) per person per year under base case and 0.020 DALYs under generous assumptions. Conclusion: Making dental care affordable could improve adult’s (age 45 and above) quality of life at a reasonable cost.

      5. Increasing burden of type 2 diabetes in Navajo youth: The SEARCH for Diabetes in Youth Studyexternal icon
        Powell J, Isom S, Divers J, Bellatorre A, Johnson M, Smiley J, Begay Q, Benally C, Hu D, Saydah S, Pettitt DJ, Pihoker C, Dabelea D.
        Pediatr Diabetes. 2019 Jul 1.
        AIM: SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. METHODS: SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002-05 (N = 53), 2006-09 (N = 68) and 2010-13 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth age 10-19 years. Changes in prevalence were tested with a 2-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. RESULTS: YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = 0.65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. CONCLUSION(S): These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation. This article is protected by copyright. All rights reserved.

      6. Data needed to respond appropriately to anemia when it is a public health problemexternal icon
        Williams AM, Addo OY, Grosse SD, Kassebaum NJ, Rankin Z, Ballesteros KE, Olsen HE, Sharma AJ, Jefferds ME, Mei Z.
        Ann N Y Acad Sci. 2019 Jul 2.
        Although the proportion of anemia amenable to change varies by population, the World Health Organization (WHO) criteria used to describe the public health severity of anemia are based on population prevalences. We describe the importance of measuring iron and other etiologic indicators to better understand what proportion of anemia could be responsive to interventions. We discuss the necessity of measuring inflammation to interpret iron biomarkers and documenting anemia of inflammation. Finally, we suggest assessing nonmodifiable genetic blood disorders associated with anemia. Using aggregated results from the Global Burden of Disease 2016, we compare population prevalence of anemia with years lived with disability (YLD) estimates, and the relative contributions of mild, moderate, and severe anemia to YLD. Anemia prevalences correlated with YLD and the relative proportion of moderate or severe anemia increased with anemia prevalence. However, individual-level survey data revealed irregular patterns between anemia prevalence, the prevalence of moderate or severe anemia, and the prevalence of iron deficiency anemia (IDA). We conclude that although the WHO population prevalence criteria used to describe the public health severity of anemia are important for policymaking, etiologic-specific metrics that take into account IDA and other causes will be necessary for effective anemia control policies.

    • Communicable Diseases
      1. Genetic characterization of measles and rubella viruses detected through global measles and rubella elimination surveillance, 2016-2018external icon
        Brown KE, Rota PA, Goodson JL, Williams D, Abernathy E, Takeda M, Mulders MN.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 5;68(26):587-591.
        All six World Health Organization (WHO) regions have established measles elimination goals, and three regions have a rubella elimination goal. Each region has established a regional verification commission to monitor progress toward measles elimination, rubella elimination, or both, and to provide verification of elimination* (1,2). To verify elimination, high-quality case-based surveillance is essential, including laboratory confirmation of suspected cases and genotyping of viruses from confirmed cases to track transmission pathways. In 2000, WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide high-quality laboratory support for surveillance for measles, rubella, and congenital rubella syndrome (3). GMRLN is the largest globally coordinated laboratory network, with 704 laboratories supporting surveillance in 191 countries (4). This report updates a previous report and describes the genetic characterization of measles and rubella viruses during 2016-2018 (5). The genetic diversity of measles viruses (MeVs) and rubella viruses (RuVs) has decreased globally following implementation of measles and rubella elimination strategies. Among 10,857 MeV sequences reported to the global Measles Nucleotide Surveillance (MeaNS) database during 2016-2018, the number of MeV genotypes detected in ongoing transmission decreased from six in 2016 to four in 2018. Among the 1,296 RuV sequences submitted to the global Rubella Nucleotide Surveillance (RubeNS) database during the same period, the number of RuV genotypes detected decreased from five in 2016 to two in 2018. To strengthen laboratory surveillance for measles and rubella elimination, specimens should be collected from all confirmed cases for genotyping, and sequences from all wild-type measles and rubella viruses should be submitted to MeaNS and RubeNS in a timely manner.

      2. Early changes in nutritional status may be predictive of subsequent HIV disease progression in people living with HIV (PLHIV). In addition to conventional anthropometric assessment using body mass index (BMI) and mid-upper arm circumferences (MUAC), measures of strength and fatigability may detect earlier changes in nutrition status which predict HIV disease progression. This study aims to examine the association between various nutritional metrics relevant in resource-scarce setting and HIV disease progression. The HIV disease progression outcome was defined as any occurrence of an incident AIDS-defining illnesses (ADI) among antiretroviral treatment (ART)-naive PLHIV. From 2008-2009, HIV+ Zambian adult men and non-pregnant women were followed for 9 months at a Doctors without Borders (Medecins Sans Frontiers, MSF) HIV clinic in Kapiri Mposhi, Zambia. Since the study was conducted in the time period when former WHO recommendations on ART (i.e., </=200 CD4 cell count as opposed to treating all individuals regardless of CD4 cell count or disease stage) were followed, caution should be applied when considering the implications from this study’s results to improve HIV case management under current clinical guidelines, or when comparing findings from this study with studies conducted in recent years. Bivariable and multivariable logistic regression was used to assess the associations between baseline nutritional measurements and the outcome of incident ADI. Self-reported loss of appetite study (AOR 1.90, 95% CI 1.04, 3.45, P = 0.036) and moderate wasting based on MUAC classification (AOR 2.40, 95% CI 1.13, 5.10, P = 0.022) were independently associated with increased odds of developing incident ADI within 9 months, while continuous increments (in psi) of median handgrip strength (AOR 0.74, 95%CI 0.60, 0.91, P = 0.004) was independently associated with decreased odds of incident ADI only among women. The association between low BMI and the short-term outcome of ADI was attenuated after controlling for these nutritional indicators. These findings warrant further research to validate the consistency of these observed associations among larger ART-naive HIV-infected populations, as well as to develop nutritional assessment tools for identifying disease progression risk among ART-naive PLHIV.

      3. Bacterial and fungal infections in persons who inject drugs – western New York, 2017external icon
        Hartnett KP, Jackson KA, Felsen C, McDonald R, Bardossy AC, Gokhale RH, Kracalik I, Lucas T, McGovern O, Van Beneden CA, Mendoza M, Bohm M, Brooks JT, Asher AK, Magill SS, Fiore A, Blog D, Dufort EM, See I, Dumyati G.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 5;68(26):583-586.
        During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).

      4. Increasing number and volume of cavitary lesions on chest computed tomography are associated with prolonged time to culture conversion in pulmonary tuberculosisexternal icon
        Hernandez-Romieu AC, Little BP, Bernheim A, Schechter MC, Ray SM, Bizune D, Kempker R.
        Open Forum Infect Dis. 2019 Jun;6(6):ofz232.
        Background: Cavitary lesions (CLs) primarily identified by chest x-ray (CXR) have been associated with worse clinical outcomes among patients with pulmonary tuberculosis (PTB). Chest computed tomography (CT), which has better resolution and increased sensitivity to detect lung abnormalities, has been understudied in PTB patients. We compared detection of CLs by CT and CXR and assessed their association with time to sputum culture conversion (tSCC). Methods: This was a retrospective cohort study of 141 PTB patients who underwent CT. We used multivariate Cox proportional hazards models to evaluate the association between CLs on CXR and the number and single largest volume of CLs on CT with tSCC. Results: Thirty (21%) and 75 (53%) patients had CLs on CXR and CT, respectively. CT detected cavities in an additional 44 patients (31%) compared with CXR. After multivariable adjustment, we observed a negative association between CLs and tSCC, with an adjusted hazard ratio (aHR) of 0.56 (95% confidence interval [CI], 0.32 to 0.97) for single CLs and 0.31 (95% CI, 0.16 to 0.60) for multiple CLs present on CT. Patients with a CL volume >/=25 mL had a prolonged tSCC (aHR, 0.39; 95% CI, 0.21 to 0.72). CLs on CXR were not associated with increased tSCC after multivariable adjustment. Conclusions: CT detected a larger number of cavities in patients with PTB relative to CXR. We observed an association between increasing number and volume of CLs on CT and delayed tSCC independent of sputum microscopy result. Our findings highlight a potential role for CT in the clinical and research setting as a tool to risk-stratify patients with PTB.

      5. Circulation and characterization of seasonal influenza viruses in Cambodia, 2012-2015external icon
        Horwood PF, Karlsson EA, Horm SV, Ly S, Heng S, Chin S, Darapheak C, Saunders D, Chanthap L, Rith S, Y P, Chea KL, Sar B, Parry A, Ieng V, Tsuyouka R, Deng YM, Hurt AC, Barr IG, Komadina N, Buchy P, Dussart P.
        Influenza Other Respir Viruses. 2019 Jun 28.
        BACKGROUND: Influenza virus circulation is monitored through the Cambodian influenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previously been characterized by year-round activity and a peak during the rainy season (June-November). OBJECTIVES: We documented the circulation of seasonal influenza in Cambodia for 2012-2015 and investigated genetic, antigenic, and antiviral resistance characteristics of influenza isolates. PATIENTS/METHODS: Respiratory samples were collected from patients presenting with influenza-like illness (ILI) at 11 hospitals throughout Cambodia. First-line screening was conducted by the National Institute of Public Health and the Armed Forces Research Institute of Medical Sciences. Confirmation of testing and genetic, antigenic and antiviral resistance characterization was conducted by Institute Pasteur in Cambodia, the NIC. Additional virus characterization was conducted by the WHO Collaborating Centre for Reference and Research on Influenza (Melbourne, Australia). RESULTS: Between 2012 and 2015, 1,238 influenza-positive samples were submitted to the NIC. Influenza A(H3N2) (55.3%) was the dominant subtype, followed by influenza B (30.9%; predominantly B/Yamagata-lineage) and A(H1N1)pdm09 (13.9%). Circulation of influenza viruses began earlier in 2014 and 2015 than previously described, coincident with the emergence of A(H3N2) clades 3C.2a and 3C.3a, respectively. There was high diversity in the antigenicity of A(H3N2) viruses, and to a smaller extent influenza B viruses, during this period, with some mismatches with the northern and southern hemisphere vaccine formulations. All isolates tested were susceptible to the influenza antiviral drugs oseltamivir and zanamivir. CONCLUSIONS: Seasonal and year-round co-circulation of multiple influenza types/subtypes were detected in Cambodia during 2012-2015.

      6. Assessing the incidence of symptomatic respiratory syncytial virus (RSV) illness within a prospective birth cohort in Managua, Nicaraguaexternal icon
        Kubale J, Kuan G, Gresh L, Ojeda S, Azziz-Baumgartner E, Sanchez N, Lopez R, Harris E, Balmaseda A, Gordon A.
        Clin Infect Dis. 2019 Jun 29.
        BACKGROUND: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among children worldwide, commonly through acute lower respiratory tract infections (ALRI). To assess the incidence of symptomatic RSV illness among young children, we conducted a prospective birth cohort study following children from 0-2 years of age in Managua, Nicaragua. METHODS: Children meeting the testing criteria (fever, history of fever, or severe respiratory symptoms [apnea, stridor, nasal flaring, wheezing, chest indrawing, and/or central cyanosis]), were tested for RSV infection using real-time reverse transcriptase-polymerase chain reaction. Acute lower respiratory infection was defined as diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyper-reactivity. Incidence was calculated, and 95% confidence intervals estimated using a Poisson distribution. RESULTS: A total of 833 children participated in the cohort, 289 (34.7%) had at least one episode of laboratory-confirmed RSV, and 156 (18.7%) of RSV-associated ALRI (RSV-ALRI). The incidence of symptomatic RSV was 248.1 cases per 1000 person-years (95% confidence interval [CI]: 223.2, 275.7). While infants aged 6-11 months had the highest incidence of symptomatic RSV (361.3/1000 person-years, 95% CI: 304.4, 428.8), infants <3 months had the highest incidence of severe RSV (RSV-associated hospitalizations and/or severe ALRI). RSV was also associated with 25.0-37.5% of deaths from medical causes (n=8). CONCLUSIONS: A substantial burden of RSV exists among children aged <2 years in Nicaraguan communities. RSV was also a leading cause of infant mortality among study participants. Development and implementation of effective RSV prevention and treatment measures represent an opportunity to substantially reduce severe illness and death among children worldwide.

      7. Risk-based prenatal hepatitis C testing practices and results, Alaska 2013-2016external icon
        Nolen LD, Gustin C, Seeman S, Murphy N, Truitt S, Schillie S, Bruce MG, Bruden D, Tiesinga J, McMahon B.
        Can J Gastroenterol Hepatol. 2019 ;2019.
        Hepatitis C virus (HCV) infection in pregnant women is of concern as it presents a health threat not only to the mother, but also to her infant. A retrospective analysis was performed to evaluate HCV testing and exposure in women who delivered infants between 2013 and 2016 at a referral hospital in Alaska. Multiple risk behaviors were evaluated, including drug dependency or abuse (drug abuse), tobacco use, alcohol dependency or abuse, and late presentation to prenatal care. Of the 2856 women who delivered between 2013 and 2016, 470 (16.5%) were tested for HCV during pregnancy and 1356 (47.5%) were tested at any time prior to delivery (including pregnancy); 62 (2.2%) were positive for HCV antibodies. Of the 162 women with a documented history of drug abuse, 95 (58.6%) were tested for HCV during pregnancy and 143 (88.3%) were tested at any time prior to delivery (including pregnancy); 30 (18.5%) were positive for HCV antibodies. Forty-nine women (34%) with a documented history of drug abuse who were not previously known to be HCV positive were not tested for HCV during their pregnancy. In conclusion, approximately 2% of pregnant women in the study population were known to have been exposed to HCV by the time of their delivery. One-third of women with documented drug abuse did not have an HCV test during pregnancy, revealing gaps in HCV testing of pregnant women. Further studies are needed to understand the full costs and benefits of risk-based screening versus universal screening in this and other populations.

      8. Differentiating new from newly detected: Melioidosis in Yap, Federated States of Micronesiaexternal icon
        Nolen LD, Lirow E, Gee JE, Elrod MG, Kolton CB, Liu L, Bower WA, Person MK, Marfel M, Blaney DD.
        Am J Trop Med Hyg. 2019 Jul 1.
        Melioidosis is a bacterial infection caused by exposure to water or soil that contains Burkholderia pseudomallei (Bp). Burkholderia pseudomallei is endemic to many tropical and subtropical areas of the world. In 2013, the first case of melioidosis was recognized in Yap, the Federated States of Micronesia. Six additional cases were identified in the subsequent 3 years. An investigation was initiated to understand the epidemiology of melioidosis in Yap. Serum from family and community members of the identified cases were tested for antibodies to Bp. Archived serum from a 2007 Zika serosurvey were also tested for antibodies to Bp. Sequencing of bacterial isolates was performed to understand bacterial phylogeny. Soil and water were tested for the presence of Bp in the environment by culture and PCR. None of the affected patients had a history of travel to melioidosis-endemic countries. Two of the 34 (5.8%) samples from the field investigation and 67 (11.7%) of the historical samples demonstrated serologic evidence of prior Bp exposure. No Bp were detected from 30 soil or water samples. Genotype analysis showed highly related Bp isolates that were unique to Yap. Melioidosis is likely to be endemic to Yap; however, it has only recently been recognized by the clinical community in country. Further investigation is needed to understand the local sites that harbor Bp and represent the highest risk to the community.

      9. Impact and effectiveness of state-level tuberculosis interventions in California, Florida, New York and Texas: A model-based analysisexternal icon
        Shrestha S, Cherng S, Hill AN, Reynolds S, Flood J, Barry PM, Readhead A, Oxtoby M, Lauzardo M, Privett T, Marks SM, Dowdy DW.
        Am J Epidemiol. 2019 Jun 28.
        The incidence of tuberculosis (TB) disease in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. But the impact of such interventions depends on local demography and heterogeneity in populations at risk. Using state-level individual-based TB transmission models, calibrated to California, Florida, New York, and Texas, we modeled two TB interventions: (i) Increased targeted testing and treatment (TTT) of high-risk populations, including people who are non-US-born, diabetic, HIV-positive, homeless, or incarcerated; and (ii) Enhanced TB contact investigation (ECI), including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016-2026) and numbers needed to screen and treat to avert one case. TTT delivered to half of the non-US-born adult population could lower TB incidence by 19.8%-26.7% over ten years. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive, homeless) and ECI were generally more efficient, but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations, and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the US, a combination of these approaches is necessary.

      10. Get in, get tested, get care: STD services in urban urgent care centersexternal icon
        Williams SP, Kinsey J, Carry MG, Terry L, Wells J, Kroeger K.
        Sex Transm Dis. 2019 Jul 1.
        BACKGROUND: Recent evidence indicates increased use of urgent care centers (UCCs) for STD testing. We sought to learn more about STD services in UCCs in a large metropolitan area. METHOD: Using a modified rapid gap assessment approach, we interviewed staff from 19 UCCs in metro Atlanta, GA USA. The UCCs were identified using two online search engines. We focused on a 50-mile radius around Atlanta. We then excluded duplicates and closed UCCs, and ones outside Atlanta’s five contiguous counties. Using a prioritization process, we visited UCCs in or adjacent to areas with mid-high local STD morbidity, or facilities from which STD cases were reported the year prior. We collected checklist-based data on STD testing, treatment and preventive services, as well as supportive services (e.g., substance use/mental health referrals). Checklist data, notes, and open-ended questions were summarized and analyzed descriptively. RESULTS: All UCCs (n=19) reported offering basic to comprehensive STD testing. Although most could treat on-site for chlamydia and gonorrhea, most relied on referrals, or prescriptions and “return to facility” practices to treat syphilis. Sources for STD information/management included the HD/CDC, online medical sites, and EMR embedded information. Challenges UCCs acknowledged included staying up-to-date with treatment guidance and lab reporting requirements, inadequate time for sexual risk reduction counseling, and linking patients with extended care needs (e.g., HIV+ case management, supportive services), or following up with patients. CONCLUSIONS: Urgent cares are STD testing resources. Service availability varies, but opportunities exists to enhance STD services in UCC settings and in communities.

    • Disease Reservoirs and Vectors
      1. Second WIN International Conference on “Integrated approaches and innovative tools for combating insecticide resistance in vectors of arboviruses”, October 2018, Singaporeexternal icon
        Corbel V, Durot C, Achee NL, Chandre F, Coulibaly MB, David JP, Devine GJ, Dusfour I, Fonseca DM, Griego J, Juntarajumnong W, Lenhart A, Kasai S, Martins AJ, Moyes C, Ng LC, Pinto J, Pompon JF, Muller P, Raghavendra K, Roiz D, Vatandoost H, Vontas J, Weetman D.
        Parasit Vectors. 2019 Jul 3;12(1):331.
        The past 40 years have seen a dramatic emergence of epidemic arboviral diseases transmitted primarily by mosquitoes. The frequency and magnitude of the epidemics, especially those transmitted by urban Aedes species, have progressively increased over time, accelerating in the past 10 years. To reduce the burden and threat of vector-borne diseases, the World Health Organization (WHO) has recently adopted the Global Vector Control Response (GVCR) in order to support countries in implementing effective sustainable vector control. The evidence-base to support vector control is however limited for arboviral diseases which make prioritization difficult. Knowledge gaps in the distribution, mechanisms and impact of insecticide resistance on vector control impedes the implementation of locally tailored Aedes control measures. This report summarizes the main outputs of the second international conference of the Worldwide Insecticide resistance Network (WIN) on “Integrated approaches and innovative tools for combating insecticide resistance in arbovirus vectors” held in Singapore, 1-3 October 2018. The aims of the conference were to review progress and achievements made in insecticide resistance surveillance worldwide, and to discuss the potential of integrated vector management and innovative technologies for efficiently controlling arboviral diseases. The conference brought together 150 participants from 26 countries.

      2. Rickettsia parkeri and Candidatus Rickettsia andeanae in tick of the Amblyomma maculatum group, Mexicoexternal icon
        Delgado-de la Mora J, Sanchez-Montes S, Licona-Enriquez JD, Delgado-de la Mora D, Paddock CD, Beati L, Colunga-Salas P, Guzman-Cornejo C, Zambrano ML, Karpathy SE, Lopez-Perez AM, Alvarez-Hernandez G.
        Emerg Infect Dis. 2019 Apr;25(4):836-838.
        We report Rickettsia parkeri and Candidatus Rickettsia andeanae in ticks of the Amblyomma maculatum group collected from dogs in Sonora, Mexico. Molecular characterization of these bacteria was accomplished by DNA amplification and sequence analysis of portions of the rickettsial genes gltA, htrA, ompA, and ompB.

      3. Resistance to insecticides can hamper the control of mosquitoes such as Culex quinquefasciatus, known to vector arboviruses such as West Nile virus and others. The strong selective pressure exerted on a mosquito population by the use of insecticides can result in heritable genetic changes associated with resistance. We sought to characterize genetic differences between insecticide resistant and susceptible Culex quinquefasciatus mosquitoes using targeted DNA sequencing. To that end, we developed a panel of 122 genes known or hypothesized to be involved in insecticide resistance, and used an Ion Torrent PGM sequencer to sequence 125 unrelated individuals from seven populations in the southern U.S. whose resistance phenotypes to permethrin and malathion were known from previous CDC bottle bioassay testing. Data analysis consisted of discovering SNPs (Single Nucleotide Polymorphism) and genes with evidence of copy number variants (CNVs) statistically associated with resistance. Ten of the seventeen genes found to be present in higher copy numbers were experimentally validated with real-time PCR. Of those, six, including the gene with the knock-down resistance (kdr) mutation, showed evidence of a >/= 1.5 fold increase compared to control DNA. The SNP analysis revealed 228 unique SNPs that had significant p-values for both a Fisher’s Exact Test and the Cochran-Armitage Test for Trend. We calculated the population frequency for each of the 64 nonsynonymous SNPs in this group. Several genes not previously well characterized represent potential candidates for diagnostic assays when further validation is conducted.

    • Environmental Health
      1. Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brominated flame retardants (FR) were introduced as replacements for polybrominated diphenyl ethers (PBDEs) after PBDEs phase-out in 2004 and 2013. Organophosphorous (OP) insecticides are mainly used in agricultural settings since the Food Quality Protection Act of 1996 phased-out most residential uses of OP insecticides in the United States. Urinary metabolites of FRs and OPs are known exposure biomarkers to FRs and OP insecticides, respectively. For large population-based studies, concurrent quantification of these metabolites using a small urine volume is desirable, but until now was not possible. We developed an analytical approach to quantify in 0.2mL urine 10 FRs and six OP insecticide metabolites: diphenyl phosphate, bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, bis(2-chloroethyl) phosphate, dicresyl phosphates, dibutyl phosphate, dibenzyl phosphate, 2,3,4,5-tetrabromobenzoic acid, 2-((isopropyl)phenyl)phenyl phosphate, 4-((tert-butyl)phenyl)phenyl phosphate, dimethyl phosphate, diethyl phosphate, dimethyl thiophosphate, dimethyl dithiophosphate, diethyl thiophosphate, and diethyl dithiophosphate. The method relies on enzymatic deconjugation, automated off-line solid phase extraction, high-performance liquid chromatography, and isotope dilution tandem mass spectrometry. Detection limits ranged from 0.05 to 0.5ngmL(-1), accuracy from 89 to 118%, and imprecision was <10%. . This method is the first to quantify simultaneously trace levels of 16 biomarkers of FRs and OP insecticides in only four drops of urine. We confirmed the method suitability for use in large epidemiological studies to assess background and occupational exposures to these classes of environmental pollutants by analyzing 303 samples collected from the general population and a group of firefighters. FR metabolite and DAPs concentrations in the general population group were lower than in the firefighters group, and within the ranges reported in the U.S. general population and other non-occupationally exposed populations.

      2. Biomonitoring of mercury and persistent organic pollutants in Michigan urban anglers and association with fish consumptionexternal icon
        Wattigney WA, Irvin-Barnwell E, Li Z, Ragin-Wilson A.
        Int J Hyg Environ Health. 2019 Jun 27.
        The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial discharges, sewer overflows and urban development. Key pollutants in fish samples from the Detroit River include mercury, polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dioxins and furans. A biomonitoring study was conducted to assess exposures to these persistent toxic substances in Detroit urban shoreline anglers who may be at high exposure risk due to consumption of locally caught fish. Using a modified venue-based sampling approach, 287 adult shoreline anglers along the Detroit River were recruited and participated in the program. Study participants provided blood and urine specimens and completed a questionnaire following informed consent. We examined percentile estimates for total blood mercury, PCBs, DDE, and dioxin-like total toxic equivalency (TEQ) concentrations among study participants. Multiple linear regression was used to identify important predictors of contaminant concentrations. Participants consumed a median of 64 Detroit River caught fish meals in the past year. The Detroit urban anglers’ median total blood mercury concentrations was 3.2 times higher than that for the general adult U.S. population. PCB concentrations among the Detroit anglers aged 18-39 years were higher than the U.S. population of the same race/ethnicity. Elevated levels of DDE and total TEQ concentrations were not observed in the cohort. Eating more locally caught fish was associated with higher total blood mercury and serum PCB concentrations. The biomonitoring data served to inform public health officials and help guide environmental public health actions to reduce harmful exposures.

    • Epidemiology and Surveillance
      1. Novel approaches for estimating female sex worker population size in conflict-affected south Sudanexternal icon
        Okiria AG, Bolo A, Achut V, Arkangelo GC, Michael AT, Katoro JS, Wesson J, Gutreuter S, Hundley L, Hakim A.
        JMIR Public Health Surveill. 2019 Mar 18;5(1):e11576.
        BACKGROUND: Limited data exist describing the population size of female sex workers (FSW) in South Sudan. A population size estimation exercise among FSW was undertaken in Juba and Nimule during the Eagle Survey. OBJECTIVE: The study aimed to estimate the number of FSW in Juba and Nimule to inform resource allocation and service provision for FSW. METHODS: We utilized service and unique object multipliers, and 3-source capture-recapture methods in conjunction with a respondent-driven sampling (RDS) survey to estimate the number of FSW in Juba and Nimule. For service multiplier, the number of FSW testing for HIV in 2015 (Juba) and 2016 (Nimule) was obtained from the LINKAGES program targeting FSW. Survey participants were asked whether they had been tested for HIV by LINKAGES during the relevant period. A total of 2 separate unique object distributions were conducted in Juba and Nimule. In Nimule, these were combined to produce a 3-source capture-recapture estimate. The exercise involved distribution of key chains and bangles to FSW, documentation of the number of those who received unique objects, and questions during RDS survey to assess whether participants received unique objects. RESULTS: In Juba, the service multiplier method yielded an estimate of 5800 (95% CI 4927-6673) FSW. The unique object estimate (key chain and RDS participation) yielded 5306 (95% CI 4673-5939). Another estimate using RDS participation and receipt of a bangle yielded a much lower estimate of 1863 (95% CI 1776-1951), as did a 2-source estimate of key chain and bangle (2120, 95% CI 2028-2211). A 3-source capture-recapture estimate could not be produced because aggregate rather than individual level data were collected during the third capture. The multiplier estimate using key chain and RDS participation was taken as the final population estimate for FSW in Juba, which constitutes more than 6% of the female population aged 15 to 64 years. In Nimule, the service multiplier method yielded an estimate of 9384 (95% CI 8511-10,257). The 2-source estimates for key chain and RDS yielded 6973 (95% CI 4759-9186); bangles and RDS yielded a higher estimate of 13,104 (95% CI 7101-19,106); key chains and bangles yielded a lower estimate of 1322 (95% CI 1223-1420). The 3-source capture-recapture method using Bayesian nonparametric latent-class model-based estimate yielded a population of 2694 (95% CI 1689-6945), and this was selected as the final estimate for Nimule, which constitutes nearly 40% of female population aged 15 to 64 years. CONCLUSIONS: The service and unique object multiplier, and 3-source capture-recapture methods were successfully used to estimate the number of FSW in Nimule, whereas service and unique object multiplier methods were successfully used in Juba. These methods yielded higher than previously estimated FSW population sizes. These estimates will inform resource allocation and advocacy efforts to support services for FSW.

    • Health Communication and Education
      1. Key factors influencing comfort in delivering and receiving sexual health education: Middle school student and teacher perspectivesexternal icon
        Rose ID, Boyce L, Crittenden Murray C, Lesesne CA, Szucs LE, Rasberry CN, Parker JT, Roberts G.
        Am J Sex Educ. 2019 .
        Sexual health education (SHE) provides students with knowledge and skills to establish healthy relationships, understand sexual development, and prevent risk behaviors; therefore, it is critical to understand how to optimize the delivery and receipt of this education. Using a grounded theory approach, interviews with middle school health education teachers (n = 13) and focus groups with students (n = 41) were conducted to examine factors that influence perceived comfort delivering and receiving SHE in a public-school district. Findings identified key barriers including disruptive behavior, insufficient time, and lack of dedicated classrooms. Some key facilitators to comfort included professional development and establishing ground rules.

    • Health Economics
      1. Cost implications of HIV retesting for verification in Africaexternal icon
        Lasry A, Kalou MB, Young PR, Rurangirwa J, Parekh B, Behel S.
        PLoS One. 2019 ;14(7):e0218936.
        INTRODUCTION: HIV misdiagnosis leads to severe individual and public health consequences. Retesting for verification of all HIV-positive cases prior to antiretroviral therapy initiation can reduce HIV misdiagnosis, yet this practice has not been not widely implemented. METHODS: We evaluated and compared the cost of retesting for verification of HIV seropositivity (retesting) to the cost of antiretroviral treatment (ART) for misdiagnosed cases in the absence of retesting (no retesting), from the perspective of the health care system. We estimated the number of misdiagnosed cases based on a review of misdiagnosis rates, and the number of positives persons needing ART initiation by 2020. We presented the total and per person costs of retesting as compared to no retesting, over a ten-year horizon, across 50 countries in Africa grouped by income level. We conducted univariate sensitivity analysis on all model input parameters, and threshold analysis to evaluate the parameter values where the total costs of retesting and the costs no retesting are equivalent. Cost data were adjusted to 2017 United States Dollars. RESULTS AND DISCUSSION: The estimated number of misdiagnoses, in the absence of retesting was 156,117, 52,720 and 29,884 for lower-income countries (LICs), lower-middle income countries (LMICs), and upper middle-income countries (UMICs), respectively, totaling 240,463 for Africa. Under the retesting scenario, costs per person initially diagnosed were: $40, $21, and $42, for LICs, LMICs, and UMICs, respectively. When retesting for verification is implemented, the savings in unnecessary ART were $125, $43, and $75 per person initially diagnosed, for LICs, LMICs, and UMICs, respectively. Over the ten-year horizon, the total costs under the retesting scenario, over all country income levels, was $475 million, and was $1.192 billion under the no retesting scenario, representing total estimated savings of $717 million in HIV treatment costs averted. CONCLUSIONS: Results show that to reduce HIV misdiagnosis, countries in Africa should implement the WHO’s recommendation of retesting for verification prior to ART initiation, as part of a comprehensive quality assurance program for HIV testing services.

      2. Cost of providing emergency obstetric care in Tanzania’s Kigoma regionexternal icon
        Mengistu T, Berruti A, Krivelyova A, Swor M, Waite R, Maro G.
        Int J Health Plann Manage. 2019 Jul 3.
        BACKGROUND: The provision of Emergency Obstetric and Neonatal Care (EmONC) is critical for reducing maternal mortality, yet little is known about the costs of EmONC services in developing countries. This study estimates these costs at six health facilities in Tanzania’s Kigoma region. METHODS: The study took a comprehensive programmatic approach considering all sources of financial and in-kind support over a 1-year period (1 July 2012 to 30 June 2013). Data were collected retrospectively and costs disaggregated by input, sources of support, programmatic activity, and patient type (nonsurgical, surgical patients, and among the latter patients undergoing caesarean sections). RESULTS: The median per-patient cost across the six facilities was $290. Personnel and equipment purchases accounted for the largest proportions of the total costs, representing 32% and 28%, respectively. Average per-patient costs varied by patient type; cost per nonsurgical patient was $80, $258 for surgical patients and $426 for patients undergoing caesarean sections. Per-patient costs also varied substantially by facility type: mean per-patient cost at health centres was $620 compared with $169 at hospitals. CONCLUSIONS: This study provides the first cost estimates of EmONC provision in Kigoma. These estimates could inform programme planning and highlight areas with potential scope for cost reductions.

      3. What will uncontrolled asthma cost in the United States?external icon
        Nurmagambetov TA, Krishnan JA.
        Am J Respir Crit Care Med. 2019 Jun 28.

        [No abstract]

      4. INTRODUCTION: Financial concerns are frequently cited by providers as a barrier to adult vaccination. This study assessed insurance reimbursements to providers for administering vaccines to adults in the private sector. METHODS: This study, conducted in 2018, used the 2016 MarketScan Commercial Claims and Encounters Database and included vaccination visits made by adults aged 19-64 years. Four routinely recommended vaccines targeted at adults were included: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); tetanus and diphtheria toxoids (Td); zoster; and influenza. The mean reimbursements for vaccine purchase and administration were reported and examined by state, metropolitan statistical area, provider type, and insurance plan type. Using the private vaccine purchase price published by the Centers for Disease Control and Prevention (CDC), the study reported the proportion of vaccination visits receiving reimbursements above the CDC-published price. RESULTS: The mean vaccine administration reimbursement was $25.80 for the first dose and $14.71 for additional doses in the same visit. The mean vaccine purchase reimbursement was $44.15 for Tdap, $25.78 for Td, and $216.05 for the zoster vaccine; the unweighted mean for the four examined influenza vaccines was $17.25. Reimbursements varied widely by state. Vaccine reimbursements exceeded the CDC-published price for most visits where Tdap (71.4%), zoster (87.8%), and three of four influenza (61.5%-88.5%) vaccines were administered but only for 25.8% of visits where Td was given. CONCLUSIONS: On average, reimbursements for administering vaccines to privately insured adults were adequate for most private practices. However, providers’ financial concerns may vary across geographic locations.

    • Immunity and Immunization
      1. INTRODUCTION: The strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies. METHODS: We conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful. RESULTS: In America, there were meaningful differences (7-45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4-27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006-2016. CONCLUSION: In countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However,these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.

      2. BACKGROUND: Recent studies of influenza vaccine effectiveness (VE) observed lower effectiveness with increasing time since vaccination, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing. METHODS: Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the U.S. population aged >/=65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012-13 as a prototypical influenza season, ~7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September. RESULTS: In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing. CONCLUSIONS: Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination.

      3. Non-replicating parenteral rotavirus (RV) vaccine candidates are in development in an attempt to overcome the lower efficacy and effectiveness of oral RV vaccines in low-income countries. One of the leading candidates is a truncated recombinant VP8* protein, expressed in Escherichia coli from original sequences of the prototype RV genotypes P[8], P[4], or P[6] isolated before 1983. Since VP8* is highly variable, it was considered useful to examine the evolutionary changes of RV strains reported worldwide over time in relation to the three P2-VP8 vaccine strains. Here, we retrieved from the GenBank 6,366 RV VP8* gene sequences of P[8], P[4], or P[6] strains isolated between 1974 and 2017, in 77 countries, and compared them with those of the three P2-VP8 vaccine strains: Wa (USA, 1974, G1P[8]), DS-1 (USA, 1976, G2P[4]), and 1076 (Sweden, 1983, G2P[6]). Phylogenetic analysis showed that 94.9% (4,328/4,560), 99.8% (1,141/1,143), and 100% (663/663) of the P[8], P[4], and P[6] strains, respectively, reported globally between 1974 and 2018 belong to non-vaccine lineages. These P[8], P[4], and P[6] RV strains have a mean of 9%, 5%, and 6% amino acid difference from the corresponding vaccine strains. Additionally, in the USA, the mean percentage difference between all the P[8] RV strains and the original Wa strain increased over time: 4% (during 1974-1980), 5% (1988-1991), and 9% (2005-2013). Our analysis substantiated high evolutionary changes in VP8* of the P[8], P[4], and P[6] major RV strains and their increasing variations from the candidate subunit vaccine strains over time. These findings may have implications for the development of new RV vaccines.

    • Laboratory Sciences
      1. Design and implementation of data exchange formats for molecular detection of drug-resistant tuberculosisexternal icon
        Bonney W, Price SF, Miramontes R.
        AMIA Jt Summits Transl Sci Proc. 2019 ;2019:686-695.
        Drug-resistant tuberculosis (TB) remains a public health threat to the United States and worldwide control of TB. Rapid and reliable drug susceptibility testing (DST) is essential for aiding clinicians in selecting an optimal treatment regimen for TB patients and to prevent ongoing transmission. Growth-based DST results for culture-confirmed cases are routinely reported to the U.S. Centers for Disease Control and Prevention through the National TB Surveillance System (NTSS). However, the NTSS currently lacks the capacity and functionality to accept laboratory results from advanced molecular methods that detect mutations associated with drug resistance. The objective of this study is to design and implement novel comprehensive data exchange formats that utilize the Health Level Seven (HL7) version 2.5.1 messaging hierarchy to capture, store, and monitor molecular DST data, thereby, improving the quality of data, specifications and exchange formats within the NTSS as well as ensuring full reporting of drug-resistant TB.

      2. The endoplasmic reticulum chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasitesexternal icon
        Kudyba HM, Cobb DW, Fierro MA, Florentin A, Ljolje D, Singh B, Lucchi NW, Muralidharan V.
        Cell Microbiol. 2019 May 14:e13042.
        The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the red blood cell is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathways. In this study, we tested the role of an uncharacterised ER protein, PfGRP170, in regulating these key functions by generating conditional mutants. Our data show that PfGRP170 localises to the ER and is essential for asexual growth, specifically required for proper development of schizonts. PfGRP170 is essential for surviving heat shock, suggesting a critical role in cellular stress response. The data demonstrate that PfGRP170 interacts with the Plasmodium orthologue of the ER chaperone, BiP. Finally, we found that loss of PfGRP170 function leads to the activation of the Plasmodium eIF2alpha kinase, PK4, suggesting a specific role for this protein in this parasite stress response pathway.

      3. Duration of seminal Zika viral RNA shedding in immunocompetent mice inoculated with Asian and African genotype virusesexternal icon
        McDonald EM, Duggal NK, Delorey MJ, Oksanish J, Ritter JM, Brault AC.
        Virology. 2019 Jun 20;535:1-10.
        Prior to the emergence of Asian genotype Zika virus (ZIKV) in the Western hemisphere, sexual transmission in humans was documented. Sexual transmission by African genotype ZIKVs has not been assessed in laboratory animal models, due to rapid and high mortality rates of immunodeficient mice following inoculation. To overcome these limitations, immunocompetent C57Bl/6 mice were used to longitudinally assess Asian and African genotype ZIKV sexual transmission potential. Furthermore, to determine if enhanced pathogenesis of African genotype ZIKVs is due to structural determinants, PRVABC59 prM/E was replaced with African MR766 prM/E (chimeric ZIKV). The African genotype and chimeric ZIKV elicited greater pathogenic effects in the male reproductive tract and generated higher viremias. Yet, the duration, magnitude and efficiency of seminal shedding of infectious virus and viral RNA were similar between chimeric-, African and Asian genotype ZIKV-inoculated mice. These data show that increased male reproductive tract pathology does not increase sexual transmission potential.

      4. Analytical evaluation of the microarray-based FluChip-8G influenza A+B assayexternal icon
        Taylor AW, Dawson ED, Blair RH, Johnson JE, Slinskey AH, Smolak AW, Toth E, Liikanen K, Stoughton RS, Smith C, Talbot S, Rowlen KL.
        J Virol Methods. 2019 Jul 1:113686.
        BACKGROUND: Influenza causes a significant annual disease burden, with characterization of the infecting virus important in clinical and public health settings. Rapid immunoassays are fast but insensitive, whereas real-time RT-PCR is sensitive but susceptible to genetic mutations and often requires multiple serial assays. The FluChip-8 G Influenza A + B Assay provides type and subtype/lineage identification of influenza A and B, including non-seasonal A viruses, in a single microarray-based assay with same day turnaround time. OBJECTIVE: To evaluate key analytical performance characteristics of the FluChip-8 G Influenza A + B Assay. STUDY DESIGN: Analytical sensitivity, cross-reactivity, and multi-site reproducibility were evaluated. RESULTS: The limit of detection (LOD) for the FluChip-8 G influenza A + B Assay ranged from 5.8 x 10(2) – 1.5 x 10(5) genome copies/mL, with most samples 2 x 10(3) genome copies/mL ( 160 genome copies/reaction). Fifty two (52) additional strains were correctly identified near the LOD, demonstrating robust reactivity. Two variant viruses (H1N1v and H3N2v) resulted in dual identification as both “non-seasonal influenza A” and A/H1N1 pdm 2009. No reproducible cross-reactivity was observed for the 34 organisms tested, however, challenges with internal control inhibition due to crude growth matrix were observed. Lastly, samples tested near the LOD showed high reproducibility (97.0% (95% CI 94.7 – 98.7)) regardless of operator, site, reagent lot, or testing day. CONCLUSION: The FluChip-8 G Influenza A + B Assay is an effective new method for detecting and identifying both seasonal and non-seasonal influenza viruses, as revealed by good sensitivity and robust reactivity to 52 unique strains of influenza virus. In addition, the lack of cross-reactivity to non-influenza pathogens and high lab-to-lab reproducibility highlight the analytical performance of the assay as an alternative to real-time RT-PCR and sequencing-based assays. Clinical validation of the technology in a multi-site clinical study is the subject of a separate investigation.

      5. Low literacy level instructions and reminder calls improve patient handling of fecal immunochemical test samplesexternal icon
        Wang A, Rachocki C, Shapiro JA, Issaka RB, Somsouk M.
        Clin Gastroenterol Hepatol. 2018 Nov 29.
        BACKGROUND & AIMS: The fecal immunochemical test (FIT) is an alternative to colonoscopy and can increase overall screening for colorectal cancer (CRC). However, little is known about the frequency of and reasons for mishandled FIT samples. METHODS: We performed a prospective study, nested within a randomized controlled trial of patients, recruited from December 2015 through August 2017, who were not up to date with colorectal cancer screening (50-75 years old). The patients were randomly assigned to usual care or outreach groups that received a mailed FIT with low literacy level instructions or a reminder call, or both. We examined frequency of and reasons for mishandled FIT samples, including absence of collection date; time from collection to laboratory receipt of more than 14 days; or mishandling of stool, buffer, or cap. The outcomes were the frequency of mishandled FIT samples, effects of outreach on mishandling, and positive results from the FIT among proper and mishandled samples. RESULTS: FIT samples were returned from 1871 patients assigned to usual care and 3045 who received the low literacy level instructions and a reminder call. In total, 19.8% of samples were mishandled; most of these (93.7%) had not labeled the date of stool collection but were still processed. Of the received samples, 1.2% of were not processed because the time from patient collection to laboratory receipt was more than 14 days. Outreach was associated with a lower proportion of mishandled samples (16.5% vs 25.0% for usual care; P < .0001). The proportion of mishandled samples was lowest among patients who received the low literacy level instruction and a reminder call (12.8%, P < .0001). There was no significant difference in proportions of positive results between properly processed samples (7.5%) and improperly processed samples (6.2%) (P = .14). CONCLUSION: In a prospective study of patients who were not up to date with colorectal cancer screening, we found that almost 20% of FIT samples were mishandled, with most patients missing the stool collection date. Patient outreach was associated with a lower proportion of mishandled samples, but there was no difference in proportions of positive results between properly and improperly handled samples. Our findings indicate that routine processing of undated FIT samples is associated with similar rates of positive results. There are limited data on test characteristics for FIT samples beyond the 14 days of stool acquisition. The inclusion of low literacy level instructions with reminder calls was associated with improved patient handling of the FIT sample. no: NCT02613260.

    • Occupational Safety and Health
      1. Cochrane corner: interventions to prevent hearing loss caused by noise at workexternal icon
        Brennan-Jones CG, Tao KF, Tikka C, Morata TC.
        Int J Audiol. 2019 Jul 2:1-4.
        This Cochrane Corner features “Interventions to prevent hearing loss caused by noise at work”, published in 2017. The aim of this Cochrane Review was to find out if hearing loss caused by noise at work is being prevented by current interventions. Tikka et al. identified 29 studies that studied the effect of preventive measures. One study evaluated legislation to reduce noise exposure, eleven studies evaluated effects of personal hearing protection devices and 17 studies evaluated effects of hearing loss prevention programmes (HLPPs). There was some very low-quality evidence that implementation of stricter legislation can reduce noise levels in workplaces and moderate-quality evidence that training of proper insertion of earplugs significantly reduces noise exposure at short-term follow-up. This Cochrane review has identified specific strategies that have shown effectiveness in reducing workplace noise, such as the implementation of stricter legislation and the need for training in the proper use of earplugs and earmuffs to reduce noise exposure to safe levels. The overall quality of evidence for the effectiveness of HLPPs in preventing hearing loss was very low, there was limited follow-up of participants receiving training for insertion of earplugs and no controlled studies examining engineering controls to reduce workplace noise.

      2. Health-related workplace absenteeism among full-time workers – United States, 2017-18 influenza seasonexternal icon
        Groenewold MR, Burrer SL, Ahmed F, Uzicanin A, Luckhaupt SE.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 5;68(26):577-582.
        During an influenza pandemic and during seasonal epidemics, more persons have symptomatic illness without seeking medical care than seek treatment at doctor’s offices, clinics, and hospitals (1). Consequently, surveillance based on mortality, health care encounters, and laboratory data does not reflect the full extent of influenza morbidity. CDC uses a mathematical model to estimate the total number of influenza illnesses in the United States (1). In addition, syndromic methods for monitoring illness outside health care settings, such as tracking absenteeism trends in schools and workplaces, are important adjuncts to conventional disease reporting (2). Every month, CDC’s National Institute for Occupational Safety and Health (NIOSH) monitors the prevalence of health-related workplace absenteeism among full-time workers in the United States using data from the Current Population Survey (CPS) (3). This report describes the results of workplace absenteeism surveillance analyses conducted during the high-severity 2017-18 influenza season (October 2017-September 2018) (4). Absenteeism increased sharply in November, peaked in January and, at its peak, was significantly higher than the average during the previous five seasons. Persons especially affected included male workers, workers aged 45-64 years, workers living in U.S. Department of Health and Human Services (HHS) Region 6* and Region 9,(dagger) and those working in management, business, and financial; installation, maintenance, and repair; and production and related occupations. Public health authorities and employers might consider results from relevant absenteeism surveillance analyses when developing prevention messages and in pandemic preparedness planning. The most effective ways to prevent influenza transmission in the workplace include vaccination and nonpharmaceutical interventions, such as staying home when sick, covering coughs and sneezes, washing hands frequently, and routinely cleaning frequently touched surfaces (5).

      3. The CHARGE study: an assessment of parental occupational exposures and autism spectrum disorderexternal icon
        McCanlies EC, Ma CC, Gu JK, Fekedulegn D, Sanderson WT, Ludena-Rodriguez YJ, Hertz-Picciotto I.
        Occup Environ Med. 2019 Jun 27.
        OBJECTIVES: The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD). METHODS: Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth. RESULTS: The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01-2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined. CONCLUSION: Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

    • Parasitic Diseases
      1. Quantifying seasonal variation in insecticide-treated net use among those with accessexternal icon
        Koenker H, Taylor C, Burgert C, Thwing J, Fish T, Kilian A.
        Am J Trop Med Hyg. 2019 Jul 1.
        Seasonal variation in the proportion of the population using an insecticide-treated net (ITN) is well documented and is widely believed to be dependent on mosquito abundance and heat, driven by rainfall and temperature. However, seasonal variation in ITN use has not been quantified controlling for ITN access. Demographic and Health Survey and Malaria Indicator Survey datasets, their georeferenced data, and public rainfall and climate layers were pooled for 21 countries. Nine rainfall typologies were developed from rainfall patterns in Koppen climate zones. For each typology, the odds of ITN use among individuals with access to an ITN within their households (“ITN use given access”) were estimated for each month of the year, controlling for region, wealth quintile, residence, year, temperature, and malaria parasitemia level. Seasonality of ITN use given access was observed over all nine rainfall typologies and was most pronounced in arid climates and less pronounced where rainfall was relatively constant throughout the year. Peak ITN use occurred 1-3 months after peak rainfall and corresponded with peak malaria incidence and average malaria transmission season. The observed lags between peak rainfall and peak ITN use given access suggest that net use is triggered by mosquito density. In equatorial areas, ITN use is likely to be high year-round, given the presence of mosquitoes and an associated year-round perceived malaria risk. These results can be used to inform behavior change interventions to improve ITN use in specific times of the year and to inform geospatial models of the impact of ITNs on transmission.

      2. Assessing performance of HRP2 antigen detection for malaria diagnosis in Mozambiqueexternal icon
        Plucinski MM, Candrinho B, Dimene M, Colborn J, Lu A, Nace D, Zulliger R, Rogier E.
        J Clin Microbiol. 2019 Jul 3.
        Background: Rapid diagnostic tests (RDTs) that detect the Plasmodium falciparum-specific histidine-rich protein 2 (PfHRP2) antigen are the primary method for malaria diagnosis in Mozambique. However, these tests do not detect infections with non-falciparum malaria or Pfhrp2/3-deleted P. falciparum parasites.Methods: To assess the appropriateness of conventional PfHRP2-only RDTs for malaria diagnosis in Mozambique, samples collected during a health facility survey conducted in three provinces of Mozambique were screened using antigen detection methods and further characterized by molecular techniques. Samples from 1861 outpatients of all ages and symptoms attending 117 randomly-selected public health facilities in 2018 were analyzed with an ultra-sensitive bead-based immunoassay for the presence of PfHRP2, pan-Plasmodium Aldolase (pAldo), and pan-Plasmodium lactate dehydrogenase (pLDH). Presence of PfHRP2 in patient blood detected using the bead-based assay was compared to the results of PfHRP2-based RDTs performed during the routine health facility consult and during the survey re-examination at exit interview. Samples with discordant antigen profiles (negative for PfHRP2 but positive for pAldo and/or pLDH) were further characterized by photo-induced electron transfer (PET)-PCR.Results: Using the bead-based laboratory assay as the gold standard, the sensitivity of the conventional RDTs administered during the routine health facility consult and the exit interview was 90% and 83%, respectively, and specificity was 91% and 97%. Of 710 samples positive for at least one antigen, 704 (99.2%) were positive for PfHRP2. Six (0.8% of total) discordant samples lacked PfHRP2 but were positive for pAldo and/or pLDH; 3 of these (0.4% of total) were P. ovale mono-infections or co-infections where P. ovale was the dominant species. The remaining 3 discordant samples were negative by PET-PCR.Conclusions: The sensitivity and specificity of the conventional RDTs performed in the routine health facility consults and survey exit interviews were acceptable, and there was no evidence of Pfhrp2/3-deleted parasites. Mono-infections with non-falciparum malaria species comprised <1% of total malaria infections. Nearly all malaria antigen-positive patients had detectable PfHRP2, confirming this antigen remains an appropriate malaria diagnostic target in the surveyed provinces.

    • Physical Activity
      1. Opportunities for employers to support physical activity through policyexternal icon
        Ablah E, Lemon SC, Pronk NP, Wojcik JR, Mukhtar Q, Grossmeier J, Pollack KM, Whitsel LP.
        Prev Chronic Dis. 2019 Jun 27;16:E84.

        [No abstract]

    • Public Health Leadership and Management
      1. Sustaining the HIV care provider workforce: Medical Monitoring Project HIV Provider Survey, 2013-2014external icon
        Weiser J, Chen G, Beer L, Boccher-Lattimore D, Armstrong W, Kurth A, Shouse RL.
        Health Serv Res. 2019 Jul 1.
        OBJECTIVE: To describe delivery of recommended HIV care and work satisfaction among infectious disease (ID) physicians, non-ID physicians, nurse practitioners (NPs), and physician assistants (PAs). DATA SOURCES: Medical Monitoring Project 2013-2014 HIV Provider Survey. STUDY DESIGN: Population-based complex sample survey. DATA COLLECTION/ANALYSIS METHODS: We surveyed 2208 HIV care providers at 505 US HIV care facilities and computed weighted percentages of provider characteristics, stratified by provider type. Rao-Scott chi-square tests and logistic regression used to compare characteristics of ID physicians with each other provider type. PRINCIPAL FINDINGS: The adjusted provider response rate was 64 percent. Among US HIV care providers, 45 percent were ID physicians, 35 percent non-ID physicians, 15 percent NPs, and 5 percent PAs. Satisfaction with administrative burden was lowest among non-ID physicians (27 percent). Compared with ID physicians, satisfaction with remuneration was lower among non-ID physicians and higher among NPs (37, 28, and 51 percent, respectively). NPs were more likely than ID physicians to report performing four of six services that are key to providing comprehensive HIV care, but more NPs planned to leave clinical practice within 5 years (19 vs 7 percent). CONCLUSION: Addressing physician dissatisfaction with remuneration and administrative burden could help prevent a provider shortage. Strengthening the role of NPs may help sustain a high-quality workforce.

    • Reproductive Health
      1. Self-reported infertility and associated pelvic inflammatory disease among women of reproductive age – National Health and Nutrition Examination Survey, United States, 2013-2016external icon
        Anyalechi GE, Hong J, Kreisel K, Torrone E, Boulet S, Gorwitz R, Kirkcaldy RD, Bernstein K.
        Sex Transm Dis. 2019 Jul;46(7):446-451.
        BACKGROUND: Sexually transmitted diseases, including chlamydia and gonorrhea, cause of pelvic inflammatory disease (PID) and infertility. We estimated the prevalence of infertility and infertility health care seeking. METHODS: We analyzed self-reported lifetime infertility and infertility health care-seeking in women aged 18 to 49 years in the 2013 and 2015 National Health and Nutrition Examination Surveys. Weighted prevalence of infertility and infertility health care seeking, prevalence ratios (PRs), and 95% confidence intervals (CIs) were calculated. RESULTS: Among 2626 eligible women, 13.8% had self-reported infertility (95% CI, 12.3-15.3) with higher prevalence by age: 960, 18 to 29 years (PR, 6.4%; 95% CI, 4.8-8.0); 799, 30 to 39 years (PR, 14.8%; 95% CI, 12.2-17.3); and 867, 40 to 49 years (PR, 20.8%; 95% CI, 17.2-24.4). Non-Hispanic white women (PR, 15.4%; 95% CI, 13.0-17.8; n = 904) and non-Hispanic black women (PR, 12.9%; 95% CI, 10.3-15.5; n = 575) had the highest infertility prevalences. Women reporting PID treatment (n = 122) had higher infertility prevalence (PR, 24.2%; 95% CI, 16.2-32.2) than women without PID treatment (PR, 13.3%; 95% CI, 11.6-15.0; n = 2,485), especially among 18- to 29-year-old women (PR, 3.8; 95% CI, 1.8-8.0). Of 327 women with infertility, 60.9% (95% CI, 56.1-65.8) sought health care. Women without health care insurance sought care less frequently than women with insurance. CONCLUSIONS: In a nationally representative sample, 13.8% of reproductive-age women reported a history of infertility, of whom 40% did not access health care. Self-reported PID was associated with infertility, especially in young women. Annual chlamydia and gonorrhea screening to avert PID may reduce the burden of infertility in the United States.

      2. Obstetric comorbidity and severe maternal morbidity among Massachusetts delivery hospitalizations, 1998-2013external icon
        Somerville NJ, Nielsen TC, Harvey E, Easter SR, Bateman B, Diop H, Manning SE.
        Matern Child Health J. 2019 Jul 2.
        OBJECTIVES: The rate of severe maternal morbidity in the United States increased approximately 200% during 1993-2014. Few studies have reported on the health of the entire pregnant population, including women at low risk for maternal morbidity. This information might be useful for interventions aimed at primary prevention of pregnancy complications. To better understand this, we sought to describe the distribution of comorbid risk among all delivery hospitalizations in Massachusetts and its association with the distribution of severe maternal morbidity. METHODS: Using an existing algorithm, we assigned an obstetric comorbidity index (OCI) score to delivery hospitalizations contained in the Massachusetts pregnancy to early life longitudinal (PELL) data system during 1998-2013. We identified which hospitalizations included severe maternal morbidity and calculated the rate and frequency of these hospitalizations by OCI score. RESULTS: During 1998-2013, PELL contained 1,185,182 delivery hospitalizations; of these 5325 included severe maternal morbidity. Fifty-eight percent of delivery hospitalizations had an OCI score of zero. The mean OCI score increased from 0.60 in 1998 to 0.82 in 2013. Hospitalizations with an OCI score of zero comprised approximately one-third of all deliveries complicated by severe maternal morbidity, but had the lowest rate of severe maternal morbidity (22.8/10,000 delivery hospitalizations). CONCLUSIONS: The mean OCI score increased during the study period, suggesting that an overall increase in risk factors has occurred in the pregnant population in Massachusetts. Interventions that can make small decreases to the mean OCI score could have a substantial impact on the number of deliveries complicated by severe maternal morbidity. Additionally, all delivery facilities should be prepared for severe complications during low-risk deliveries.

      3. Adolescent pregnancy prevention: Application of CDC evidence-based contraception guidanceexternal icon
        Zapata LB, Jatlaoui TC, Curtis KM.
        Adolesc Med State Art Rev. 2019 ;30(1):10-23.
        Adolescents at risk for unintended pregnancy should have access to highly effective contraception. Health care professionals can use evidence-based contraception guidance from the Centers for Disease Control and Prevention (CDC) to remove unnecessary barriers and increase adolescents’ access to safe and effective contraception. Adolescents are medically eligible to use all methods of contraception based on age alone. Most females, including adolescents, can initiate contraception at any time (including the day of the initial visit). Health care professionals can use the CDC recommendations to determine the safety of contraceptive methods for adolescents with medical conditions and to provide evidence-based care for starting and continuing contraceptive use.

    • Substance Use and Abuse
      1. Lc-ms/ms analysis of sugars, alditols, and humectants in smokeless tobacco productsexternal icon
        Wang L, Stanfill S, Valentin-Blasini L, Watson CH, Cardenas RB.
        Beitrage zur Tabakforschung International/ Contributions to Tobacco Research. 2019 ;28(5):203-213.
        Globally, smokeless tobacco (ST) includes a wide array of chemically diverse products generally used in the oral cavity. Although ST has been widely investigated, this study was undertaken to determine the levels of sugars (mono- and di-saccharides), alditols, and humectants present in major ST categories/subcategories by using high performance liquid chromatography coupled with a triple quadrupole mass spectrometer (HPLC-MS/MS). The products studied included chewing tobacco (loose leaf, plug, twist), US moist snuff, Swedish snus, creamy snuff, dry snuff, dissolvable tobacco products, and tobacco-coated toothpicks. The highest mean sugar level was detected in chewing tobacco (9.3-27.5%, w/w), followed by dissolvable tobacco (2.1%); all other products were lower than 1%. Creamy snuff had the highest mean alditol levels (22.6%), followed by dissolvable tobacco (15.4%); all others had levels lower than 1%. The detected mean humectant levels ranged from non-detectable to 5.9%. This study demonstrates the broad chemical diversity among ST. This research may aid researchers and public health advocates investigating the exposures and risks of ST. [Beitr. Tabakforsch. Int. 28 (2019) 203-213]

    • Zoonotic and Vectorborne Diseases
      1. Use of photography to identify free-roaming dogs during sight-resight surveys: Impacts on estimates of population size and vaccination coverage, Haiti 2016external icon
        Cleaton JM, Blanton JD, Dilius P, Ludder F, Crowdis K, Medley A, Chipman R, Estime F, Maciel E, Wallace RM.
        Vaccine: X. 2019 ;2.
        Background: Enumerating dog populations is essential to plan and evaluate rabies vaccination campaigns. To estimate vaccination coverage and dog population size in a Haitian commune, 15 sight-resight counts were conducted over two days following a government-sponsored vaccination campaign. Methods: Dogs received temporary laminated collars and livestock wax marks on the head and sides at the time of rabies vaccination. After the vaccination campaign, pairs of surveyors walked pre-defined routes through targeted neighborhoods, photographing and recording characteristics and location of each dog seen on a standardized data sheet. On the second survey day, surveyors retraced the prior day’s track, followed the same procedure, and indicated in addition whether they believed the dogs were resighted from the prior day. After completion of the field survey, two independent evaluators reviewed photographs and characteristics of each dog to assess which had vaccination marks and which were resighted. Surveyor and photo-reviewer sight-resight decisions were compared using Cohen’s kappa, and population estimates were compared using Lincoln-Petersen 95% confidence intervals. Results: Field-surveyors identified dogs consistent with the photograph evaluations in 629 out of 800 instances (78.6%, Cohen’s kappa of 0.12). Despite this inconsistency, the population estimates resulting from the field and final determinations were not significantly different at 1,789 (95% CI 1,677 to 1,901) and 1,978 (95% CI 1,839 to 2,118). Vaccination coverage was also the same at 55% and 56%; however, an observed vaccination mark loss of 13.8% suggests that the true coverage may have been closer to 64%. Conclusion: Using photos improved dog identification during the sight-resight study, leading to a higher population estimate. Despite using a 2-mark system to temporarily identify vaccinated dogs, a significant proportion had lost all identifying marks by the second day of field surveys. Efforts to estimate vaccination coverage using sight-resight surveys should consider improvement of marking techniques or better accounting for potential loss of marks in their free-roaming dog vaccination coverage assessments.

      2. Updated baseline prevalence of birth defects potentially related to Zika virus infectionexternal icon
        Olson SM, Delaney A, Jones AM, Carr CP, Liberman RF, Forestieri NE, Tong VT, Gilboa SM, Honein MA, Moore CA, Cragan JD.
        Birth Defects Res. 2019 Jul 2.

        [No abstract]

      3. Antibody titers reactive with Rickettsia rickettsii in blood donors and implications for surveillance of spotted fever rickettsiosis in the United Statesexternal icon
        Straily A, Stuck S, Singleton J, Brennan S, Marcum S, Condit M, Lee C, Kato C, Tonnetti L, Stramer SL, Paddock CD.
        J Infect Dis. 2019 Jul 2.
        BACKGROUND: Since 2000, the reported prevalence of tick-borne spotted fever group rickettsioses (SFGR) has increased considerably. We compared the level of antibody reactivity among healthy blood donors from two widely separated regions of the United States, and evaluated the impact of antibody prevalence on public health surveillance in one of these regions. METHODS: Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G antibodies reactive with Rickettsiarickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment. RESULTS: Of the Georgia donors (N = 1,493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers >/= 64, whereas 6.3% of donors from Oregon and Washington (N =1,511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (N = 93) of all donors had titers >/= 128. During 2016, GDPH interviewed 243 seropositive case-patients; only 28% (N = 69) met criteria defined in the national SFGR case definition. CONCLUSIONS: These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of SFGR.

      4. Veterinarians play a crucial role in zoonotic disease detection in animals and prevention of disease transmission; reporting these zoonoses to public health officials is an important first step to protect human and animal health. Evidence suggests veterinarians and their staff are at higher risk for exposure to zoonoses because of possible interactions with infected animals. We examined the knowledge, attitudes, and practices of veterinarians regarding zoonotic disease reporting to public health agencies and associated infection prevention (IP) practices such as personal protective equipment (PPE) use, and the need for targeted education and outreach for veterinarians in Arizona. An online questionnaire was developed and distributed by email in September 2015 and was available through November 2015 to all 1,100 members of the Arizona Veterinary Medical Association. Chi-square and logistic regression analyses were performed. In total, 298 (27%) veterinarians from all 15 Arizona counties completed the survey; the majority (70%) were female, practiced small animal medicine (84%), and reported practicing veterinary medicine for >=10 years (75%). Only 57% reported they knew when to report a suspected zoonotic disease and 60% reported they knew how to make that type of report. The majority said they would report rabies (97%), plague (96%), and highly pathogenic avian influenza (91%) to a state agency. Most respondents reported using PPE (e.g., masks, face shields, and gloves) when performing a surgical procedure (96%) or necropsy (94%), although fewer reported using PPE for handling clinically ill animals (37%) or healthy animals (17%). Approximately 70% reported always using PPE when in contact with animal birthing fluids, urine, or feces, and 47% for contact with animal blood, saliva, or other body fluids. Veterinarians who agreed that they knew the appropriate actions to protect themselves from zoonotic disease exposures were more likely to report always washing their hands before eating or drinking at work (OR = 3.81, 95% confidence interval (CI) [1.97-7.35], P < 0.01). Responses for when to make a report and how to report were not significantly different by gender, years of practice, or holding additional degrees, but did differ by practice type, age, and number of veterinarians in the practice. Small animal veterinarians were less likely to report knowing when to make a report compared to other veterinarians (P < 0.01). Respondents demonstrated suboptimal zoonotic disease reporting and IP practices, including PPE use. Public health agencies should improve outreach and education to veterinarians to facilitate better zoonotic disease prevention practices and reporting.

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

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