Volume 12, Issue 29, August 25, 2020

CDC Science Clips: Volume 12, Issue 29, August 25, 2020

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

This week’s Science Clips is pleased to feature articles under the topic of vaccine-preventable disease (VPD) in conjunction with National Immunization Awareness Month (NIAM). NIAM is an annual observance held in August to highlight the importance of vaccination for people of all ages. Because local prevention needs vary with the communities, CDC has provided diverse campaigns to choose from with different prevention focuses and audiences. Articles are unique because they include at least one CDC author and make use of artificial intelligence/machine learning (Ai/ML) as follows:

  • Classification
    • Authors used Support Vector Machineexternal icon models to introduce a novel approach to rapidly determine cladistic information for any number of genes without the need for time-consuming sequence alignment, phylogenetic tree construction, or manual annotation.
    • Authors used Online Adaptive Lasso Auto Regressiveexternal icon methods to dynamically combine two distinct influenza tracking techniques to achieve improved state-level influenza activity estimates in the United States.
    • Authors used Fast Artificial Neural Networksexternal icon to verify and validate the performance of the FluChip-8G Insight assay for the detection and positive identification of human and animal origin non-seasonal influenza A specimens.
    • Authors used Random Forestexternal icon models to describe mothers' knowledge and attitudes about influenza illnesses and vaccination, and identify characteristics associated with mothers' intent to vaccinate their child.
    • Authors discuss how machine learningexternal icon has been used in vaccine informatics.
  • Natural Language Processing
    • Authors used Finite State Machineexternal icon to describe negation in surveillance reports of adverse events following immunizations.
    • Authors used rule-basedexternal icon algorithms to create a spelling error correction tool for surveillance reports of adverse events following immunizations.
    • Authors used pyConText/NegExexternal icon software to identify local reaction associated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in the Vaccine Safety Datalink.
    • Authors used Stanford NLPexternal icon algorithms to identify vaccine-related anaphylaxis from plain-text clinical notes.
  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Informatics - Artificial Intelligence/Machine Learning
      1. Emerging vaccine informaticsexternal icon
        He Y, Rappuoli R, De Groot AS, Chen RT.
        J Biomed Biotechnol. 2010 ;2010:218590.
        Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning.

      2. Improved state-level influenza nowcasting in the United States leveraging Internet-based data and network approachesexternal icon
        Lu FS, Hattab MW, Clemente CL, Biggerstaff M, Santillana M.
        Nat Commun. 2019 Jan 11;10(1):147.
        In the presence of health threats, precision public health approaches aim to provide targeted, timely, and population-specific interventions. Accurate surveillance methodologies that can estimate infectious disease activity ahead of official healthcare-based reports, at relevant spatial resolutions, are important for achieving this goal. Here we introduce a methodological framework which dynamically combines two distinct influenza tracking techniques, using an ensemble machine learning approach, to achieve improved state-level influenza activity estimates in the United States. The two predictive techniques behind the ensemble utilize (1) a self-correcting statistical method combining influenza-related Google search frequencies, information from electronic health records, and historical flu trends within each state, and (2) a network-based approach leveraging spatio-temporal synchronicities observed in historical influenza activity across states. The ensemble considerably outperforms each component method in addition to previously proposed state-specific methods for influenza tracking, with higher correlations and lower prediction errors.

      3. LABEL: fast and accurate lineage assignment with assessment of H5N1 and H9N2 influenza A hemagglutininsexternal icon
        Shepard SS, Davis CT, Bahl J, Rivailler P, York IA, Donis RO.
        PLoS One. 2014 ;9(1):e86921.
        The evolutionary classification of influenza genes into lineages is a first step in understanding their molecular epidemiology and can inform the subsequent implementation of control measures. We introduce a novel approach called Lineage Assignment By Extended Learning (LABEL) to rapidly determine cladistic information for any number of genes without the need for time-consuming sequence alignment, phylogenetic tree construction, or manual annotation. Instead, LABEL relies on hidden Markov model profiles and support vector machine training to hierarchically classify gene sequences by their similarity to pre-defined lineages. We assessed LABEL by analyzing the annotated hemagglutinin genes of highly pathogenic (H5N1) and low pathogenicity (H9N2) avian influenza A viruses. Using the WHO/FAO/OIE H5N1 evolution working group nomenclature, the LABEL pipeline quickly and accurately identified the H5 lineages of uncharacterized sequences. Moreover, we developed an updated clade nomenclature for the H9 hemagglutinin gene and show a similarly fast and reliable phylogenetic assessment with LABEL. While this study was focused on hemagglutinin sequences, LABEL could be applied to the analysis of any gene and shows great potential to guide molecular epidemiology activities, accelerate database annotation, and provide a data sorting tool for other large-scale bioinformatic studies.

      4. Concept negation in free text components of vaccine safety reportsexternal icon
        Tolentino H, Matters M, Walop W, Law B, Tong W, Liu F, Fontelo P, Kohl K, Payne D.
        AMIA Annu Symp Proc. 2006 ;2006:1122.
        Large amounts of information are locked up in free text components of clinical reports. Surveillance systems that monitor adverse events following immunizations (AEFI) can utilize these components after concept extraction using natural language processing (NLP). Specifically, our method for the identification and filtering of negated concepts using the Unified Medical Language System (UMLS) potentially improves the quality of AEFI surveillance systems.

      5. A UMLS-based spell checker for natural language processing in vaccine safetyexternal icon
        Tolentino HD, Matters MD, Walop W, Law B, Tong W, Liu F, Fontelo P, Kohl K, Payne DC.
        BMC Med Inform Decis Mak. 2007 Feb 12;7:3.
        BACKGROUND: The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. METHODS: We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. RESULTS: We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74-75), 100% (95% CI: 100-100), and 47% (95% CI: 46%-48%), respectively. CONCLUSION: We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the specificity was much superior. The slow processing speed may be improved by trimming it down to the most useful component algorithms. Other investigators may find the methods we developed useful for cleaning text using lexicons specific to their area of interest.

      6. FluChip-8G Insight: HA and NA subtyping of potentially pandemic influenza A viruses in a single assayexternal icon
        Toth E, Dawson ED, Taylor AW, Stoughton RS, Blair RH, Johnson JE, Slinskey A, Fessler R, Smith CB, Talbot S, Rowlen K.
        Influenza Other Respir Viruses. 2020 Jan;14(1):55-60.
        BACKGROUND: Global influenza surveillance in humans and animals is a critical component of pandemic preparedness. The FluChip-8G Insight assay was developed to subtype both seasonal and potentially pandemic influenza viruses in a single assay with a same day result. FluChip-8G Insight uses whole gene segment RT-PCR-based amplification to provide robustness against genetic drift and subsequent microarray detection with artificial neural network-based data interpretation. OBJECTIVES: The objective of this study was to verify and validate the performance of the FluChip-8G Insight assay for the detection and positive identification of human and animal origin non-seasonal influenza A specimens. METHODS: We evaluated the ability of the FluChip-8G Insight technology to type and HA and NA subtype a sample set consisting of 297 results from 180 unique non-seasonal influenza A strains (49 unique subtypes). RESULTS: FluChip-8G Insight demonstrated a positive percent agreement ≥93% for 5 targeted HA and 5 targeted NA subtypes except for H9 (88%), and negative percent agreement exceeding 95% for all targeted subtypes. CONCLUSIONS: The FluChip-8G Insight neural network-based algorithm used for virus identification performed well over a data set of 297 naïve sample results, and can be easily updated to improve performance on emerging strains without changing the underlying assay chemistry.

      7. Intent to obtain pediatric influenza vaccine among mothers in four middle income countriesexternal icon
        Wagner AL, Gordon A, Tallo VL, Simaku A, Porter RM, Edwards LJ, Duka E, Abu-Khader I, Gresh L, Sciuto C, Azziz-Baumgartner E, Bino S, Sanchez F, Kuan G, de Jesus JN, Simões EA, Hunt DR, Arbaji AK, Thompson MG.
        Vaccine. 2020 Jun 2;38(27):4325-4335.
        BACKGROUND: Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers' knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers' intent to vaccinate their child. METHODS: From 2015 to 2017, infants 0-11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6-11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis. RESULTS: In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample. CONCLUSION: Intent to vaccinate infants aged 6-11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants.

      8. The use of natural language processing to identify vaccine-related anaphylaxis at five health care systems in the Vaccine Safety Datalinkexternal icon
        Yu W, Zheng C, Xie F, Chen W, Mercado C, Sy LS, Qian L, Glenn S, Tseng HF, Lee G, Duffy J, McNeil MM, Daley MF, Crane B, McLean HQ, Jackson LA, Jacobsen SJ.
        Pharmacoepidemiol Drug Saf. 2020 Feb;29(2):182-188.
        PURPOSE: The objective was to develop a natural language processing (NLP) algorithm to identify vaccine-related anaphylaxis from plain-text clinical notes, and to implement the algorithm at five health care systems in the Vaccine Safety Datalink. METHODS: The NLP algorithm was developed using an internal NLP tool and training dataset of 311 potential anaphylaxis cases from Kaiser Permanente Southern California (KPSC). We applied the algorithm to the notes of another 731 potential cases (423 from KPSC; 308 from other sites) with relevant codes (ICD-9-CM diagnosis codes for anaphylaxis, vaccine adverse reactions, and allergic reactions; Healthcare Common Procedure Coding System codes for epinephrine administration). NLP results were compared against a reference standard of chart reviewed and adjudicated cases. The algorithm was then separately applied to the notes of 6 427 359 KPSC vaccination visits (9 402 194 vaccine doses) without relevant codes. RESULTS: At KPSC, NLP identified 12 of 16 true vaccine-related cases and achieved a sensitivity of 75.0%, specificity of 98.5%, positive predictive value (PPV) of 66.7%, and negative predictive value of 99.0% when applied to notes of patients with relevant diagnosis codes. NLP did not identify the five true cases at other sites. When NLP was applied to the notes of KPSC patients without relevant codes, it captured eight additional true cases confirmed by chart review and adjudication. CONCLUSIONS: The current study demonstrated the potential to apply rule-based NLP algorithms to clinical notes to identify anaphylaxis cases. Increasing the size of training data, including clinical notes from all participating study sites in the training data, and preprocessing the clinical notes to handle special characters could improve the performance of the NLP algorithms. We recommend adding an NLP process followed by manual chart review in future vaccine safety studies to improve sensitivity and efficiency.

      9. The use of natural language processing to identify Tdap-related local reactions at five health care systems in the Vaccine Safety Datalinkexternal icon
        Zheng C, Yu W, Xie F, Chen W, Mercado C, Sy LS, Qian L, Glenn S, Lee G, Tseng HF, Duffy J, Jackson LA, Daley MF, Crane B, McLean HQ, Jacobsen SJ.
        Int J Med Inform. 2019 Jul;127:27-34.
        OBJECTIVE: Local reactions are the most common vaccine-related adverse event. There is no specific diagnosis code for local reaction due to vaccination. Previous vaccine safety studies used non-specific diagnosis codes to identify potential local reaction cases and confirmed the cases through manual chart review. In this study, a natural language processing (NLP) algorithm was developed to identify local reaction associated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in the Vaccine Safety Datalink. METHODS: Presumptive cases of local reactions were identified among members ≥ 11 years of age using ICD-9-CM codes in all care settings in the 1-6 days following a Tdap vaccination between 2012 and 2014. The clinical notes were searched for signs and symptoms consistent with local reaction. Information on the timing and the location of a sign or symptom was also extracted to help determine whether or not the sign or symptom was vaccine related. Reactions triggered by causes other than Tdap vaccination were excluded. The NLP algorithm was developed at the lead study site and validated on a stratified random sample of 500 patients from five institutions. RESULTS: The NLP algorithm achieved an overall weighted sensitivity of 87.9%, specificity of 92.8%, positive predictive value of 82.7%, and negative predictive value of 95.1%. In addition, using data at one site, the NLP algorithm identified 3326 potential Tdap-related local reactions that were not identified through diagnosis codes. CONCLUSION: The NLP algorithm achieved high accuracy, and demonstrated the potential of NLP to reduce the efforts of manual chart review in vaccine safety studies.

  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. Are there regional differences in triple negative breast cancer among non-Hispanic Black women?external icon
        Bartley SJ, Wu M, Benard V, Ambrosone C, Richardson LC.
        J Natl Med Assoc. 2020 Aug 7.
        BACKGROUND: Non-Hispanic black women (NHB) are diagnosed with triple negative breast cancer (TNBC) more often than other ethnic or racial groups in the United States (US). This study describes regional differences in TNBC incidence among NHB women in the US from 2011 to 2015. METHODS: We analyzed data from the United States Cancer Statistics (USCS) that includes incidence data from the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) programs. RESULTS: Compared to the incidence rate for NHB women in the South, rates were significantly lower in the Northeast (22.6 per 100,000), higher in the Midwest (25.5 per 100,000) and similar in the West. These regional differences might be explained by genetic admixture among people with different geographic ancestral origins. CONCLUSIONS: Results from this study highlight the need to extend etiological research and evidence-based cancer prevention and control efforts to women at high risk of this disease in order to decrease cancer disparities.

      2. Exploring reasons for state-level variation in incidence of dialysis-requiring acute kidney injury (AKI-D) in the United Statesexternal icon
        Chen Z, McCulloch CE, Powe NR, Heung M, Saran R, Pavkov ME, Burrows NR, Hsu RK, Hsu CY.
        BMC Nephrol. 2020 Aug 10;21(1):336.
        BACKGROUND: There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. METHODS: National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. RESULTS: The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly < 3-fold difference in range) were larger than the state-level differences in prevalence for each chronic health condition (mostly < 2.5-fold difference in range). A significant correlation was shown between AKI-D incidence and prevalence of diabetes, ASHD, and COPD, as well as between AKI-D incidence and rate of hospitalization with hypertension. In regression models, after adjusting for age, sex, and race, AKI-D incidence was associated with prevalence of and rates of hospitalization with five chronic health conditions--diabetes, hypertension, CKD, ASHD and COPD--and rates of hospitalization with cancer. CONCLUSIONS: Results from this ecological analysis suggest that state-level variation in AKI-D incidence may be influenced by state-level variations in prevalence of and rates of hospitalization with several chronic health conditions. For most of the explored chronic conditions, AKI-D correlated stronger with rates of hospitalizations with the health conditions rather than with their prevalences, suggesting that better disease management strategies that prevent hospitalizations may translate into lower incidence of AKI-D.

      3. This study used the most recent national data on epilepsy from the 2017 National Health Interview Survey (NHIS) to examine the distribution of types of provider visits in the last 12 months among 2.9 million adult respondents aged ≥18 years with active epilepsy (self-reported doctor-diagnosed epilepsy taking antiseizure medications and/or having ≥1 seizure in the past year) and compared these estimates with 2010 NHIS data. We calculated age-standardized percentages of visits to a general doctor and an epilepsy specialist during the past 12 months, accounting for the complex survey design. Among US adults with active epilepsy in 2017, 27.1% saw a general doctor only, 9.0% saw a neurologist/epilepsy specialist only, 53.0% visited both a general doctor and a neurologist/epilepsy specialist, and 11.4% did not see either a general doctor or a neurologist/specialist. Overall, 62.0% [95% confidence interval (CI) = 55.2%-67.5%] of adults with active epilepsy visited a neurologist or epilepsy specialist in the past year. A visit in the past 12 months with both provider types was not significantly different in 2017 compared with 2010 (53.0% vs 46.2%) while seeing a general doctor only had declined (41.8% vs 27.1%, p < 0.05). Given that 79.8% of US adults with active epilepsy reported being seen by a general doctor within the past 12 months, epilepsy stakeholders have an opportunity to enhance epilepsy care by ensuring that general practitioners have access to the latest information about epilepsy diagnosis and new treatment options. National Health Interview Survey data can be used to track the distribution of provider visits in the coming decade to assess changes in access to primary care, specialty care, or other types of healthcare for people with epilepsy.

      4. All-cause opioid prescriptions dispensed: The outsized role of adults with arthritisexternal icon
        Murphy LB, Cisternas MG, Theis KA, Brady TJ, Bohm MK, Guglielmo D, Hootman JM, Barbour KE, Boring MA, Helmick CG.
        Am J Prev Med. 2020 Jul 9.
        INTRODUCTION: Limited estimates of prescribed opioid use among adults with arthritis exist. All-cause (i.e., for any condition) prescribed opioid dispensed (referred to as opioid prescription in the remainder of this abstract) in the past 12 months among U.S. adults aged ≥18 years (n=35,427) were studied, focusing on adults with arthritis (n=12,875). METHODS: In 2018-2019, estimates were generated using Medical Expenditure Panel Survey data: (1) 2015 prevalence of 1 or more opioid prescriptions to U.S. adults overall and by arthritis status and (2) in 2014-2015, among adults with arthritis, multivariable-adjusted associations between 1 or more opioid prescriptions and sociodemographic characteristics, health status, and healthcare utilization characteristics. RESULTS: In 2015, the age-standardized prevalence of 1 or more opioid prescriptions among adults with arthritis (29.6%) was almost double of that for all adults (15.4%). Adults with arthritis represented more than half of all adults (55.3%) with at least 1 opioid prescription; among those with 1 or more prescriptions, 43.2% adults had 4 or more prescriptions. The strongest multivariable-adjusted associations with 1 or more opioid prescriptions were ambulatory care visits (1-4: prevalence ratios=1.9-2.0, 5-8: prevalence ratios=2.5-2.7, 9 or more: prevalence ratios=3.4-3.7) and emergency room visits (1: prevalence ratios=1.6, 2-3: prevalence ratios=1.9-2.0, 4 or more: prevalence ratios=2.4); Ref for both: no visits. CONCLUSIONS: Adults with arthritis are a high-need target group for improving pain management, representing more than half of all U.S. adults with 1 or more opioid prescriptions. The association with ambulatory care visits suggests that providers have routine opportunities to discuss comprehensive and integrative pain management strategies, including low-cost evidence-based self-management approaches (e.g., physical activity, self-management education programs, cognitive behavioral therapy). Those with multiple opioid prescriptions may need extra support if transitioning to nonopioid and nonpharmacologic pain management strategies.

      5. Thematic analysis of hospice mentions in the health records of veterans with advanced kidney diseaseexternal icon
        O'Hare AM, Butler CR, Taylor JS, Wong SP, Vig EK, Laundry RS, Wachterman MW, Hebert PL, Liu CF, Rios-Burrows N, Richards CA.
        J Am Soc Nephrol. 2020 Aug 6.
        BACKGROUND: Patients with advanced kidney disease are less likely than many patients with other types of serious illness to enroll in hospice. Little is known about real-world clinical decision-making related to hospice for members of this population. METHODS: We used a text search tool to conduct a thematic analysis of documentation pertaining to hospice in the electronic medical record system of the Department of Veterans Affairs, for a national sample of 1000 patients with advanced kidney disease between 2004 and 2014 who were followed until October 8, 2019. RESULTS: Three dominant themes emerged from our qualitative analysis of the electronic medical records of 340 cohort members with notes containing hospice mentions: (1) hospice and usual care as antithetical care models: clinicians appeared to perceive a sharp demarcation between services that could be provided under hospice versus usual care and were often uncertain about hospice eligibility criteria. This could shape decision-making about hospice and dialysis and made it hard to individualize care; (2) hospice as a last resort: patients often were referred to hospice late in the course of illness and did not so much choose hospice as accept these services after all treatment options had been exhausted; and (3) care complexity: patients' complex care needs at the time of hospice referral could complicate transitions to hospice, stretch the limits of home hospice, and promote continued reliance on the acute care system. CONCLUSIONS: Our findings underscore the need to improve transitions to hospice for patients with advanced kidney disease as they approach the end of life.

      6. The IARC Monographs: Updated procedures for modern and transparent evidence synthesis in cancer hazard identificationexternal icon
        Samet JM, Chiu WA, Cogliano V, Jinot J, Kriebel D, Lunn RM, Beland FA, Bero L, Browne P, Fritschi L, Kanno J, Lachenmeier DW, Lan Q, Lasfargues G, Le Curieux F, Peters S, Shubat P, Sone H, White MC, Williamson J, Yakubovskaya M, Siemiatycki J, White PA, Guyton KZ, Schubauer-Berigan MK, Hall AL, Grosse Y, Bouvard V, Benbrahim-Tallaa L, El Ghissassi F, Lauby-Secretan B, Armstrong B, Saracci R, Zavadil J, Straif K, Wild CP.
        J Natl Cancer Inst. 2020 Jan 1;112(1):30-37.
        The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

      7. Evaluating the ability of economic models of diabetes to simulate new cardiovascular outcomes trials: A report on the Ninth Mount Hood Diabetes Challengeexternal icon
        Si L, Willis MS, Asseburg C, Nilsson A, Tew M, Clarke PM, Lamotte M, Ramos M, Shao H, Shi L, Zhang P, McEwan P, Ye W, Herman WH, Kuo S, Isaman DJ, Schramm W, Sailer F, Brennan A, Pollard D, Smolen HJ, Leal J, Gray A, Patel R, Feenstra T, Palmer AJ.
        Value in Health. 2020 .
        Objectives: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication. Methods: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class. Results: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME–calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit. Conclusions: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed.

    • Communicable Diseases
      1. Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2: A systematic reviewexternal icon
        Abrams JY, Godfred-Cato SE, Oster ME, Chow EJ, Koumans EH, Bryant B, Leung JW, Belay ED.
        J Pediatr. 2020 Aug 5.
        OBJECTIVE: To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to SARS-CoV-2, by conducting a systematic analysis of studies from different settings which used various inclusion criteria. STUDY DESIGN: MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020 through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. RESULTS: Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: three studies selected patients diagnosed with Kawasaki disease (KD), two required cardiovascular involvement, and three had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for SARS-CoV-2 RT-PCR tests ranged from 13 to 69% and for serology, from 75 to 100%. MIS-C patients had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. CONCLUSIONS: This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

      2. BACKGROUND: Flu Near You (FNY) is an online participatory syndromic surveillance system that collects health related information. In this manuscript, we summarized the health-care seeking behavior of FNY participants who reported influenza-like illness (ILI) symptoms. METHODS: We applied inverse probability weighting to calculate age-adjusted estimates of the percentage of FNY participants in the United States who sought health care for ILI symptoms during the 2015-16 through 2018-19 influenza season and compared seasonal trends across different demographic and regional subgroups, including age group, sex, census region, and place of care using adjusted Chi-square tests. RESULTS: The overall age-adjusted percentage of FNY participants who sought health care for ILI symptoms varied by season and ranged from 22.8% to 35.6%. Across all seasons, health care seeking was highest for the <18 and 65+ age groups, females had a greater percentage compared with males, and the South census region had the largest percentage while the West census region had the smallest percentage. CONCLUSIONS: The percentage of FNY participants who sought health care for ILI symptoms varied by season, geographical region, age group, and sex. FNY compliments existing surveillance systems and informs estimates of influenza-associated illness by adding important real-time insights into health-care seeking behavior.

      3. Natural history of disseminated coccidioidomycosis: Examination of the VA-Armed Forces Databaseexternal icon
        Bays DJ, Thompson GR, Reef S, Snyder L, Freifeld AJ, Huppert M, Salkin D, Wilson MD, Galgiani JN.
        Clin Infect Dis. 2020 Aug 11.
        BACKGROUND: The natural history of non-central nervous system (CNS) disseminated coccidioidomycosis (DCM) has not been previously characterized. The historical VA-Armed Forces coccidioidomycosis patient group provides a unique cohort of patients not treated with standard antifungal therapy allowing for characterization of the natural history of coccidioidomycosis. METHODS: We conducted a retrospective study of 531 VA-Armed Forces coccidioidomycosis patients diagnosed between 1955-1958 and followed to 1966. Groups were identified as non-disseminated coccidioidomycosis (non-DCM, 462 patients), DCM (44 patients), and CNS (25 patients). The duration of initial infection, fate of primary infection, all-cause mortality and mortality secondary to coccidioidomycosis were assessed and compared between groups. RESULTS: Mortality due to coccidioidomycosis at last known follow up was significantly different across the groups: 0.65% in non-DCM, 25% in DCM, and 88% in CNS (P<0.001). The primary fate of pulmonary infection demonstrated key differences with pulmonary nodules observed in 39.61% in non-DCM, 13.64% in DCM, and 20% in CNS (P<0.001). There were differences in cavity formation with 34.20% in non-DCM, 9.09% DCM, and 8 % in CNS (P <0.001). Forty-one percent and 56% of patients in the non-CNS DCM and CNS groups, respectively, developed dissemination as the presenting manifestation or concurrent with initial infection. CONCLUSIONS: This large retrospective cohort study helps characterize the natural history of DCM, provides insight into the host immunologic response, and has direct clinical implications for the management and follow-up of patients.

      4. Individual model forecasts can be misleading, but together they are usefulexternal icon
        Buckee CO, Johansson MA.
        Eur J Epidemiol. 2020 Aug 11:1-2.

      5. Racial and ethnic disparities among COVID-19 cases in workplace outbreaks by industry sector - Utah, March 6-June 5, 2020external icon
        Bui DP, McCaffrey K, Friedrichs M, LaCross N, Lewis NM, Sage K, Barbeau B, Vilven D, Rose C, Braby S, Willardson S, Carter A, Smoot C, Winquist A, Dunn A.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1133-1138.
        Improved understanding of the overall distribution of workplace coronavirus disease 2019 (COVID-19) outbreaks by industry sector could help direct targeted public health action; however, this has not been described. The Utah Department of Health (UDOH) analyzed COVID-19 surveillance data to describe workplace outbreaks by industry sectors. In this report, workplaces refer to non-health care, noncongregate-living, and noneducational settings. As of June 5, 2020, UDOH reported 277 COVID-19 outbreaks, 210 (76%) of which occurred in workplaces. Approximately 12% (1,389 of 11,448) of confirmed COVID-19 cases in Utah were associated with workplace outbreaks. The 210 workplace outbreaks occurred in 15 of 20 industry sectors;* nearly one half of all workplace outbreaks occurred in three sectors: Manufacturing (43; 20%), Construction (32; 15%) and Wholesale Trade (29; 14%); 58% (806 of 1,389) of workplace outbreak-associated cases occurred in these three sectors. Although 24% of Utah's workforce in all 15 affected sectors identified as Hispanic or Latino (Hispanic) or a race other than non-Hispanic white (nonwhite(†)) (1), 73% (970 of 1,335) of workplace outbreak-associated COVID-19 cases were in persons who identified as Hispanic or nonwhite. Systemic social inequities have resulted in the overrepresentation of Hispanic and nonwhite workers in frontline occupations where exposure to SARS-CoV-2, the virus that causes COVID-19, might be higher (2); extra vigilance in these sectors is needed to ensure prevention and mitigation strategies are applied equitably and effectively to workers of racial and ethnic groups disproportionately affected by COVID-19. Health departments can adapt workplace guidance to each industry sector affected by COVID-19 to account for different production processes and working conditions.

      6. Notes from the field: COVID-19 prevention practices in state prisons - Puerto Rico, 2020external icon
        Davlantes E, Toro M, Villalobos R, Sanchez-Gonzalez L.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1144.

      7. PEPFAR's response to the convergence of the HIV and COVID-19 pandemics in Sub-Saharan Africaexternal icon
        Golin R, Godfrey C, Firth J, Lee L, Minior T, Phelps BR, Raizes EG, Ake JA, Siberry GK.
        J Int AIDS Soc. 2020 Aug;23(8):e25587.
        INTRODUCTION: The COVID-19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemic would have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. This commentary reviews PEPFAR's COVID-19 technical guidance and provides country-specific examples of programme adaptions in sub-Saharan Africa. DISCUSSION: The COVID-19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over-burdened health systems. Although there is currently limited understanding of how COVID-19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID-19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in-person home and facility visits and other direct contact when COVID-19 control measures are in effect. PEPFAR-supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID-19 in sub-Saharan Africa. CONCLUSIONS: As community transmission of COVID-19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data-driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID-19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.

      8. Mass testing for SARS-CoV-2 in 16 prisons and jails - six jurisdictions, United States, April-May 2020external icon
        Hagan LM, Williams SP, Spaulding AC, Toblin RL, Figlenski J, Ocampo J, Ross T, Bauer H, Hutchinson J, Lucas KD, Zahn M, Chiang C, Collins T, Burakoff A, Bettridge J, Stringer G, Maul R, Waters K, Dewart C, Clayton J, de Fijter S, Sadacharan R, Garcia L, Lockett N, Short K, Sunder L, Handanagic S.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1139-1143.
        Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).

      9. Gaps in HIV testing and treatment among female sex workers in Lae and Mt. Hagen, Papua New Guineaexternal icon
        Hakim AJ, Coy K, Amos A, Willie B, Badman SG, Narokobi R, Gabuzzi J, Pekon S, Kupul M, Hou P, Aeno H, Boli RN, Nembari J, Ase S, Weikum D, Dala N, Callens S, Kaldor JM, Vallely AJ, Kelly-Hanku A.
        AIDS Behav. 2020 Aug 6.
        We conducted biobehavioral surveys among female sex workers (FSW) in Lae and Mt. Hagen, Papua New Guinea (January-December 2017). Respondent-driven sampling was used to recruit FSW aged ≥ 12 years, who were assigned female sex at birth, who spoke English or Tok Pisin, and who sold or exchanged sex for money, goods, or services in the last 6 months. When adjusted for viral suppression, 48.9% of FSW Lae and 61.9% in Mt. Hagen were aware of their HIV positive status. Of these women, 95.3% in Lae and 98.9% in Mt. Hagen were on antiretroviral therapy, and of these, 83.5% in Lae and 87.0% in Mt. Hagen had suppressed viral load. Renewed efforts are needed to increase HIV testing among FSW and provide support to FSW on treatment in both cities to attain viral suppression.

      10. Bioaerosol sampling of a ventilated patient with COVID-19external icon
        Lane MA, Brownsword EA, Morgan JS, Babiker A, Vanairsdale SA, Lyon GM, Mehta AK, Ingersoll JM, Lindsley WG, Kraft CS.
        Am J Infect Control. 2020 Aug 4.
        Bioaerosol samples were collected in an airborne infection isolation room, bathroom and anteroom of a ventilated patient with coronavirus disease 2019. Twenty-eight samples were negative for SARS-CoV-2 nucleic acid, possibly due to the patient being on a closed-circuit ventilator or the efficiency of the air exchanges in the room.

      11. Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after studyexternal icon
        Lebelonyane R, Bachanas P, Block L, Ussery F, Abrams W, Roland M, Theu J, Kapanda M, Matambo S, Lockman S, Gaolathe T, Makhema J, Moore J, Jarvis JN.
        Lancet HIV. 2020 Aug;7(8):e545-e553.
        BACKGROUND: Ensuring that individuals who are living with HIV rapidly initiate antiretroviral therapy (ART) is an essential step in meeting the 90-90-90 targets. We evaluated the feasibility and outcomes of rapid ART initiation in the Botswana Combination Prevention Project (BCPP). We aimed to establish whether simplified ART initiation with the offer of same-day treatment could increase uptake and reduce time from clinic linkage to treatment initiation, while maintaining rates of retention in care and viral suppression. METHODS: We did a quasi-experimental before and after study with use of data from the BCPP. The BCPP was a community-randomised HIV-prevention trial done in 30 communities across Botswana from Oct 1, 2013, to June 30, 2018. Participants in the 15 intervention clusters, who were HIV-positive and not already taking ART were offered universal HIV-treatment and same-day ART with a dolutegravir-based regimen at first clinic visit. This rapid ART intervention was implemented mid-way through the trial on June 1, 2016, enabling us to determine the effect of rapid ART guidelines on time to ART initiation and rates of retention in care and viral suppression at 1 year in the BCPP intervention group. FINDINGS: We assessed 1717 adults linked to study clinics before rapid ART introduction and 800 after rapid ART introduction. During the rapid ART period, 457 (57·1%, 95% CI 53·7-60·6) individuals initiated ART within 1 day of linkage, 589 (73·7%, 70·6-76·7) of 799 within 1 week, 678 (84·9%, 82·4-87·3) of 799 within 1 month, and 744 (93·5%, 91·6-95·1) of 796 within 1 year. Before the introduction of rapid ART, 163 (9·5%, 95% CI 8·2-11·0) individuals initiated ART within 1 day of linkage, 276 (16·1%, 14·4-17·9) within 1 week, 839 (48·9%, 46·5-51·3) within 1 month, and 1532 (89·2%, 87·7-90·6) within 1 year. 1 year after ART initiation, 1472 (90·5%, 87·4-92·8) of 1627 individuals who linked in the standard ART period were in care and had a viral load of less than 400 copies per mL, compared with 578 (91·6%, 88·1-94·1) of 631 in the rapid ART period (risk ratio 1·01, 95% CI 0·92-1·11). INTERPRETATION: Our findings provide support for the WHO recommendations for rapid ART initiation, and add to the accumulating evidence showing the feasibility, acceptability, and safety of rapid ART initiation in low-income and middle-income country settings. FUNDING: US President's Emergency Plan for AIDS Relief.

      12. COVID-19 and the workplace: Research questions for the aerosol science communityexternal icon
        Lindsley WG, Blachere FM, Burton NC, Christensen B, Estill CF, Fisher EM, Martin SB, Mead KR, Noti JD, Seaton M.
        Aerosol Sci Technol. 2020 .

      13. Clinical effectiveness of integrase strand transfer inhibitor-based antiretroviral regimens among adults with human immunodeficiency virus: a collaboration of cohort studies in the United States and Canadaexternal icon
        Lu H, Cole SR, Westreich D, Hudgens MG, Adimora AA, Althoff KN, Silverberg MJ, Buchacz K, Li J, Edwards JK, Rebeiro PF, Lima VD, Marconi VC, Sterling TR, Horberg MA, Gill MJ, Kitahata MM, Eron JJ, Moore RD.
        Clin Infect Dis. 2020 Aug 11.
        BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus. But evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. METHODS: We included participants from clinical cohorts in the North American AIDS Cohort Collaboration who initiated their first ART regimen, containing either InSTI (i.e., raltegravir, dolutegravir, and elvitegravir/cobicstat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RD), and hazard ratios (HR) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal diseases, end-stage liver diseases, or death. RESULTS: Of 15,993 participants, 5,824 (36%) initiated an InSTI-based, and 10,169 (64%) initiated an EFV-based, regimen. During the 6-year follow-up, 440 of the InSTI group and 1,097 of the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% for the InSTI group and 14.3% for the EFV group, corresponding with a RD of 0.3 percentage point (95% CI: -2.7, 3.3), and HR was 1.08 (95% CI: 0.97, 1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding with a RD was 0.3 percentage point (95% CI: -3.0, 3.7), and HR was 1.09 (95% CI: 0.96, 1.25). CONCLUSIONS: InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.

      14. Overcoming barriers to HIV care: Findings from a peer-delivered, community-based, linkage case management program (CommLink), Eswatini, 2015-2018external icon
        MacKellar D, Williams D, Dlamini M, Byrd J, Dube L, Mndzebele P, Mazibuko S, Pathmanathan I, Tilahun E, Ryan C.
        AIDS Behav. 2020 Aug 11.
        To help persons living with HIV (PLHIV) in Eswatini initiate antiretroviral therapy (ART), the CommLink case-management program provided a comprehensive package of linkage services delivered by HIV-positive, peer counselors. Of 1250 PLHIV participants aged ≥ 15 years diagnosed in community settings, 75% reported one or more barriers to care (e.g., fearing stigmatization). Peer counselors helped resolve 1405 (65%) of 2166 identified barriers. During Test and Treat (October 2016-September 2018), the percentage of participants who initiated ART and returned for ≥ 1 antiretroviral refills was 92% overall (759/824); 99% (155/156) among participants without any identified barriers; 96% (544/564) among participants whose counselors helped resolve all or all but one barrier; and 58% (59/102) among participants who had ≥ 2 unresolved barriers to care. The success of CommLink is attributed, at least in part, to peer counselors who helped their clients avoid or at least temporarily resolve many well-known barriers to HIV care.

      15. Roles for pharmacists in the "Ending the HIV Epidemic: A Plan for America" initiativeexternal icon
        McCree DH, Byrd KK, Johnston M, Gaines M, Weidle PJ.
        Public Health Rep. 2020 Aug 11.
        In 2019, President Trump announced a new initiative, Ending the HIV Epidemic: A Plan for America (EHE). EHE will use 3 key strategies-diagnose, treat, and prevent-to reduce new HIV infections at least 90% by 2030, as well as new laboratory methods and epidemiological techniques to respond quickly to potential outbreaks. Partnerships are an important component in the initiative's success. Pharmacists and pharmacies can play important roles in EHE, including dispensing antiretroviral therapy and providing HIV screening, adherence counseling, medication therapy management, preexposure prophylaxis, and nonprescription syringe sales. The objective of this report is to discuss potential roles that pharmacists and pharmacies can play under the key strategies of EHE.

      16. Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 states, February-June 2020external icon
        Moore JT, Ricaldi JN, Rose CE, Fuld J, Parise M, Kang GJ, Driscoll AK, Norris T, Wilson N, Rainisch G, Valverde E, Beresovsky V, Agnew Brune C, Oussayef NL, Rose DA, Adams LE, Awel S, Villanueva J, Meaney-Delman D, Honein MA.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1122-1126.
        During January 1, 2020-August 10, 2020, an estimated 5 million cases of coronavirus disease 2019 (COVID-19) were reported in the United States.* Published state and national data indicate that persons of color might be more likely to become infected with SARS-CoV-2, the virus that causes COVID-19, experience more severe COVID-19-associated illness, including that requiring hospitalization, and have higher risk for death from COVID-19 (1-5). CDC examined county-level disparities in COVID-19 cases among underrepresented racial/ethnic groups in counties identified as hotspots, which are defined using algorithmic thresholds related to the number of new cases and the changes in incidence.(†) Disparities were defined as difference of ≥5% between the proportion of cases and the proportion of the population or a ratio ≥1.5 for the proportion of cases to the proportion of the population for underrepresented racial/ethnic groups in each county. During June 5-18, 205 counties in 33 states were identified as hotspots; among these counties, race was reported for ≥50% of cumulative cases in 79 (38.5%) counties in 22 states; 96.2% of these counties had disparities in COVID-19 cases in one or more underrepresented racial/ethnic groups. Hispanic/Latino (Hispanic) persons were the largest group by population size (3.5 million persons) living in hotspot counties where a disproportionate number of cases among that group was identified, followed by black/African American (black) persons (2 million), American Indian/Alaska Native (AI/AN) persons (61,000), Asian persons (36,000), and Native Hawaiian/other Pacific Islander (NHPI) persons (31,000). Examining county-level data disaggregated by race/ethnicity can help identify health disparities in COVID-19 cases and inform strategies for preventing and slowing SARS-CoV-2 transmission. More complete race/ethnicity data are needed to fully inform public health decision-making. Addressing the pandemic's disproportionate incidence of COVID-19 in communities of color can reduce the community-wide impact of COVID-19 and improve health outcomes.

      17. Diversity of the hepatitis C virus NS5B gene during HIV co-infectionexternal icon
        Ngwaga T, Kong L, Lin D, Schoborg C, Taylor LE, Mayer KH, Klein RS, Celentano DD, Sobel JD, Jamieson DJ, King CC, Tavis JE, Blackard JT.
        PLoS One. 2020 ;15(8):e0237162.
        Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.

      18. The impact of maternal HIV infection on the burden of respiratory syncytial virus among pregnant women and their infants, western Kenyaexternal icon
        Nyawanda BO, Otieno NA, Otieno MO, Emukule GO, Bigogo G, Onyango CO, Lidechi S, Nyaundi J, Langley GE, Widdowson MA, Chaves SS.
        J Infect Dis. 2020 Aug 10.
        BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of respiratory illness worldwide, however, burden data on mother-infant pairs remain sparse in sub-Saharan Africa where HIV is prevalent. We evaluated the impact of maternal HIV infection on the burden of RSV among mothers and their infants in western Kenya. METHODS: We enrolled pregnant women (≤20 weeks gestation) and followed them and their newborns weekly for up to 3-6 months post-partum, to document cases of acute respiratory illness (ARI). Nasal/ oropharyngeal swabs were collected and tested for RSV using polymerase chain reaction. Analyses were stratified by maternal HIV-status, and incidence computed per 1,000 person-months. RESULTS: Compared to RSV-negative ARI cases, RSV-positive cases were associated with cough, apnoea and hospitalization among infants. RSV incidence per 1,000 person-months among mothers was 4.0 (95% confidence interval (CI), 3.2-4.4), and was twice that among the HIV-infected (8.4; 95% CI, 5.7-12.0) compared to the HIV-uninfected mothers (3.1; 95% CI 2.3-4.0). Among infants, incidence per 1,000 person-months was 15.4 (95% CI, 12.5-18.8); incidence did not differ by HIV exposure or prematurity. CONCLUSION: HIV-infection may increase the risk of RSV illness among pregnant women. Future maternal RSV vaccines may have added benefit in high HIV prevalence areas.

      19. Trends in number and distribution of COVID-19 hotspot counties - United States, March 8-July 15, 2020external icon
        Oster AM, Kang GJ, Cha AE, Beresovsky V, Rose CE, Rainisch G, Porter L, Valverde EE, Peterson EB, Driscoll AK, Norris T, Wilson N, Ritchey M, Walke HT, Rose DA, Oussayef NL, Parise ME, Moore ZS, Fleischauer AT, Honein MA, Dirlikov E, Villanueva J.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1127-1132.
        The geographic areas in the United States most affected by the coronavirus disease 2019 (COVID-19) pandemic have changed over time. On May 7, 2020, CDC, with other federal agencies, began identifying counties with increasing COVID-19 incidence (hotspots) to better understand transmission dynamics and offer targeted support to health departments in affected communities. Data for January 22-July 15, 2020, were analyzed retrospectively (January 22-May 6) and prospectively (May 7-July 15) to detect hotspot counties. No counties met hotspot criteria during January 22-March 7, 2020. During March 8-July 15, 2020, 818 counties met hotspot criteria for ≥1 day; these counties included 80% of the U.S. population. The daily number of counties meeting hotspot criteria peaked in early April, decreased and stabilized during mid-April-early June, then increased again during late June-early July. The percentage of counties in the South and West Census regions* meeting hotspot criteria increased from 10% and 13%, respectively, during March-April to 28% and 22%, respectively, during June-July. Identification of community transmission as a contributing factor increased over time, whereas identification of outbreaks in long-term care facilities, food processing facilities, correctional facilities, or other workplaces as contributing factors decreased. Identification of hotspot counties and understanding how they change over time can help prioritize and target implementation of U.S. public health response activities.

      20. Optimal testing choice and diagnostic strategies for latent tuberculosis infection among U.S.-born people living with HIVexternal icon
        Pettit AC, Stout JE, Belknap R, Benson CA, Seraphin MN, Lauzardo M, Horne DJ, Garfein RS, Maruri F, Ho CS.
        Clin Infect Dis. 2020 Aug 6.
        BACKGROUND: Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with HIV (PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. METHODS: We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of U.S.-born PLWH ≥5 years old with valid results for all three LTBI tests using standard U.S. cutoffs (≥5mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. RESULTS: Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. CONCLUSIONS: LTBI prevalence among this cohort of U.S.-born PLWH was low compared to non-U.S. born persons. TSPOT's higher PPV may make it preferable for testing U.S.-born PLWH at low risk for TB exposure and with high CD4+ counts.

      21. Pertussis Infections among pregnant women in the United States, 2012-2017external icon
        Skoff TH, Faulkner AE, Liang JL, Barnes M, Kudish K, Thomas E, Kenyon C, Hoffman M, Pradhan E, Liko J, Hariri S.
        Clin Infect Dis. 2020 Aug 7.
        BACKGROUND: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used CDC's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and non-pregnant women of childbearing age. METHODS: Pertussis cases in women aged 18-44 years with cough onset between 1/1/2012-12/31/2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interview and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. RESULTS: 1,582 pertussis cases were identified among women aged 18-44 years; 5.1% (76/1499) of patients with known pregnancy status were pregnant at cough onset. Of pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median age of pregnant and non-pregnant patients was 29.0 and 33.0 years, respectively. Most pregnant and non-pregnant patients were white (78.3% vs. 86.4%, p=0.09) and non-Hispanic (72.6% vs. 77.3%, p=0.35). Average annual pertussis incidence was 5.7/100,000 among pregnant and 7.3/100,000 among non-pregnant women. Compared to non-pregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%), post-tussive vomiting (58.1% vs. 47.9%) and apnea (37.3% vs. 29.0%); however, differences were not statistically significant (p>0.05 for all). A similar proportion of pregnant and non-pregnant patients reported ever having received Tdap (31.6% vs. 32.7%, p=0.84). CONCLUSIONS: Our analysis suggests that pertussis incidence and clinical characteristics of disease are similar among pregnant and non-pregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women.

      22. Pneumonia hospitalization coding changes associated with transition from the 9th to 10th Revision of International Classification of Diseasesexternal icon
        Smithee RB, Markus TM, Soda E, Grijalva CG, Xing W, Shang N, Griffin MR, Lessa FC.
        Health Serv Res Manag Epidemiol. 2020 Jan-Dec;7.
        OBJECTIVES: To evaluate the impact of International Classification of Disease, 10th revision, Clinical Modification (ICD-10-CM) implementation on pneumonia hospitalizations rates, which had declined following pneumococcal conjugate vaccine introduction for infants in 2000. METHODS: We randomly selected records from a single hospital 1 year before (n = 500) and after (n = 500) October 2015 implementation of ICD-10-CM coding. We used a validated ICD-9-CM algorithm and translation of that algorithm to ICD-10-CM to identify pneumonia hospitalizations pre- and post-implementation, respectively. We recoded ICD-10-CM records to ICD-9-CM and vice versa. We calculated sensitivity and positive predictive value (PPV) of the ICD-10-CM algorithm using ICD-9-CM coding as the reference. We used sensitivity and PPV values to calculate an adjustment factor to apply to ICD-10 era rates to enable comparison with ICD-9-CM rates. We reviewed primary diagnoses of charts not meeting the pneumonia definition when recoded. RESULTS: Sensitivity and PPV of the ICD-10-CM algorithm were 94% and 92%, respectively, for young children and 74% and 79% for older adults. The estimated adjustment factor for ICD-10-CM period rates was -2.09% (95% credible region [CR], -7.71% to +3.0%) for children and +6.76% (95% CR, -3.06% to +16.7%) for older adults. We identified a change in coding adult charts that met the ICD-9-CM pneumonia definition that led to recoding in ICD-10-CM as chronic obstructive pulmonary disease (COPD) exacerbation. CONCLUSIONS: The ICD-10-CM algorithm derived from a validated ICD-9-CM algorithm should not introduce substantial bias for evaluating pneumonia trends in children. However, changes in coding of pneumonia associated with COPD in adults warrant further study.

      23. HIV policy advancements in PEPFAR partner countries: a review of data from 2010-2016external icon
        Verani AR, Lane J, Lim T, Kaliel D, Katz A, Palen J, Timberlake J.
        Glob Public Health. 2020 Aug 4:1-11.
        This paper aims to describe and analyse progress with domestic HIV-related policies in PEPFAR partner countries, utilising data collected as part of PEPFAR's routine annual program reporting from U.S. government fiscal years 2010 through 2016. 402 policies were monitored for one or more years across more than 50 countries using the PEPFAR policy tracking tool across five policy process stages: 1. Problem identification, 2. Policy development, 3. Policy endorsement, 4. Policy implementation, and 5. Policy evaluation. This included 219 policies that were adopted and implemented by partner governments, many in Africa. Policies were tracked across a wide variety of subject matter areas, with HIV Testing and Treatment being the most common. Our review also illustrates challenges with policy reform using varied, national examples. Challenges include the length of time (often years) it may take to reform policies, local customs that may differ from policy goals, and insufficient public funding for policy implementation. Limitations included incomplete data, variability in the amount of data provided due to partial reliance on open-ended text boxes, and data that reflect the viewpoints of submitting PEPFAR country teams.

    • Disaster Control and Emergency Services
      1. Conducting an evaluation of CBRN canister protection capabilities against emerging chemical and radiological hazardsexternal icon
        Greenawald LA, Karwacki CJ, Palya F, Browe MA, Bradley D, Szalajda JV.
        J Occup Environ Hyg. 2020 Aug 10:1-15.
        In the event of a chemical, biological, radiological, or nuclear (CBRN) hazard release, emergency responders rely on respiratory protection to prevent inhalation of these hazards. The National Institute for Occupational Safety and Health's (NIOSH) CBRN Statement of Standard calls for CBRN respirator canisters to be challenged with 11 different chemical test representative agents (TRAs) during certification testing, which represent hazards from 7 distinct Chemical Families; these 11 TRAs were identified during the original 2001 CBRN hazard assessment. CBRN hazards are constantly evolving in type, intent of use, and ways of dissemination. Thus, new and emerging hazards must be identified to ensure CBRN canisters continue to provide protection to emergency responders against all hazards that would most likely be used in an intentional or unintentional event. The objectives are to: (1) update the CBRN list of hazards to ensure NIOSH-approved CBRN canisters continue to provide adequate protection capabilities from newly emerging chemical and radiological hazards and (2) identify the need to update NIOSH TRAs to ensure testing conditions represent relevant hazards. These objectives were accomplished by reviewing recent hazard assessments to identify a list of chemical and radiological respiratory hazards, evaluate chemical/physical properties and filtration behavior for these hazards, group the hazards based on NIOSH's current Chemical Families, and finally compare the hazards to the current TRAs based on anticipated filtration behavior, among other criteria. Upon completion of the evaluation process, 237 hazards were identified and compared to NIOSH's current CBRN TRAs. Of these 237 hazards, 203 were able to be categorized into one of NIOSH's current seven Chemical Families. Five were identified for further evaluation. Based on reviewing key chemical/physical properties of each hazard, NIOSH's current 11 TRAs remain representative of the identified respiratory CBRN hazards to emergency responders and should continue to be used during NIOSH certification testing. Thus, NIOSH's CBRN Statement of Standard remains unchanged. The process developed standardizes a methodology for future hazard evaluations.

    • Disease Reservoirs and Vectors
      1. Tick-borne diseases are increasing in North America. Knowledge of which tick species and associated human pathogens are present locally can inform the public and medical community about the acarological risk for tick bites and tick-borne infections. Citizen science (also called community-based monitoring, volunteer monitoring, or participatory science) is emerging as a potential approach to complement traditional tick record data gathering where all aspects of the work is done by researchers or public health professionals. One key question is how citizen science can best be used to generate high-quality data to fill knowledge gaps that are difficult to address using traditional data gathering approaches. Citizen science is particularly useful to generate information on human-tick encounters and may also contribute to geographical tick records to help define species distributions across large areas. Previous citizen science projects have utilized three distinct tick record data gathering methods including submission of: 1) physical tick specimens for identification by professional entomologists, 2) digital images of ticks for identification by professional entomologists, and 3) data where the tick species and life stage were identified by the citizen scientist. We explore the benefits and drawbacks of citizen science, relative to the traditional scientific approach, to generate data on tick records, with special emphasis on data quality for species identification and tick encounter locations. We recognize the value of citizen science to tick research but caution that the generated information must be interpreted cautiously with data quality limitations firmly in mind to avoid misleading conclusions.

    • Epidemiology and Surveillance
      1. Community-based surveillance advances the Global Health Security Agenda in Ghanaexternal icon
        Merali S, Asiedu-Bekoe F, Clara A, Adjabeng M, Baffoenyarko I, Frimpong JA, Avevor PM, Walker C, Balajee SA.
        PLoS One. 2020 ;15(8):e0237320.
        Ghana Health Service (GHS) has strengthened community-based surveillance (CBS) to facilitate early detection and rapid reporting of health events of all origins. Since June 2017, GHS has employed an event-based surveillance approach at the community level in a phased manner. CBS coverage has broadened from 2 to 30 districts across Ghana. Through this effort, capacity was built across all administrative levels in these districts to detect, report, triage, and verify signals, and to perform risk assessment and investigate events. Data were collected and analyzed during an evaluation of initial 2-district implementation in March 2018 and during expanded 30-district implementation in March 2019. Between September 2018 and March 2019, 317 health events were detected through CBS. These events included vaccine-preventable disease cases, acute hemorrhagic conjunctivitis outbreaks, clusters of unexpected animal deaths, and foodborne illness clusters. Eighty-nine percent of the 317 events were reported to district-level public health staff within 24 hours of detection at the community level, and 87% of all detected events were responded to within 48 hours of detection. CBS detected 26% of all suspected vaccine-preventable disease cases that were reported from implementing districts through routine disease surveillance. GHS strengthened CBS in Ghana to function as an early warning system for health events of all origins, advancing the Global Health Security Agenda.

    • Food Safety
      1. Investigating the meat pathway as a source of human nontyphoidal Salmonella bloodstream infections and diarrhea in East Africaexternal icon
        Crump JA, Thomas KM, Benschop J, Knox MA, Wilkinson DA, Midwinter AC, Munyua P, Ochieng JB, Bigogo GM, Verani JR, Widdowson MA, Prinsen G, Cleaveland S, Karimuribo ED, Kazwala RR, Mmbaga BT, Swai ES, French NP, Zadoks RN.
        Clin Infect Dis. 2020 Aug 10.
        BACKGROUND: Salmonella Enteritidis and Salmonella Typhimurium are major causes of bloodstream infection and diarrheal disease in East Africa. Sources of human infection, including the role of the meat pathway, are poorly understood. METHODS: We collected cattle, goat, and poultry meat pathway samples from December 2015 through August 2017 in Tanzania and isolated Salmonella using standard methods. Meat pathway isolates were compared with nontyphoidal Salmonella (NTS) isolated from persons with bloodstream infection and diarrheal disease from 2007 through 2017 from Kenya by core genome multi-locus sequence typing (cgMLST). Isolates were characterized for antimicrobial resistance, virulence genes, and diversity. RESULTS: We isolated NTS from 164 meat pathway samples. Of 172 human NTS isolates, 90 (52.3%) from stool and 82 (47.7%) from blood, 53 (30.8%) were Salmonella Enteritidis ST11 and 62 (36.0%) Salmonella Typhimurium ST313. We identified cgMLST clusters within Salmonella Enteritidis ST11, Salmonella Heidelberg ST15, Salmonella Typhimurium ST 19, and Salmonella II 42:r:- ST1208 that included both human and meat pathway isolates. Salmonella Typhimurium ST313 was isolated exclusively from human samples. Human and poultry isolates bore more antimicrobial resistance and virulence genes and were less diverse than isolates from other sources. CONCLUSIONS: Our findings suggest that the meat pathway may be an important source of human infection by some clades of Salmonella Enteritidis ST11 in East Africa, but not of human Salmonella Typhimurium ST313 infection. Research is needed to systematically examine the contribution of other types of meat, animal products, produce, water, and environmental exposures to nontyphoidal Salmonella disease in East Africa.

    • Genetics and Genomics
      1. STROBE-metagenomics: a STROBE extension statement to guide the reporting of metagenomics studiesexternal icon
        Bharucha T, Oeser C, Balloux F, Brown JR, Carbo EC, Charlett A, Chiu CY, Claas EC, de Goffau MC, de Vries JJ, Eloit M, Hopkins S, Huggett JF, MacCannell D, Morfopoulou S, Nath A, O'Sullivan DM, Reoma LB, Shaw LP, Sidorov I, Simner PJ, Van Tan L, Thomson EC, van Dorp L, Wilson MR, Breuer J, Field N.
        Lancet Infect Dis. 2020 Aug 5.
        The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving.

    • Health Disparities
      1. Permanent supportive housing with housing first to reduce homelessness and promote health among homeless populations with disability: A Community Guide systematic reviewexternal icon
        Peng Y, Hahn RA, Finnie RK, Cobb J, Williams SP, Fielding JE, Johnson RL, Montgomery AE, Schwartz AF, Muntaner C, Garrison VH, Jean-Francois B, Truman BI, Fullilove MT.
        J Public Health Manag Pract. 2020 Sep/Oct;26(5):404-411.
        CONTEXT: Poor physical and mental health and substance use disorder can be causes and consequences of homelessness. Approximately 2.1 million persons per year in the United States experience homelessness. People experiencing homelessness have high rates of emergency department use, hospitalization, substance use treatment, social services use, arrest, and incarceration. OBJECTIVES: A standard approach to treating homeless persons with a disability is called Treatment First, requiring clients be "housing ready"-that is, in psychiatric treatment and substance-free-before and while receiving permanent housing. A more recent approach, Housing First, provides permanent housing and health, mental health, and other supportive services without requiring clients to be housing ready. To determine the relative effectiveness of these approaches, this systematic review compared the effects of both approaches on housing stability, health outcomes, and health care utilization among persons with disabilities experiencing homelessness. DESIGN: A systematic search (database inception to February 2018) was conducted using 8 databases with terms such as "housing first," "treatment first," and "supportive housing." Reference lists of included studies were also searched. Study design and threats to validity were assessed using Community Guide methods. Medians were calculated when appropriate. ELIGIBILITY CRITERIA: Studies were included if they assessed Housing First programs in high-income nations, had concurrent comparison populations, assessed outcomes of interest, and were written in English and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing stability, physical and mental health outcomes, and health care utilization. RESULTS: Twenty-six studies in the United States and Canada met inclusion criteria. Compared with Treatment First, Housing First programs decreased homelessness by 88% and improved housing stability by 41%. For clients living with HIV infection, Housing First programs reduced homelessness by 37%, viral load by 22%, depression by 13%, emergency departments use by 41%, hospitalization by 36%, and mortality by 37%. CONCLUSIONS: Housing First programs improved housing stability and reduced homelessness more effectively than Treatment First programs. In addition, Housing First programs showed health benefits and reduced health services use. Health care systems that serve homeless patients may promote their health and well-being by linking them with effective housing services.

      2. BACKGROUND: It is not known whether reductions in socioeconomic and racial disparities in incidence of invasive pneumococcal disease (defined as the isolation of Streptococcus pneumoniae from a normally sterile body site) noted after pneumococcal conjugate vaccine introduction have been sustained. METHODS: Individual-level data collected from twenty Tennessee counties participating in Active Bacterial Core surveillance over 19 years were linked to neighborhood-level socioeconomic factors. Incidence rates were analyzed across three periods, pre-PCV7 (1998-1999), pre-PCV13 (2001-2009) and post-PCV13 (2011-2016) by socioeconomic factors. RESULTS: 8,491 cases of invasive pneumococcal disease were identified. Incidence for invasive pneumococcal disease decreased from 22.9 (1998-1999) to 17.9 (2001-2009) to 12.7 (2011-2016) cases per 100,000-person years. Post-PCV13 incidence of PCV13-serotype disease in high and low poverty neighborhoods were 3.1 (95% CI: 2.7-3.5) and 1.4 (1.0-1.8) respectively, compared with pre-PCV7 incidence of 17.8 (15.7-19.9) and 6.4 (4.9-7.9). Before PCV introduction, incidence of PCV13-serotype disease was higher in blacks than whites (black: 17.3 [15.10-19.50]; white: 11.8 [10.6-13.0]); after introduction, PCV13-type disease incidence was greatly reduced in both groups (white: 2.7 [2.4-3.0]; black: 2.2 [1.8-2.6]).

    • Health Economics
      1. PURPOSE: To review the published evidence of the impact of alcohol screening and brief intervention (SBI) delivered in emergency departments (EDs) on healthcare utilization and costs. PRINCIPAL RESULTS: This scoping review used existing literature reviews supplemented with an electronic database. We included studies if they assessed SBIs for alcohol delivered in an ED setting and reported healthcare utilization and/or costs. We abstracted methodological approaches and healthcare utilization outcomes from each study and categorized them based on substance of focus (alcohol only vs. alcohol and other substances). We updated cost estimates from each study to 2018 U.S. dollars. We identified seven studies published between 2010 and 2019 that met study inclusion criteria. Two of the seven studies evaluated SBI that targeted both alcohol and other substances. Six studies found a reduction in healthcare utilization or costs, and one found an increase in healthcare utilization. MAJOR CONCLUSIONS: This literature review suggests that SBI delivered in ED settings can be a cost-reducing approach to treating excessive alcohol consumption, a factor that policy-makers and payers might consider in prioritizing interventions.

    • Healthcare Associated Infections
      1. Chlorhexidine gluconate (CHG) is an antiseptic that is widely used in healthcare due to its excellent safety profile and wide spectrum of activity. Daily bathing with CHG has proven to be effective in the prevention of healthcare-associated infections and multi-drug resistant pathogen decolonization. Despite the proven benefits of CHG use, there remain concerns and unanswered questions about the potential for unintended microbial consequences of routine CHG bathing. This review aims to explore some of these questions.

      2. Flexible endoscopes require cleaning, high-level disinfection, and sterilization between each patient use to reduce risk of transmitting pathogens. Public health investigations have identified concerns, including endoscope damage, mishandling, and reprocessing deficiencies, placing patients at risk for transmission of bacterial, viral, and other pathogens. Findings from outbreak investigations and other studies have led to innovations in endoscope design, use, and reprocessing, yet infection risks related to contaminated or damaged endoscopes remain. Strict adherence to infection control guidelines and manufacturer instructions for use, utilization of supplemental guidance, and training and oversight of reprocessing personnel, reduce risk of pathogen transmission by flexible endoscopes.

      3. OBJECTIVE: Antibiotic resistance (AR) is a growing and highly prevalent problem in nursing homes. We describe selected AR phenotypes from pathogens causing urinary tract infections (UTIs) reported by nursing homes to the National Healthcare Safety Network (NHSN). DESIGN: Pathogens and antibiotic susceptibility testing results for UTI events in nursing homes between January 2013 and December 2017 were analyzed. The pathogen distribution and pooled mean proportion of isolates that tested resistant to select antibiotic agents are reported. SETTING AND PARTICIPANTS: US nursing homes voluntarily participating in the Long-Term Care Facility component of the NHSN. RESULTS: Overall, 243 nursing homes reported 1 or more UTIs: 121 (50%) were nonprofit facilities, median bed size was 91 (range: 9-801), and average occupancy was 87%. In total, 6,157 pathogens were reported for 5,485 UTI events. Moreover, 9 pathogens accounted for 90% of all reported UTIs; the 3 most frequently identified were Escherichia coli (41%), Proteus species (14%), and Klebsiella pneumoniae/oxytoca (13%). Among E. coli, fluoroquinolone, and extended-spectrum cephalosporin resistance were most prevalent (50% and 20%, respectively). Although Staphylococcus aureus and Enterococcus faecium represented <5% of pathogens reported, they had the highest rates of resistance (67% methicillin resistant and 60% vancomycin resistant, respectively). Multidrug resistance was most common in Pseudomonas aeruginosa (11%). For the resistant phenotypes we assessed, 36% of all UTIs reported were associated with a resistant pathogen. CONCLUSIONS: This is the first summary of AR among common pathogens causing UTIs reported to NHSN by nursing homes. Improved understanding of the resistance burden among common infections helps inform facility infection prevention and antibiotic stewardship efforts.

      4. Optimizing peritoneal dialysis-associated peritonitis prevention in the United States: From standardized peritoneal dialysis-associated peritonitis reporting and beyondexternal icon
        Perl J, Fuller DS, Boudville N, Kliger AS, Schaubel DE, Teitelbaum I, Warady BA, Neu AM, Patel PR, Piraino B, Schreiber M, Pisoni RL.
        Clin J Am Soc Nephrol. 2020 Aug 6.
        Peritoneal dialysis (PD)-associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.

    • Immunity and Immunization
      1. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years - United States, 2019external icon
        Elam-Evans LD, Yankey D, Singleton JA, Sterrett N, Markowitz LE, Williams CL, Fredua B, McNamara L, Stokley S.
        MMWR Morb Mortal Wkly Rep. 2020 Aug 21;69(33):1109-1116.
        Three vaccines are recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescents aged 11-12 years to protect against 1) pertussis; 2) meningococcal disease caused by types A, C, W, and Y; and 3) human papillomavirus (HPV)-associated cancers (1). At age 16 years, a booster dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended. Persons aged 16-23 years can receive serogroup B meningococcal vaccine (MenB), if determined to be appropriate through shared clinical decision-making. CDC analyzed data from the 2019 National Immunization Survey-Teen (NIS-Teen) to estimate vaccination coverage among adolescents aged 13-17 years in the United States.* Coverage with ≥1 dose of HPV vaccine increased from 68.1% in 2018 to 71.5% in 2019, and the percentage of adolescents who were up to date(†) with the HPV vaccination series (HPV UTD) increased from 51.1% in 2018 to 54.2% in 2019. Both HPV vaccination coverage measures improved among females and males. An increase in adolescent coverage with ≥1 dose of MenACWY (from 86.6% in 2018 to 88.9% in 2019) also was observed. Among adolescents aged 17 years, 53.7% received the booster dose of MenACWY in 2019, not statistically different from 50.8% in 2018; 21.8% received ≥1 dose of MenB, a 4.6 percentage point increase from 17.2% in 2018. Among adolescents living at or above the poverty level,(§) those living outside a metropolitan statistical area (MSA)(¶) had lower coverage with ≥1 dose of MenACWY and with ≥1 HPV vaccine dose, and a lower percentage were HPV UTD, compared with those living in MSA principal cities. In early 2020, the coronavirus disease 2019 (COVID-19) pandemic changed the way health care providers operate and provide routine and essential services. An examination of Vaccines for Children (VFC) provider ordering data showed that vaccine orders for HPV vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); and MenACWY decreased in mid-March when COVID-19 was declared a national emergency (Supplementary Figure 1, Ensuring that routine immunization services for adolescents are maintained or reinitiated is essential to continuing progress in protecting persons and communities from vaccine-preventable diseases and outbreaks.

      2. This report updates the 2019-20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020-21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020-21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture-based IIV4 (ccIIV4) or RIV4.The 2020-21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020-21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)-licensed indications. Updates and other information are available from CDC's influenza website ( Vaccination and health care providers should check this site periodically for additional information.

      3. Adverse events among young adults following a third dose of measles-mumps-rubella vaccineexternal icon
        Marin M, Fiebelkorn AP, Bi D, Coleman LA, Routh J, Curns AT, McLean HQ.
        Clin Infect Dis. 2020 Aug 7.
        BACKGROUND: A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received two doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a non-outbreak setting. METHODS: Young adults with two documented MMR doses were administered MMR3. From two weeks before until four weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs. pre-vaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from post-vaccination rates of significantly different symptoms to estimate number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for three post-vaccination injection-site symptoms. RESULTS: The 662 participants were aged 18-28 years (median=20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher post-vaccination vs. baseline. We estimate 119 participants (18%) reported more symptoms after MMR3 than pre-vaccination. By symptom, 13%, 10%, 8%, and 6% experienced more headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. Median onset was days 3-6 post-vaccination; median duration was 1-2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); median duration was 1-2 days. CONCLUSIONS: Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults.

      4. Whole genome and in-silico analyses of G1P[8] rotavirus strains from pre- and post-vaccination periods in Rwandaexternal icon
        Rasebotsa S, Mwangi PN, Mogotsi MT, Sabiu S, Magagula NB, Rakau K, Uwimana J, Mutesa L, Muganga N, Murenzi D, Tuyisenge L, Jaimes J, Esona MD, Bowen MD, Mphahlele MJ, Seheri ML, Mwenda JM, Nyaga MM.
        Sci Rep. 2020 Aug 10;10(1):13460.
        Rwanda was the first low-income African country to introduce RotaTeq vaccine into its Expanded Programme on Immunization in May 2012. To gain insights into the overall genetic make-up and evolution of Rwandan G1P[8] strains pre- and post-vaccine introduction, rotavirus positive fecal samples collected between 2011 and 2016 from children under the age of 5 years as part of ongoing surveillance were genotyped with conventional RT-PCR based methods and whole genome sequenced using the Illumina MiSeq platform. From a pool of samples sequenced (n = 158), 36 were identified as G1P[8] strains (10 pre-vaccine and 26 post-vaccine), of which 35 exhibited a typical Wa-like genome constellation. However, one post vaccine strain, RVA/Human-wt/RWA/UFS-NGS:MRC-DPRU442/2012/G1P[8], exhibited a RotaTeq vaccine strain constellation of G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3, with most of the gene segments having a close relationship with a vaccine derived reassortant strain, previously reported in USA in 2010 and Australia in 2012. The study strains segregated into two lineages, each containing a paraphyletic pre- and post-vaccine introduction sub-lineages. In addition, the study strains demonstrated close relationship amongst each other when compared with globally selected group A rotavirus (RVA) G1P[8] reference strains. For VP7 neutralization epitopes, amino acid substitutions observed at positions T91A/V, S195D and M217T in relation to the RotaTeq vaccine were radical in nature and resulted in a change in polarity from a polar to non-polar molecule, while for the VP4, amino acid differences at position D195G was radical in nature and resulted in a change in polarity from a polar to non-polar molecule. The polarity change at position T91A/V of the neutralizing antigens might play a role in generating vaccine-escape mutants, while substitutions at positions S195D and M217T may be due to natural fluctuation of the RVA. Surveillance of RVA at whole genome level will enhance further assessment of vaccine impact on circulating strains, the frequency of reassortment events under natural conditions and epidemiological fitness generated by such events.

    • Injury and Violence
      1. Introduction. Falls among older adults (age ≥65) are a common and costly health issue. Knowing where falls occur and whether this location differs by sex and age can inform prevention strategies. Objective. To determine where injurious falls that result in emergency department (ED) visits commonly occur among older adults in the United States, and whether these locations differ by sex and age. Methods. Using 2015 National Electronic Injury Surveillance System-All Injury Program data we reviewed narratives for ED patients aged ≥65 who had an unintentional fall as the primary cause of injury. Results. More fall-related ED visits (71.6%) resulted from falls that occurred indoors. A higher percentage of men’s falls occurred outside (38.3%) compared to women’s (28.4%). More fall-related ED visits were due to falls at home (79.2%) compared to falls not at home (20.8%). The most common locations for a fall at home were the bedroom, bathroom, and stairs. Conclusion. The majority of falls resulting in ED visits among older adults occurred indoors and varied by sex and age. Knowing common locations of injurious falls can help older adults and caregivers prioritize home modifications. Understanding sex and age differences related to fall location can be used to develop targeted prevention messages.

      2. OBJECTIVE: Because of the growing concern about the potential effects of traumatic brain injuries (TBIs) on a child's developing brain and the potential impact of lifetime depression and risk behaviors associated with TBI, further exploration is warranted. SETTING AND PARTICIPANTS: Data (N = 4917) from the 2017 North Carolina Behavioral Risk Factors Surveillance System (BRFSS). DESIGN: Cross-sectional. MAIN MEASURES: Examine whether a lifetime history of TBI with loss of consciousness (LOC) or having a history of TBI with LOC prior to 18 years of age was associated with a greater likelihood of lifetime depression, current binge drinking, and current cigarette and e-cigarette smoking. RESULTS: Respondents with a history of TBI with LOC had 2.1 (95% CI, 1.6-2.8) times higher odds of lifetime depression and 1.7 to 1.8 (95% CI, 1.02-2.97) times higher odds of all risk behaviors than those without a lifetime history of TBI with LOC. There were no statistical differences between age of first TBI with LOC and lifetime depression, binge drinking, cigarette smoking, and e-cigarette use after controlling for key demographics. CONCLUSION: These findings underscore the importance of increasing awareness among healthcare providers of the prevalence of lifetime depression and risk behaviors among individuals with a history of TBI and the need for improved screening and referrals to evidence-based services.

    • Laboratory Sciences
      1. Pentaplex real-time PCR for differential detection of Yersinia pestis and Y. pseudotuberculosis and application for testing fleas collected during plague epizooticsexternal icon
        Bai Y, Motin V, Enscore RE, Osikowicz L, Rosales Rizzo M, Hojgaard A, Kosoy M, Eisen RJ.
        Microbiologyopen. 2020 Aug 12:e1105.
        Upon acquiring two unique plasmids (pMT1 and pPCP1) and genome rearrangement during the evolution from Yersinia pseudotuberculosis, the plague causative agent Y. pestis is closely related to Y. pseudotuberculosis genetically but became highly virulent. We developed a pentaplex real-time PCR assay that not only detects both Yersinia species but also differentiates Y. pestis strains regarding their plasmid profiles. The five targets used were Y. pestis-specific ypo2088, caf1, and pst located on the chromosome, plasmids pMT1 and pPCP1, respectively; Y. pseudotuberculosis-specific chromosomal gene opgG; and 18S ribosomal RNA gene as an internal control for flea DNA. All targets showed 100% specificity and high sensitivity with limits of detection ranging from 1 fg to 100 fg, with Y. pestis-specific pst as the most sensitive target. Using the assay, Y. pestis strains were differentiated 100% by their known plasmid profiles. Testing Y. pestis and Y. pseudotuberculosis-spiked flea DNA showed there is no interference from flea DNA on the amplification of targeted genes. Finally, we applied the assay for testing 102 fleas collected from prairie dog burrows where prairie dog die-off was reported months before flea collection. All flea DNA was amplified by 18S rRNA; no Y. pseudotuberculosis was detected; one flea was positive for all Y. pestis-specific targets, confirming local Y. pestis transmission. Our results indicated the assay is sensitive and specific for the detection and differentiation of Y. pestis and Y. pseudotuberculosis. The assay can be used in field investigations for the rapid identification of the plague causative agent.

      2. Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17external icon
        Jackson S, Peret TC, Ziegler TT, Thornburg NJ, Besselaar T, Broor S, Barr I, Baumeister E, Chadha M, Chittaganpitch M, Darmaa B, Ellis J, Fasce R, Herring B, Herve K, Hirve S, Li Y, Pisareva M, Moen A, Naguib A, Palekar R, Potdar V, Siqueira M, Treurnicht F, Tivane A, Venter M, Wairagkar N, Zambon M, Zhang W.
        Influenza Other Respir Viruses. 2020 Jul 30.
        BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

      3. Efficacy of high-intensity resistance exercise becomes progressively compromised with aging. Previously, to investigate this, we developed a rodent model of high-intensity training consisting of stretch-shortening contractions (SSCs) and determined that following one month of training, young rats exhibit a robust stress response and 20% performance increase, whereas old rats display a muted stress response and 30% performance decrease. Whether these age-specific responses occur early in training and constitute primary factors in adaptation/maladaptation was not addressed. The aim of the present study was to characterize performance, remodeling, and stress response transcriptional profile 6-120 h following acute SSC exposure. For young rats, the stress response pathway was highly regulated (≥20 differentially expressed genes at each time point) and was accompanied by robust DNA demethylation, tissue remodeling, and isometric torque recovery. For old rats, a muted transcriptional profile (13 and 2 differentially expressed genes at 6 and 120 h, respectively) coincided with deficiencies in demethylation, muscle remodeling, and torque recovery. These findings occurred in the context of heightened chronic levels of stress response gene expression with aging. This demonstrates that age-related constitutive elevations in stress response gene expression was accompanied by diminished SSC-induced responsiveness in epigenomic regulation and tissue remodeling.

      4. An optimized reverse genetics system suitable for efficient recovery of simian, human and murine-like rotavirusesexternal icon
        Sanchez-Tacuba L, Feng N, Meade NJ, Mellits KH, Jais PH, Yasukawa LL, Resch TK, Jiang B, Lopez S, Ding S, Greenberg HB.
        J Virol. 2020 Aug 5.
        An entirely plasmid-based reverse genetics (RG) system was recently developed for rotavirus (RV), opening new avenues for in-depth molecular dissection of RV biology, immunology, and pathogenesis. Several improvements to further optimize the RG efficiency have now been described. However, only a small number of individual RV strains have been recovered to date. None of the current methods have supported the recovery of murine RV, impeding the study of RV replication and pathogenesis in an in vivo suckling mouse model. Here, we describe useful modifications to the RG system that significantly improve rescue efficiency of multiple RV strains. In addition to the 11 RVA segment-specific (+)ssRNAs, a chimeric plasmid was transfected, from which the capping enzyme NP868R of African swine fever virus (ASFV) and the T7 RNA polymerase were expressed. Secondly, a genetically modified MA104 cell line was used in which several compounds of the innate immune were degraded. Using this RG system, we successfully recovered the simian RV RRV strain, the human RV CDC-9 strain, a reassortant between murine RV D6/2 and simian RV SA11 strains, and several reassortants and reporter RVs. All these recombinant RVs were rescued at a high efficiency (≥80% success rate) and could not be reliably rescued using several recently published RG strategies (<20%). This improved system represents an important tool and great potential for the rescue of other hard-to-recover RV strains such as low replicating attenuated vaccine candidates or low cell culture passage clinical isolates from humans or animals.IMPORTANCE Group A rotavirus (RV) remains as the single most important cause of severe acute gastroenteritis among infants and young children worldwide. An entirely plasmid-based reverse genetics (RG) system was recently developed opening new ways for in-depth molecular study of RV. Despite several improvements to further optimize the RG efficiency, it has been reported that current strategies do not enable the rescue of all cultivatable RV strains. Here, we described helpful modification to the current strategies and established a tractable RG system for the rescue of the simian RRV strain, the human CDC-9 strain and a murine-like RV strain, which is suitable for both in vitro and in vivo studies. This improved RV reverse genetics system will facilitate study of RV biology in both in vitro and in vivo systems that will facilitate the improved design of RV vaccines, better antiviral therapies and expression vectors.

    • Maternal and Child Health
      1. Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defectsexternal icon
        Anderson KN, Lind JN, Simeone RM, Bobo WV, Mitchell AA, Riehle-Colarusso T, Polen KN, Reefhuis J.
        JAMA Psychiatry. 2020 Aug 5.
        IMPORTANCE: Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks. OBJECTIVE: To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions. DESIGN, SETTING, AND PARTICIPANTS: The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection. EXPOSURES: Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants. MAIN OUTCOMES AND MEASURES: We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period. RESULTS: This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83). CONCLUSIONS AND RELEVANCE: We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.

      2. Increasing early childhood screening in primary care through a quality improvement collaborativeexternal icon
        Flower KB, Massie S, Janies K, Bassewitz JB, Coker TR, Gillespie RJ, Macias MM, Whitaker TM, Zubler J, Steinberg D, DeStigter L, Earls MF.
        Pediatrics. 2020 Aug 7.
        OBJECTIVES: Multiple early childhood screenings are recommended, but gaps persist in implementation. Our aim for this project was to improve screening, discussion, referral, and follow-up of development, autism spectrum disorder (ASD), maternal depression, and social determinants of health (SDoH) to 90% by July 2018. METHODS: This 1-year national quality improvement collaborative involved 19 pediatric primary care practices. Supported by virtual and in-person learning opportunities, practice teams implemented changes to early childhood screening. Monthly chart reviews were used to assess screening, discussion, referral, and follow-up for development, ASD, maternal depression, and SDoH. Parent surveys were used to assess parent-reported screening and referral and/or resource provision. Practice self-ratings and team surveys were used to assess practice-level changes. RESULTS: Participating practices included independent, academic, hospital-affiliated, and multispecialty group practices and community health centers in 12 states. The collaborative met development and ASD screening goals of >90%. Largest increases in screening occurred for maternal depression (27% to 87%; +222%; P < .001) and SDoH (26% to 76%; +231%; P < .001). Statistically significant increases in discussion of results occurred for all screening areas. For referral, significant increases were seen for development (53% to 86%; P < .001) and maternal depression (23% to 100%; P = .008). Parents also reported increased screening and referral and/or resource provision. Practice-level changes included improved systems to support screening. CONCLUSIONS: Practices successfully implemented multiple screenings and demonstrated improvement in subsequent discussion, referral, and follow-up steps. Continued advocacy for adequate resources to support referral and follow-up is needed to translate increased screening into improved health outcomes.

      3. The impact of supply-side and demand-side interventions on use of antenatal and maternal services in western Kenya: a qualitative studyexternal icon
        Hirai M, Morris J, Luoto J, Ouda R, Atieno N, Quick R.
        BMC Pregnancy Childbirth. 2020 Aug 8;20(1):453.
        BACKGROUND: Antenatal care (ANC) and delivery by skilled providers have been well recognized as effective strategies to prevent maternal and neonatal mortality. ANC and delivery services at health facilities, however, have been underutilized in Kenya. One potential strategy to increase the demand for ANC services is to provide health interventions as incentives for pregnant women. In 2013, an integrated ANC program was implemented in western Kenya to promote ANC visits by addressing both supply- and demand-side factors. Supply-side interventions included nurse training and supplies for obstetric emergencies and neonatal resuscitation. Demand-side interventions included SMS text messages with appointment reminders and educational contents, group education sessions, and vouchers to purchase health products. METHODS: To explore pregnant mothers' experiences with the intervention, ANC visits, and delivery, we conducted focus group discussions (FGDs) at pre- and post-intervention. A total of 19 FGDs were held with pregnant mothers, nurses, and community health workers (CHWs) during the two assessment periods. We performed thematic analyses to highlight study participants' perceptions and experiences. RESULTS: FGD data revealed that pregnant women perceived the risks of home-based delivery, recognized the benefits of facility-based delivery, and were motivated by the incentives to seek care despite barriers to care that included poverty, lack of transport, and poor treatment by nurses. Nurses also perceived the value of incentives to attract women to care but described obstacles to providing health care such as overwork, low pay, inadequate supplies and equipment, and insufficient staff. CHWs identified the utility and limitations of text messages for health education. CONCLUSIONS: Future interventions should ensure that adequate workforce, training, and supplies are in place to respond to increased demand for maternal and child health services stimulated by incentive programs.

    • Nutritional Sciences
      1. Intraindividual double burden of overweight and micronutrient deficiencies or anemia among preschool childrenexternal icon
        Engle-Stone R, Guo J, Ismaily S, Addo OY, Ahmed T, Oaks B, Suchdev PS, Flores-Ayala R, Williams AM.
        Am J Clin Nutr. 2019 Aug 1;112(Supplement_1):478s-487s.
        BACKGROUND: Child overweight prevalence is increasing globally, but micronutrient deficiencies persist. OBJECTIVES: We aimed to 1) describe the prevalence and distribution of intraindividual double burden of malnutrition (DBM), defined as coexistence of overweight or obesity (OWOB) and either micronutrient deficiencies or anemia, among preschool children; 2) assess the independence of DBM components, e.g., whether the prevalence of DBM is greater than what would be expected by chance; and 3) identify predictors of intraindividual DBM, to guide intervention targeting. METHODS: We analyzed data from 24 population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (separately by survey; n = 226 to n = 7166). We defined intraindividual DBM as coexisting OWOB and ≥1 micronutrient deficiency [e.g., Micronutrient Deficiency Index (MDI) > 0; DBM-MDI] or anemia (DBM-Anemia). We assessed independence of DBM components with the Rao-Scott chi-square test and examined predictors of DBM and its components with logistic regression. RESULTS: DBM prevalence ranged from 0% to 9.7% (median: 2.5%, DBM-MDI; 1.4%, DBM-Anemia), reflecting a lower prevalence of OWOB (range: 0%-19.5%) than of micronutrient deficiencies and anemia, which exceeded 20% in most surveys. OWOB was generally not significantly associated with micronutrient deficiencies or anemia. In more than half of surveys, children 6-23 mo of age, compared with ≥24 mo, had greater adjusted odds of DBM-Anemia, anemia, and micronutrient deficiencies. Child sex and household socioeconomic status, urban location, and caregiver education did not consistently predict DBM or its components. CONCLUSIONS: Intraindividual DBM among preschool children was low but might increase as child OWOB increases. The analysis does not support the hypothesis that DBM components cluster within individuals, suggesting that population-level DBM may be addressed by programs to reduce DBM components without targeting individuals with DBM.

      2. BACKGROUND: Accurate assessment of iron and vitamin A status is needed to inform public health decisions, but most population-level iron and vitamin A biomarkers are independently influenced by inflammation. OBJECTIVES: We aimed to assess the reproducibility of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) regression approach to adjust iron [ferritin, soluble transferrin receptor (sTfR)] and vitamin A [retinol-binding protein (RBP), retinol] biomarkers for inflammation (α-1-acid glycoprotein and C-reactive protein). METHODS: We conducted a sensitivity analysis comparing unadjusted and adjusted estimates of iron and vitamin A deficiency using the internal-survey regression approach from BRINDA phase 1 (16 surveys in children, 10 surveys in women) and 13 additional surveys for children and women (BRINDA phase 2). RESULTS: The relations between inflammation and iron or vitamin A biomarkers were statistically significant except for vitamin A biomarkers in women. Heterogeneity of the regression coefficients across surveys was high. Among children, internal-survey adjustments increased the estimated prevalence of depleted iron stores (ferritin <12 µg/L) by a median of 11 percentage points (pp) (24 pp and 9 pp in BRINDA phase 1 and phase 2, respectively), whereas estimates of iron-deficient erythropoiesis (sTfR >8.3 mg/L) decreased by a median of 15 pp (15 pp and 20 pp in BRINDA phase 1 and phase 2, respectively). Vitamin A deficiency (RBP <0.7 µmol/L or retinol <0.7 µmol/L) decreased by a median of 14 pp (18 pp and 8 pp in BRINDA phase 1 and phase 2, respectively) in children. Adjustment for inflammation in women resulted in smaller differences in estimated iron deficiency than in children. CONCLUSIONS: Our findings are consistent with previous BRINDA conclusions that not accounting for inflammation may result in an underestimation of iron deficiency and overestimation of vitamin A deficiency. Research is needed to understand the etiology of the heterogeneity in the regression coefficients before a meta-analyzed regression correction can be considered.

      3. Intraindividual double burden of overweight or obesity and micronutrient deficiencies or anemia among women of reproductive age in 17 population-based surveysexternal icon
        Williams AM, Guo J, Addo OY, Ismaily S, Namaste SM, Oaks BM, Rohner F, Suchdev PS, Young MF, Flores-Ayala R, Engle-Stone R.
        Am J Clin Nutr. 2019 Aug 1;112(Supplement_1):468s-477s.
        BACKGROUND: Rising prevalence of overweight/obesity (OWOB) alongside persistent micronutrient deficiencies suggests many women face concomitant OWOB and undernutrition. OBJECTIVES: We aimed to 1) describe the prevalence of the double burden of malnutrition (DBM) among nonpregnant women of reproductive age, defined as intraindividual OWOB and either ≥1 micronutrient deficiency [micronutrient deficiency index (MDI) > 0; DBM-MDI] or anemia (DBM-anemia); 2) test whether the components of the DBM were independent; and 3) identify factors associated with DBM-MDI and DBM-anemia. METHODS: With data from 17 national surveys spanning low- and middle-income countries (LMICs) and high-income countries from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (n = 419 to n = 9029), we tested independence of over- and undernutrition using the Rao-Scott chi-square test and examined predictors of the DBM and its components using logistic regression for each survey. RESULTS: Median DBM-MDI was 21.9% (range: 1.6%-39.2%); median DBM-anemia was 8.6% (range: 1.0%-18.6%). OWOB and micronutrient deficiencies or anemia were independent in most surveys. Where associations existed, OWOB was negatively associated with micronutrient deficiencies and anemia in LMICs. In 1 high-income country, OWOB women were more likely to experience micronutrient deficiencies and anemia. Age was consistently positively associated with OWOB and the DBM, whereas the associations with other sociodemographic characteristics varied. Higher socioeconomic status tended to be positively associated with OWOB and the DBM in LMICs, whereas in higher-income countries the association was reversed. CONCLUSIONS: The independence of OWOB and micronutrient deficiencies or anemia within individuals suggests that these forms of over- and undernutrition may have unique etiologies. Decision-makers should still consider the prevalence, consequences, and etiology of the individual components of the DBM as programs move towards double-duty interventions aimed at addressing OWOB and undernutrition simultaneously.

      4. Association between anemia and household water source or sanitation in preschool children: the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) projectexternal icon
        Yu EX, Addo OY, Williams AM, Engle-Stone R, Ou J, Huang W, Guo J, Suchdev PS, Young MF.
        Am J Clin Nutr. 2019 Aug 1;112(Supplement_1):488s-497s.
        BACKGROUND: The associations between anemia and household water source and sanitation remain unclear. OBJECTIVES: We aimed to assess the associations between anemia and household water source or sanitation in preschool children (PSC; age 6-59 mo) using population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. METHODS: We analyzed national and subnational data from 21 surveys, representing 19 countries (n = 35,963). Observations with hemoglobin (Hb) and ≥1 variable reflecting household water source or sanitation were included. Anemia was defined as an altitude-adjusted Hb concentration <110 g/L. Household water source and sanitation variables were dichotomized as "improved" or "unimproved." Poisson regressions with robust variance estimates were conducted for each survey, adjusting for child sex, age, household socioeconomic status, maternal education, and type of residence. RESULTS: Access to an improved water source and improved sanitation ranged from 29.9% (Burkina Faso) to 98.4% (Bangladesh, 2012), and from 0.2% (Kenya, 2007) to 97.4% (Philippines), respectively. Prevalence of anemia ranged from 20.1% (Nicaragua) to 83.5% (Bangladesh, 2010). Seven surveys showed negative associations between anemia and improved sanitation. Three surveys showed association between anemia and improved water, with mixed directions. Meta-analyses suggested a protective association between improved household sanitation and anemia [adjusted prevalence ratio (aPR) = 0.88; 95% CI: 0.79, 0.98], and no association between improved household water and anemia (aPR = 1.00; 95% CI: 0.91, 1.10). There was heterogeneity across surveys for sanitation (P < 0.01; I2 = 66.3%) and water (P < 0.01; I2 = 55.8%). CONCLUSIONS: Although improved household sanitation was associated with reduced anemia prevalence in PSC in some surveys, this association was not consistent. Access to an improved water source in general had no association with anemia across surveys. Additional research could help clarify the heterogeneity between these conditions across countries to inform anemia reduction programs.

    • Occupational Safety and Health
      1. OBJECTIVES: We explored the impact of workplace injury on receiving opioid prescriptions from employer-sponsored private group health insurances (GHI) and how long injured workers receive opioid prescriptions after injury. METHODS: We used the difference-in-differences method and MarketScan® databases for the years 2013 to 2015. RESULTS: Estimated odds for injured workers relative to non-injured workers to receive opioid prescriptions from the GHI within 60 and 180 days from the index date of injury were 4.9 and 1.5, respectively. In addition, the number of opioid prescriptions received within 60 days of injury was 2.5 times higher. CONCLUSION: Workplace injury could be a risk factor for both short and long-term prescription opioid use. Studies that use only workers' compensation medical claim data likely underestimate the magnitude of the impact of workplace injuries on opioid prescriptions.

      2. The Occupational Information Network (O*NET) database has been used as a valuable source of occupational exposure information. Although good agreement between O*NET and self-reported measures has been reported, little attention has been paid to O*NET's utility in racially/ethnically diverse samples. Because O*NET offers job-level information, if different racial groups have different experiences under the same job title, O*NET measure would introduce systematic measurement error. Using the General Social Survey data (n = 7,041; 437 occupations), we compared self-report and O*NET-derived measures of job control in their associations with self-rated health (SRH) for non-Hispanic whites and racial/ethnic minorities. The correlation between self-report and O*NET job control measures were moderate for all gender-race groups (Pearson's r = .26 - .40). However, the logistic regression analysis showed that the association between O*NET job control and SRH was markedly weaker for racial/ethnic minorities than for non-Hispanic whites. The self-reported job control was associated with SRH in similar magnitudes for both groups, which precluded the possibility that job control was relevant only for non-Hispanic whites. O*NET may not capture job experience for racial/ethnic minorities, and thus its utility depends on the racial/ethnic composition of the sample.

      3. Introduction: Injuries at work may negatively influence mental health due to lost or reduced working hours and financial burden of treatment. Our objective was to investigate, in U.S. workers (a) the prevalence of serious psychological distress (SPD) by injury status (occupational, non-occupational, and no injury) and injury characteristics, and (b) the association between injury status and SPD. Methods: Self-reported injuries within the previous three months were collected annually for 225,331 U.S. workers in the National Health Interview Survey (2004–2016). Psychological distress during the past 30 days was assessed using the Kessler 6 (K6) questions with Likert-type scale (0–4, total score range: 0–24). SPD was defined as K6 ≥ 13. Prevalence ratios (PR) from fitted logistic regression models were used to assess relationships between injury and SPD after controlling for covariates. Results: The prevalence of SPD was 4.74%, 3.58%, and 1.56% in workers reporting occupational injury (OI), non-occupational injury (NOI), and no injury, respectively. Workers with head and neck injury had the highest prevalence of SPD (Prevalence: OI = 7.71%, NOI = 6.17%), followed by workers with scrape/bruise/burn/bite (6.32% for those with OI). Workers reporting OI were two times more likely to have SPD compared to those without injury (PR = 2.19, 95%CI: 1.62–2.96). However, there was no significant difference in SPD between workers with OI and workers with NOI (PR = 0.98, 95%CI: 0.65–1.48). Conclusion: The prevalence of SPD varied by injury status with the highest being among workers reporting OI. We found that the workers reporting OI were significantly more likely to have SPD than those without injury, but not more than those with NOI. Practical Applications: Mental health management programs by employers are necessary for workers who are injured in the workplace.

    • Occupational Safety and Health - Mining
      1. An improved method to calculate the heat release rate of a mine fire in underground minesexternal icon
        Zhou L, Yuan L, Thomas R, Bahrami D, Rowland J.
        Min Metall Explor. 2020 .
        Continuous monitoring of carbon monoxide and other fire-related parameters by means of an atmospheric monitoring system (AMS) has been used by the mining industry for early fire detection in underground mines. The National Institute for Occupational Safety and Health (NIOSH) initiated a project to integrate real-time AMS sensor data with NIOSH’s mine fire simulation program, MFIRE 3.0, to simulate and predict the spread of smoke that would provide assistance to mine fire emergency response personnel. Determining the heat release rate of a fire using the monitored sensor data was a critical component of the successful completion of this project. NIOSH researchers developed a direct method to calculate the heat release rate when a fire is within close range of sensors. However, this method is only applicable to the case where a fire occurs in AMS-monitored airways. This paper presents an improved method for determining the fire heat release rate for complicated scenarios where a fire is distant from sensors and airflow splits and merges are present. The method was validated using a full-scale diesel fuel fire test conducted in the Safety Research Coal Mine at the Pittsburgh Mining Research Division and can help mine operators and safety personnel make informed decisions during a fire emergency.

    • Parasitic Diseases
      1. A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Burkina Fasoexternal icon
        Gutman JR, Stephens DK, Tiendrebeogo J, Badolo O, Dodo M, Burke D, Williamson J, Vibbert K, Youll SJ, Savadogo Y, Brieger WR.
        Malar J. 2020 Aug 5;19(1):282.
        BACKGROUND: Malaria in pregnancy is responsible for 8-14% of low birth weight and 20% of stillbirths in sub-Saharan Africa. To prevent these adverse consequences, the World Health Organization recommends intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine be administered at each ANC visit starting as early as possible in the second trimester. Global IPTp coverage in targeted countries remains unacceptably low. Community delivery of IPTp was explored as a means to improve coverage. METHODS: A cluster randomized, controlled trial was conducted in 12 health facilities in a 1:1 ratio to either an intervention group (IPTp delivered by CHWs) or a control group (standard practice, with IPTp delivered at HFs) in three districts of Burkina Faso to assess the effect of IPTp administration by community health workers (CHWs) on the coverage of IPTp and antenatal care (ANC). The districts and facilities were purposively selected taking into account malaria epidemiology, IPTp coverage, and the presence of active CHWs. Pre- and post-intervention surveys were carried out in March 2017 and July-August 2018, respectively. A difference in differences (DiD) analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. RESULTS: Altogether 374 and 360 women were included in the baseline and endline surveys, respectively. At baseline, women received a median of 2.1 doses; by endline, women received a median of 1.8 doses in the control group and 2.8 doses in the intervention group (p-value < 0.0001). There was a non-statistically significant increase in the proportion of women attending four ANC visits in the intervention compared to control group (DiD = 12.6%, p-value = 0.16). By the endline, administration of IPTp was higher in the intervention than control, with a DiD of 17.6% for IPTp3 (95% confidence interval (CI) - 16.3, 51.5; p-value 0.31) and 20.0% for IPTp4 (95% CI - 7.2, 47.3; p-value = 0.15). CONCLUSIONS: Community delivery of IPTp could potentially lead to a greater number of IPTp doses delivered, with no apparent decrease in ANC coverage.

      2. Contribution of hospitals to the occurrence of enteric protists in urban wastewaterexternal icon
        Jiang W, Roellig DM, Li N, Wang L, Guo Y, Feng Y, Xiao L.
        Parasitol Res. 2020 Sep;119(9):3033-3040.
        We assessed the potential contribution of hospitals to contaminations of wastewater by enteric protists, including Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in raw wastewater. Wastewater samples were collected from storage tanks in two hospitals and one associated wastewater treatment plant in Shanghai, China, from March to November 2009. Enteric pathogens were detected and identified using PCR and DNA sequencing techniques. Among a total of 164 samples analyzed, 31 (18.9%), 45 (27.4%), and 122 (74.4%) were positive for Cryptosporidium spp., G. duodenalis, and E. bieneusi, respectively. Altogether, three Cryptosporidium species, four G. duodenalis assemblages, and 12 E. bieneusi genotypes were detected. Cryptosporidium hominis, G. duodenalis sub-assemblage AII, and E. bieneusi genotype D were the dominant ones in wastewater from both hospitals and the wastewater treatment plant. A similar distribution in genotypes of enteric pathogens was seen between samples from hospitals and the wastewater treatment plant, suggesting that humans are one of the major sources for these pathogens and hospitals are important contributors of enteric parasites in urban wastewater. Data from this study might be useful in the formulation of preventive measures against environmental contamination of waterborne pathogens.

      3. School-based sero-surveys to assess the validity of using routine health facility data to target malaria interventions in the Central Highlands of Madagascarexternal icon
        Steinhardt L, Ravaoarisoa E, Wiegand R, Harimanana A, Hedje J, Cotte AH, Zigirumugabe S, Kesteman T, Rasoloharimanana TL, Rakotomalala E, Randriamoramanana AM, Rakotondramanga JM, Razanatsiorimalala S, Mercereau-Puijalon O, Perraut R, Ratsimbasoa A, Butts J, Rogier C, Piola P, Randrianarivelojosia M, Vigan-Womas I.
        J Infect Dis. 2020 Aug 6.
        BACKGROUND: In low-malaria-transmission areas of Madagascar, annual parasite incidence (API) from routine data has been used to target indoor residual spraying at sub-district commune levels. To assess validity of this approach, we conducted school-based serological surveys and health facility (HF) data quality assessments in seven districts to compare API to "gold-standard" commune-level serological measures. METHODS: At two primary schools in each of 93 communes, 60 students were randomly selected along with parents and teachers. Capillary blood was drawn for rapid diagnostic tests (RDTs) and serology. Multiplex bead-based immunoassays to detect antibodies to five Plasmodium falciparum antigens were conducted, and finite mixture models used to characterize seronegative and seropositive populations. Reversible catalytic models generated commune-level annual seroconversion rates (SCRs). HF register data were abstracted to assess completeness and accuracy. RESULTS: RDT positivity from 12,770 samples was 0.5%. Seroprevalence to tested antigens ranged from 17.9% (MSP-1) to 59.7% (PF13). Median commune-level SCR was 0.0108 (range: 0.001, 0.075). Compared to SCRs, API identified 71% (95% CI: 51%, 87%) of the 30% highest-transmission communes; sensitivity declined at lower levels. Routine data accuracy did not substantially affect API performance. CONCLUSIONS: API performs reasonably well at identifying higher-transmission communes, but sensitivity declined at lower transmission levels.

      4. Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission: A WWARN individual patient meta-analysisexternal icon
        Stepniewska K, Humphreys GS, Gonçalves BP, Craig E, Gosling R, Guerin PJ, Price RN, Barnes KI, Raman J, Smit MR, D'Alessandro U, Stone WJ, Bjorkman A, Samuels AM, Arroyo-Arroyo MI, Bastiaens GJ, Brown JM, Dicko A, El-Sayed BB, Elzaki SG, Eziefula AC, Kariuki S, Kwambai TK, Maestre AE, Martensson A, Mosha D, Mwaiswelo RO, Ngasala BE, Okebe J, Roh ME, Sawa P, Tiono AB, Chen I, Drakeley CJ, Bousema T.
        J Infect Dis. 2020 Aug 11.
        BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

      5. Modelling the incremental benefit of introducing malaria screening strategies to antenatal care in Africaexternal icon
        Walker PG, Cairns M, Slater H, Gutman J, Kayentao K, Williams JE, Coulibaly SO, Khairallah C, Taylor S, Meshnick SR, Hill J, Mwapasa V, Kalilani-Phiri L, Bojang K, Kariuki S, Tagbor H, Griffin JT, Madanitsa M, Ghani AC, Desai M, Ter Kuile FO.
        Nat Commun. 2020 Jul 30;11(1):3799.
        Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess whether screening at antenatal visits improves upon current intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP). We estimate that RDTs in primigravidae at first antenatal visit are substantially more sensitive than in non-pregnant adults (OR = 17.2, 95% Cr.I. 13.8-21.6), and that sensitivity declines in subsequent visits and with gravidity, likely driven by declining susceptibility to placental infection. Monthly ISTp with standard RDTs, even with highly effective drugs, is not superior to monthly IPTp-SP. However, a hybrid strategy, recently adopted in Tanzania, combining testing and treatment at first visit with IPTp-SP may offer benefit, especially in areas with high-grade SP resistance. Screening and treatment in the first trimester, when IPTp-SP is contraindicated, could substantially improve pregnancy outcomes.

    • Substance Use and Abuse
      1. Association of tobacco control policies with cigarette smoking among school youth aged 13-15 years in the Philippines, 2000-2015external icon
        Arrazola RA, Dutra LM, Twentyman E, Seidenberg AB, Hemendez-Gonzales R, Ahluwalia IB.
        Tob Prev Cessat. 2020 ;6:35.
        INTRODUCTION: In 2003, the Philippines implemented legislation that prohibited the sale of tobacco products to youth, placed text warning labels on tobacco products, and prohibited tobacco smoking in public places. This study assessed if this legislation was associated with reduced cigarette smoking among youth. METHODS: Data came from the 2000-2015 Philippines Global Youth Tobacco Survey (GYTS), a nationally representative, cross-sectional survey of students aged 13-15 years. GYTS data were used to determine associations between tobacco control legislation and current, past 30-day, current cigarette smoking (CCS). Logistic regression models were adjusted for age, sex, current other tobacco product use (COTPU), and price per cigarette stick (PPCS). RESULTS: In the unadjusted model, the 2003 legislation was not associated with CCS (OR=0.77; 95% CI: 0.54-1.10). After adjusting for covariates, it was negatively associated (AOR=0.65; 95% CI: 0.53-0.80). Being 15 years old (OR=1.31; 95% CI: 1.08-1.58), male (OR=2.54; 95% CI: 2.17-2.98), and COTPU (OR=4.12; 95% CI: 3.47-4.91) were positively associated with CCS in unadjusted models. In adjusted models, being 14 years old (AOR=1.29; 95% CI: 1.08-1.53), 15 years old (AOR=1.55; 95% CI: 1.31-1.84), male (AOR=2.49; 95% CI: 2.13-2.91), and COTPU (AOR=3.96; 95% CI: 3.32-4.73), were associated with CCS. PPCS was not associated with CCS in either the unadjusted (OR=1.32; 95% CI: 0.82-2.11) or adjusted (AOR=1.32; 95% CI: 0.79-2.18) models. CONCLUSIONS: After adjusting for covariates, the 2003 tobacco control legislation was associated with lower current cigarette smoking, but price per cigarette stick was not.

      2. A brief overview of the national outbreak of e-cigarette, or vaping, product use ─associated lung injury (EVALI) and the primary causesexternal icon
        Kiernan E, Click ES, Melstrom P, Evans ME, Layer MR, Weissman DN, Reagan-Steiner S, Wiltz JL, Hocevar S, Goodman AB, Twentyman E.
        Chest. 2020 Aug 3.

      3. Patterns and related factors of bidi smoking in Indiaexternal icon
        Mbulo L, Palipudi KM, Smith T, Yin S, Munish VG, Sinha DN, Gupta PC, Swasticharan L.
        Tob Prev Cessat. 2020 ;6:28.
        INTRODUCTION: Bidis are the most commonly smoked tobacco product in India. Understanding bidi smoking is important to reducing overall tobacco smoking and health-related consequences in India. We analyzed 2009-2010 and 2016-2017 Global Adult Tobacco Survey (GATS) India data to examine bidi smoking and its associated sociodemographic correlates and perceptions of dangers of smoking. METHODS: GATS is a nationally representative household survey of adults aged ≥15 years, designed to measure tobacco use and tobacco control indicators. Current bidi smoking was defined as current smoking of one or more bidis during a usual week. We computed bidi smoking prevalence estimates and relative change during 2009-2010 and 2016-2017. Used pooled multilevel logistic regression to identify individual-level determinants of bidi smoking and neighborhood-level and state-level variations. RESULTS: Overall, 9.2% and 7.7% of adults smoked bidis in India during 2009-2010 and 2016-2017, respectively, reflecting 16.4% significant relative decline. In pooled analysis, male, older age, rural residence, lower education level, lower wealth index, less knowledge about harms of smoking, and survey year were associated with increased odds of bidi smoking. Results also showed variance in odds of smoking bidis is associated with neighborhood (15.9%) and state (31.8%) level. CONCLUSIONS: Higher odds of bidi smoking were found among males, older age groups, and among those with lower socioeconomic status. Accordingly, health education interventions designed for these groups across India and other population-level interventions, such as WHO recommendation on increasing price on tobacco products, could help reduce bidi smoking. In addition, state/neighborhood-specific interventions could also help address differential bidi smoking across India.

      4. Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case seriesexternal icon
        Reagan-Steiner S, Gary J, Matkovic E, Ritter JM, Shieh WJ, Martines RB, Werner AK, Lynfield R, Holzbauer S, Bullock H, Denison AM, Bhatnagar J, Bollweg BC, Patel M, Evans ME, King BA, Rose DA, Baldwin GT, Jones CM, Krishnasamy V, Briss PA, Weissman DN, Meaney-Delman D, Zaki SR.
        Lancet Respir Med. 2020 Aug 4.
        BACKGROUND: Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. METHODS: Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. FINDINGS: 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. INTERPRETATION: Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. FUNDING: US Centers for Disease Control and Prevention.

      5. Temporal trends in online posts about vaping of cannabis productsexternal icon
        Sumner SA, Haegerich TM, Jones CM.
        J Addict Med. 2020 Aug 4.

    • Zoonotic and Vectorborne Diseases
      1. Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, March 2016-March 2019external icon
        Alzahrani A, Kujawski SA, Abedi GR, Tunkar S, Biggs HM, Alghawi N, Jokhdar H, Assiri AM, Watson JT.
        Emerg Infect Dis. 2020 Jul;26(7):1571-1574.
        During March 2016-March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response.

      2. Evaluation for arboviral infection among children hospitalized in Colorado with aseptic meningitis and encephalitisexternal icon
        Gould CV, Messacar K, Dominguez SR, Panella A, Tobolowsky F, Fischer M.
        Pediatr Infect Dis J. 2020 Aug 5.
        Among 39 children hospitalized in Colorado with aseptic meningitis or encephalitis, 16 (41%) had an etiology identified, including 2 (5%) with West Nile virus infection. Despite extensive testing, no other arboviral infections were identified. Arboviral infection should be considered in children with neuroinvasive disease during arboviral season with testing directed toward viruses endemic to the region and type of exposure.

      3. Zika virus detection with 2013 serosurvey, Mombasa, Kenyaexternal icon
        Hunsperger E, Odhiambo D, Makio A, Alando M, Ochieng M, Omballa V, Munyua P, Bigogo G, Njenga MK, Widdowson MA.
        Emerg Infect Dis. 2020 Jul;26(7):1603-1605.
        Acute Zika virus (ZIKV) infection has not been confirmed in Kenya. In 2018, we used specimens collected in a 2013 dengue serosurvey study in Mombasa to test for ZIKV IgM. We confirmed specific ZIKV IgM positivity in 5 persons. These results suggest recent ZIKV transmission in the coastal region of Kenya.

      4. Zika virus disease and pregnancy outcomes in Colombiaexternal icon
        Ospina ML, Tong VT, Gonzalez M, Valencia D, Mercado M, Gilboa SM, Rodriguez AJ, Tinker SC, Rico A, Winfield CM, Pardo L, Thomas JD, Avila G, Villanueva JM, Gomez S, Jamieson DJ, Prieto F, Meaney-Delman D, Pacheco O, Honein MA.
        N Engl J Med. 2020 Aug 6;383(6):537-545.
        BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

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