Issue 30, August 24, 2021

CDC Science Clips: Volume 13, Issue 30, August 24, 2021

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Disparities in hemoglobin A(1c) testing during the transition to adulthood and association with diabetes outcomes in youth-onset type 1 and type 2 Diabetes: The SEARCH for Diabetes in Youth Studyexternal icon
        Sauder KA, Stafford JM, Ehrlich S, Lawrence JM, Liese AD, Marcovina S, Mottl AK, Pihoker C, Saydah S, Shah AS, D'Agostino RB, Dabelea D.
        Diabetes Care. 2021 Aug 10.
        OBJECTIVE: To identify correlates of hemoglobin A(1c) (HbA(1c)) testing frequency and associations with HbA(1c) levels and microvascular complications in youth-onset diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years (n=1,885 type 1, n=230 type 2) and 13 years (n=649 type 1, n = 84 type 2) diabetes duration. We identified correlates of reporting ≥3 HbA(1c) tests/year using logistic regression. We examined associations of HbA(1c) testing with HbA(1c) levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression. RESULTS: For type 1 diabetes, odds of reporting ≥3 HbA(1c) tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (odds ratio [OR] 0.91 [95% CI 0.88-0.95]), longer duration of diabetes (OR 0.90 [0.82-0.99]), not having a personal doctor (OR 0.44 [0.30-0.65]), and lapses in health insurance (OR 0.51 [0.27-0.96]). HbA(1c) testing ≥3 times/year over time was associated with lower HbA(1c) levels (OR -0.36% [-0.65 to -0.06]) and lower odds of microvascular complications (OR 0.64 [0.43-0.97]) at 13 years duration, but associations were attenuated after adjustment for HbA(1c) testing correlates (OR -0.17 [-0.46 to 0.13] and 0.70 [0.46-1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased the odds of reporting ≥3 HbA(1c) tests/year over time (OR 0.19 [0.06-0.63]), but HbA(1c) testing frequency was not associated with HbA(1c) levels or microvascular complications. CONCLUSIONS: We observed disparities in HbA(1c) testing frequency predominately by health care-related factors, which were associated with diabetes outcomes in type 1 diabetes.

    • Communicable Diseases
      • Cabotegravir for HIV prevention in cisgender men and transgender womenexternal icon
        Landovitz RJ, Donnell D, Clement ME, Hanscom B, Cottle L, Coelho L, Cabello R, Chariyalertsak S, Dunne EF, Frank I, Gallardo-Cartagena JA, Gaur AH, Gonzales P, Tran HV, Hinojosa JC, Kallas EG, Kelley CF, Losso MH, Madruga JV, Middelkoop K, Phanuphak N, Santos B, Sued O, Valencia Huamaní J, Overton ET, Swaminathan S, Del Rio C, Gulick RM, Richardson P, Sullivan P, Piwowar-Manning E, Marzinke M, Hendrix C, Li M, Wang Z, Marrazzo J, Daar E, Asmelash A, Brown TT, Anderson P, Eshleman SH, Bryan M, Blanchette C, Lucas J, Psaros C, Safren S, Sugarman J, Scott H, Eron JJ, Fields SD, Sista ND, Gomez-Feliciano K, Jennings A, Kofron RM, Holtz TH, Shin K, Rooney JF, Smith KY, Spreen W, Margolis D, Rinehart A, Adeyeye A, Cohen MS, McCauley M, Grinsztejn B.
        N Engl J Med. 2021 Aug 12;385(7):595-608.
        BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 number, NCT02720094.).

    • Genetics and Genomics
      • Comparative genomic and transcriptomic analysis of Naegleria fowleri clinical and environmental isolatesexternal icon
        Joseph SJ, Park S, Kelley A, Roy S, Cope JR, Ali IK.
        mSphere. 2021 Aug 11:e0063721.
        Out of over 40 species of Naegleria, which are free-living thermophilic amebae found in freshwater and soil worldwide, only Naegleria fowleri infects humans, causing primary amebic meningoencephalitis (PAM), a typically fatal brain disease. To understand the population structure of Naegleria species and the genetic relationships between N. fowleri isolates and to detect pathogenic factors, we characterized 52 novel clinical and environmental N. fowleri genomes and a single Naegleria lovaniensis strain, along with transcriptomic data for a subset of 37 N. fowleri isolates. Whole-genome analysis of 56 isolates from three Naegleria species (N. fowleri, N. lovaniensis, and Naegleria gruberi) identified several genes unique to N. fowleri that have previously been linked to the pathogenicity of N. fowleri, while other unique genes could be associated with novel pathogenicity factors in this highly fatal pathogen. Population structure analysis estimated the presence of 10 populations within the three Naegleria species, of which 7 populations were within N. fowleri. The whole-nuclear-genome (WNG) phylogenetic analysis showed an overall geographical clustering of N. fowleri isolates, with few exceptions, and provided higher resolution in identifying potential clusters of isolates beyond that of the traditional locus typing. There were only 34 genes that showed significant differences in gene expression between the clinical and environmental isolates. Genomic data generated in this study can be used for developing rapid molecular assays and to conduct future population-based global genomic analysis and will also be a valuable addition to genomic reference databases, where shotgun metagenomics data from routine water samples could be searched for the presence of N. fowleri strains. IMPORTANCE N. fowleri, the only known Naegleria species to infect humans, causes fatal brain disease. PAM cases from 1965 to 2016 showed <20 cases per year globally. Out of approximately 150 cases in North America since 1962, only four PAM survivors are known, yielding a >97% case fatality rate, which is critically high. Although the pathogenesis of N. fowleri has been studied for the last 50 years, pathogenetic factors that lead to human infection and breaching the blood-brain barrier remain unknown. In addition, little is known regarding the genomic diversity both within N. fowleri isolates and among Naegleria species. In this study, we generated novel genome sequences and performed comparative genomic and transcriptomic analysis of a set of 52 N. fowleri draft genome sequences from clinical and environmental isolates derived from all over the world in the last 53 years, which will help shape future genome-wide studies and develop sensitive assays for routine surveillance.

    • Health Disparities
      • Racial and ethnic disparities in multisystem inflammatory syndrome in children in the United States, March 2020 to February 2021external icon
        Stierman B, Abrams JY, Godfred-Cato SE, Oster ME, Meng L, Yip L, Patel P, Balachandran N, Prezzato E, Pierce T, Hsu KK, Burns M, Peterson Pompa X, Lauro P, Hartley A, Jones C, Gretsch S, Reid H, Lim S, Campbell AP, Belay ED.
        Pediatr Infect Dis J. 2021 Aug 10.
        BACKGROUND: The incidence of multisystem inflammatory syndrome in children (MIS-C) varies by race and ethnicity. This study assessed whether disparities in MIS-C in the United States by race and ethnicity exceed known disparities in coronavirus disease 2019 (COVID-19) incidence. METHODS: We compared the distribution of race and ethnicity among patients with MIS-C (aged <21 years, termed children) with onset March 2020 to February 2021 to that of children with COVID-19 and in the general population. Analysis was restricted to 369 counties with high completeness of race and ethnicity reporting for MIS-C and COVID-19. For each racial and ethnic group, observed numbers of patients with MIS-C were compared with expected numbers (observed/expected ratio) in children with COVID-19 and in the general population within these counties. RESULTS: Compared with children in the general population, MIS-C was more frequent among Hispanic (139% of expected) and non-Hispanic Black children (183%) and less frequent among non-Hispanic White (64%) and non-Hispanic Asian children (48%). Compared with children with COVID-19, MIS-C was more frequent in non-Hispanic Black children (207% of expected) and less frequent in non-Hispanic White children (68%); however, frequency was not different among Hispanic (102%) and non-Hispanic Asian (74%) children. CONCLUSIONS: Disparities in MIS-C by race and ethnicity exist, even after controlling for COVID-19 disparities and geographic variations. The high proportion of MIS-C among Hispanic children and low proportion among non-Hispanic Asian children align with COVID-19 rates, while the high proportion among non-Hispanic Black children and low proportion among non-Hispanic White children are not explainable by COVID-19 rates.

    • Immunity and Immunization
      • Global experience with rotavirus vaccinesexternal icon
        Burke RM, Tate JE, Parashar UD.
        J Infect Dis. 2021 Aug 10.
        Rotavirus is a major cause of severe pediatric diarrhea worldwide. In 2006, two live, oral rotavirus vaccines, Rotarix and RotaTeq, were licensed for use in infants and were rapidly adopted in many high- and middle-income settings where efficacy had been demonstrated in clinical trials. Following completion of additional successful trials in low-income settings, the World Health Organization (WHO) recommended rotavirus vaccination for all infants globally in 2009. In 2018, two new rotavirus vaccines, Rotasiil and Rotavac, were prequalified by WHO, further expanding global availability. As of March 2021, rotavirus vaccines have been introduced nationally in 106 countries. Since introduction, rotavirus vaccines have demonstrated effectiveness against severe disease and mortality, even among age groups not eligible for vaccination. Cross-genotypic protection has also been demonstrated, and the favorable benefit-risk profile of these vaccines continues to be confirmed via post-marketing surveillance. Ongoing research seeks to better understand reasons for the lower effectiveness observed in lower-resource settings, and to use these findings to optimize vaccine strategies worldwide.

    • Informatics
      • Current surveillance methods may not capture the full extent of COVID-19 spread in high-risk settings like food establishments. Thus, we propose a new method for surveillance that identifies COVID-19 cases among food establishment workers from news reports via web-scraping and natural language processing (NLP). First, we used web-scraping to identify a broader set of articles (n = 67,078) related to COVID-19 based on keyword mentions. In this dataset, we used an open-source NLP platform (ClarityNLP) to extract location, industry, case, and death counts automatically. These articles were vetted and validated by CDC subject matter experts (SMEs) to identify those containing COVID-19 outbreaks in food establishments. CDC and Georgia Tech Research Institute SMEs provided a human-labeled test dataset containing 388 articles to validate our algorithms. Then, to improve quality, we fine-tuned a pretrained RoBERTa instance, a bidirectional transformer language model, to classify articles containing ≥ 1 positive COVID-19 cases in food establishments. The application of RoBERTa decreased the number of articles from 67,078 to 1,112 and classified (≥ 1 positive COVID-19 cases in food establishments) articles with 88% accuracy in the human-labeled test dataset. Therefore, by automating the pipeline of web-scraping and COVID-19 case prediction using RoBERTa, we enable an efficient human in-the-loop process by which COVID-19 data could be manually collected from articles flagged by our model, thus reducing the human labor requirements. Furthermore, our approach could be used to predict and monitor locations of COVID-19 development by geography and could also be extended to other industries and news article datasets of interest. © 2021, Springer Nature Switzerland AG.

      • A modified public health automated case event reporting platform for enhancing electronic laboratory reports with clinical data: Design and implementation studyexternal icon
        Mishra N, Duke J, Karki S, Choi M, Riley M, Ilatovskiy AV, Gorges M, Lenert L.
        J Med Internet Res. 2021 Aug 11;23(8):e26388.
        BACKGROUND: Public health reporting is the cornerstone of public health practices that inform prevention and control strategies. There is a need to leverage advances made in the past to implement an architecture that facilitates the timely and complete public health reporting of relevant case-related information that has previously not easily been available to the public health community. Electronic laboratory reporting (ELR) is a reliable method for reporting cases to public health authorities but contains very limited data. In an earlier pilot study, we designed the Public Health Automated Case Event Reporting (PACER) platform, which leverages existing ELR infrastructure as the trigger for creating an electronic case report. PACER is a FHIR (Fast Health Interoperability Resources)-based system that queries the electronic health record from where the laboratory test was requested to extract expanded additional information about a case. OBJECTIVE: This study aims to analyze the pilot implementation of a modified PACER system for electronic case reporting and describe how this FHIR-based, open-source, and interoperable system allows health systems to conduct public health reporting while maintaining the appropriate governance of the clinical data. METHODS: ELR to a simulated public health department was used as the trigger for a FHIR-based query. Predetermined queries were translated into Clinical Quality Language logics. Within the PACER environment, these Clinical Quality Language logical statements were managed and evaluated against the providers' FHIR servers. These predetermined logics were filtered, and only data relevant to that episode of the condition were extracted and sent to simulated public health agencies as an electronic case report. Design and testing were conducted at the Georgia Tech Research Institute, and the pilot was deployed at the Medical University of South Carolina. We evaluated this architecture by examining the completeness of additional information in the electronic case report, such as patient demographics, medications, symptoms, and diagnoses. This additional information is crucial for understanding disease epidemiology, but existing electronic case reporting and ELR architectures do not report them. Therefore, we used the completeness of these data fields as the metrics for enriching electronic case reports. RESULTS: During the 8-week study period, we identified 117 positive test results for chlamydia. PACER successfully created an electronic case report for all 117 patients. PACER extracted demographics, medications, symptoms, and diagnoses from 99.1% (116/117), 72.6% (85/117), 70.9% (83/117), and 65% (76/117) of the cases, respectively. CONCLUSIONS: PACER deployed in conjunction with electronic laboratory reports can enhance public health case reporting with additional relevant data. The architecture is modular in design, thereby allowing it to be used for any reportable condition, including evolving outbreaks. PACER allows for the creation of an enhanced and more complete case report that contains relevant case information that helps us to better understand the epidemiology of a disease.

    • Injury and Violence
      • Unintentional injury deaths in children and youth, 2010–2019external icon
        West BA, Rudd RA, Sauber-Schatz EK, Ballesteros MF.
        J Saf Res. 2021 .
        Background: Unintentional injuries are the leading cause of death for children and youth aged 1–19 in the United States. The purpose of this report is to describe how unintentional injury death rates among children and youth aged 0–19 years have changed during 2010–2019. Method: CDC analyzed 2010–2019 data from the National Vital Statistics System (NVSS) to determine two-year average annual number and rate of unintentional injury deaths for children and youth aged 0–19 years by sex, age group, race/ethnicity, mechanism, county urbanization level, and state. Results: From 2010–2011 to 2018–2019, unintentional injury death rates decreased 11% overall—representing over 1,100 fewer annual deaths. However, rates increased among some groups—including an increase in deaths due to suffocation among infants (20%) and increases in motor-vehicle traffic deaths among Black children (9%) and poisoning deaths among Black (37%) and Hispanic (50%) children. In 2018–2019, rates were higher for males than females (11.3 vs. 6.6 per 100,000 population), children aged < 1 and 15–19 years (31.9 and 16.8 per 100,000) than other age groups, among American Indian or Alaska Native (AIAN) and Blacks than Whites (19.4 and 12.4 vs. 9.0 per 100,000), motor-vehicle traffic (MVT) than other causes of injury (4.0 per 100,000), and rates increased as rurality increased (6.8 most urban [large central metro] vs. 17.8 most rural [non-core/non-metro] per 100,000). From 2010–2011 to 2018–2019, 49 states plus DC had stable or decreasing unintentional injury death rates; death rates increased only in California (8%)—driven by poisoning deaths. Conclusion and Practical Application: While the overall injury death rates improved, certain subgroups and their caregivers can benefit from focused prevention strategies, including infants and Black, Hispanic, and AIAN children. Focusing effective strategies to reduce suffocation, MVT, and poisoning deaths among those at disproportionate risk could further reduce unintentional injury deaths among children and youth in the next decade. © 2021

    • Laboratory Sciences
      • Development, characterization and in vivo pharmacokinetic assessment of rectal suppositories containing combination antiretroviral drugs for HIV preventionexternal icon
        Jhunjhunwala K, Dobard CW, Sharma S, Makarova N, Holder A, Dinh C, Mitchell J, Wang L, Zhang J, Patel SK, Heneine W, Rohan LC.
        Pharmaceutics. 2021 ;13(8).
        Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat-and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1-and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      • Thermostability of measles and rubella vaccines in a microneedle patchexternal icon
        Joyce JC, Collins ML, Rota PA, Prausnitz MR.
        Adv Ther. 2021 .
        Measles and rubella vaccinations are highly effective at reducing disease prevalence; however, logistic issues related to subcutaneous administration and vaccine wastage limit the extent of vaccination coverage. Microneedle (MN) patches can increase coverage by easing logistics through simplified administration and improved stability. This study demonstrates the thermostability of a bivalent measles and rubella vaccine MN patch. The data show that rubella vaccine stability requires pH buffering during drying; potassium phosphate buffer at neutral pH is optimal for both vaccines. Screening 43 excipients for their ability to retain potency during drying and storage yields sucrose-threonine-potassium phosphate buffer formulation at pH 7.5 as an optimal formulation. MN patches made with this formulation have no significant loss of vaccine titer after 1 month and remain within a one log10 titer loss cutoff after 3–4 months at 5, 25, and 40 °C. Finally, these patches are shown to be immunogenic in juvenile rhesus macaques. This work demonstrates the potential for MN patches for measles and rubella vaccination to be removed from the cold chain, which is expected to decrease vaccine cost and wastage, and increase vaccination coverage. This article is a U.S. Government work and is in the public domain in the USA.

    • Occupational Safety and Health - Mining
      • A taxonomy of surface mining slip, trip, and fall hazards as a guide to research and practiceexternal icon
        Nasarwanji MF, Dempsey PG, Pollard J, Whitson A, Kocher L.
        Appl Ergon. 2021 Aug 7;97:103542.
        Slips, trips, and falls (STFs) are the second leading cause of non-fatal injuries and can lead to fatal incidents in the mining industry. Hazard identification is an essential first step in remediating STF hazards and creating a safer work environment. Previous research has identified industry-specific risk factors for STFs, evaluated exposures to those risk factors, and developed taxonomies of the hazards for the construction and farming sectors. In comparison, ErgoMine-a mobile device application-based ergonomics audit tool-is the only systematic evaluation tool that covers STF hazards in the mining industry. However, ErgoMine was not specifically developed to address STF hazards. This paper describes the development of a taxonomy that helps identify STF hazards at surface mining sites and provides recommendations to address these hazards to inform future evaluation tools. The objective was to develop a taxonomy that was self-explanatory, observable, repeatable, and solution oriented. In addition to current regulations, standards and guidelines were used to develop the taxonomy to ensure the focus was beyond basic compliance. A detailed description of how the STF hazard taxonomy was created for walkways, stairways, and fixed ladders is provided, along with two specific applications of its use. The STF hazard taxonomy can be used to develop tools like checklists and ergonomics audits to identify and remediate slip, trip, and fall hazards at surface mining facilities, thereby improving worker safety.

    • Substance Use and Abuse
      • Cannabis sales increases during COVID-19: Findings from Alaska, Colorado, Oregon, and Washingtonexternal icon
        Schauer GL, Dilley JA, Roehler DR, Sheehy TJ, Filley JR, Broschart SC, Holland KM, Baldwin GT, Holmes-Chavez AK, Hoots BE.
        Int J Drug Policy. 2021 Aug 3;98:103384.
        BACKGROUND AND AIMS: Following emergency declarations related to COVID-19 in the United States, many states issued stay-at-home orders and designated essential business categories. Most states allowed medical and/or non-medical adult-use cannabis retailers to remain open. This study assesses changes in cannabis sales across Alaska, Colorado, Oregon, and Washington before and during the pandemic. METHODS: Pre-tax sales data from cannabis marketplaces in four states were analyzed to identify trends from January 2018-December 2020. Mean monthly sales and relative percent change in mean monthly sales were compared by state from April-December (coinciding with the pandemic) in 2018, 2019, and 2020. Differences were assessed using the nonparametric Mann-Whitney-U test. RESULTS: Mean monthly cannabis sales in all four states were higher during the pandemic period in 2020 compared to the same period in 2019. Sales reached a three-year peak in Washington in May 2020 and in Alaska, Colorado, and Oregon in July 2020. From April-December, the percent change in mean monthly sales from 2019 to 2020 was significantly higher than 2018-2019 in all four states, though Alaska saw similar increases between 2018-2019 and 2019-2020. CONCLUSION: To date, cannabis sales in Alaska, Colorado, Oregon, and Washington have increased more during the COVID-19 pandemic than in the previous two years. In light of these increases, data monitoring by states and CDC is warranted to understand how patterns of use are changing, which populations are demonstrating changes in use, and how such changes may affect substance use and related public health outcomes.

  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. Evaluation of hemoglobin cutoff levels to define anemia among healthy individualsexternal icon
        Babb S, Yu EX, Williams AM, Young MF, Sharma AJ, Mei Z, Kassebaum NJ, Jefferds ME, Suchdev PS.
        JAMA Netw Open. 2021 Aug 2;4(8):e2119123.
        IMPORTANCE: Anemia, defined as low hemoglobin (Hb) concentration insufficient to meet an individual's physiological needs, is the most common blood condition worldwide. OBJECTIVE: To evaluate the current World Health Organization (WHO) Hb cutoffs for defining anemia among persons who are apparently healthy and to assess threshold validity with a biomarker of tissue iron deficiency and physiological indicator of erythropoiesis (soluble transferrin receptor [sTfR]) using multinational data. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, data were collected and evaluated from 30 household, population-based nutrition surveys of preschool children aged 6 to 59 months and nonpregnant women aged 15 to 49 years during 2005 to 2016 across 25 countries. Data analysis was performed from March 2020 to April 2021. EXPOSURE: Anemia defined according to WHO Hb cutoffs. MAIN OUTCOMES AND MEASURES: To define the healthy population, persons with iron deficiency (ferritin <12 ng/mL for children or <15 ng/mL for women), vitamin A deficiency (retinol-binding protein or retinol <20.1 μg/dL), inflammation (C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L), or known malaria were excluded. Survey-specific, pooled Hb fifth percentile cutoffs were estimated. Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia. RESULTS: A total of 79 950 individuals were included in the original surveys. The final healthy sample was 13 445 children (39.9% of the original sample of 33 699 children; 6750 boys [50.2%]; mean [SD] age 32.9 [16.0] months) and 25 880 women (56.0% of the original sample of 46 251 women; mean [SD] age, 31.0 [9.5] years). Survey-specific Hb fifth percentile among children ranged from 7.90 g/dL (95% CI, 7.54-8.26 g/dL in Pakistan) to 11.23 g/dL (95% CI, 11.14-11.33 g/dL in the US), and among women from 8.83 g/dL (95% CI, 7.77-9.88 g/dL in Gujarat, India) to 12.09 g/dL (95% CI, 12.00-12.17 g/dL in the US). Intersurvey variance around the Hb fifth percentile was low (3.5% for women and 3.6% for children). Pooled fifth percentile estimates were 9.65 g/dL (95% CI, 9.26-10.04 g/dL) for children and 10.81 g/dL (95% CI, 10.35-11.27 g/dL) for women. The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at Hb of 9.61 g/dL (95% CI, 9.55-9.67 g/dL) among children and 11.01 g/dL (95% CI, 10.95-11.09 g/dL) among women. CONCLUSIONS AND RELEVANCE: Current WHO cutoffs to define anemia are higher than the pooled fifth percentile of Hb among persons who are outwardly healthy and from nearly all survey-specific estimates. The lower proposed Hb cutoffs are statistically significant but also reflect compensatory increased erythropoiesis. More studies based on clinical outcomes could further confirm the validity of these Hb cutoffs for anemia.

      2. Glycemic control is associated with dyslipidemia over time in youth with type 2 diabetes: the SEARCH for Diabetes in Youth Studyexternal icon
        Brady RP, Shah AS, Jensen ET, Stafford JM, D'Agostino RB, Dolan LM, Knight L, Imperatore G, Turley CB, Liese AD, Urbina EM, Lawrence JM, Pihoker C, Marcovina S, Dabelea D.
        Pediatr Diabetes. 2021 Aug 7.
        BACKGROUND: Dyslipidemia has been documented in youth with type 2 diabetes. There is a paucity of studies examining dyslipidemia over time in youth with type 2 diabetes and associated risk factors. OBJECTIVES: To evaluate lipids at baseline and follow-up and associated risk factors in youth with type 2 diabetes. METHODS: We studied 212 youth with type 2 diabetes at baseline and after an average of 7 years of follow-up in the SEARCH for Diabetes in Youth Study. Abnormal lipids were defined as HDL-C <35, LDL-C >100, or triglycerides >150 (all mg/dL). We evaluated participants for progression to abnormal lipids (normal lipids at baseline, abnormal at follow-up), regression (abnormal lipids at baseline, normal at follow-up), stable normal and stable abnormal lipids over time for HDL-C, LDL-C and triglycerides. Associations between HbA1c and adiposity over time (area under the curve, AUC) with progression and stable abnormal lipids were evaluated. RESULTS: HDL-C progressed, regressed, was stable normal, and stable abnormal in 12.3%, 11.3%, 62.3%, and 14.2% of participants, respectively. Corresponding LDL-C percentages were 15.6%, 12.7%, 42.9% and 28.8% and triglycerides were 17.5%, 10.8%, 55.7% and 16.0%. Each 1% increase in HbA1c AUC was associated with a 13% higher risk of progression and stable abnormal triglycerides and a 20% higher risk of progression and stable abnormal LDL-C. Higher adiposity AUC was marginally (p=0.049) associated with abnormal HDL-C. CONCLUSIONS: Progression and stable abnormal LDL-C and triglycerides occur in youth with type 2 diabetes and are associated with higher HbA1c. This article is protected by copyright. All rights reserved.

      3. Monogenic diabetes in youth with presumed type 2 diabetes: Results from the Progress in Diabetes Genetics in Youth (ProDiGY) Collaborationexternal icon
        Todd JN, Kleinberger JW, Zhang H, Srinivasan S, Tollefsen SE, Levitsky LL, Levitt Katz LE, Tryggestad JB, Bacha F, Imperatore G, Lawrence JM, Pihoker C, Divers J, Flannick J, Dabelea D, Florez JC, Pollin TI.
        Diabetes Care. 2021 Aug 6.
        OBJECTIVE: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS: Of 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006). CONCLUSIONS: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.

    • Communicable Diseases
      1. Mortality in children aged <5 years with severe acute respiratory illness in a high HIV-prevalence urban and rural areas of South Africa, 2009-2013external icon
        Ayeni OA, Walaza S, Tempia S, Groome M, Kahn K, Madhi SA, Cohen AL, Moyes J, Venter M, Pretorius M, Treurnicht F, Hellferscee O, von Gottberg A, Wolter N, Cohen C.
        PLoS One. 2021 ;16(8):e0255941.
        BACKGROUND: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas. OBJECTIVE: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009-2013. METHODS: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death. RESULTS: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4-24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0-9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3-7.1) and age <1 year (OR: 3.7, 95% CI: 1.9-7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3-0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3-0.8) were negatively associated with death. CONCLUSION: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed.

      2. HIV stigma among a national probability sample of adults with diagnosed HIV-United States, 2018-2019external icon
        Beer L, Tie Y, McCree DH, Demeke HB, Marcus R, Padilla M, Khalil G, Shouse RL.
        AIDS Behav. 2021 Aug 10.
        HIV stigma is a barrier to achieving the goals of the US Ending the HIV Epidemic initiative. We analyzed data from the Medical Monitoring Project (MMP) collected during 6/2018-5/2019 from 4050 US adults with diagnosed HIV. We reported national estimates of HIV stigma and assessed their associations with sociodemographic and clinical characteristics. Disclosure concerns and stigma related to negative public attitudes were common. Stigma was higher among younger age groups, women and transgender people, Black and Hispanic/Latino men and women, and Black and Hispanic/Latino men who have sex with men. Stigma was associated with lower antiretroviral therapy use and adherence, missed HIV care visits, and symptoms of depression or anxiety. The estimates presented provide a benchmark from which the nation can monitor its progress. The findings suggest the need for enhanced stigma-reduction efforts among specific groups and the importance of addressing stigma around disclosure and community attitudes.

      3. Testing practices for fungal respiratory infections and SARS-CoV-2 among infectious disease specialists, United Statesexternal icon
        Benedict K, Williams S, Beekmann SE, Polgreen PM, Jackson BR, Toda M.
        J Fungi. 2021 ;7(8).
        In an online poll, 174 infectious disease physicians reported that testing frequencies for coccidioidomycosis, histoplasmosis, blastomycosis, and cryptococcosis were similar before and during the COVID-19 pandemic, indicating that these physicians remain alert for these fungal infections and were generally not concerned about the possibility of under-detection. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      4. Risk factors for death among hospitalized patients aged 21-64 years diagnosed with COVID-19-New York City, March 13-April 9, 2020external icon
        Bushman D, Davidson A, Pathela P, Greene SK, Weiss D, Reddy V, New York City Fatal Case-Control Study Team , Latash J.
        J Racial Ethn Health Disparities. 2021 Aug 9:1-16.
        BACKGROUND: COVID-19 mortality studies have primarily focused on persons aged ≥ 65 years; less is known about decedents aged <65 years. METHODS: We conducted a case-control study among NYC residents aged 21-64 years hospitalized with COVID-19 diagnosed March 13-April 9, 2020, to determine risk factors for death. Case-patients (n=343) were hospitalized decedents with COVID-19 and control-patients (n=686) were discharged from hospitalization with COVID-19 and matched 2:1 to case-patients on age and residential neighborhood. Conditional logistic regression models were adjusted for patient sex, insurance status, and marital status. Matched adjusted odds ratios (aORs) were calculated for selected underlying conditions, combinations of conditions, and race/ethnic group. RESULTS: Median age of both case-patients and control-patients was 56 years (range: 23-64 years). Having ≥ 1 selected underlying condition increased odds of death 4.45-fold (95% CI: 2.33-8.49). Patients with diabetes; morbid obesity; heart, kidney, or lung disease; cancer; neurologic/neurodevelopmental conditions; mental health conditions; or HIV had significantly increased odds of death. Compared with having neither condition, having both diabetes and obesity or diabetes and heart disease was associated with approximately threefold odds of death. Five select underlying conditions were more prevalent among non-Hispanic Black control-patients than among control-patients of other races/ethnicities. CONCLUSIONS AND RELEVANCE: Selected underlying conditions were risk factors for death, and most prevalent among racial/ethnic minorities. Social services; health care resources, including vaccination; and tailored public health messaging are important for COVID-19 prevention. Strengthening these strategies for racial/ethnic minority groups could minimize COVID-19 racial/ethnic disparities.

      5. Trends in HIV care outcomes among adults and adolescents - 33 jurisdictions, United States, 2014-2018external icon
        Dailey A, Johnson AS, Hu X, Gant Z, Lyons SJ, Adih W.
        J Acquir Immune Defic Syndr. 2021 Aug 4.
        BACKGROUND: With significant improvements in the diagnosis and treatment of HIV, the number of people with HIV in the United States steadily increases. Monitoring trends in HIV-related care outcomes is needed to inform programs aimed at reducing new HIV infections in the United States. SETTING: The setting is 33 United States jurisdictions that as of December 2019 had complete laboratory reporting for specimens through September 2019. METHODS: Estimated annual percent change (EAPC) and 95% confidence intervals (CIs) were calculated to assess trends in stage of disease at time of diagnosis, linkage to HIV medical care within 1 month after HIV diagnosis, and viral suppression within 6 months after HIV diagnosis. Differences in percentages were analyzed by gender, age, race/ethnicity, and transmission category for persons with HIV diagnosed from 2014-2018. RESULTS: Among 133,477 persons with HIV diagnosed during 2014-2018, the percentage of persons that received a diagnosis classified as stage 0 increased 13.7% , stages 1-2 (early infections) increased 2.9%, stage 3 (AIDS) declined 1.5%, linkage to HIV medical care within 1 month after HIV diagnosis increased 2.3%, and viral suppression within 6 months after HIV diagnosis increased 6.5% per year, on average. Subpopulations and areas that showed the least progress were persons aged 45-54 years, American Indian/Alaska Native persons, Asian persons, Native Hawaiian/other Pacific Islander persons, and rural areas with substantial HIV prevalence. CONCLUSIONS: New infections will continue to occur unless improvements are made in implementing the EHE strategies of diagnosing, treating, and preventing HIV infection.

      6. Clinical trends among U.S. adults hospitalized with COVID-19, March to December 2020: A cross-sectional studyexternal icon
        Garg S, Patel K, Pham H, Whitaker M, O'Halloran A, Milucky J, Anglin O, Kirley PD, Reingold A, Kawasaki B, Herlihy R, Yousey-Hindes K, Maslar A, Anderson EJ, Openo KP, Weigel A, Teno K, Ryan PA, Monroe ML, Reeg L, Kim S, Como-Sabetti K, Bye E, Shrum Davis S, Eisenberg N, Muse A, Barney G, Bennett NM, Felsen CB, Billing L, Shiltz J, Sutton M, Abdullah N, Talbot HK, Schaffner W, Hill M, Chatelain R, Wortham J, Taylor C, Hall A, Fry AM, Kim L, Havers FP.
        Ann Intern Med. 2021 Aug 10.
        BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

      7. Clostridium botulinum produces botulinum neurotoxin (BoNT), which can lead to death if untreated. In the United States, over 90% of wound botulism cases are associated with injection drug use of black tar heroin. We sought to determine the phylogenetic relatedness of C. botulinum isolated from an injection drug use wound botulism case and isolates from endogenous infant botulism cases in Hawaii. Nineteen C. botulinum type B isolates from Hawaii and one type B isolate from California were analyzed by whole-genome sequencing. The botulinum toxin gene (bont) subtype was determined using CLC Genomics Workbench, and the seven-gene multi-locus sequence type (MLST) was identified by querying PubMLST. Mashtree and pairwise average nucleotide identity were used to find nearest neighbors, and Lyve-SET approximated a phylogeny. Eighteen of the isolates harbored the bont/B5 gene: of those, 17 were classified as sequence type ST36 and one was classified as ST104. A single isolate from Hawaii harbored bont/B1 and was determined to belong to ST110, and the isolate from California harbored bont/B1 and belonged to ST30. A tree constructed with Lyve-SET showed a high degree of homology among all the Hawaiian C. botulinum isolates that harbor the bont/B5 gene. Our results indicate that the bont/B-expressing isolates recovered from Hawaii are closely related to each other, suggesting local contamination of the drug paraphernalia or the wound itself with spores rather than contamination of the drug at manufacture or during transport. These findings may assist in identifying interventions to decrease wound botulism among persons who inject drugs.

      8. Hepatitis C treatment among commercially or Medicaid-insured individuals, 2014-2018external icon
        Harris AM, Khan MA, Osinubi A, Nelson NP, Thompson WW.
        Am J Prev Med. 2021 Aug 3.
        INTRODUCTION: The proportion of individuals infected with hepatitis C virus that receive direct-acting antiviral treatment is unclear. METHODS: The proportion of commercially or Medicaid-insured patients receiving hepatitis C virus treatment was estimated using administrative claims data obtained from MarketScan and Multi-State Medicaid obtained on January 6, 2020. Validated algorithms derived from standardized procedures and International Classification of Diseases diagnosis codes were used to identify enrollees with chronic hepatitis C; analysis (performed November 30, 2020) was restricted to adults continuously enrolled with prescription drug coverage for >6 months before and after their index hepatitis C viral load test claim date from January 2014 through December 2018. Prescription drug claims using National Drug Codes were used for hepatitis C virus drugs. The proportion of treated patients by demographic and clinical characteristics was described, and associations with treatment were modeled using multivariable-adjusted hazard ratios and 95% CIs by insurance status. RESULTS: Of patients with chronic hepatitis C, 12,090 of 17,562 (69%) with commercial insurance and 8,112 of 27,328 (30%) with Medicaid were treated. Commercially insured patients with opioid use disorder (hazard ratio=0.78, 95% CI=0.72, 0.85), alcohol use disorder (hazard ratio=0.85, 95% CI=0.79, 0.91), severe mental illness (hazard ratio=0.92, 95% CI=0.87, 0.98), chronic kidney disease (hazard ratio=0.75, 95% CI=0.69, 0.82), or HIV infection (hazard ratio=0.74, 95% CI=0.66, 0.82) were less likely to be treated. Medicaid patients with opioid (hazard ratio=0.64, 95% CI=0.61, 0.68) or alcohol use disorders (hazard ratio=0.83, 95% CI=0.79, 0.88) were less likely to be treated. CONCLUSIONS: Hepatitis C virus treatment gaps were identified using administrative claims data among patients with commercial and Medicaid insurance.

      9. Rapid increase in circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant - Mesa County, Colorado, April-June 2021external icon
        Herlihy R, Bamberg W, Burakoff A, Alden N, Severson R, Bush E, Kawasaki B, Berger B, Austin E, Shea M, Gabrieloff E, Matzinger S, Burdorf A, Nichols J, Goode K, Cilwick A, Stacy C, Staples E, Stringer G.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1084-1087.
        On May 5, 2021, the Colorado Department of Public Health and Environment (CDPHE) identified the first five COVID-19 cases caused by the SARS-CoV-2 B.1.617.2 (Delta) variant in Mesa County in western Colorado (population 154,933, <3% of the state population). All five initial cases were associated with school settings. Through early June, Mesa County experienced a marked increase in the proportion of Delta variant cases identified through sequencing: the 7-day proportion of sequenced specimens identified as B.1.617.2 in Mesa County more than doubled, from 43% for the week ending May 1 to 88% for the week ending June 5. As of June 6, more than one half (51%) of sequenced B.1.617.2 specimens in Colorado were from Mesa County. CDPHE assessed data from surveillance, vaccination, laboratory, and hospital sources to describe the preliminary epidemiology of the Delta variant and calculate crude vaccine effectiveness (VE). Vaccination coverage in early May in Mesa County was lower (36% of eligible residents fully vaccinated) than that in the rest of the state (44%). Compared with that in all other Colorado counties, incidence, intensive care unit (ICU) admissions, and COVID-19 case fatality ratios were significantly higher in Mesa County during the analysis period, April 27-June 6, 2021. In addition, during the same time period, the proportion of COVID-19 cases in persons who were fully vaccinated (vaccine breakthrough cases) was significantly higher in Mesa County compared with that in all other Colorado counties. Estimated crude VE against reported symptomatic infection for a 2-week period ending June 5 was 78% (95% confidence interval [CI] = 71%-84%) for Mesa County and 89% (95% CI = 88%-91%) for other Colorado counties. Vaccination is a critical strategy for preventing infection, serious illness, and death from COVID-19. Enhanced mitigation strategies, including masking in indoor settings irrespective of vaccination status, should be considered in areas with substantial or high case rates.

      10. Influenza polymerase inhibitor resistance: Assessment of the current state of the art - A report of the isirv Antiviral Groupexternal icon
        Ison MG, Hayden FG, Hay AJ, Gubareva LV, Govorkova EA, Takashita E, McKimm-Breschkin JL.
        Antiviral Res. 2021 Aug 4;194:105158.
        It is more than 20 years since the neuraminidase inhibitors, oseltamivir and zanamivir were approved for the treatment and prevention of influenza. Guidelines for global surveillance and methods for evaluating resistance were established initially by the Neuraminidase Inhibitor Susceptibility Network (NISN), which merged 10 years ago with the International Society for influenza and other Respiratory Virus Diseases (isirv) to become the isirv-Antiviral Group (isirv-AVG). With the ongoing development of new influenza polymerase inhibitors and recent approval of baloxavir marboxil, the isirv-AVG held a closed meeting in August 2019 to discuss the impact of resistance to these inhibitors. Following this meeting and review of the current literature, this article is intended to summarize current knowledge regarding the clinical impact of resistance to polymerase inhibitors and approaches for surveillance and methods for laboratory evaluation of resistance, both in vitro and in animal models. We highlight limitations and gaps in current knowledge and suggest some strategies for addressing these gaps, including the need for additional clinical studies of influenza antiviral drug combinations. Lessons learned from influenza resistance monitoring may also be helpful for establishing future drug susceptibility surveillance and testing for SARS-CoV-2.

      11. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort studyexternal icon
        Jassat W, Cohen C, Tempia S, Masha M, Goldstein S, Kufa T, Murangandi P, Savulescu D, Walaza S, Bam JL, Davies MA, Prozesky HW, Naude J, Mnguni AT, Lawrence CA, Mathema HT, Zamparini J, Black J, Mehta R, Parker A, Chikobvu P, Dawood H, Muvhango N, Strydom R, Adelekan T, Mdlovu B, Moodley N, Namavhandu EL, Rheeder P, Venturas J, Magula N, Blumberg L.
        Lancet HIV. 2021 Aug 4.
        BACKGROUND: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15-49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. METHODS: In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. FINDINGS: Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27-1·43), past tuberculosis (1·26, 1·15-1·38), current tuberculosis (1·42, 1·22-1·64), and both past and current tuberculosis (1·48, 1·32-1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22-1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. INTERPRETATION: Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. FUNDING: South African National Government.

      12. Opportunities for closing the gap in HIV diagnosis, treatment, and viral load suppression in children in Malawi: Results from a 2015-2016 population-based HIV Impact Assessment Surveyexternal icon
        Jonnalagadda S, Auld A, Jahn A, Saito S, Bello G, Sleeman K, Ogollah FM, Cuervo-Rojas J, Radin E, Kayira D, Kim E, Payne D, Burnett J, Hrapcak S, Patel H, Voetsch AC.
        Pediatr Infect Dis J. 2021 Aug 10.
        BACKGROUND: Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. METHODS: In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection. RESULTS: Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1-1.9) and 8.0% (95% CI: 5.6-10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028-149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3-41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8-95.6) were on ART and 57.9% (95% CI: 41.4-74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0-70.5) had unsuppressed VL. CONCLUSIONS: Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions.

      13. Evaluating the effect of a community score card among pregnant and breastfeeding women living with HIV in two districts in Malawiexternal icon
        Kays M, Woelk G, Callahan T, Katirayi L, Montandon M, Chauwa F, Laterra A, Sampathkumar V, Kayira D, Kalua T, Kazemi E, Hoffman H, Modi S.
        PLoS One. 2021 ;16(8):e0255788.
        Malawi faces challenges with retaining women in prevention of mother-to-child HIV transmission (PMTCT) services. We evaluated Cooperative for Assistance and Relief Everywhere, Inc. (CARE's) community score card (CSC) in 11 purposively selected health facilities, assessing the effect on: (1) retention in PMTCT services, (2) uptake of early infant diagnosis (EID), (3) collective efficacy among clients, and (4) self-efficacy among health care workers (HCWs) in delivering quality services. The CSC is a participatory community approach. In this study, HCWs and PMTCT clients identified issues impacting PMTCT service quality and uptake and implemented actions for improvement. A mixed-methods, pre- and post-intervention design was used to evaluate the intervention. We abstracted routine clinical data on retention in PMTCT services for HIV-positive clients attending their first antenatal care visit and EID uptake for their infants for 8-month periods before and after implementation. To assess collective efficacy and self-efficacy, we administered questionnaires and conducted focus group discussions (FGDs) pre- and post-intervention with PMTCT clients recruited from CSC participants, and HCWs providing HIV care from facilities. Retention of HIV-positive women in PMTCT services at three and six months and EID uptake was not significantly different pre- and post-implementation. For the clients, the collective efficacy scale average improved significantly post-intervention, (p = 0.003). HCW self-efficacy scale average did not improve. Results from the FGDs highlighted a strengthened relationship between HCWs and PMTCT clients, with clients reporting increased satisfaction with services. However, the data indicated continued challenges with stigma and fear of disclosure. While CSC may foster mutual trust and respect between HCWs and PMTCT clients, we did not find it improved PMTCT retention or EID uptake within the short duration of the study period. More research is needed on ways to improve service quality and decrease stigmatized behaviors, such as HIV testing and treatment services, as well as the longer-term impacts of interventions like the CSC on clinical outcomes.

      14. To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approachexternal icon
        Lebelonyane R, Bachanas P, Block L, Ussery F, Alwano MG, Marukutira T, El Halabi S, Roland M, Abrams W, Ussery G, Miller JA, Lockman S, Gaolathe T, Holme MP, Hader S, Mills LA, Wirth K, Bock N, Moore J.
        PLoS One. 2021 ;16(8):e0255227.
        BACKGROUND: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. METHODS: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression. RESULTS: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. CONCLUSIONS: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. CLINICAL TRIAL NUMBER: NCT01965470.

      15. Factors associated with unawareness of HIV-positive status in urban Ethiopia: Evidence from the Ethiopia population-based HIV impact assessment 2017-2018external icon
        Lulseged S, Belete W, Ahmed J, Gelibo T, Teklie H, West CW, Melaku Z, Demissie M, Farhani M, Eshetu F, Birhanu S, Getaneh Y, Patel H, Voetsch AC.
        PLoS One. 2021 ;16(8):e0255163.
        BACKGROUND: The HIV epidemic in Ethiopia is concentrated in urban areas. Ethiopia conducted a Population-based HIV Impact Assessment (EPHIA) in urban areas between October 2017 and April 2018 to measure the status of the country's response to the epidemic. METHODS: We conducted field data collection and HIV testing in randomly selected households using the national, rapid testing algorithm with laboratory confirmation of seropositive samples using a supplemental assay. In addition to self-report on HIV diagnosis and treatment, all HIV-positive participants were screened for a set of HIV antiretroviral (ARV) drugs indicative of the first- and second-line regimens. We calculated weighted frequencies and 95% confidence intervals to assess regional variation in participants' level of unawareness of their HIV-positive status (adjusted for ARV status). RESULTS: We interviewed 20,170 survey participants 15-64 years of age, of which 19,136 (95%) were tested for HIV, 614 (3.2%) tested positive, and 119 (21%) of HIV-positive persons were unaware of their HIV status. Progress towards the UNAIDS first 90 target (90% of people living with HIV would be aware of their HIV status by 2020) substantially differed by administrative region of the country. In the bivariate analysis using log binomial regression, three regions (Oromia, Addis Ababa, and Harari), male gender, and young age (15-24 years) were significantly associated with awareness of HIV positive status. In multivariate analysis, the same variables were associated with awareness of HIV-positive status. CONCLUSION: One-fifth of the HIV-positive urban population were unaware of their HIV-positive status. The number of unaware HIV-positive individuals has a different distribution than the HIV prevalence. National and regional planning and monitoring activities could address this potentially substantial source of undetected HIV infection by increasing HIV testing among young people, men and individuals who do not use condoms.

      16. Detection of SARS-CoV-2 on surfaces in households of persons with COVID-19external icon
        Marcenac P, Park GW, Duca LM, Lewis NM, Dietrich EA, Barclay L, Tamin A, Harcourt JL, Thornburg NJ, Rispens J, Matanock A, Kiphibane T, Christensen K, Pawloski LC, Fry AM, Hall AJ, Tate JE, Vinjé J, Kirking HL, Pevzner E.
        Int J Environ Res Public Health. 2021 Aug 2;18(15).
        SARS-CoV-2 transmission from contaminated surfaces, or fomites, has been a concern during the COVID-19 pandemic. Households have been important sites of transmission throughout the COVID-19 pandemic, but there is limited information on SARS-CoV-2 contamination of surfaces in these settings. We describe environmental detection of SARS-CoV-2 in households of persons with COVID-19 to better characterize the potential risks of fomite transmission. Ten households with ≥1 person with laboratory-confirmed COVID-19 and with ≥2 members total were enrolled in Utah, U.S.A. Nasopharyngeal and anterior nasal swabs were collected from members and tested for the presence of SARS-CoV-2 by RT-PCR. Fifteen surfaces were sampled in each household and tested for presence and viability of SARS-CoV-2. SARS-CoV-2 RNA was detected in 23 (15%) of 150 environmental swab samples, most frequently on nightstands (4/6; 67%), pillows (4/23; 17%), and light switches (3/21; 14%). Viable SARS-CoV-2 was cultured from one sample. All households with SARS-CoV-2-positive surfaces had ≥1 person who first tested positive for SARS-CoV-2 ≤ 6 days prior to environmental sampling. SARS-CoV-2 surface contamination occurred early in the course of infection when respiratory transmission is most likely, notably on surfaces in close, prolonged contact with persons with COVID-19. While fomite transmission might be possible, risk is low.

      17. Model-based small area estimation methods and precise district-level HIV prevalence estimates in Ugandaexternal icon
        Ouma J, Jeffery C, Awor CA, Muruta A, Musinguzi J, Wanyenze RK, Biraro S, Levin J, Valadez JJ.
        PLoS One. 2021 ;16(8):e0253375.
        BACKGROUND: Model-based small area estimation methods can help generate parameter estimates at the district level, where planned population survey sample sizes are not large enough to support direct estimates of HIV prevalence with adequate precision. We computed district-level HIV prevalence estimates and their 95% confidence intervals for districts in Uganda. METHODS: Our analysis used direct survey and model-based estimation methods, including Fay-Herriot (area-level) and Battese-Harter-Fuller (unit-level) small area models. We used regression analysis to assess for consistency in estimating HIV prevalence. We use a ratio analysis of the mean square error and the coefficient of variation of the estimates to evaluate precision. The models were applied to Uganda Population-Based HIV Impact Assessment 2016/2017 data with auxiliary information from the 2016 Lot Quality Assurance Sampling survey and antenatal care data from district health information system datasets for unit-level and area-level models, respectively. RESULTS: Estimates from the model-based and the direct survey methods were similar. However, direct survey estimates were unstable compared with the model-based estimates. Area-level model estimates were more stable than unit-level model estimates. The correlation between unit-level and direct survey estimates was (β1 = 0.66, r2 = 0.862), and correlation between area-level model and direct survey estimates was (β1 = 0.44, r2 = 0.698). The error associated with the estimates decreased by 37.5% and 33.1% for the unit-level and area-level models, respectively, compared to the direct survey estimates. CONCLUSIONS: Although the unit-level model estimates were less precise than the area-level model estimates, they were highly correlated with the direct survey estimates and had less standard error associated with estimates than the area-level model. Unit-level models provide more accurate and reliable data to support local decision-making when unit-level auxiliary information is available.

      18. Survey of adherence with COVID-19 prevention behaviors during the 2020 thanksgiving and winter holidays among members of the COVID-19 Community Research Partnershipexternal icon
        Peacock JE, Herrington DM, Edelstein SL, Seals AL, Plumb ID, Saydah S, Lagarde WH, Runyon MS, Maguire PD, Correa A, Weintraub WS, Wierzba TF, Sanders JW.
        J Community Health. 2021 Aug 12:1-8.
        Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.

      19. Evaluating locally developed interventions to promote PrEP among racially/ethnically diverse transgender women in the United States: A unique CDC initiativeexternal icon
        Rhodes SD, Kuhns LM, Alexander J, Alonzo J, Bessler PA, Courtenay-Quirk C, Denson DJ, Evans K, Galindo CA, Garofalo R, Gelaude DJ, Hotton AL, Johnson AK, Mann-Jackson L, Muldoon A, Ortiz R, Paul JL, Perloff J, Pleasant K, Reboussin BA, Refugio Aviles L, Song EY, Tanner AE, Trent S.
        AIDS Educ Prev. 2021 Aug;33(4):345-360.
        In the United States, transgender women are disproportionately affected by HIV. However, few evidence-based prevention interventions exist for this key population. We describe two promising, locally developed interventions that are currently being implemented and evaluated through the Centers for Disease Control and Prevention Combination HIV Prevention for Transgender Women Project: (a) ChiCAS, designed to promote the uptake of pre-exposure prophylaxis (PrEP), condom use, and medically supervised hormone therapy among Spanish-speaking transgender Latinas, and (b) TransLife Care, designed to address the structural drivers of HIV risk through access to housing, employment, legal services, and medical services, including HIV preventive care (e.g., PrEP use) among racially/ethnically diverse urban transgender women. If the evaluation trials determine that these interventions are effective, they will be among the first such interventions for use with transgender women incorporating PrEP, thereby contributing to the evidence-based resources that may be used to reduce HIV risk among this population.

      20. Pregnant individuals infected with SARS-CoV-2 have higher rates of ICU admission, oxygen requirement, need for mechanical ventilation and death than non-pregnant individuals. Increased COVID-19 disease severity may be associated with increased risk for viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, that can be either placentally-mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1-3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. NIH/NICHD convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in-situ hybridization with anti-sense probe (detects replication) and/or a sense probe (detects viral genome or immunohistochemistry to detect viral nucleocapsid (N) or spike (S) proteins. If the above methods are not possible, RT-PCR detection and/or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling, as well as the use of validated reagents and sample protocols (included as appendices).

      21. The Great Chlamydia Control Bake Off: the same ingredients (evidence) but different recipes for successexternal icon
        Soldan K, Anyalechi GE, Kreisel KM, Hocking JS, Bernstein K.
        Sex Transm Infect. 2021 Aug 11.

      22. Alternative methods for grouping race and ethnicity to monitor COVID-19 outcomes and vaccination coverageexternal icon
        Yoon P, Hall J, Fuld J, Mattocks SL, Lyons BC, Bhatkoti R, Henley J, McNaghten AD, Daskalakis D, Pillai SK.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1075-1080.
        Population-based analyses of COVID-19 data, by race and ethnicity can identify and monitor disparities in COVID-19 outcomes and vaccination coverage. CDC recommends that information about race and ethnicity be collected to identify disparities and ensure equitable access to protective measures such as vaccines; however, this information is often missing in COVID-19 data reported to CDC. Baseline data collection requirements of the Office of Management and Budget's Standards for the Classification of Federal Data on Race and Ethnicity (Statistical Policy Directive No. 15) include two ethnicity categories and a minimum of five race categories (1). Using available COVID-19 case and vaccination data, CDC compared the current method for grouping persons by race and ethnicity, which prioritizes ethnicity (in alignment with the policy directive), with two alternative methods (methods A and B) that used race information when ethnicity information was missing. Method A assumed non-Hispanic ethnicity when ethnicity data were unknown or missing and used the same population groupings (denominators) for rate calculations as the current method (Hispanic persons for the Hispanic group and race category and non-Hispanic persons for the different racial groups). Method B grouped persons into ethnicity and race categories that are not mutually exclusive, unlike the current method and method A. Denominators for rate calculations using method B were Hispanic persons for the Hispanic group and persons of Hispanic or non-Hispanic ethnicity for the different racial groups. Compared with the current method, the alternative methods resulted in higher counts of COVID-19 cases and fully vaccinated persons across race categories (American Indian or Alaska Native [AI/AN], Asian, Black or African American [Black], Native Hawaiian or Other Pacific Islander [NH/PI], and White persons). When method B was used, the largest relative increase in cases (58.5%) was among AI/AN persons and the largest relative increase in the number of those fully vaccinated persons was among NH/PI persons (51.6%). Compared with the current method, method A resulted in higher cumulative incidence and vaccination coverage rates for the five racial groups. Method B resulted in decreasing cumulative incidence rates for two groups (AI/AN and NH/PI persons) and decreasing cumulative vaccination coverage rates for AI/AN persons. The rate ratio for having a case of COVID-19 by racial and ethnic group compared with that for White persons varied by method but was <1 for Asian persons and >1 for other groups across all three methods. The likelihood of being fully vaccinated was highest among NH/PI persons across all three methods. This analysis demonstrates that alternative methods for analyzing race and ethnicity data when data are incomplete can lead to different conclusions about disparities. These methods have limitations, however, and warrant further examination of potential bias and consultation with experts to identify additional methods for analyzing and tracking disparities when race and ethnicity data are incomplete.

    • Disease Reservoirs and Vectors
      1. Free-living aquatic turtles as sentinels of Salmonella spp. for water bodiesexternal icon
        Hernandez SM, Maurer JJ, Yabsley MJ, Peters VE, Presotto A, Murray MH, Curry S, Sanchez S, Gerner-Smidt P, Hise K, Huang J, Johnson K, Kwan T, Lipp EK.
        Front Vet Sci. 2021 ;8:674973.
        Reptile-associated human salmonellosis cases have increased recently in the United States. It is not uncommon to find healthy chelonians shedding Salmonella enterica. The rate and frequency of bacterial shedding are not fully understood, and most studies have focused on captive vs. free-living chelonians and often in relation to an outbreak. Their ecology and significance as sentinels are important to understanding Salmonella transmission. In 2012-2013, Salmonella prevalence was determined for free-living aquatic turtles in man-made ponds in Clarke and Oconee Counties, in northern Georgia (USA) and the correlation between species, basking ecology, demographics (age/sex), season, or landcover with prevalence was assessed. The genetic relatedness between turtle and archived, human isolates, as well as, other archived animal and water isolates reported from this study area was examined. Salmonella was isolated from 45 of 194 turtles (23.2%, range 14-100%) across six species. Prevalence was higher in juveniles (36%) than adults (20%), higher in females (33%) than males (18%), and higher in bottom-dwelling species (31%; common and loggerhead musk turtles, common snapping turtles) than basking species (15%; sliders, painted turtles). Salmonella prevalence decreased as forest cover, canopy cover, and distance from roads increased. Prevalence was also higher in low-density, residential areas that have 20-49% impervious surface. A total of 9 different serovars of two subspecies were isolated including 3 S. enterica subsp. arizonae and 44 S. enterica subsp. enterica (two turtles had two serotypes isolated from each). Among the S. enterica serovars, Montevideo (n = 13) and Rubislaw (n = 11) were predominant. Salmonella serovars Muenchen, Newport, Mississippi, Inverness, Brazil, and Paratyphi B. var L(+) tartrate positive (Java) were also isolated. Importantly, 85% of the turtle isolates matched pulsed-field gel electrophoresis patterns of human isolates, including those reported from Georgia. Collectively, these results suggest that turtles accumulate Salmonella present in water bodies, and they may be effective sentinels of environmental contamination. Ultimately, the Salmonella prevalence rates in wild aquatic turtles, especially those strains shared with humans, highlight a significant public health concern.

    • Environmental Health
      1. Urinary concentrations of phenols, parabens, and triclocarban in relation to uterine leiomyomata incidence and growthexternal icon
        Wesselink AK, Weuve J, Fruh V, Bethea TN, Claus Henn B, Harmon QE, Hauser R, Williams PL, Calafat AM, McClean M, Baird DD, Wise LA.
        Fertil Steril. 2021 Aug 5.
        OBJECTIVE: To examine the association of urinary concentrations of phenols, parabens, and triclocarban with incidence and growth of uterine leiomyomata (UL; fibroids). DESIGN: Case-cohort study, nested within the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study. SETTING: Clinic visits at baseline and every 20 months for 60 months. PATIENT(S): 754 Black women aged 23-35 years residing in the Detroit, Michigan area (enrolled during 2010-2012). INTERVENTION: None. MAIN OUTCOME MEASURE(S): At each study visit, women underwent transvaginal ultrasound for measurement of UL incidence and growth and provided urine specimens in which we quantified concentrations of seven phenols, four parabens, and triclocarban. We used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) characterizing the relation of urinary biomarker concentrations with UL incidence during the 60 months of follow-up. In a subset of UL detected and measured at multiple time points, we used linear regression to assess the associations between biomarker concentrations and UL growth. RESULT(S): Urinary biomarker concentrations were generally inversely associated with UL incidence, but the associations were weak and nonmonotonic. For example, hazard ratios comparing concentrations ≥90th with <50th percentile were 0.77 (95% CI: 0.46, 1.27) for bisphenol A, 0.72 (95% CI: 0.40, 1.28) for bisphenol S, and 0.76 (95% CI: 0.43, 1.33) for methylparaben. Biomarker concentrations were not strongly associated with UL growth. CONCLUSION(S): In this study of reproductive-aged Black women, urinary phenols, parabens, and triclocarban biomarkers were neither strongly nor consistently associated with UL incidence and growth.

    • Genetics and Genomics
      1. Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 childrenexternal icon
        Pitsava G, Feldkamp ML, Pankratz N, Lane J, Kay DM, Conway KM, Shaw GM, Reefhuis J, Jenkins MM, Almli LM, Olshan AF, Pangilinan F, Brody LC, Sicko RJ, Hobbs CA, Bamshad M, McGoldrick D, Nickerson DA, Finnell RH, Mullikin J, Romitti PA, Mills JL.
        Am J Med Genet A. 2021 Aug 5.
        Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired-end exome sequencing in 26 child/mother/father trios. Three children had rare (allele frequency ≤ 0.0001 in several public databases) inherited variants in TSPAN4, one with a loss-of-function variant and two with missense variants. Two children had loss-of-function variants in TUBE1. Four children had rare missense or nonsense variants (one per child) in WNT3, CRKL, MYH9, or LZTR1, genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss-of-function variants (AKR1C2, PRRX1, PPM1D) in three children (one per child). We also detected rare compound heterozygous loss-of-function variants in PLCH2 and CLEC4M and rare inherited missense or loss-of-function variants in additional genes applying autosomal recessive (three genes) and X-linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (TUBE1) and adhesion (TSPAN4) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.

    • Health Disparities
      1. A rapid review of disparities in HIV prevention and care outcomes among Hispanic/Latino men who have sex with men in the United Statesexternal icon
        Crepaz N, Mullins MM, Higa D, Gunn JK, Salabarría-Peña Y.
        AIDS Educ Prev. 2021 Aug;33(4):276-289.
        In the United States, Hispanic/Latino men who have sex with men (HLMSM) are disproportionally affected by HIV. We conducted a rapid review of national surveillance data to examine disparities in HIV prevention and care outcomes among HLMSM. Thirteen reports provided relevant data from 2011 to 2018. Compared to White MSM, a higher percentage of HIV-negative HLMSM reported not taking PrEP and engaging in condomless sex; a lower percentage of HIV-negative HLMSM at risk for HIV reported PrEP awareness and use; and a lower percentage of HIV-positive HLMSM were aware of their status, linked to HIV care, and virally suppressed. Viral suppression rates in HLMSM were better among Ryan White clients than the national rates, suggesting that access to comprehensive care/services reduces disparities. Findings also call for identifying individual, social, and structural factors contributing to condomless sex without PrEP use and HIV status unawareness and identifying best approaches for scaling up comprehensive care/services.

    • Healthcare Associated Infections

      1. Aztreonam-avibactam susceptibility testing program for metallo-beta-lactamase-producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020external icon
        Bhatnagar A, Boyd S, Sabour S, Bodnar J, Nazarian E, Peinovich N, Wagner C, Craft B, Snippes Vagnone P, Simpson J, Stone VN, Therrien M, Bateman A, Lower D, Huang JY, Gumbis S, Lonsway D, Lutgring JD, Karlsson M, Brown AC.
        Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0048621.
        Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC(50) and MIC(90) values of aztreonam-avibactam were 0.5/4 μg/ml and 8/4 μg/ml, respectively. Aztreonam-avibactam displayed potent in vitro activity against the MBL-producing Enterobacterales tested.

      2. The role of interspecies recombination in the evolution of antibiotic-resistant pneumococciexternal icon
        D'Aeth JC, van der Linden MP, McGee L, de Lencastre H, Turner P, Song JH, Lo SW, Gladstone RA, Sá-Leão R, Ko KS, Hanage WP, Breiman RF, Beall B, Bentley SD, Croucher NJ.
        Elife. 2021 Jul 14;10.
        Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn1207.1-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.

      3. Genomic diversity of azole-resistant Aspergillus fumigatus in the United Statesexternal icon
        Etienne KA, Berkow EL, Gade L, Nunnally N, Lockhart SR, Beer K, Jordan IK, Rishishwar L, Litvintseva AP.
        mBio. 2021 Aug 10:e0180321.
        Azole resistance in pathogenic Aspergillus fumigatus has become a global public health issue threatening the use of medical azoles. The environmentally occurring resistance mutations, TR(34)/L98H (TR(34)) and TR(46)/Y121F/T289A (TR(46)), are widespread across multiple continents and emerging in the United States. We used whole-genome single nucleotide polymorphism (SNP) analysis on 179 nationally represented clinical and environmental A. fumigatus genomes from the United States along with 18 non-U.S. genomes to evaluate the genetic diversity and foundation of the emergence of azole resistance in the United States. We demonstrated the presence of clades of A. fumigatus isolates: clade A (17%) comprised a global collection of clinical and environmental azole-resistant strains, including all strains with the TR(34)/L98H allele from India, The Netherlands, the United Kingdom, and the United States, and clade B (83%) consisted of isolates without this marker mainly from the United States. The TR(34)/L98H polymorphism was shared among azole-resistant A. fumigatus strains from India, The Netherlands, the United Kingdom, and the United States, suggesting the common origin of this resistance mechanism. Six percent of azole-resistant A. fumigatus isolates from the United States with the TR(34) resistance marker had a mixture of clade A and clade B alleles, suggestive of recombination. Additionally, the presence of equal proportions of both mating types further suggests the ongoing presence of recombination. This study demonstrates the genetic background for the emergence of azole resistance in the United States, supporting a single introduction and subsequent propagation, possibly through recombination of environmentally driven resistance mutations. IMPORTANCE Aspergillus fumigatus is one of the most common causes of invasive mold infections in patients with immune deficiencies and has also been reported in patients with severe influenza and severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2). Triazole drugs are the first line of therapy for this infection; however, their efficacy has been compromised by the emergence of azole resistance in A. fumigatus, which was proposed to be selected for by exposure to azole fungicides in the environment [P. E. Verweij, E. Snelders, G. H. J. Kema, E. Mellado, et al., Lancet Infect Dis 9:789-795, 2009,]. Isolates with environmentally driven resistance mutations, TR(34)/L98H (TR(34)) and TR(46)/Y121F/T289A (TR(46)), have been reported worldwide. Here, we used genomic analysis of a large sample of resistant and susceptible A. fumigatus isolates to demonstrate a single introduction of TR(34) in the United States and suggest its ability to spread into the susceptible population is through recombination between resistant and susceptible isolates.

      4. Trends in US outpatient antibiotic prescriptions during the coronavirus disease 2019 pandemicexternal icon
        King LM, Lovegrove MC, Shehab N, Tsay S, Budnitz DS, Geller AI, Lind JN, Roberts RM, Hicks LA, Kabbani S.
        Clin Infect Dis. 2021 Aug 2;73(3):e652-e660.
        BACKGROUND: The objective of our study was to describe trends in US outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies from January 2017 through May 2020. We averaged estimates from 2017 through 2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017-2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected because of seasonal trends alone, possibly related to the coronavirus disease 2019 pandemic and associated mitigation measures.

      5. Absence of SARS-CoV-2 infections among patients with end-stage renal disease following facility-wide testing in four outpatient hemodialysis facilitiesexternal icon
        Wilson WW, Bardossy AC, Gable P, Herzig C, Beshearse E, Gualandi N, Sabour S, Brown N, Brown AC, Kutty P, Tobin-D'Angelo M, Lea JP, Apata IW, Novosad S, Hudson M, Hernandez-Romieu AC, Tobolowsky F, Lyons A, Gilbert S, Soda E, Biedron C, Korhonen L.
        Am J Infect Control. 2021 Aug 7.
        Facility-wide testing performed at four outpatient hemodialysis facilities in the absence of an outbreak or escalating community incidence did not identify new SARS-CoV-2 infections and illustrated key logistical considerations essential to successful implementation of SARS-CoV-2 screening. Facilities could consider prioritizing facility-wide SARS-CoV-2 testing during suspicion of an outbreak in the facility or escalating community spread without robust infection control strategies in place. Being prepared to address operational considerations will enhance implementation of facility-wide testing in the outpatient dialysis setting.

    • Immunity and Immunization
      1. Reduced risk of reinfection with SARS-CoV-2 after COVID-19 vaccination - Kentucky, May-June 2021external icon
        Cavanaugh AM, Spicer KB, Thoroughman D, Glick C, Winter K.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1081-1083.
        Although laboratory evidence suggests that antibody responses following COVID-19 vaccination provide better neutralization of some circulating variants than does natural infection (1,2), few real-world epidemiologic studies exist to support the benefit of vaccination for previously infected persons. This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May-June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58-3.47). These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. To reduce their risk of infection, all eligible persons should be offered vaccination, even if they have been previously infected with SARS-CoV-2.

      2. Effects of prior season vaccination on current season vaccine effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 through 2017-2018external icon
        Kim SS, Flannery B, Foppa IM, Chung JR, Nowalk MP, Zimmerman RK, Gaglani M, Monto AS, Martin ET, Belongia EA, McLean HQ, Jackson ML, Jackson LA, Patel M.
        Clin Infect Dis. 2021 Aug 2;73(3):497-505.
        BACKGROUND: We compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated. METHODS: Our analysis included data from the US Flu Vaccine Effectiveness Network among participants ≥9 years old with acute respiratory illness from 2012-2013 through 2017-2018. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination among prior vaccinated. RESULTS: A total of 31 819 participants were included. Vaccine protection against any influenza averaged 42% (95% confidence interval [CI], 38%-47%) among those vaccinated only the current season, 37% (95% CI, 33-40) among those vaccinated both seasons, and 26% (95% CI, 18%-32%) among those vaccinated only the prior season, compared with participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (95% CI, 37%-46%), including 57%, 27%, and 55% against A(H1N1), A(H3N2), and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (95% CI, 7%-23%), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2). CONCLUSIONS: Our findings support Advisory Committee on Immunization Practices recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.

      3. Influenza vaccine acceptance and hesitancy among adults hospitalized with severe acute respiratory illnesses, United States 2019-2020external icon
        Lytle KL, Collins SP, Feldstein LR, Baughman AH, Brown SM, Casey JD, Erickson HL, Exline MC, Files DC, Gibbs KW, Ginde AA, Gong MN, Grijalva CG, Khan A, Lindsell CJ, Peltan ID, Prekker ME, Rice TW, Shapiro NI, Steingrub JS, Stubblefield WB, Tenforde MW, Womack KN, Patel MM, Self WH.
        Vaccine. 2021 Aug 7.
        INTRODUCTION: Understanding patient factors associated with not being vaccinated is essential for successful implementation of influenza vaccination programs. METHODS: We enrolled adults hospitalized with severe acute respiratory illness at 10 United States (US) hospitals during the 2019-2020 influenza season. We interviewed patients to collect data about influenza vaccination, sociodemographic characteristics, and vaccine perceptions. RESULTS: Among 679 participants, 264 (38.9%) reported not receiving influenza vaccination. Among those not vaccinated, 135 (51.1%) reported choosing not to receive a vaccine because of perceived ineffectiveness (36.7%) or risk (14.4%) of influenza vaccination. Sociodemographic factors associated with not being vaccinated included no medical insurance (aOR = 6.42; 95% CI: 2.52-16.38) and being non-White or Hispanic (aOR = 1.54, 95% CI: 1.02-2.32). CONCLUSIONS: Optimizing uptake of influenza vaccination in the US may be improved by educational programs regarding vaccine safety and effectiveness and enhancing vaccine access, particularly among non-White and Hispanic Americans and those without medical insurance.

      4. Effectiveness of COVID-19 vaccines in preventing hospitalization among adults aged ≥65 Years - COVID-NET, 13 states, February-April 2021external icon
        Moline HL, Whitaker M, Deng L, Rhodes JC, Milucky J, Pham H, Patel K, Anglin O, Reingold A, Chai SJ, Alden NB, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Farley MM, Ryan PA, Kim S, Nunez VT, Como-Sabetti K, Lynfield R, Sosin DM, McMullen C, Muse A, Barney G, Bennett NM, Bushey S, Shiltz J, Sutton M, Abdullah N, Talbot HK, Schaffner W, Chatelain R, Ortega J, Murthy BP, Zell E, Schrag SJ, Taylor C, Shang N, Verani JR, Havers FP.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1088-1093.
        Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI] = 94%-98%) for Pfizer-BioNTech, 96% (95% CI = 95%-98%) for Moderna, and 84% (95% CI = 64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI = 87%-94%) for Pfizer-BioNTech, 96% (95% CI = 93%-98%) for Moderna, and 85% (95% CI = 72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization.

      5. The clinical presentation of culture-positive and culture-negative, quantitative polymerase chain reaction (qPCR)-attributable shigellosis in the Global Enteric Multicenter Study and derivation of a shigella severity score: Implications for pediatric Shigella vaccine trialsexternal icon
        Pavlinac PB, Platts-Mills JA, Tickell KD, Liu J, Juma J, Kabir F, Nkeze J, Okoi C, Operario DJ, Uddin J, Ahmed S, Alonso PL, Antonio M, Becker SM, Breiman RF, Faruque AS, Fields B, Gratz J, Haque R, Hossain A, Hossain MJ, Jarju S, Qamar F, Iqbal NT, Kwambana B, Mandomando I, McMurry TL, Ochieng C, Ochieng JB, Ochieng M, Onyango C, Panchalingam S, Kalam A, Aziz F, Qureshi S, Ramamurthy T, Roberts JH, Saha D, Sow SO, Stroup SE, Sur D, Tamboura B, Taniuchi M, Tennant SM, Roose A, Toema D, Wu Y, Zaidi A, Nataro JP, Levine MM, Houpt ER, Kotloff KL.
        Clin Infect Dis. 2021 Aug 2;73(3):e569-e579.
        BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.

      6. Use of COVID-19 vaccines after reports of adverse events among adult recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021external icon
        Rosenblum HG, Hadler SC, Moulia D, Shimabukuro TT, Su JR, Tepper NK, Ess KC, Woo EJ, Mba-Jonas A, Alimchandani M, Nair N, Klein NP, Hanson KE, Markowitz LE, Wharton M, McNally VV, Romero JR, Talbot HK, Lee GM, Daley MF, Mbaeyi SA, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1094-1099.
        In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.

      7. Effectiveness of SARS-CoV-2 mRNA vaccines for preventing Covid-19 hospitalizations in the United Statesexternal icon
        Tenforde MW, Patel MM, Ginde AA, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, Gaglani M, McNeal T, Ghamande S, Shapiro NI, Gibbs KW, Files DC, Hager DN, Shehu A, Prekker ME, Erickson HL, Exline MC, Gong MN, Mohamed A, Henning DJ, Peltan ID, Brown SM, Martin ET, Monto AS, Khan A, Hough CT, Busse L, Ten Lohuis CC, Duggal A, Wilson JG, Gordon AJ, Qadir N, Chang SY, Mallow C, Gershengorn HB, Babcock HM, Kwon JH, Halasa N, Chappell JD, Lauring AS, Grijalva CG, Rice TW, Jones ID, Stubblefield WB, Baughman A, Womack KN, Lindsell CJ, Hart KW, Zhu Y, Olson SM, Stephenson M, Schrag SJ, Kobayashi M, Verani JR, Self WH.
        Clin Infect Dis. 2021 Aug 6.
        BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

    • Informatics
      1. Feasibility of replacing the ICD-10-CM with the ICD-11 for morbidity coding: A content analysisexternal icon
        Fung KW, Xu J, McConnell-Lamptey S, Pickett D, Bodenreider O.
        J Am Med Inform Assoc. 2021 Aug 12.
        OBJECTIVE: The study sought to assess the feasibility of replacing the International Classification of Diseases-Tenth Revision-Clinical Modification (ICD-10-CM) with the International Classification of Diseases-11th Revision (ICD-11) for morbidity coding based on content analysis. MATERIALS AND METHODS: The most frequently used ICD-10-CM codes from each chapter covering 60% of patients were identified from Medicare claims and hospital data. Each ICD-10-CM code was recoded in the ICD-11, using postcoordination (combination of codes) if necessary. Recoding was performed by 2 terminologists independently. Failure analysis was done for cases where full representation was not achieved even with postcoordination. After recoding, the coding guidance (inclusions, exclusions, and index) of the ICD-10-CM and ICD-11 codes were reviewed for conflict. RESULTS: Overall, 23.5% of 943 codes could be fully represented by the ICD-11 without postcoordination. Postcoordination is the potential game changer. It supports the full representation of 8.6% of 943 codes. Moreover, with the addition of only 9 extension codes, postcoordination supports the full representation of 35.2% of 943 codes. Coding guidance review identified potential conflicts in 10% of codes, but mostly not affecting recoding. The majority of the conflicts resulted from differences in granularity and default coding assumptions between the ICD-11 and ICD-10-CM. CONCLUSIONS: With some minor enhancements to postcoordination, the ICD-11 can fully represent almost 60% of the most frequently used ICD-10-CM codes. Even without postcoordination, 23.5% full representation is comparable to the 24.3% of ICD-9-CM codes with exact match in the ICD-10-CM, so migrating from the ICD-10-CM to the ICD-11 is not necessarily more disruptive than from the International Classification of Diseases-Ninth Revision-Clinical Modification to the ICD-10-CM. Therefore, the ICD-11 (without a CM) should be considered as a candidate to replace the ICD-10-CM for morbidity coding.

      2. Health information technology to improve care for people with multiple chronic conditionsexternal icon
        Samal L, Fu H, Djibril C, Wang J, Bierman A, Dorr DA.
        Health Serv Res. 2021 Aug 6.
        OBJECTIVE: To review evidence regarding the use of Health Information Technology (health IT) interventions aimed at improving care for people living with multiple chronic conditions (PLWMCC) in order to identify critical knowledge gaps. DATA SOURCES: We searched MEDLINE, CINAHL, PsycINFO, EMBASE, Compendex, and IEEE Xplore databases for studies published in English between 2010-2020. STUDY DESIGN: We identified studies of health IT interventions for PLWMCC across three domains: self-management support, care coordination, and algorithms to support clinical decision-making. DATA COLLECTION/EXTRACTION METHODS: Structured search queries were created and validated. Abstracts were reviewed iteratively to refine inclusion and exclusion criteria. The search was supplemented by manually searching the bibliographic sections of the included studies. The search included a forward citation search of studies nested within a clinical trial to identify the clinical trial protocol and published clinical trial results. Data was extracted independently by two reviewers. PRINCIPAL FINDINGS: The search yielded 1907 articles; 44 were included. Nine randomized controlled trials (RCTs) and 35 other studies including quasi-experimental, usability, feasibility, qualitative studies, or development/validation studies of analytic models. Five RCTs had positive results and the remaining four RCTs showed that the interventions had no effect. The studies address individual patient engagement and assess patient-centered outcomes such as quality of life. Few RCTs assess outcomes such as disability and none assess mortality. CONCLUSIONS: Despite a growing body of literature on health IT interventions or multicomponent interventions including a health IT component for chronic disease management, current evidence for applying health IT solutions to improve care for PLWMCC is limited. The body of literature included in this review provides critical information on the state of the science as well as the many gaps that need to be filled for digital health to fulfill its promise in supporting care delivery that meets the needs of PLWMCC. This article is protected by copyright. All rights reserved.

    • Injury and Violence
      1. BACKGROUND: Multi-victim homicides are a persistent public health problem confronting the United States. Previous research shows that homicide rates in the U.S. are approximately seven times higher than those of other high-income countries, driven by firearm homicide rates that are 25 times higher; 31% of public mass shootings in the world also occur in the U.S.. The purpose of this analysis is to examine the characteristics of mass, multiple, and single homicides to help identify prevention points that may lead to a reduction in different types of homicides. METHODS: We used all available years (2003-2017) and U.S. states/jurisdictions (35 states, the District of Columbia, and Puerto Rico) included in CDC's National Violent Death Reporting System (NVDRS), a public health surveillance system which combines death certificate, coroner/medical examiner, and law enforcement reports into victim- and incident-level data on violent deaths. NVDRS includes up to 600 standard variables per incident; further information on types of mental illness among suspected perpetrators and incident resolution was qualitatively coded from case narratives. Data regarding number of persons nonfatally shot within incidents were cross-validated when possible with several other resources, including government reports and the Gun Violence Archive. Mass homicides (4+ victims), multiple homicides (2-3 victims) and single homicides were analyzed to assess group differences using Chi-square tests with Bonferroni-corrected post-hoc comparisons. RESULTS: Mass homicides more often had female, child, and non-Hispanic white victims than other homicide types. Compared with victims of other homicide types, victims of mass homicides were more often killed by strangers or someone else they did not know well, or by family members. More than a third were related to intimate partner violence. Approximately one-third of mass homicide perpetrators had suicidal thoughts/behaviors noted in the time leading up to the incident. Multi-victim homicides were more often perpetrated with semi-automatic firearms than single homicides. When accounting for nonfatally shot victims, over 4 times as many incidents could have resulted in mass homicide. CONCLUSIONS: These findings underscore the important interconnections among multiple forms of violence. Primary prevention strategies addressing shared risk and protective factors are key to reducing these incidents.

    • Laboratory Sciences
      1. Detection of cytomegalovirus in urine dried on filter paperexternal icon
        Amin MM, Wong P, McCann M, Dollard SC.
        J Pediatric Infect Dis Soc. 2021 Aug 7.
        Urine is the best specimen for the diagnosis of congenital cytomegalovirus, but collection and processing of liquid urine are impractical for screening. Urine dried on filter paper was processed by the same convenient, low-cost method used by newborn screening to test blood spots and showed high sensitivity and specificity. To explore low cost, high-throughput methods to diagnose congenital cytomegalovirus infection (cCMV), we processed CMV-positive urine dried on filter paper by the same method used for processing blood spots for newborn screening. The results showed high sensitivity and specificity.

      2. RATIONALE: Over 2800 e-cigarette, or vaping, product use-associated lung injury (EVALI) cases were reported to the Centers for Disease Control and Prevention (CDC) during August 2019 to February 2020. Bronchoalveolar lavage (BAL) fluid samples from 51 EVALI and 99 non-EVALI cases were analyzed for toxicants including terpenes. We describe a novel method to measure selected terpenes in BAL fluid by gas chromatography/tandem mass spectrometry (GC/MS/MS). METHODS: α-Pinene, β-pinene, β-myrcene, 3-carene, and limonene were measured in BAL fluid specimens by headspace solid-phase microextraction/gas chromatography/tandem mass spectrometry. We created and characterized BAL fluid pools from non-EVALI individuals to determine assay accuracy, precision, linearity, limits of detection, and analytical specificity. All measurements were conducted in accordance with the CDC's Division of Laboratory Sciences rigorous method validation procedures. RESULTS: Matrix validation experiments showed that calibration curves in BAL fluid and saline had similar slopes, with differences of less than 7%. The assay precision ranged from 2.52% to 5.30%. In addition, the limits of detection for the five analytes ranged from 1.80 to 16.8 ng/L, and the linearity was confirmed with R(2) values >0.99. CONCLUSIONS: We developed and validated a method to quantify selected terpenes in BAL fluid specimens using GC/MS/MS. The assay provided accurate and precise analyses of EVALI and non-EVALI BAL fluid specimens in support of CDC's EVALI response. This method is applicable to the determination of a broad range of terpenes in BAL fluid specimens.

      3. A system for controlled generation of peracetic acid (PAA) atmospheres used to test and evaluate sampling and measurement devices was developed and characterized. Stable atmospheric conditions were maintained in a dynamic flow system for hours while multiple sensors were simultaneously exposed to equivalent atmospheres of PAA vapors. Atmospheres characterized by a range of PAA concentrations at a controlled flow rate, temperature, and humidity were generated. Presented herein is a system for vaporization of PAA solutions to generate controlled atmospheres with less than 3% relative standard deviation (RSD) of the PAA concentrations over time.

      4. The detection of phleboviruses (family: Phenuiviridae) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their predominantly nondescript clinical associations, and a related lack of awareness among some clinicians and lab-oratorians. Here, we seek to inform the detection of human phlebovirus infections by providing a brief introduction to clinically relevant phleboviruses, as well as key targets and approaches for their detection. Given the diversity of pathogens within the genus, this report focuses on diagnostic attributes that are generally shared among these agents and should be used as a complement to, rather than a replacement of, more detailed discussions on the detection of phleboviruses at the individual virus level. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      5. National biosafety management system: A combined framework approach based on 15 key elementsexternal icon
        Orelle A, Nikiema A, Zakaryan A, Albetkova AA, Rayfield MA, Peruski LF, Pierson A, Kachuwaire O.
        Front Public Health. 2021 ;9:609107.
        The pervasive nature of infections causing major outbreaks have elevated biosafety and biosecurity as a fundamental component for resilient national laboratory systems. In response to international health security demands, the Global Health Security Agenda emphasizes biosafety as one of the prerequisites to respond effectively to infectious disease threats. However, biosafety management systems (BMS) in low-medium income countries (LMIC) remain weak due to fragmented implementation strategies. In addition, inefficiencies in implementation have been due to limited resources, inadequate technical expertise, high equipment costs, and insufficient political will. Here we propose an approach to developing a strong, self-sustaining BMS based on extensive experience in LMICs. A conceptual framework incorporating 15 key components to guide implementers, national laboratory leaders, global health security experts in building a BMS is presented. This conceptual framework provides a holistic and logical approach to the development of a BMS with all critical elements. It includes a flexible planning matrix with timelines easily adaptable to different country contexts as examples, as well as resources that are critical for developing sustainable technical expertise.

      6. The recent introduction of large-scale, population-based serologic surveys in several nations where human African trypanosomiasis (HAT) remains endemic could provide an opportunity to better map the remaining disease foci and to identify asymptomatic, seropositive individuals who are infected with the more chronic form of the parasite, Trypanosoma brucei gambiense (gHAT). We have incorporated a soluble form of variant surface glycoprotein 117 and a recombinant invariant surface glycoprotein 65.1 into a multiplex bead assay (MBA) method that is commonly used for the detection of IgG antibody responses to other neglected tropical diseases. A positive result was defined as reactivity to both antigens. MBA sensitivity and specificity for gHAT infection were 92% and 96%, respectively. Assay specificity for the acute form of disease caused by T.b. rhodesiense (rHAT) was 94%, but the sensitivity was only 63.6%. In the future, additional antigens could be incorporated into the multiplex assay to improve rHAT sensitivity.

      7. Validation of a redesigned pan-poliovirus assay and real-time PCR platforms for the global poliovirus laboratory networkexternal icon
        Sun H, Harrington C, Gerloff N, Mandelbaum M, Jeffries-Miles S, Apostol LN, Valencia MA, Shaukat S, Angez M, Sharma DK, Nalavade UP, Pawar SD, Pukuta Simbu E, Andriamamonjy S, Razafindratsimandresy R, Vega E.
        PLoS One. 2021 ;16(8):e0255795.
        Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key to the surveillance workflow, where viruses are screened after cell culture isolation before a subset are verified by sequencing. The ITD kit is a series of real-time RT-PCR assays that screens cytopathic effect (CPE)-positive cell cultures using the standard WHO method for virus isolation. Because ITD screening is a critical procedure in the poliovirus identification workflow, validation of performance of real-time PCR platforms is a core requirement for the detection of poliovirus using the ITD kit. In addition, the continual update and improvement of the ITD assays to simplify interpretation in all platforms is necessary to ensure that all real-time machines are capable of detecting positive real-time signals. Four platforms (ABI7500 real-time systems, Bio-Rad CFX96, Stratagene MX3000P, and the Qiagen Rotor-Gene Q) were validated with the ITD kit and a redesigned poliovirus probe. The poliovirus probe in the real-time RT-PCR pan-poliovirus (PanPV) assay was re-designed with a double-quencher (Zen™) to reduce background fluorescence and potential false negatives. The updated PanPV probe was evaluated with a panel consisting of 184 polioviruses and non-polio enteroviruses. To further validate the updated PanPV probe, the new assay was pilot tested in five Global Polio Laboratory Network (GPLN) laboratories (Madagascar, India, Philippines, Pakistan, and Democratic Republic of Congo). The updated PanPV probe performance was shown to reduce background fluorescence and decrease the number of false positives compared to the standard PanPV probe.

    • Nutritional Sciences
      1. PURPOSE: During a pandemic, persons might experience worry because of threats (real or perceived), or as part of stress-related reactions. We aimed to provide insight into Americans' worry about food during COVID-19. Design, Subjects, Measures: Online survey data from June 2020 (n = 4,053 U.S. adults; 62.7% response rate) was used to assess 2 outcomes: worry about food availability (FA); food safety (FS). Adults with missing information about FA and FS were excluded from analysis (final n = 3,652). ANALYSIS: We used descriptive statistics and multivariable logistic regression to examine characteristics associated with the outcomes and estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) for associations between sociodemographic variables and outcomes. RESULTS: 58.3% of respondents reported worry about FA; 57.5% about FS, with higher odds of worry for FA and FS (versus referents) in lower income households (FA: aOR = 1.76 95%CI [1.30, 2.39]; FS: 1.84[1.35, 2.51]); unemployed (1.54[1.05, 2.28]; 1.90[1.26,2.81]); non-Hispanic Black (1.55[1.14,2.12]); 2.25[1.65,3.07]); Hispanic (1.39[1.06,1.82]; 1.94[1.46,2.56]). CONCLUSION: Findings highlight the importance of strategies to reduce consumer worry about FA and FS and negative food behaviors, and the need for continued access to hunger safety net programs, which could have positive effects on nutrition security.

    • Parasitic Diseases
      1. Assessment of the Chad guinea worm surveillance information system: A pivotal foundation for eradicationexternal icon
        Karki S, Weiss A, Dcruz J, Hunt D, Haigood B, Ouakou PT, Chop E, Zirimwabagabo H, Rubenstein BL, Yerian S, Roy SL, Kamb ML, Guagliardo SA.
        PLoS Negl Trop Dis. 2021 Aug 9;15(8):e0009675.
        BACKGROUND: In the absence of a vaccine or pharmacological treatment, prevention and control of Guinea worm disease is dependent on timely identification and containment of cases to interrupt transmission. The Chad Guinea Worm Eradication Program (CGWEP) surveillance system detects and monitors Guinea worm disease in both humans and animals. Although Guinea worm cases in humans has declined, the discovery of canine infections in dogs in Chad has posed a significant challenge to eradication efforts. A foundational information system that supports the surveillance activities with modern data management practices is needed to support continued program efficacy. METHODS: We sought to assess the current CGWEP surveillance and information system to identify gaps and redundancies and propose system improvements. We reviewed documentation, consulted with subject matter experts and stakeholders, inventoried datasets to map data elements and information flow, and mapped data management processes. We used the Information Value Cycle (IVC) and Data-Information System-Context (DISC) frameworks to help understand the information generated and identify gaps. RESULTS: Findings from this study identified areas for improvement, including the need for consolidation of forms that capture the same demographic variables, which could be accomplished with an electronic data capture system. Further, the mental models (conceptual frameworks) IVC and DISC highlighted the need for more detailed, standardized workflows specifically related to information management. CONCLUSIONS: Based on these findings, we proposed a four-phased roadmap for centralizing data systems and transitioning to an electronic data capture system. These included: development of a data governance plan, transition to electronic data entry and centralized data storage, transition to a relational database, and cloud-based integration. The method and outcome of this assessment could be used by other neglected tropical disease programs looking to transition to modern electronic data capture systems.

      2. A wandering missionary's burden: Persistent fever and progressive somnolence in a returning travelerexternal icon
        Yagnik KJ, Pezo-Salazar A, Rosenbaum D, Jaso JM, Cavuoti D, Nelson B, Chancey RJ, McKenna ML, Castellino LM.
        Open Forum Infect Dis. 2021 Aug;8(8):ofab377.
        Human African trypanosomiasis incidence has declined, but diagnosis remains difficult, especially in nonendemic areas. Our patient presented with fever, progressive lethargy, and weight loss for 5 months and had previously traveled to Ghana and Cameroon but had not been to areas with recently reported African trypanosomiasis. Extensive workup was negative, except for lymphocytic pleocytosis in cerebrospinal fluid; ultimately, a bone marrow aspiration revealed necrotizing granulomatous inflammation with 2 trypanosomes discovered on the aspirate smear, consistent with Trypanosoma brucei. The patient was treated with combination nifurtimox and eflornithine with full recovery.

    • Social and Behavioral Sciences
      1. How right now? Supporting mental health and resilience amid COVID-19external icon
        Burke-Garcia A, Johnson-Turbes A, Mitchell E, Vallery Verlenden JM, Puddy R, Mercado MC, Nelson P, Rabinowitz L, Xia K, Wagstaff L, Feng M, Caicedo L, Tolbert E.
        Traumatology. 2021 Aug.
        The How Right Now communication initiative (HRN) was developed to facilitate resilience amid the COVID-19 pandemic in the United States. HRN was designed as a conduit for promoting mental health and addressing feelings of grief, worry, and stress experienced during this time. This article provides an overview of the rapid, mixed-method, culturally responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN's disproportionately affected audiences (adults aged 65 and older and their caregivers, adults with preexisting physical and mental health conditions, adults experiencing violence, and adults experiencing economic distress) describe and discuss emotional resilience, what they need to be resilient, and what factors contribute to the perceptions of their ability to "bounce back" from the conditions caused by the COVID-19 pandemic. Data collection methods included an environmental scan (n >= 700 publications), social listening (n >= 1 million social media posts), partner needs-assessment calls (n = 16), partner-convened listening sessions with community members (n = 29), online focus groups (n = 58), and a national probability survey (n = 731), all in English and Spanish. Results revealed that HRN's audiences have diverse perceptions of what constitutes resilience. However, common factors were identified across populations to support resilience amid the COVID-19 pandemic, including informal and formal social support and access to services to meet basic needs, including food and housing resources. Stress, anxiety, depression, and experience with stigma and discrimination were also linked to resilience. Understanding the perspectives and experiences of disproportionately affected populations is vital to identifying supports and services, including the engagement of community stakeholders. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

    • Substance Use and Abuse
      1. Syringe service programs (SSP) increasingly serve rural areas of the United States, yet little is known about access and perceived need for their services. Objectives: This paper presents the HIV and viral hepatitis prevention, testing, and treatment, and, substance use disorder treatment and overdose prevention services offered at three SSPs and which services their clients accessed. Across the three SSPs, 45 clients (people who inject drugs [PWID]), 11 staff, and five stakeholders were interviewed. Results: Most clients (n = 34) reported accessing SSP services weekly and primarily for sterile syringes and injection-related supplies. All clients reported testing for HIV at least once, though concern for acquiring or transmitting HIV was divided between some or no concern. Most clients (n = 43) reported testing for hepatitis C virus (HCV). Concern for acquiring or transmitting HCV was also mixed. Vaccination for hepatitis A and/or B teetered around half (HAV: n = 23) to a third (HBV: n = 15). Most clients (n = 43) knew where to access the overdose countering medication, Narcan. Feelings about substance use treatment options varied, yet most felt not enough were available. Of note, not all assessed services were offered by the sampled SSPs. Conclusions/Importance: The findings help us understand PWIDs' rationale regarding services accessed and preference for particular services. The need for some services was not perceived by those at risk for the illness the services addressed. Discussing risk and providing tailored education is important when providing SSP services to rural residing PWIDs.

      2. Nicotine pouch unit sales in the US, 2016-2020external icon
        Marynak KL, Wang X, Borowiecki M, Kim Y, Tynan MA, Emery S, King BA.
        Jama. 2021 Aug 10;326(6):566-568.
        This study uses retail scanner data to assess nicotine pouch sales in the US between 2016 and 2020.

      3. Validation of the wave 1 and wave 2 Population Assessment of Tobacco and Health (PATH) study indicators of tobacco dependence using biomarkers of nicotine exposure across tobacco productsexternal icon
        Strong DR, Leas E, Noble M, White M, Glasser A, Taylor K, Edwards KC, Frissell KC, Compton WM, Conway KP, Lambert E, Kimmel HL, Silveira ML, Hull LC, van Bemmel D, Schroeder MJ, Cummings KM, Hyland A, Feng J, Blount B, Lanqing W, Niaura R.
        Nicotine Tob Res. 2021 Aug 12.
        INTRODUCTION: This study examined the predictive relationships between biomarkers of nicotine exposure and 16-item self-reported level of tobacco dependence (TD) and subsequent tobacco use outcomes. METHODS: The Population Assessment of Tobacco and Health (PATH) Study surveyed adult current established tobacco users who provided urine biospecimens at Wave 1 (September 2013-December 2014) and completed the Wave 2 (October 2014-October 2015) interview (n=6872). Mutually exclusive user groups at Wave 1 included: Cigarette Only, E-cigarette Only, Cigar Only, Hookah Only, Smokeless Tobacco Only, Cigarette Plus E-cigarette, multiple tobacco product users who smoked cigarettes, and multiple tobacco product users who did not smoke cigarettes. Total Nicotine Equivalents (TNE-2) and TD were measured at Wave 1. Approximate one-year outcomes included frequency/quantity used, quitting, and adding/switching to different tobacco products. RESULTS: For Cigarette Only smokers and multiple tobacco product users who smoked cigarettes, higher TD and TNE-2 were associated with: a tendency to smoke more, smoking more frequently over time, decreased likelihood of switching away from cigarettes, and decreased probability of quitting after one year. For other product user groups, Wave 1 TD and/or TNE-2 were less consistently related to changes in quantity and frequency of product use, or for adding or switching products, but higher TNE-2 was more consistently predictive of decreased probability of quitting. CONCLUSIONS: Self-reported TD and nicotine exposure assess common and independent aspects of dependence in relation to tobacco use behaviors for cigarette smokers. For other product user groups, nicotine exposure is a more consistent predictor of quitting than self-reported TD. IMPLICATIONS: This study suggests that smoking cigarettes leads to the most coherent pattern of associations consistent with a syndrome of TD. Because cigarettes continue to be prevalent and harmful, efforts to decrease their use may be accelerated via conventional means (e.g., smoking cessation interventions and treatments), but also perhaps by decreasing their dependence potential. The implications for noncombustible tobacco products are less clear as the stability of tobacco use patterns that include products such as e-cigarettes continue to evolve. TD, nicotine exposure measures, and consumption could be used in studies that attempt to understand and predict product-specific tobacco use behavioral outcomes.

    • Zoonotic and Vectorborne Diseases
      1. Integrated human-animal sero-surveillance of Brucellosis in the pastoral Afar and Somali regions of Ethiopiaexternal icon
        Tschopp R, Gebregiorgis A, Tassachew Y, Andualem H, Osman M, Waqjira MW, Hattendorf J, Mohammed A, Hamid M, Molla W, Mitiku SA, Walke H, Negron M, Kadzik M, Mamo G.
        PLoS Negl Trop Dis. 2021 Aug 6;15(8):e0009593.
        BACKGROUND: Brucellosis is widespread in Ethiopia with variable reported prevalence depending on the geographical area, husbandry practices and animal species. However, there is limited information on the disease prevalence amongst pastoral communities, whose life is intricately linked with their livestock. METHODOLOGY: We conducted an integrated human-animal brucellosis sero-surveillance study in two adjacent pastoral regions, Afar and Somali region (SRS). This cross-sectional study included 13 woredas (districts) and 650 households. Blood samples were collected from people and livestock species (cattle, camel, goats and sheep). Sera were analyzed with C-ELISA for camels and shoats (sheep and goats), with I-ELISA for cattle and IgG ELISA for humans. Descriptive and inferential statistics analyses were performed. RESULTS: A total of 5469 sera were tested by ELISA. Prevalence of livestock was 9.0% in Afar and 8.6% in SRS (ranging from 0.6 to 20.2% at woreda level). In humans, prevalence was 48.3% in Afar and 34.9% in SRS (ranging from 0.0 to 74.5% at woreda level). 68.4% of all households in Afar and 57.5% of households in SRS had at least one animal reactor. Overall, 4.1% of animals had a history of abortion. The proportion of animals with abortion history was higher in seropositive animals than in seronegative animals. Risk factor analysis showed that female animals were significantly at higher risk of being reactors (p = 0.013). Among the species, cattle had the least risk of being reactors (p = 0.014). In humans, there was a clear regional association of disease prevalence (p = 0.002). The older the people, the highest the odds of being seropositive. CONCLUSION: Brucellosis is widespread in humans and animals in pastoral communities of Afar and SRS with the existence of geographical hotspots. No clear association was seen between human and particular livestock species prevalence, hence there was no indication as whether B. abortus or B. melitensis are circulating in these areas, which warrants further molecular research prior to embarking on a national control programs. Such programs will need to be tailored to the pastoral context.

      2. West Nile virus and other domestic nationally notifiable arboviral diseases - United States, 2019external icon
        Vahey GM, Mathis S, Martin SW, Gould CV, Staples JE, Lindsey NP.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1069-1074.
        Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses, including La Crosse, Jamestown Canyon, Powassan, eastern equine encephalitis, and St. Louis encephalitis viruses, cause sporadic disease and occasional outbreaks. This report summarizes surveillance data for nationally notifiable domestic arboviruses reported to CDC for 2019. For 2019, 47 states and the District of Columbia (DC) reported 1,173 cases of domestic arboviral disease, including 971 (83%) WNV disease cases. Among the WNV disease cases, 633 (65%) were classified as neuroinvasive disease, for a national incidence of 0.19 cases per 100,000 population, 53% lower than the median annual incidence during 2009-2018. More Powassan and eastern equine encephalitis virus disease cases were reported in 2019 than in any previous year. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform recommended diagnostic testing, and promptly report cases to public health authorities. Because arboviral diseases continue to cause serious illness, and annual incidence of individual viruses continues to vary with sporadic outbreaks, maintaining surveillance is important in directing prevention activities. Prevention depends on community and household efforts to reduce vector populations and personal protective measures to prevent mosquito and tick bites such as use of Environmental Protection Agency-registered insect repellent and wearing protective clothing.*(,)(†).

      3. Notes from the field: Recurrence of a multistate outbreak of Salmonella Typhimurium infections linked to contact with hedgehogs - United States and Canada, 2020external icon
        Waltenburg MA, Nichols M, Waechter H, Higa J, Cronquist L, Lowe AM, Adams JK, McFadden K, McConnell JA, Blank R, Basler C.
        MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1100-1102.

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