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Issue 35, August 30, 2022

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CDC Science Clips: Volume 14, Issue 35, August 30, 2022

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. Invasive group a streptococcal penicillin binding protein 2× variants associated with reduced susceptibility to β-lactam antibiotics in the United States, 2015-2021
        Chochua S, Metcalf B, Li Z, Mathis S, Tran T, Rivers J, Fleming-Dutra KE, Li Y, McGee L, Beall B.
        Antimicrob Agents Chemother. 2022 Aug 15:e0080222.
        All known group A streptococci [GAS] are susceptible to β-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (emm43.4/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to β-lactams. We aimed to quantitate PBP2x variants, small changes in β-lactam MICs, and lineages within contemporary population-based iGAS. PBP2x substitutions were comprehensively identified among 13,727 iGAS recovered during 2015-2021, in the USA. Isolates were subjected to antimicrobial susceptibility testing employing low range agar diffusion and PBP2x variants were subjected to phylogenetic analyses. Fifty-five variants were defined based upon substitutions within an assigned PBP2x transpeptidase domain. Twenty-nine of these variants, representing 338/13,727 (2.5%) isolates and 16 emm types, exhibited slightly elevated β-lactam MICs, none of which were above clinical breakpoints. The emm43.4/PBP2x-T553K variant, comprised of two isolates, displayed the most significant phenotype (ampicillin MIC 0.25 μg/ml) and harbored missense mutations within 3 non-PBP genes with known involvement in antibiotic efflux, membrane insertion of PBP2x, and peptidoglycan remodeling. The proportion of all PBP2x variants with elevated MICs remained stable throughout 2015-2021 (<3.0%). The predominant lineage (emm4/PBP2x-M593T/ermT) was resistant to macrolides/lincosamides and comprised 129/340 (37.9%) of isolates with elevated β-lactam MICs. Continuing β-lactam selective pressure is likely to have selected PBP2x variants that had escaped scrutiny due to MICs that remain below clinical cutoffs. Higher MICs exhibited by emm43.4/PBP2x-T553K are probably rare due to the requirement of additional mutations. Although elevated β-lactam MICs remain uncommon, emm43.4/PBP2x-T553K and emm4/PBP2x-M593T/ermT lineages indicate that antibiotic stewardship and strain monitoring is necessary.

      2. Genomic diversity, antimicrobial resistance, and virulence gene profiles of Salmonella serovar Kentucky isolated from humans, food, and animal ceca content sources in the United States
        Tate H, Hsu CH, Chen JC, Han J, Foley SL, Folster JP, Francois Watkins LK, Reynolds J, Tillman GE, Nyirabahizi E, Zhao S.
        Foodborne Pathog Dis. 2022 Aug;19(8):509-521.
        Salmonella serovar Kentucky is frequently isolated from chickens and dairy cattle, but recovery from humans is comparatively low based on the U.S. National Antimicrobial Resistance Monitoring System (NARMS) reports. We aimed to better describe the genetic diversity, antimicrobial resistance, and virulence determinants of Salmonella Kentucky isolates from humans, food animal ceca, retail meat and poultry products, imported foods and food products, and other samples. We analyzed the genomes of 774 Salmonella Kentucky isolates and found that 63% (54/86) of human isolates were sequence type (ST)198, 33% (29/86) were ST152, and 3.5% (3/86) were ST314. Ninety-one percent (570/629) of cecal isolates and retail meat and poultry isolates were ST152 or ST152-like (one allele difference), and 9.2% (58/629) were ST198. Isolates from imported food were mostly ST198 (60%, 22/37) and ST314 (29.7%, 11/37). ST198 isolates clustered into two main lineages. Clade ST198.2 comprised almost entirely isolates from humans and imported foods, all containing triple mutations in the quinolone resistance-determining region (QRDR) that confer resistance to fluoroquinolones. Clade ST198.1 contained isolates from humans, ceca, retail meat and poultry products, and imported foods that largely lacked QRDR mutations. ST152 isolates from cattle had a lineage (Clade 2) distinct from ST152 isolates from chicken (Clade 4), and half of ST152 human isolates clustered within two other clades (Clades 1 and 3), largely distinct from Clades 2 and 4. Although clinical illness associated with Salmonella Kentucky is low, ST198 appears to account for most human infections in the Unites States but is uncommon among ceca of domestic food animals and retail meat and poultry products. These findings, combined with human exposure data, suggest that fluoroquinolone-resistant ST198 infections may be linked to the consumption of food products that are imported or consumed while traveling. We also found unique differences in the composition of virulence genes and antimicrobial resistance genes among the clades, which may provide clues to the host specificity and pathogenicity of Salmonella Kentucky lineages.

      3. Implementation and outcomes of a clinician-directed intervention to improve antibiotic prescribing for acute respiratory tract infections within the Veterans' Affairs Healthcare System
        Madaras-Kelly KJ, Rovelsky SA, McKie RA, Nevers MR, Ying J, Haaland BA, Kay CL, Christopher ML, Hicks LA, Samore MH.
        Infect Control Hosp Epidemiol. 2022 Aug 15:1-9.
        OBJECTIVE: To determine whether a clinician-directed acute respiratory tract infection (ARI) intervention was associated with improved antibiotic prescribing and patient outcomes across a large US healthcare system. DESIGN: Multicenter retrospective quasi-experimental analysis of outpatient visits with a diagnosis of uncomplicated ARI over a 7-year period. PARTICIPANTS: Outpatients with ARI diagnoses: sinusitis, pharyngitis, bronchitis, and unspecified upper respiratory tract infection (URI-NOS). Outpatients with concurrent infection or select comorbid conditions were excluded. INTERVENTION(S): Audit and feedback with peer comparison of antibiotic prescribing rates and academic detailing of clinicians with frequent ARI visits. Antimicrobial stewards and academic detailing personnel delivered the intervention; facility and clinician participation were voluntary. MEASURE(S): We calculated the probability to receive antibiotics for an ARI before and after implementation. Secondary outcomes included probability for a return clinic visits or infection-related hospitalization, before and after implementation. Intervention effects were assessed with logistic generalized estimating equation models. Facility participation was tracked, and results were stratified by quartile of facility intervention intensity. RESULTS: We reviewed 1,003,509 and 323,023 uncomplicated ARI visits before and after the implementation of the intervention, respectively. The probability to receive antibiotics for ARI decreased after implementation (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78-0.86). Facilities with the highest quartile of intervention intensity demonstrated larger reductions in antibiotic prescribing (OR, 0.69; 95% CI, 0.59-0.80) compared to nonparticipating facilities (OR, 0.89; 95% CI, 0.73-1.09). Return visits (OR, 1.00; 95% CI, 0.94-1.07) and infection-related hospitalizations (OR, 1.21; 95% CI, 0.92-1.59) were not different before and after implementation within facilities that performed intensive implementation. CONCLUSIONS: Implementation of a nationwide ARI management intervention (ie, audit and feedback with academic detailing) was associated with improved ARI management in an intervention intensity-dependent manner. No impact on ARI-related clinical outcomes was observed.

    • Chronic Diseases and Conditions
      1. At the intersection of sexual and reproductive health and HIV services: use of moderately effective family planning among female sex workers in Kampala, Uganda
        Hakim AJ, Ogwal M, Doshi RH, Kiyingi H, Sande E, Serwadda D, Musinguzi G, Standish J, Hladik W.
        BMC Pregnancy Childbirth. 2022 Aug 17;22(1):646.
        BACKGROUND: Female sex workers are vulnerable to HIV, sexually transmitted diseases, and unintended pregnancies; however, the literature on female sex workers (FSW) focuses primarily on HIV and is limited regarding these other health issues. METHODS: We conducted a respondent-driven sampling (RDS) survey during April-December 2012 to characterize the reproductive health of and access to contraceptives FSW in Kampala, Uganda. Eligibility criteria included age ≥ 15 years, residence in greater Kampala, and having sold sex to men in ≤ 6 months. Data were analyzed using RDS-Analyst. Survey logistic regression was used in SAS. RESULTS: We enrolled 1,497 FSW with a median age of 27 years. Almost all FSW had been pregnant at least once. An estimated 33.8% of FSW were currently not using any form of family planning (FP) to prevent pregnancy; 52.7% used at least moderately effective FP. Among those using FP methods, injectable contraception was the most common form of FP used (55.4%), followed by condoms (19.7%), oral contraception (18.1%), and implants (3.7%). HIV prevalence was 31.4%, syphilis prevalence was 6.2%, and 89.8% had at least one symptom of a sexually transmitted disease in the last six months. Using at least a moderately effective method of FP was associated with accessing sexually transmitted disease treatment in a stigma-free environment in the last six months (aOR: 1.6, 95% CI: 1.1-2.4), giving birth to 2-3 children (aOR: 2.5, 95% CI: 1.4-4.8) or 4-5 children (aOR: 2.9, 95% CI: 1.4-5.9). It is plausible that those living with HIV are also less likely than those without it to be using a moderately effective method of FP (aOR: 0.7, 95% CI: 0.5-1.0). CONCLUSIONS: The provision of integrated HIV and sexual and reproductive health services in a non-stigmatizing environment has the potential to facilitate increased health service uptake by FSW and decrease missed opportunities for service provision.

      2. Depression, stigma and social isolation: the psychosocial trifecta of primary chronic cutaneous lupus erythematosus, a cross-sectional and path analysis
        Drenkard C, Theis KA, Daugherty TT, Helmick CG, Dunlop-Thomas C, Bao G, Aspey L, Lewis TT, Lim SS.
        Lupus Sci Med. 2022 Aug;9(1).
        OBJECTIVE: Depression is common in individuals with chronic cutaneous lupus erythematosus (CCLE). However, how CCLE may impact patients' psychological well-being is poorly understood, particularly among disproportionally affected populations. We examined the relationships between depression and psychosocial factors in a cohort of predominantly Black patients with primary CCLE (CCLE without systemic manifestations). METHODS: Cross-sectional assessment of individuals with dermatologist-validated diagnosis of primary CCLE. NIH-PROMIS short-forms were used to measure depression, disease-related stigma, social isolation and emotional support. Linear regression analyses (ɑ=0.05) were used to test an a priori conceptual model of the relationship between stigma and depression and the effect of social isolation and emotional support on that association. RESULTS: Among 121 participants (87.6% women; 85.1% Black), 37 (30.6%) reported moderate to severe depression. Distributions of examined variables divided equally among those which did (eg, work status, stigma (more), social isolation (more), emotional support (less)) and did not (eg, age, sex, race, marital status) significantly differ by depression. Stigma was significantly associated with depression (b=0.77; 95% CI0.65 to 0.90), whereas social isolation was associated with both stigma (b=0.85; 95% CI 0.72 to 0.97) and depression (b=0.70; 95% CI0.58 to 0.92). After controlling for confounders, stigma remained associated with depression (b=0.44; 95% CI0.23 to 0.66) but lost significance (b=0.12; 95% CI -0.14 to 0.39) when social isolation (b=0.40; 95% CI 0.19 to 0.62) was added to the model. Social isolation explained 72% of the total effect of stigma on depression. Emotional support was inversely associated with depression in the univariate analysis; however, no buffer effect was found when it was added to the multivariate model. CONCLUSION: Our findings emphasise the psychosocial challenges faced by individuals living with primary CCLE. The path analysis suggests that stigmatisation and social isolation might lead to depressive symptoms. Early clinical identification of social isolation and public education demystifying CCLE could help reduce depression in patients with CCLE.

      3. Integrating hypertension and HIV care in Namibia: A quality improvement collaborative approach
        Basenero A, Neidel J, Ikeda DJ, Ashivudhi H, Mpariwa S, Kamangu JW, Mpalang Kakubu MA, Hans L, Mutandi G, Jed S, Tjituka F, Hamunime N, Agins BD.
        PLoS One. 2022 ;17(8):e0272727.
        BACKGROUND: Hypertension (HTN) is highly prevalent among people with HIV (PWH) in Namibia, but screening and treatment for HTN are not routinely offered as part of HIV care delivery. We report the implementation of a quality improvement collaborative (QIC) to accelerate integration of HTN and HIV care within public-sector health facilities in Namibia. METHODS: Twenty-four facilities participated in the QIC with the aim of increasing HTN screening and treatment among adult PWH (>15 years). HTN was defined according to national treatment guidelines (i.e., systolic blood pressure >140 and/or diastolic blood pressure >90 across three measurements and at least two occasions), and decisions regarding initiation of treatment were made by physicians only. Teams from participating hospitals used quality improvement methods, monthly measurement of performance indicators, and small-scale tests of change to implement contextually tailored interventions. Coaching of sites was performed on a monthly basis by clinical officers with expertise in QI and HIV, and sites were convened as part of learning sessions to facilitate diffusion of effective interventions. RESULTS: Between March 2017 and March 2018, hypertension screening occurred as part of 183,043 (86%) clinical encounters at participating facilities. Among 1,759 PWH newly diagnosed with HTN, 992 (56%) were initiated on first-line treatment. Rates of treatment initiation were higher in facilities with an on-site physician (61%) compared to those without one (51%). During the QIC, facility teams identified fourteen interventions to improve HTN screening and treatment. Among barriers to implementation, teams pointed to malfunctions of blood pressure machines and stock outs of antihypertensive medications as common challenges. CONCLUSIONS: Implementation of a QIC provided a structured approach for integrating HTN and HIV services across 24 high-volume facilities in Namibia. As rates of HTN treatment remained low despite ongoing facility-level changes, policy-level interventions-such as task sharing and supply chain strengthening-should be pursued to further improve delivery of HTN care among PWH beyond initial screening.

    • Communicable Diseases
      1. Characteristics and treatment of hospitalized pregnant women with Coronavirus Disease 2019, COVID-19
        Sekkarie A, Woodruff R, Whitaker M, Kramer MR, Zapata LB, Ellington SR, Meaney-Delman DM, Pham H, Patel K, Taylor CA, Chai SJ, Kawasaki B, Meek J, Openo KP, Weigel A, Leegwater L, Como-Sabetti K, Ropp SL, Muse A, Bennett NM, Billing LM, Sutton M, Talbot HK, Hill M, Havers FP.
        Am J Obstet Gynecol MFM. 2022 Aug 12:100715.
        BACKGROUND: Pregnant women less frequently receive Coronavirus Disease 2019 (COVID-19) vaccination and are at increased risk for adverse pregnancy outcomes from COVID-19. OBJECTIVES: First, describe the vaccination status, treatment, and outcomes of hospitalized, symptomatic pregnant women with COVID-19 and second, estimate whether treatment differs by pregnancy status among treatment-eligible (i.e., requiring supplemental oxygen per National Institutes of Health guidelines at the time of the study) women. STUDY DESIGN: During January-November 2021, the COVID-19-Associated Hospitalization Surveillance Network completed medical chart abstraction for a probability sample of 2,715 hospitalized women aged 15-49 years with laboratory-confirmed SARS-CoV-2 infection. Of these, 1,950 women had symptoms of COVID-19 upon admission; 336 were pregnant. We calculated weighted prevalence estimates of demographic and clinical characteristics, vaccination status, and outcomes among pregnant women with symptoms of COVID-19 upon admission. We used propensity score matching to estimate prevalence ratios (PR), and 95% confidence intervals (CI) of treatment-eligible patients who received remdesivir or systemic steroids by pregnancy status. RESULTS: Among 336 hospitalized pregnant women with symptomatic COVID-19, 39.6% were non-Hispanic Black, 24.8% were Hispanic or Latino, and 61.9% were aged 25-34 years. Among those with known COVID-19 vaccination status, 92.9% were unvaccinated. One-third (32.7%) were treatment-eligible. Among treatment-eligible pregnant women, 74.1% received systemic steroids and 61.4% received remdesivir. Among those that were no longer pregnant at discharge (n=180), 5.4% had spontaneous abortions and 3.5% had stillbirths. Of the 159 live births, 29.0% were pre-term. Among a propensity score-matched cohort of treatment-eligible hospitalized women of reproductive age, pregnant women were less likely than non-pregnant women to receive remdesivir (PR: 0.82, 95% CI 0.69-0.97) and systemic steroids (PR: 0.80, 95% CI 0.73-0.87). CONCLUSION: Most hospitalized pregnant patients with symptomatic COVID-19 were unvaccinated. Hospitalized pregnant patients were less likely to receive recommended remdesivir and systemic steroids compared to similar hospitalized non-pregnant women. Our results underscore the need to identify opportunities for improving COVID-19 vaccination, implementation of treatment of pregnant women, and the inclusion of pregnant women in clinical trials.

      2. Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi
        Bello G, Kagoli M, Chipeta S, Auld A, Chang JC, DeVos JR, Kim E, Mkungudza J, Payne D, Eliya M, Nyirenda R, Jahn A, Mzumara T, Mvula B, Dadabhai S, Namakhoma I, Babaye Y, Giron A, Jordan MR, Bertagnolio S, O'Malley G, Wadonda-Kabondo N.
        Antivir Ther. 2022 Aug;27(4):13596535221121225.
        BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

      3. Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season
        Ramay BM, Jara J, Moreno MP, Lupo P, Serrano C, Alvis JP, Arriola CS, Veguilla V, Kaydos-Daniels SC.
        BMC Public Health. 2022 Aug 13;22(1):1541.
        OBJECTIVES: We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices. METHODS: A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants' ILI-associated self-medication practices were documented using a questionnaire. RESULTS: Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased. CONCLUSIONS: During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens.

      4. COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review
        Drzymalla E, Green RF, Knuth M, Khoury MJ, Dotson WD, Gundlapalli A.
        Clin Immunol. 2022 Aug 13:109097.
        A better understanding of COVID-19 in people with primary immunodeficiency (PI), rare inherited defects in the immune system, is important for protecting this population, especially as population-wide approaches to mitigation change. COVID-19 outcomes in the PI population could have broader public health implications because some people with PI might be more likely to have extended illnesses, which could lead to increased transmission and emergence of variants. We performed a systematic review on COVID-19-associated morbidity and mortality in people with PI. Of the 1114 articles identified through the literature search, we included 68 articles in the review after removing 1046 articles because they were duplicates, did not involve COVID-19, did not involve PI, were not in English, were commentaries, or could not be accessed. The 68 articles included outcomes for 459 people with PI and COVID-19. Using data from these 459 people, we calculated a case fatality rate of 9%, hospitalization rate of 49%, and oxygen supplementation rate of 29%. Studies have indicated that a number of people with PI showed at least some immune response to COVID-19 vaccination, with responses varying by type of PI and other factors, although vaccine effectiveness against hospitalization was lower in the PI population than in the general population. In addition to being up-to-date on vaccinations, current strategies for optimizing protection for people with PI can include pre-exposure prophylaxis for those eligible and use of therapeutics. Overall, people with PI, when infected, tested positive and showed symptoms for similar lengths of time as the general population. However, a number of people with x-linked agammaglobulinemia (XLA) or other B-cell pathway defects were reported to have prolonged infections, measured by time from first positive SARS-CoV-2 test to first negative test. As prolonged infections might increase the likelihood of genetic variants emerging, SARS-CoV2 isolates from people with PI and extended illness would be good candidates to prioritize for whole genome sequencing.

      5. SARS-CoV-2 testing and detection during peripartum hospitalizations among a multi-center cohort of pregnant persons, March 2020-February 2021
        Delahoy MJ, Munoz F, Li K, Arriola CS, Bond NL, Daugherty M, Ferber J, Ferguson N, Hadden L, Henderson JT, Irving SA, Juergens M, Kancharla V, Greenberg M, Odouli R, Newes-Adeyi G, Nicholson EG, Reichle L, Sanyang M, Snead M, Dawood FS, Naleway AL.
        Clin Infect Dis. 2022 Aug 12.
        BACKGROUND: Identifying SARS-CoV-2 infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 U.S. integrated healthcare networks (Sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 prenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. RESULTS: Among 17,858 pregnant persons, 10,863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10,683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% CI: 1.03-1.79; referent: White) (Site 1), Hispanic or Latina ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (Site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (Site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [Site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [Site 2]). CONCLUSIONS: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.

      6. Genomic surveillance of SARS-CoV-2 in Puerto Rico enabled early detection and tracking of variants
        Santiago GA, Flores B, González GL, Charriez KN, Huertas LC, Volkman HR, Van Belleghem SM, Rivera-Amill V, Adams LE, Marzán M, Hernández L, Cardona I, O'Neill E, Paz-Bailey G, Papa R, Muñoz-Jordan JL.
        Commun Med (Lond). 2022 ;2:100.
        BACKGROUND: Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island's population and became a critical threat to public health. METHODS: We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. RESULTS: Our analyses reveal that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after ~4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated in Puerto Rico from September to December 2020 and subsequently spread to the United States. CONCLUSIONS: The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses.

      7. First episodes of norovirus and sapovirus gastroenteritis protect against subsequent episodes in a Nicaraguan birth cohort
        Vielot NA, Reyes Y, Blette B, González F, Toval-Ruiz C, Gutiérrez L, Vilchez S, Diez-Valcarce M, Vinjé J, Becker-Dreps S, Bucardo F.
        Epidemiology. 2022 Sep 1;33(5):650-653.
        BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.

      8. HIV risk factors and risk perception among adolescent girls and young women: Results from a population-based survey in Western Kenya, 2018
        Kamire V, Magut F, Khagayi S, Kambona C, Muttai H, Nganga L, Kwaro D, Joseph RH.
        J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):17-25.
        BACKGROUND: In sub-Saharan Africa, HIV prevalence in adolescent girls and young women (AGYW) is 2-fold to 3-fold higher than that in adolescent boys and young men. Understanding AGYW's perception of HIV risk is essential for HIV prevention efforts. METHODS: We analyzed data from a HIV biobehavioral survey conducted in western Kenya in 2018. Data from AGYW aged 15-24 years who had a documented HIV status were included. We calculated weighted prevalence and evaluated factors associated with outcomes of interest (HIV infection and high risk perception) using generalized linear models to calculate prevalence ratios. RESULTS: A total of 3828 AGYW were included; 63% were aged 15-19 years. HIV prevalence was 4.5% and 14.5% of sexually active AGYW had high risk perception. Over 70% of participants had accessed HIV testing and counseling in the past 12 months. Factors associated with both HIV infection and high risk perception included having an HIV-positive partner or partner with unknown status and having a sexually transmitted infection in the past 12 months. Having an older (by ≥10 years) partner was associated with HIV infection, but not high risk perception. Less than 30% of sexually active AGYW with 3 or more HIV risk factors had high perception of HIV risk. CONCLUSION: Gaps in perceived HIV risk persist among AGYW in Kenya. High access to HIV testing and prevention services in this population highlights platforms through which AGYW may be reached with improved risk counseling, and to increase uptake of HIV prevention strategies.

      9. Outcomes of HIV positive children and adolescents initiated on antiretroviral treatment in Nigeria (2007-2016)
        Anukam O, Blanco N, Jumare J, Lo J, Babatunde E, Odafe S, Onotu D, Ene U, Fagbamigbe J, Carpenter D, Rivadeneira ED, Omoigberale AI, Charurat M, Swaminathan M, Stafford KA.
        J Int Assoc Provid AIDS Care. 2022 Jan-Dec;21:23259582221117009.
        Background: This manuscript aimed to examine treatment outcomes of HIV-positive children and adolescents. Methods: We retrospectively analyzed data of a sample of patients aged 0-19 years who initiated ART (October 2007-September 2016) in participating sites in 30 states and the Federal Capital Territory in Nigeria. Results: Among 4006 patients alive at the end of the follow up period, 138 (3.4%) were LTFU. Adolescents had a significantly higher risk of being LTFU than children aged 3-5 years (HR 2.47 [95% CI 1.40-4.34]). Patients with advanced disease had a significantly higher risk of being LTFU (Stage IV HR, 3.66 [95% CI: 2.00-6.68]). On average, optimal ART refill adherence was met by 67.3% of patients. Conclusion: Our findings suggest that focusing on preventing and managing advanced disease and interventions supporting adolescents when transferring to adult care is warranted.

      10. Health care utilization in the 6 months following SARS-CoV-2 infection
        Tartof SY, Malden DE, Liu IA, Sy LS, Lewin BJ, Williams JT, Hambidge SJ, Alpern JD, Daley MF, Nelson JC, McClure D, Zerbo O, Henninger ML, Fuller C, Weintraub E, Saydah S, Qian L.
        JAMA Netw Open. 2022 Aug 1;5(8):e2225657.
        IMPORTANCE: After SARS-CoV-2 infection, many patients present with persistent symptoms for at least 6 months, collectively termed post-COVID conditions (PCC). However, the impact of PCC on health care utilization has not been well described. OBJECTIVES: To estimate COVID-19-associated excess health care utilization following acute SARS-CoV-2 infection and describe utilization for select PCCs among patients who had positive SARS-CoV-2 test results (including reverse transcription-polymerase chain reaction and antigen tests) compared with control patients whose results were negative. DESIGN, SETTING, AND PARTICIPANTS: This matched retrospective cohort study included patients of all ages from 8 large integrated health care systems across the United States who completed a SARS-CoV-2 diagnostic test during March 1 to November 1, 2020. Patients were matched on age, sex, race and ethnicity, site, and date of SARS-CoV-2 test and were followed-up for 6 months. Data were analyzed from March 18, 2021, to June 8, 2022. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Ratios of rate ratios (RRRs) for COVID-19-associated health care utilization were calculated with a difference-in-difference analysis using Poisson regression models. RRRs were estimated overall, by health care setting, by select population characteristics, and by 44 PCCs. COVID-19-associated excess health care utilization was estimated by health care setting. RESULTS: The final matched cohort included 127 859 patients with test results positive for SARS-CoV-2 and 127 859 patients with test results negative for SARS-CoV-2. The mean (SD) age of the study population was 41.2 (18.6) years, 68 696 patients in each group (53.7%) were female, and each group included 66 211 Hispanic patients (51.8%), 9122 non-Hispanic Asian patients (7.1%), 7983 non-Hispanic Black patients (6.2%), and 34 326 non-Hispanic White patients (26.9%). Overall, SARS-CoV-2 infection was associated with a 4% increase in health care utilization over 6 months (RRR, 1.04 [95% CI, 1.03-1.05]), predominantly for virtual encounters (RRR, 1.14 [95% CI, 1.12-1.16]), followed by emergency department visits (RRR, 1.08 [95% CI, 1.04-1.12]). COVID-19-associated utilization for 18 PCCs remained elevated 6 months from the acute stage of infection, with the largest increase in COVID-19-associated utilization observed for infectious disease sequelae (RRR, 86.00 [95% CI, 5.07-1458.33]), COVID-19 (RRR, 19.47 [95% CI, 10.47-36.22]), alopecia (RRR, 2.52 [95% CI, 2.17-2.92]), bronchitis (RRR, 1.85 [95% CI, 1.62-2.12]), pulmonary embolism or deep vein thrombosis (RRR, 1.74 [95% CI, 1.36-2.23]), and dyspnea (RRR, 1.73 [95% CI, 1.61-1.86]). In total, COVID-19-associated excess health care utilization amounted to an estimated 27 217 additional medical encounters over 6 months (212.9 [95% CI, 146.5-278.4] visits per 1000 patients). CONCLUSIONS AND RELEVANCE: This cohort study documented an excess health care burden of PCC in the 6 months after the acute stage of infection. As health care systems evolve during a highly dynamic and ongoing global pandemic, these data provide valuable evidence to inform long-term strategic resource allocation for patients previously infected with SARS-CoV-2.

      11. Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections
        Wiegand RE, Fleming FM, de Vlas SJ, Odiere MR, Kinung'hi S, King CH, Evans D, French MD, Montgomery SP, Straily A, Utzinger J, Vounatsou P, Secor WE.
        Lancet Glob Health. 2022 Sep;10(9):e1355-e1359.
        WHO's 2021-30 road map for neglected tropical diseases (NTDs) outlines disease-specific and cross-cutting targets for the control, elimination, and eradication of NTDs in affected countries. For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ≥50 Schistosoma haematobium eggs per 10 mL of urine or ≥400 Schistosoma mansoni eggs per g of stool). However, we believe the evidence supporting this definition of EPHP is inadequate and the shifting distribution of schistosomiasis morbidity towards more subtle, rather than severe, morbidity in the face of large-scale control programmes requires guidelines to be adapted. In this Viewpoint, we outline the need for more accurate measures to develop a robust evidence-based monitoring and evaluation framework for schistosomiasis. Such a framework is crucial for achieving the goal of widespread EPHP of schistosomiasis and to meet the WHO road map targets. We encourage use of overall prevalence of schistosome infection (instead of the prevalence of heavy-intensity infections), development of species-dependent and age-dependent morbidity markers, and construction of a standardised monitoring and evaluation protocol.

      12. Interim guidance for prevention and treatment of Monkeypox in persons with HIV infection - United States, August 2022
        O'Shea J, Filardo TD, Morris SB, Weiser J, Petersen B, Brooks JT.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1023-1028.
        Monkeypox virus, an orthopoxvirus sharing clinical features with smallpox virus, is endemic in several countries in Central and West Africa. The last reported outbreak in the United States, in 2003, was linked to contact with infected prairie dogs that had been housed or transported with African rodents imported from Ghana (1). Since May 2022, the World Health Organization (WHO) has reported a multinational outbreak of monkeypox centered in Europe and North America, with approximately 25,000 cases reported worldwide; the current outbreak is disproportionately affecting gay, bisexual, and other men who have sex with men (MSM) (2). Monkeypox was declared a public health emergency in the United States on August 4, 2022.(†) Available summary surveillance data from the European Union, England, and the United States indicate that among MSM patients with monkeypox for whom HIV status is known, 28%-51% have HIV infection (3-10). Treatment of monkeypox with tecovirimat as a first-line agent is available through CDC for compassionate use through an investigational drug protocol. No identified drug interactions would preclude coadministration of tecovirimat with antiretroviral therapy (ART) for HIV infection. Pre- and postexposure prophylaxis can be considered with JYNNEOS vaccine, if indicated. Although data are limited for monkeypox in patients with HIV, prompt diagnosis, treatment, and prevention might reduce the risk for adverse outcomes and limit monkeypox spread. Prevention and treatment considerations will be updated as more information becomes available.

      13. Epidemiologic and clinical characteristics of Monkeypox cases - United States, May 17-July 22, 2022
        Philpott D, Hughes CM, Alroy KA, Kerins JL, Pavlick J, Asbel L, Crawley A, Newman AP, Spencer H, Feldpausch A, Cogswell K, Davis KR, Chen J, Henderson T, Murphy K, Barnes M, Hopkins B, Fill MA, Mangla AT, Perella D, Barnes A, Hughes S, Griffith J, Berns AL, Milroy L, Blake H, Sievers MM, Marzan-Rodriguez M, Tori M, Black SR, Kopping E, Ruberto I, Maxted A, Sharma A, Tarter K, Jones SA, White B, Chatelain R, Russo M, Gillani S, Bornstein E, White SL, Johnson SA, Ortega E, Saathoff-Huber L, Syed A, Wills A, Anderson BJ, Oster AM, Christie A, McQuiston J, McCollum AM, Rao AK, Negrón ME.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1018-1022.
        Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with monkeypox,(†) regardless of whether the rash is disseminated or was preceded by prodrome. Likewise, although most cases to date have occurred among gay, bisexual, and other men who have sex with men, any patient with rash consistent with monkeypox should be considered for testing. CDC is continually evaluating new evidence and tailoring response strategies as information on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available.(§).

      14. COVID-19 self-test data: Challenges and opportunities - United States, October 31, 2021-June 11, 2022
        Ritchey MD, Rosenblum HG, Del Guercio K, Humbard M, Santos S, Hall J, Chaitram J, Salerno RM.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1005-1010.
        Self-tests* to detect current infection with SARS-CoV-2, the virus that causes COVID-19, are valuable tools that guide individual decision-making and risk reduction(†) (1-3). Increased self-test use (4) has likely contributed to underascertainment of COVID-19 cases (5-7), because unlike the requirements to report results of laboratory-based and health care provider-administered point-of-care COVID-19 tests,(§) public health authorities do not require reporting of self-test results. However, self-test instructions include a recommendation that users report results to their health care provider so that they can receive additional testing and treatment if clinically indicated.(¶) In addition, multiple manufacturers of COVID-19 self-tests have developed websites or companion mobile applications for users to voluntarily report self-test result data. Federal agencies use the data reported to manufacturers, in combination with manufacturing supply chain information, to better understand self-test availability and use. This report summarizes data voluntarily reported by users of 10.7 million self-tests from four manufacturers during October 31, 2021-June 11, 2022, and compares these self-test data with data received by CDC for 361.9 million laboratory-based and point-of-care tests performed during the same period. Overall trends in reporting volume and percentage of positive results, as well as completeness of reporting demographic variables, were similar across test types. However, the limited amount and quality of data reported from self-tests currently reduces their capacity to augment existing surveillance. Self-tests provide important risk-reduction information to users, and continued development of infrastructure and methods to collect and analyze data from self-tests could improve their use for surveillance during public health emergencies.

      15. Vital signs: Hepatitis C treatment among insured adults - United States, 2019-2020
        Thompson WW, Symum H, Sandul A, Gupta N, Patel P, Nelson N, Mermin J, Wester C.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1011-1017.
        INTRODUCTION: Over 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C. METHODS: Data from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18-69 years with HCV infection diagnosed during January 30, 2019-October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51-0.57) and Medicare (aOR = 0.62; 95% CI = 0.56-0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18-29 and 30-39 years with Medicaid or private insurance, compared with those aged 50-59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74-0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88-0.99) or other race (aOR = 0.73; 95% CI = 0.62-0.88) than those whose race was coded as White. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Few insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis-related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.

      16. Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first International Meeting On Endemic Mycoses Of The Americas (IMEMA)
        Caceres DH, Echeverri Tirado LC, Bonifaz A, Adenis A, Gomez BL, Flores CL, Canteros CE, Santos DW, Arathoon E, Soto ER, Queiroz-Telles F, Schwartz IS, Zurita J, Damasceno LS, Garcia N, Fernandez NB, Chincha O, Araujo P, Rabagliati R, Chiller T, Giusiano G.
        Mycoses. 2022 Jul 30.
        BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-β-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

      17. Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014-2018
        Raz KM, Talarico S, Althomsons SP, Kammerer JS, Cowan LS, Haddad MB, McDaniel CJ, Wortham JM, France AM, Powell KM, Posey JE, Silk BJ.
        Tuberculosis (Edinb). 2022 Aug 9;136:102232.
        OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity.

      18. Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison)
        Ritter JM, Wilson TM, Gary JM, Seixas JN, Martines RB, Bhatnagar J, Bollweg BC, Lee E, Estetter L, Silva-Flannery L, Bullock HA, Towner JS, Cossaboom CM, Wendling NM, Amman BR, Harvey RR, Taylor D, Rettler H, Barton Behravesh C, Zaki SR.
        Vet Pathol. 2022 Jul;59(4):681-695.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.

    • Community Health Services
      1. Notes from the field: School-based and laboratory-based reporting of positive COVID-19 test results among school-aged children - New York, September 11, 2021-April 29, 2022
        Shircliff EJ, Rosenberg ES, Collens LM, Hoefer D, Lutterloh E, Silk BJ, Winn AK, O'Donnell TT.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1029-1031.

    • Environmental Health
      1. Principles and procedures for assessment of acute toxicity incorporating in silico methods
        Zwickl C, Graham J, Jolly R, Bassan A, Ahlberg E, Amberg A, Anger L, Beilke L, Bellion P, Brigo A, Burleigh-Flayer H, Cronin MD, Devlin A, Fish T, Glowienke S, Gromek K, Karmaus A, Kemper R, Kulkarni S, Lo Piparo E, Madia F, Martin M, Masuda-Herrera M, McAtee B, Mestres J, Milchak L, Moudgal C, Mumtaz M, Muster W, Neilson L, Patlewicz G, Paulino A, Roncaglioni A, Ruiz P, Szabo D, Valentin J, Vardakou I, Woolley D, Myatt G.
        Comput Toxicol. 2022 ;24.
        Acute toxicity in silico models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an in silico analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including in silico methods and in vitro or in vivo experiments. In silico methods that can assist the prediction of in vivo outcomes (i.e., LD50) are analyzed concluding that predictions obtained using in silico approaches are now well-suited for reliably supporting assessment of LD50-based acute toxicity for the purpose of the Globally Harmonized System (GHS) classification. A general overview is provided of the endpoints from in vitro studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of in vitro data allow for a shift away from assessments solely based on endpoints such as LD50, to mechanism-based endpoints that can be accurately assessed in vitro or by using in silico prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how in silico approaches support the assessment of acute toxicity. 2022 Elsevier B.V.

      2. Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study
        Li Z, Lewin M, Ruiz P, Nigra AE, Henderson N, Jarrett JM, Ward C, Zhu J, Umans JG, O'Leary M, Zhang Y, Ragin-Wilson A, Navas-Acien A.
        Environ Res. 2022 Aug 14:114101.
        BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from 2014 participants (all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The blood mercury median of the SHS population was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

    • Food Safety
      1. The power, potential, benefits, and challenges of implementing high-throughput sequencing in food safety systems
        Imanian B, Donaghy J, Jackson T, Gummalla S, Ganesan B, Baker RC, Henderson M, Butler EK, Hong Y, Ring B, Thorp C, Khaksar R, Samadpour M, Lawless KA, MacLaren-Lee I, Carleton HA, Tian R, Zhang W, Wan J.
        NPJ Sci Food. 2022 Aug 16;6(1):35.
        The development and application of modern sequencing technologies have led to many new improvements in food safety and public health. With unprecedented resolution and big data, high-throughput sequencing (HTS) has enabled food safety specialists to sequence marker genes, whole genomes, and transcriptomes of microorganisms almost in real-time. These data reveal not only the identity of a pathogen or an organism of interest in the food supply but its virulence potential and functional characteristics. HTS of amplicons, allow better characterization of the microbial communities associated with food and the environment. New and powerful bioinformatics tools, algorithms, and machine learning allow for development of new models to predict and tackle important events such as foodborne disease outbreaks. Despite its potential, the integration of HTS into current food safety systems is far from complete. Government agencies have embraced this new technology, and use it for disease diagnostics, food safety inspections, and outbreak investigations. However, adoption and application of HTS by the food industry have been comparatively slow, sporadic, and fragmented. Incorporation of HTS by food manufacturers in their food safety programs could reinforce the design and verification of effectiveness of control measures by providing greater insight into the characteristics, origin, relatedness, and evolution of microorganisms in our foods and environment. Here, we discuss this new technology, its power, and potential. A brief history of implementation by public health agencies is presented, as are the benefits and challenges for the food industry, and its future in the context of food safety.

    • Genetics and Genomics
      1. Genome sequences of 16 enterovirus isolates from environmental sewage in Guatemala, 2019 to 2021
        Harrington C, Sayyad L, Castro C, Hill J, Jeffries-Miles S, Belgasmi H, Rey-Benito G, Mendoza Prillwitz ML, Castillo Signor L, Gerloff N.
        Microbiol Resour Announc. 2022 Aug 11:e0056222.
        Enteroviruses can cause human infectious disease. We report 16 near-complete genome sequences of enteroviruses that were isolated through environmental surveillance of wastewater in Guatemala.

      2. Complete genome sequences of four macrolide-resistant nondiphtheritic corynebacterium isolates
        Xiaoli L, Peng Y, Williams MM, Cassiday PK, Nobles S, Unoarumhi Y, Weil LM, Shirin T, Habib ZH, Tondella ML, Weigand MR.
        Microbiol Resour Announc. 2022 Aug 11:e0049222.
        This report describes the complete genome sequences of four isolates of the nondiphtheritic Corynebacterium (NDC) species Corynebacterium pseudodiphtheriticum and Corynebacterium propinquum, recovered during investigation of a large diphtheria outbreak in Bangladesh. These data will assist in better delineating the boundary between these related species and understanding their virulence potential.

      3. Evaluation of various distance computation methods for construction of haplotype-based phylogenies from large MLST dataset
        Jacobson D, Zheng Y, Plucinski MM, Qvarnstrom Y, Barratt JL.
        Mol Phylogenet Evol. 2022 Aug 10:107608.
        Multi-locus sequence typing (MLST) is widely used to investigate genetic relationships among eukaryotic taxa, including parasitic pathogens. MLST analysis workflows typically involve construction of alignment-based phylogenetic trees - i.e., where tree structures are computed from nucleotide differences observed in a multiple sequence alignment (MSA). Notably, alignment-based phylogenetic methods require that all isolates/taxa are represented by a single sequence. When multiple loci are sequenced these sequences may be concatenated to produce one tree that includes information from all loci. Alignment-based phylogenetic techniques are robust and widely used yet possess some shortcomings, including how heterozygous sites are handled, intolerance for missing data (i.e., partial genotypes), and differences in the way insertions-deletions (indels) are scored/treated during tree construction. In certain contexts, 'haplotype-based' methods may represent a viable alternative to alignment-based techniques, as they do not possess the aforementioned limitations. This is namely because haplotype-based methods assess genetic similarity based on numbers of shared (i.e., intersecting) haplotypes as opposed to similarities in nucleotide composition observed in an MSA. For haplotype-based comparisons, choosing an appropriate distance statistic is fundamental, and several statistics are available to choose from. However, a comprehensive assessment of various available statistics for their ability to produce a robust haplotype-based phylogenetic reconstruction has not yet been performed. We evaluated seven distance statistics by applying them to extant MLST datasets from the gastrointestinal parasite Cyclospora cayetanensis and two species of pathogenic nematode of the genus Strongyloides. We compare the genetic relationships identified using each statistic to epidemiologic, geographic, and host metadata. We show that Barratt's heuristic definition of genetic distance was the most robust among the statistics evaluated. Consequently, it is proposed that Barratt's heuristic represents a useful approach for use in the context of challenging MLST datasets possessing features (i.e., high heterozygosity, partial genotypes, and indel or repeat-based polymorphisms) that confound or preclude the use of alignment-based methods.

      4. Large scale screening of CRISPR guide RNAs using an optimized high throughput robotics system
        Spangler JR, Leski TA, Schultzhaus Z, Wang Z, Stenger DA.
        Sci Rep. 2022 Aug 17;12(1):13953.
        All CRISPR/CAS systems utilize CRISPR guide RNAs (crRNAs), the design of which depend on the type of CAS protein, genetic target and the environment/matrix. While machine learning approaches have recently been developed to optimize some crRNA designs, candidate crRNAs must still be screened for efficacy under relevant conditions. Here, we demonstrate a high-throughput method to screen hundreds of candidate crRNAs for activation of Cas13a collateral RNA cleavage. Entire regions of a model gene transcript (Y. pestis lcrV gene) were tiled to produce overlapping crRNA sets. We tested for possible effects that included crRNA/target sequence, size and secondary structures, and the commercial source of DNA oligomers used to generate crRNAs. Detection of a 981 nt target RNA was initially successful with 271 out of 296 tested guide RNAs, and that was improved to 287 out of 296 (97%) after protocol optimizations. For this specific example, we determined that crRNA efficacy did not strongly depend on the target region or crRNA physical properties, but was dependent on the source of DNA oligomers used for RNA preparation. Our high-throughput methods for screening crRNAs has general applicability to the optimization of Cas12 and Cas13 guide RNA designs.

    • Health Economics
      1. Antihypertensive and statin medication adherence among Medicare beneficiaries
        Jackson SL, Nair PR, Chang A, Schieb L, Loustalot F, Wall HK, Sperling LS, Ritchey MD.
        Am J Prev Med. 2022 ;63(3):313-323.
        Introduction: Medication adherence is important for optimal management of chronic conditions, including hypertension and hypercholesterolemia. This study describes adherence to antihypertensive and statin medications, individually and collectively, and examines variation in adherence by demographic and geographic characteristics. Methods: The 2017 prescription drug event data for beneficiaries with Medicare Part D coverage were assessed. Beneficiaries with a proportion of days covered ≥80% were considered adherent. Adjusted prevalence ratios were estimated to quantify the associations between demographic and geographic characteristics and adherence. Adherence estimates were mapped by county of residence using a spatial empirical Bayesian smoothing technique to enhance stability. Analyses were conducted in 2019‒2021. Results: Among the 22.5 million beneficiaries prescribed antihypertensive medications, 77.1% were adherent; among the 16.1 million prescribed statin medications, 81.9% were adherent; and among the 13.5 million prescribed antihypertensive and statin medications, 70.3% were adherent to both. Adherence varied by race/ethnicity: American Indian/Alaska Native (adjusted prevalence ratio=0.83, 95% confidence limit=0.82, 0.842), Hispanic (adjusted prevalence ratio=0.90, 95% confidence limit=0.90, 0.91), and non-Hispanic Black (adjusted prevalence ratio=0.87, 95% confidence limit=0.86, 0.87) beneficiaries were less likely to be adherent than non-Hispanic White beneficiaries. County-level adherence ranged across the U.S. from 25.7% to 88.5% for antihypertensive medications, from 36.0% to 93.8% for statin medications, and from 20.8% to 92.9% for both medications combined and tended to be the lowest in the southern U.S. Conclusions: This study highlights opportunities for efforts to remove barriers and support medication adherence, especially among racial/ethnic minority groups and within the regions at greatest risk for adverse cardiovascular outcomes. © 2022

      2. Cost-effectiveness of implementing HIV and HIV/syphilis dual testing among key populations in Viet Nam: a modelling analysis
        Coomes D, Green D, Barnabas R, Sharma M, Barr-DiChiara M, Jamil MS, Baggaley R, Owiredu MN, Macdonald V, Nguyen VT, Vo SH, Taylor M, Wi T, Johnson C, Drake AL.
        BMJ Open. 2022 Aug 11;12(8):e056887.
        OBJECTIVES: Key populations, including sex workers, men who have sex with men, and people who inject drugs, have a high risk of HIV and sexually transmitted infections. We assessed the health and economic impacts of different HIV and syphilis testing strategies among three key populations in Viet Nam using a dual HIV/syphilis rapid diagnostic test (RDT). SETTING: We used the spectrum AIDS impact model to simulate the HIV epidemic in Viet Nam and evaluated five testing scenarios among key populations. We used a 15-year time horizon and a provider perspective for costs. PARTICIPANTS: We simulate the entire population of Viet Nam in the model. INTERVENTIONS: We modelled five testing scenarios among key populations: (1) annual testing with an HIV RDT, (2) annual testing with a dual RDT, (3) biannual testing using dual RDT and HIV RDT, (4) biannual testing using HIV RDT and (5) biannual testing using dual RDT. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is incremental cost-effectiveness ratios. Secondary outcomes include HIV and syphilis cases. RESULTS: Annual testing using a dual HIV/syphilis RDT was cost-effective (US$10 per disability-adjusted life year (DALY)) and averted 3206 HIV cases and treated 27 727 syphilis cases compared with baseline over 15 years. Biannual testing using one dual test and one HIV RDT (US$1166 per DALY), or two dual tests (US$5672 per DALY) both averted an additional 875 HIV cases, although only the former scenario was cost-effective. Annual or biannual HIV testing using HIV RDTs and separate syphilis tests were more costly and less effective than using one or two dual RDTs. CONCLUSIONS: Annual HIV and syphilis testing using dual RDT among key populations is cost-effective in Vietnam and similar settings to reach global reduction goals for HIV and syphilis.

      3. Direct outpatient health care costs among commercially insured persons for common foodborne pathogens and acute gastroenteritis, 2012-2015
        Whitham HK, Gilliland AE, Collier SA, Scallan Walter E, Hoffmann S.
        Foodborne Pathog Dis. 2022 Aug;19(8):558-568.
        Foodborne illness is common in the United States with most, but not all, foodborne pathogens causing symptoms of acute gastroenteritis (AGI). Outpatient care is the most frequent type of medical care sought; however, more accurate estimates of outpatient costs are needed to inform food safety policy decision. Using the U.S. MarketScan Commercial Claims and Encounters database, we quantified the per-visit cost of outpatient visits with any AGI-related diagnosis (including pathogen-specific and nonspecific or symptom-based diagnoses) and for those with a pathogen-specific diagnosis for 1 of 29 pathogens commonly transmitted through food (including pathogens that cause AGI and some that do not). Our estimates included the per-case cost of office visits and associated laboratory tests and procedures as well as the conservative estimates of prescription cost. Most AGI outpatient visits were coded using nonspecific codes (e.g., infectious gastroenteritis), rather than pathogen-specific codes (e.g., Salmonella). From 2012 to 2015, we identified more than 3.4 million initial outpatient visits with any AGI diagnosis and 45,077 with a foodborne pathogen-specific diagnosis. As is typical of treatment cost data, severe cases of illness drove mean costs above median. The mean cost of an outpatient visit with any AGI was $696 compared with the median of $162. The mean costs of visits with pathogen-specific diagnoses ranged from $254 (median $131; interquartile range [IQR]: $98-184) for Streptococcus spp. Group A (n = 22,059) to $1761 (median $161; IQR: $104-$1101) for Clostridium perfringens (n = 30). Visits with two of the most common causes of foodborne illness, nontyphoidal Salmonella and norovirus, listed as a diagnosis, had mean costs of $841 and $509, respectively. Overall, the median per-case costs of outpatient visits increased with age, with some variation by pathogen. More empirically based estimates of outpatient costs for AGI and specific pathogens can enhance estimates of the economic cost of foodborne illness used to guide food policy and focus prevention efforts.

      4. ENDS advertising expenditures in English language media in the USA, 2015-2020
        Welding K, Marynak KL, Trigger S, Kelley D, Jewler L, Kennedy RD.
        Tob Control. 2022 Aug 16.
        BACKGROUND: Electronic nicotine delivery system (ENDS) advertising is associated with ENDS purchase and use. This study assessed trends in ENDS advertisement (ad) expenditures in the USA from 2015 to 2020 overall, by media channel and by advertiser. METHODS: Data came from Numerator, which conducts surveillance of ads and estimates expenditures. The estimates are dollars spent (adjusted to 2020) by the advertiser for each ad occurrence for print, radio, television and digital (online, mobile) media channels. ENDS ad expenditures were assessed by quarter, media channel and the top five advertisers based on ad occurrences. RESULTS: Overall ENDS ad expenditures increased from $38 million in 2015 to $217 million in 2019 before decreasing to a low of $22 million in 2020. By media channel, print expenditures led the channels with more than twice as much spent as television, four times more than radio and 10 times more than digital. By advertiser, JUUL led in ENDS ad expenditures from 2015 to 2020 with almost $189 million spent, followed by British American Tobacco (BAT, $105 million) and Imperial Tobacco ($62 million). CONCLUSIONS: Overall ad expenditures were relatively stable from 2015 to mid-2018 when large expenditures by JUUL and subsequent expenditures by BAT and Imperial Tobacco led to expenditure highs in 2019. E-cigarette and vaping-associated lung injury (EVALI), the JUUL self-imposed ad suspension and COVID-19 likely all played a role in advertising lows in 2020. The absence of popular Puff Bar brand ads from the traditional media channels studied highlights the importance of monitoring direct and indirect advertising on newer media channels like social media.

    • Health Equity and Health Disparities
      1. The boundary of HIV care: Barriers and facilitators to care engagement among people with HIV in the United States
        Padilla M, Carter B, Gutierrez M, Fagan J.
        AIDS Patient Care STDS. 2022 Aug;36(8):321-331.
        Treating people with HIV (PWH) quickly and effectively to achieve viral suppression is a key strategy for Ending the HIV Epidemic. Understanding barriers and facilitators to HIV care engagement could improve outcomes among PWH and reduce HIV infections. We sampled PWH who participated in the Medical Monitoring Project from June 2018 to May 2019 and were not engaged in HIV care to participate in 60-min semistructured telephone interviews on barriers and facilitators to HIV care engagement. We used applied thematic analysis and placed codes into themes based on their frequency and salience. Participants reported various intrapersonal, health system, and structural barriers to care. We conceptualize the boundary of care as the space between the stages of the HIV care continuum, where PWH may find themselves when they lack intrapersonal, health system, and structural support. Research and interventions tackling these barriers are needed to improve outcomes among PWH and reduce HIV infections.

      2. REPRINT OF: Racism, sexism, and social class: Implications for studies of health, disease, and well-being
        Krieger N, Rowley DL, Herman AA, Avery B, Phillips MT.
        Am J Prev Med. 2022 Jun;62(6):816-863.
        Editor's Note: This article is a reprint of a previously published article. For citation purposes, please use the original publication details: Krieger N, Rowley DL, Herman AA, Avery B, Phillips MT. Racism, sexism, and social class: implications for studies of health, disease, and well-being. Am J Prev Med. 1993;9(6 suppl):82-122.

    • Healthcare Associated Infections
      1. A cluster of gram-negative bloodstream infections in Connecticut hemodialysis patients associated with contaminated wall boxes and prime buckets
        Backman L, Dumigan DG, Oleksiw M, Carusillo E, Patel PR, Nguyen DB, Moulton-Meissner H, Boyce JM.
        Am J Infect Control. 2022 Aug 12.
        BACKGROUND: Maintenance hemodialysis (HD) patients are at increased risk of bloodstream infections (BSI). We investigated a cluster of Delftia acidovorans infections among patients undergoing HD at an outpatient unit (Facility A). METHODS: A case was defined as a Facility A HD patient with ≥1 culture positive for Delftia acidovorans between February 1 - April 30, 2018. An investigation included review of patient records, facility policies, practice observations, and environmental cultures. RESULTS: The cluster included two patients with confirmed D. acidovorans BSI. Both patients had recently been dialyzed at Station #2, where a wall box culture yielded D. acidovorans. One patient also had a BSI due to Enterobacter asburiae, which was recovered from several other wall boxes and saline prime buckets (SPB). Observations revealed leakage of wastewater from wall boxes onto the floor, and that SPBs were not always disinfected and dried appropriately before reuse. Multiple deficiencies in hand hygiene and station disinfection were observed. No deficiencies in water treatment practices were identified, and water cultures were negative for the observed pathogens. CONCLUSIONS: The cluster of D. acidovorans infections was most likely due to indirect exposures to contaminated wall boxes and possibly SPBs due to poor hand hygiene and station disinfection.

      2. Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study
        Mathur P, Malpiedi P, Walia K, Srikantiah P, Gupta S, Lohiya A, Chakrabarti A, Ray P, Biswal M, Taneja N, Rupali P, Balaji V, Rodrigues C, Lakshmi Nag V, Tak V, Venkatesh V, Mukhopadhyay C, Deotale V, Padmaja K, Wattal C, Bhattacharya S, Karuna T, Behera B, Singh S, Nath R, Ray R, Baveja S, Fomda BA, Sulochana Devi K, Das P, Khandelwal N, Verma P, Bhattacharyya P, Gaind R, Kapoor L, Gupta N, Sharma A, VanderEnde D, Siromany V, Laserson K, Guleria R.
        Lancet Glob Health. 2022 Sep;10(9):e1317-e1325.
        BACKGROUND: Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available. METHODS: A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis. FINDINGS: 26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp. INTERPRETATION: The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies. FUNDING: US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

      3. Risk factors for acute gastroenteritis among patients hospitalized in 5 Veterans Affairs Medical Centers, 2016-2019
        Balachandran N, Cates J, Kambhampati AK, Marconi VC, Whitmire A, Morales E, Brown ST, Lama D, Rodriguez-Barradas MC, Moronez RG, Domiguez GR, Beenhouwer DO, Poteshkina A, Matolek ZA, Holodniy M, Lucero-Obusan C, Agarwal M, Cardemil C, Parashar U, Mirza SA.
        Open Forum Infect Dis. 2022 Aug;9(8):ofac339.
        BACKGROUND: In the United States, ∼179 million acute gastroenteritis (AGE) episodes occur annually. We aimed to identify risk factors for all-cause AGE, norovirus-associated vs non-norovirus AGE, and severe vs mild/moderate AGE among hospitalized adults. METHODS: We enrolled 1029 AGE cases and 624 non-AGE controls from December 1, 2016, to November 30, 2019, at 5 Veterans Affairs Medical Centers. Patient interviews and medical chart abstractions were conducted, and participant stool samples were tested using the BioFire Gastrointestinal Panel. Severe AGE was defined as a modified Vesikari score of ≥11. Multivariate logistic regression was performed to assess associations between potential risk factors and outcomes; univariate analysis was conducted for norovirus-associated AGE due to limited sample size. RESULTS: Among 1029 AGE cases, 551 (54%) had severe AGE and 44 (4%) were norovirus positive. Risk factors for all-cause AGE included immunosuppressive therapy (adjusted odds ratio [aOR], 5.6; 95% CI, 2.7-11.7), HIV infection (aOR, 3.9; 95% CI, 1.8-8.5), severe renal disease (aOR, 3.1; 95% CI, 1.8-5.2), and household contact with a person with AGE (aOR, 2.9; 95% CI, 1.3-6.7). Household (OR, 4.4; 95% CI, 1.6-12.0) and non-household contact (OR, 5.0; 95% CI, 2.2-11.5) with AGE was associated with norovirus-associated AGE. Norovirus positivity (aOR, 3.4; 95% CI, 1.3-8.8) was significantly associated with severe AGE. CONCLUSIONS: Patients with immunosuppressive therapy, HIV, and severe renal disease should be monitored for AGE and may benefit from targeted public health messaging regarding AGE prevention. These results may also direct future public health interventions, such as norovirus vaccines, to specific high-risk populations.

    • Immunity and Immunization
      1. Vaccine effectiveness against influenza hospitalization and emergency department visits in 2 A(H3N2) dominant influenza seasons among children <18 years old-new vaccine surveillance network 2016-2017 and 2017-2018
        Kim SS, Naioti EA, Halasa NB, Stewart LS, Williams JV, Michaels MG, Selvarangan R, Harrison CJ, Staat MA, Schlaudecker EP, Weinberg GA, Szilagyi PG, Boom JA, Sahni LC, Englund JA, Klein EJ, Ogokeh CE, Campbell AP, Patel MM.
        J Infect Dis. 2022 Aug 12;226(1):91-96.
        Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016-2017 and 2017-2018 seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (<18 years old) during the 2016-2017 and 2017-2018 seasons. Effectiveness was 71% (95% confidence interval, 59%-79%), 46% (35%-55%), and 45% (33%-55%) against A(H1N1)pdm09, A(H3N2), and B viruses respectively, across both seasons. During high-severity seasons with concerns for vaccine mismatch, vaccination offered substantial protection against severe influenza outcomes requiring hospitalization or emergency department visits among children.

      2. BACKGROUND: Anecdotal reports of menstrual irregularities after receiving COVID-19 vaccines have been observed in post-authorisation and post-licensure monitoring. We aimed to identify and classify reports of menstrual irregularities and vaginal bleeding after COVID-19 vaccination submitted to a voluntary active surveillance system. METHODS: This observational cohort study included recipients of a COVID-19 vaccine who were aged 18 years and older and reported their health experiences to v-safe, a voluntary smartphone-based active surveillance system for monitoring COVID-19 vaccine safety in the USA, from Dec 14, 2020, to Jan 9, 2022. Responses to survey questions on reactions after vaccination were extracted, and a pre-trained natural language inference model was used to identify and classify free-text comments related to menstruation and vaginal bleeding in response to an open-ended prompt about any symptoms at intervals after vaccination. Related responses were further categorised into themes of timing, severity, perimenopausal and postmenopausal bleeding, resumption of menses, and other responses. We examined associations between symptom theme and respondent characteristics, including vaccine type and dose number received, solicited local and systemic reactions reported, and health care sought. FINDINGS: 63 815 respondents reported on menstrual irregularities or vaginal bleeding, which included 62 679 female respondents (1·0% of 5 975 363 female respondents aged ≥18 years). Common themes identified included timing of menstruation (70 981 [83·6%] responses) and severity of menstrual symptoms (56 890 [67·0%] responses). Other themes included menopausal bleeding (3439 [4·0%] responses) and resumption of menses (2378 [2·8%] responses). Respondents submitting reports related to menopausal bleeding were more likely to seek health care than were those submitting reports related to other menstruation and vaginal bleeding themes. INTERPRETATION: Reports of heterogeneous symptoms related to menstruation or vaginal bleeding after COVID-19 vaccination are being submitted to v-safe, although this study is unable to characterise the relationship of these symptoms to COVID-19 vaccination. Methods that leverage pretrained models to interpret and classify unsolicited signs and symptoms in free-text reports offer promise in the initial evaluation of unexpected adverse events potentially associated with use of newly authorised or licensed vaccines. FUNDING: Centers for Disease Control and Prevention.

      3. Safety of mRNA COVID-19 vaccines during pregnancy
        Ellington S, Olson CK.
        Lancet Infect Dis. 2022 Aug 11.

      4. Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial
        Velasquez-Portocarrero DE, Wang X, Cortese MM, Snider CJ, Anand A, Costantini VP, Yunus M, Aziz AB, Haque W, Parashar U, Sisay Z, Soeters HM, Hyde TB, Jiang B, Zaman K.
        Lancet Infect Dis. 2022 Aug 9.
        BACKGROUND: A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse. METHODS: We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, >37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026. FINDINGS: Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p<0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p<0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p<0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine. INTERPRETATION: RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings. FUNDING: US Centers for Disease Control and Prevention.

      5. Human papillomavirus vaccine effectiveness by number of doses: Updated systematic review of data from national immunization programs
        Markowitz LE, Drolet M, Lewis RM, Lemieux-Mellouki P, Pérez N, Jit M, Brotherton JM, Ogilvie G, Kreimer AR, Brisson M.
        Vaccine. 2022 Aug 11.
        BACKGROUND: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies. METHODS: We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding. RESULTS: Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses. CONCLUSION: Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates.

    • Injury and Violence
      1. Effects of unilateral eye closure on middle ear muscle contractions
        Tasko SM, Deiters KK, Flamme GA, Smith MV, Murphy WJ, Jones HG, Greene NT, Ahroon WA.
        Hear Res. 2022 Jul 28;424:108594.
        Middle ear muscle contractions (MEMCs) are most commonly considered a response to high-level acoustic stimuli. However, MEMCs have also been observed in the absence of sound, either as a response to somatosensory stimulation or in concert with other motor activity. The relationship between MEMCs and non-acoustic sources is unclear. This study examined associations between measures of voluntary unilateral eye closure and impedance-based measures indicative of middle ear muscle activity while controlling for demographic and clinical factors in a large group of participants (N=190) with present clinical acoustic reflexes and no evidence of auditory dysfunction. Participants were instructed to voluntarily close the eye ipsilateral to the ear canal containing a detection probe at three levels of effort. Orbicularis oculi muscle activity was measured using surface electromyography. Middle ear muscle activity was inferred from changes in total energy reflected in the ear canal using a filtered (0.2 to 8 kHz) click train. Results revealed that middle ear muscle activity was positively associated with eye muscle activity. MEMC occurrence rates for eye closure observed in this study were generally higher than previously published rates for high-level brief acoustic stimuli in the same participant pool suggesting that motor activity may be a more reliable elicitor of MEMCs than acoustic stimuli. These results suggest motor activity can serve as a confounding factor for auditory exposure studies as well as complicate the interpretation of any impulsive noise damage risk criteria that assume MEMCs serve as a consistent, uniform protective factor. The mechanism linking eye and middle ear muscle activity is not understood and is an avenue for future research.

    • Laboratory Sciences
      1. Evaluation of MALDI Biotyper mycobacteria library for identification of nontuberculous mycobacteria
        Toney NC, Zhu W, Jensen B, Gartin J, Anderson K, Lonsway D, Karlsson M, Rasheed JK.
        J Clin Microbiol. 2022 Aug 15:e0021722.
        The Bruker Biotyper matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) platform was assessed on its ability to accurately identify 314 nontuberculous mycobacteria (NTM) representing 73 species. All NTM isolates, representing 183 rapidly growing and 131 slowly growing organisms, were previously identified by Sanger DNA sequencing of the full-length 16S rRNA gene, and region V of the rpoB gene. An optimized version of the Bruker bead-beating procedure for protein extraction of NTM isolates was used to ensure high quality spectra for all NTM isolates, including less frequently encountered species. NTM spectra were analyzed using Bruker's research use only, Mycobacteria Library v6.0, supplemented by the MicrobeNet database. Identification of NTM by MALDI-TOF had an accuracy of 94% (296/314). The identification accuracy for rapidly growing mycobacteria was higher at 99% (182/183) than it was for slowly growing mycobacteria at 87% (114/131). While MALDI-TOF performed well against Sanger sequencing of the 16S rRNA gene alone, there were 11 species that required additional sequencing of rpoB. Most discrepancies between MALDI-TOF and sequencing results are likely due to underrepresentation of some species in the libraries used. Overall, the results of this study support Bruker's MALDI-TOF platform as an accurate and reliable method for the identification of NTM.

    • Maternal and Child Health
      1. Infectious aetiologies of neonatal illness in South Asia classified using WHO definitions: a primary analysis of the ANISA study
        Arvay ML, Shang N, Qazi SA, Darmstadt GL, Islam MS, Roth DE, Liu A, Connor NE, Hossain B, Sadeq-Ur Rahman Q, El Arifeen S, Mullany LC, Zaidi AK, Bhutta ZA, Soofi SB, Shafiq Y, Baqui AH, Mitra DK, Panigrahi P, Panigrahi K, Bose A, Isaac R, Westreich D, Meshnick SR, Saha SK, Schrag SJ.
        Lancet Glob Health. 2022 Sep;10(9):e1289-e1297.
        BACKGROUND: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. METHODS: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. FINDINGS: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. INTERPRETATION: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. FUNDING: The Bill and Melinda Gates Foundation.

    • Nutritional Sciences
      1. Maternal diet quality moderates associations between parabens and birth outcomes
        Pacyga DC, Talge NM, Gardiner JC, Calafat AM, Schantz SL, Strakovsky RS.
        Environ Res. 2022 Aug 11:114078.
        BACKGROUND: /objective: Maternal paraben exposure and diet quality are both independently associated with birth outcomes, but whether these interact is unknown. We assessed sex-specific associations of parabens with birth outcomes and differences by maternal diet quality. METHODS: Illinois pregnant women (n = 458) provided five first-morning urines collected at 8-40 weeks gestation, which we pooled for quantification of ethylparaben, methylparaben, and propylparaben concentrations. We collected/measured gestational age at delivery, birth weight, body length, and head circumference within 24 h of birth, and calculated sex-specific birth weight-for-gestational-age z-scores and weight/length ratio. Women completed three-month food frequency questionnaires in early and mid-to-late pregnancy, which we used to calculate the Alternative Healthy Eating Index (AHEI)-2010. Linear regression models evaluated sex-specific associations of parabens with birth outcomes, and differences in associations by average pregnancy AHEI-2010. RESULTS: In this predominately non-Hispanic white, college-educated sample, maternal urinary paraben concentrations were modestly inversely associated with head circumference and gestational length. However, methylparaben and propylparaben were inversely associated with birth weight, birth weight z-scores, body length, and weight/length ratio in female, but not male newborns. For example, each 2-fold increase in methylparaben concentrations was associated with -46.61 g (95% CI: -74.70, -18.51) lower birth weight, -0.09 (95% CI: -0.15, -0.03) lower birth weight z-scores, -0.21 cm (95% CI: -0.34, -0.07) shorter body length, and -0.64 g/cm (95% CI: -1.10, -0.19) smaller weight/length ratio in females. These inverse associations were more prominent in females of mothers with poorer diets (AHEI-2010 < median), but attenuated in those with healthier diets (AHEI-2010 ≥ median). In newborn males of mothers with healthier diets, moderate inverse associations emerged for propylparaben with gestational length and head circumference. CONCLUSIONS: Maternal diet may moderate associations of parabens with birth size in a sex-specific manner. Additional studies may consider corroborating these findings in other populations.

    • Occupational Safety and Health
      1. A comprehensive summary of disease variants implicated in metal allergy
        Roach K, Roberts J.
        J Toxicol Environ Health B Crit Rev. 2022 Aug 16:1-63.
        Allergic disease represents one of the most prominent global public health crises of the 21(st) century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy - including allergic contact dermatitis - are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed - from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described.Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet.

    • Occupational Safety and Health - Mining
      1. Exploration of limestone pillar stability in multiple-level mining conditions using numerical models
        Rashed G, Slaker B, Murphy M.
        Min Metall Explor. 2022 Jul:[Epub ahead of print].
        Pillar stability continues to be a significant concern in multiple-level mining conditions, particularly for deep mines when pillars are not stacked or the thickness of interburden between mining levels is thin. The National Institute for Occupational Safety and Health (NIOSH) is currently conducting research to investigate the stability of pillars in multiple-level limestone mines. In this study, FLAC3D models were created to investigate the effect of interburden thickness, the degree of pillar offset between mining levels, and in situ stress conditions on pillar stability at various depths of cover. The FLAC3D models were validated through in situ monitoring that was conducted at a multiple-level stone mine. The critical interburden thickness required to minimize the interaction between the mining levels on top-level pillar stability was explored, where the top level mine was developed first followed by the bottom level mine. The model results showed that there is an interaction between numerous factors that control the stability of pillars in multiple-level conditions. A combination of these factors may lead to various degrees of pillar instabilities. The highest degree of local pillar instability occurred when pillar overlap ranges between 10 and 70%. On the contrary, the highest degree of stability occurs when the pillars are stacked, the underlying assumption is that the interburden between mining levels is elastic (never fails). Generally, for depths of cover investigated in this study, the stability of top-level pillars shallower than 100 m (328 ft) or with interburden thicknesses greater than 1.33 times the roof span - 16 m (52.4 ft) in this study - does not appear significantly impacted by pillar offset. The results of this study improve understanding of multiple-level interactions and advances the ultimate goal of reducing the risk of pillar instability in underground stone mines.

    • Public Health Leadership and Management
      1. A career filled with viruses
        Goldsmith CS.
        Microsc Microanal. 2022 ;28:1380-1381.

    • Substance Use and Abuse
      1. Anabasine and anatabine exposure attributable to cigarette smoking: National Health and Nutrition Examination Survey (NHANES) 2013-2014
        Bendik PB, Rutt SM, Pine BN, Sosnoff CS, Blount BC, Zhu W, Feng J, Wang L.
        Int J Environ Res Public Health. 2022 Aug 8;19(15).
        Anabasine and anatabine are minor alkaloids in tobacco products and are precursors for tobacco-specific nitrosamines (TSNAs). The levels of these two compounds have been used to differentiate tobacco product sources, monitor compliance with smoking cessation programs, and for biomonitoring in TSNA-related studies. The concentrations of urinary anabasine and anatabine were measured in a representative sample of U.S. adults who smoked cigarettes (N = 770) during the 2013-2014 National Health and Nutrition Examination Survey (NHANES) study cycle, which was the first cycle where urinary anabasine and anatabine data became available. Weighted geometric means (GM) and geometric least squares means (LSM) with 95% confidence intervals were calculated for urinary anabasine and anatabine categorized by tobacco-use status [cigarettes per day (CPD) and smoking frequency] and demographic characteristics. Smoking ≥20 CPD was associated with 3.6× higher anabasine GM and 4.8× higher anatabine GM compared with smoking &lt;10 CPD. Compared with non-daily smoking, daily smoking was associated with higher GMs for urinary anabasine (1.41 ng/mL vs. 6.28 ng/mL) and anatabine (1.62 ng/mL vs. 9.24 ng/mL). Urinary anabasine and anatabine concentrations exceeded the 2 ng/mL cut point in 86% and 91% of urine samples from people who smoke (PWS) daily, respectively; in comparison, 100% of them had serum cotinine concentrations greater than the established 10 ng/mL cut point. We compared these minor tobacco alkaloid levels to those of serum cotinine to assess their suitability as indicators of recent tobacco use at established cut points and found that their optimal cut point values would be lower than the established values. This is the first time that anabasine and anatabine are reported for urine collected from a U.S. population-representative sample of NHANES study participants, providing a snapshot of exposure levels for adults who smoked during 2013-2014. The results of this study serve as an initial reference point for future analysis of NHANES cycles, where changes in the national level of urinary anabasine and anatabine can be monitored among people who smoke to show the effect of changes in tobacco policy.

      2. Notes from the field: Overdose deaths involving eutylone (psychoactive bath salts) - United States, 2020
        Gladden RM, Chavez-Gray V, O'Donnell J, Goldberger BA.
        MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1032-1034.

      3. Opioid-involved overdose vulnerability in Wyoming: Measuring risk in a rural environment
        Pustz J, Shrestha S, Newsky S, Taylor M, Fowler L, Van Handel M, Lingwall C, Stopka TJ.
        Subst Use Misuse. 2022 Aug 17:1-12.
        BACKGROUND: Between 2009 and 2019 opioid-involved fatal overdose rates increased by 45% and the average opioid dispensing rate in Wyoming was higher than the national average. The opioid crisis is shaped by a complex set of socioeconomic, geopolitical, and health-related variables. We conducted a vulnerability assessment to identify Wyoming counties at higher risk of opioid-related harm, factors associated with this risk, and areas in need of overdose treatment access to inform priority responses. METHODS: We compiled 2016 to 2018 county-level aggregated and de-identified data. We created risk maps and ran spatial analyses in a geographic information system to depict the spatial distribution of overdose-related measures. We used addresses of opioid treatment programs and buprenorphine providers to develop drive-time maps and ran 2-step floating catchment area analyses to measure accessibility to treatment. We used a straightforward and replicable weighted ranks approach to calculate final county vulnerability scores and rankings from most to least vulnerable. FINDINGS: We found Hot Springs, Carbon, Natrona, Fremont, and Sweetwater Counties to be most vulnerable to opioid-involved overdose fatalities. Opioid prescribing rates were highest in Hot Springs County (97 per 100 persons), almost two times the national average (51 per 100 persons). Statewide, there were over 90 buprenorphine-waivered providers, however accessibility to these clinicians was limited to urban centers. Most individuals lived further than a four-hour round-trip drive to the nearest methadone treatment program. CONCLUSIONS: Identifying Wyoming counties with high opioid overdose vulnerabilities and limited access to overdose treatment can inform public health and harm reduction responses.

    • Telehealth and Telemedicine
      1. Effectiveness of an interactive, highly tailored "video doctor" intervention to suppress viral load and retain patients with HIV in clinical care: A randomized clinical trial
        Lewis MA, Harshbarger C, Bann C, Marconi VC, Somboonwit C, Piazza MD, Swaminathan S, Burrus O, Galindo C, Borkowf CB, Marks G, Karns S, Zulkiewicz B, Ortiz A, Abdallah I, Garner BR, Courtenay-Quirk C.
        J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):58-67.
        BACKGROUND: To determine whether Positive Health Check, a highly tailored video doctor intervention, can improve viral suppression and retention in care. SETTING: Four clinics that deliver HIV primary care. METHODS: A hybrid type 1 effectiveness-implementation randomized trial design was used to test study hypotheses. Participants (N = 799) who were not virally suppressed, were new to care, or had fallen out of care were randomly assigned to receive Positive Health Check or the standard of care alone. The primary endpoint was viral load suppression, and the secondary endpoint was retention in care, both assessed at 12 months, using an intention-to-treat approach. A priori subgroup analyses based on sex assigned at birth and race were examined as well. RESULTS: There were no statistically significant differences between Positive Health Check (N = 397) and standard of care (N = 402) for either endpoint. However, statistically significant group differences were identified from a priori subgroup analyses. Male participants receiving Positive Health Check were more likely to achieve suppression at 12 months than male participants receiving standard of care adjusted risk ratio [aRR] [95% confidence interval (CI)] = 1.14 (1.00 to 1.29), P = 0.046}. For retention in care, there was a statistically significant lower risk for a 6-month visit gap in the Positive Health Check arm for the youngest participants, 18-29 years old [aRR (95% CI) = 0.55 (0.33 to 0.92), P = 0.024] and the oldest participants, 60-81 years old [aRR (95% CI) = 0.49 (0.30 to 0.81), P = 0.006]. CONCLUSIONS: Positive Health Check may help male participants with HIV achieve viral suppression, and younger and older patients consistently attend HIV care. REGISTRY NAME: Positive Health Check Evaluation Trial. Trial ID: 1U18PS004967-01. URL: https://clinicaltrials.gov/ct2/show/NCT03292913.

    • Veterinary Medicine
      1. Activity patterns and burrowing ecology of the giant pouched rat (Cricetomys emini) in Tshuapa Province, D. R. Congo
        Kalemba LN, Morgan CN, Nakazawa YJ, Mauldin MR, Malekani JM, Doty JB.
        Mammalia. 2022 .
        Rodents of the genus Cricetomys have been reported to be nocturnal with a bimodal activity pattern and to frequently change burrows. However, no studies to date have examined these ecological aspects with the use of radio-telemetry. Five C. emini were captured and radio-collared to study their activity patterns and burrowing ecology from 9 March to 15 April 2016. Nocturnal activity ranged between the hours of 18:00 and 05:00 with a probable reduction of activities between 20:00-23:00 and around 04:00 with diurnal activity between 06:00 and 17:00 h with a reduction of activity between 11:00 and 14:00. While the present study does confirm nocturnal activity and a bimodal pattern, this study also suggests greater diurnal activity as compared to previous studies. Additionally, data presented here also suggest that C. emini may not change burrows as frequently as previously reported. © 2022 Walter de Gruyter GmbH, Berlin/Boston 2022.

    • Zoonotic and Vectorborne Diseases
      1. Multistate reptile- and amphibian-associated salmonellosis outbreaks in humans, United States, 2009–2018
        Waltenburg MA, Perez A, Salah Z, Karp BE, Whichard J, Tolar B, Gollarza L, Koski L, Blackstock A, Basler C, Nichols M.
        Zoonoses Public Health. 2022 .
        Non-typhoidal Salmonella cause an estimated 1.4 million human illnesses, 26,000 hospitalizations and 400 deaths annually in the United States. Approximately 11% of these infections are attributed to animal contact. Reptiles and amphibians are known sources of salmonellosis; young children (aged <5 years) are disproportionately affected by reptile- and amphibian-associated salmonellosis (RAAS) outbreaks. We describe multistate RAAS outbreaks to characterize illnesses and inform prevention efforts. RAAS outbreaks were defined as ≥2 culture-confirmed human Salmonella infections with similar pulsed-field gel electrophoresis patterns and epidemiologic, laboratory or traceback evidence linking them to a common reptile/amphibian exposure. Data sources included the Animal Contact Outbreak Surveillance System; CDC Outbreak Response and Prevention Branch's outbreak management database; PulseNet, the national molecular subtyping network for foodborne disease surveillance in the United States; and the National Antimicrobial Resistance Monitoring System. Twenty-six RAAS outbreaks were reported during 2009–2018, resulting in 1465 illnesses and 306 hospitalizations. The outbreaks were associated with turtles (19), lizards (5), snakes (1) and frogs (1). Sixteen (61.5%) outbreaks were linked to small turtles (<4 inches), resulting in 914 illnesses. Forty-nine percent of outbreak-associated patients were aged <5 years. Of 362 patients/caregivers interviewed, 111 (30.7%) were aware that reptiles/amphibians can carry Salmonella. Among 267 patient isolates with antimicrobial susceptibility information, 20 (7.5%) were non-susceptible to ≥1 antibiotic used to treat human salmonellosis. RAAS outbreaks result in considerable morbidity, particularly among young children. Illnesses linked to small turtles are preventable through education, targeted outreach to caregivers and paediatricians, and when appropriate, enforcement. Historically, individual states and jurisdictions have enforced existing or promulgated new authorities to address outbreaks. Preventing future RAAS outbreaks requires addressing challenges related to the illegal sale/distribution of small turtles; and for legal reptile sales, providing information on RAAS risk to consumers at point of sale to support informed pet ownership decisions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Zoonoses and Public Health published by Wiley-VCH GmbH.


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Content source: Centers for Disease Control and Prevention