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Issue 31, August 2, 2022

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CDC Science Clips: Volume 14, Issue 31, August 2, 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. Clinical and genomic epidemiology of mcr-9-carrying carbapenem-resistant Enterobacterales isolates in metropolitan Atlanta, 2012 to 2017
        Babiker A, Bower C, Lutgring JD, Petit RA, Howard-Anderson J, Ansari U, McAllister G, Adamczyk M, Breaker E, Satola SW, Jacob JT, Woodworth MH.
        Microbiol Spectr. 2022 Jul 20:e0252221.
        Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012 and 2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole-genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9-positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between mcr-9-positive and -negative isolates. However, rates of resistance were higher among mcr-9-positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both mcr-9-positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. mcr-9-positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; P < 0.001) than did mcr-9-negative isolates. Pangenome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes, but continued genomic surveillance to monitor for emergence of AMR genes is warranted. IMPORTANCE Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. A recently described allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, has been widely reported among Enterobacterales species. However, its clinical and public health significance remains unclear. We compared characteristics and outcomes of mcr-9-positive and -negative CRE cases. All cases were acquired in the health care setting and associated with a high rate of mortality. The presence of mcr-9 was not associated with significant changes in colistin resistance, heteroresistance, or inducible resistance but was associated with resistance to other antimicrobials and antimicrobial resistance (AMR), virulence, and heavy metal resistance (HMR) genes. Overall, the presence of mcr-9 was not associated with significant phenotypic changes or clinical outcomes. However, given the increase in AMR and HMR gene content and potential clinical impact, continued genomic surveillance of multidrug-resistant organisms to monitor for emergence of AMR genes is warranted.

      2. Development of an electronic algorithm to target outpatient antimicrobial stewardship efforts for acute bronchitis and pharyngitis
        Lautenbach E, Hamilton KW, Grundmeier R, Neuhauser MM, Hicks LA, Jaskowiak-Barr A, Cressman L, James T, Omorogbe J, Frager N, Menon M, Kratz E, Dutcher L, Chiotos K, Gerber JS.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac273.
        BACKGROUND: A major challenge for antibiotic stewardship programs is the lack of accurate and accessible electronic data to target interventions. We developed and validated separate electronic algorithms to identify inappropriate antibiotic use for adult outpatients with bronchitis and pharyngitis. METHODS: We used International Classification of Diseases, 10th Revision, diagnostic codes to identify patient encounters for acute bronchitis and pharyngitis at outpatient practices between 3/15/17 and 3/14/18. Exclusion criteria included immunocompromising conditions, complex chronic conditions, and concurrent infections. We randomly selected 300 eligible subjects each with bronchitis and pharyngitis. Inappropriate antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm, which was constructed using only data in the electronic data warehouse. Criteria for appropriate prescribing, choice of antibiotic, and duration were based on established guidelines. RESULTS: Of 300 subjects with bronchitis, 167 (55.7%) received an antibiotic inappropriately based on chart review. The electronic algorithm demonstrated 100% sensitivity and 95.3% specificity for detection of inappropriate prescribing. Of 300 subjects with pharyngitis, 94 (31.3%) had an incorrect prescribing decision. Among 29 subjects with a positive rapid streptococcal antigen test, 27 (93.1%) received an appropriate antibiotic and 29 (100%) received the correct duration. The electronic algorithm demonstrated very high sensitivity and specificity for all outcomes. CONCLUSIONS: Inappropriate antibiotic prescribing for bronchitis and pharyngitis is common. Electronic algorithms for identifying inappropriate prescribing, antibiotic choice, and duration showed excellent test characteristics. These algorithms could be used to efficiently assess prescribing among practices and individual clinicians. Interventions based on these algorithms should be tested in future work.

    • Chronic Diseases and Conditions
      1. The shifting prevalence of asthma and allergic disease in United States children
        Pate CA, Zahran HS, Malilay J, Hsu J.
        Ann Allergy Asthma Immunol. 2022 Jul 13.
        BACKGROUND: Asthma is a chronic lung disease that affected 5 million children. Allergy is a common comorbidity of asthma. Having both conditions is associated with unfavorable health outcomes and impaired quality of life. OBJECTIVE: Purpose of this study was to assess allergy and its association with asthma by select characteristics among children to determine differences by populations. METHODS: National Health Interview Survey data (2007-2018) were used to assess asthma and allergy status, trends, the association between allergy and asthma by select characteristics among U.S. children (aged 0-17 years). RESULTS: Prevalence of asthma decreased among all children (slope(-) p<0.001) and among those with allergy (slope(-) p=0.002). More children had respiratory allergy (14.7%), followed by skin allergy (12.7%) and food allergy (6.4%). Prevalence of respiratory allergy significantly decreased among White non-Hispanic children, food allergy increased among White non-Hispanic and Hispanic children, and skin allergy increased among Hispanic children. Depending on number and type, children with allergy were 2 to 8 times (skin allergy only and having all three allergies, respectively) more likely to have current asthma than were children without allergy. Among children with current asthma, having any allergy was significantly associated with missed school days (adjusted prevalence ratio [aPR]: 1.33[1.03, 1.72]) and taking preventive medication daily (aPR: 1.89[1.32, 2.71]). CONCLUSION: Trends in allergies across years differed by race and ethnicity. Strength of association between asthma and allergy differed by type and number of allergies, being highest among children having all three types of allergies. Having both asthma and allergy was associated with unfavorable asthma outcomes.

      2. Smoking cessation efforts among WISEWOMAN program participants, 2014-2018
        Vaid I, Blum E, Ahmed K.
        J Womens Health (Larchmt). 2022 Jul;31(7):911-916.
        Smoking is a preventable risk factor for cardiovascular disease (CVD), indicating the importance of smoking cessation. The Centers for Disease Control and Prevention's Well-Integrated Screening and Evaluation for WOMen Across the Nation (WISEWOMAN) Program funded 21 recipients to provide preventative health services, including healthy behavior support services, to low-income, uninsured, or underinsured women, between 40 to 64 years of age, aimed at lowering CVD risk for women from January 2014 to June 2018. This article explores WISEWOMAN's smoking prevalence and smoking cessation efforts. Analyses were conducted to assess smoking status and other CVD risk factors among 71,671 unique women from all 21 WISEWOMAN funded recipients. Information on CVD risk factors, including smoking status, were collected. Women who were identified as currently smoking during their initial visit were referred to smoking cessation services and their smoking status was revisited during their rescreening. The overall smoking cessation prevalence was 16.9% during the funding cycle. This small increase from the previous iteration of WISEWOMAN (14.9%), supports WISEWOMAN's continued emphasis on smoking cessation through community-clinical linkages. The distribution of smoking cessation did vary by race and ethnicity (p < 0.001). Hispanic women had a higher smoking cessation (38.1%) compared to non-Hispanic American Indian/Alaska Native, non-Hispanic Black, and non-Hispanic White women (17.4%, 15.1%, and 13.7% respectively). In the next iteration of the WISEWOMAN Program, it is anticipated that continued emphasis will be placed on achieving health equity among women who smoke, to reduce CVD risk.

      3. The National Diabetes Prevention Program (National DPP) is a partnership of public and private organizations working to build a nationwide delivery system for a lifestyle change program (LCP), which is proved to prevent or delay onset of type 2 diabetes in adults with prediabetes. Through this program, the Centers for Disease Control and Prevention (CDC) establishes partnerships with organizations to prevent or delay the onset of type 2 diabetes by using the evidence-based and audience-tailored LCP. The DP17-1705 cooperative agreement aims to expand the reach of the program in underserved areas and to populations currently underrepresented in the program relative to their risk. This article highlights a successful adaptation of the National DPP PreventT2 curriculum to address the needs of women who are Black funded by this cooperative agreement. The Change your Lifestyle, Change your Life (CYL(2)) program resulted from a partnership between CDC and the Black Women's Health Imperative. Successes and challenges associated with this program are highlighted. Lessons learned from these efforts can be used by practitioners to inform future type 2 diabetes prevention initiatives.

    • Communicable Diseases
      1. Impact of the COVID-19 pandemic on prescriptions for antiretroviral drugs for HIV treatment in the United States, 2019-2021
        Zhu W, Huang YA, Weiner J, Neblett-Fanfair R, Kourtis AP, Hall HI, Hoover KW.
        AIDS. 2022 Jul 15.
        OBJECTIVE: To access disruption in healthcare services for HIV treatment by national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic in the United States. DESIGN: Time-series analysis. METHODS: We analyzed the IQVIA Real World Data-Longitudinal Prescriptions Database and calculated time trends in the weekly number of persons with active antiretroviral (ARV) prescriptions for HIV treatment, and of persons who obtained ARV prescriptions during January 2017-March 2021. We used interrupted time-series models to estimate the impact of the COVID-19 pandemic on antiretroviral therapy (ART) use between March 2020 and March 2021. RESULTS: We found that the weekly number of persons with active ARV prescriptions decreased by an average 2.5% (95% confidence interval [CI]: -3.8% to -1.1%), compared to predicted use, during March 2020 through March 2021. The weekly number of persons who obtained ARV prescriptions decreased 4.5% (95% CI: -6.0% to -3.0%), compared to the predicted number. Men, persons aged ≤34 years, privately insured persons, and persons in medication assistance programs had greater decreases than other groups. CONCLUSIONS: We demonstrated a decrease in the number of persons with active ARV prescriptions during the first year of the COVID-19 pandemic and the number did not return to levels expected in the absence of the pandemic. Disruptions in HIV care and decreased ART may lead to lower levels of viral suppression and immunologic control, and increased HIV transmission in the community.

      2. Adolescent girls and young women (AGYW) living with HIV have poor antiretroviral therapy (ART) outcomes. We examined the relationship between psychosocial factors with knowledge of HIV-positive status and antiretroviral therapy exposure among AGYW living with HIV in South Africa. Participants 15-24 years responded to a survey including socio-demographics, psychosocial factors, and HIV testing. Blood was collected to determine HIV status and ART exposure. Multivariable analyses were conducted using R. Of 568 participants with HIV, 356 had knowledge of their HIV-positive status. Social support from family [aOR 1.14 (95% CI 1.04-1.24)] or from a special person [aOR 1.12 (95% CI 1.02-1.23)] was associated with knowledge of HIV-positive status. Resilience [aOR 1.05 (95% CI 1.01-1.08)] was the only psychosocial factor associated with a higher odds of ART exposure. Social support and resilience may increase knowledge of HIV-positive status and ART exposure among South African AGYW.

      3. HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype
        Li SS, Hickey A, Shangguan S, Ehrenberg PK, Geretz A, Butler L, Kundu G, Apps R, Creegan M, Clifford RJ, Pinyakorn S, Eller LA, Luechai P, Gilbert PB, Holtz TH, Chitwarakorn A, Sacdalan C, Kroon E, Phanuphak N, de Souza M, Ananworanich J, O'Connell RJ, Robb ML, Michael NL, Vasan S, Thomas R.
        Cell Host Microbe. 2022 Jul 15.
        Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.

      4. Preexisting heterotypic ligand-blocking antibody does not protect against genogroup II norovirus episodes in young children
        Becker-Dreps S, Brewer-Jensen PD, González F, Reyes Y, Mallory ML, Gutiérrez L, Vielot NA, Diez-Valcarce M, Vinjé J, Baric RS, Lindesmith LC, Bucardo F.
        J Pediatric Infect Dis Soc. 2022 Jul 18.
        A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibodies provide cross-protection within the GII genogroup. We found that almost one-half of children who experienced a norovirus GII episode had preexisting antibodies heterotypic to the infecting genotype; therefore, these antibodies did not provide cross-protection.

      5. Clinical presentation and severity of adenovirus detection alone vs adenovirus co-detection with other respiratory viruses in US children with acute respiratory illness from 2016 to 2018
        Probst V, Spieker AJ, Stopczynski T, Stewart LS, Haddadin Z, Selvarangan R, Harrison CJ, Schuster JE, Staat MA, McNeal M, Weinberg GA, Szilagyi PG, Boom JA, Sahni LC, Piedra PA, Englund JA, Klein EJ, Michaels MG, Williams JV, Campbell AP, Patel M, Gerber SI, Halasa NB.
        J Pediatric Infect Dis Soc. 2022 Jul 18.
        BACKGROUND: Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses. METHODS: We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1-4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS). RESULTS: Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11-2.34]), RSV (aOR = 4.48; 95% CI = [2.81-7.14]), HMPV (aOR = 3.39; 95% CI = [1.69-6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14-3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS. CONCLUSIONS: HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone.

      6. Trends in percentages of the US population covered by state-issued COVID-19 nonpharmaceutical interventions, March 1, 2020-August 15, 2021
        Joo H, Howard-Williams M, McCord RF, Sunshine G, Fuller JA, Maskery BA.
        J Public Health Manag Pract. 2022 Sep-Oct 01;28(5):491-495.
        Trends in the percentages of the US population covered by state-issued nonpharmaceutical interventions (NPIs), including restaurant and bar restrictions, stay-at-home orders, gathering limits, and mask mandates, were examined by using county-specific data sets on state-issued orders for NPIs from March 1, 2020, to August 15, 2021. Most of the population was covered by multiple NPIs early in the pandemic. Most state-issued orders were lifted or relaxed as COVID-19 cases decreased during summer 2020. Few states reimplemented strict NPIs during later surges in US COVID-19 cases over the winter of 2020-2021. The exceptions were mask mandates, which covered about 80% of the population between August 2020 and February 2021, and the most restrictive gathering limits, which covered a maximum of 66% of the population in early 2020 and 68% of the population in winter 2020-2021. Most NPIs were lifted by the end of the analysis period.

      7. Incidence of respiratory virus illness and hospitalizations in a Panama and El Salvador birth cohort, 2014–2018
        Azziz-Baumgartner E, Duca LM, González R, Calvo A, Kaydos-Daniels SC, Olson N, MacNeil A, Veguilla V, Domínguez R, Vicari A, Rauda R, Vuong N, Ropero AM, Armero J, Porter R, Franco D, Pascale JM.
        Lancet Reg Health Americas. 2022 ;13.
        Background: Respiratory viruses remain a key cause of early childhood illness, hospitalization, and death globally. The recent pandemic has rekindled interest in the control of respiratory viruses among paediatric populations. We estimate the burden of such viruses among children <2 years. Methods: Enrolled neonates were followed until two years of age. Weekly active symptom monitoring for the development of acute respiratory illnesses (ARI) defined as cough, rhinorrhoea, difficulty breathing, asthenia, anorexia, irritability, or vomiting was conducted. When the child had ARI and fever, nasopharyngeal swabbing was performed, and samples were tested through singleplex RT-PCR. Incidence of respiratory viruses was calculated by dividing the number of laboratory-confirmed detections by the person-time accrued during weeks when that virus was detectable through national surveillance then corrected for under-ascertainment among untested children. Findings: During December 2014–November 2017, 1567 enrolled neonates contributed 2,186.9 person-years (py). Six in ten (64·4%) children developed ARI (total 2493 episodes). Among children <2 years, incidence of respiratory syncytial virus (RSV)-associated ARI episodes (21·0, 95%CI 19·3–22·8, per 100py) and rhinovirus-associated (20·5, 95%CI 20·4–20·7) were similar and higher than parainfluenza 1–3-associated (14·2, 95%CI 12·2–16·1), human metapneumovirus-associated (9·2, 95%CI 7·7–10·8), influenza-associated (5·9, 95%CI 4·4–7·5), and adenovirus-associated ARI episodes (5·1, 95%CI 5·0–5·2). Children aged <3 months had the highest rates of RSV ARI (49·1, 95%CI 44·0–54·1 per 100py) followed by children aged 3–5 (25·1, 95%CI 20·1–30·0), 6–11 (17·6, 95%CI 13·2–21·9), and 12–23 months (11·9, 95%CI 10·8–12·9). One in ten children with RSV was referred to the hospital (2·5, 95%CI 2·1–2·8, per 100py). Interpretation: Children frequently developed viral ARI and a substantive proportion required hospital care. Such findings suggest the importance of exploring the value of new interventions and increasing uptake of existing prevention measures to mitigate burden of epidemic-prone respiratory viruses. Funding: The study was supported by the Centers for Disease Control and Prevention. © 2022

      8. Pediatric HIV case identification across 22 PEPFAR-supported countries during the COVID-19 pandemic, October 2019-September 2020
        Traub AM, Medley A, Gross J, Sloan M, Amzel A, Gleason MM, Fernando NB, Wong V, Grillo MP, Wolf HT, Al-Samarrai T, Frawley A, Segwabe M, Motswere C, Baramperanye E, Nzima V, Mange Mayer M, Balachandra S, N'Siesi F X, Longuma HO, Nyembo P, Mazibuko S, Tilahun T, Teferi W, Desinor O, Reginald JL, Simiyu T, Nyabiage L, Mirembe J, Ts'oeu M, Zomba G, Nyangulu M, Wate A, Greenberg Cowan J, Mali D, Pietersen I, Ogundehin D, Onotu D, Ikpeazu A, Niyonsaba E, Bamwesigye J, Mabasa H, Kindra G, Bunga S, Rwegerera F, Machage E, King'ori G, Calnan J, Nazziwa E, Lingenda G, Musokotwane K, Bulaya-Tembo R, Maphosa T, Srivastava M.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 15;71(28):894-898.
        During 2020, an estimated 150,000 persons aged 0-14 years acquired HIV globally (1). Case identification is the first step to ensure children living with HIV are linked to life-saving treatment, achieve viral suppression, and live long, healthy lives. Successful interventions to optimize pediatric HIV testing during the COVID-19 pandemic are needed to sustain progress toward achieving Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.* Changes in HIV testing and diagnoses among persons aged 1-14 years (children) were assessed in 22 U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries during October 1, 2019-September 30, 2020. This period corresponds to the two fiscal quarters before the COVID-19 pandemic (i.e., Q1 and Q2) and the two quarters after the pandemic began (i.e., Q3 and Q4). Testing was disaggregated by age group, testing strategy, and fiscal year quarter. During October 2019-September 2020, PEPFAR supported 4,312,343 HIV tests and identified 74,658 children living with HIV (CLHIV). The number of HIV tests performed was similar during Q1 and Q2, decreased 40.1% from Q2 to Q3, and increased 19.7% from Q3 to Q4. The number of HIV cases identified among children aged 1-14 years (cases identified) increased 7.4% from Q1 to Q2, decreased 29.4% from Q2 to Q3, and increased 3.3% from Q3 to Q4. Although testing in outpatient departments decreased 21% from Q1 to Q4, testing from other strategies increased during the same period, including mobile testing by 38%, facility-based index testing (offering an HIV test to partners and biological children of persons living with HIV) by 8%, and testing children with signs or symptoms of malnutrition within health facilities by 7%. In addition, most tests (61.3%) and cases identified (60.9%) were among children aged 5-14 years (school-aged children), highlighting the need to continue offering HIV testing to older children. These findings provide important information on the most effective strategies for identifying CLHIV during the COVID-19 pandemic. HIV testing programs should continue to use programmatic, surveillance, and financial data at both national and subnational levels to determine the optimal mix of testing strategies to minimize disruptions in pediatric case identification during the COVID-19 pandemic.

      9. Phylogenomic comparison of Neisseria gonorrhoeae causing disseminated gonococcal infections and uncomplicated gonorrhea in Georgia, United States
        Cartee JC, Joseph SJ, Weston E, Pham CD, Thomas JC, Schlanger K, St Cyr SB, Farley MM, Moore AE, Tunali AK, Cloud C, Raphael BH.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac247.
        Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination.

      10. Spatial distribution and determinants of HIV prevalence among adults in urban Ethiopia: Findings from the Ethiopia Population-based HIV Impact Assessment Survey (2017-2018)
        Gelibo T, Lulseged S, Eshetu F, Abdella S, Melaku Z, Ajiboye S, Demissie M, Solmo C, Ahmed J, Getaneh Y, Kaydos-Daniels SC, Abate E.
        PLoS One. 2022 ;17(7):e0271221.
        The design and evaluation of national HIV programs often rely on aggregated national data, which may obscure localized HIV epidemics. In Ethiopia, even though the national adult HIV prevalence has decreased, little information is available about local areas and subpopulations. To inform HIV prevention efforts for specific populations, we identified geographic locations and drivers of HIV transmission. We used data from adults aged 15-64 years who participated in the Ethiopian Population-based HIV Impact Assessment survey (October 2017-April 2018). Location-related information for the survey clusters was obtained from the 2007 Ethiopia population census. Spatial autocorrelation of HIV prevalence data were analyzed via a Global Moran's I test. Geographically weighted regression analysis was used to show the relationship of covariates. The finding indicated that uncircumcised men in certain hotspot towns and divorced or widowed individuals in hotspot woredas/towns might have contributed to the average increase in HIV prevalence in the hotspot areas. Hotspot analysis findings indicated that, localized, context-specific intervention efforts tailored to at-risk populations, such as divorced or widowed women or uncircumcised men, could decrease HIV transmission and prevalence in urban Ethiopia.

      11. An examination of SARS-CoV-2 transmission based on classroom distancing in schools with other preventive measures in place-Missouri, January-March 2021
        Donovan CV, Worrell MC, Steinberg J, Montgomery BK, Young R, Richardson G, Dawson P, Dinh TH, Botkin N, Fitzpatrick T, Fields A, Rains CM, Fritz S, Malone S, Tong S, Mooney J, Newland JG, Barrios LC, Neatherlin JC, Salzer JS.
        Public Health Rep. 2022 Jul 16:333549221109003.
        OBJECTIVES: Classroom layout plays a central role in maintaining physical distancing as part of a multicomponent prevention strategy for safe in-person learning during the COVID-19 pandemic. We conducted a school investigation to assess layouts and physical distancing in classroom settings with and without in-school SARS-CoV-2 transmission. METHODS: We assessed, measured, and mapped 90 K-12 (kindergarten through grade 12) classrooms in 3 Missouri public school districts during January-March 2021, prior to widespread prevalence of the Delta variant; distances between students, teachers, and people with COVID-19 and their contacts were analyzed. We used whole-genome sequencing to further evaluate potential transmission events. RESULTS: The investigation evaluated the classrooms of 34 students and staff members who were potentially infectious with COVID-19 in a classroom. Of 42 close contacts (15 tested) who sat within 3 ft of possibly infectious people, 1 (2%) probable transmission event occurred (from a symptomatic student with a longer exposure period [5 days]); of 122 contacts (23 tested) who sat more than 3 ft away from possibly infectious people with shorter exposure periods, no transmission events occurred. CONCLUSIONS: Reduced student physical distancing is one component of mitigation strategies that can allow for increased classroom capacity and support in-person learning. In the pre-Delta variant period, limited physical distancing (<6 ft) among students in K-12 schools was not associated with increased SARS-CoV-2 transmission.

      12. Recent incarceration among individuals infected with hepatitis A virus during person-to-person community outbreaks, United States, 2016-2020
        Hagan LM, Montgomery MP, Lauro PL, Cima M, Stringer G, Kupferman NM, Leapley A, Gandhi AP, Nims D, Iberg Johnson J, Bouton L, Burkholder C, Grilli GA, Kittle T, Hansen K, Sievers MM, Newman AP, Albertson JP, Taylor B, Pietrowski M, Stous S, Qiu-Shultz Z, Jones C, Barbeau B, Nicolai LA, McCombs K, Chan M, Cooley L, Gupta N, Nelson N.
        Public Health Rep. 2022 Jul 20:333549221108413.
        OBJECTIVES: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. METHODS: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. RESULTS: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016-January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. CONCLUSIONS: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response.

      13. Sociodemographic and clinical characteristics associated with recent incarceration among people with HIV, United States, 2015-2017
        Reyes JV, Myles RL, Luo Q, Beer L, Burton DC.
        Public Health Rep. 2022 Jul 16:333549221106646.
        OBJECTIVES: We examined sociodemographic, clinical, and behavioral factors associated with previous incarceration among people with diagnosed HIV to inform HIV care efforts for this population. METHODS: We used 2015-2017 data from a cross-sectional, nationally representative sample of US adults with diagnosed HIV (N = 11 739). We computed weighted percentages and 95% CIs to compare the characteristics of people with HIV incarcerated in the past 12 months (ie, recently) with people with HIV not recently incarcerated. We used adjusted prevalence ratios (aPRs) with predicted marginal means to examine associations between selected factors and incarceration status. RESULTS: Adults with HIV who were recently incarcerated, when compared with those who were not, were more likely to be aged 18-29 years (prevalence ratio [PR] = 2.51), non-Hispanic Black (PR = 1.39), less educated (<high school diploma; PR = 1.41), unemployed (PR = 1.32), or living at or below the federal poverty level (PR = 1.64); to have recently experienced homelessness (PR = 4.56); and to have recently used drugs (PR = 1.68). Clinically, they were more likely to have been diagnosed with HIV in the past 5 years (aPR = 1.26), have lower CD4 counts (aPR = 1.45), have recently used the emergency department (aPR = 1.15), and have experienced severe anxiety (aPR = 1.50) and less likely to be retained in care, be recently virally suppressed, or have sustained viral suppression. CONCLUSIONS: Among people with HIV, recent incarceration was associated with increased health risks and worse health outcomes. Pre- and postrelease linkage-to-care interventions and reentry services might improve the health of recently incarcerated people with HIV.

      14. Chlamydial Pgp3 seropositivity and population-attributable fraction among women with tubal factor infertility
        Anyalechi GE, Hong J, Kirkcaldy RD, Wiesenfeld HC, Horner P, Wills GS, McClure MO, Hammond KR, Haggerty CL, Kissin DM, Hook EW, Steinkampf MP, Bernstein K, Geisler WM.
        Sex Transm Dis. 2022 Aug 1;49(8):527-533.
        BACKGROUND: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay. METHODS: In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI. RESULTS: All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%-33.8%) for non-Black cases, 15.2% (95% CI, 12.3%-18.7%) for non-Black controls, 66.0% (95% CI, 51.7%-77.8%) for Black cases, and 71.7% (95% CI, 59.2%-81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%-32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis). CONCLUSIONS: Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women.

      15. Shigellosis cases with bacterial sexually transmitted infections: Population-based data from 6 US jurisdictions, 2007 to 2016
        Ridpath AD, Vanden Esschert KL, Bragg S, Campbell S, Convery C, Cope A, Devinney K, Diesel JC, Kikuchi N, Lee N, Lewis FM, Matthias J, Pathela P, Pugsley R, Sanderson Slutsker J, Schillinger JA, Thompson C, Tingey C, Wilson J, Newman DR, Marsh ZA, Garcia-Williams AG, Kirkcaldy RD.
        Sex Transm Dis. 2022 Aug 1;49(8):576-581.
        BACKGROUND: Shigella species, which cause acute diarrheal disease, are transmitted via fecal-oral and sexual contact. To better understand the overlapping populations affected by Shigella infections and sexually transmitted infections (STIs) in the United States, we examined the occurrence of reported STIs within 24 months among shigellosis case-patients. METHODS: Culture-confirmed Shigella cases diagnosed from 2007 to 2016 among residents of 6 US jurisdictions were matched to reports of STIs (chlamydia, gonorrhea, and all stages of syphilis) diagnosed 12 months before or after the shigellosis case. We examined epidemiologic characteristics and reported temporal trends of Shigella cases by sex and species. RESULTS: From 2007 to 2016, 10,430 shigellosis cases were reported. The annual number of reported shigellosis cases across jurisdictions increased 70%, from 821 cases in 2007 to 1398 cases in 2016; males saw a larger increase compared with females. Twenty percent of male shigellosis case-patients had an STI reported in the reference period versus 4% of female case-patients. The percentage of male shigellosis case-patients with an STI increased from 11% (2007) to 28% (2016); the overall percentage among females remained low. CONCLUSIONS: We highlight the substantial proportion of males with shigellosis who were diagnosed with STIs within 24 months and the benefit of matching data across programs. Sexually transmitted infection screening may be warranted for male shigellosis case-patients.

    • Disease Reservoirs and Vectors
      1. Feral swine, Sus scrofa L., have become a nuisance to landowners across the United States by damaging agriculture, property, and ecosystems. Additionally, these animals have been found to host various ixodid ticks including Amblyomma americanum (L.), Amblyomma maculatum Koch, Dermacentor variabilis (Say), and Ixodes scapularis Say, which can maintain and transmit several rickettsial pathogens to livestock, wildlife, and humans. Though previous research has identified the maintenance cycle of several rickettsial pathogens in ticks and native wildlife, little is known about the role S. scrofa plays in supporting ixodid ticks and the pathogens these ticks could be harboring. This study sought to identify rickettsial agents (Rickettsiales: Anaplasmataceae and Rickettsiaceae) in ticks collected from S. scrofa obtained in Florida and South Carolina. Overall, ticks from four species (A. americanum, D. variabilis, I. scapularis, and A. maculatum) totaling 258 collected individuals were obtained from S. scrofa (n = 45). We found an Ehrlichia chaffeensis Anderson et al. infection prevalence in A. americanum of 2.7% and 2.9% in Florida and South Carolina, respectively. A Rickettsia parkeri Lackman et al. prevalence of 100% and 33% was found in A. maculatum from Florida and South Carolina, respectively. Additionally, a 0.9% infection prevalence of R. parkeri was identified in A. americanum collected in South Carolina. A 1.9% Ehrlichia ewingii Anderson et al. infection prevalence was documented in collected A. americanum in South Carolina. Further studies are warranted to better understand the role S. scrofa plays in the natural maintenance of rickettsial agents in various regions of the United States. © 2022 Georgia Entomological Society Inc.. All rights reserved.

      2. Needs assessment of Southeastern United States vector control agencies: Capacity improvement is greatly needed to prevent the next vector-borne disease outbreak
        Dye-Braumuller KC, Gordon JR, Johnson D, Morrissey J, McCoy K, Dinglasan RR, Nolan MS.
        Trop Med Infect Dis. 2022 May 13;7(5).
        A national 2017 vector control capacity survey was conducted to assess the United States' (U.S.'s) ability to prevent emerging vector-borne disease. Since that survey, the southeastern U.S. has experienced continued autochthonous exotic vector-borne disease transmission and establishment of invasive vector species. To understand the current gaps in control programs and establish a baseline to evaluate future vector control efforts for this vulnerable region, a focused needs assessment survey was conducted in early 2020. The southeastern U.S. region was targeted, as this region has a high probability of novel vector-borne disease introduction. Paper copies delivered in handwritten envelopes and electronic copies of the survey were delivered to 386 unique contacts, and 150 returned surveys were received, corresponding to a 39% response rate. Overall, the survey found vector control programs serving areas with over 100,000 residents and those affiliated with public health departments had more core capabilities compared to smaller programs and those not affiliated with public health departments. Furthermore, the majority of vector control programs in this region do not routinely monitor for pesticide resistance. Taken as a whole, these results suggest that the majority of the southeastern U.S. is vulnerable to vector-borne disease outbreaks. Results from this survey raise attention to the critical need of providing increased resources to bring all vector control programs to a competent level, ensuring that public health is protected from the threat of vector-borne disease.

    • Environmental Health
      1. Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study
        Chen WJ, Robledo C, Davis EM, Goodman JR, Xu C, Hwang J, Janitz AE, Garwe T, Calafat AM, Peck JD.
        Environ Res. 2022 Jul 15;214(Pt 2):113897.
        Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

    • Genetics and Genomics
      1. Evaluation of urethrotropic-clade meningococcal infection by urine metagenomic shotgun sequencing
        Retchless AC, Itsko M, Bazan JA, Turner AN, Hu F, Joseph SJ, Carter A, Brown M, Snyder B, Wang X.
        J Clin Microbiol. 2022 Feb 16;60(2):e0173221.
        Urethral infections caused by an emerging nongroupable (NG) urethrotropic clade of Neisseria meningitidis were first reported in the United States in 2015 (the "U.S. NmNG urethritis clade"). Here, we evaluate for the presence of other urethral pathogens in men with U.S. NmNG urethritis clade infection. We evaluated 129 urine specimens collected from men at a sexual health clinic, including 33 from patients with culture-confirmed or suspected urethral N. meningitidis infection and 96 specimens in which nucleic acid amplification test detected Neisseria gonorrhoeae, Chlamydia trachomatis, both pathogens, or neither pathogen. N. meningitidis was detected first by real-time PCR, followed by metagenomic shotgun sequencing of 91 specimens to identify coinfections. N. meningitidis genomes were sequenced following selective whole-genome amplification when possible. Metagenomic sequencing detected N. meningitidis in 16 of 17 specimens from culture-confirmed N. meningitidis cases, with no coinfection by other conventional urethral pathogens. Metagenomic sequencing also detected N. meningitidis in three C. trachomatis-positive specimens, one specimen positive for both N. gonorrhoeae and C. trachomatis, and nine specimens with negative N. gonorrhoeae and C. trachomatis results, eight of which had suspected Neisseria infections. N. meningitidis from culture-confirmed N. meningitidis cases belonged to the U.S. NmNG urethritis clade, while N. meningitidis identified in other specimens belonged to multiple clonal complexes. Additional urethral pathogens were predominant in non-N. meningitidis specimens, including N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and herpes simplex virus 2. Coinfection with other conventional urethral pathogens is rare in men with culture-confirmed U.S. NmNG urethritis clade infection and points to the strong association of this clade with disease.

    • Health Economics
      1. OBJECTIVE: To describe characteristics of a nationally representative sample of patient visits that ended with a referral for follow-up medical care after discharge from hospital emergency department (ED) visits. METHODS: We used 2018 National Hospital Ambulatory Medical Care Survey data to identify patient characteristics associated with higher rates of visits with referrals for follow-up medical care after ED discharge from nonfederal short-stay and general hospitals throughout the United States. Referral included categories of all disposition variables that indicated referral to a source of care consistent with the patient's clinical condition at ED discharge. RESULTS: Approximately 97 million of 130 million visits (29 700/100 000 US resident population) were referred for follow-up medical care during 2018. Visit referral rates were higher among females (33 100) than among males (26 300/100 000 population); higher among Black patients (61 700) than among White patients (25 600/100 000 population); highest in the South (33 200/100 000 population); and similar rates in Nonmetropolitan (29 900/100 000 population) and Metropolitan Statistical Areas (30 200/100 000 population). Visit referral rates were higher for patients with Medicaid/Children's Health Insurance Program (CHIP) (66 900) than those with Medicare (31 500) or private insurance (14 000/100 000 population). Abnormal clinical findings and injuries were the discharge diagnoses most often referred for follow-up medical care. CONCLUSION: Higher visit referral rates were observed among female sex, non-Hispanic Black race, Medicaid/CHIP, abnormal clinical findings, and injuries. Future studies might reveal reasons that prompted higher referral rates among various patients' characteristics.

    • Health Equity and Health Disparities
      1. Food insecurity and the risk of HIV acquisition: findings from population-based surveys in six sub-Saharan African countries (2016-2017)
        Low A, Gummerson E, Schwitters A, Bonifacio R, Teferi M, Mutenda N, Ayton S, Juma J, Ahpoe C, Ginindza C, Patel H, Biraro S, Sachathep K, Hakim AJ, Barradas D, Hassani AS, Kirungi W, Jackson K, Goeke L, Philips N, Mulenga L, Ward J, Hong S, Rutherford G, Findley S.
        BMJ Open. 2022 Jul 12;12(7):e058704.
        OBJECTIVE: To assess the potential bidirectional relationship between food insecurity and HIV infection in sub-Saharan Africa. DESIGN: Nationally representative HIV impact assessment household-based surveys. SETTING: Zambia, Eswatini, Lesotho, Uganda and Tanzania and Namibia. PARTICIPANTS: 112 955 survey participants aged 15-59 years with HIV and recency test results. MEASURES: Recent HIV infection (within 6 months) classified using the HIV-1 limited antigen avidity assay, in participants with an unsuppressed viral load (>1000 copies/mL) and no detectable antiretrovirals; severe food insecurity (SFI) defined as having no food in the house ≥three times in the past month. RESULTS: Overall, 10.3% of participants lived in households reporting SFI. SFI was most common in urban, woman-headed households, and in people with chronic HIV infection. Among women, SFI was associated with a twofold increase in risk of recent HIV infection (adjusted relative risk (aRR) 2.08, 95% CI 1.09 to 3.97). SFI was also associated with transactional sex (aRR 1.28, 95% CI 1.17 to 1.41), a history of forced sex (aRR 1.36, 95% CI 1.11 to 1.66) and condom-less sex with a partner of unknown or positive HIV status (aRR 1.08, 95% CI 1.02 to 1.14) in all women, and intergenerational sex (partner ≥10 years older) in women aged 15-24 years (aRR 1.23, 95% CI 1.03 to 1.46). Recent receipt of food support was protective against HIV acquisition (aRR 0.36, 95% CI 0.14 to 0.88). CONCLUSION: SFI increased risk for HIV acquisition in women by twofold. Heightened food insecurity during climactic extremes could imperil HIV epidemic control, and food support to women with SFI during these events could reduce HIV transmission.

      2. Urban-rural differences in health care utilization for inflammatory bowel disease in the USA, 2017
        Xu F, Carlson SA, Liu Y, Greenlund KJ.
        Dig Dis Sci. 2022 Aug;67(8):3601-3611.
        BACKGROUND: Urban-rural differences in IBD-specific health care utilization at the national level have not been examined in the USA. AIMS: We compared urban and rural rates of IBD-related office visits and IBD-specific (Crohn's disease (CD) or ulcerative colitis (UC)) hospitalizations and emergency department (ED) visits. METHODS: From multiple national data sources, we compared national rates using Z test and compared estimates of patient and hospital characteristics and hospitalization outcomes between urban and rural areas using Chi-square and t tests. RESULTS: In 2015 and 2016, digestive disease-related office visit rates, per 100 adults, were 3.1 times higher in urban than in rural areas (8.7 vs 2.8, P < 0.001). In 2017, age-adjusted rates per 100,000 adults were significantly higher in rural than urban areas for CD-specific hospitalizations (26.3 vs 23.6, P = 0.03) and ED visits (49.3 vs 39.5, P = 0.002). Compared with their urban counterparts, rural adults hospitalized for CD or UC in 2017 were more likely to be older and non-Hispanic white, have lower household income, Medicare coverage, and an elective admission, and were discharged from hospitals that were large, non-federal government owned, and in the Midwest or South. There were no significant urban-rural differences in length of stay and 30-day readmission rate. CONCLUSIONS: While IBD or digestive disease-related office visit rates were lower in rural compared to urban areas, CD-specific hospitalization and ED visit rates were higher. Strategies that improve office-based care among rural patients with IBD may help to avoid more costly forms of health care use.


      4. Sexually transmitted infection testing among unstably housed, sexually active persons with HIV in the United States, 2018-2019
        Marcus R, Tie Y, Dasgupta S, Crim SM, Beer L, Williams SP, Weiser J.
        Sex Transm Dis. 2022 Jul 21.
        Unstably housed sexually active people with HIV (PWH) experience both a high incidence of sexually transmitted infections (STIs) and barriers to annual STI screening recommended by CDC guidelines. We used Medical Monitoring Project data to describe STI testing among unstably housed PWH by attendance at Ryan White HIV/AIDS Program-funded facilities.

    • Immunity and Immunization
      1. Effectiveness of COVID-19 vaccination against SARS-CoV-2 infection among residents of US nursing homes, before and during the Delta variant predominance, December 2020 - November 2021
        Hatfield KM, Baggs J, Wolford H, Fang M, Sattar AA, Montgomery KS, Jin S, Jernigan J, Pilishvili T.
        Clin Infect Dis. 2022 Jul 20.
        BACKGROUND: Residents of nursing homes experience disproportionate morbidity and mortality related to COVID-19 and were prioritized for vaccine introduction. We evaluated COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infections among nursing home residents. METHODS: We used a retrospective cohort of 4,315 nursing home residents during December 14, 2020 - November 9, 2021. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a completed vaccination series to unvaccinated among those with and without prior SARS-CoV-2 infection (identified using positive SARS-CoV-2 tests and/or diagnosis codes), by vaccine product, and by period (before and during Delta variant predominance). VE was estimated as one minus the hazard ratio times 100%. RESULTS: Overall adjusted VE for the completed vaccination series was 58% (95%CI: 44%, 69%) among residents without a history of SARS-CoV-2 infection. During the pre-Delta period, the VE within 150 days of receipt of the second dose of Pfizer-BioNTech (67%, 95%CI: 40%, 82%) and Moderna (75%, 95%CI: 32%, 91%) was similar. During the Delta period, VE measured >150 days after the second dose was 33% (95%CI: -2%, 56%) for Pfizer-BioNTech and 77% (95%CI: 48%, 91%) for Moderna. Rates of infection were 78% lower (95%CI: 67%, 85%) among residents with prior SARS-CoV-2 infection and completed vaccination series compared to unvaccinated residents without a history of SARS-CoV-2 infection. CONCLUSIONS: COVID-19 vaccines were effective in preventing SARS-CoV-2 infections among nursing home residents and history of prior SARS-CoV-2 infection provided additional protection. Maintaining high coverage of recommended doses of COVID-19 vaccines remains a critical tool for preventing infections in nursing homes.

      2. Reactogenicity of simultaneous COVID-19 mRNA booster and influenza vaccination in the US
        Hause AM, Zhang B, Yue X, Marquez P, Myers TR, Parker C, Gee J, Su J, Shimabukuro TT, Shay DK.
        JAMA Netw Open. 2022 Jul 1;5(7):e2222241.
        IMPORTANCE: COVID-19 and seasonal influenza vaccines are essential in preventing respiratory infections and their potentially severe complications. Simultaneous administration of vaccines is efficient and may improve coverage with each vaccine. However, the safety of simultaneous administration of COVID-19 and influenza vaccines has not been well described. OBJECTIVE: To evaluate adverse events and health impacts associated with simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines in the US population. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, self-reported vaccine data were collected on days 0 to 7 after vaccination from September 22, 2021, through May 1, 2022, through v-safe, a voluntary smartphone-based monitoring system established by the Centers for Disease Control and Prevention. Participants were persons who voluntarily registered in v-safe following COVID-19 vaccination. EXPOSURE: Receipt of simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines or COVID-19 mRNA booster alone. MAIN OUTCOMES AND MEASURES: Local injection site and systemic reactions (eg, fatigue, headache, and myalgia) and health impacts reported by v-safe respondents in the week following COVID-19 mRNA booster vaccination. Adjusted odds ratios (aORs) were estimated for simultaneous administration compared with booster dose alone, controlling for sex, age, and week of vaccination. RESULTS: Of a total of 981 099 persons aged 12 years or older registered with v-safe, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was reported by 92 023 (9.4%) v-safe respondents; of these respondents, 54 926 (59.7%) were female, 36 234 (39.4%) were male, and sex was unknown for 863 (0.9%). In the week following vaccination, any systemic reactions were reported by 36 144 (58.9%) of 61 390 respondents who simultaneously received Pfizer-BioNTech booster and influenza vaccines and 21 027 (68.6%) of 30633 respondents who simultaneously received Moderna booster and influenza vaccines. Respondents who simultaneously received influenza and Pfizer-BioNTech booster vaccines (aOR, 1.08; 95% CI, 1.06-1.10) or influenza and Moderna booster vaccines (aOR, 1.11; 95% CI, 1.08-1.14) were slightly more likely to report any systemic reaction in the week following simultaneous vaccination than respondents who received only a COVID-19 mRNA vaccine booster. CONCLUSIONS AND RELEVANCE: In this study, compared with administration of COVID-19 mRNA booster vaccines alone, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions during days 0 to 7 following vaccination. These results may help better characterize the outcomes associated with simultaneously administered COVID-19 booster and influenza vaccines in the US population.

      3. Achieving high immunogenicity against poliovirus with fractional doses of inactivated poliovirus vaccine in Ecuador-Results from a cross-sectional serological survey
        Trueba G, Jeyaseelan V, Lopez L, Mainou BA, Zhang Y, Whittembury A, Valarezo AJ, Baquero G, de Aguinaga RR, Salinas LJ, Mancheno MG, Chacho DE, Quentin E, Chevez AE, Rey-Benito G, Mach O.
        Lancet Reg Health Am. 2022 Jul;11:None.
        BACKGROUND: In January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; and bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titres of polio antibodies achieved by the past and the current immunization schedules. METHODS: This was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay. FINDINGS: We obtained 321 analysable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50·0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 - 3·5 vs. 4·8, CI95%= 4·5 - 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients. INTERPRETATION: Ecuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and potentially a cost-effective option in polio immunization. FUNDING: WHO obtained funds for the study from Rotary International.

      4. SARS-CoV-2 convalescent sera binding and neutralizing antibody concentrations compared with COVID-19 vaccine efficacy estimates against symptomatic infection
        Schuh AJ, Satheshkumar PS, Dietz S, Bull-Otterson L, Charles M, Edens C, Jones JM, Bajema KL, Clarke KE, McDonald LC, Patel S, Cuffe K, Thornburg NJ, Schiffer J, Chun K, Bastidas M, Fernando M, Petropoulos CJ, Wrin T, Cai S, Adcock D, Sesok-Pizzini D, Letovsky S, Fry AM, Hall AJ, Gundlapalli AV.
        Microbiol Spectr. 2022 Jul 20:e0124722.
        Previous COVID-19 vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 from COVID-19-unvaccinated persons with detectable anti-SARS-CoV-2 antibodies. Neutralizing and binding antibody concentrations were severalfold lower in the unvaccinated study population compared to published concentrations at 28 days postvaccination. In this convenience sample, ~88% of neutralizing and ~63 to 86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection; ~30% of neutralizing and 1 to 14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. Our study not only supports observations of infection-induced immunity and current recommendations for vaccination postinfection to maximize protection against COVID-19, but also provides a large data set of pre-COVID-19 vaccination anti-SARS-CoV-2 antibody concentrations that will serve as an important comparator in the current setting of vaccine-induced and hybrid immunity. As new SARS-CoV-2 variants emerge and displace circulating virus strains, we recommend that standardized binding antibody assays that include spike protein-based antigens be utilized to estimate antibody concentrations correlated with protection from COVID-19. These estimates will be helpful in informing public health guidance, such as the need for additional COVID-19 vaccine booster doses to prevent symptomatic infection. IMPORTANCE Although COVID-19 vaccine efficacy (VE) studies have estimated antibody concentrations that correlate with protection from COVID-19, how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. We assessed quantitative neutralizing and binding antibody concentrations using standardized assays on serum specimens collected from COVID-19-unvaccinated persons with detectable antibodies. We found that most unvaccinated persons with qualitative antibody evidence of prior infection had quantitative antibody concentrations that met or exceeded concentrations associated with 70% VE against COVID-19. However, only a small proportion had antibody concentrations that met or exceeded concentrations associated with 90% VE, suggesting that persons with prior COVID-19 would benefit from vaccination to maximize protective antibody concentrations against COVID-19.

      5. Safety monitoring of COVID-19 mRNA vaccine first booster doses among persons aged ≥12 years with presumed immunocompromise status - United States, January 12, 2022-March 28, 2022
        Hause AM, Baggs J, Marquez P, Abara WE, Baumblatt JG, Thompson D, Su JR, Myers TR, Gee J, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 15;71(28):899-903.
        Persons with moderate to severe immunocompromising conditions are at risk for severe COVID-19, and their immune response to COVID-19 vaccination might not be as robust as the response in persons who are not immunocompromised* (1). The Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised persons aged ≥12 years complete a 3-dose primary mRNA COVID-19 vaccination series followed by a first booster dose (dose 4) ≥3 months after dose 3 and a second booster dose (dose 5) ≥4 months after dose 4.(†) To characterize the safety of first booster doses among immunocompromised persons aged ≥12 years during January 12, 2022-March 28, 2022, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) during the week after receipt of an mRNA COVID-19 first booster dose. V-safe is a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination. VAERS is a passive surveillance system for all vaccine-associated adverse events co-managed by CDC and the Food and Drug Administration (FDA). A fourth mRNA dose reported to v-safe or VAERS during January 12, 2022-March 28, 2022, was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person because no other population was authorized to receive a fourth dose during that period (2,3). In the United States, during January 12, 2022-March 28, 2022, approximately 518,113 persons aged ≥12 years received a fourth dose. Among 4,015 v-safe registrants who received a fourth dose, local and systemic reactions were less frequently reported than were those following dose 3 of their primary series. VAERS received 145 reports after fourth doses; 128 (88.3%) were nonserious and 17 (11.7%) were serious. Health care providers, immunocompromised persons, and parents of immunocompromised children should be aware that local and systemic reactions are expected after a first booster mRNA COVID-19 vaccine dose, serious adverse events are rare, and safety findings were consistent with those previously described among nonimmunocompromised persons (4,5).

      6. Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011
        Palmsten K, Suhl J, Conway KM, Kharbanda EO, Ailes EC, Cragan JD, Nestoridi E, Papadopoulos EA, Kerr SM, Young SG, DeStefano F, Romitti PA.
        Pharmacoepidemiol Drug Saf. 2022 Aug;31(8):851-862.
        PURPOSE: To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. STUDY DESIGN: We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. RESULTS: There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). CONCLUSIONS: Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

    • Informatics
      1. Assessing concordance of HIV risk behaviors collected by different surveillance systems
        Panneer N, Balaji AB, Crim SM, Bosh KA, Shouse RL, Fagan JL, Beer L.
        AIDS. 2022 Jul 15.
        OBJECTIVES: Assess concordance of assigned transmission category between National HIV Surveillance System (NHSS) and Medical Monitoring Project (MMP); assess persistence of behaviors by comparing transmission category to current behavior. DESIGN: Retrospective analysis of HIV surveillance data. METHODS: For 4034 participants in the 2016 MMP cycle, transmission category was assigned in NHSS and MMP by applying a hierarchy to acquisition risk behaviors and selecting the most likely risk behavior that led to HIV acquisition. We assessed concordance of transmission category between systems, the number of persons with an updated transmission category in NHSS after incorporating MMP data, and concordance of transmission category and current behavior. RESULTS: Concordance of transmission category between NHSS and MMP was 87% for men with evidence of male-to-male sexual contact and ranged from 27% to 62% in persons with other transmission categories. Transmission category in NHSS was updated for 9% of persons after incorporating MMP data, mostly affecting those with no identified risk in NHSS. Current behavior aligned with updated NHSS transmission category in 56% of men with a transmission category of male-to-male sexual contact. However, only 8% of men and 5% of women with a transmission category of injection drug use had recently injected drugs. CONCLUSION: HIV surveillance systems can better inform prevention efforts with more complete risk information. Sexual behaviors are more persistent over time than injection drug use. In addition to promoting viral suppression, routinely assessing risk and tailoring prevention activities accordingly can improve health outcomes.

    • Injury and Violence
      1. Preventing suicidal behavior among American Indian and Alaska Native adolescents and young adults
        Mpofu JJ, Crosby A, Flynn MA, LaFromboise T, Iskander J, Hall JE, Penman-Aguilar A, Thorpe P.
        Public Health Rep. 2022 Jul 20:333549221108986.
        From 2009 to 2018, overall suicide rates in the United States increased by 20.3% and increased by 43.5% among non-Hispanic American Indian and Alaska Native (AI/AN) communities. Combining years 2009 through 2018, suicide rates per 100 000 population among non-Hispanic AI/AN adolescents and young adults aged 15 to 34 years were 2 to 4 times higher than those of adolescents and young adults of other races and ethnicities. An estimated 14% to 27% of non-Hispanic AI/AN adolescents attempted suicide during that time. The elevated rates of suicidal behavior among non-Hispanic AI/AN adolescents and young adults reflect inequities in the conditions that create health. In this topical review, we describe school-based educational efforts that are driven by local AI/AN communities, such as the American Indian Life Skills curriculum, that teach stress and coping skills and show promise in reducing suicidal ideation attempts and fatalities among AI/AN adolescents. Using a social-determinants-of-health lens, we review the availability and quality of employment as an important influencer of suicidal behavior, as well as the role of the workplace as an environment for suicide prevention in AI/AN communities. Working with tribal, state, local, and federal colleagues, the public health community can implement programs known to be effective and create additional comprehensive strategies to reduce inequities and ultimately reduce suicide rates.

    • Laboratory Sciences

      2. Rapid diagnostic testing for response to the monkeypox outbreak - Laboratory Response Network, United States, May 17-June 30, 2022
        Aden TA, Blevins P, York SW, Rager S, Balachandran D, Hutson CL, Lowe D, Mangal CN, Wolford T, Matheny A, Davidson W, Wilkins K, Cook R, Roulo RM, White MK, Berman L, Murray J, Laurance J, Francis D, Green NM, Berumen RA, Gonzalez A, Evans S, Hudziec M, Noel D, Adjei M, Hovan G, Lee P, Tate L, Gose RB, Voermans R, Crew J, Adam PR, Haydel D, Lukula S, Matluk N, Shah S, Featherston J, Ware D, Pettit D, McCutchen E, Acheampong E, Buttery E, Gorzalski A, Perry M, Fowler R, Lee RB, Nickla R, Huard R, Moore A, Jones K, Johnson R, Swaney E, Jaramillo J, Reinoso Webb C, Guin B, Yost J, Atkinson A, Griffin-Thomas L, Chenette J, Gant J, Sterkel A, Ghuman HK, Lute J, Smole SC, Arora V, Demontigny CK, Bielby M, Geeter E, Newman KA, Glazier M, Lutkemeier W, Nelson M, Martinez R, Chaitram J, Honein MA, Villanueva JM.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 15;71(28):904-907.
        As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

      3. Testing for cryptococcosis at a major commercial laboratory-United States, 2019-2021
        Benedict K, Gold JA, Dietz S, Anjum S, Williamson PR, Jackson BR.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac253.
        BACKGROUND: Cryptococcosis is a serious opportunistic fungal disease, and the proportion of cases among patients with immunosuppressive conditions other than HIV or organ transplant has increased. Understanding laboratory testing patterns for cryptococcosis is useful for estimating its true burden and developing testing guidance. METHODS: We identified cryptococcosis tests (cryptococcal antigen [CrAg], cryptococcal antibody, and fungal cultures) performed at a major national commercial laboratory ordered during March 1, 2019-October 1, 2021, and analyzed test results, patient and provider features, reasons for testing, geography, and temporal trends. RESULTS: Among 29 180 serum CrAg tests, 4422 (15.2%) were positive, and among 10 724 cerebrospinal fluid (CSF) CrAg tests, 492 (4.6%) were positive. Frequent reasons for serum CrAg testing in nonhospital settings (10 882 tests) were HIV (44.6%) and cryptococcosis (17.0%); other underlying conditions were uncommonly listed (<10% total). Serum CrAg positivity declined from 25.6% in October 2019 to 11.3% in September 2021. The South had the highest positivity for serum CrAg tests (16.6%), CSF CrAg tests (4.7%), and fungal cultures (0.15%). Among 5009 cryptococcal antibody tests, 5 (0.1%) were positive. CONCLUSIONS: Few outpatient serum CrAg tests were performed for patients with immunocompromising conditions other than HIV, suggesting potential missed opportunities for early detection. Given the high positive predictive value of CrAg testing, research is needed to improve early diagnosis, particularly in patients without HIV. Conversely, the low yield of antibody testing suggests that it may be of low value. The decline in CrAg positivity during the COVID-19 pandemic warrants further investigation.

    • Maternal and Child Health
      1. Assessment of underuse and overuse of screening tests for co-occurring conditions among children with obesity
        Sharifi M, Goodman AB, Chua KP.
        JAMA Netw Open. 2022 Jul 1;5(7):e2222101.
        IMPORTANCE: The American Academy of Pediatrics (AAP) recommends laboratory screening for diabetes, dyslipidemia, and liver disease every 2 years among children aged 10 years and older with obesity. Routine screening for hypothyroidism or hyperinsulinemia is not recommended. National data on rates of adherence to AAP-recommended screening and rates of potentially unnecessary endocrine testing are unavailable. OBJECTIVE: To assess rates of AAP-adherent screening and potentially unnecessary endocrine testing among privately and publicly insured children diagnosed with obesity at well-child visits. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the 2018-2019 IBM MarketScan Commercial Database (which contains claims from privately insured patients across the US) and the 2018-2019 IBM MarketScan Multi-State Medicaid Database (which contains claims from Medicaid patients in multiple states). A total of 156 773 children aged 10 to 18 years with obesity diagnosis codes at a well-child visit from December 1, 2018, through November 30, 2019, were included. Analysis was performed from May 1 to October 31, 2021. MAIN OUTCOMES AND MEASURES: Primary outcomes were the proportion of children who received AAP-adherent screening during the 729 days before to 30 days after a well-child visit and the proportion of children who received 1 or more potentially unnecessary thyroid or insulin tests during the same period. Proportions of children by payer type were compared using logistic regression models adjusted for age and sex. To assess screening that was potentially ordered by primary care clinicians, the proportion of children without AAP-adherent screening before visits who received this screening within 30 days was calculated. RESULTS: Of 156 773 children, the mean (SD) age was 13.5 years (2.5) years; 83 305 (53.1%) were male, and 97 595 (62.3%) were publicly insured. Among publicly insured children, 13 167 (13.5%) were Hispanic or Latino, 34 792 (35.6%) were non-Hispanic Black, 42 029 (43.1%) were non-Hispanic White, 3850 (3.9%) were of other race and/or ethnicity (specific races and ethnicities were not available in the database), and 3757 (3.8%) were of unknown race and ethnicity. Race and ethnicity were not available for privately insured children because these data are not reported in the commercial claims database. During the 729 days before to 30 days after well-child visits, 42 849 patients (27.3%) received AAP-adherent screening, including 13 939 (23.6%) of 59 178 privately insured children and 28 910 (29.6%) of 97 595 publicly insured children (average marginal effect for public insurance: 6.8 [95% CI, 6.3-7.2] percentage points). In addition, 46 592 children (29.7%) received potentially unnecessary thyroid or insulin tests, including 12 834 (21.7%) of 59 178 privately insured children and 23 198 (23.8%) of 97 595 publicly insured children (average marginal effect for public insurance: 2.4 [95% CI, 2.0-2.8] percentage points). Among 129 104 children who did not receive AAP-adherent screening before visits, 15 090 (11.7%) received this screening within 30 days. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, similar proportions of children diagnosed with obesity at well-child visits received recommended and nonrecommended screening tests for obesity-related co-occurring conditions, suggesting that specific actionable guidelines and interventions are needed to prevent overuse and underuse of screening tests among children with obesity.

    • Occupational Safety and Health
      1. The impact of traumatic experiences, coping mechanisms, and workplace benefits on the mental health of U.S. public health workers during the COVID-19 pandemic
        Kone A, Horter L, Rose C, Rao CY, Orquiola D, Thomas I, Byrkit R, Bryant-Genevier J, Lopes-Cardozo B.
        Ann Epidemiol. 2022 Jul 15.
        PURPOSE: To evaluate the association between risk factors, mitigating factors, and adverse mental health outcomes among United States public health workers. METHODS: Cross-sectional online survey data were collected March to April 2021. The survey was distributed to public health workers who worked in a state, tribal, local, or territorial public health department since March 2020. RESULTS: In total, 26,174 United States state and local public health workers completed the survey. Feeling isolated was a risk factor for anxiety (PR, 1.84; 95% CI, 1.74-1.95), depression (PR, 1.84; 95% CI, 1.75-1.94), post-traumatic stress disorder (PR, 1.50; 95% CI, 1.43-1.57), and suicidal ideation (PR, 3.23; 95% CI, 2.82-3.69). The ability to take time off was linked to fewer reported symptoms of anxiety (PR, 0.87; 95% CI, 0.83-0.90), depression (PR, 0.86; 95% CI, 0.83-0.89), post-traumatic stress disorder (PR, 0.84; 95% CI, 0.81-0.88), and suicidal ideation (PR, 0.84; 95% CI, 0.77-0.92). CONCLUSIONS: Since COVID-19 was declared a pandemic, respondents who felt isolated and alone were at an increased risk for adverse mental health outcomes. Findings from this study call for public health organizations to provide their workforce with services and resources to mitigate adverse mental health outcomes.

    • Parasitic Diseases
      1. An epidemiologic examination of the strategy of malaria eradication
        Scholtens RG, Kaiser RL, Langmuir AD.
        Int J Epidemiol. 2022 ;51(2):372-381.
        The concept of malaria eradication developed over the first half of the twentieth century, gradually changing from multiple means of control to the single method of indoor insecticide spraying. Because of the dramatic effects of DDT and the fear of insecticide resistance malaria eradication programs - consisting of preparatory measures, an attack phase during which houses are sprayed and active case detection begins, a consolidation phase when spraying is discontinued and the few remaining cases of malaria are eliminated by case detection and treatment, and finally a maintenance phase when malaria surveillance responsibilities are transferred to the normal health services of the country - were planned to achieve their goals in five to ten years. But by 1970 it was evident that the total eradication of malaria through use of residual insecticides was not feasible, and the 23rd World Health Assembly adopted a revised strategy recognizing the need for malaria control and the use of diverse antimalarial methods. While there has been much success in the fight against malaria, with more than one-third of the population formerly at risk now living in malaria-free areas, there has been little progress and some regression in recent years. The case of India illustrates the predicament, including the relative importance of technical problems, operational difficulties, and the demand on resources by a multiplicity of health and social problems. The realization that the problem of malaria will continue, that it is only one of many pressing health needs, and that suitable locally-devised measures for its control are necessary is inescapable. © 2022 Oxford University Press. All rights reserved.

      2. Public health surveillance and reporting for human toxoplasmosis - Six states, 2021
        McCall J, Rothfeldt L, Giesbrecht K, Hunt A, Bauck L, Scheftel J, Birn R, Buss B, Schroeder B, Haupt TE, Klos R, Straily A.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 15;71(28):889-893.
        Toxoplasmosis is caused by infection with the zoonotic parasite Toxoplasma gondii. Although disease tends to be mild (e.g., self-limiting influenza-like symptoms) or asymptomatic in immunocompetent persons, toxoplasmosis is more severe in immunocompromised persons, who can develop potentially fatal encephalopathy (1). In addition, primary infections acquired during pregnancy might result in a range of adverse outcomes, including fetal ocular infection, cranial and neurologic deformities, stillbirth, and miscarriage (1,2). An estimated 11% of the U.S. population aged ≥6 years are seropositive for toxoplasmosis, based on analysis of sera collected through the National Health and Nutrition Examination Survey during 2011-2014 (3). Toxoplasmosis is not a nationally notifiable disease in the United States, and currently no national public health surveillance data are available; however, it is reportable in eight states. To better understand how surveillance data are collected and used, reviews of state-level toxoplasmosis surveillance were conducted during June-July 2021 using semistructured interviews with health officials in six states (Arkansas, Kentucky, Minnesota, Nebraska, Pennsylvania, and Wisconsin) where toxoplasmosis is currently reportable. Why or when toxoplasmosis became reportable could not be determined, and many of the states had limited capacity to respond to reported cases. Case definitions varied considerably in terms of clinical description, laboratory criteria, and case classification (i.e., confirmed, probable, or suspect), limiting disease estimates and comparisons among states. Implementation of a standardized case definition would help ensure that cases are counted consistently, enabling better use of surveillance data to characterize disease. Identifying newly acquired cases is challenging because most acute cases among immunocompetent persons (including pregnant women) are asymptomatic, disease among immunocompromised persons is likely reactivation of latent disease, and congenital infections might not manifest until later in life.

      3. Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for antimalarial intervention deployment
        Njoroge H, Van't Hof A, Oruni A, Pipini D, Nagi SC, Lynd A, Lucas ER, Tomlinson S, Grau-Bove X, McDermott D, Wat'senga FT, Manzambi EZ, Agossa FR, Mokuba A, Irish S, Kabula B, Mbogo C, Bargul J, Paine MJ, Weetman D, Donnelly MJ.
        Mol Ecol. 2022 Jul 1.
        Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expansion of LLIN distributions. Identifying genetic mechanisms underlying high-level resistance is crucial for the development and deployment of resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar-like transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border, with stepwise replacement of the double-mutant (Zanzibar-like TE and Cyp6p4-236 M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolize pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin. Importantly, there was increased mortality in mosquitoes carrying the triple-mutation when exposed to nets cotreated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid cotreated LLINs across African countries.

      4. Missed plasmodium ovale infections among symptomatic persons in Angola, Mozambique, and Ethiopia
        Leonard CM, Hwang J, Assefa A, Zulliger R, Candrinho B, Dimbu PR, Saifodine A, Plucinski M, Rogier E.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac261.
        The majority of symptomatic malaria in sub-Saharan Africa is caused by Plasmodium falciparum. Infection with Plasmodium ovale is often not recorded and not considered clinically relevant. Here, we describe 8 cases of P ovale infection from 3 African countries-all of which were misdiagnosed at the presenting health facility.

    • Reproductive Health
      1. Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya
        Dabee S, Mugo N, Mudhune V, McLellan-Lemal E, Peacock S, O'Connor S, Njoroge B, Nyagol B, Thurman AR, Ouma E, Ridzon R, Wiener J, Haugen HS, Gasper M, Feng C, Allen SA, Doncel GF, Jaspan HB, Heffron R.
        Sci Rep. 2022 Jul 14;12(1):12040.
        In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18-34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of Candida spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log(10)0.57 and log(10)0.27 decrease respectively; p > 0.05). The TFV/LNG IVR was more 'stabilizing': 50% of the participants' microbiota community state types remained unchanged and 50% shifted towards higher Lactobacillus abundance. Specifically, TFV/LNG IVR use was accompanied by increased abundances of Lactobacillus gasseri/hominis/johnsonii/taiwanensis (16.3-fold) and L. fermentum/reuteri/vaginalis (7.0-fold; all p < 0.01). A significant shift in the overall microbial α-diversity or β-diversity was not observed for either IVR, and IVR use did not influence Candida spp. prevalence. TFV/LNG and TFV IVRs did not adversely affect the genital microbiota and are safe to use. Our findings support further studies assessing their efficacy in preventing HIV/HSV-2 and unintended pregnancies.

    • Substance Use and Abuse
      1. Trends in unit sales of cooling flavoured e-cigarettes, USA, 2017-2021
        Ali FR, Seaman EL, Diaz MC, Ajose J, King BA.
        Tob Control. 2022 Jul 15.
        OBJECTIVE: Flavours that produce a cooling sensation, such as menthol, enhance the appeal of e-cigarettes among youth; but not all e-cigarettes that produce cooling sensations are labelled as menthol. This study assessed trends in unit sales of cooling flavoured e-cigarettes in the USA. DESIGN: E-cigarette retail sales during 26 January 2017 to 28 November 2021 were licensed from Information Resources, Inc, which records brick-and-mortar retail scanner sales but not online or vape shop sales. Cooling flavours were identified using six descriptors: menthol, ice, cool, chill, freeze or frost; ambiguous flavours were verified using online searches. Cooling flavours were categorised by characterising flavour (menthol, mint, other) and product type (prefilled cartridges, disposables, e-liquids). Joinpoint regression was used to assess sales and price trends. RESULTS: During January 2017 to November 2021, unit sales of cooling flavoured e-cigarettes increased by 693.0% (1.5 to 12.0 million units); the percentage of these sales from total sales increased from 26.4% to 54.9%. Among cooling flavours, percentage of menthol sales decreased from 94.5% to 73.0% (p<0.001). Among menthol cooling flavours, percentage of prefilled cartridges increased from 67.2% to 96.6% (p<0.001); among non-menthol cooling flavours, percentage of disposable e-cigarettes increased from 5.2% to 99.2% (p<0.001). There were no significant price differences between cooling and non-cooling flavoured disposable e-cigarettes. CONCLUSION: The percentage of cooling flavoured e-cigarette sales from total sales doubled during 2017-2021, and sales of non-menthol cooling disposable e-cigarettes experienced the highest percentage increase. Cooling flavoured e-cigarettes are important to consider when developing strategies to address flavoured e-cigarette use among youth.

    • Zoonotic and Vectorborne Diseases
      1. OBJECTIVES: Zika virus (ZIKV) can be sexually transmitted, and ZIKV infection during pregnancy can cause birth defects. Contraception is a medical countermeasure to reduce unintended pregnancy and ZIKV-associated birth defects. We estimated the prevalence of condom use and associated factors among women at risk for unintended pregnancy in Puerto Rico during the 2016 ZIKV outbreak. DESIGN: Secondary analysis of a cross-sectional, population-based, cell-phone survey. SETTING AND PARTICIPANTS: Women, 18-49 years, living in Puerto Rico during July-November 2016. We limited our analytical sample (n=1840) to women at risk for unintended pregnancy, defined as those who were sexually active with a man in the last 3 months and did not report menopause, hysterectomy, current pregnancy or desiring pregnancy. OUTCOME MEASURES: We estimated the weighted prevalence of any condom use among women at risk for unintended pregnancy. We calculated crude and adjusted prevalence ratios (aPRs) to examine the association between condom use and ZIKV-related factors, stratified by use of more effective versus less effective or no contraception. RESULTS: Overall, 32.7% (95% CI: 30.2% to 35.1%) of women reported any condom use in the last 3 months. Among women using more effective contraception, condom use was higher for women who received ZIKV counselling (aPR: 1.61, 95% CI: 1.15 to 2.25) and those worried about having a child with a ZIKV-associated birth defect (aPR: 1.47, 95% CI: 1.03 to 2.10). Among women using less effective or no contraception, condom use was associated with being worried (aPR: 1.20, 95% CI: 1.01 to 1.43) compared with those not worried about ZIKV infection or with a previous known infection. CONCLUSIONS: During the 2016 ZIKV outbreak, one in three women at risk for unintended pregnancy reported any condom use. Counselling to promote consistent and correct condom use may address concerns regarding ZIKV among women of reproductive age, which may differ by use of effective contraception.

      2. Longitudinal surveillance and comparative characterization of Escherichia albertii in wild raccoons in the United States
        Hinenoya A, Wang H, Patrick EM, Zeng X, Cao L, Li XP, Lindsey RL, Gillespie B, He Q, Yamasaki S, Lin J.
        Microbiol Res. 2022 Sep;262:127109.
        Escherichia albertii is an emerging enteric bacterial pathogen causing watery diarrhea, abdominal distension, vomiting and fever in humans. E. albertii has caused many foodborne outbreaks in Japan and was also reported in other countries worldwide. However, the important animal reservoirs of this pathogen are still largely unknown, impeding us to combat this emerging pathogen. Recently, we reported that wild raccoons (Procyon lotor) and broiler chickens are significant reservoirs of E. albertii in Japan and the U.S., respectively. Here, we performed a longitudinal surveillance to monitor prevalence of E. albertii in wild raccoons in the U.S. and conducted comprehensive comparative analyses of the E. albertii of different origins. A total of 289 fecal swab samples were collected from wild raccoons in Tennessee and Kentucky in the U.S. (2018-2020). Approximately 26% (74/289) of the raccoons examined were PCR-positive for E. albertii and eventually 22 E. albertii isolates were obtained. PFGE analysis showed the U.S. raccoon E. albertii were phylogenetically distant even though the corresponding raccoons were captured from a small area. Unlike the high prevalence of multidrug resistance (83%) observed in previous chicken E. albertii survey, antibiotic resistance was rarely observed in all the U.S. raccoon and 22 Japan raccoon strains with only one Japan strain displaying multidrug resistance (2%). Whole genome sequencing of 54 diverse E. albertii strains and subsequent comparative genomics analysis revealed unique clusters that displayed close evolutionary relationships and similar virulence gene profiles among the strains of different origins in terms of geographical locations (e.g., U.S. and Japan) and hosts (raccoon, chicken, swine, and human). Challenge experiment demonstrated raccoon E. albertii strains could successfully colonize in the chicken intestine at 3 and 8 days postinfection. A pilot environmental survey further showed all the four tested water samples from Tennessee river were E. albertii-positive; two different E. albertii strains, isolated from a single water sample, showed close relationships to those of human origin. Together, the findings from this study provide new insights into the ecology, evolution, and pathobiology of E. albertii, and underscore the need to control the emerging E. albertii in a complex ecosystem using One Health approach.

      3. A comparison of horizontal and transovarial transmission efficiency of Borrelia miyamotoi by Ixodes scapularis
        Lynn GE, Breuner NE, Hojgaard A, Oliver J, Eisen L, Eisen RJ.
        Ticks Tick Borne Dis. 2022 Jul 14;13(5):102003.
        Borrelia miyamotoi is a relapsing fever spirochete carried by Ixodes spp. ticks throughout the northern hemisphere. The pathogen is acquired either transovarially (vertically) or horizontally through blood-feeding and passed transtadially across life stages. Despite these complementary modes of transmission, infection prevalence of ticks with B. miyamotoi is typically low (<5%) in natural settings and the relative contributions of the two transmission modes have not been studied extensively. Horizontal transmission of B. miyamotoi (strain CT13-2396 or wild type strain) was initiated using infected Ixodes scapularis larvae or nymphs to expose rodents, which included both the immunocompetent CD-1 laboratory mouse (Mus musculus) and a natural reservoir host, the white-footed mouse (Peromyscus. leucopus), to simulate natural enzootic transmission. Transovarial transmission was evaluated using I. scapularis exposed to B. miyamotoi as either larvae or nymphs feeding on immunocompromised SCID mice (M. musculus) and subsequently fed as females on New Zealand white rabbits. Larvae from infected females were qPCR-tested individually to assess transovarial transmission rates. Tissue tropism of B. miyamotoi in infected ticks was demonstrated using in situ hybridization. Between 1 and 12% of ticks were positive (post-molt) for B. miyamotoi after feeding on groups of CD-1 mice or P. leucopus with evidence of infection, indicating that horizontal transmission was inefficient, regardless of whether infected larvae or nymphs were used to challenge the mice. Transovarial transmission occurred in 7 of 10 egg clutches from infected females. Filial infection prevalence in larvae ranged from 3 to 100% (median 71%). Both larval infection prevalence and spirochete load were highly correlated with maternal spirochete load. Spirochetes were disseminated throughout the tissues of all three stages of unfed ticks, including the salivary glands and female ovarian tissue. The results indicate that while multiple transmission routes contribute to enzootic maintenance of B. miyamotoi, transovarial transmission is likely to be the primary source of infected ticks and therefore risk assessment and tick control strategies should target adult female ticks.


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