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Issue 47, November 22, 2022

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CDC Science Clips: Volume 14, Issue 47, November 22, 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.
    • Chronic Diseases and Conditions
      1. Impacts of the COVID-19 pandemic on nationwide chronic disease prevention and health promotion activities
        Balasuriya L, Briss PA, Twentyman E, Wiltz JL, Richardson LC, Bigman ET, Wright JS, Petersen R, Hannan CJ, Thomas CW, Barfield WD, Kittner DL, Hacker KA.
        Am J Prev Med. 2022 Oct 17.

      2. Seroprevalence of AAV neutralizing antibodies in males with Duchenne muscular dystrophy
        Verma S, Nwosu SN, Razdan R, Upadhyayula SR, Phan HC, Koroma AA, Leguizamo I, Correa NS, Kuipa M, Lee D, Vanderford TH, Gardner MR.
        Hum Gene Ther. 2022 Nov 2.
        Adeno-associated virus (AAV) based gene therapies are emerging strategies in Duchenne muscular dystrophy (DMD) treatment. Exposure to wild-type AAV can lead to development of neutralizing antibodies (NAb) and block AAV transduction, thereby limiting the delivery of AAV vector-based gene therapy. Therefore, it is imperative to check for the presence of AAV NAbs in a patient who is a candidate for gene therapy. We prospectively enrolled 101 genetically confirmed males with DMD (median age 11 years, 48% ambulatory, 59% on steroids) and performed AAV neutralization assays against AAV2, AAV8, AAV9, and AAVrh74 serotypes. Serotype analysis showed AAV9 (36%) and AAVrh74 (32%) seroprevalence was lower compared to AAV2 (56%) and AAV8 (47%). Interestingly, age was not correlated with NAb titer for any of the capsids. NAb responses were observed at a higher frequency in African American participants and at a lower frequency for Caucasian participants for all four serotypes. Further analysis showed no significant differences in NAb titers depending, regardless of serotype, on whether participants were taking steroids. Finally, we observed higher AAV8, AAV9, and AAVrh74 seroprevalence and significantly higher AAV2 and AAV8 NAb titers in participants that were ambulatory compared to the non-ambulatory participants. Overall, these data identify AAV9 and AAVrh74 as the two serotypes with lower preexisting NAbs in this study's cohort of 101 males with DMD, possibly showing their utility for future gene therapy applications to treat this cohort men with DMD.

      3. Prevalence of age-related macular degeneration in the US in 2019
        Rein DB, Wittenborn JS, Burke-Conte Z, Gulia R, Robalik T, Ehrlich JR, Lundeen EA, Flaxman AD.
        JAMA Ophthalmol. 2022 Nov 3.
        IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of vision loss and blindness. AMD prevalence has not been estimated for the US in over a decade and early-stage AMD prevalence estimates are scarce and inconsistently measured. OBJECTIVE: To produce estimates of early- and late-stage AMD prevalence overall and by age, gender, race and ethnicity, county, and state. DESIGN, SETTING, AND PARTICIPANTS: The study team conducted a bayesian meta-regression analysis of relevant data sources containing information on the prevalence of AMD among different population groups in the US. DATA SOURCES: We included data from the American Community Survey (2019), the National Health and Nutrition Examination Survey (2005-2008), US Centers for Medicare & Medicaid Services claims for fee-for-service beneficiaries (2018), and population-based studies (2004-2016). STUDY SELECTION: We included all relevant data from the US Centers for Disease Control and Prevention's Vision and Eye Health Surveillance System. DATA EXTRACTION AND SYNTHESIS: The prevalence of early- and late-stage AMD was estimated and stratified when possible by factors including county, age group, gender, and race and ethnicity. Data analysis occurred from June 2021 to April 2022. MAIN OUTCOMES OR MEASURES: The prevalence of early- (defined as retinal pigment epithelium abnormalities or the presence of drusen 125 or more microns in diameter in either eye) and late-stage (defined as choroidal neovascularization and/or geographic atrophy in either eye) manifestations of AMD. RESULTS: This study used data from nationally representative and local population-based studies that represent the populations in which they were conducted. For 2019, we estimated that there were 18.34 million people 40 years and older (95% uncertainty interval [UI], 15.30-22.03) living with early-stage AMD, corresponding to a crude prevalence rate of 11.64% (95% UI, 9.71-13.98). We estimated there were 1.49 million people 40 years and older (95% UI, 0.97-2.15) living with late-stage AMD, corresponding to a crude prevalence rate of 0.94% (95% UI, 0.62-1.36). Prevalence rates of early- and late-stage AMD varied by demographic characteristics and geography. CONCLUSIONS AND RELEVANCE: We estimated a higher prevalence of early-stage AMD and a similar prevalence of late-stage AMD as compared with earlier studies. State-level and county-level AMD estimates may help guide public health practice.

      4. Epidemiology of cutaneous lupus erythematosus among adults over four decades (1976-2018): A Lupus Midwest Network (LUMEN) Study
        Hocaoğlu M, Davis MD, Osei-Onomah SA, Valenzuela-Almada MO, Dabit JY, Duong SQ, Yang JX, Helmick CG, Crowson C, Duarte-García A.
        Mayo Clin Proc. 2022 Nov 5.
        OBJECTIVE: To characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota. PATIENTS AND METHODS: In this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project. RESULTS: The overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time. CONCLUSION: In the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.

      5. Prevalence and characteristics of arthritis among caregivers - 17 states, 2017 and 2019
        Jackson EM, Omura JD, Boring MA, Odom EL, Foster AL, Olivari BS, McGuire LC, Croft JB.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44):1389-1395.
        Caregiving provides numerous benefits to both caregivers and care recipients; however, it can also negatively affect caregivers' mental and physical health (1-4), and caregiving tasks often require physical exertion (1). Approximately 44% of adults with arthritis report limitations attributable to arthritis, including trouble doing daily activities (5). These limitations might affect caregivers' ability to provide care, but little is known about arthritis among caregivers. To assess arthritis among caregivers of a family member or friend, CDC examined data from 17 states that administered both the arthritis and caregiving modules as part of the Behavioral Risk Factor Surveillance System (BRFSS) in either 2017 or 2019. Approximately one in five adults (20.6%) was a caregiver. Prevalence of arthritis was higher among caregivers (35.1%) than noncaregivers (24.5%). Compared with caregivers without arthritis, those with arthritis provided similar types of care and were more likely to have provided care for ≥5 years and for ≥40 hours per week. In addition, higher proportions of caregivers with arthritis reported disabilities compared with those without arthritis, including mobility issues (38.0% versus 7.3%). Arthritis among caregivers might affect their own health as well as the care they can provide. Caregivers can discuss their arthritis and related limitations with a health care professional to identify ways to increase their physical activity and participation in lifestyle management programs.* Such interventions might ease arthritis pain and related limitations and might support them in their ongoing caregiving role. Public health professionals can implement strategies to support caregivers throughout the caregiving process.(†).

      6. Risk factors for new neurologic diagnoses in hospitalized patients with COVID-19: A case-control study in New York city
        Thakur KT, Chu VT, Hughes C, Kim CY, Fleck-Derderian S, Barrett CE, Matthews E, Balbi A, Bilski A, Chomba M, Lieberman O, Jacobson SD, Agarwal S, Roh D, Park S, Ssonko V, Silver WG, Vargas WD, Geneslaw A, Bell M, Waters B, Rao A, Claassen J, Boehme A, Willey JZ, Elkind MS, Sobieszczyk ME, Zucker J, McCollum A, Sejvar J.
        Neurol Clin Pract. 2022 ;12(4):E66-E74.
        Background and ObjectivesThere have been numerous reports of neurologic manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurologic symptoms and diagnoses, define the time course of their development, and examine readmission rates and mortality risk posthospitalization in a multiethnic urban cohort.MethodsWe identify the occurrence of new neurologic diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed on 532 cases (hospitalized patients with new neurologic diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020, and August 31, 2020). We compare demographic and clinical features of the 532 cases with 532 controls (hospitalized COVID-19 patients without neurologic diagnoses) in a case-control study with one-to-one matching and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hospitalization in a secondary case-only analysis.ResultsAmong the 532 cases, the most common new neurologic diagnoses included encephalopathy (478, 89.8%), stroke (66, 12.4%), and seizures (38, 7.1%). In the case-control study, cases were more likely than controls to be male (58.6% vs 52.8%, p = 0.05), had baseline neurologic comorbidities (36.3% vs 13.0%, p < 0.0001), and were to be treated in an intensive care unit (62.0% vs 9.6%, p < 0.0001). Of the 394 (74.1%) cases who survived acute hospitalization, more than half (220 of 394, 55.8%) were readmitted within 6 months, with a mortality rate of 23.2% during readmission.DiscussionHospitalized patients with SARS-CoV-2 and new neurologic diagnoses have significant morbidity and mortality postdischarge. Further research is needed to define the effect of neurologic diagnoses during acute hospitalization on longitudinal post-COVID-19-related symptoms including neurocognitive impairment. © American Academy of Neurology.

    • Communicable Diseases
      1. Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness, United States, 2022
        Tenforde MW, Patel MM, Lewis NM, Adams K, Gaglani M, Steingrub JS, Shapiro NI, Duggal A, Prekker ME, Peltan ID, Hager DN, Gong MN, Exline MC, Ginde AA, Mohr NM, Mallow C, Martin ET, Talbot HK, Gibbs KW, Kwon JH, Chappell JD, Halasa N, Lauring AS, Lindsell CJ, Swan SA, Hart KW, Womack KN, Baughman A, Grijalva CG, Self WH.
        Clin Infect Dis. 2022 Nov 3.
        BACKGROUND: The COVID-19 pandemic was associated with historically low influenza circulation during the 2020-2021 season, followed by increase in influenza circulation during the 2021-2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain. METHODS: To understand the effectiveness of the 2021-2022 vaccine against hospitalized influenza illness, a multi-state sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI) and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by including SARS-CoV-2 positive controls. RESULTS: A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2 negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2 positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95%CI: -14 to 52%) among adults aged 18-64 years, -3% (95%CI: -54 to 31%) among adults aged ≥65 years, and 50% (95%CI: 15 to 71%) among adults 18-64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2-positive controls. CONCLUSIONS: During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted.

      2. Consolidated overview of notifiable adverse events in the U.S. President's Emergency Plan for AIDS Relief's voluntary medical male circumcision program through 2020
        Lucas T, Cooney C, Prainito A, Godfrey C, Kiggundu V, Thomas AG, Ridzon R, Toledo C.
        Curr HIV/AIDS Rep. 2022 Nov 8.
        PURPOSE OF REVIEW: Through December 2020, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supported more than 25 million voluntary medical male circumcisions (VMMC) as part of the combined HIV prevention strategy in 15 African countries. PEPFAR monitors defined adverse events (AEs) occurring within 30 days of VMMC through its notifiable adverse event reporting system (NAERS). All NAERS reports through December 2020 were reviewed to quantify AE type, severity, and relation to the VMMC procedure. Interventions to improve client safety based on NAERS findings are described. RECENT FINDINGS: Fourteen countries reported 446 clients with notifiable adverse events (NAEs); 394/446 (88%) were determined VMMC-related, representing approximately 18 NAE reports per million circumcisions. Fatalities comprised 56/446 (13%) with 24/56 (43%) of fatalities determined VMMC-related, representing 0.96 VMMC-related fatalities per million circumcisions. The remaining 390 NAEs were non-fatal with 370/390 (95%) VMMC-related. Multiple programmatic changes have been made based on NAERS data to improve client safety. Client safety is paramount in this surgical program designed for individual and population-level benefit. Surveillance of rare but severe complications following circumcision has identified pre-existing or new safety concerns and guided continuous programmatic improvement.

      3. Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques
        Makarova N, Singletary T, Peet MM, Mitchell J, Holder A, Dinh C, Agrahari V, Mendoza M, Pan Y, Heneine W, Clark MR, García-Lerma JG, Smith JM, Doncel GF.
        EBioMedicine. 2022 Nov 4;86:104338.
        BACKGROUND: Topical on-demand forms for HIV pre-exposure prophylaxis (PrEP) may be a desirable alternative for people that prefer not to use daily PrEP. CONRAD has developed inserts containing tenofovir alafenamide (TAF) and elvitegravir (EVG) for on-demand vaginal or rectal pericoital use. We assessed the pharmacokinetics (PK) and pre-exposure efficacy of rectally applied TAF/EVG inserts in macaques. METHODS: PK was assessed in 12 pigtailed macaques. Tenofovir (TFV) and EVG levels were assayed in rectal biopsies and secretions, and tenofovir-diphosphate (TFV-DP) levels in biopsies and peripheral blood mononuclear cells (PBMC). Drug biodistribution was evaluated in 10 animals at necropsy 4 h post-dosing. For efficacy assessments, one or two TAF/EVG inserts were administered to macaques (n = 6) 4 h before repeated rectal SHIV162p3 challenges. FINDINGS: One TAF/EVG insert resulted in rapid and high EVG and TFV-DP in rectal tissue 4 h after application. Adding a second insert led to a 10-fold increase in EVG and TFV-DP in rectal tissue. Efficacy of one and two TAF/EVG inserts were 72.6% (CI 24.5%-92.6%) and 93.1% (CI 73.3%-99.2%), respectively. INTERPRETATION: Although high TFV-DP and EVG levels were observed with one rectal TAF/EVG insert, it only conferred partial protection from rectal SHIV challenges. Adding a second insert led to an increase in TFV and EVG in rectal tissues resulting in higher (>90%) efficacy. These results highlight the high efficacy of TAF/EVG inserts as topical on-demand rectal PrEP, as well as the need for appropriate drug coverage in the deep rectum and colon to achieve high protection. FUNDING: The work related to animal studies was funded by CDC intramural funds and an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002). The work related to the insert formulation was funded by U.S. PEPFAR through USAID under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School. The findings and conclusions of this manuscript are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC), USAID, President's Emergency Plan for AIDS Relief (PEPFAR), Eastern Virginia Medical School (EVMS), or the US government.

      4. Household transmission dynamics of seasonal human coronaviruses
        Quandelacy TM, Hitchings MD, Lessler J, Read JM, Vukotich C, Azman AS, Salje H, Zimmer S, Gao H, Zheteyeva Y, Uzicanin A, Cummings DA.
        J Infect Dis. 2022 Nov 9.
        BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over two respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, HCoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. RESULTS: Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children (<19y) displayed ILI symptoms than infected adults (relative risk 3.0, 95% credible interval (CrI) 1.5, 6.9). The estimated weekly household transmission probability was 9% (95% CrI 6, 13) and weekly community acquisition probability was 7% (95% CrI 5, 10). We found no evidence for differences in community or household transmission probabilities by age or symptom status. Simulations suggest that our study was underpowered to detect such differences. CONCLUSION: Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs.

      5. Changes in distribution of severe neurologic involvement in US pediatric inpatients with COVID-19 or multisystem inflammatory syndrome in children in 2021 vs 2020
        LaRovere KL, Poussaint TY, Young CC, Newhams MM, Kucukak S, Irby K, Kong M, Schwartz SP, Walker TC, Bembea MM, Wellnitz K, Havlin KM, Cvijanovich NZ, Hall MW, Fitzgerald JC, Schuster JE, Hobbs CV, Halasa NB, Singh AR, Mack EH, Bradford TT, Gertz SJ, Schwarz AJ, Typpo KV, Loftis LL, Giuliano JS, Horwitz SM, Biagas KV, Clouser KN, Rowan CM, Maddux AB, Soma VL, Babbitt CJ, Aguiar CL, Kolmar AR, Heidemann SM, Harvey H, Zambrano LD, Campbell AP, Randolph AG.
        JAMA Neurol. 2022 Nov 7.
        IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). RESULTS: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. CONCLUSIONS AND RELEVANCE: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.

      6. Factors associated with syphilis transmission and acquisition among men who have sex with men: Protocol for a multisite egocentric network study
        Copen CE, Rushmore J, De Voux A, Kirkcaldy RD, Fakile YF, Tilchin C, Duchen J, Jennings JM, Spahnie M, Norris Turner A, Miller WC, Novak RM, Schneider JA, Trotter AB, Bernstein KT.
        JMIR Res Protoc. 2022 Nov 4;11(11):e40095.
        BACKGROUND: In the United States, the rates of primary and secondary syphilis have increased more rapidly among men who have sex with men (MSM) than among any other subpopulation. Rising syphilis rates among MSM reflect changes in both individual behaviors and the role of sexual networks (eg, persons linked directly or indirectly by sexual contact) in the spread of the infection. Decades of research examined how sexual networks influence sexually transmitted infections (STIs) among MSM; however, few longitudinal data sources focusing on syphilis have collected network characteristics. The Centers for Disease Control and Prevention, in collaboration with 3 sites, enrolled a prospective cohort of MSM in 3 US cities to longitudinally study sexual behaviors and STIs, including HIV, for up to 24 months. OBJECTIVE: The Network Epidemiology of Syphilis Transmission (NEST) study aimed to collect data on the factors related to syphilis transmission and acquisition among MSM. METHODS: The NEST study was a prospective cohort study that enrolled 748 MSM in Baltimore, Maryland; Chicago, Illinois; and Columbus, Ohio. NEST recruitment used a combination of convenience sampling, venue-based recruitment, and respondent-driven sampling approaches. At quarterly visits, participants completed a behavioral questionnaire and were tested for syphilis, HIV, gonorrhea, and chlamydia. The participants also provided a list of their sexual partners and described their 3 most recent partners in greater detail. RESULTS: The NEST participants were enrolled in the study from July 2018 to December 2021. At baseline, the mean age of the participants was 31.5 (SD 9.1) years. More than half (396/727. 54.5%) of the participants were non-Hispanic Black, 29.8% (217/727) were non-Hispanic White, and 8.8% (64/727) were Hispanic or Latino. Multiple recruitment strategies across the 3 study locations, including respondent-driven sampling, clinic referrals, flyers, and social media advertisements, strengthened NEST participation. Upon the completion of follow-up visits in March 2022, the mean number of visits per participant was 5.1 (SD 3.2; range 1-9) in Baltimore, 2.2 (SD 1.6; range 1-8) in Chicago, and 7.2 (SD 2.9; range 1-9) in Columbus. Using a community-based participatory research approach, site-specific staff were able to draw upon collaborations with local communities to address stigma concerning STIs, particularly syphilis, among potential NEST participants. Community-led efforts also provided a forum for staff to describe the NEST study objectives and plans for research dissemination to the target audience. Strategies to bolster data collection during the COVID-19 pandemic included telehealth visits (all sites) and adaptation to self-collection of STI specimens (Baltimore only). CONCLUSIONS: Data from NEST will be used to address important questions regarding individual and partnership-based sexual risk behaviors among MSM, with the goal of informing interventions to prevent syphilis in high-burden areas. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/40095.

      7. Effect of UTT on viral suppression and ART adherence
        Bachanas P, Moore J.
        Lancet HIV. 2022 Nov;9(11):e738-e739.

      8. Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi
        Toledo G, Landes M, van Lettow M, Tippett Barr BA, Bailey H, Crichton S, Msungama W, Thorne C.
        Matern Child Nutr. 2022 Nov 9:e13451.
        Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.

      9. Epidemiologic and clinical features of children and adolescents aged <18 years with monkeypox - United States, May 17-September 24, 2022
        Hennessee I, Shelus V, McArdle CE, Wolf M, Schatzman S, Carpenter A, Minhaj FS, Petras JK, Cash-Goldwasser S, Maloney M, Sosa L, Jones SA, Mangla AT, Harold RE, Beverley J, Saunders KE, Adams JN, Stanek DR, Feldpausch A, Pavlick J, Cahill M, O'Dell V, Kim M, Alarcón J, Finn LE, Goss M, Duwell M, Crum DA, Williams TW, Hansen K, Heddy M, Mallory K, McDermott D, Cuadera MK, Adler E, Lee EH, Shinall A, Thomas C, Ricketts EK, Koonce T, Rynk DB, Cogswell K, McLafferty M, Perella D, Stockdale C, Dell B, Roskosky M, White SL, Davis KR, Milleron RS, Mackey S, Barringer LA, Bruce H, Barrett D, D'Angeli M, Kocharian A, Klos R, Dawson P, Ellington SR, Mayer O, Godfred-Cato S, Labuda SM, McCormick DW, McCollum AM, Rao AK, Salzer JS, Kimball A, Gold JA.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44).

      10. Severe monkeypox in hospitalized patients - United States, August 10-October 10, 2022
        Miller MJ, Cash-Goldwasser S, Marx GE, Schrodt CA, Kimball A, Padgett K, Noe RS, McCormick DW, Wong JM, Labuda SM, Borah BF, Zulu I, Asif A, Kaur G, McNicholl JM, Kourtis A, Tadros A, Reagan-Steiner S, Ritter JM, Yu Y, Yu P, Clinton R, Parker C, Click ES, Salzer JS, McCollum AM, Petersen B, Minhaj FS, Brown E, Fischer MP, Atmar RL, DiNardo AR, Xu Y, Brown C, Goodman JC, Holloman A, Gallardo J, Siatecka H, Huffman G, Powell J, Alapat P, Sarkar P, Hanania NA, Bruck O, Brass SD, Mehta A, Dretler AW, Feldpausch A, Pavlick J, Spencer H, Ghinai I, Black SR, Hernandez-Guarin LN, Won SY, Shankaran S, Simms AT, Alarcón J, O'Shea JG, Brooks JT, McQuiston J, Honein MA, O'Connor SM, Chatham-Stephens K, O'Laughlin K, Rao AK, Raizes E, Gold JA, Morris SB.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44):1412-1417.
        As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

      11. Predictors of severe acute respiratory syndrome coronavirus 2 seropositivity before coronavirus disease 2019 vaccination among children 0-4 years and their household members in the SEARCh Study
        Garcia Quesada M, Hetrich MK, Zeger S, Sharma J, Na YB, Veguilla V, Karron RA, Dawood FS, Knoll MD.
        Open Forum Infect Dis. 2022 Oct;9(10):ofac507.
        BACKGROUND: Estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and risk factors for seropositivity are scarce. Using data from a prospective cohort study of households during the pre-coronavirus disease 2019 (COVID-19) vaccine period, we estimated SARS-CoV-2 seroprevalence by age and evaluated risk factors for SARS-CoV-2 seropositivity. METHODS: The SARS-CoV-2 Epidemiology and Response in Children (SEARCh) study enrolled 175 Maryland households (690 participants) with ≥1 child aged 0-4 years during November 2020-March 2021; individuals vaccinated against COVID-19 were ineligible. At enrollment, participants completed questionnaires about sociodemographic and health status and work, school, and daycare attendance. Participants were tested for SARS-CoV-2 antibodies in sera. Logistic regression models with generalized estimating equations (GEE) to account for correlation within households assessed predictors of individual- and household-level SARS-CoV-2 seropositivity. RESULTS: Of 681 (98.7%) participants with enrollment serology results, 55 (8.1%; 95% confidence interval [CI], 6.3%-10.4%) participants from 21 (12.0%) households were seropositive for SARS-CoV-2. Among seropositive participants, fewer children than adults reported being tested for SARS-CoV-2 infection before enrollment (odds ratio [OR] = 0.23; 95% CI, .06-.73). Seropositivity was similar by age (GEE OR vs 0-4 years: 1.19 for 5-17 years, 1.36 for adults; P = .16) and was significantly higher among adults working outside the home (GEE adjusted OR = 2.2; 95% CI, 1.1-4.4) but not among children attending daycare or school. CONCLUSIONS: Before study enrollment, children and adults in this cohort had similar rates of SARS-CoV-2 infection as measured by serology. An adult household member working outside the home increased a household's odds of SARS-CoV-2 infection, whereas a child attending daycare or school in person did not.

      12. Costs of providing preexposure prophylaxis for HIV prevention at community health centers in the United States
        Shrestha RK, Davis N, Coleman M, Rusie LK, Smith DK.
        Public Health Rep. 2022 Nov 8:333549221133071.
        OBJECTIVE: Preexposure prophylaxis (PrEP) is recommended for people at risk of acquiring HIV. We assessed billable costs associated with PrEP delivery at community health centers. METHODS: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) study is an observational cohort of people receiving daily oral PrEP at participating federally qualified health centers and other community health centers. We assessed health care utilization and billable costs of providing PrEP at 2 health centers, 1 in Chicago, Illinois, and 1 in Washington, DC, from 2014 to 2018. The health centers followed the clinical practice guidelines for PrEP provision, including regular visits with health care providers and ongoing laboratory monitoring. Using clinic billing records and Current Procedural Terminology (CPT) coding, we retrospectively extracted data on the frequency and costs (in 2017 US dollars) of PrEP clinic visits and laboratory screening, for each patient, for 12 months since first PrEP prescription. RESULTS: The average annual number of PrEP clinic visits and associated laboratory screens per patient was 5.1 visits and 25.2 screens in Chicago (n = 482 patients) and 5.4 visits and 24.8 screens in Washington, DC (n = 56 patients). The average annual PrEP billable cost per patient was $583 for clinic visits and $1070 for laboratory screens in Chicago and $923 for clinic visits and $1018 for laboratory screens in Washington, DC. The average annual total cost per patient was $1653 (95% CI, $1639-$1668) in Chicago and $1941 (95% CI, $1811-$2071) in Washington, DC. CONCLUSIONS: Our analysis, which provides PrEP billable cost estimates based on empirical data, may help inform health care providers who are considering implementing this HIV prevention strategy.

    • Community Health Services
      1. Endotracheal intubation strategy, success, and adverse events among emergency department patients during the COVID-19 pandemic
        Mohr NM, Santos Leon E, Carlson JN, Driver B, Krishnadasan A, Harland KK, Ten Eyck P, Mower WR, Foley TM, Wallace K, McDonald LC, Kutty PK, Santibanez S, Talan DA.
        Ann Emerg Med. 2022 Nov 3.
        STUDY OBJECTIVE: To describe endotracheal intubation practices in emergency departments by staff intubating patients early in the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Multicenter prospective cohort study of endotracheal intubations conducted at 20 US academic emergency departments from May to December 2020, stratified by known or suspected COVID-19 status. We used multivariable regression to measure the association between intubation strategy, COVID-19 known or suspected status, first-pass success, and adverse events. RESULTS: There were 3,435 unique emergency department endotracheal intubations by 586 participating physicians or advanced practice providers; 565 (18%) patients were known or suspected of having COVID-19 at the time of endotracheal intubation. Compared with patients not known or suspected of COVID-19, endotracheal intubations of patients with known or suspected COVID-19 were more often performed using video laryngoscopy (88% versus 82%, difference 6.3%; 95% confidence interval [CI], 3.0% to 9.6%) and passive nasal oxygenation (44% versus 39%, difference 5.1%; 95% CI, 0.9% to 9.3%). First-pass success was not different between those who were and were not known or suspected of COVID-19 (87% versus 86%, difference 0.6%; 95% CI, -2.4% to 3.6%). Adjusting for patient characteristics and procedure factors in those with low anticipated airway difficulty (n=2,374), adverse events (most commonly hypoxia) occurred more frequently in patients with known or suspected COVID-19 (35% versus 19%, adjusted odds ratio 2.4; 95% CI, 1.7 to 3.3). CONCLUSION: Compared with patients not known or suspected of COVID-19, endotracheal intubation of those confirmed or suspected to have COVID-19 was associated with a similar first-pass intubation success rate but higher risk-adjusted adverse events.

      2. Accuracy of point-of-care HIV and CD4 field testing by lay healthcare workers in the Botswana combination prevention project
        Bile EC, Bachanas PJ, Jarvis JN, Maurice F, Makovore V, Chebani L, Jackson KG, Birhanu S, Maphorisa C, Mbulawa MB, Alwano MG, Sexton C, Modise S, Bapati W, Segolodi T, Moore J, Fonjungo PN.
        J Virol Methods. 2022 Nov 4:114647.
        Accurate HIV and CD4 testing are critical in program implementation, with HIV misdiagnosis having serious consequences at both the client and/or community level. We implemented a comprehensive training and Quality Assurance (QA) program to ensure accuracy of point-of-care HIV and CD4 count testing by lay counsellors during the Botswana Combination Prevention Project (BCPP). We compared the performance of field testing by lay counselors to results from an accredited laboratory to ascertain accuracy of testing. All trained lay counselors passed competency assessments and performed satisfactorily in proficiency testing panel evaluations in 2013, 2014, and 2015. There was excellent agreement (99.6%) between field and laboratory-based HIV test results; of the 3002 samples tested, 960 and 2030 were concordantly positive and negative respectively, with 12 misclassifications (kappa score 0.99, p < 0.0001). Of the 149 HIV-positive samples enumerated for CD4 count in the field using PIMA at a threshold of ≤350 cells/µL; there was 86% agreement with laboratory testing, with only 21 misclassified. The mean difference between field and lab CD4 testing was -16.16 cells/µL (95% CI -5.4 - 26.9). Overall, there was excellent agreement between field and laboratory results for both HIV rapid test and PIMA CD4 results. A standard training package to train lay counselors to accurately perform HIV and CD4 point-of-care testing in field settings was feasible, with point-of-care results obtained by lay counselors comparable to laboratory-based testing.

      3. Engagement in the MI-SIGHT Glaucoma Screening Program: Comparing the effect of clinic versus community-based recruitment strategies
        Elam AR, Mobolaji I, Flaharty K, Niziol LM, Woodward MA, Zhang J, Musch DC, Johnson L, Kershaw M, Bicket A, Saaddine J, John D, Newman-Casey PA.
        Ophthalmol Glaucoma. 2022 Nov 1.
        PURPOSE: To determine the effectiveness of adding community-based recruitment to clinic-based recruitment to engage participants in a glaucoma detection program. DESIGN: Prospective cohort study. SUBJECTS: Anyone ≥ 18 years of age who do not meet exclusion criteria METHODS: The Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) Program tests a novel way of improving glaucoma detection in communities with populations at high risk for disease, including people who identify as Black and Hispanic and those living with low socio-economic status. The MI-SIGHT program is conducted in a free clinic (Ypsilanti, MI) and in a federally qualified health center (FQHC; Flint, MI). Community-engagement methods were used to identify outreach strategies to enhance recruitment. Participants were asked "How did you hear about the MI-SIGHT program?" and responses were summarized overall and by clinic and compared between clinic-based and community-based recruitment strategies. MAIN OUTCOME MEASURES: Proportion recruited by location, within or outside of the clinic. RESULTS: 647 participants were recruited in the first eleven months of the study, 356 (55.0%) at the free clinic over 11 months and 291 (45.0%) at the FQHC over 6 months. Participants were on average 54.4 years old (SD=14.2), 60.9% female, 45.6% Black, 37.8% White, 9.6% Hispanic, and 10.9% had < high school education. Participants reported hearing about the MI-SIGHT program from a clinic phone call (n=168, 26.1%), a friend (n=112, 17.4%), non-medical clinic staff (n=100, 15.5%), a clinic doctor (n=77, 11.9%), an in-clinic brochure or flyer (n=51, 7.9%), a community flyer (n=44, 6.8%), the clinic website or social media (n=28, 4.3%), or an "other" source (n=65, 10.1%). Recruiting from the community outside the medical clinics increased participation by 265% at the free clinic and 46% at the FQHC. CONCLUSIONS: The Community Advisory Board recommendation to use community-based recruitment strategies in addition to clinic-based strategies for recruitment resulted in increased program participation.

    • Environmental Health
      1. Microbial characterization, factors contributing to contamination, and household use of cistern water, U.S. Virgin Islands
        Rao G, Kahler A, Voth-Gaeddert L, Cranford H, Libbey S, Galloway R, Molinari N, Ellis E, Yoder J, Mattioli M, Ellis B.
        ACS ES T Water. 2022 2022/10/18.
        Households in the United States Virgin Islands (USVI) heavily rely on roof-harvested rainwater stored in cisterns for their daily activities. However, there are insufficient data on cistern water microbiological and physicochemical characteristics to inform appropriate cistern water management. Cistern and kitchen tap water samples were collected from 399 geographically representative households across St. Croix, St. Thomas, and St. John and an administered survey captured household site and cistern characteristics and water use behaviors. Water samples were analyzed for Escherichia coli by culture, and a subset of cistern water samples (N = 47) were analyzed for Salmonella, Naegleria fowleri, pathogenic Leptospira, Cryptosporidium, Giardia, and human-specific fecal contamination using real-time polymerase chain reaction (PCR). Associations between E. coli cistern contamination and cistern and site characteristics were evaluated to better understand possible mechanisms of contamination. E. coli was detected in 80% of cistern water samples and in 58% of kitchen tap samples. For the subset of samples tested by PCR, at least one of the pathogens was detected in 66% of cisterns. Our results suggest that covering overflow pipes with screens, decreasing animal presence at the household, and preventing animals or insects from entering the cisterns can decrease the likelihood of E. coli contamination in USVI cistern water.

      2. Reducing the particles generated by flushing institutional toilets
        Cai C, Kim P, Connor TH, Liu Y, Floyd EL.
        J Occup Environ Hyg. 2022 May;19(5):318-326.
        Airborne particles play a significant role in the transmission of SARS-CoV-2, the virus that causes COVID-19. A previous study reported that institutional flush-O-meter (FOM) toilets can generate 3-12 times as many droplets as other toilets by splashing (large droplets) and bubble bursting (fine droplets). In this study, an aerosol suppression lid was evaluated to measure the reduction of particles by size using three metrics; number, surface area, and mass concentrations. To quantify toilet flush aerosol over time, detailed particle size distributions (from 0.016-19.81 µm across 152 size bins) were measured from a FOM toilet in a controlled-environment test chamber, without ventilation, with and without use of the suppression lid. Prior to each flushing trial, the toilet bowl water was seeded with 480 mL fluorescein at 10 mg/mL. A high-speed camera was used to record the large droplet movements after flushing. An ultraviolet-visible spectrophotometer was used to analyze the wipe samples to evaluate the contamination on the lid. The particle number, surface area, and mass concentrations without a lid were elevated compared to a lid in the first 90 sec. Overall, the lid reduced 48% of total number concentration, 76% of total surface area concentration, and 66% of total mass concentration, respectively. Depending on the particle size, the number concentration reduction percentage ranged from 48-100% for particles larger than 0.1 µm. Large droplets created by splashing were captured by the high-speed camera. Similar studies can be used for future particle aerodynamic studies. The fluorescein droplets deposited on the lid back sections, which were closer to the FOM accounted for 82% of the total fluorescein. Based on two-way ANOVA analysis, there were significant differences among both the experimental flushes (p = 0.0185) and the sections on the lid (p = 0.0146). Future work should explore the aerosolization produced by flushing and the performance of the lid in real restroom environments, where feces and urine exist in the bowl water and the indoor ventilation system is in operation.

      3. Wildfire smoke and symptoms affecting mental health among adults in the U.S. state of Oregon
        Mirabelli MC, Vaidyanathan A, Pennington AF, Ye D, Trenga CA.
        Prev Med. 2022 Nov 3;164:107333.
        The physical and mental health impacts of wildfires are wide-ranging. We assessed associations between exposure to wildfire smoke and self-reported symptoms affecting mental health among adults living in Oregon. We linked by interview date and county of residence survey responses from 5807 adults who responded to the 2018 Behavioral Risk Factor Surveillance System's depression and anxiety module with smoke plume density, a proxy for wildfires and wildfire smoke exposure. Associations between weeks in the past year with medium and heavy smoke plume densities and symptoms affecting mental health during the two weeks before the interview date were estimated using predicted marginal probabilities from logistic regression models. In the year before completing the interview, 100% of respondents experienced ≥2 weeks of medium or heavy smoke, with an average exposure duration of 32 days. Nearly 10% reported being unable to stop or control their worrying more than half the time over the past two weeks. Medium or heavy smoke for 6 or more weeks in the past year, compared to ≤4 weeks in the past year, was associated with a 30% higher prevalence of being unable to stop or control worrying more than half the time during the past two weeks (prevalence ratio: 1.30, 95% confidence interval: 1.03, 1.65). Among adults in Oregon, selected symptoms affecting mental health were associated with extended durations of medium and heavy smoke. These findings highlight the burden of such symptoms among adults living in communities affected by wildfires and wildfire smoke.

    • Epidemiology and Surveillance
      1. Wastewater testing and detection of poliovirus type 2 genetically linked to virus isolated from a paralytic polio case - New York, March 9-October 11, 2022
        Ryerson AB, Lang D, Alazawi MA, Neyra M, Hill DT, St George K, Fuschino M, Lutterloh E, Backenson B, Rulli S, Ruppert PS, Lawler J, McGraw N, Knecht A, Gelman I, Zucker JR, Omoregie E, Kidd S, Sugerman DE, Jorba J, Gerloff N, Ng TF, Lopez A, Masters NB, Leung J, Burns CC, Routh J, Bialek SR, Oberste MS, Rosenberg ES.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44):1418-1424.
        In July 2022, a case of paralytic poliomyelitis resulting from infection with vaccine-derived poliovirus (VDPV) type 2 (VDPV2)(§) was confirmed in an unvaccinated adult resident of Rockland County, New York (1). As of August 10, 2022, poliovirus type 2 (PV2)(¶) genetically linked to this VDPV2 had been detected in wastewater** in Rockland County and neighboring Orange County (1). This report describes the results of additional poliovirus testing of wastewater samples collected during March 9-October 11, 2022, and tested as of October 20, 2022, from 48 sewersheds (the community area served by a wastewater collection system) serving parts of Rockland County and 12 surrounding counties. Among 1,076 wastewater samples collected, 89 (8.3%) from 10 sewersheds tested positive for PV2. As part of a broad epidemiologic investigation, wastewater testing can provide information about where poliovirus might be circulating in a community in which a paralytic case has been identified; however, the most important public health actions for preventing paralytic poliomyelitis in the United States remain ongoing case detection through national acute flaccid myelitis (AFM) surveillance(††) and improving vaccination coverage in undervaccinated communities. Although most persons in the United States are sufficiently immunized, unvaccinated or undervaccinated persons living or working in Kings, Orange, Queens, Rockland, or Sullivan counties, New York should complete the polio vaccination series as soon as possible.

      2. Excess all-cause mortality in the USA and Europe during the COVID-19 pandemic, 2020 and 2021
        Rossen LM, Nørgaard SK, Sutton PD, Krause TG, Ahmad FB, Vestergaard LS, Mølbak K, Anderson RN, Nielsen J.
        Sci Rep. 2022 Nov 3;12(1):18559.
        Both the USA and Europe experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This retrospective observational study included data on deaths from all causes occurring in the USA and 25 European countries or subnational areas participating in the network for European monitoring of excess mortality for public health action (EuroMOMO). We applied the EuroMOMO algorithm to estimate excess all-cause mortality in the USA and Europe during the first two years of the COVID-19 pandemic, 2020-2021, and compared excess mortality by age group and time periods reflecting three primary waves. During 2020-2021, the USA experienced 154.5 (95% Uncertainty Interval [UI]: 154.2-154.9) cumulative age-standardized excess all-cause deaths per 100,000 person years, compared with 110.4 (95% UI: 109.9-111.0) for the European countries. Excess all-cause mortality in the USA was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020-2021. If the USA had experienced an excess mortality rate similar to Europe, there would have been approximately 391 thousand (36%) fewer excess deaths in the USA.

    • Genetics and Genomics
      1. Complete genome sequence of O'nyong Nyong virus isolated from a febrile patient in 2017 in Uganda
        Ledermann JP, Kayiwa JT, Perinet LC, Apangu T, Acayo S, Lutwama JJ, Powers AM, Mossel EC.
        Microbiol Resour Announc. 2022 Nov 3:e0069222.
        Despite causing numerous large outbreaks in the 20th century, few isolates of o'nyong nyong virus (ONNV) have been fully sequenced. Here, we report the complete genome sequence of an isolate of ONNV obtained from a febrile patient in northwest Uganda in 2017, designated ONNV UVRI0804.

    • Health Equity and Health Disparities
      1. Research that explores the intra-racial socio-demographic and clinical characteristics associated with perceived discrimination in healthcare settings in the US is lacking. We examined the prevalence of self-reported discrimination in HIV care settings during the past 12 months among Black persons from a nationally representative sample of US adults with diagnosed HIV collected 6/2018-5/2019. We assessed the prevalence of self-reported discrimination in HIV care settings during the past 12 months, perceived reasons for discrimination, and factors associated with discrimination among Black persons with diagnosed HIV (n = 1,631). Overall, 22% reported experiencing discrimination in a healthcare setting; discrimination was most often attributed to HIV status. Those reporting discrimination were younger, MSM, and living at or below the federal poverty level. They also experienced homelessness, incarceration and illicit substance use in the past 12 months, and anxiety and depression symptoms in the past 2 weeks. They were less likely to use ART or report 100% ART dose adherence in the past 30 days. No associations were found with viral suppression. Systems are needed to monitor, evaluate reports of, and address discrimination in healthcare settings. Incorporating anti-discrimination policies and continuing education opportunities for providers and staff may reduce experiences of discrimination among persons with HIV.

      2. Racial, ethnic, and rural/urban disparities in HIV and sexually transmitted infections in South Carolina
        Giannouchos TV, Crouch E, Merrell MA, Brown MJ, Harrison SE, Pearson WS.
        J Community Health. 2022 Nov 4:1-8.
        Examining the current incidence rates of HIV and STIs among racial and ethnic minority and rural residents is crucial to inform and expand initiatives and outreach efforts to address disparities and minimize the health impact of these diseases. A retrospective, cross-sectional study was conducted using Medicaid administrative claims data over a 2-year period (July 2019-June 2021) in South Carolina. Our main outcomes of interest were claims for chlamydia, gonorrhea, syphilis, and HIV. Any beneficiary with at least one claim for a relevant diagnosis throughout the study period was considered to have one of these diseases. Descriptive analyses and multivariable regression models were used to estimate the association between STIs, HIV, race and ethnicity, and rurality. Overall, 158,731 Medicaid beneficiaries had at least one medical claim during the study period. Most were female (86.6%), resided in urban areas (66.6%), and were of non-Hispanic Black race/ethnicity (42.6%). In total, 6.3% of beneficiaries had at least one encounter for chlamydia, 3.2% for gonorrhea, 0.5% for syphilis, and 0.8% for HIV. In multivariable models, chlamydia, gonorrhea, and HIV claims were significantly associated with non-Hispanic Black or other minority race/ethnicity compared to non-Hispanic white race/ethnicity. Rural residents were more likely to have a claim associated with chlamydia and gonorrhea compared to urban residents. The opposite was observed for syphilis and HIV. Providing updated evidence on disparities in STIs and HIV among racial/ethnic minority and rural populations in a southern state is essential for shaping state Medicaid policies to address health disparities.

    • Healthcare Associated Infections
      1. Recurrent candidemia: Trends and risk factors among persons residing in 4 US states, 2011-2018
        Seagle EE, Jackson BR, Lockhart SR, Jenkins EN, Revis A, Farley MM, Harrison LH, Schaffner W, Markus TM, Pierce RA, Zhang AY, Lyman MM.
        Open Forum Infect Dis. 2022 Oct;9(10):ofac545.
        BACKGROUND: Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors. METHODS: We analyzed population-based candidemia surveillance data collected during 2011-2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not. RESULTS: Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19-44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10-4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12-2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27-2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58-2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12-2.43]). CONCLUSIONS: Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia.

    • Immunity and Immunization
      1. Meeting report: 34th International Conference On Antiviral Research
        Brancale A, Carter K, Delang L, Deval J, Durantel D, Gentry BG, Jordan R, Julander JG, Lo MK, Pérez-Pérez MJ, Schang LM, Seley-Radtke KL, Shi PY, Vasudevan SG, Whitley RJ, Spengler JR.
        Antivir Chem Chemother. 2022 Jan-Dec;30:20402066221130853.
        As a result of the multiple gathering and travels restrictions during the SARS-CoV-2 pandemic, the annual meeting of the International Society for Antiviral Research (ISAR), the International Conference on Antiviral Research (ICAR), could not be held in person in 2021. Nonetheless, ISAR successfully organized a remote conference, retaining the most critical aspects of all ICARs, a collegiate gathering of researchers in academia, industry, government and non-governmental institutions working to develop, identify, and evaluate effective antiviral therapy for the benefit of all human beings. This article highlights the 2021 remote meeting, which presented the advances and objectives of antiviral and vaccine discovery, research, and development. The meeting resulted in a dynamic and effective exchange of ideas and information, positively impacting the prompt progress towards new and effective prophylaxis and therapeutics.

      2. Routine immunization rates in the United States (US) declined immediately after the US declared COVID-19 a public health emergency in March 2020. Decreases in childhood vaccination place children at risk for vaccine-preventable diseases and communities at risk for outbreaks from these diseases. The US Department of Health and Human Services (HHS) launched "Catch Up to Get Ahead" in August 2020 to promote routine childhood immunization. The decline in mean coverage of the combined 7-vaccine series among children aged 19-35 months was less in Indian Health Service (IHS) federal health centers that implemented "Catch Up to Get Ahead" compared to IHS federal health centers that did not. The effort to promote catch-up vaccination may have showed promise in minimizing the decline in childhood vaccination coverage during the pandemic. However, the effort was not enough to reach pre-pandemic levels, indicating the need for more robust and sustained efforts to catch children up on all delayed immunizations.

      3. SARS-CoV-2 antibody seroprevalence in Jakarta, Indonesia
        Ariawan I, Jusril H, Farid MN, Riono P, Wahyuningsih W, Widyastuti , Handayani DO, Wahyuningsih ES, Daulay R, Henderiawati R, Malik SG, Noviyanti R, Trianty L, Fadila N, Myint KS, Yudhaputri FA, Venkateswaran N, Venkateswaran K, Udhayakumar V, Hawley WA, Morgan J, Pronyk PM.
        Kesmas. 2022 ;17(3):169-174.
        The SARS-CoV-2 transmission dynamics in low- and middle-income countries remain poorly understood. This study aimed to estimate the SARS-CoV-2 antibodies seroprevalence in Jakarta, Indonesia, and to increase knowledge of SARS-CoV-2 transmission in urban settings. A population-based serosurvey among individuals aged one year or older was conducted in Jakarta. Employing a multistage sampling design, samples were stratified by district, slum and non-slum residency, sex, and age group. Blood samples were tested for IgG against three different SARS-CoV-2 antigens. Seroprevalence was estimated after applying sample weights and adjusting for cluster characteristics. In March 2021, this study collected 4,919 respondents. The weighted estimate of seroprevalence was 44.5% (95% CI = 42.5-46.5). Seroprevalence was highest among adults aged 30-49 years, with higher seroprevalence in women and the overweight/obese group. Respondents residing in slum areas were 1.3-fold more likely to be seropositive than non-slum residents. It was estimated that 4,717,000 of Jakarta's 10.6 million residents had prior SARS-CoV-2 infection. This suggests that approximately 10 infections were undiagnosed/underreported for every reported case. About one year after the first COVID-19 case was confirmed, close to half of Jakarta's residents have been infected by SARS-CoV-2. Copyright © 2022, Kesmas: Jurnal Kesehatan Masyarakat Nasional (National Public Health Journal)

      4. Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials
        Wahid R, Mercer LD, De Leon T, DeAntonio R, Sáez-Llorens X, Macadam A, Chumakov K, Strating J, Koel B, Konopka-Anstadt JL, Oberste MS, Burns CC, Andino R, Tritama E, Bandyopadhyay AS, Aguirre G, Rüttimann R, Gast C, Konz JO.
        Lancet Microbe. 2022 Nov 1.
        BACKGROUND: Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks. METHODS: In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model. FINDINGS: Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log(10) 50% cell culture infectious dose (CCID(50)) and 76·7% at the 5 log(10) CCID(50) inoculum levels, with rates of 2·8% for 4 log(10) CCID(50) and 11·8% for 5 log(10) CCID(50) observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log(10) of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients. INTERPRETATION: The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses. FUNDING: Bill & Melinda Gates Foundation.

      5. Safety monitoring of bivalent COVID-19 mRNA vaccine booster doses among persons aged ≥12 years - United States, August 31-October 23, 2022
        Hause AM, Marquez P, Zhang B, Myers TR, Gee J, Su JR, Blanc PG, Thomas A, Thompson D, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44):1401-1406.
        On August 31, 2022, the Food and Drug Administration (FDA) authorized bivalent formulations of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines; these vaccines include mRNA encoding the spike protein from the original (ancestral) strain of SARS-CoV-2 (the virus that causes COVID-19) and from the B.1.1.529 (Omicron) variants BA.4 and BA.5 (BA.4/BA.5). These bivalent mRNA vaccines were authorized for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination; Pfizer-BioNTech bivalent booster was authorized for persons aged ≥12 years and Moderna for adults aged ≥18 years.*(,)(†) On September 1, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥12 years receive an age-appropriate bivalent mRNA booster dose.(§) To characterize the safety of bivalent mRNA booster doses, CDC reviewed adverse events and health impacts reported after receipt of bivalent Pfizer-BioNTech and Moderna booster doses during August 31-October 23, 2022, to v-safe,(¶) a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and the Vaccine Adverse Event Reporting System (VAERS),** a U.S. passive vaccine safety surveillance system managed by CDC and FDA (1). During August 31-October 23, 2022, approximately 14.4 million persons aged ≥12 years received a bivalent Pfizer-BioNTech booster dose, and 8.2 million adults aged ≥18 years received a bivalent Moderna booster dose.(††) Among the 211,959 registrants aged ≥12 years who reported receiving a bivalent booster dose to v-safe, injection site and systemic reactions were frequently reported in the week after vaccination (60.8% and 54.8%, respectively); fewer than 1% of v-safe registrants reported receiving medical care. VAERS received 5,542 reports of adverse events after bivalent booster vaccination among persons aged ≥12 years; 95.5% of reports were nonserious and 4.5% were serious events. Health care providers and patients can be reassured that adverse events reported after a bivalent booster dose are consistent with those reported after monovalent doses. Health impacts after COVID-19 vaccination are less frequent and less severe than those associated with COVID-19 illness (2).

      6. Routine vaccination coverage - Worldwide, 2021
        Rachlin A, Danovaro-Holliday MC, Murphy P, Sodha SV, Wallace AS.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 4;71(44):1396-1400.
        In 2020, the World Health Assembly endorsed the Immunization Agenda 2030, an ambitious global immunization strategy to reduce morbidity and mortality from vaccine-preventable diseases (1). This report updates a 2020 report (2) with global, regional,* and national vaccination coverage estimates and trends through 2021. Global estimates of coverage with 3 doses of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) decreased from an average of 86% during 2015-2019 to 83% in 2020 and 81% in 2021. Worldwide in 2021, 25.0 million infants (19% of the target population) were not vaccinated with DTPcv3, 2.1 million more than in 2020 and 5.9 million more than in 2019. In 2021, the number of infants who did not receive any DTPcv dose by age 12 months (18.2 million) was 37% higher than in 2019 (13.3 million). Coverage with the first dose of measles-containing vaccine (MCV1) decreased from an average of 85% during 2015-2019 to 84% in 2020 and 81% in 2021. These are the lowest coverage levels for DTPcv3 and MCV1 since 2008. ​Global coverage estimates were also lower in 2021 than in 2020 and 2019 for bacillus Calmette-Guérin vaccine (BCG) as well as for the completed series of Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HepB), polio vaccine (Pol), and rubella-containing vaccine (RCV). The COVID-19 pandemic has resulted in disruptions to routine immunization services worldwide. Full recovery to immunization programs will require context-specific strategies to address immunization gaps by catching up missed children, prioritizing essential health services, and strengthening immunization programs to prevent outbreaks (3).

      7. Understanding thrombosis with thrombocytopenia syndrome after COVID-19 vaccination
        Buoninfante A, Andeweg A, Baker AT, Borad M, Crawford N, Dogné JM, Garcia-Azorin D, Greinacher A, Helfand R, Hviid A, Kochanek S, López-Fauqued M, Nazy I, Padmanabhan A, Pavord S, Prieto-Alhambra D, Tran H, Wandel Liminga U, Cavaleri M.
        NPJ Vaccines. 2022 Nov 9;7(1):141.

      8. Kawasaki disease following the 13-valent pneumococcal conjugate vaccine and rotavirus vaccines
        Kamidani S, Panagiotakopoulos L, Licata C, Daley MF, Yih WK, Zerbo O, Tseng HF, DeSilva MB, Nelson JC, Groom HC, Williams JT, Hambidge SJ, Donahue JG, Belay ED, Weintraub ES.
        Pediatrics. 2022 Nov 9.
        BACKGROUND: Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. METHODS: We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children <2 years of age who were born from 2006 to 2017. All hospitalized KD cases identified by International Classification of Diseases diagnosis codes that fell within predefined risk (days 1-28 postvaccination) and control (days 29-56 for doses 1 and 2, and days 43-70 for doses 3 and 4) intervals were confirmed by manual chart review. RESULTS: During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47-1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40-1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. CONCLUSIONS: PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children <2 years of age. Our findings provide additional evidence for the overall safety of PCV13 and rotavirus vaccines.

      9. BACKGROUND: Neisseria gonorrhoeae cross-protection was suggested in a New Zealand meningitis B vaccine. We modeled the potential impact of similar vaccines on gonorrhea prevalence in heterosexuals in the United States. METHODS: Our mathematical model incorporated infection, behavior, and vaccination dynamics. Approximate Bayesian Computation calibrated our model to US prevalence. Primary analyses assumed New Zealand vaccine characteristics: 30% efficacy and 2-year duration of protection. We estimated impact under two vaccine coverages (20%, 50%). RESULTS: Reduction in gonorrhea prevalence ranged from 4.8 to 39.4%, depending on vaccine coverage. Vaccine impact was correlated with both size of the highly sexually active subpopulation and sexual mixing between high and low activity subpopulations. CONCLUSIONS: A meningitis vaccine providing low efficacy cross-protection against gonorrhea acquisition and short duration of protection could result in a large reduction in gonorrhea prevalence in the United States. Potential dual protective effects can be considered when making vaccine recommendations.

      10. Recombinant zoster vaccine (RZV) second-dose series completion in adults aged 50-64 years in the United States
        Leung J, Gray EB, Anderson TC, Sharkey SM, Dooling K.
        Vaccine. 2022 Nov 5.
        In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥ 50 years, with the 2nd dose recommended 2-6 months after the 1st dose. We estimated second-dose RZV series completion in the U.S. among 50-64-year-olds using two administrative databases. Second-dose RZV series completion was ∼70% within 6-months and 80% within 12-months of first dose. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 96% had a missed opportunity for a second-dose vaccination, defined as a provider or pharmacy visit, among whom 36% had a visit for influenza or pneumococcal vaccination within 2-12 months of their first-dose of RZV. We found that RZV series completion rates in 50-64-year-olds was high. Availability of RZV at pharmacies has potentially helped increase series completion, but missed opportunities remain.

      11. Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system
        Malden DE, Gee J, Glenn S, Li Z, Mercado C, Ogun OA, Kim S, Lewin BJ, Ackerson BK, Jazwa A, Weintraub ES, McNeil MM, Tartof SY.
        Vaccine. 2022 Nov 3.
        BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: We conducted an observational study using data from a digital survey and EHR of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope). RESULTS: The study recruited 7,077 participants aged 5-11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising<0.5 % of children. No encounters were related to myocarditis. CONCLUSION: While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5-11 years, our data showed that in most cases they were transient and did not require medical care.

      12. Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo
        Priyamvada L, Carson WC, Ortega E, Navarra T, Tran S, Smith TG, Pukuta E, Muyamuna E, Kabamba J, Nguete BU, Likafi T, Kokola G, Lushima RS, Tamfum JM, Okitolonda EW, Kaba DK, Monroe BP, McCollum AM, Petersen BW, Satheshkumar PS, Townsend MB.
        Vaccine. 2022 Nov 4.
        The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

      13. Surveillance to track progress towards polio eradication - worldwide, 2020-2021
        Wilkinson AL, Diop OM, Jorba J, Gardner T, Snidera CJ, Ahmed J.
        Weekly Epidemiological Record. 2022 ;97(15/16):157-168.
        Less than 99.99% of recorded cases of poliomyelitis have occurred since the Global Polio Eradication Initiative (GPEI) was established in 1988. By the end of 2021, only Afghanistan and Pakistan will still have endemic wild poliovirus (WPV). While Malawi reported a case of wild poliovirus type 1 (WPV1) with paralysis onset in 2021, just over a year after the WHO African Region (AFR) was proclaimed WPV-free, 31 nations reported incidences of circulating vaccine-derived poliovirus (cVDPV) between 2020 and 2021. Monitoring for acute flaccid paralysis (AFP) in people under the age of 15 is the main way to identify poliovirus transmission, and confirmation comes from testing stool samples at WHO-accredited labs. In all WHO regions in 2020, the COVID-19 pandemic had an impact on polio vaccination and surveillance; from January to September 2020, fewer AFP cases were reported, and there was a longer delay between collecting stools and labs receiving them than there had been during the same period in 2019. A significant increase from 2020, when only 23 (53%) of the priority countries attained the national targets for the two key surveillance performance metrics, was shown in 2021. High-performance surveillance is necessary to track the spread of the poliovirus. Gaps in surveillance indicators might be found, improvements could be made, and the overall sensitivity and promptness of poliovirus detection might be enhanced in order to successfully eradicate polio. The collection of adequate stool specimens8 from AFP patients, with a target of 80% adequate stool specimens, and the nonpolio AFP (NPAFP) rate, which is a rate of 2 per 100,000 people aged 15 years and considered sufficiently sensitive for detecting circulating poliovirus, are two key performance indicators used to assess the quality of AFP surveillance. 43 priority nations experiencing or at high risk of poliovirus transmission were the subject of an analysis of surveillance indicators as of 25 March 2022.

    • Informatics
      1. COVID-19-Related manuscripts: lag from preprint to publication
        Drzymalla E, Yu W, Khoury MJ, Gwinn M.
        BMC Res Notes. 2022 Nov 5;15(1):340.
        OBJECTIVE: Preprints have had a prominent role in the swift scientific response to COVID-19. Two years into the pandemic, we investigated how much preprints had contributed to timely data sharing by analyzing the lag time from preprint posting to journal publication. RESULTS: To estimate the median number of days between the date a manuscript was posted as a preprint and the date of its publication in a scientific journal, we analyzed preprints posted from January 1, 2020, to December 31, 2021 in the NIH iSearch COVID-19 Portfolio database and performed a Kaplan-Meier (KM) survival analysis using a non-mixture parametric cure model. Of the 39,243 preprints in our analysis, 7712 (20%) were published in a journal, after a median lag of 178 days (95% CI: 175-181). Most of the published preprints were posted on the bioRxiv (29%) or medRxiv (65%) servers, which allow authors to choose a subject category when posting. Of the 20,698 preprints posted on these two servers, 7358 (36%) were published, including approximately half of those categorized as biochemistry, biophysics, and genomics, which became published articles within the study interval, compared with 29% categorized as epidemiology and 26% as bioinformatics.

      2. Cleaning of anthropometric data from PCORnet electronic health records using automated algorithms
        Lin PD, Rifas-Shiman SL, Aris IM, Daley MF, Janicke DM, Heerman WJ, Chudnov DL, Freedman DS, Block JP.
        JAMIA Open. 2022 Dec;5(4):ooac089.
        OBJECTIVE: To demonstrate the utility of growthcleanr, an anthropometric data cleaning method designed for electronic health records (EHR). MATERIALS AND METHODS: We used all available pediatric and adult height and weight data from an ongoing observational study that includes EHR data from 15 healthcare systems and applied growthcleanr to identify outliers and errors and compared its performance in pediatric data with 2 other pediatric data cleaning methods: (1) conditional percentile (cp) and (2) PaEdiatric ANthropometric measurement Outlier Flagging pipeline (peanof). RESULTS: 687 226 children (<20 years) and 3 267 293 adults contributed 71 246 369 weight and 51 525 487 height measurements. growthcleanr flagged 18% of pediatric and 12% of adult measurements for exclusion, mostly as carried-forward measures for pediatric data and duplicates for adult and pediatric data. After removing the flagged measurements, 0.5% and 0.6% of the pediatric heights and weights and 0.3% and 1.4% of the adult heights and weights, respectively, were biologically implausible according to the CDC and other established cut points. Compared with other pediatric cleaning methods, growthcleanr flagged the most measurements for exclusion; however, it did not flag some more extreme measurements. The prevalence of severe pediatric obesity was 9.0%, 9.2%, and 8.0% after cleaning by growthcleanr, cp, and peanof, respectively. CONCLUSION: growthcleanr is useful for cleaning pediatric and adult height and weight data. It is the only method with the ability to clean adult data and identify carried-forward and duplicates, which are prevalent in EHR. Findings of this study can be used to improve the growthcleanr algorithm.

    • Laboratory Sciences
      1. Optimising courier specimen collection time improves patient access to HIV viral load testing in South Africa
        Girdwood SJ, Crompton T, Cassim N, Olsen F, Sejake P, Diallo K, Berrie L, Chimhamhiwa D, Stevens W, Nichols B.
        Afr J Lab Med. 2022 ;11(1):1725.
        BACKGROUND: South Africa uses a courier network for transporting specimens to public laboratories. After the daily collection of specimens from the facility by the courier, patients not yet attended to are unlikely to receive same-day blood draws, potentially inhibiting access to viral load (VL) testing for HIV patients. OBJECTIVE: We aimed to design an optimised courier network and assess whether this improves VL testing access. METHODS: We optimised the specimen transport network in South Africa for 4046 facilities (November 2019). For facilities with current specimen transport times (n = 356), we assessed the relationship between specimen transport time and VL testing access (number of annual VL tests per antiretroviral treatment patient) using regression analysis. We compared our optimised transport times with courier collection times to determine the change in access to same-day blood draws. RESULTS: The number of annual VL tests per antiretroviral treatment patient (1.14, standard deviation: 0.02) was higher at facilities that had courier collection after 13:36 (the average latest collection time) than those that had their last collection before 13:36 (1.06, standard deviation: 0.03), even when adjusted for facility size. Through network optimisation, the average time for specimen transport was delayed to 14:35, resulting in a 6% - 13% increase in patient access to blood draws. CONCLUSION: Viral load testing access depends on the time of courier collection at healthcare facilities. Simple solutions are frequently overlooked in the quest to improve healthcare. We demonstrate how simply changing specimen transportation timing could markedly improve access to VL testing.

      2. Performance of existing and novel symptom- and antigen testing-based COVID-19 case definitions in a community setting
        Lee S, Almendares O, Prince-Guerra J, Anderson M, Heilig CM, Tate JE, Kirking HL.
        Am J Epidemiol. 2022 Nov 7.
        Point-of-care antigen tests are an important tool for SARS-CoV-2 detection yet are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this analysis was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.53 for antigen testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and our code is publicly available to aid public health practitioners in developing or fine-tuning their own case definitions.

      3. An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance
        Patel MC, Flanigan D, Feng C, Chesnokov A, Nguyen HT, Elal AA, Steel J, Kondor RJ, Wentworth DE, Gubareva LV, Mishin VP.
        Antiviral Res. 2022 Nov 1;208:105457.
        Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of virus-infected cells. For convenience, this new assay was named IRINA (Influenza Replication Inhibition Neuraminidase-based Assay). IRINA was successfully validated to assess inhibitory activity of baloxavir on virus replication by testing a large set (>150) of influenza A and B viruses, including drug resistant strains and viruses collected during 2017-2022. To test its versatility, IRINA was utilized to evaluate neutralization activity of a broadly reactive human anti-HA monoclonal antibody, FI6, and post-infection ferret antisera, as well as the inhibition of NA enzyme activity by NA inhibitors. Performance of IRINA was tested in parallel using respective conventional assays. IRINA offers an attractive alternative to current phenotypic assays, while maintaining reproducibility and high throughput capacity. Additionally, the improved turnaround time may prove to be advantageous when conducting time sensitive studies, such as investigating a new virus outbreak. This assay can meet the needs of surveillance laboratories by providing a streamlined and cost-effective approach for virus characterization.

      4. Diagnostics to support mycetoma management - Development of two target product profiles
        Fongwen N, Asiedu KB, Bakhiet S, Bonifaz A, Cruz I, Argaw D, Estrada-Chavez G, Fahal AH, Litvintseva A, Marks M, Salinas-Carmona MC, Sow D, van de Sande WW.
        Trop Med Int Health. 2022 Nov 3.
        OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different micro-organisms and identified by WHO as one of the high-priority diseases for developing diagnostic tests. To ensure production of diagnostic assays for use by clinical staff in endemic regions, Target Product Profiles (TPP) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another which would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a one-month online public consultation on 25 October 2021 and the final TPP was posted online on 05 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them.

    • Maternal and Child Health
      1. Assessing the validity of the Baby Pediatric Symptom Checklist using a nationally representative household survey
        Zablotsky B, Black LI, Sheldrick RC, Perrin EC, Blumberg SJ.
        Acad Pediatr. 2022 Nov 6.
        OBJECTIVE: The Baby Pediatric Symptom Checklist (BPSC) is a screening tool developed for detecting behavioral or emotional concerns among parents of children younger than 18 months. Nationally representative survey data have not yet been used to assess the validity of the BPSC, nor to evaluate its appropriateness for use among children between 18 and 23 months old. The current study assesses the validity of the BPSC using data from the National Health Interview Survey (NHIS). METHODS: Data from the 2019 NHIS were used to evaluate the 12-item BPSC screening tool among a nationally representative sample of children 2-23 months. Confirmatory factor analysis (CFA) and differential item functioning (DIF) were used to assess construct and predictive validity and test how response items differed by selected sociodemographics. Quantile regression was used to calculate 50(th), 70(th), and 90(th) percentiles for age-based normative curves of the previously established domains of irritability, inflexibility, and difficulty with routines. RESULTS: A three-factor CFA produced comparable results to the original study. Tests of DIF did not reveal any significant effects for the child's sex, race and Hispanic origin, household urbanization level, number of children in family, or respondent type (mother, father, other). In addition, DIF was not found between children aged 2-17 months and 18-23 months. Age-based normative data were calculated for each subscale. CONCLUSIONS: The use of the BPSC in a nationally representative survey produced findings comparable to those of the original-validation study. The NHIS can be used to track BPSC scores over time at the population-level.

      2. Risk factors for community-acquired bacterial infection among young infants in South Asia: a longitudinal cohort study with nested case-control analysis
        Connor NE, Islam MS, Mullany LC, Shang N, Bhutta ZA, Zaidi AK, Soofi S, Nisar I, Panigrahi P, Panigrahi K, Satpathy R, Bose A, Isaac R, Baqui AH, Mitra DK, Sadeq-Ur Rahman Q, Hossain T, Schrag SJ, Winchell JM, Arvay ML, Diaz MH, Waller JL, Weber MW, Hamer DH, Hibberd P, Nawshad Uddin Ahmed AS, Islam M, Hossain MB, Qazi SA, El Arifeen S, Darmstadt GL, Saha SK.
        BMJ Glob Health. 2022 Nov;7(11).
        OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship. METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build a Bayesian partial latent class model (PLCM) capable of attributing the probable cause of each infant's infection in the ANISA study. The collected risk factors from all mother-child pairs were classified and analysed against the PLCM using bivariate and stepwise logistic multivariable regression modelling to determine risk factors of probable bacterial infection. RESULTS: Among 63 114 infants born, 14 655 were assessed and 6022 had signs of pSBI; of these, 81% (4859) provided blood samples for culture, 71% (4216) provided blood samples for quantitative PCR (qPCR) and 86% (5209) provided respiratory qPCR samples. Risk factors associated with bacterial-attributed infections included: low (relative risk (RR) 1.73, 95% credible interval (CrI) 1.42 to 2.11) and very low birth weight (RR 5.77, 95% CrI 3.73 to 8.94), male sex (RR 1.27, 95% CrI 1.07 to 1.52), breathing problems at birth (RR 2.50, 95% CrI 1.96 to 3.18), premature rupture of membranes (PROMs) (RR 1.27, 95% CrI 1.03 to 1.58) and being in the lowest three socioeconomic status quintiles (first RR 1.52, 95% CrI 1.07 to 2.16; second RR 1.41, 95% CrI 1.00 to 1.97; third RR 1.42, 95% CrI 1.01 to 1.99). CONCLUSION: Distinct risk factors: birth weight, male sex, breathing problems at birth and PROM were significantly associated with the development of bacterial sepsis across South Asian community settings, supporting refined clinical discernment and targeted use of antimicrobials.

      3. Associations of gestational exposure to organophosphate esters with gestational age and neonatal anthropometric measures: The HOME study
        Yang W, Braun JM, Vuong AM, Percy Z, Xu Y, Xie C, Deka R, Calafat AM, Ospina M, Burris HH, Yolton K, Cecil KM, Lanphear BP, Chen A.
        Environ Pollut. 2022 Oct 28;316(Pt 1):120516.
        Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

      4. Surveillance of ADHD among children in the United States: Validity and reliability of parent report of provider diagnosis
        Cree RA, Bitsko RH, Danielson ML, Wanga V, Holbrook J, Flory K, Kubicek LF, Evans SW, Owens JS, Cuffe SP.
        J Atten Disord. 2022 Nov 3:10870547221131979.
        OBJECTIVE: To evaluate the appropriateness of parent-reported diagnosis of ADHD as a surveillance tool. METHOD: We assessed agreement over time and concordance of parent-reported diagnosis against Diagnostic and Statistical Manual (DSM)-based criteria. We compared concordance of diagnosis and DSM-based criteria by child characteristics, including treatment. RESULTS: Among parents who reported their child had ADHD, 95.7% reported it again 2 years later. Comparing diagnosis with DSM-based criteria, specificity and negative predictive value were high, sensitivity was moderate, and positive predictive value was low. Most children with an ADHD diagnosis who did not meet DSM-based criteria met sub-threshold criteria or took medication for ADHD. Concordance differed by child characteristics and treatment. CONCLUSION: Parent-reported diagnosed ADHD is reliable over time. Although differences in parent-reported diagnosis and DSM-based criteria were noted, these may reflect children with milder symptoms or treated ADHD. Parent-report of child ADHD ever diagnosis may be a good single-item indicator for prevalence.

      5. Children's rates of BMI change prepandemic and during two COVID-19 pandemic periods, IQVIA AEMR, January 2018-November 2021
        Pierce SL, Kompaniyets L, Freedman DS, Goodman AB, Blanck HM.
        Obesity (Silver Spring). 2022 Nov 9.
        OBJECTIVE: Many U.S. youth experienced accelerated weight gain during the early COVID-19 pandemic. Using an ambulatory electronic health record dataset, we compared children's rates of BMI change in three periods: prepandemic (January 2018-February 2020), early pandemic (March-December 2020), and later pandemic (January-November 2021). METHODS: We used mixed-effects models to examine differences in rates of change in BMI, weight, and obesity prevalence among the three periods. Covariates included time as a continuous variable; a variable indicating in which period each BMI was taken; sex; age; and initial BMI category. RESULTS: In a longitudinal cohort of 241,600 children aged 2-19 years with ≥4 BMIs, the monthly rates of BMI change (kg/m(2) ) were 0.056 (95%CI: 0.056, 0.057) prepandemic, 0.104 (95%CI: 0.102, 0.106) in the early pandemic, and 0.035 (95%CI: 0.033, 0.036) in the later pandemic. The estimated prevalence of obesity in this cohort was 22.5% by November 2021. CONCLUSIONS: In this large geographically-diverse cohort of U.S. youth, accelerated rates of BMI change observed during 2020 were largely attenuated in 2021. Positive rates indicate continued weight gain rather than loss, albeit at a slower rate. Childhood obesity prevalence remained high, which raises concern about long-term consequences of excess weight and underscores the importance of healthy lifestyle interventions. This article is protected by copyright. All rights reserved.

    • Occupational Safety and Health
      1. Birth defects associated with paternal firefighting in the National Birth Defects Prevention Study
        Siegel MR, Rocheleau CM, Hollerbach BS, Omari A, Jahnke SA, Almli LM, Olshan AF.
        Am J Ind Med. 2022 Nov 8.
        BACKGROUND: Few studies have evaluated birth defects among children of firefighters. We investigated associations between birth defects and paternal work as a firefighter compared to work in non-firefighting and police officer occupations. METHODS: We analyzed 1997-2011 data from the multi-site case-control National Birth Defects Prevention Study. Cases included fetuses or infants with major structural birth defects and controls included a random sample of live-born infants without major birth defects. Mothers of infants self-reported information about parents' occupations held during pregnancy. We investigated associations between paternal firefighting and birth defect groups using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Referent groups included families reporting fathers working non-firefighting and police officer jobs. RESULTS: Occupational groups included 227 firefighters, 36,285 non-firefighters, and 433 police officers. Twenty-nine birth defects were analyzed. In adjusted analyses, fathers of children with total anomalous pulmonary venous return (TAPVR) (OR=3.1; 95% CI=1.1- 8.7), cleft palate (OR=1.8; 95% CI=1.0- 3.3), cleft lip (OR=2.2; 95% CI=1.2- 4.2), and transverse limb deficiency (OR=2.2; 95% CI=1.1- 4.7) were more likely than fathers of controls to be firefighters versus non-firefighters. In police-referent analyses, fathers of children with cleft palate were 2.4 times more likely to be firefighters than fathers of controls (95% CI=1.1-5.4). CONCLUSIONS: Paternal firefighting may be associated with an elevated risk of birth defects in offspring. Additional studies are warranted to replicate these findings. Further research may contribute to a greater understanding of the reproductive health of firefighters and their families for guiding workplace practices. This article is protected by copyright. All rights reserved.

      2. Consensus statements on deployment-related respiratory disease, inclusive of constrictive bronchiolitis: A modified Delphi study
        Falvo MJ, Sotolongo AM, Osterholzer JJ, Robertson MW, Kazerooni EA, Amorosa JK, Garshick E, Jones KD, Galvin JR, Kreiss K, Hines SE, Franks TJ, Miller RF, Rose CS, Arjomandi M, Krefft SD, Morris MJ, Polosukhin VV, Blanc PD, D'Armiento JM.
        Chest. 2022 Nov 4.
        BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including utilizing consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What is the recommended diagnostic workup, and associated terminology, of respiratory symptoms in previously deployed individuals? STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: 25 of 28 statements reached consensus, including the definition of CB as a histological pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms distinguishing assessments best performed at a local or specialty referral center. Also, 'deployment-related respiratory disease' (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through non-invasive evaluation, or when surgical lung biopsy reveals evidence of multi-compartmental lung injury which may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of post-deployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and define other features of its natural history, which could better inform and lead to evolution in this nosology.

      3. Machine learning for detection and risk assessment of lifting action
        Thomas B, Lu M, Jha R, Bertrand J.
        IEEE Trans Hum Mach Syst. 2022 :1-9.
        Repetitive occupational lifting has been shown to create an increased risk for incidence of back pain. Ergonomic workstations that promote proper lifting technique can reduce risk, but it is difficult to assess the workstations without constant risk monitoring. Machine learning systems using inertial measurement unit (IMU) data have been successful in various human activity recognition (HAR) applications, but limited work has been done regarding tasks for which it is difficult to collect significant amounts of data, such as manual lifting tasks. In this article, we discuss why traditional methods of data expansion may fail to improve performance on IMU data, and we present a machine learning system capable of detecting lifting action for assessing the risk for back pain using a relatively small amount of data. The proposed models outperform baseline HAR models and function on raw time-series data with minimal preprocessing for efficient real-time application. Author

      4. Boron nitride nanotubes (BNNT) are produced by many different methods leading to variances in physicochemical characteristics and impurities in the final product. These differences can alter the toxicity profile. The importance of understanding the potential pathological implications of this high aspect ratio nanomaterial is increasing as new approaches to synthesize and purify in large scale are being developed. In this review, we discuss the various factors of BNNT production that can influence its toxicity followed by summarizing the toxicity findings from in vitro and in vivo studies conducted to date, including a review of particle clearance observed with various exposure routes. To understand the risk to workers and interpret relevance of toxicological findings, exposure assessment at manufacturing facilities was discussed. Workplace exposure assessment of BNNT from two manufacturing facilities measured boron concentrations in personal breathing zones from non-detectable to 0.95 µg/m3 and TEM structure counts of 0.0123 ± 0.0094 structures/cm3, concentrations well below what was found with other engineered high aspect ratio nanomaterials like carbon nanotubes and nanofibers. Finally, using a purified BNNT, a “read-across” toxicity assessment was performed to demonstrate how known hazard data and physicochemical characteristics can be utilized to evaluate potential inhalation toxicity concerns. Graphical abstract: [Figure not available: see fulltext.]. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

    • Occupational Safety and Health - Mining
      1. Review of current coal rib control practices
        Guner D, Nowak S, Sherizadeh T, Sunkpal M, Mohamed K, Xue Y.
        Underground Space (China). 2023 ;9:53-75.
        The instability of coal ribs in underground mines continues to result in the injuries and fatalities of mine workers. The proper estimation and evaluation of primary and secondary support for coal ribs is still a challenging problem in the field of ground control science and requires further research and study. Although mining operations have various support design criteria and support methodologies for strata control, most rib support designs are still based on experience and local practices. This review study is intended to summarize the currently applied practices for rib support and control in various countries and mining conditions. Firstly, critical parameters that control the amount and type of required rib support are considered and evaluated. The study revealed that among these parameters that control the stability of coal ribs, mining depth, rib height, cleat orientation/condition, and coal strength are the most significant parameters. Secondly, current rib support application methods were also summarized. Similar to rock mass classification systems, some studies proposed a rib control rating system for practical estimation of the current rib condition and to estimate primary support requirements. These studies are classified and summarized into two groups (categorical and empirical) based on the required inputs and methodologies. Empirically based coal rib rating systems were closely examined, and the usefulness and intuitive aspects of each rating system were compared. This comprehensive literature review demonstrates that the Australian rating system, Analysis and Design of Rib Support (ADRS), and the new U.S. rating system, Coal Pillar Rib Rating (CPRR), are highly applicable for their regions. © 2022

    • Parasitic Diseases
      1. Novel application of one-step pooled molecular testing and maximum likelihood approaches to estimate the prevalence of malaria parasitaemia among rapid diagnostic test negative samples in Western Kenya
        Shah MP, Chebore W, Lyles RH, Otieno K, Zhou Z, Plucinski M, Waller LA, Odongo W, Lindblade KA, Kariuki S, Samuels AM, Desai M, Mitchell RM, Shi YP.
        Malar J. 2022 Nov 6;21(1):319.
        BACKGROUND: Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy. METHODS: A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area. RESULTS: The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6-15.3%) by individual qPCR, 9.5% (95% CI (8.5-10.5%) by strategy A, and 13.9% (95% CI 12.6-15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4-14.7%) in the main subset, 8.9% (95% CI 7.9-9.9%) by strategy A, 11.4% (95% CI 9.9-12.9%) by strategy B, and 12.8% (95% CI 11.2-14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing. CONCLUSIONS: Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost.

    • Reproductive Health
      1. Urinary phenol concentrations and fecundability and early pregnancy loss
        Rosen Vollmar AK, Weinberg CR, Baird DD, Wilcox AJ, Calafat AM, Deziel NC, Johnson CH, Jukic AM.
        Hum Reprod. 2022 Nov 8.
        STUDY QUESTION: Are urinary phenol concentrations of methylparaben, propylparaben, butylparaben, triclosan, benzophenone-3, 2,4-dichlorophenol or 2,5-dichlorophenol associated with fecundability and early pregnancy loss? SUMMARY ANSWER: 2,5-dichlorophenol concentrations were associated with an increased odds of early pregnancy loss, and higher concentrations of butylparaben and triclosan were associated with an increase in fecundability. WHAT IS KNOWN ALREADY: Phenols are chemicals with endocrine-disrupting potential found in everyday products. Despite plausible mechanisms of phenol reproductive toxicity, there are inconsistent results across few epidemiologic studies examining phenol exposure and reproductive function in non-fertility treatment populations. STUDY DESIGN, SIZE, DURATION: Specimens and data were from the North Carolina Early Pregnancy Study prospective cohort of 221 women attempting to conceive naturally from 1982 to 1986. This analysis includes data from 221 participants across 706 menstrual cycles, with 135 live births, 15 clinical miscarriages and 48 early pregnancy losses (before 42 days after the last menstrual period). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants collected daily first-morning urine specimens. For each menstrual cycle, aliquots from three daily specimens across the cycle were pooled within individuals and analyzed for phenol concentrations. To assess sample repeatability, we calculated intraclass correlation coefficients (ICCs) for each phenol. We evaluated associations between phenol concentrations from pooled samples and time to pregnancy using discrete-time logistic regression and generalized estimating equations (GEE), and early pregnancy loss using multivariable logistic regression and GEE. MAIN RESULTS AND THE ROLE OF CHANCE: ICCs for within-person variability across menstrual cycles in pooled phenol concentrations ranged from 0.42 to 0.75. There was an increased odds of early pregnancy loss with 2,5-dichlorophenol concentrations although the CIs were wide (5th vs 1st quintile odds ratio (OR): 4.79; 95% CI: 1.06, 21.59). There was an increased per-cycle odds of conception at higher concentrations of butylparaben (OR: 1.62; 95% CI: 1.08, 2.44) and triclosan (OR: 1.49; 95% CI: 0.99, 2.26) compared to non-detectable concentrations. No associations were observed between these endpoints and concentrations of other phenols examined. LIMITATIONS, REASONS FOR CAUTION: Limitations include the absence of phenol measurements for male partners and a limited sample size, especially for the outcome of early pregnancy loss, which reduced our power to detect associations. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to use repeated pooled measures to summarize phenol exposure and the first to investigate associations with fecundability and early pregnancy loss. Within-person phenol concentration variability underscores the importance of collecting repeated samples for future studies. Exposure misclassification could contribute to differences between the findings of this study and those of other studies, all of which used one urine sample to assess phenol exposure. This study also contributes to the limited literature probing potential associations between environmental exposures and early pregnancy loss, which is a challenging outcome to study as it typically occurs before a pregnancy is clinically recognized. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health (award number F31ES030594), the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (project numbers ES103333 and ES103086) and a doctoral fellowship at the Yale School of Public Health. The authors declare they have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

    • Substance Use and Abuse
      1. Evidence of the emergence of illicit benzodiazepines from online drug forums
        Sarker A, Al-Garadi MA, Ge Y, Nataraj N, McGlone L, Jones CM, Sumner SA.
        Eur J Public Health. 2022 Nov 7.
        Illicit or 'designer' benzodiazepines are a growing contributor to overdose deaths. We employed natural language processing (NLP) to study benzodiazepine mentions over 10 years on 270 online drug forums (subreddits) on Reddit. Using NLP, we automatically detected mentions of illicit and prescription benzodiazepines, including their misspellings and non-standard names, grouping relative mentions by quarter. On a collection of 17 861 755 posts between 2012 and 2021, we searched for 26 benzodiazepines (8 prescription; 18 illicit), detecting 173 275 mentions. The rate of posts about both prescription and illicit benzodiazepines increased consistently with increases in deaths involving both drug classes, illustrating the utility of surveillance via Reddit.

      2. Prevention and care opportunities for people who inject drugs in an HIV outbreak - Kanawha County, West Virginia, 2019-2021
        Bonacci RA, Moorman AC, Bixler D, Penley M, Wilson S, Hudson A, McClung RP.
        J Gen Intern Med. 2022 Nov 2.

      3. Tobacco use profiles by respiratory disorder status for adults in the wave 1-wave 4 Population Assessment of Tobacco and Health (PATH) study
        Cordova J, Pfeiffer RM, Choi K, Grana Mayne R, Baker L, Bachand J, Constantine K, Altekruse S, Reyes-Guzman C.
        Prev Med Rep. 2022 Dec;30:102016.
        Limited evidence exists on the association between electronic nicotine delivery systems (ENDS) and chronic respiratory disorders. This study examines the association of combustible tobacco and ENDS use with chronic respiratory disorders among US adults. Public-use data from the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014), Wave 2 (2014-2015), Wave 3 (2015-2016), and Wave 4 (2016-2018) were pooled. Analyses focused on adults with W1-W4 respiratory disorder data and current tobacco use at W4, as well as youth entering the adult cohort at W2 through W4 (N = 26,072). We fit weighted multivariable logistic regression models for each respiratory outcome (asthma, COPD, bronchitis) using W4 longitudinal weights. Cigarette smokers (adjusted odds ratio [AOR] = 0.8, 95 % CI 0.7-0.9) were less likely to report an asthma diagnosis (p = 0.013). In contrast, ENDS users (AOR = 6.5, 95 % CI 3.7-11.5), cigarette smokers (AOR = 6.1, 95 % CI 4.0-9.1), dual users of cigarettes and ENDS (AOR = 5.4, 95 % CI 3.4-8.7), current users of non-cigarette combustible, smokeless, and polytobacco products (AOR = 4.4, 95 % CI 3.1-6.4), and former users of any product (AOR = 3.0, 95 % CI 1.9-4.7) had significantly elevated odds of reporting a diagnosis of COPD (p < 0.001). Similar patterns to COPD were observed for bronchitis (p < 0.001). Current and former tobacco use, including ENDS, were significantly associated with prevalence of self-reported COPD and bronchitis after controlling for demographic and psychosocial confounders.

    • Zoonotic and Vectorborne Diseases
      1. Genomic comparisons confirm Giardia duodenalis sub-assemblage AII as a unique species
        Seabolt MH, Roellig DM, Konstantinidis KT.
        Front Cell Infect Microbiol. 2022 ;12:1010244.
        <i>Giardia duodenalis</i> is a parasitic flagellated protozoan which infects a wide range of mammalian hosts, including humans, and is subdivided into at least eight genetic assemblages commonly thought to represent cryptic species. Molecular studies have shown that <i>G. duodenalis</i> assemblage A, which parasitizes humans and animals, contains several phylogenetically distinct groupings known as sub-assemblages. Molecular studies employing poor phylogenetic-resolution markers routinely recover these sub-assemblages, implying that they represent evolutionarily distinct clades and possibly cryptic species, a hypothesis which is supported by epidemiologic trends. Here, we further tested this hypothesis by using available data from 41 whole genomes to characterize sub-assemblages and coalescent techniques for statistical estimation of species boundaries coupled to functional gene content analysis, thereby assessing the stability and distinctiveness of clades. Our analysis revealed two new sub-assemblage clades as well as novel signatures of gene content geared toward differential host adaptation and population structuring <i>via</i> vertical inheritance rather than recombination or panmixia. We formally propose sub-assemblage AII as a new species, <i>Giardia hominis</i>, while preserving the name <i>Giardia duodenalis</i> for sub-assemblage AI. Additionally, our bioinformatic methods broadly address the challenges of identifying cryptic microbial species to advance our understanding of emerging disease epidemiology, which should be broadly applicable to other lower eukaryotic taxa of interest. Giardia hominis n. sp. Zoobank LSID: urn:lsid: zoobank.org:pub:4298F3E1-E3EF-4977-B9DD-5CC59378C80E.

      2. Yellow fever resurgence: An avoidable crisis?
        Lindsey NP, Horton J, Barrett AD, Demanou M, Monath TP, Tomori O, Van Herp M, Zeller H, Fall IS, Cibrelus L, Erin Staples J.
        NPJ Vaccines. 2022 Nov 2;7(1):137.

      3. Morbidity and functional outcomes following Rocky Mountain spotted fever hospitalization-Arizona, 2002-2017
        Drexler NA, Close R, Yaglom HD, Traeger M, Parker K, Venkat H, Villarroel L, Brislan J, Pastula DM, Armstrong PA.
        Open Forum Infect Dis. 2022 Oct;9(10):ofac506.
        BACKGROUND: Rocky Mountain spotted fever (RMSF) is a deadly tickborne disease disproportionately affecting Arizona tribal communities. While the acute clinical effects of RMSF are well-documented, more complete understanding of the long-term health consequences is needed to provide guidance for providers and patients in highly impacted areas. METHODS: We performed a retrospective review of hospitalized RMSF cases from 2 tribal communities in Arizona during 2002-2017. Medical records from acute illness were abstracted for information on clinical presentation, treatment, and status at discharge. Surviving patients were interviewed about disease recovery, and patients reporting incomplete recovery were eligible for a neurologic examination. RESULTS: Eighty hospitalized cases of RMSF met our inclusion criteria and were reviewed. Of these, 17 (21%) resulted in a fatal outcome. Among surviving cases who were interviewed, most (62%) reported full recovery, 15 (38%) reported ongoing symptoms or reduced function following RMSF illness, and 9 (23%) had evidence of neurologic sequelae at the time of examination. Sequelae included impaired cognition, weakness, decreased deep tendon reflexes, seizures, and cranial nerve dysfunction. Longer hospitalization (25.5 days vs 6.2 days, P < .001), a higher degree of disability at discharge (median modified Rankin score 1 vs 0, P = .03), and delayed doxycycline administration (6.2 days vs 4.1 days, P = .12) were associated with long-term sequelae by logistic regression. CONCLUSIONS: Although the etiology of sequelae is not able to be determined using this study design, life-altering sequelae were common among patients surviving severe RMSF illness. Delayed administration of the antibiotic doxycycline after day 5 was the strongest predictor of morbidity.


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