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Issue 14, April 5, 2022

CDC Science Clips: Volume 14, Issue 14, April 5, 2022

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. High prevalence of pre-treatment HIV drug resistance in Papua New Guinea: findings from the first nationally representative pre-treatment HIV drug resistance studyexternal icon
        Gare J, Toto B, Pokeya P, Le LV, Dala N, Lote N, John B, Yamba A, Soli K, DeVos J, Paulin H, Wagar N, Zheng DP, Nishijima T, Boas P, Kelly-Hanku A, Gurung A.
        BMC Infect Dis. 2022 Mar 19;22(1):266.
        BACKGROUND: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. METHODS: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. RESULTS: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8-24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6-23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6-17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1-56.4%). CONCLUSIONS: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.

    • Chronic Diseases and Conditions
      1. Reported cases of end-stage kidney disease - United States, 2000-2019external icon
        Burrows NR, Koyama A, Pavkov ME.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):412-415.
        End-stage kidney disease (ESKD) (kidney failure requiring dialysis or transplantation) is a costly and disabling condition that often results in premature death (1). During 2019, Medicare fee-for-service expenditures for ESKD were $37.3 billion, accounting for approximately 7% of Medicare paid claims costs (1). Diabetes and hypertension remain the leading causes of ESKD, accounting for 47% and 29%, respectively, of patients who began ESKD treatment in 2019 (1). Compared with White persons, Black, Hispanic, and American Indian or Alaska Native persons are more likely to develop ESKD (1,2) and to have diagnosed diabetes (3). After declining for more than a decade, the incidence rate of ESKD with diabetes reported as the primary cause (ESKD from diabetes) has leveled off since 2010 (1,4). Further, after increasing for many years, the prevalence of diagnosed diabetes has also leveled off (4). Although these flattening trends in rates are important from a population perspective, the trend in the number of ESKD cases is important from a health systems resources perspective. Using United States Renal Data System (USRDS) 2000-2019 data, CDC examined trends in the number of incident and prevalent ESKD cases by demographic characteristics and by primary cause of ESKD. During 2000-2019, the number of incident ESKD cases increased by 41.8%, and the number of prevalent ESKD cases increased by 118.7%. Higher percentage changes in both incident and prevalent ESKD cases were among Asian, Hispanic, and Native Hawaiian or other Pacific Islander persons and among cases with hypertension or diabetes as the primary cause. Interventions to improve care and better manage ESKD risk factors among persons with diabetes and hypertension, along with increased use of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), and sodium-glucose cotransporter 2 (SGLT2) inhibitors shown to have kidney-protective benefits (5,6) might slow the increase and eventually reverse the trend in incident ESKD cases.

      2. Time to diagnosis of Duchenne muscular dystrophy remains unchanged: Findings from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), 2000-2015external icon
        Thomas S, Conway KM, Fapo O, Street N, Mathews KD, Mann J, Romitti PA, Soim A, Westfield C, Fox DJ, Ciafaloni E.
        Muscle Nerve. 2022 Mar 21.
        INTRODUCTION/AIMS: With current and anticipated disease-modifying treatments including gene therapy, an early diagnosis for Duchenne muscular dystrophy (DMD) is crucial to assure maximum benefit. In 2009 a study from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) showed an average diagnosis age of five years among males with DMD born from 1/1/1982 to 12/31/2000. Initiatives were implemented by the Centers for Disease Control and Prevention (CDC) and patient organizations to reduce time to diagnosis. We conducted a follow up study in a surveillance cohort born after 1/1/2000 to determine whether there has been an improvement in time to diagnosis. METHODS: We assessed the age of diagnosis among males with DMD born from 1/1/2000-12/31/2015 using data collected by six US MD STARnet surveillance sites (Colorado, Iowa, Western New York State, Piedmont region of North Carolina, South Carolina, and Utah). The analytic cohort included 221 males with definite or probable DMD diagnosis without a documented family history. We computed frequency counts and percentages for categorical variables; and means, medians, and standard deviations (SD) for continuous variables. RESULTS: The mean [median] ages in years of diagnostic milestones were: first signs 2.7 [2.0], first creatine kinase (CK) 4.6 [4.6], DNA/muscle biopsy testing 4.9 [4.8], and time from first signs to diagnostic confirmation 2.2 [1.4]. DISCUSSION: The time interval between first signs of DMD and diagnosis remains unchanged at 2.2 years. This results in lost opportunities for timely genetic counseling, implementation of standards of care, initiation of glucocorticoids and participation in clinical trials. This article is protected by copyright. All rights reserved.

    • Communicable Diseases
      1. Novel regimens of bedaquiline-pyrazinamide combined with moxifloxacin, rifabutin, delamanid and/or OPC-167832 in murine tuberculosis modelsexternal icon
        Tasneen R, Garcia A, Converse PJ, Zimmerman MD, Dartois V, Kurbatova E, Vernon AA, Carr W, Stout JE, Dooley KE, Nuermberger EL.
        Antimicrob Agents Chemother. 2022 Mar 22:e0239821.
        A recent landmark trial showed a 4-month regimen of rifapentine, pyrazinamide, moxifloxacin, and isoniazid (PZMH) to be noninferior to the 6-month standard of care. Here, two murine models of tuberculosis were used to test whether novel regimens replacing rifapentine and isoniazid with bedaquiline and another drug would maintain or increase the sterilizing activity of the regimen. In BALB/c mice, replacing rifapentine in the PZM backbone with bedaquiline (i.e., BZM) significantly reduced both lung CFU counts after 1 month and the proportion of mice relapsing within 3 months after completing 1.5 months of treatment. The addition of rifabutin to BZM (BZMRb) further increased the sterilizing activity. In the C3HeB/FeJ mouse model characterized by caseating lung lesions, treatment with BZMRb resulted in significantly fewer relapses than PZMH after 2 months of treatment. A regimen combining the new DprE1 inhibitor OPC-167832 and delamanid (BZOD) also had superior bactericidal and sterilizing activity compared to PZM in BALB/c mice and was similar in efficacy to PZMH in C3HeB/FeJ mice. Thus, BZM represents a promising backbone for treatment-shortening regimens. Given the prohibitive drug-drug interactions between bedaquiline and rifampin or rifapentine, the BZMRb regimen represents the best opportunity to combine, in one regimen, the treatment-shortening potential of the rifamycin class with that of BZM and deserves high priority for evaluation in clinical trials. Other 4-drug BZM-based regimens and BZOD represent promising opportunities for extending the spectrum of treatment-shortening regimens to rifamycin- and fluoroquinolone-resistant tuberculosis.

      2. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020external icon
        Govorkova EA, Takashita E, Daniels RS, Fujisaki S, Presser LD, Patel MC, Huang W, Lackenby A, Nguyen HT, Pereyaslov D, Rattigan A, Brown SK, Samaan M, Subbarao K, Wong S, Wang D, Webby RJ, Yen HL, Zhang W, Meijer A, Gubareva LV.
        Antiviral Res. 2022 Mar 12;200:105281.
        Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted.

      3. Detection of SARS-CoV-2 in neonatal autopsy tissues and placentaexternal icon
        Reagan-Steiner S, Bhatnagar J, Martines RB, Milligan NS, Gisondo C, Williams FB, Lee E, Estetter L, Bullock H, Goldsmith CS, Fair P, Hand J, Richardson G, Woodworth KR, Oduyebo T, Galang RR, Phillips R, Belyaeva E, Yin XM, Meaney-Delman D, Uyeki TM, Roberts DJ, Zaki SR.
        Emerg Infect Dis. 2022 Mar;28(3):510-517.
        Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

      4. Binding and neutralizing antibody responses to SARS-CoV-2 in young children exceed those in adultsexternal icon
        Karron RA, Garcia Quesada M, Schappell EA, Schmidt SD, Deloria Knoll M, Hetrich MK, Veguilla V, Doria-Rose NA, Dawood FS.
        JCI Insight. 2022 Mar 22.
        BACKGROUND: SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. METHODS: We compared Receptor Binding Domain binding antibody (RBDAb) titers and SARS-CoV-2 neutralizing antibody titers measured by pseudovirus neutralizing antibody assay (PsVNA) in serum specimens obtained from children aged 0-4 years, 5-17 years, and in adults aged 18-62 years at the time of enrollment in a prospective longitudinal household study of SARS-CoV-2 infection. RESULTS: Among 56 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (416 vs. 31, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had only 2-fold higher neutralizing Ab than adults, resulting in higher binding to neutralizing (B/N) Ab ratios compared to adults (2.36 vs. 0.35 for ID50, P=0.0002). CONCLUSIONS: These findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutralizing Ab to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years. FUNDING: Supported by CDC Award 75D30120C08737.

      5. SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-21external icon
        Cohen C, Kleynhans J, von Gottberg A, McMorrow ML, Wolter N, Bhiman JN, Moyes J, du Plessis M, Carrim M, Buys A, Martinson NA, Kahn K, Tollman S, Lebina L, Wafawanaka F, du Toit JD, Gómez-Olivé FX, Dawood FS, Mkhencele T, Sun K, Viboud C, Tempia S.
        Lancet Infect Dis. 2022 Mar 14.
        BACKGROUND: By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa. METHODS: We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members). FINDINGS: 222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals. INTERPRETATION: In this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up. FUNDING: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.

      6. Hospitalization of infants and children aged 0-4 years with laboratory-confirmed COVID-19 - COVID-NET, 14 States, March 2020-February 2022external icon
        Marks KJ, Whitaker M, Agathis NT, Anglin O, Milucky J, Patel K, Pham H, Kirley PD, Kawasaki B, Meek J, Anderson EJ, Weigel A, Kim S, Lynfield R, Ropp SL, Spina NL, Bennett NM, Shiltz E, Sutton M, Talbot HK, Price A, Taylor CA, Havers FP.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):429-436.
        The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, has been the predominant circulating variant in the United States since late December 2021.* Coinciding with increased Omicron circulation, COVID-19-associated hospitalization rates increased rapidly among infants and children aged 0-4 years, a group not yet eligible for vaccination (1). Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)(†) data were analyzed to describe COVID-19-associated hospitalizations among U.S. infants and children aged 0-4 years since March 2020. During the period of Omicron predominance (December 19, 2021-February 19, 2022), weekly COVID-19-associated hospitalization rates per 100,000 infants and children aged 0-4 years peaked at 14.5 (week ending January 8, 2022); this Omicron-predominant period peak was approximately five times that during the period of SARS-CoV-2 B.1.617.2 (Delta) predominance (June 27-December 18, 2021, which peaked the week ending September 11, 2021).(§) During Omicron predominance, 63% of hospitalized infants and children had no underlying medical conditions; infants aged <6 months accounted for 44% of hospitalizations, although no differences were observed in indicators of severity by age. Strategies to prevent COVID-19 among infants and young children are important and include vaccination among currently eligible populations (2) such as pregnant women (3), family members, and caregivers of infants and young children (4).

      7. Two-month follow-up of persons with SARS-CoV-2 infection-Zambia, September 2020: a cohort studyexternal icon
        Zulu JE, Banda D, Hines JZ, Luchembe M, Sivile S, Siwingwa M, Kampamba D, Zyambo KD, Chirwa R, Chirwa L, Malambo W, Barradas D, Sinyange N, Agolory S, Mulenga LB, Fwoloshi S.
        Pan Afr Med J. 2022 ;41:26.
        INTRODUCTION: COVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms. METHODS: in September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose polymerase chain reaction (PCR) tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions. RESULTS: of 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms. CONCLUSION: a notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ´post-acute COVID-19 clinics´ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.

      8. Factors associated with active syphilis among men and women aged 15 years and older in the Zimbabwe Population-based HIV Impact Assessment (2015-2016)external icon
        Ruangtragool L, Silver R, Machiha A, Gwanzura L, Hakim A, Lupoli K, Musuka G, Patel H, Mugurungi O, Tippett Barr BA, Rogers JH.
        PLoS One. 2022 ;17(3):e0261057.
        INTRODUCTION: Ulcerative STIs, including syphilis, increase the risk for HIV acquisition and transmission due to the presence of ulcers/chancres that serve as a point-of-entry and exit for HIV. In Zimbabwe, diagnosis of syphilis often occurs in pregnant women who seek ANC services where syphilis testing is offered, and among men and women who seek health care for STIs. Zimbabwe's national syphilis estimates are based on these diagnosed cases, with little information available about the prevalence of untreated syphilis among the general population. This analysis uses data from ZIMPHIA (2015-2016) to describe factors associated with active syphilis among men and women ages 15 years and older. METHODS: ZIMPHIA collected blood specimens for HIV and syphilis testing from 22,501 consenting individuals (ages 15 years and older). Household HIV testing used the national HIV rapid-testing algorithm with HIV-positive results confirmed at satellite laboratories using Geenius HIV-1/2 rapid test (Bio-rad, Hercules, California, USA). Point-of-care non-Treponemal and Treponemal syphilis testing was performed using Chembio's Dual-Path Platform Syphilis Screen & Confirm Assay. Factors associated with active syphilis were explored using multiple variable, weighted logistic regression and were stratified by gender. RESULTS: The likelihood of active syphilis in HIV-positive females was 3.7 times greater in HIV-positive females than HIV-negative females (aOR: 3.7, 95% CI 2.3-5.9). Among males odds of having active syphilis was 5 times higher among those that engaged in transactional sex than those who did not have sex or transactional sex (aOR: 5.3, 95% CI 1.9-14.7), and 6 times higher if HIV positive versus negative (aOR: 5.9, 95% CI 3.0-12.0). Urban residence, province, education (highest attended), marital status, number of sex partners, consistency of condom use, pregnancy status (females), and circumcision status (males) were not significant in the adjusted model for either females or males. CONCULSION: HIV status was found to be the only factor associated with active syphilis in both females and males. Given the persistent link between HIV and active syphilis, it is prudent to link individuals' diagnoses and treatments, as recommended by the WHO. Enhanced integration of STI and HIV services in health delivery points such as ANC, reproductive services, or male circumcision clinics, combined with consistent, targeted outreach to high-risk populations and their partners, may assist the MOHCC to eliminate active syphilis in Zimbabwe.

      9. The impact of COVID-19 pandemic on the 2020 hepatitis C cascade of care in the Republic of Georgiaexternal icon
        Gamkrelidze A, Handanagic S, Shadaker S, Turdziladze A, Tsereteli M, Getia V, Aslanikashvili A, Surguladze S, Gvinjilia L, Kuchuloria T, Tskhomelidze I, Armstrong PA.
        Public Health. 2022 Feb 9;205:182-186.
        OBJECTIVES: In 2015, the Republic of Georgia initiated a National Hepatitis C Elimination Program, with a goal of 90% reduction in prevalence of chronic hepatitis C virus (HCV) infections by 2020. In this article, we explore the impact of the COVID-19 pandemic on the 2020 hepatitis C cascade of care in Georgia. STUDY DESIGN: Retrospective analytic study. METHODS: We used a national screening registry that includes hospitals, blood banks, antenatal clinics, harm reduction sites, and other programs and services to collect data on hepatitis C screening. A separate national treatment database was used to collect data on viremia and diagnostic testing, treatment initiation, and outcome including testing for and achieving sustained virologic response (SVR). We used these databases to create hepatitis C care cascades for 2020 and 2019. Bivariate associations for demographic characteristics and screening locations per year and care cascade comparisons were assessed using a chi-squared test. RESULTS: In 2020 compared to 2019, the total number of persons screened for HCV antibodies decreased by 25% (from 975,416 to 726,735), 59% fewer people with viremic infection were treated for HCV infection (3188 vs. 7868), 46% fewer achieved SVR (1345 vs. 2495), a significantly smaller percentage of persons with viremic infection initiated treatment for HCV (59% vs. 62%), while the percentage of persons who achieved SVR (99.2% vs. 99.3%) remained stable. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the hepatitis C elimination program in Georgia. To ensure Georgia reaches its elimination goals, mitigating unintended consequences of delayed diagnosis and treatment of hepatitis C due to the COVID-19 pandemic are paramount.

      10. BACKGROUND: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) disproportionately affect men who have sex with men (MSM). Data on the prevalence, anatomical distribution, and correlates of NG and CT infections among MSM in Vietnam are limited. METHODS: Between July 2017 and April 2019, MSM 16 years or older, without HIV were enrolled into an observational cohort study. Baseline data, including sociodemographics, sexual behavior, and HIV status were collected. NG and CT testing were performed on urine, rectal, and pharyngeal specimens. Multivariate logistic regression models identified factors associated with NG and CT infections at baseline. RESULTS: In total, 1489 participants underwent NG/CT testing. The median age was 22 years (IQR: 20 - 26). There were 424 (28.5%) NG or CT infections; 322 (21.6%) with CT and 173 (11.6%) with NG. Rectal infections were most common for CT (73.9%), while pharyngeal infections were most common for NG (70.5%). Independent risk factors for CT or NG infection included: ≥2 sex partners in the prior month (adjusted odds ratio [aOR] = 2.04; 95% CI: 1.44, 2.91), condomless anal sex (aOR = 1.44, 95% CI: 1.12, 1.86), and meeting sex partners online (aOR = 1.35; 95% CI: 1.03, 1.76). Recent genitourinary or rectal symptoms were not associated with infections. CONCLUSIONS: The overall and extragenital prevalence of NG and CT infections were high within this sample of young MSM without HIV in Hanoi. Testing limited to urethral specimens would have missed nearly three-quarters of CT and NG infections, supporting the need for routine testing at multiple anatomic sites.

      11. Primary and secondary syphilis among men who have sex with men and women, 2010-2019external icon
        Learner ER, Grey JA, Bernstein K, Kirkcaldy RD, Torrone EA.
        Sex Transm Dis. 2022 Mar 10.
        The relative proportion of cases of P&S syphilis among men who have sex with men and women reported through national case report data from 2010 through 2019 appeared stable overall and stratified by race/ethnicity, region, and age group, but case counts increased.

      12. Unrecognized introductions of SARS-CoV-2 into the US state of Georgia shaped the early epidemicexternal icon
        Babiker A, Martin MA, Marvil C, Bellman S, Petit Iii RA, Bradley HL, Stittleburg VD, Ingersoll J, Kraft CS, Li Y, Zhang J, Paden CR, Read TD, Waggoner JJ, Koelle K, Piantadosi A.
        Virus Evol. 2022 ;8(1):veac011.
        In early 2020, as diagnostic and surveillance responses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ramped up, attention focused primarily on returning international travelers. Here, we build on existing studies characterizing early patterns of SARS-CoV-2 spread within the USA by analyzing detailed clinical, molecular, and viral genomic data from the state of Georgia through March 2020. We find evidence for multiple early introductions into Georgia, despite relatively sparse sampling. Most sampled sequences likely stemmed from a single or small number of introductions from Asia three weeks prior to the state's first detected infection. Our analysis of sequences from domestic travelers demonstrates widespread circulation of closely related viruses in multiple US states by the end of March 2020. Our findings indicate that the exclusive focus on identifying SARS-CoV-2 in returning international travelers early in the pandemic may have led to a failure to recognize locally circulating infections for several weeks and point toward a critical need for implementing rapid, broadly targeted surveillance efforts for future pandemics.

    • Community Health Services
      1. Factors associated with retention in HIV prevention and treatment clinical services among female sex workers enrolled in a Sex Workers' Outreach Program (SWOP) in Nairobi, Kenyaexternal icon
        Eshikumo P, Awuor P, Blanco N, Lavoie MC, Whittington A, Wangusi R, Kimani J, Ngunu C, Omai J, Obwiri W, Mutisya I, Koech E.
        AIDS Behav. 2022 Mar 17.
        Female sex workers (FSWs) are among the key populations (KP) prioritized for comprehensive HIV programming in Kenya. Retention in the program is critical for prevention of HIV acquisition and transmission among FSWs and their sexual partners. We conducted a retrospective cohort analysis of data collected from FSWs enrolled between October 2016 and September 2017 at seven drop-in centers (DICs) in Nairobi, Kenya, to assess factors associated with retention in HIV prevention and treatment services. We found a 3- and 12- month retention of 24% and 17%, respectively. FSWs aged 20-34 years old were less likely to be retained compared to those 50 years or older. FSWs enrolled in a DIC located in their sub-county of residence or reporting ever using HIV pre- or post-exposure prophylaxis were more likely to be retained. Engaging young FSWs to identify strategies to enhance retention should be prioritized. Strengthening the referral system across DICs may provide opportunities to enhance retention in facilities closer to their residence. Implementation research is needed to gain an additional understanding of the health services needs and preferences among FSWs to optimize retention for this population.

      2. Door-to-door hepatitis C screening in Georgia: An innovative model to increase testing and linkage to careexternal icon
        Butsashvili M, Zurashvili T, Kamkamidze G, Kajaia M, Gulbiani L, Gamezardashvili A, Gvinjilia L, Kuchuloria T, Gamkrelidze A, Shadaker S, Nasrullah M, Averhoff F, Armstrong PA.
        J Med Screen. 2022 Mar 16:9691413221086497.
        OBJECTIVES: Georgia has a high prevalence of hepatitis C virus (HCV) infection. In 2015 a national HCV elimination program was launched providing free access to screening and treatment. To achieve elimination, innovative approaches to increase screening coverage and linkage to care are needed. This study estimates feasibility, acceptability, and outcomes of the door-to-door pilot HCV testing program in three cities. METHODS: Households were approached by system random sampling and all members were invited for study participation. Researchers used a detailed guide for conducting door-to-door testing and served as case navigators to link anti-HCV-positive individuals to care. RESULTS: Testing acceptance rate was high. In total 4804 individuals were tested and 48 (1.0%) were HCV positive. Among the entire sample of newly and previously tested individuals, overall HCV antibody prevalence was 3.6%. Through case navigation, of 48 newly identified and 26 previously identified anti-HCV-positive individuals, 42 (87.5%) and 17 (65.4%), respectively, were successfully linked to care. CONCLUSIONS: Door-to-door HCV testing has potential to increase testing uptake. Such community-based approaches not only improve testing, but can also serve to increase linkage to care, which is important in achieving the goal of HCV elimination. The study provides a model for high prevalence countries aiming to eliminate hepatitis C.

      3. Remote health: Optimizing the delivery of sexual health careexternal icon
        Habel MA, Sullivan P, Hall C, Aral S.
        Sex Transm Dis. 2022 Mar 21.

      4. BACKGROUND: Human immunodeficiency virus (HIV) partner services are an essential component of comprehensive HIV prevention and care. We examined factors associated with partner notification, HIV testing, and HIV positivity among partners of HIV-diagnosed persons (index persons) contacted by Centers for Disease Control and Prevention (CDC)-funded state and local health departments. METHODS: We analyzed partner service data submitted to the CDC by 61 state and local health departments from 2013 to 2017. Using multivariate Poisson regression-adjusted for clustering effects among partners reported by a common index person-we assessed associations between 3 outcomes of interest (partner notification, HIV testing, and HIV positivity) and the demographic characteristics, risk behaviors, geographic region, and service year of index persons and their partners. RESULTS: A total of 51,368 sexual and/or needle-sharing partners were matched with 33,524 index persons. Of notifiable partners, 97.2% were notified of their potential HIV exposure, and 52.3% were tested for HIV. Among 21,842 notified and tested partners, 23.8% were newly diagnosed with an HIV infection. Partner notification, HIV testing, and HIV positivity were associated with both partner and index person characteristics (individually and interactively), geographic region, and year of service. CONCLUSIONS: Partner service programs provided through CDC-funded health departments were effective in both partner notification and identification of undiagnosed HIV infection among partners. However, HIV testing rate among notified partners remained low. Implementing strategies to address gaps in HIV testing can contribute toward ending the HIV epidemic in the United States.

      5. Testing modality associated with fast-track ART initiation in Botswanaexternal icon
        Lavoie MC, Blanco N, Keapoletswe K, Marima R, Ntwayagae OA, Sebina KB, Loeto P, Mogomotsi PG, Saleeb PG, Ndwapi N, Stafford KA.
        Trop Med Int Health. 2022 Mar 17.
        OBJECTIVES: The aim of this study was to identify community testing modalities associated with fast-track ART initiation in Botswana. METHODS: We conducted a retrospective cohort study that included all Botswana citizens 15 years or older who were newly identified as HIV-positive from 1 May 2017 to 31 January 2019, in Mahalapye and Southern districts. We used Poisson regression with robust error variance and generalised linear mixed models to control for cluster effects to model risk of ART initiation within 7 and 30 days of HIV diagnosis, testing modality factors. RESULTS: A total of 1436 individuals were newly identified HIV-positive, with men accounting for 60% across all testing modalities. 22% of all HIV-positive individuals were initiated on ART within 7 days. Clients diagnosed through index testing were more likely to be started on ART within 7 days (adjusted risk ratio [aRR] = 1.38, 95% CI 1.37-1.38) and 30 days (aRR = 1.17, 95% CI 1.09-1.26) than those diagnosed through mobile/outreach testing. CONCLUSIONS: Community HIV testing can complement facility-based testing by reaching individuals who may be less likely to seek HIV services at a facility, such as men. Monitoring ART initiation by testing modalities is critical to identify the optimal ones and to guide continuous programme improvement.

    • Disease Reservoirs and Vectors
      1. Effective oral RNA interference (RNAi) administration to adult Anopheles gambiae mosquitoesexternal icon
        Taracena M, Hunt C, Pennington P, Andrew D, Jacobs-Lorena M, Dotson E, Wells M.
        J Vis Exp. 2022 Mar 1(181).
        RNA interference has been a heavily utilized tool for reverse genetic analysis for two decades. In adult mosquitoes, double-stranded RNA (dsRNA) administration has been accomplished primarily via injection, which requires significant time and is not suitable for field applications. To overcome these limitations, here we present a more efficient method for robust activation of RNAi by oral delivery of dsRNA to adult Anopheles gambiae. Long dsRNAs were produced in Escherichia coli strain HT115 (DE3), and a concentrated suspension of heat-killed dsRNA-containing bacteria in 10% sucrose was offered on cotton balls ad-libitum to adult mosquitoes. Cotton balls were replaced every 2 days for the duration of the treatment. Use of this method to target doublesex (a gene involved in sex differentiation) or fork head (which encodes a salivary gland transcription factor) resulted in reduced target gene expression and/or protein immunofluorescence signal, as measured by quantitative Real-Time PCR (qRT-PCR) or fluorescence confocal microscopy, respectively. Defects in salivary gland morphology were also observed. This highly flexible, user-friendly, low-cost, time-efficient method of dsRNA delivery could be broadly applicable to target genes important for insect vector physiology and beyond.

    • Environmental Health
      1. Investigating dilution ventilation control strategies in a modern U.S. school bus in the context of the COVID-19 pandemicexternal icon
        Van Dyke M, King B, Esswein E, Adgate J, Dally M, Kosnett M.
        J Occup Environ Hyg. 2022 Mar 21:1-16.
        Fresh air ventilation has been identified as a widely accepted engineering control effective at diluting air contaminants in enclosed environments. The goal of this study was to evaluate the effects of selected ventilation measures on air change rates in school buses. Air changes per hour (ACH) of outside air were measured using a well-established carbon dioxide (CO(2)) tracer gas decay method. Ventilation was assessed while stationary and while traversing standardized route during late autumn/winter months in Colorado. Seven CO(2) sensors located at the driver's seat and at passenger seats in the front, middle, and rear of the bus yielded similar and consistent measurements. Buses exhibited little air exchange in the absence of ventilation (ACH =0.13 when stationary; ACH =1.85 when mobile). Operating the windshield defroster to introduce fresh outside air increased ACH by approximately 0.5-1 ACH during mobile and stationary phases. During the mobile phase (average speed of 23 miles per hour (mph) ), the combination of the defroster and two open ceiling hatches (with a powered fan on the rear hatch) yielded an ACH of approximately 9.3 ACH. A mobile phase ACH of 12.4 was achieved by the combination of the defroster, ceiling hatches, and six passenger windows open 2 inches in the middle area of the bus. A maximum mobile phase ACH of 22.1 was observed by using the defroster, open ceiling hatches, driver window open 4 inches, and every other passenger window open 2 inches. For reference, ACHs recommended in patient care settings where patients are being treated for airborne infectious diseases range from 6 to ≥12 ACHs. The results indicate that practical ventilation protocols on school buses can achieve air change rates thought to be capable of reducing airborne viral transmission to the bus driver and student passengers during the COVID-19 pandemic.

    • Epidemiology and Surveillance
      1. Acceptability and feasibility of HIV recent infection surveillance by healthcare workers using a rapid test for recent infection at HIV testing sites - Malawi, 2019external icon
        Arons MM, Curran KG, Msukwa M, Theu J, O'Malley G, Ernst A, Namakhoma I, Bello G, Telford C, Shanmugam V, Parekh B, Kim E, Dobbs T, Payne D, Gugsa S.
        BMC Health Serv Res. 2022 Mar 15;22(1):341.
        BACKGROUND: The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities. SETTING: At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS). METHODS: Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text. RESULTS: We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients. CONCLUSION: This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.

      2. Cloud-based influenza surveillance system in emergency departments using molecular-based testing: Advances and challengesexternal icon
        Shaw-Saliba K, Hansoti B, Burkom H, Martinez DA, DuVal A, Lee B, Chau P, McBride B, Hsieh YH, Sathananthan V, Persing D, Turnlund M, Shively R, Dugas A, Rothman RE.
        West J Emerg Med. 2022 Feb 14;23(2):115-123.
        INTRODUCTION: Electronic influenza surveillance systems aid in health surveillance and clinical decision-making within the emergency department (ED). While major advances have been made in integrating clinical decision-making tools within the electronic health record (EHR), tools for sharing surveillance data are often piecemeal, with the need for data downloads and manual uploads to shared servers, delaying time from data acquisition to end-user. Real-time surveillance can help both clinicians and public health professionals recognize circulating influenza earlier in the season and provide ongoing situational awareness. METHODS: We created a prototype, cloud-based, real-time reporting system in two large, academically affiliated EDs that streamed continuous data on a web-based dashboard within hours of specimen collection during the influenza season. Data included influenza test results (positive or negative) coupled with test date, test instrument geolocation, and basic patient demographics. The system provided immediate reporting to frontline clinicians and to local, state, and federal health department partners. RESULTS: We describe the process, infrastructure requirements, and challenges of developing and implementing the prototype system. Key process-related requirements for system development included merging data from the molecular test (GeneXpert) with the hospitals' EHRs, securing data, authorizing/authenticating users, and providing permissions for data access refining visualizations for end-users. CONCLUSION: In this case study, we effectively integrated multiple data systems at four distinct hospital EDs, relaying data in near real time to hospital-based staff and local and national public health entities, to provide laboratory-confirmed influenza test results during the 2014-2015 influenza season. Future innovations need to focus on integrating the dashboard within the EHR and clinical decision tools.

    • Food Safety
      1. Tools and techniques to promote proper food cooling in restaurantsexternal icon
        Hedeen ND, Schaffner D, Brown LG.
        J Environ Health. 2022 ;84(7):8-11.
        Slow cooling of hot foods is a common pathogen proliferation factor contributing to restaurant-related outbreaks. The Food and Drug Administration (FDA) model Food Code provides guidelines on the time and temperatures needed for proper cooling and recommends several methods to facilitate rapid food cooling. Restaurants continue to struggle with proper cooling even given these guidelines (Hedeen &amp; Smith, 2020). Research summarized in this guest commentary indicates that portioning foods into containers with a depth of &lt;3 in. and ventilating the containers during the cooling process promote rapid cooling. Restaurant operators and health department inspectors could use these cooling methods to maximize cooling efforts. Additionally, a simple method (using a mathematical equation) could help restaurant operators and inspectors to estimate the cooling rates of foods. This simple method uses only two food temperatures taken at any two points in the cooling process (using the equation [Log(T1 - Tdf) - Log(T2 - Tdf)]/δt) to estimate whether the food is expected to meet FDA cooling guidelines. This method allows operators and inspectors to identify foods unlikely to meet FDA guidelines and take corrective actions on those foods without having to monitor food temperatures for the entire cooling process, which typically takes 6 hr. More research is underway to further refine aspects of this method. © 2022, National Environmental Health Association. All rights reserved.

    • Global Health
      1. Cross-sectional survey of SARS-CoV-2 testing at US airports and one health department's proactive management of travelersexternal icon
        Shaum A, Figueroa A, Lee D, Ertl A, Rothney E, Borntrager D, Davenport E, Gulati RK, Brown CM.
        Trop Dis Travel Med Vaccines. 2022 Mar 20;8(1):8.
        BACKGROUND: Many health departments and private enterprises began offering SARS-CoV-2 testing to travelers at US airports in 2020. Persons with positive SARS-CoV-2 test results who have planned upcoming travel may be subject to US federal public health travel restrictions. We assessed availability of testing for SARS-CoV-2 at major US airports. We then describe the management of cases and close contacts at Denver International Airport's testing site. METHODS: We selected 100 US airports. Online surveys were conducted during November-December 2020 and assessed availability of testing for air travelers, flight crew, and airport employees. Respondents included health department (HD) staff or airport directors. We analyzed testing data and management practices for persons who tested positive and their close contacts at one airport (Denver International) from 12/21/2020 to 3/31/2021. RESULTS: Among the 100 selected airports, we received information on 77 airports; 38 (49%) had a testing site and several more planned to offer one (N = 7; 9%). Most sites began testing in the fall of 2020. The most frequently offered tests were RT-PCR or other NAAT tests (N = 28). Denver International Airport offered voluntary SARS-CoV-2 testing. Fifty-four people had positive results among 5724 tests conducted from 12/21/2020 to 3/31/2021 for a total positivity of < 1%. Of these, 15 were travelers with imminent flights. The Denver HD issued an order requiring the testing site to immediately report cases and notify airlines to cancel upcoming flight itineraries for infected travelers and their traveling close contacts, minimizing the use of federal travel restrictions. CONCLUSIONS: As of December 2020, nearly half of surveyed US airports had SARS-CoV-2 testing sites. Such large-scale adoption of airport testing for a communicable disease is unprecedented and presents new challenges for travelers, airlines, airports, and public health authorities. This assessment was completed before the US and other countries began enforcing entry testing requirements; testing at airports will likely increase as travel demand returns and test requirements for travel evolve. Lessons from Denver demonstrate how HDs can play a key role in engaging airport testing sites to ensure people who test positive for SARS-CoV-2 immediately before travel do not travel on commercial aircraft.

    • Health Communication and Education

      1. Increases in student knowledge and protective behaviors following enhanced supports for sexual health education in a large, urban school districtexternal icon
        Rasberry CN, Young E, Szucs LE, Murray C, Sheremenko G, Parker JT, Roberts G, Lesesne CA.
        J Adolesc Health. 2022 Apr;70(4):588-597.
        PURPOSE: School-based sexual health education (SHE) can teach students critical knowledge and skills. For effective SHE, school districts can offer support, including strong curricula and professional development. This study assessed changes in students' sexual health knowledge and sexual behaviors following implementation of enhanced support for SHE delivery in one school district. METHODS: Sexual health knowledge was assessed at the beginning and end of middle and high school health education classes in a large, urban district (n = 7,555 students). Sexual behaviors were assessed using Youth Risk Behavior Survey data from the district (2015 and 2017) and state (2017). Analyses explored differences in behavior from 2015 (n = 2,596) to 2017 (n = 3,371) among intervention district students and compared intervention district students (n = 3,371) to other students in the same state (n = 1,978). RESULTS: Hierarchical linear model regression analyses revealed significant knowledge gains among students. Logistic regression results revealed that among students in the intervention district, 6 of 16 examined behaviors moved in the intended direction from 2015 to 2017; 1 moved in the unintended direction. Logistic regression results of 2017 data revealed that in comparison of intervention district students to other students in the state, intervention district students had significantly higher odds of reporting condom use at last sex (adjusted odds ratio [AOR] = 1.36, 95% confidence interval [CI] = 1.07-1.72) and significantly lower odds of reporting having had sex with 4+ persons (AOR = .72, 95% CI = .55-.94) or alcohol or drug use before last sex (AOR = .63, 95% CI = .42-.94). CONCLUSIONS: Findings suggest potential effects of the district's SHE in increasing knowledge and improving behaviors and experiences among youth.

    • Health Economics
      1. Monetised estimated quality-adjusted life year (QALY) losses for non-fatal injuriesexternal icon
        Miller GF, Florence C, Barnett SB, Peterson C, Lawrence BA, Miller TR.
        Inj Prev. 2022 Mar 16.
        BACKGROUND: Quality-adjusted life years (QALYs) provide a means to compare injuries using a common measurement which allows quality of life and duration of life from an injury to be considered. A more comprehensive picture of the economic losses associated with injuries can be found when QALY estimates are combined with medical and work loss costs. This study provides estimates of QALY loss. METHODS: QALY loss estimates were assigned to records in the 2018 National Electronic Injury Surveillance System - All Injury Program. QALY estimates by body region and nature of injury were assigned using a combination of previous research methods. Injuries were rated on six dimensions, which identify a set of discrete qualitative impairments. Additionally, a seventh dimension, work-related disability, was included. QALY loss estimates were produced by intent and mechanism, for all emergency department-treated cases, by two disposition groups. RESULTS: Lifetime QALY losses ranged from 0.0004 to 0.388 for treated and released injuries, and from 0.031 to 3.905 for hospitalised injuries. The 1-year monetary value of QALY losses ranged from $136 to $437 000 among both treated and released and hospitalised injuries. The lifetime monetary value of QALY losses for hospitalised injuries ranged from $16 000 to $2.1 million. CONCLUSIONS: These estimates provide information to improve knowledge about the comprehensive economic burden of injuries; direct cost elements that can be measured through financial transactions do not capture the full cost of an injury. Comprehensive assessment of the long-term cost of injuries, including quality of life losses, is critical to accurately estimate the economic burden of injuries.

      2. We investigate associations between a diabetes diagnosis and financial and instrumental transfers between parents and adult children. Data are from the Panel Study of Income Dynamics, a nationally representative household cohort from the USA with prospective data on diabetes and cross-sectional data on transfers for households in which the head and partner had adult children (n = 4210) or surviving parents (n = 6930). We used survey-adjusted multivariate logistic regressions to compare the probabilities of receiving and giving intergenerational transfers in households where the head and/or partner were recently diagnosed with diabetes or had diabetes-related limitations in daily activities. Households with a diabetes diagnosis in the previous 2 years were less likely than those without diabetes to give money to adult children (OR = 0.46, p < 0.01). While recent onset of diabetes was not consistently associated with receiving transfers, transfers were more likely with progressing disease: households in which the head or partner had been diagnose more than 5 years earlier were more likely to receive instrumental help from an adult child (OR = 1.24; p < 0.05); those with diabetes-related limitations were more likely to receive assistance, especially instrumental help from adult children (OR = 1.43; p < 0.01) than households without diabetes. The onset of a chronic health condition affects not only individuals’ own health and financial wellbeing; it also has implications for their adult children and parents, for family relations, time allocation, and financial resources. These broader implications of chronic disease may perpetuate health and economic inequalities across generations. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

      3. Cost-effectiveness of hepatitis B testing and vaccination of adults seeking care for sexually transmitted infectionsexternal icon
        Hutton D, Toy M, Salomon JA, Conners EE, Nelson NP, Harris AM, So S.
        Sex Transm Dis. 2022 Mar 19.
        BACKGROUND: The estimated number of people living with hepatitis B virus (HBV) infection acquired through sexual transmission was 103,000 in 2018, with an estimated incidence of 8,300 new cases per year. While hepatitis B (HepB) vaccination is recommended by the Advisory Committee for Immunization Practices for persons seeking evaluation and treatment for sexually transmitted infections (STI), pre-vaccination testing is not yet recommended. Screening may link persons with chronic hepatitis B (CHB) to care and reduce unnecessary vaccination. METHODS: We used a Markov model to calculate the health impact, and cost-effectiveness of one-time HBV testing combined with the first dose of the hepatitis B vaccine for adults seeking care for STI. We ran a lifetime, societal perspective analysis for a hypothetical population of 100,000 ages 18-69 years. The disease progression estimates were taken from recent cohort studies and meta-analyses. In the US, an intervention that costs less than $100,000 per quality adjusted life year (QALY) is generally considered cost-effective. The strategies that were compared were: 1) vaccination without HBV screening, 2) vaccination and HBsAg screening, 3) vaccination and screening with HBsAg and anti-HBs, and 4) vaccination and screening with HBsAg, anti-HBs and anti-HBc. Data were obtained from Centers for Medicare and Medicaid services reimbursement, the CDC vaccine price list, and additional cost-effectiveness literature. RESULTS: Compared with current recommendations, the addition of one-time HBV testing is cost saving and would prevent an additional 138 cases of cirrhosis, 47 cases of decompensated cirrhosis, 90 cases of hepatocellular carcinoma, 33 liver transplants, and 163 HBV-related deaths, and gain 2185 QALYs, per 100,000 adults screened. Screening with the 3-tests panel would save $41.6-$42.7 million /100,000 adults tested compared with $41.5-$42.5 million for the 2-tests panel and $40.2-$40.3 million for HBsAg alone. CONCLUSIONS: One-time HBV pre-vaccination testing in addition to HepB vaccination for unvaccinated adults seeking care for STI would save lives, prevent new infections and unnecessary vaccination, and is cost saving.

    • Health Equity and Health Disparities
      1. Stigma, social cohesion, and HIV risk among sexual and gender minorities in two cities in Zimbabweexternal icon
        Miller SS, Mantell JE, Parmley LE, Musuka G, Chingombe I, Mapingure M, Rogers JH, Wu Y, Hakim AJ, Mugurungi O, Samba C, Harris TG.
        AIDS Behav. 2022 Mar 18.
        Though stigma is a recognized contributor to the disproportionate HIV burden among sexual and gender minorities (SGM) in sub-Saharan Africa, data describing this association among Zimbabwean SGM are limited. We examined relationships between SGM stigma and HIV and the potential for social cohesion to moderate the association among Zimbabwean men who have sex with men, transgender women, and genderqueer individuals. Consenting participants (n = 1511) recruited through respondent-driven sampling for a biobehavioral survey in Harare and Bulawayo completed structured interviews and received HIV testing. Reported SGM stigma was common (68.9% in Harare and 65.3% in Bulawayo) and associated with HIV infection in Harare (adjusted prevalence ratio [aPR] = 1.82, 95% confidence interval [CI] = 1.27-2.62) and Bulawayo (aPR = 1.51, 95% CI = 1.15-2.00) in relative risk regression. Social cohesion did not moderate these relationships. Findings demonstrate stigma's association with HIV vulnerability among Zimbabwean SGM, highlighting the need for stigma-mitigation to reduce HIV transmission in this population.

      2. Utility of diabetes type-specific genetic risk scores for the classification of diabetes type among multiethnic youthexternal icon
        Oram RA, Sharp SA, Pihoker C, Ferrat L, Imperatore G, Williams A, Redondo MJ, Wagenknecht L, Dolan LM, Lawrence JM, Weedon MN, D'Agostino R, Hagopian WA, Divers J, Dabelea D.
        Diabetes Care. 2022 Mar 21.
        OBJECTIVE: Genetic risk scores (GRSs) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S. RESEARCH DESIGN AND METHODS: We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRSs in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/-) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other). RESULTS: T1D and T2D GRSs were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA-/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA-/IS individuals had a greater probability of T1D than T2D. In DAA- individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency. CONCLUSIONS: Diabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA- children.

    • Healthcare Associated Infections
      1. Mathematical models are used to gauge the impact of interventions for healthcare-associated infections. As with any analytic method, such models require many assumptions. Two common assumptions are that asymptomatically colonized individuals are more likely to be hospitalized and that they spend longer in the hospital per admission because of their colonization status. These assumptions have no biological basis and could impact the estimated effects of interventions in unintended ways. Therefore, we developed a model of methicillin-resistant Staphylococcus aureus transmission to explicitly evaluate the impact of these assumptions. We found that assuming that asymptomatically colonized individuals were more likely to be admitted to the hospital or spend longer in the hospital than uncolonized individuals biased results compared to a more realistic model that did not make either assumption. Results were heavily biased when estimating the impact of an intervention that directly reduced transmission in a hospital. In contrast, results were moderately biased when estimating the impact of an intervention that decolonized hospital patients. Our findings can inform choices modelers face when constructing models of healthcare-associated infection interventions and thereby improve their validity.

    • Immunity and Immunization
      1. INTRODUCTION: National Immunization Survey-Child data are used widely to assess childhood vaccination coverage in the U.S. This study compares National Immunization Survey-Child coverage estimates with estimates using other supplementary data sources. METHODS: Retrospective analyses in 2021 assessed vaccination coverage of privately insured children for vaccines recommended by the Advisory Committee on Immunization Practices by age 2 years, using the 2015-2018 MarketScan Commercial Claims and Encounters databases and the 2018-2019 Healthcare Effectiveness Data and Information Set. The coverage estimates were compared statistically with those using the 2016-2018 National Immunization Survey-Child. RESULTS: Estimated coverage ranged from 69.9% (≥2 doses of influenza vaccine) to 95.0% (≥3 doses of diphtheria, tetanus toxoids, and acellular pertussis vaccine) using the MarketScan Commercial Claims and Encounters data and from 68.0% (≥2 doses of influenza vaccine) to 92.2% (≥1 dose of measles, mumps, and rubella vaccine) using the Healthcare Effectiveness Data and Information Set. The difference between the MarketScan Commercial Claims and Encounters and National Immunization Survey-Child estimates ranged from 0.1 to 4.3 percentage points and was statistically significant for 6 of the 13 assessed vaccines/doses and percentage of children receiving no vaccinations. The difference between the Healthcare Effectiveness Data and Information Set and National Immunization Survey-Child estimates ranged from 0.4 to 7.2 percentage points and was statistically significant for 6 of the 10 assessed vaccines/doses. CONCLUSIONS: For certain vaccines and populations of interest, the National Immunization Survey-Child, MarketScan Commercial Claims and Encounters, and Healthcare Effectiveness Data and Information Set data might give comparable coverage of privately insured children.

      2. Risk for shoulder conditions after vaccination: A population-based study using real-world dataexternal icon
        Zheng C, Duffy J, Liu IA, Sy LS, Chen W, Qian L, Navarro RA, Ryan DS, Kim SS, Mercado C, Jacobsen SJ.
        Ann Intern Med. 2022 Mar 22.
        BACKGROUND: Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited. OBJECTIVE: To estimate the risk for shoulder conditions after vaccination and assess possible risk factors. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PARTICIPANTS: Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017. MEASUREMENTS: A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared. RESULTS: Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons. LIMITATION: Generalizability to other health care settings, use of administrative data, and residual confounding. CONCLUSION: These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

      3. Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster doseexternal icon
        Bruce MG, Bruden D, Hurlburt D, Morris J, Bressler S, Thompson G, Lecy D, Rudolph K, Bulkow L, Hennessy T, Simons BC, Weng MK, Nelson N, McMahon BJ.
        Hepatology. 2022 Mar 23.
        BACKGROUND: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were 6 months or older. METHODS: We tested persons for anti-HBs levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days post-booster. RESULTS: Among the 320 recruited, 112 persons had not participated in the 22 nor 30-year follow-up study (Group 1) and 208 persons had participated but were not given an HBV booster dose (Group 2). Among the 112 persons in Group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28/38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for anti-HBc, none tested positive for HBsAg nor HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.

      4. Changes in cervical cytology results and human papillomavirus types among persons screened for cervical cancer, 2007 and 2015-2017external icon
        Lewis RM, Naleway AL, Klein NP, Crane B, Hsiao A, Aukes L, Timbol J, Querec TD, Steinau M, Weinmann S, Unger ER, Markowitz LE.
        J Low Genit Tract Dis. 2022 Apr 1;26(2):135-139.
        OBJECTIVES: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007. MATERIALS AND METHODS: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017. RESULTS: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups. CONCLUSIONS: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.

      5. Effectiveness of 2-Dose BNT162b2 (Pfizer BioNTech) mRNA vaccine in preventing SARS-CoV-2 infection among children aged 5-11 years and adolescents aged 12-15 years - PROTECT Cohort, July 2021-February 2022external icon
        Fowlkes AL, Yoon SK, Lutrick K, Gwynn L, Burns J, Grant L, Phillips AL, Ellingson K, Ferraris MV, LeClair LB, Mathenge C, Yoo YM, Thiese MS, Gerald LB, Solle NS, Jeddy Z, Odame-Bamfo L, Mak J, Hegmann KT, Gerald JK, Ochoa JS, Berry M, Rose S, Lamberte JM, Madhivanan P, Pubillones FA, Rai RP, Dunnigan K, Jones JT, Krupp K, Edwards LJ, Bedrick EJ, Sokol BE, Lowe A, McLeland-Wieser H, Jovel KS, Fleary DE, Khan SM, Poe B, Hollister J, Lopez J, Rivers P, Beitel S, Tyner HL, Naleway AL, Olsho LE, Caban-Martinez AJ, Burgess JL, Thompson MG, Gaglani M.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):422-428.
        The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT(†) prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

      6. The Advisory Committee on Immunization Practices' Recommendation for Use of Moderna COVID-19 Vaccine in Adults Aged ≥18 Years and Considerations for Extended Intervals for Administration of Primary Series Doses of mRNA COVID-19 Vaccines - United States, February 2022external icon
        Wallace M, Moulia D, Blain AE, Ricketts EK, Minhaj FS, Link-Gelles R, Curran KG, Hadler SC, Asif A, Godfrey M, Hall E, Fiore A, Meyer S, Su JR, Weintraub E, Oster ME, Shimabukuro TT, Campos-Outcalt D, Morgan RL, Bell BP, Brooks O, Talbot HK, Lee GM, Daley MF, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):416-421.
        The mRNA-1273 (Moderna) COVID-19 vaccine is a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. During December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA), and the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use among persons aged ≥18 years (1), which was adopted by CDC. During December 19, 2020-January 30, 2022, approximately 204 million doses of Moderna COVID-19 vaccine were administered in the United States (2) as a primary series of 2 intramuscular doses (100 μg [0.5 mL] each) 4 weeks apart. On January 31, 2022, FDA approved a Biologics License Application (BLA) for use of the Moderna COVID-19 vaccine (Spikevax, ModernaTX, Inc.) in persons aged ≥18 years (3). On February 4, 2022, the ACIP COVID-19 Vaccines Work Group conclusions regarding recommendations for the use of the Moderna COVID-19 vaccine were presented to ACIP at a public meeting. The Work Group's deliberations were based on the Evidence to Recommendation (EtR) Framework,* which incorporates the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach(†) to rank evidence quality. In addition to initial clinical trial data, ACIP considered new information gathered in the 12 months since issuance of the interim recommendations, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. ACIP also considered comparisons of mRNA vaccine effectiveness and safety in real-world settings when first doses were administered 8 weeks apart instead of the original intervals used in clinical trials (3 weeks for BNT162b2 [Pfizer-BioNTech] COVID-19 vaccine and 4 weeks for Moderna COVID-19 vaccine). Based on this evidence, CDC has provided guidance that an 8-week interval might be optimal for some adolescents and adults. The additional information gathered since the issuance of the interim recommendations increased certainty that the benefits of preventing symptomatic and asymptomatic SARS-CoV-2 infection, hospitalization, and death outweigh vaccine-associated risks of the Moderna COVID-19 vaccine. On February 4, 2022, ACIP modified its interim recommendation to a standard recommendation(§) for use of the fully licensed Moderna COVID-19 vaccine in persons aged ≥18 years.

      7. Policy and practice of checking vaccination status at school in 2018, a global overviewexternal icon
        Sadigh K, Fox G, Khetsuriani N, Gao H, Shendale S, Ward K.
        Vaccine. 2022 Mar 17.
        BACKGROUND: Checking vaccination status at school is widely recommended as a strategy to strengthen routine childhood vaccination coverage. Documentation of approaches, challenges, strengths, and impact of this strategy in a variety of contexts is key to enhancing adoption and implementation. However, there is limited information about the prevalence of policies and the implementation of checking vaccination status at school globally. METHODS: A one-time supplementary survey was circulated with the annual World Health Organization (WHO) and United Nations International Children's Emergency Fund (UNICEF) Joint Reporting Form in 2019 to all WHO member states and non-member state reporting entities. Additional publicly available country-level data, including primary school enrollment, home-based record (HBR) ownership, and World Bank income classification were linked to the supplementary survey responses, which were descriptively analyzed. RESULTS: We received survey responses from 130 of the 194 (67%) WHO member states and 15 non-member state reporting entities. Almost half (46%) of the respondents reported having a law requiring proof of vaccination to enter at least one level of education, and 60% of the respondents reported having a law that requires checking vaccination status at school in 2018. Three-quarters of the respondents (77%) reported the practice of routinely checking vaccination status at school. Both laws and the practice of checking were more common in the WHO Region of the Americas and the WHO European Region, and in high- and upper-middle-income countries. Individual HBR was the document most frequently checked. Catch-up vaccination occurred most frequently at health centers. Evaluation of checking vaccination status at school to determine what has worked and its effect was infrequently reported. CONCLUSION: Despite widespread implementation of checking vaccination status at school in 2018, documentation of the experiences in planning and implementing this strategy, and its effects remains sparse, particularly in low- and middle-income countries.

      8. Safety of measles and pertussis-containing vaccines in children with autism spectrum disordersexternal icon
        Zerbo O, Modaressi S, Goddard K, Lewis E, Fireman B, Daley MF, Irving SA, Jackson LA, Donahue JG, Qian L, Getahun D, DeStefano F, McNeil MM, Klein NP.
        Vaccine. 2022 Mar 18.
        OBJECTIVES: To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. METHODS: The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. RESULTS: The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. CONCLUSION: Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

    • Injury and Violence
      1. Injury-related emergency department visits during the COVID-19 pandemicexternal icon
        Law RK, Wolkin AF, Patel N, Alic A, Yuan K, Ahmed K, Idaikkadar N, Haileyesus T.
        Am J Prev Med. 2022 Feb 21.
        INTRODUCTION: On March 13, 2020, the U.S. declared COVID-19 to be a national emergency. As communities adopted mitigation strategies, there were potential changes in the trends of injuries treated in emergency department. This study provides national estimates of injury-related emergency department visits in the U.S. before and during the pandemic. METHODS: A secondary retrospective cohort study was conducted using trained, on-site hospital coders collecting data for injury-related emergency department cases from medical records from a nationally representative sample of 66 U.S. hospital emergency departments. Injury emergency department visit estimates in the year before the pandemic (January 1, 2019-December 31, 2019) were compared with estimates of the year of pandemic declaration (January 1, 2020-December 31, 2020) for overall nonfatal injury-related emergency department visits, motor vehicle, falls-related, self-harm-, assault-related, and poisoning-related emergency department visits. RESULTS: There was an estimated 1.7 million (25%) decrease in nonfatal injury-related emergency department visits during April through June 2020 compared with those of the same timeframe in 2019. Similar decreases were observed for emergency department visits because of motor vehicle‒related injuries (199,329; 23.3%) and falls-related injuries (497,971; 25.1%). Monthly 2020 estimates remained relatively in line with 2019 estimates for self-harm‒, assault-, and poisoning-related emergency department visits. CONCLUSIONS: These findings provide updates for clinical and public health practitioners on the changing profile of injury-related emergency department visits during the COVID-19 pandemic. Understanding the short- and long-term impacts of the pandemic is important to preventing future injuries.

      2. Sexual violence (SV) among adolescents continues to be a major public health concern with numerous consequences. Research, predominantly with male collegiate samples, has suggested an association between sports participation and SV perpetration, and has included other important risk factors such as substance use and attitudes. However, more research is needed in this area among adolescents. The current study uses latent class analysis (LCA) to examine data- driven classes of high school student athletes (N = 665) engaged in three risk factor areas for SV: sport contact level, likelihood of substance use, and attitudes dismissive of SV. Once classes were enumerated and fit separately for male and female samples, pairwise comparisons were conducted on scores on two forms of SV (perpetration of sexual harassment and unwanted sexual contact) as a function of class membership. A 5-class solution was retained for both males and females. In the female sample, regarding SV-harassment, those most likely to perpetrate sexual harassment were those characterized by high likelihood of use of cigarettes, marijuana, alcohol, vape products, and those who played any type of sport. Too few females endorsed perpetration of unwanted sexual contact for pairwise comparisons to be conducted. For males, the classes most likely to perpetrate both forms of SV were those who were likely to endorse high likelihood to use of cigarettes, marijuana, alcohol, vape products, endorse attitudes dismissive of SV, and play any type of sport but especially high contact sports. These findings implicate high school athletic spaces as important venues for sexual violence prevention efforts.

      3. Evaluating the impact of a youth-led sexual violence prevention program: Youth leadership retreat outcomesexternal icon
        Edwards KM, Banyard VL, Waterman EA, Mitchell KJ, Jones LM, Kollar LM, Hopfauf S, Simon B.
        Prev Sci. 2022 Mar 18.
        Involving youth in developing and implementing prevention programs to reduce sexual violence (SV) has the potential to improve prevention outcomes. However, there has been little focus on youth-led SV prevention programs, and limited evaluation research to help guide efforts. The current study examined the effectiveness of Youth Voices in Prevention (Youth VIP) leadership retreats on SV victimization and perpetration, forms of violence related to SV (e.g., bullying), SV bystander behaviors and readiness, and perceptions of norms related to SV prevention. Results identified mixed findings for program impact, with variations in outcomes that can help guide future youth-led prevention program initiatives. Youth attending a large "kick-off" leadership retreat (that was less youth-led that subsequent smaller retreats) later reported more bystander behaviors, but also reported increased perpetration and victimization, compared to non-attending youth. However, youth attending smaller, more focused leadership retreats held during the school year, reported reductions in sexual harassment perpetration and improved bystander behaviors and attitudes compared to non-attending youth. Evaluation of moderator variables suggests that program impact was generally stronger for younger participants, sexual minority youth, and non-White youth (which were largely Native American youth in this sample). Findings suggest promise for youth-led prevention work but also highlight the need for testing the impact of different training structures and modalities. Clinical trials number: NCT03207386.

    • Laboratory Sciences
      1. Relationship of SARS-CoV-2 antigen and reverse transcription PCR positivity for viral culturesexternal icon
        Currie DW, Shah MM, Salvatore PP, Ford L, Whaley MJ, Meece J, Ivacic L, Thornburg NJ, Tamin A, Harcourt JL, Folster J, Medrzycki M, Jain S, Wong P, Goffard K, Gieryn D, Kahrs J, Langolf K, Zochert T, Hsu CH, Kirking HL, Tate JE.
        Emerg Infect Dis. 2022 Mar;28(3):717-720.
        We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated from some antigen-negative and RT-PCR‒positive paired specimens, providing support for the Centers for Disease Control and Prevention antigen testing algorithm.

      2. Direct real-time pcr for the detection and serotyping of haemophilus influenzae without DNA extractionexternal icon
        Marasini D, Whaley MJ, Jenkins LT, Hu F, Jiang W, Topaz N, Chen A, Schmink S, Dolan Thomas J, Harcourt BH, Marjuki H, Wang X.
        J Clin Microbiol. 2022 Mar 21:e0211121.
        To monitor the burden and changes in Haemophilus influenzae (Hi) disease, direct real-time PCR (drt-PCR) assays have been developed for Hi detection in monoplex form and its six serotypes in triplex form, directly from cerebrospinal fluid (CSF) specimens. These assays target the phoB gene for the species detection (Hi-phoB) and serotype-specific genes in region II of the capsule biosynthesis locus (Hi-abf and Hi-cde), identified through comparative analysis of Hi and non-Hi whole-genome sequences. The lower limit of detection (LLD) is 293 CFU/mL for the Hi-phoB assay and ranged from 11 to 130 CFU/mL for the triplex serotyping assays. Using culture as a reference method, the sensitivity and specificity of Hi-phoB, Hi-abf, and Hi-cde were 100%. Triplex serotyping assays also showed 100% agreement for each serotype compared to their corresponding monoplex serotyping assay. These highly sensitive and specific drt-PCR assays do not require DNA extraction and thereby reduce the time, cost, and handling required to process CSF specimens. Furthermore, triplex drt-PCR assays combine the detection of three serotypes in a single reaction, further improving testing efficiency, which is critical for laboratories that process high volumes of Hi specimens for surveillance and diagnostic purposes.

    • Maternal and Child Health
      1. Rapid population-based surveillance of prenatal and postpartum experiences during public health emergencies, Puerto Rico, 2016‒2018external icon
        Salvesen von Essen B, D'Angelo DV, Shulman HB, Virella WH, Kortsmit K, Herrera BR, Díaz PG, Taraporewalla A, Harrison L, Warner L, Vargas Bernal M.
        Am J Public Health. 2022 Apr;112(4):574-578.
        The Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response study, implemented in Puerto Rico during the Zika virus outbreak (2016-2017) and after Hurricanes Irma and María (2017-2018), collected pregnancy-related data using postpartum hospital-based surveys and telephone follow-up surveys. Response rates of 75% or more were observed across five study surveys. The study informed programs, increased the Puerto Rico Department of Health's capacity to conduct maternal‒infant health surveillance, and demonstrated the effectiveness of this methodology for collecting data during public health emergencies. (Am J Public Health. 2022;112(4):574-578. https://doi.org/10.2105/AJPH.2021.306687).

      2. Progress toward achieving and sustaining maternal and neonatal tetanus elimination - worldwide, 2000-2020external icon
        Kanu FA, Yusuf N, Kassogue M, Ahmed B, Tohme RA.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):406-411.
        Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after unhygienic deliveries, especially in low-income countries (1). In 1989, the World Health Assembly endorsed elimination(†) of neonatal tetanus; the activity was relaunched in 1999 as the MNT elimination (MNTE)(§) initiative, targeting 59(¶) priority countries. MNTE strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV2+)** among women of reproductive age through routine and supplementary immunization activities (SIAs)(††) in high-risk districts,(§§) 2) achieving ≥70% of deliveries by a skilled birth attendant,(¶¶) and 3) implementing neonatal tetanus case-based surveillance (2). This report summarizes progress toward achieving and sustaining MNTE during 2000-2020 and updates a previous report (3). By December 2020, 52 (88%) of 59 priority countries had conducted TTCV SIAs. Globally, infants protected at birth*** against tetanus increased from 74% (2000) to 86% (2020), and deliveries assisted by a skilled birth attendant increased from 64% (2000-2006) to 83% (2014-2020). Reported neonatal tetanus cases worldwide decreased by 88%, from 17,935 (2000) to 2,229 (2020), and estimated deaths decreased by 92%, from 170,829 (2000) to 14,230 (2019).(†††) By December 2020, 47 (80%) of 59 priority countries were validated to have achieved MNTE, five of which conducted postvalidation assessments.(§§§) To achieve elimination in the 12 remaining countries and sustain elimination, innovation is needed, including integrating SIAs to cover multiple vaccine preventable diseases and implementing TTCV life course vaccination.

      3. Out of school time providers innovate to support school-aged children during the COVID-19 pandemicexternal icon
        Sliwa SA, Lee SM, Gover LE, Morris DD.
        Prev Chronic Dis. 2022 Mar 17;19:E12.

      4. A systematic review and meta-analysis of prenatal, birth, and postnatal factors associated with attention-deficit/hyperactivity disorder in childrenexternal icon
        Bitsko RH, Holbrook JR, O'Masta B, Maher B, Cerles A, Saadeh K, Mahmooth Z, MacMillan LM, Rush M, Kaminski JW.
        Prev Sci. 2022 Mar 18.
        Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal ("pregnancy-related") risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1-1.6 ORs, -0.16-0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD.

      5. Recent incarceration exposure among parents of live-born infants and maternal and child healthexternal icon
        Lee RD, D'Angelo DV, Dieke A, Burley K.
        Public Health Rep. 2022 Mar 18:333549221081808.
        OBJECTIVE: Women who have direct exposure to incarceration or indirect exposure through their partner are at high risk for poor health behaviors and outcomes, which may have lasting impacts on their children. The objectives of this study were to estimate the prevalence of recent incarceration exposure among women with a recent live birth and assess the relationship between incarceration exposure and maternal and child health. METHODS: We used data from the Pregnancy Risk Assessment Monitoring System (36 states and New York City, 2012-2015; N = 146 329) to estimate the prevalence of women reporting that they or their husband/partner spent time in jail during the 12 months before giving birth. We used multivariable logistic regression to assess associations between incarceration exposure and maternal and infant health conditions. RESULTS: The prevalence of incarceration exposure shortly before or during pregnancy was 3.7% (95% CI, 3.6%-3.9%). Women with incarceration exposure had increased odds of prepregnancy hypertension (adjusted odds ratio [aOR] = 1.51; 95% CI, 1.26-1.81), prepregnancy and postpartum depressive symptoms (aOR = 1.95 [95% CI, 1.73-2.19] and 1.49 [95% CI, 1.32-1.67], respectively), and having an infant admitted to the neonatal intensive care unit (aOR = 1.18; 95% CI, 1.04-1.33). CONCLUSION: Because a parent's incarceration exposure is an adverse childhood experience with the potential to disrupt important developmental periods and have negative impacts on the socioemotional and health outcomes of children, it is critical for researchers and health care providers to better understand its impact on maternal and infant health. Prenatal and postnatal care may provide opportunities to address incarceration-related health risks.

    • Nutritional Sciences
      1. Convenience and corner store fruit and vegetable access: attitudes and intentions among Colorado adults, 2014external icon
        James K, Calanan R, Macaluso F, Li Y, Levinson A.
        J Public Health. 2022 ;30(4):871-878.
        Aim: The term food desert generally refers to areas where healthy food options, such as fresh fruits and vegetables, are unavailable within a certain number of miles. However, other factors besides distance may affect the ability to purchase healthier foods. The goal of this study was to understand Colorado adults' perceptions of their access to healthy food options and to assess how other structural and socio-demographic factors may affect that access. Subject and methods: Colorado adults were asked questions about self-reported access to healthy food, likelihood of buying fresh fruits and vegetables from convenience/corner stores if available, perceived characteristics of fruits and vegetables available for purchase near respondents' residence, and demographics. Results: A majority of Colorado adults in 2013–14 reported wanting fresh fruits and vegetables to be more available, more varied, higher quality, and/or less expensive. Socioeconomic status, race/ethnicity, and regular shopping habits were significantly associated with reported likelihood of purchasing fruits and vegetables from a convenience/corner store if available. Conclusion: Factors other than proximity to a grocery store affect Colorado adults' perceived access to healthy food options and should be considered in the development and implementation of public health programs and policies geared toward improving healthy food access.

    • Occupational Safety and Health
      1. Measuring the ultimate impact of research on health and economic well-being has presented challenges that have rarely been surmounted, and research on preventing occupational injuries and illnesses is no exception. Nevertheless, there is an increasing need to demonstrate the value of publicly funded research. The National Institute for Occupational Safety and Health (NIOSH) recently contracted with the RAND Corporation to conduct six in-depth case studies that aimed to quantify the benefits of key NIOSH research efforts using economic metrics. These case studies focused on silica exposure in asphalt pavement milling, firefighter cancer risks, a multi-industry matching-grant program for purchase of safety equipment, personal coal dust monitors for coal miners, re-design of ambulance patient compartments for safety, and workplace amputation surveillance. In this article, we summarize what we learned about how measurement of research benefits may be pursued. We summarize the benefit measurement methods that were used and the results of these research efforts in terms of costs saved, injuries and illnesses prevented, and the statistical value of reductions in risk of death or illness. We then distill some observations about the characteristics of research efforts that make measurement of research benefits feasible and suggest steps that could make it feasible to apply the same methods more widely. We also outline key NIOSH activities that appear not to be amenable to benefit measurement but suggest potentials for progress toward at least partial or qualitative benefit assessment. Finally, we discuss implications of the benefit measurement case studies for strategic research planning.

      2. Effective coordination, collaboration, communication, and partnering are needed to close the gaps for occupational PFAS exposureexternal icon
        Moore SM, Brown C, Kiederer M, Calkins MM, Burgess JL, D'Alessandro M, Davis R, Fenton SE, Morrison P, Reh CM.
        Am J Ind Med. 2022 Mar 15.

      3. Research gaps and needs for preventing worker fatigue in the transportation and utilities industriesexternal icon
        Sieber WK, Chen GX, Krueger GP, Lincoln JE, Menéndez CC, O'Connor MB.
        Am J Ind Med. 2022 Mar 17.
        BACKGROUND: The transportation and utilities industries include establishments engaged in the movement of passengers and freight, or the provision of public power, water, and other services. Along with the warehousing industry, they make up the US National Occupational Research Agenda's Transportation, Warehousing and Utilities (TWU) industry sector. In 2018 the sector composed 5% of the US workforce, with approximately 8 million workers. TWU workers experienced 19% of all fatalities among U.S. workers in 2018 and 7% of total occupational injuries and illnesses. METHODS: Around-the-clock operations, heavy workloads, long and irregular shifts, complicated schedules, and time pressures characterize work across the US TWU sector. However, there are considerable differences in worker priorities and concerns between TWU industries. Major areas of concern within the sector include disparities in work schedules; required training for employee fatigue awareness and prevention; physical and mental job demands; and safety culture. RESULTS: Strategies for fatigue mitigation are critical to reduce the prevalence of injuries, safety-critical events, and crashes in TWU workers. Further research on the incidence and characterization of fatigue among TWU workers will guide the development of effective mitigation strategies. The influence of work scheduling on missed sleep opportunities and disrupted circadian rhythms should be determined. Evaluation of fatigue mitigation strategies can lead to the adoption of the most effective ones for each TWU industry. CONCLUSION: Implementation of effective strategies is critical for the health, safety, wellbeing, and productivity of workers in the TWU sector.

      4. Rapid review of dermal penetration and absorption of inorganic lead compounds for occupational risk assessmentexternal icon
        Niemeier RT, Maier A, Reichard JF.
        Ann Work Expo Health. 2022 Mar 15;66(3):291-311.
        Lead (Pb) exposure continues to be a significant public health issue in both occupational and non-occupational settings. The vast majority of exposure and toxicological studies have focused on effects related to inhalation and gastrointestinal exposure routes. Exposure to inorganic Pb compounds through dermal absorption has been less well studied, perhaps due to the assumption that the dermal pathway is a minor contributor to aggregate exposures to Pb compounds. The aim of this rapid review was to identify and evaluate published literature on dermal exposures to support the estimation of key percutaneous absorption parameters (Kp, flux, diffusion rate) for use in occupational risk assessment. Eleven articles were identified containing information from both in vitro and in vivo systems relevant to percutaneous absorption kinetics. These articles provided 24 individual study summaries and information for seven inorganic Pb compounds. The vast majority of study summaries evaluated (n = 22, 92%) reported detectable amounts of dermal absorption of inorganic Pb. Data were identified for four Pb compounds (Pb acetate, Pb nitrate, Pb oxide, and Pb metal) that may be sufficient to use in evaluating physiologically based pharmacokinetic models. Average calculated diffusion rates for the pool of animal and human skin data ranged from 10-7 to 10-4 mg cm-2 h-1, and Kp values ranged from 10-7 to 10-5 cm h-1. Study design and documentation were highly variable, and only one of the studies identified was conducted using standard test guideline-compliant methodologies. Two studies provided quality estimates on the impacts of dermal absorption from water-insoluble Pb compounds on blood Pb levels. These two studies reported that exposures via dermal routes could elevate blood Pb by over 6 µg dl-1. This estimation could represent over 100% of 5 µg dl-1, the blood Pb associated with adverse health effects in adults. The utility of these estimates to occupational dermal exposures is limited, because the confidence in the estimates is not high. The literature, while of limited quality, overall strongly suggests inorganic Pb has the potential for dermal uptake in meaningful amounts associated with negative health outcomes based on upper bound diffusion rate estimates. Future standard test guideline-compliant studies are needed to provide high-confidence estimates of dermal uptake. Such data are needed to allow for improved evaluation of Pb exposures in an occupational risk assessment context.

      5. What does non-standard employment look like in the United States? An empirical typology of employment qualityexternal icon
        Peckham T, Flaherty B, Hajat A, Fujishiro K, Jacoby D, Seixas N.
        Soc Indic Res. 2022 .
        Despite significant interest in the changing nature of employment as a critical social and economic challenge facing society—especially the decline in the so-called Standard Employment Relationship (SER) and rise in more insecure, precarious forms of employment—scholars have struggled to operationalize the multifaceted and heterogeneous nature of contemporary worker-employer relationships within empirical analyses. Here we investigate the character and distribution of employment relationships in the U.S., drawing on a representative sample of wage-earners and self-employed from the General Social Survey (2002–2018). We use the multidimensional construct of employment quality, which includes both contractual (e.g., wages, contract type) and relational (e.g., employee representation and participation) aspects of employment. We further employ a typological measurement approach, using latent class analysis, to explicitly examine how the multiple aspects of employment cluster together in modern labor markets. We present eight distinct employment types in the U.S., including one resembling the historical conception of the SER model (24% of the total workforce), and others representing various constellations of favorable and adverse employment features. These employment types are unevenly distributed across society, in terms of who works these jobs and where they are found in the labor market. Importantly, women, those with lower education, and younger workers are more likely to be in precarious forms of employment. More generally, our typology reveals limitations associated with binary conceptions of standard vs. non-standard employment, or insider–outsider dichotomies envisioned within dual labor market theories. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

    • Occupational Safety and Health - Mining
      1. Effects of heat strain on cognitive function among a sample of minersexternal icon
        Yeoman K, Weakley A, DuBose W, Honn K, McMurry T, Eiter B, Baker B, Poplin G.
        Appl Ergon. 2022 Mar 18;102:103743.
        Heat stress is associated with workplace injuries, likely through a combination of fatigue, reduced cognitive function, and thermal discomfort. The purpose of this study was to evaluate four cognitive tasks for sensitivity to heat stress. Eight participants performed treadmill exercise followed by assessments of serial reaction time (RT), Stroop effect, verbal delayed memory, and continuous performance working memory in an environmental chamber. A control (21.1 °C) trial, and "Hot 1" and "Hot 2" (both 37.8 °C) trials were run sequentially on two separate days to evaluate the four cognitive tasks. Heat strain (comparing Hot 1 and Hot 2 with the control trial) resulted in impairments in the serial RT test response and Stroop accuracy. Delayed memory was impacted only in the Hot 2 trial compared with the control trial. Given the demonstrated impact of heat on cognitive processes relevant to workers' real-world functioning in the workplace, understanding how to assess and monitor vigilant attention in the workplace is essential.

      2. Diesel aerosols in an underground coal mineexternal icon
        Bugarski AD, Vanderslice S, Hummer JA, Barone T, Mischler SE, Peters S, Cochrane S, Winkler J.
        Min Metall Explor. 2022 .
        The case study was conducted in an underground coal mine to characterize submicron aerosols at a continuous miner (CM) section, assess the concentrations of diesel aerosols at the longwall (LW) section, and assess the exposures of selected occupations to elemental carbon (EC) and total carbon (TC). The results show that aerosols at the CM sections were a mixture of aerosols freshly generated at the outby portion of the CM section and those generated in the main drifts that supply “fresh air” to the section. The relatively low ambient concentrations and personal exposures of selected occupations suggest that currently applied control strategies and technologies are relatively effective in curtailing exposures to diesel aerosols. Further reductions in EC and TC concentrations and personal exposures to those would be possible by more effective curtailment of emissions from high-emitting light duty (LD) vehicles. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

    • Substance Use and Abuse
      1. BACKGROUND: COVID-19 stay-at-home orders may reduce access to substance use treatment and naloxone, an opioid overdose reversal drug. The objective of this analysis was to compare monthly trends in pharmacy-based dispensing rates of medications for opioid use disorder (MOUD) (buprenorphine and extended-release [ER] naltrexone) and naloxone in the United States during March 2019-December 2020 by age and sex. METHODS: We calculated monthly prescription dispensing rates per 100,000 persons using IQVIA New to Brand. We used Joinpoint regression to calculate monthly percent change in dispensing rates and Wilcoxon Rank Sum tests to examine differences in median monthly rates overall, and by age and sex between March 2019-December 2019 and March 2020-December 2020. RESULTS: Buprenorphine dispensing increased among those aged 40-64 years and ≥ 65 years from March 2019 to December 2020. Median rates of total ER naltrexone dispensing were lower in March 2020-December 2020 compared to March 2019-December 2019 for the total population, and for females and males. From March 2019 to December 2020, ER naltrexone dispensing decreased and naloxone dispensing increased for those aged 20-39 years. CONCLUSIONS: Dispensing ER naltrexone declined during the study period. Given the increase in substance use during the COVID-19 pandemic, maintaining equivalent access to MOUD may not be adequate to accommodate rising numbers of new patients with opioid use disorder. Access to all MOUD and naloxone could be further expanded to meet potential needs during and after the public health emergency, given their importance in preventing opioid overdose-related harms.

      2. Nicotine exposure in the U.S. population: Total urinary nicotine biomarkers in NHANES 2015–2016external icon
        Mazumder S, Shia W, Bendik PB, Achilihu H, Sosnoff CS, Alexander JR, Luo Z, Zhu W, Pine BN, Feng J, Blount BC, Wang L.
        Int J Environ Res Public Health. 2022 ;19(6).
        We characterize nicotine exposure in the U.S. population by measuring urinary nicotine and its major (cotinine, trans-3′-hydroxycotinine) and minor (nicotine 1′-oxide, cotinine N-oxide, and 1-(3-pyridyl)-1-butanol-4-carboxylic acid, nornicotine) metabolites in participants from the 2015–2016 National Health and Nutrition Examination Survey. This is one of the first U.S. population-based urinary nicotine biomarker reports using the derived total nicotine equivalents (i.e., TNEs) to characterize exposure. Serum cotinine data is used to stratify tobacco non-users with no detectable serum cotinine (−sCOT), non-users with detectable serum cotinine (+sCOT), and individuals who use tobacco (users). The molar concentration sum of cotinine and trans-3′-hydroxycotinine was calculated to derive the TNE2 for non-users. Additionally, for users, the molar concentration sum of nicotine and TNE2 was calculated to derive the TNE3, and the molar concentration sum of the minor metabolites and TNE3 was calculated to derive the TNE7. Sample-weighted summary statistics are reported. We also generated multiple linear regression models to analyze the association between biomarker concentrations and tobacco use status, after adjusting for select demographic factors. We found TNE7 is positively correlated with TNE3 and TNE2 (r = 0.99 and 0.98, respectively), and TNE3 is positively correlated with TNE2 (r = 0.98). The mean TNE2 concentration was elevated for the +sCOT compared with the −sCOT group (0.0143 [0.0120, 0.0172] µmol/g creatinine and 0.00188 [0.00172, 0.00205] µmol/g creatinine, respectively), and highest among users (33.5 [29.6, 37.9] µmol/g creatinine). Non-daily tobacco use was associated with 50% lower TNE7 concentrations (p &lt; 0.0001) compared with daily use. In this report, we show tobacco use frequency and passive exposure to nicotine are important sources of nicotine exposure. Furthermore, this report provides more information on non-users than a serum biomarker report, which underscores the value of urinary nicotine biomarkers in extending the range of trace-level exposures that can be characterized. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

      3. Tobacco product use among adults - United States, 2020external icon
        Cornelius ME, Loretan CG, Wang TW, Jamal A, Homa DM.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 18;71(11):397-405.
        Although cigarette smoking has declined over the past several decades, a diverse landscape of combustible and noncombustible tobacco products has emerged in the United States (1-4). To assess recent national estimates of commercial tobacco product use among U.S. adults aged ≥18 years, CDC analyzed data from the 2020 National Health Interview Survey (NHIS). In 2020, an estimated 47.1 million U.S. adults (19.0%) reported currently using any commercial tobacco product, including cigarettes (12.5%), e-cigarettes (3.7%), cigars (3.5%), smokeless tobacco (2.3%), and pipes* (1.1%).(†) From 2019 to 2020, the prevalence of overall tobacco product use, combustible tobacco product use, cigarettes, e-cigarettes, and use of two or more tobacco products decreased. Among those who reported current tobacco product use, 79.6% reported using combustible products (e.g., cigarettes, cigars, or pipes), and 17.3% reported using two or more tobacco products.(§) The prevalence of any current commercial tobacco product use was higher among the following groups: 1) men; 2) adults aged <65 years; 3) non-Hispanic American Indian or Alaska Native (AI/AN) adults and non-Hispanic adults categorized as of "Other" race(¶); 4) adults in rural (nonmetropolitan) areas; 5) those whose highest level of educational attainment was a general educational development certificate (GED); 6) those with an annual household income <$35,000; 7) lesbian, gay, or bisexual adults; 8) uninsured adults or those with Medicaid; 9) adults living with a disability; and 10) those who regularly had feelings of anxiety or depression. Continued monitoring of tobacco product use and tailored strategies and policies that reduce the effects of inequitable conditions could aid in reducing disparities in tobacco use (1,4).

    • Zoonotic and Vectorborne Diseases
      1. Defective interfering viral particle treatment reduces clinical signs and protects hamsters from lethal Nipah virus diseaseexternal icon
        Welch SR, Spengler JR, Harmon JR, Coleman-McCray JD, Scholte FE, Genzer SC, Lo MK, Montgomery JM, Nichol ST, Spiropoulou CF.
        mBio. 2022 Mar 17:e0329421.
        Defective interfering particles (DIs) contain a considerably smaller genome than the parental virus but retain replication competency. As DIs can directly or indirectly alter propagation kinetics of the parental virus, they offer a novel approach to antiviral therapy, capitalizing on knowledge from natural infection. However, efforts to translate in vitro inhibition to in vivo screening models remain limited. We investigated the efficacy of virus-like particles containing DI genomes (therapeutic infectious particles [TIPs]) in the Syrian hamster model of lethal Nipah virus (NiV) disease. We found that coadministering a high dose of TIPs intraperitoneally with virus challenge improved clinical course and reduced lethality. To mimic natural exposure, we also evaluated lower-dose TIP delivery and virus challenge intranasally, finding equally efficacious reduction in disease severity and overall lethality. Eliminating TIP replicative capacity decreased efficacy, suggesting protection via direct inhibition. These data provide evidence that TIP-mediated treatment can confer protection against disease and lethal outcome in a robust animal NiV model, supporting further development of TIP treatment for NiV and other high-consequence pathogens. IMPORTANCE Here, we demonstrate that treatment with defective interfering particles (DIs), a natural by-product of viral infection, can significantly improve the clinical course and outcome of viral disease. When present with their parental virus, DIs can directly or indirectly alter viral propagation kinetics and exert potent inhibitory properties in cell culture. We evaluated the efficacy of a selection of virus-like particles containing DI genomes (TIPs) delivered intranasally in a lethal hamster model of Nipah virus disease. We demonstrate significantly improved clinical outcomes, including reduction in both lethality and the appearance of clinical signs. This work provides key efficacy data in a robust model of Nipah virus disease to support further development of TIP-mediated treatment against high-consequence viral pathogens.


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