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Issue 48, November 29, 2022

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CDC Science Clips: Volume 14, Issue 48, November 29, 2022

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD-3 study
        Nikšić M, Minicozzi P, Weir HK, Zimmerman H, Schymura MJ, Rees JR, Coleman MP, Allemani C.
        Cancer Commun (Lond). 2022 Nov 9.
        BACKGROUND: Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US. METHODS: This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years. RESULTS: Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women. CONCLUSIONS: Gaps in 1- and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure.

      2. Five priority public health actions to reduce chronic disease through improved nutrition and physical activity
        O'Toole TP, Blanck HM, Flores-Ayala R, Rose K, Galuska DA, Gunn J, O'Connor A, Petersen R, Hacker K.
        Health Promot Pract. 2022 Nov;23(1_suppl):5s-11s.

      3. Association of asthma with treatments and outcomes in children with critical influenza
        Maddux AB, Grunwell JR, Newhams MM, Chen SR, Olson SM, Halasa NB, Weiss SL, Coates BM, Schuster JE, Hall MW, Nofziger RA, Flori HR, Gertz SJ, Kong M, Sanders RC, Irby K, Hume JR, Cullimore ML, Shein SL, Thomas NJ, Miller K, Patel M, Fitzpatrick AM, Phipatanakul W, Randolph AG.
        J Allergy Clin Immunol Pract. 2022 Nov 12.
        BACKGROUND: Hospitalization for severe influenza infection in childhood may result in post-discharge sequelae. OBJECTIVE(S): To evaluate inpatient management and post-discharge sequelae in children with critical respiratory illness due to influenza with or without pre-existing asthma. METHODS: Prospective, observational multicenter study of children (8-months to 17-years-old) admitted to a pediatric intensive care or high-acuity unit (11/2019-4/2020) for influenza. Results were stratified by pre-existing asthma. Pre-hospital status, hospital treatments and outcomes were collected. Surveys at approximately 90 days post-discharge evaluated post-discharge health resource use, functional status, and respiratory symptoms. RESULTS: 165 children with influenza: 56 (33.9%) with and 109 (66.1%) without pre-existing asthma (41.1% and 39.4% fully vaccinated against influenza, respectively). Fifteen (26.7%) patients with and 34 (31.1%) without pre-existing asthma were intubated. More patients with versus without pre-existing asthma received pharmacologic asthma treatments during hospitalization (76.7% vs 28.4%). Of 136 (82.4%) patients with 90-day survey data (46 [33.8%] with and 90 [66.1%] without pre-existing asthma), a similar proportion had an Emergency Department/urgent care visit (4.3%, 6.6%) or hospital readmission (8.6%, 3.3%) for a respiratory condition. Patients with pre-existing asthma more frequently experienced asthma symptoms (78.2% vs 3.3%) and had respiratory specialist visits (52% vs 20%) post-discharge. Ten of 109 (11.1%) patients without pre-existing asthma reported being newly diagnosed with asthma. CONCLUSIONS: Respiratory health resource use and symptoms are important post-discharge outcomes after influenza critical illness in children with and without pre-existing asthma. Less than half of children were vaccinated for influenza, a tool that could mitigate critical illness and its sequelae.

      4. Long-term opioid therapy among patients with systemic lupus erythematosus in the community. A Lupus Midwest Network study
        Figueroa-Parra G, Jeffery MM, Dabit JY, Chevet B, Valenzuela-Almada MO, Hocaoglu M, Osei-Onomah SA, Kurani S, Vallejo S, Achenbach SJ, Hooten WM, Barbour KE, Crowson CS, Duarte-García A.
        J Rheumatol. 2022 Nov 15.
        OBJECTIVE: There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE. METHODS: Patients with SLE were matched with non-SLE controls in a population-based cohort on January 1, 2015. We captured demographics, manifestations of lupus, comorbidities (fibromyalgia, mood disorders, osteoarthritis, chronic low back pain [CLBP], chronic kidney disease, avascular necrosis, osteoporosis, fragility fractures, and cancer), and the area deprivation index (ADI). Opioid prescription data were used to assess prevalence of LTOT, defined as contiguous prescriptions (gaps of <30 days between prescriptions) and receiving opioid therapy ≥90 days or ≥10 prescriptions before index date. RESULTS: 465 SLE patients and 465 non-SLE controls were included; 13% of SLE patients and 3% of non-SLE controls were receiving opioid therapy (P<0.001), and 11% of SLE patients were on LTOT versus 1% of non-SLE controls. Among SLE patients, acute pericarditis (OR: 3.92; 95% CI: 1.78-8.66), fibromyalgia (OR: 7.78; 95% CI: 3.89-15.55), fragility fractures (OR: 3.72; 95% CI: 1.25-11.07), CLBP (OR: 4.00; 95% CI: 2.13-7.51), and mood disorders (OR: 2.76; 95% CI: 1.47-5.16) were associated with LTOT. We did not find an association between opioid therapy and ADI. CONCLUSION: Patients with SLE have higher LTOT than controls. Among patients with SLE, LTOT was associated with pericarditis and several comorbidities. However, LTOT was not associated with kidney disease despite the limited pain control options in these patients.

      5. Background: Treatment by a gynecologic oncologist is an important part of ovarian cancer care; however, implementation strategies are needed to increase care by these specialists. We partnered with National Comprehensive Cancer Control Programs in Iowa, Michigan, and Rhode Island in a demonstration project to deepen the evidence base for promising strategies that would facilitate care for ovarian cancer by gynecologic oncologists. Methods: Five main implementation strategies (increase knowledge/awareness; improve models of care; improve payment structures; increase insurance coverage; enhance workforce) were identified in the literature and used to develop initiatives. Specific activities were chosen by state programs according to feasibility and needs. Results: Activities included: (1) qualitative interviews with patients to determine barriers to receipt of specialized care; (2) development of patient/provider educational materials; (3) creation of patient/provider checklists to facilitate appropriate referrals; (4) expansion of a toll-free patient navigation hotline for ovarian cancer patients; (5) training of the health care workforce. The programs developed resources (educational handouts, toolkits, 2 webinars, 2 podcasts); trained 167 medical and nursing students during 8 Survivors Teaching Students(®) workshops; and conducted 3 provider education sessions reaching 362 providers in 45 states. Evaluations showed increases in providers' knowledge, awareness, abilities, and intentions to refer ovarian cancer patients to a gynecologic oncologist. Conclusion: The state program resources we discussed are available for other cancer control programs interested in initiating or expanding activities to improve access/referrals to gynecologic oncologists for ovarian cancer care. They serve as a valuable repository for public health professionals seeking to implement similar interventions.

      6. Venous thromboembolism among Medicare acute ischaemic stroke patients with and without COVID-19
        Tong X, Yang Q, Asaithambi G, Merritt RK.
        Stroke Vasc Neurol. 2022 Nov 15.
        BACKGROUND: COVID-19 is associated with an increased risk of venous thromboembolism (VTE). This study examined the prevalence of VTE among acute ischaemic stroke (AIS) patients with and without a history of COVID-19. METHODS: We identified AIS hospitalisations of Medicare fee-for-service (FFS) beneficiaries aged ≥65 years from 1 April 2020 to 31 March 2022. We compared the prevalence and adjusted prevalence ratio of VTE among AIS patients with and without a history of COVID-19. RESULTS: Among 283 034 Medicare FFS beneficiaries with AIS hospitalisations, the prevalence of VTE was 4.51%, 2.96% and 2.61% among those with a history of hospitalised COVID-19, non-hospitalised COVID-19 and without COVID-19, respectively. As compared with patients without a history of COVID-19, the prevalence of VTE among patients with a history of hospitalised or non-hospitalised COVID-19 were 1.62 (95% CI 1.54 to 1.70) and 1.13 (95% CI 1.03 to 1.23) times greater, respectively. CONCLUSIONS: There appeared to be a notably higher prevalence of VTE among Medicare beneficiaries with AIS accompanied by a current or prior COVID-19. Early recognition of coagulation abnormalities and appropriate interventions may help improve patients' clinical outcomes.

    • Communicable Diseases
      1. BACKGROUND: The National HIV Behavioral Surveillance (NHBS) is a comprehensive system for biobehavioral surveillance conducted since 2003 in 3 populations disproportionately affected by HIV: gay, bisexual, and other men who have sex with men (MSM); people who inject drugs; and heterosexually active persons at increased risk for HIV infection (HET). This ongoing and systematic collection and analysis of data is needed to identify baseline prevalence of behavioral risk factors and prevention service use, as well as to measure progress toward meeting HIV prevention goals among key populations disproportionately affected by HIV. OBJECTIVE: This manuscript provides an overview of NHBS from 2003 to 2019. METHODS: NHBS is conducted in rotating, annual cycles; these 3 annual cycles are considered a round. Venue-based, time-space sampling is used for the MSM population. Respondent-driven sampling is used for people who inject drugs and HET populations. A standardized, anonymous questionnaire collects information on HIV-related behavioral risk factors, HIV testing, and use of prevention services. In each cycle, approximately 500 eligible persons from each participating area are interviewed and offered anonymous HIV testing. RESULTS: From 2003 to 2019, 168,600 persons were interviewed and 143,570 agreed to HIV testing across 17 to 25 cities in the United States. In the fifth round (2017 to 2019), over 10,000 (10,760-12,284) persons were interviewed each of the 3 population cycles in 23 cities. Of those, most (92%-99%) agreed to HIV testing. Several cities also conducted sexually transmitted infection or hepatitis C testing. CONCLUSIONS: NHBS is critical for monitoring the impact of the Ending the HIV Epidemic in the United States initiative. Data collected from NHBS are key to describe trends in key populations and tailor new prevention activities to ensure high prevention impact. NHBS data provide valuable information for monitoring and evaluating national HIV prevention goals and guiding national and local HIV prevention efforts. Furthermore, NHBS data can be used by public health officials and researchers to identify HIV prevention needs, allocate prevention resources, and develop and improve prevention programs directed to the populations of interest and their communities.

      2. Epidemiologic features of the monkeypox outbreak and the public health response - United States, May 17-October 6, 2022
        Kava CM, Rohraff DM, Wallace B, Mendoza-Alonzo JL, Currie DW, Munsey AE, Roth NM, Bryant-Genevier J, Kennedy JL, Weller DL, Christie A, McQuiston JH, Hicks P, Strid P, Sims E, Negron ME, Iqbal K, Ellington S, Smith DK.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 11;71(45):1449-1456.
        On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response (1,2). CDC's emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17-October 6, 2022, a total of 26,384 probable and confirmed* U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity,(†) 23,683 (95%) occurred in cisgender men. Among 13,997 cisgender men with information on recent sexual or close intimate contact,(§) 10,440 (75%) reported male-to-male sexual contact (MMSC) ≤21 days preceding symptom onset. Among 21,211 (80%) cases in persons with information on race and ethnicity,(¶) 6,879 (32%), 6,628 (31%), and 6,330 (30%) occurred in non-Hispanic Black or African American (Black), Hispanic or Latino (Hispanic), and non-Hispanic White (White) persons, respectively. Among 5,017 (20%) cases in adults with information on HIV infection status, 2,876 (57%) had HIV infection. Prevention efforts, including vaccination, should be prioritized among persons at highest risk within groups most affected by the monkeypox outbreak, including gay, bisexual, and other men who have sex with men (MSM); transgender, nonbinary, and gender-diverse persons; racial and ethnic minority groups; and persons who are immunocompromised, including persons with advanced HIV infection or newly diagnosed HIV infection.

      3. Notes from the field: Outbreak of ebola virus disease caused by Sudan ebolavirus - Uganda, August-October 2022
        Kiggundu T, Ario AR, Kadobera D, Kwesiga B, Migisha R, Makumbi I, Eurien D, Kabami Z, Kayiwa J, Lubwama B, Okethwangu D, Nabadda S, Bwire G, Mulei S, Harris JR, Dirlikov E, Fitzmaurice AG, Nabatanzi S, Tegegn Y, Muruta AN, Kyabayinze D, Boore AL, Kagirita A, Kyobe-Bosa H, Mwebesa HG, Atwine D, Aceng Ocero JR.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 11;71(45):1457-1459.

      4. Infection, immunity, and surveillance of COVID-19
        Suthar AB, Dye C.
        PLoS Med. 2022 Nov;19(11):e1004132.
        Dr Amitabh Suthar and Dr Christopher Dye give their perspective on infection, immunity and surveillance of COVID-19.

      5. Seroprevalence, distribution, and risk factors for human leptospirosis in the United States Virgin Islands
        Artus A, Schafer IJ, Cossaboom CM, Haberling DL, Galloway R, Sutherland G, Browne AS, Roth J, France V, Cranford HM, Kines KJ, Pompey J, Ellis BR, Walke H, Ellis EM.
        PLoS Negl Trop Dis. 2022 Nov;16(11):e0010880.
        BACKGROUND: The first documented human leptospirosis cases in the U.S. Virgin Islands (USVI) occurred following 2017 Hurricanes Irma and Maria. We conducted a representative serosurvey in USVI to estimate the seroprevalence and distribution of human leptospirosis and evaluate local risk factors associated with seropositivity. METHODOLOGY/PRINCIPAL FINDINGS: A stratified, two-stage cluster sampling design was used and consisted of three island strata and random selection of census blocks and then households. All eligible members of selected households were invited to participate (≥5 years old, resided in USVI ≥6 months and ≥6 months/year). Household and individual-level questionnaires were completed, and serum collected from each enrolled individual. Microscopic agglutination test serology was conducted, and bivariate and logistic regression analyses completed to identify risk factors for seropositivity. In March 2019, 1,161 individuals were enrolled from 918 households in St. Croix, St. Thomas, and St. John. The territory-wide weighted seroprevalence was 4.0% (95% CI:2.3-5.7). Characteristics/exposures independently associated with seropositivity using logistic regression included contact with cows (OR: 39.5; 95% CI: 9.0-172.7), seeing rodents/rodent evidence or contact with rodents (OR: 2.6; 95% CI: 1.1-5.9), and increasing age (OR: 1.02; 95% CI: 1.002-1.04); full or partial Caucasian/White race was negatively correlated with seropositivity (OR: 0.02, 95% CI: 0.04-0.7). Bivariate analysis showed self-reported jaundice since the 2017 hurricanes (pRR: 5.7; 95% CI: 1.0-33.4) was associated with seropositivity and using a cover/lid on cisterns/rainwater collection containers (pRR: 0.3; 95% CI: 0.08-0.8) was protective against seropositivity. CONCLUSIONS/SIGNIFICANCE: Leptospirosis seropositivity of 4% across USVI demonstrates an important human disease that was previously unrecognized and emphasizes the importance of continued leptospirosis surveillance and investigation. Local risk factors identified may help guide future human and animal leptospirosis studies in USVI, strengthen leptospirosis public health surveillance and treatment timeliness, and inform targeted education, prevention, and control efforts.

    • Community Health Services
      1. School district prevention policies and risk of COVID-19 among in-person K-12 educators, Wisconsin, 2021
        DeJonge PM, Pray IW, Gangnon R, McCoy K, Tomasallo C, Meiman J.
        Am J Public Health. 2022 Dec;112(12):1791-1799.
        Objectives. To assess the rate of COVID-19 among in-person K-12 educators and the rate's association with various COVID-19 prevention policies in school districts. Methods. We linked actively working, in-person K-12 educators in Wisconsin to COVID-19 cases with onset from September 2 to November 24, 2021. A mixed-effects Cox proportional hazards model, adjusted for pertinent person- and community-level confounders, compared the hazard rate of COVID-19 among educators working in districts with and without specific COVID-19 prevention policies. Results. In-person educators working in school districts that required masking for students and staff experienced 19% lower hazards of COVID-19 than did those in districts without any masking policy (hazard ratio = 0.81; 95% confidence interval = 0.72, 0.92). Reduced COVID-19 hazards were consistent and remained statistically significant when educators were stratified by elementary, middle, and high school environments. Conclusions. In Wisconsin's K-12 school districts, during the fall 2021 academic semester, a policy that required both students and staff to mask was associated with significantly reduced risk of COVID-19 among in-person educators across all grade levels. (Am J Public Health. 2022;112(12):1791-1799. https://doi.org/10.2105/AJPH.2022.307095).


      3. Strategies to increase the intention to get vaccinated against COVID-19: Findings from a nationally representative survey of US adults, October 2020 to October 2021
        Naeim A, Guerin RJ, Baxter-King R, Okun AH, Wenger N, Sepucha K, Stanton AL, Rudkin A, Holliday D, Rossell Hayes A, Vavreck L.
        Vaccine. 2022 Sep 12.
        OBJECTIVES: We examined COVID-19 vaccination status, intention, and hesitancy and the effects of five strategies to increase the willingness of unvaccinated adults (≥18 years) to get a COVID vaccine. METHODS: Online surveys were conducted between October 1-17, 2020 (N = 14,946), December 4-16, 2020 (N = 15,229), April 8-22, 2021 (N = 14,557), June 17-July 6, 2021 (N = 30,857), and September 3-October 4, 2021 (N = 33,088) with an internet-based, non-probability opt-in sample of U.S. adults matching demographic quotas. Respondents were asked about current COVID-19 vaccination status, intention and hesitancy to get vaccinated, and reasons for vaccine hesitancy. Unvaccinated respondents were assigned to treatment groups to test the effect of five strategies (endorsements, changing social restrictions, financial incentives, vaccine requirements for certain activities, and vaccine requirements for work). Chi-square tests of independence were performed to detect differences in the response distributions. RESULTS: Willingness to be vaccinated (defined as being vaccinated or planning to be) increased over time from 47.6 % in October 2020 to 81.1 % in October 2021. By October 2021, across most demographic groups, over 75 % of survey respondents had been or planned to be vaccinated. In terms of strategies: (1) endorsements had no positive effect, (2) relaxing the need for masks and social distancing increased Intention to Get Vaccinated (IGV) by 6.4 % (p < 0.01), (3) offering financial incentives increased the IGV between 12.3 and 18.9 % (p <.001), (4) vaccine requirements for attending sporting events or traveling increased IGV by 7.8 % and 9.1 %, respectively (p = 0.02), and vaccine requirement for work increased IGV by 35.4 %. The leading causes (not mutually exclusive) for hesitancy were concerns regarding vaccine safety (52.5 %) or side effects (51.6 %), trust in the government's motives (41.0 %), and concerns about vaccine effectiveness (37.6 %). CONCLUSIONS: These findings suggest that multiple strategies may be effective and needed to increase COVID-19 vaccination among hesitant adults during the pandemic.

    • Disaster Preparedness and Emergency Services
      1. From evidence-based implementation guides to meaningful action: Public health practitioners use readiness assessments to build bridges to successful community prevention implementation
        Walker JR, Anding JD, Dudensing RM, Lavinghouze SR, Jauregui V, Coats K.
        Health Promot Pract. 2022 Nov;23(1_suppl):118s-127s.
        Readiness has been cited as a determining factor in whether a community can effectively implement, support, and sustain an initiative. Through readiness assessments and technical assistance, public health practitioners can be the bridge between the gap of reaching goals outlined in Healthy People 2030, or another funder's guides, and actionable, successful, implementation. Readiness assessments are practical tools for implementing change in public health. Here we discuss three readiness assessment activities that we developed for four Texas counties: a partnership mapping tool, an Ease and Impact score, and a round table discussion. Through the assessments, we ascertained both readiness and the relevance of Policy, Systems and Environment opportunities. We used readiness assessments to translate our funder's implementation guide to meet the needs of four counties. Data allowed us to determine whether communities were ready to move forward with minimal technical assistance, needed further assessment to better understand relevance and feasibility within the community to implement the initiative, or whether this opportunity was not a good fit at the time. We adapted readiness tools based on components of the R = MC(2) framework so we could assess the readiness (motivation [M]; general organizational capacity [C]; and innovation-specific capacities [C]) of the participant groups and based on that assessment, we provided appropriate, tailored technical assistance. Public health practitioners and local supporters can use readiness tools and technical assistance to build a bridge from implementation guide(s) to effective community program implementation.

      2. Influenza A(H7N9) pandemic preparedness: Assessment of the breadth of heterologous antibody responses to emerging viruses from multiple pre-pandemic vaccines and population immunity
        Levine MZ, Holiday C, Bai Y, Zhong W, Liu F, Jefferson S, Gross FL, Tzeng WP, Fries L, Smith G, Boutet P, Friel D, Innis BL, Mallett CP, Davis CT, Wentworth DE, York IA, Stevens J, Katz JM, Tumpey T.
        Vaccines (Basel). 2022 Nov 1;10(11).
        Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03(A); 2. inactivated vaccine with 5.75 μg HA/dose + AS03(A;) 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

    • Disease Reservoirs and Vectors
      1. Among disease vectors, Aedes aegypti (L.) (Diptera: Culicidae) is one of the most insidious species in the world. The disease burden created by this species has dramatically increased in the past 50 years, and during this time countries have relied on pesticides for control and prevention of viruses borne by Ae. aegypti. The small number of available insecticides with different modes of action had led to increases in insecticide resistance, thus, strategies, like the "Incompatible Insect Technique" using Wolbachia's cytoplasmic incompatibility are desirable. We evaluated the effect of releases of Wolbachia infected Ae. aegypti males on populations of wild Ae. aegypti in the metropolitan area of Houston, TX. Releases were conducted by the company MosquitoMate, Inc. To estimate mosquito population reduction, we used a mosquito abundance Bayesian hierarchical estimator that accounted for inefficient trapping. MosquitoMate previously reported a reduction of 78% for an intervention conducted in Miami, FL. In this experiment we found a reduction of 93% with 95% credibility intervals of 86% and 96% after six weeks of continual releases. A similar result was reported by Verily Life Sciences, 96% [94%, 97%], in releases made in Fresno, CA.

    • Environmental Health
      1. Exposure to glyphosate in the United States: Data from the 2013-2014 National Health and Nutrition Examination Survey
        Ospina M, Schütze A, Morales-Agudelo P, Vidal M, Wong LY, Calafat AM.
        Environ Int. 2022 Nov 4;170:107620.
        BACKGROUND: Exposure to glyphosate, the most used herbicide in the United States, is not well characterized. We assessed glyphosate exposure in a representative sample of the U.S. population ≥ 6 years from the 2013-2014 National Health and Nutrition Examination Survey. METHODS: We quantified glyphosate in urine (N = 2,310) by ion chromatography isotope-dilution tandem mass spectrometry. We conducted univariate analysis using log-transformed creatinine-corrected glyphosate concentrations with demographic and lifestyle covariates we hypothesized could affect glyphosate exposure based on published data including race/ethnicity, sex, age group, family income to poverty ratio, fasting time, sample collection season, consumption of food categories (including cereal consumption) and having used weed killer products. We used multiple logistic regression to examine the likelihood of glyphosate concentrations being above the 95th percentile and age-stratified multiple linear regression to evaluate associations between glyphosate concentrations and statistically significant covariates from the univariate analysis: race/ethnicity, sex, age group, fasting time, cereal consumption, soft drink consumption, sample collection season, and urinary creatinine. RESULTS: Glyphosate weighted detection frequency was 81.2 % (median (interquartile range): 0.392 (0.263-0.656) μg/L; 0.450 (0.266-0.753) μg/g creatinine). Glyphosate concentration decreased from age 6-11 until age 20-59 and increased at 60+ years in univariate analyses. Children/adolescents and adults who fasted > 8 h had significantly lower model-adjusted geometric means (0.43 (0.37-0.51) μg/L and 0.37 (0.33-0.39) μg/L) than those fasting ≤ 8 h (0.51 (0.46-0.56) μg/L and 0.44 (0.41-0.48) μg/L), respectively. The likelihood (odds ratio (95 % CI)) of glyphosate concentrations being > 95th percentile was 1.94 (1.06-3.54) times higher in people who fasted ≤ 8 h than people fasting > 8 h (P = 0.0318). CONCLUSIONS: These first nationally representative data suggest that over four-fifths of the U.S. general population ≥ 6 years experienced recent exposure to glyphosate. Variation in glyphosate concentration by food consumption habits may reflect diet or lifestyle differences.

      2. Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study
        Weber KA, Yang W, Carmichael SL, Collins RT, Luben TJ, Desrosiers TA, Insaf TZ, Le MT, Evans SP, Romitti PA, Yazdy MM, Nembhard WN, Shaw GM.
        Environ Res. 2022 Nov 7;216(Pt 3):114760.
        BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.

      3. Differences in rural built environment perceptions across demographic and social environment characteristics
        Baxter SL, Jackson E, Onufrak S, Parisi MA, Griffin SF.
        Health Promot Pract. 2022 Nov;23(1_suppl):44s-54s.
        The benefits of physical activity to health and obesity prevention are well established. However, attributes of the built environment influence participation in physical activity. The purpose of this study is to assess differences in perceptions of neighborhood walkability across demographic characteristics and social environment factors among rural residents. In a telephone survey, adult respondents (N = 448) across nine rural counties in a southeastern state answered questions about perceived neighborhood walkability, demographic characteristics, and their neighborhood social environment. Study recruitment for a convenience sample occurred through collaborations with local community organizations. Prevalence of destinations and barriers were estimated according to demographic and neighborhood social environment characteristics. Multiple logistic regression models assessed the association of demographic and neighborhood social environment characteristics with neighborhood walkability and calculated adjusted prevalence. Relaxing places to walk were the most often reported destinations (62.0%), followed by retail destinations (45.7%), and communal destinations (42.6%). Traffic was the most reported barrier to safe walking (40.4%), followed by animals (37.5%), and crime (30.5%). Perceptions of retail and communal destinations varied by age and race. Perceptions of traffic and crime as barriers varied by race, weight status, and income. Community belonging and social cohesion were associated with lower perceptions of barriers. Study findings present demographic characteristics and social environment attributes as key factors that shape perceived neighborhood walkability. Findings can help inform programmatic efforts and environmental change strategies to improve walking in rural areas.

    • Epidemiology and Surveillance
      1. Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard
        Nakayama SF, St-Amand A, Pollock T, Apel P, Bamai YA, Barr DB, Bessems J, Calafat AM, Castaño A, Covaci A, Duca RC, Faure S, Galea KS, Hays S, Hopf NB, Ito Y, Jeddi MZ, Kolossa-Gehring M, Kumar E, LaKind JS, López ME, Louro H, Macey K, Makris KC, Melnyk L, Murawski A, Naiman J, Nassif J, Noisel N, Poddalgoda D, Quirós-Alcalá L, Rafiee A, Rambaud L, Silva MJ, Ueyama J, Verner MA, Waras MN, Werry K.
        Int J Hyg Environ Health. 2022 Nov 7;247:114046.
        Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

      2. Agreement between pregnant individuals' self-report of coronavirus disease 2019 (COVID-19) vaccination and medical record documentation
        Wielgosz K, Dawood FS, Stockwell MS, Varner M, Newes-Adeyi G, Ellington S, Vargas C, Bruno AM, Powers E, Morrill T, Reichle L, Battarbee AN, Tita AT.
        Obstet Gynecol. 2022 Nov 3.
        For public health research such as vaccine uptake or effectiveness assessments, self-reported coronavirus disease 2019 (COVID-19) vaccination status may be a more efficient measure than verifying vaccination status from medical records if agreement between sources is high. We assessed agreement between self-reported and medical record-documented COVID-19 vaccination status among pregnant individuals followed in a cohort during August 2020-October 2021. At end of pregnancy, participants completed questionnaires about COVID-19 vaccine receipt during pregnancy; staff verified vaccination status using medical records. Agreement was assessed between self-reported and medical record vaccination status using Cohen's kappa. There was high agreement between self-reported and medical record vaccination status (Kappa coefficient=0.94, 95% CI 0.91-0.98), suggesting that self-report may be acceptable for ascertaining COVID-19 vaccination status during pregnancy.

    • Food Safety
      1. Bi-national outbreak of Salmonella newport infections linked to onions: The United States experience
        McCormic ZD, Patel K, Higa J, Bancroft J, Donovan D, Edwards L, Cheng J, Adcock B, Bond C, Pereira E, Doyle M, Wise ME, Gieraltowski L.
        Epidemiol Infect. 2022 Nov 16:1-23.

    • Genetics and Genomics
      1. Editorial: DNA-based population screening for precision public health
        Milko LV, Khoury MJ.
        Front Genet. 2022 ;13:1061329.

      2. SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference
        Bendall EE, Paz-Bailey G, Santiago GA, Porucznik CA, Stanford JB, Stockwell MS, Duque J, Jeddy Z, Veguilla V, Major C, Rivera-Amill V, Rolfes MA, Dawood FS, Lauring AS.
        mSphere. 2022 Nov 15:e0040022.
        The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

    • Health Behavior and Risk
      1. Trends in preexposure prophylaxis use among sex partners as reported by persons with HIV - United States, May 2015-June 2020
        Beer L, Tie Y, Dasgupta S, McManus T, Smith DK, Shouse RL.
        AIDS. 2022 Dec 1;36(15):2161-2169.
        OBJECTIVE: To estimate trends in the proportion of sexually active U.S. adults with HIV (PWH) reporting an HIV-discordant sexual partner taking preexposure prophylaxis (PrEP) and proportion of partners taking PrEP. DESIGN: The Medical Monitoring Project is a complex sample survey of U.S. adults with diagnosed HIV. METHODS: We used annual cross-sectional data collected during June 2015-May 2020 to estimate the annual percentage change (EAPC), overall and by selected characteristics, in reported partner PrEP use among PWH with HIV-discordant partners (N = 8707) and reported PrEP use among these partners (N = 15 844). RESULTS: The proportion of PWH reporting PrEP use by one or more HIV-discordant sex partner rose 19.5% annually (11.3 to 24.4%). The prevalence rose from 6.0 to 17.4% (EAPC, 25.8%) among Black PWH, 10.1 to 26.0% (EAPC, 19.5%) among Hispanic/Latino PWH, and 20.8 to 34.6% (EAPC, 16.3%) among White PWH. Among MSM with HIV, the prevalence increased from 9.6 to 32.6% (EAPC, 28.2%) among Black MSM, 16.6 to 36.0% (EAPC, 15.6%) among Hispanic/Latino MSM, and 24.9 to 44.1% (EAPC, 17.9%) among White MSM. Among HIV-discordant sex partners, the proportion reported to be taking PrEP increased 21.1% annually (7.8 to 18.8%). Reported PrEP use rose from 4.9 to 14.2% (EAPC, 29.9%) among Black partners, 6.5 to 16.8% (EAPC, 20.3%) among Hispanic/Latino partners, and 12.7 to 26.1% (EAPC, 17.0%) among White partners. CONCLUSIONS: One in five HIV-discordant sexual partners of PWH was reported to be taking PrEP. PrEP use rose among all examined populations, although the increases did not eliminate disparities in PrEP use.

      2. Changes in sexual behavior over the COVID-19 pandemic among a community-based cohort of men who have sex with men in Columbus, Ohio
        Ricks JM, Spahnie M, Matthews A, Copen CE, Rushmore J, Bernstein KT, Miller WC, Turner AN.
        Sex Transm Dis. 2022 Dec 1;49(12):844-850.
        BACKGROUND: The purpose was to assess COVID-19 beliefs and attitudes and examine COVID-19-related changes in sexual behavior of men who have sex with men during 3 time periods: April-July 2020 (T1), August-December 2020 (T2), January-May 2021 (T3). METHODS: Data were analyzed from 157 men who have sex with men in Ohio recruited to participate in a longitudinal multisite network study of syphilis epidemiology in 3 US cities: Columbus, Ohio; Baltimore, Maryland; and Chicago, Illinois. In April 2020, a COVID-19 module was appended to existing baseline and follow-up surveys to assess beliefs, attitudes, and changes in sexual behavior. Sample characteristics were summarized. Correlations between demographic variables (age, racial identity) and COVID-19 outcomes were examined. RESULTS: In response to COVID-19 social distancing restrictions and self-reported anxiety, some men limited sexual activity at T1, but the majority (n = 105 [67%]) continued to engage in sex. The number of men engaging in sex increased over time (T2: n = 124 [79%]; T3: n = 121 [77%]). At T1, men not in a relationship more frequently reported having less sex compared with prepandemic (n = 39 [57%]). By T3, men in a relationship more frequently reported less sex (n = 32 [54%]). Increased anxiety about sex and condom use was positively correlated with identifying as a man of color (P < 0.001). Most of the sample reported either starting or increasing online sexual activity during each time period. CONCLUSIONS: Future efforts to target sexual health during a pandemic or other health emergencies should prioritize men of color and address the unique perspective of both single and partnered men.

    • Health Equity and Health Disparities
      1. Spatial modeling of vaccine deserts as barriers to controlling SARS-CoV-2
        Rader B, Astley CM, Sewalk K, Delamater PL, Cordiano K, Wronski L, Rivera JM, Hallberg K, Pera MF, Cantor J, Whaley CM, Bravata DM, Lee L, Patel A, Brownstein JS.
        Commun Med (Lond). 2022 Nov 10;2(1):141.
        BACKGROUND: COVID-19 vaccine distribution is at risk of further propagating the inequities of COVID-19, which in the United States (US) has disproportionately impacted the elderly, people of color, and the medically vulnerable. We sought to measure if the disparities seen in the geographic distribution of other COVID-19 healthcare resources were also present during the initial rollout of the COVID-19 vaccine. METHODS: Using a comprehensive COVID-19 vaccine database (VaccineFinder), we built an empirically parameterized spatial model of access to essential resources that incorporated vaccine supply, time-willing-to-travel for vaccination, and previous vaccination across the US. We then identified vaccine deserts-US Census tracts with localized, geographic barriers to vaccine-associated herd immunity. We link our model results with Census data and two high-resolution surveys to understand the distribution and determinates of spatially accessibility to the COVID-19 vaccine. RESULTS: We find that in early 2021, vaccine deserts were home to over 30 million people, >10% of the US population. Vaccine deserts were concentrated in rural locations and communities with a higher percentage of medically vulnerable populations. We also find that in locations of similar urbanicity, early vaccination distribution disadvantaged neighborhoods with more people of color and older aged residents. CONCLUSION: Given sufficient vaccine supply, data-driven vaccine distribution to vaccine deserts may improve immunization rates and help control COVID-19. COVID-19 has affected the elderly, people of color, and individuals with chronic illnesses more than the general population. Large barriers to accessing the COVID-19 vaccine could make this problem worse. We used a website called VaccineFinder, which has information on the location of most COVID-19 vaccine doses in the US, to measure vaccine accessibility in early 2021. We then identified vaccine deserts, defined as small US regions with poor access to the COVID-19 vaccine. We found that over 10% of the US lived in a vaccine desert. Overall, we found that vaccines were less available to people in rural areas, people of color, and individuals with chronic illnesses. It will be important to reverse this pattern and ensure enough vaccines are sent to these communities to help reduce the spread of COVID-19. eng

      2. BACKGROUND: To reduce health disparities and improve the health of Americans overall, addressing community-level social and structural factors, such as social vulnerability, may help explain the higher rates of HIV diagnoses among and between race/ethnicity groups. METHODS: Data were obtained from CDC's National HIV Surveillance System (NHSS) and the CDC/ATSDR social vulnerability index (SVI). NHSS data for Black, Hispanic/Latino, and White adults with HIV diagnosed in 2018 were linked to SVI data. To measure the relative disparity, rate ratios (RRs) with 95% CIs were calculated to examine the relative difference comparing census tracts with the lowest SVI scores (quartile 1, Q1) to those with the highest SVI scores (quartile 4, Q4) by sex assigned at birth for age group and region of residence. Differences in the numbers of diagnoses across the quartiles were analyzed by sex assigned at birth and transmission category. RESULTS: There were 13,807 Black, 8747 Hispanic/Latino, and 8325 White adults who received a diagnosis of HIV infection in the United States in 2018-with the highest HIV diagnosis rates among adults who lived in census tracts with the highest vulnerability (Q4). For each race/ethnicity and both sexes, the rate of HIV diagnoses increased as social vulnerability increased. The highest disparities in HIV diagnosis rates by SVI were among persons who inject drugs, and the highest within-group RRs were typically observed among older persons and persons residing in the Northeast. CONCLUSION: To reach the goals of several national HIV initiatives, efforts are needed to address the social vulnerability factors that contribute to racial and ethnic disparities in acquiring HIV and receiving care and treatment.

      3. Health care access and use among adults with and without vision impairment: Behavioral Risk Factor Surveillance System, 2018
        Cheng Q, Okoro CA, Mendez I, Lundeen EA, Saaddine JB, Stein R, Holbrook J.
        Prev Chronic Dis. 2022 Nov 10;19:E70.
        INTRODUCTION: Adults with vision impairment may have unique needs when accessing health care to maintain good health. Our study examined the relationship between vision status and access to and use of health care. METHODS: We analyzed data on adults aged 18 years or older who participated in the 2018 Behavioral Risk Factor Surveillance System. Vision impairment was identified by a yes response to the question "Are you blind or do you have serious difficulty seeing, even when wearing glasses?" Survey questions assessed health care access over the past year (having health insurance coverage, a usual health care provider, or unmet health care needs because of cost) and use of health care during that period (routine checkup and dental visit). We estimated age-adjusted prevalence of our outcomes of interest and used bivariate analyses to compare estimates of the outcomes by vision impairment status. RESULTS: The prevalence of self-reported vision impairment was 5.3%. Compared with adults without impaired vision, adults with vision impairment had a lower prevalence of having health insurance coverage (80.6% vs 87.6%), a usual health care provider (71.9% vs 75.7%), or a dental visit in the past year (52.9% vs 67.2%) and a higher prevalence of having an unmet health care need in the past year because of cost (29.2% vs 12.6%). CONCLUSION: Adults with vision impairment reported lower access to and use of health care than those without. Further research can better identify and understand barriers to care to improve access to and use of health care among this population.

      4. Explaining demographic differences in COVID-19 vaccination stage in the United States - April-May 2021
        Huang Q, Abad N, Bonner KE, Baack B, Petrin R, Hendrich MA, Lewis Z, Brewer NT.
        Prev Med. 2022 Nov 10:107341.
        COVID-19 vaccine coverage in the US has marked demographic and geographical disparities, but few explanations exist for them. Our paper aimed to identify behavioral and social drivers that explain these vaccination disparities. Participants were a national sample of 3562 American adults, recruited from the Ipsos KnowledgePanel. Participants completed an online survey in spring 2021, when COVD-19 vaccination was available for higher-risk groups but not yet available to all US adults. The survey assessed COVID-19 vaccination stage (intentions and vaccine uptake), constructs from the Increasing Vaccination Model (IVM) domains (thinking and feeling, social processes, and direct behavior change), self-reported exposure to COVID-19 vaccine information, and demographic characteristics. Analyses used multiple imputation to address item nonresponse and linear regressions to conduct mediation analyses. Higher COVID-19 vaccination stage was strongly associated with older age, liberal political ideology, and higher income in adjusted analyses (all p < .001). Vaccination stage was more modestly associated with urbanicity, white race, and Hispanic ethnicity (all p < .05). Some key mediators that explained more than one-third of demographic differences in vaccination stage were perceived vaccine effectiveness, social norms, and recommendations from family and friends across most demographic characteristics (all p < .05). Other mediators included safety concerns, trust, altruism, provider recommendation, and information seeking. Access to vaccination, barriers to vaccination, and self-efficacy explained few demographic differences. One of the most reliable explanations for demographic differences in COVID-19 vaccination stage is social processes, including social norms, recommendations, and altruism. Interventions to promote COVID-19 vaccination should address social processes and other domains in the IVM.

    • Immunity and Immunization
      1. Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 Delta and beyond
        Kwon HJ, Kosikova M, Tang W, Ortega-Rodriguez U, Radvak P, Xiang R, Mercer KE, Muskhelishvili L, Davis K, Ward JM, Kosik I, Holly J, Kang I, Yewdell JW, Plant EP, Chen WH, Shriver MC, Barnes RS, Pasetti MF, Zhou B, Wentworth DE, Xie H.
        iScience. 2022 Nov 5:105507.
        Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2(nd) dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3(rd) vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections.

      2. Expected rates of select adverse events after immunization for coronavirus disease 2019 vaccine safety monitoring
        Abara WE, Gee J, Delorey M, Tun Y, Mu Y, Shay DK, Shimabukuro T.
        J Infect Dis. 2022 May 4;225(9):1569-1574.
        Using meta-analytic methods, we calculated expected rates of 20 potential adverse events of special interest (AESI) that would occur after coronavirus disease 2019 (COVID-19) vaccination within 1-, 7-, and 42-day intervals without causal associations. Based on these expected rates, if 10 000 000 persons are vaccinated, (1) 0.5, 3.7, and 22.5 Guillain-Barre syndrome cases, (2) 0.3, 2.4, and 14.3 myopericarditis cases, (3) and 236.5, 1655.5, and 9932.8 all-cause deaths would occur coincidentally within 1, 7, and 42 days postvaccination, respectively. Expected rates of potential AESI can contextualize events associated temporally with immunization, aid in safety signal detection, guide COVID-19 vaccine health communications, and inform COVID-19 vaccine benefit-risk assessments.

      3. Interim recommendations from the Advisory Committee on Immunization Practices for the use of bivalent booster doses of COVID-19 vaccines - United States, October 2022
        Rosenblum HG, Wallace M, Godfrey M, Roper LE, Hall E, Fleming-Dutra KE, Link-Gelles R, Pilishvili T, Williams J, Moulia DL, Brooks O, Talbot HK, Lee GM, Bell BP, Daley MF, Meyer S, Oliver SE, Twentyman E.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 11;71(45):1436-1441.
        Four COVID-19 vaccines are currently approved for primary series vaccination in the United States under a Biologics License Application or authorized under an emergency use authorization (EUA) by the Food and Drug Administration (FDA), and recommended for primary series vaccination by the Advisory Committee on Immunization Practices (ACIP): 1) the 2- or 3-dose monovalent mRNA BNT162b2 (Pfizer-BioNTech, Comirnaty) COVID-19 vaccine; 2) the 2- or 3-dose monovalent mRNA mRNA-1273 (Moderna, Spikevax) COVID-19 vaccine; 3) the single-dose adenovirus vector-based Ad26.COV.S (Janssen [Johnson & Johnson]) COVID-19 vaccine; and 4) the 2-dose adjuvanted, protein subunit-based NVX-CoV2373 (Novavax) COVID-19 vaccine. The number of doses recommended is based on recipient age and immunocompromise status (1). For additional protection, FDA has amended EUAs to allow for COVID-19 booster doses in eligible persons (1). Because COVID-19 vaccines have demonstrated decreased effectiveness during the period when the Omicron variant (B.1.1.529) of SARS-CoV-2 predominated, bivalent booster doses (i.e., vaccine with equal components from the ancestral and Omicron strains) were considered for the express purpose of improving protection conferred by COVID-19 vaccine booster doses (2). During September-October 2022, FDA authorized bivalent mRNA vaccines for use as a booster dose in persons aged ≥5 years who completed any FDA-approved or FDA-authorized primary series and removed EUAs for monovalent COVID-19 booster doses (1). Pfizer-BioNTech and Moderna bivalent booster vaccines each contain equal amounts of spike mRNA from the ancestral and Omicron BA.4/BA.5 strains. After the EUA amendments, ACIP and CDC recommended that all persons aged ≥5 years receive 1 bivalent mRNA booster dose ≥2 months after completion of any FDA-approved or FDA-authorized monovalent primary series or monovalent booster doses.

      4. Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster
        Laing KJ, Ouwendijk WJ, Campbell VL, McClurkan CL, Mortazavi S, Elder Waters M, Krist MP, Tu R, Nguyen N, Basu K, Miao C, Schmid DS, Johnston C, Verjans G, Koelle DM.
        Nat Commun. 2022 Nov 15;13(1):6957.
        Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.

      5. Burden of medically attended influenza infection and cases averted by vaccination - United States, 2016/17 through 2018/19 influenza seasons
        Jackson ML, Phillips CH, Wellwood S, Kiniry E, Jackson LA, Martin ET, Monto AS, McLean HQ, Belongia EA, Gaglani M, Dunnigan K, Raiyani C, Murthy K, Flannery B, Chung JR.
        Vaccine. 2022 Nov 12.
        BACKGROUND: Epidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by vaccination in four ambulatory care sites in the United States, during seasons when overall influenza VE ranged from 29% to 40%. METHODS: We conducted active surveillance for influenza at ambulatory care settings at four sites within the United States Influenza Vaccine Effectiveness Network. We extrapolated the total number of influenza cases in the source populations served by these organizations based on incidence of medically attended acute respiratory illness in the source population and influenza test results in those actively tested for influenza. We estimated the number of medically attended influenza cases averted based on incidence, vaccine coverage, and VE. RESULTS: From 2016/17 through 2018/19, incidence of ambulatory visits for laboratory-confirmed influenza ranged from 31 to 51 per 1,000 population. Incidence was highest in children aged 9-17 years (range, 56 to 81 per 1,000) and lowest in adults aged 18-49 years (range, 23-32 per 1,000). Medically attended cases averted by vaccination ranged from a high of 46.6 (95 % CI, 12.1- 91.9) per 1,000 vaccinees in children aged 6 months to 8 years, to a low of 6.9 (95 % CI, -5.1- 27.3) per 1,000 vaccinees in adults aged ≥ 65 years. DISCUSSION: Even in seasons with low vaccine effectiveness for a particular virus subtype, influenza vaccines can still lead to clinically meaningful reductions in ambulatory care visits for influenza.

      6. OBJECTIVE: To use a model-based approach to estimate vaccination coverage of routinely recommended childhood and adolescent vaccines for the United States. METHODS: We used a hierarchical model with retrospective cohort data from eleven IIS jurisdictions, which contains vaccination records submitted by providers. Numerators included data from 2014 to 2019 at the county level for 2.4 million children at age 2 months and 14.4 million adolescents aged 13-17. Age-appropriate Census populations were used as denominators. Covariates associated with childhood and adolescent vaccinations were included in the model. Model-based estimates for each county were generated and aggregated to the national level to produce national vaccination coverage estimates and compared to National Immunization Survey (NIS) estimates of vaccination coverage. Trends of estimated vaccination coverage were compared between the model-based approach and NIS. RESULTS: From 2014 to 18, model-based national vaccination coverage estimates were within ten percentage points of NIS-Child vaccination coverage estimates for most vaccines among children at age 24 months. One notable difference was higher model-based vaccination coverage estimates for hepatitis B birth dose compared to NIS-Child coverage estimates. From 2014 to 19, model-based national vaccination coverage estimates were within ten percentage points of NIS-Teen vaccination coverage estimates for most vaccines among adolescents aged 13-17 years. Model-based vaccination coverage estimates were notably lower for varicella, MMR, and Hepatitis B compared to NIS-Teen coverage estimates among adolescents. Trends in estimates of national vaccination coverage were similar between model-based estimates for children and adolescents as compared to NIS-Child and NIS-Teen, respectively. CONCLUSIONS: A hierarchical model applied to data from IIS may be used to estimate coverage for routinely recommended vaccines among children and adolescents and allows for timely analyses of childhood and adolescent vaccines to quickly assess trends in vaccination coverage across the United States. Monitoring real-time vaccination coverage can help promote immunizations to protect children and adolescents against vaccine-preventable diseases.

      7. Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults
        Tompkins LK, Baggs J, Myers TR, Gee JM, Marquez PL, Kennedy SB, Peake D, Dua D, Hause AM, Strid P, Abara W, Rossetti R, Shimabukuro TT, Shay DK.
        Vaccine. 2022 Nov 1.
        BACKGROUND: Risk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0-7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs. METHODS: We conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0-7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories. RESULTS: Follow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0-7 following dose 2 was not common among case-patients or controls. CONCLUSIONS: History of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.

      8. Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States
        Turbyfill C, Adams K, Tenforde MW, Murray NL, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Keipp Talbot H, Casey JD, Mohr NM, Zepeski A, Shapiro NI, Gibbs KW, Clark Files D, Hager DN, Shehu A, Prekker ME, Frosch AE, Exline MC, Gong MN, Mohamed A, Johnson NJ, Srinivasan V, Steingrub JS, Peltan ID, Brown SM, Martin ET, Lauring AS, Khan A, Busse LW, Ten Lohuis CC, Duggal A, Wilson JG, June Gordon A, Qadir N, Chang SY, Mallow C, Rivas C, Kwon JH, Halasa N, Chappell JD, Grijalva CG, Rice TW, Stubblefield WB, Baughman A, Rhoads JP, Lindsell CJ, Hart KW, McMorrow M, Surie D, Self WH, Patel MM.
        Vaccine. 2022 Nov 15;40(48):6979-6986.
        BACKGROUND: Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls. METHODS: Adults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group. RESULTS: 5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64 years, VE was 93 % (95 % CI: 90-94) using syndrome-negative controls and 91 % (95 % CI: 88-93) using test-negative controls. CONCLUSIONS: Despite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.

    • Informatics
      1. Accuracy of COVID-19-like-illness diagnoses in electronic health record data: Retrospective cohort study
        Rao S, Bozio C, Butterfield K, Reynolds S, Reese S, Ball S, Steffens A, Demarco M, McEvoy C, Thompson M, Rowley E, Porter R, Fink R, Irving S, Naleway A.
        JMIR Form Res. 2022 Sep 30.
        BACKGROUND: Electronic health record (EHR) data provide a unique opportunity to study the epidemiology of COVID-19, clinical outcomes, comparative effectiveness of therapies and vaccine effectiveness but require a well-defined computable phenotype of COVID-19-like illness (CLI). OBJECTIVE: The study objective was to evaluate the performance of pathogen-specific and other acute respiratory illness ICD-9 and 10 codes in identifying COVID-19 cases in emergency department/urgent care (ED/UC) and inpatient settings. METHODS: We conducted a retrospective observational cohort study using EHR, claims, and laboratory information systems data of ED/UC and inpatient encounters from four health systems in the US. Patients aged ≥18 years of age with an ED/UC or inpatient encounter for an acute respiratory illness (ARI) who underwent a SARS-CoV-2 PCR test between March 1, 2020 through March 31, 2021 were included. We evaluated various CLI definitions using combinations of ICD-10 codes as follows: a) COVID-19-specific codes; b) CLI definition used in VISION network studies (VISION CLI); c) ARI signs, symptoms and diagnosis codes only; d) signs and symptoms of ARI only; and e) random forest model definitions. We evaluated sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of each CLI definition using a positive SARS-CoV-2 PCR test as the reference standard. We evaluated the performance of each CLI definition for distinct hospitalization and ED/UC cohorts. RESULTS: Among 90,952 hospitalizations and 137,067 ED/UC visits, 5,627 (6.2%) and 9,866 (7.2%) were positive for SARS-CoV-2, respectively. COVID-19-specific codes had high sensitivity (91.6%) and specificity (99.6%) in identifying patients with SARS-CoV-2 positivity for hospitalized patients. The VISION CLI definition maintained high sensitivity (95.8%) but lowered specificity (45.5%). In contrast, signs and symptoms of acute respiratory illness had low sensitivity and PPV (28.9% and 11.8% respectively), but higher specificity and NPV (85.3% and 94.7% respectively). ARI diagnoses or signs and symptoms alone had low predictive performance. All CLI definitions had lowered sensitivity for ED/UC encounters. Random forest approaches identified distinct CLI definitions with high performance for hospital encounters, and moderate performance for ED/UC encounters. CONCLUSIONS: COVID-19-specific codes have high sensitivity and specificity for identifying adults with positive SARS-CoV-2 tests. Separate combinations of COVID-19-specific codes and ARI codes enhance the utility of CLI definitions for studies using EHR data in hospital and ED/UC settings.

    • Laboratory Sciences
      1. A multilingual tool for standardized laboratory biosafety and biosecurity assessment and monitoring
        Orelle A, Nikiema A, Zakaryan A, Albetkova AA, Keita MS, Rayfield MA, Peruski LF, Pierson A.
        Health Secur. 2022 Nov 16.
        Control of infectious diseases requires the handling of infectious materials by both clinical and public health laboratories with exposure risks for laboratory personnel and environment. A comprehensive tool for assessing the capacity to manage these risks could enable the development of action plans for mitigation. Under the framework of the Global Health Security Agenda action package for biosafety and biosecurity, the authors developed a tool dedicated to assessing laboratory biosafety and biosecurity. The Biosafety and Biosecurity Laboratory Assessment Tool (BSS LAT) assesses the status of all laboratory biosafety core requirements across 10 different modules. It consists of a standardized spreadsheet-based tool that provides automatic scoring. It is designed to support national, regional, and global efforts to strengthen biosafety in clinical, public health, and veterinary laboratories. The BSS LAT was first used in Burkina Faso in collaboration with the African Society for Laboratory Medicine and the US Centers for Disease Control and Prevention to support the country in strengthening their biorisk management system. Since then, it has been successfully used in other countries (ie, Armenia, Burundi, Cameroon, Ghana, Guinea, Kazakhstan, Liberia), various settings (medical and veterinary laboratories), and translated into several languages (eg, English, French, Russian). The BSS LAT is a multipurpose tool that assists with standardization of biosafety and biosecurity requirements for all laboratories working with infectious materials, serves as a self-assessment guide for laboratories to develop improvement plans and reinforce capacities, and serves as a training guide for individual laboratories and networks or at the national level. The BSS LAT can also be used as a monitoring tool for the assessment of biosafety and biosecurity across all laboratories working with infectious materials at the national, regional, and global levels.

    • Maternal and Child Health
      1. Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011
        Palmsten K, Suhl J, Conway KM, Kharbanda EO, Scholz TD, Ailes EC, Cragan JD, Nestoridi E, Papadopoulos EA, Kerr SM, Young SG, Olson C, Romitti PA.
        Birth Defects Res. 2022 Nov 11.
        BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

      2. Patterns in mothers' recollection of health care providers' young child feeding recommendations
        McGowan A, Boundy EO, Nelson JM, Hamner HC.
        J Nutr Educ Behav. 2022 Nov;54(11):1024-1033.
        OBJECTIVE: Characterize feeding guidance mothers recall receiving from their child's health care provider (HCP). DESIGN: Cross-sectional study of mothers participating in the 2017-2019 National Survey of Family Growth. PARTICIPANTS: US mothers reporting (n = 1,302) information about their youngest child (aged 6 months to 5 years). VARIABLES MEASURED: Weighted percentage of mothers who recalled their child's HCP discussing 6 different feeding topics by demographic characteristics. ANALYSIS: Logistic regression assessing the relationship between recall of feeding guidance and demographics. RESULTS: In this sample, 36.9% of mothers (95% confidence interval, 32.3-41.4) recalled HCPs recommending solid food before 6 months old (34.6% at 4-5 months, and 2.3% before 4 months). Mothers who were older or had a higher education level were more likely than their counterparts to recall their HCP discussing several of the feeding topics examined. CONCLUSION AND IMPLICATIONS: Mothers reported high recollection of early childhood nutrition guidance from their HCP; however, certain topics (eg, appropriate timing of solid food introduction) could be prioritized, and some subpopulations may need additional focus to improve receipt of messages. A better understanding of variability in recall of feeding guidance could provide information for interventions to address barriers to receiving and retaining guidance.

      3. Postdischarge glucocorticoid use and clinical outcomes of multisystem inflammatory syndrome in children
        Son MB, Berbert L, Young C, Dallas J, Newhams M, Chen S, Ardoin SP, Basiaga ML, Canny SP, Crandall H, Dhakal S, Dhanrajani A, Sagcal-Gironella AC, Hobbs CV, Huie L, James K, Jones M, Kim S, Lionetti G, Mannion ML, Muscal E, Prahalad S, Schulert GS, Tejtel KS, Villacis-Nunez DS, Wu EY, Zambrano LD, Campbell AP, Patel MM, Randolph AG.
        JAMA Netw Open. 2022 Nov 1;5(11):e2241622.
        IMPORTANCE: Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C). OBJECTIVES: To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months. EXPOSURES: Glucocorticoid treatment. MAIN OUTCOMES AND MEASURES: Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness. RESULTS: Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91). CONCLUSIONS AND RELEVANCE: In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

      4. Timing of positive hepatitis C virus test results during and 1 year before pregnancy
        Woodworth KR, Newton SM, Olsen EO, Tannis A, Sizemore L, Wingate H, Orkis L, Reynolds B, Longcore N, Thomas N, Bocour A, Wills A, Kim SY, Panagiotakopoulos L, Wester C, Delman Meaney D, Gilboa SM, Tong VT.
        Obstet Gynecol. 2022 Nov 3.
        The incidence of hepatitis C virus (HCV) infection in reproductive-aged adults quadrupled during the past decade. Hepatitis C can progress to advanced liver disease and be transmitted perinatally. Highly effective curative hepatitis C treatment is available but is not recommended in pregnancy. Using the Surveillance for Emerging Threats to Mothers and Babies Network, we describe timing of positive RNA testing among pregnant people with HCV (HCV RNA detected during or within one year prior to pregnancy). Four US jurisdictions reported 1161 pregnancies during 2018-2021 among people with hepatitis C: 75.9% were multiparous; and 21.4% had their first peri-pregnancy HCV RNA detected prior to pregnancy, indicating potential missed treatment opportunities to improve maternal health and prevent perinatal transmission.

      5. Maternal hepatitis C prevalence and trends by county, US: 2016-2020
        Ahrens KA, Rossen LM, Burgess AR, Palmsten K, Ziller EC.
        Paediatr Perinat Epidemiol. 2022 Nov 13.
        BACKGROUND: Trends in the prevalence of hepatitis C virus (HCV) infection among women delivering live births may differ in rural vs. urban areas of the United States, but estimation of trends based on observed counts may lead to unstable estimates in rural counties due to small numbers. OBJECTIVES: The objective of the study was to use small area estimation methods to provide updated county-level prevalence estimates and, for the first time, trends in maternal HCV infection among live births by county-level rurality. METHODS: Cross-sectional natality data from 2016 to 2020 were used to estimate maternal hepatitis C prevalence using hierarchical Bayesian models with spatiotemporal random effects to produce annual county-level estimates of maternal HCV infection and trends over time. Models included a 6-level rural-urban county classification, year, maternal characteristics and county-specific covariates. Data were analysed in 2022. RESULTS: There were 90,764/18,905,314 live births (4.8 per 1000) with HCV infection reported on the birth certificate. Hepatitis C prevalence was higher among rural counties as compared to urban counties. Rural counties had the largest annual increases in maternal hepatitis C prevalence (per 1000 births) from 2016 to 2020 (micropolitan: 0.39; noncore: 0.40), with smaller increases among less densely populated urban counties (medium metro: 0.28; small metro: 0.28) and urban counties (large central metro:0.11; large fringe metro: 0.14). CONCLUSIONS: The prevalence of maternal HCV infection was the highest in rural counties, and rural counties saw the greatest average prevalence increase during 2016-2020. County-level data can help in monitoring rural-urban trends in maternal HCV infection to reduce geographic disparities.

    • Occupational Safety and Health
      1. Intensity of physical therapy services: Association with work and health outcomes in injured workers with back pain in Washington State
        Chin B, Rundell SD, Sears JM, Fulton-Kehoe D, Spector JT, Franklin GM.
        Am J Ind Med. 2022 Nov 12.
        BACKGROUND: Associations between the intensity of physical therapy (PT) treatments and health outcomes among individuals with back pain have been examined in the general population; however, few studies have explored these associations in injured workers. Our study objective was to examine whether intensity of PT treatments is positively associated with work and health outcomes in injured workers with back pain. METHODS: We conducted a secondary analysis of prospective data collected from the Washington State Workers' Compensation (WC) Disability Risk Identification Study Cohort (D-RISC). D-RISC combined survey results with WC data from the Washington State Department of Labor and Industries. Workers with a State Fund WC claim for back injuries between June 2002 and April 2004 and who received PT services within the first year of injury were eligible. Intensity of PT treatment was measured as the type and amount of PT services within 28 days from the first PT visit. Outcome measures included work disability and self-reported measures for working for pay, pain intensity, and functional status at 1-year follow-up. We conducted linear and logistic regression models to test associations. RESULTS: We identified 662 eligible workers. In adjusted models, although the intensity of PT treatment was not significantly associated with work disability at 1-year follow-up, it was associated with lower odds of working for pay, decreased pain intensity, and improved functional status. CONCLUSIONS: Our findings suggest that there may be small benefits from receiving active PT, manual therapy, and frequent PT treatments within 28 days of initiating PT care.

      2. Cardiovascular disease among adults with work-related asthma, 2012-2017
        Dodd KE, Blackley DJ, Mazurek JM.
        Am J Prev Med. 2022 Nov 9.
        INTRODUCTION: Asthma is associated with an increased risk for cardiovascular disease, and adults with persistent, severe asthma have a significantly higher risk of cardiovascular disease than adults with intermittent or no asthma. METHODS: The objective of this cross-sectional study was to assess the association between work-related asthma status and cardiovascular disease among ever-employed adults (aged 18-64 years) with current asthma using data from the 2012-2017 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey from 37 states and the District of Columbia. Weighted prevalence ratios and 95% CIs, adjusted for age, sex, race/ethnicity, education, household income, smoking status, chronic obstructive pulmonary disease, diabetes, and BMI, were calculated. In addition, the associations of cardiovascular disease with adverse asthma outcomes and asthma control among adults with work-related asthma were examined. Analyses were conducted in 2021. RESULTS: Among an estimated annualized 14.8 million ever-employed adults aged 18-64 years with current asthma, adults with work-related asthma (prevalence ratio=1.5; 95% CI=1.2, 1.8) and possible work-related asthma (prevalence ratio=1.2; 95% CI=1.0, 1.5) were significantly more likely to have cardiovascular disease than adults with non-work-related asthma. Among adults with work-related asthma, those with very poorly controlled asthma (prevalence ratio=1.8; 95% CI=1.3, 2.5) and an asthma-related emergency room visit (prevalence ratio=1.5; 95% CI=1.1, 2.0) were significantly more likely to have cardiovascular disease. CONCLUSIONS: Adults with work-related asthma were more likely to have cardiovascular disease than those with non-work-related asthma. Primary prevention, early diagnosis, and implementation of optimal work-related asthma management are essential for workers' health. Cardiovascular disease should be considered where appropriate when diagnosing and recommending treatment and interventions for adults with work-related asthma.

      3. Occupations associated with SARS-CoV-2 infection and vaccination, U.S. Blood donors, July 2021-December 2021
        Shah MM, Spencer BR, Feldstein LR, Haynes JM, Benoit TJ, Saydah SH, Groenewold MR, Stramer SL, Jones JM.
        Clin Infect Dis. 2022 Nov 14.
        BACKGROUND: There are limited data on the risk of SARS-CoV-2 infection in the U.S. by occupation. We identified occupations at higher risk for prior SARS-CoV-2 infection as defined by the presence of infection-induced antibodies among U.S. blood donors. METHODS: Using a nested case-control study design, blood donors during May-December 2021 with anti-nucleocapsid (anti-N) testing were sent an electronic survey on employment status, vaccination, and occupation. The association between previous SARS-CoV-2 infection and occupation-specific in-person work was estimated using multivariable logistic regression adjusting for sex, age, month of donation, race/ethnicity, education, vaccination, and telework. RESULTS: Among 85,986 included survey respondents, 9,504 (11.1%) were anti-N reactive. Healthcare support (20.3%), protective service (19.9%), and food preparation and serving related occupations (19.7%) had the highest proportion of prior infection. After adjustment, prior SARS-CoV-2 infection was associated with healthcare practitioners (adjusted OR [aOR] 2.10, 95% CI 1.74-2.54) and healthcare support (aOR 1.83, 95% CI 1.39-2.40) occupations compared with computer and mathematical occupations as the referent group. Lack of COVID-19 vaccination (aOR 16.13, 95% CI 15.01-17.34) and never teleworking (aOR 1.17, 95% CI 1.05-1.30) were also independently associated with prior SARS-CoV-2 infection. Protective service occupations had the highest proportion of unvaccinated workers (30.0%). CONCLUSIONS: Workers in healthcare, protective services, and food preparation had the highest prevalence of prior SARS-CoV-2 infection. Occupational risks for SARS-CoV-2 infection remained after adjusting for vaccination, telework, and demographic factors. These findings underscore the need for mitigation measures and personal protection in healthcare settings and other workplaces.

      4. Body models of law enforcement officers for cruiser cab accommodation simulation
        Hsiao H, Kau TY, Whisler R, Zwiener J.
        Hum Factors. 2022 Nov 14:187208221140220.
        OBJECTIVES: This study developed multivariate law enforcement officer (LEO) body models for digital simulation of LEO accommodation in police cruiser cabs. BACKGROUND: Anthropometrically accurate digital LEO body models, representing the United States LEOs, for computerized LEO cruiser interface simulations are lacking. METHODS: Twenty body dimensions (with and without gear combined) of 756 male and 218 female LEOs were collected through a stratified national survey using a data collection trailer that traveled across the US. A multivariate Principal Component Analysis (PCA) approach was used to develop digital LEO body models. RESULTS: Fifteen men and 15 women representing unique body size and shape composition of the LEO population were identified. A combined set of 24 male and female models (removal of 6 redundant models for which female and male models overlapped) is suggested. CONCLUSIONS: A set of 24 digital LEO body models in 3-dimensional form, along with their anthropometric measurements, were developed to facilitate LEO cruiser cab design. APPLICATION: Digital modeling software developers can use the models and their anthropometric data to build digital avatars for simulated evaluation of LEO cruiser cab configuration, console communication-equipment fitting, and cruiser ingress/egress access arrangement. LEO vehicle and equipment designers also can use eight key body dimensions (i.e., stature, buttock-popliteal length, eye height sitting, knee height sitting, shoulder-grip length, popliteal height, sitting height, and body weight) of the body models to recruit 24 human subjects to physically evaluate their vehicle prototypes for improved vehicle and equipment design.

      5. Research studying the intersection of occupational safety and health (OSH) and direct reading and sensor technologies (DRST) is sparse, with a specific lack of research available that has empirically considered ways that DRST may impact worker well-being. In this paper, the authors examine how organizations could utilize core elements of their health and safety management system (HSMS) to coordinate and execute DRST in the workplace to support worker well-being. National Institute for Occupational Safety and Health (NIOSH) researchers developed a 39-item questionnaire targeting OSH professionals to understand attitudes toward DRST and the current and intended uses of DRST at their place of employment. Eighty-eight OSH professionals completed the questionnaire between August and December 2021. Descriptive results of the study sample are provided but the focus of the study applies the open-ended responses to two questions, which was deductively analyzed. Descriptive results show that reliability and validity of data was a top concern while the open-ended qualitative feedback revealed three primary themes: (1) acceptability and trust in technology; (2) ease of use; and (3) support and guidelines. Results provide an opening to use core HSMS elements (i.e., management commitment and leadership, communication and coordination, and employee involvement) during DRST integration to demonstrate support for workers during times of ambiguity and change.

      6. Occurrences of workplace violence related to the COVID-19 Pandemic, United States, March 2020 to August 2021
        Marsh SM, Rocheleau CM, Carbone EG, Hartley D, Reichard AA, Tiesman HM.
        Int J Environ Res Public Health. 2022 Nov 3;19(21).
        As businesses dealt with an increasingly anxious public during the COVID-19 pandemic and were frequently tasked with enforcing various COVID-19 prevention policies such as mask mandates, workplace violence and harassment (WPV) emerged as an increasing important issue affecting worker safety and health. Publicly available media reports were searched for WPV events related to the COVID-19 pandemic that occurred during 1 March 2020, and 31 August 2021, using Google News aggregator services scans with data abstraction and verification. The search found 408 unique WPV events related to COVID-19. Almost two-thirds involved mask disputes. Over half (57%) of the 408 events occurred in retail (38%) and food service (19%). We also conducted a comparison of events identified in this search to a similar study of media reports between March 2020 to October 2020 that used multiple search engines to identify WPV events. Despite similar conclusions, a one-to-one comparison of relevant data from these studies found only modest overlap in the incidents identified, suggesting the need to make improvements to future efforts to extract data from media reports. Prevention resources such as training and education for workers may help industries de-escalate or prevent similar WPV events in the future.

      7. CC16 polymorphisms in asthma, asthma subtypes, and asthma control in adults from the Agricultural Lung Health Study
        Gribben KC, Wyss AB, Poole JA, Farazi PA, Wichman C, Richards-Barber M, Beane Freeman LE, Henneberger PK, Umbach DM, London SJ, LeVan TD, Gribben KC.
        Respir Res. 2022 Nov 9;23(1):305.
        BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects and is a potential early biomarker of lung damage. The CC16 single nucleotide polymorphism (SNP) rs3741240 risk allele (A) has been inconsistently linked to asthma; other tagging SNPs in the gene have not been explored. The aim was to determine whether CC16 tagging polymorphisms are associated with adult asthma, asthma subtypes or asthma control in the Agricultural Lung Health Study (ALHS). METHODS: The ALHS is an asthma case-control study nested in the Agricultural Health Study cohort. Asthma cases were individuals with current doctor diagnosed asthma, likely undiagnosed asthma, or asthma-COPD overlap defined by questionnaire. We also examined asthma subtypes and asthma control. Five CC16 tagging SNPs were imputed to 1000 Genomes Integrated phase 1 reference panel. Logistic regression was used to estimate associations between CC16 SNPs and asthma outcomes adjusted for covariates. RESULTS: The sample included 1120 asthma cases and 1926 controls of European ancestry, with a mean age of 63 years. The frequency of the risk genotype (AA) for rs3741240 was 12.5% (n = 382). CC16 rs3741240 was not associated with adult asthma outcomes. A tagging SNP in the CC16 gene, rs12270961 was associated with uncontrolled asthma (n = 208, OR(adj)= 1.4, 95% CI 1.0, 1.9; p = 0.03). CONCLUSION: This study, the largest study to investigate associations between CC16 tagging SNPs and asthma phenotypes in adults, did not confirm an association of rs3741240 with adult asthma. A tagging SNP in CC16 suggests a potential relationship with asthma control.

      8. Influence of impurities from manufacturing process on the toxicity profile of boron nitride nanotubes
        Kodali V, Kim KS, Roberts JR, Bowers L, Wolfarth MG, Hubczak J, Xin X, Eye T, Friend S, Stefaniak AB, Leonard SS, Jakubinek M, Erdely A.
        Small. 2022 Nov 14:e2203259.
        The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufacturing processes and purification employed. Four BNNTs manufactured by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purification, water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including infrared and X-ray spectroscopy, thermogravimetric analysis, size, charge, surface area, and density captured the alteration in physicochemical properties as the material went through sequential purification. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.

    • Parasitic Diseases
      1. Assessment of factors related to individuals who were never treated during mass drug administration for lymphatic filariasis in Ambon City, Indonesia
        Titaley CR, Worrell CM, Ariawan I, Taihuttu YM, de Lima F, Naz SF, Que BJ, Krentel A.
        PLoS Negl Trop Dis. 2022 Nov 11;16(11):e0010900.
        BACKGROUND: One challenge to achieving Lymphatic filariasis (LF) elimination is the persistent coverage-compliance gap during annual mass drug administration (MDA) and the risk of ongoing transmission among never treated individuals. Our analysis examined factors associated with individuals who were never treated during MDA. METHODS: Data were derived from two cross-sectional surveys conducted in Waihaong and Air Salobar Health Center in 2018 and 2019. We analyzed information from 1915 respondents aged 18+ years. The study outcome was individuals who self-reported never treatment during any round of MDA. All potential predictors were grouped into socio-demographic, health system, therapy and individual factors. Logistic regression analyses were used to examine factors associated with never treatment in any year of MDA. RESULTS: Nearly half (41%) of respondents self-reported they were never treated during any round of MDA. Factors associated with increased odds of never treatment were respondents working in formal sectors (aOR = 1.75, p = 0.040), living in the catchment area of Waihaong Health Center (aOR = 2.33, p = 0.029), and those perceiving the possibility of adverse events after swallowing LF drugs (aOR = 2.86, p<0.001). Respondents reporting difficulty swallowing all the drugs (aOR = 3.12, p<0.001) and having difficulties remembering the time to swallow the drugs (aOR = 1.53, p = 0.049) also had an increased odds of never treatment. The highest odds of never treatment were associated with respondents reporting almost none of their family members took LF drugs (aOR = 3.93, p<0.001). Respondents confident that they knew how to swallow LF drugs had a reduced odds (aOR = 0.26, p<0.001) of never treatment. CONCLUSIONS: Efforts to reassure community members about adverse events, specific instructions on how to take LF drugs, and improving awareness that MDA participation is part of one's contribution to promoting community health are essential drivers for uptake with LF drugs during MDA.

    • Public Health Leadership and Management
      1. From practice to publication: The promise of writing workshops
        Lavinghouze SR, Kettel Khan L, Auld ME, Sammons Hackett D, Brittain DR, Brown DR, Greaney E, Harris DM, Maynard LM, Onufrak S, Robillard AG, Schwartz R, Siddique S, Youngner CG, Wright LS, O'Toole TP.
        Health Promot Pract. 2022 Nov;23(1_suppl):21s-33s.
        Practitioners in health departments, university extension programs, and nonprofit organizations working in public health face varied challenges to publishing in the peer-reviewed literature. These practitioners may lack time, support, skills, and efficacy needed for manuscript submission, which keeps them from sharing their wisdom and experience-based evidence. This exclusion can contribute to literature gaps, a failure of evidence-based practice to inform future research, reduced ability to educate partners, and delays in advancing public health practice. Our article describes the writing workshops offered to Division of Nutrition, Physical Activity, and Obesity (DNPAO), Centers for Disease Control and Prevention (CDC) funded programs in 2021. This project consisted of three 60-minute introductory writing webinars open to all recipients, followed by a Writing for Publications workshop, an 8- to 9-week virtual learning/writing intensive for selected writing team applicants. The Society for Public Health Education staff, consultants, and CDC/DNPAO staff developed, refined, and presented the curriculum. The workshop for public health practitioner writing teams was offered to two cohorts and included extensive coaching and focused on potential submission to a Health Promotion Practice supplement, "Reducing Chronic Disease through Physical Activity and Nutrition: Public Health Practice in the Field" (see Supplemental Material), which was supported by CDC/DNPAO. We describe the webinars, the workshop design, modifications, evaluation methods and results.

    • Reproductive Health
      1. Factors beyond compensation associated with uptake of voluntary medical male circumcision in Zambia
        Ong KS, Laube C, Mohan D, Iverson L, Kaonga A, Chituwo O, Kamboyi R, Kabila M, Toledo C.
        AIDS Behav. 2022 Nov 11.
        Voluntary medical male circumcision (VMMC) provides partial protection against female-to-male transmission of HIV. The Maximizing the Impact of Voluntary Medical Male Circumcision in Zambia (MAXZAM) project was a phased implementation of a demand generation strategy for VMMC through economic compensation. Previously published findings showed increased uptake of VMMC when compensation was provided. This paper is a follow-up evaluation of the MAXZAM project exploring additional factors associated with uptake of VMMC. Factors found associated include the outreach setting in which men were approached, number of information sources seen, heard, or read about VMMC, their self-reported HIV risk behaviors, their self-reported intention to go through the procedure, and their behavioral-psychographic profile. The findings highlight the importance of considering general (e.g., intensifying mass communications and targeting specific settings) and person-centered demand generation approaches (e.g., considering the client's psychographic profile and HIV risk level) to maximize effect on VMMC uptake.

      2. The association of state insurance coverage mandates with Assisted Reproductive Technology Care discontinuation
        Lee JC, DeSantis CE, Yartel AK, Kissin DM, Kawwass JF.
        Am J Obstet Gynecol. 2022 Nov 8.

      3. Defining the global research and programmatic agenda and priority actions for voluntary medical male circumcision for HIV prevention
        Peck ME, Lucas T, Ong KS, Grund JM, Davis S, Yansaneh A, Kiggundu VL, Thomas AG, Curran K, Laube C, Sundaram M, Ameyan W, Zembe L, Toledo C.
        Curr HIV/AIDS Rep. 2022 Nov 11:1-11.
        PURPOSE OF REVIEW: Since 2007, voluntary medical male circumcision (VMMC) programs have been associated with substantially reduced HIV incidence across 15 prioritized countries in Eastern and Southern Africa. Drawing on the programmatic experience of global VMMC leaders, this report reviews progress made in the first 15 years of the program, describes programmatic and research gaps, and presents considerations to maximize the impact of VMMC. RECENT FINDINGS: Overall, key programmatic and research gaps include a lack of robust male circumcision coverage estimates due to limitations to the data and a lack of standardized approaches across programs; challenges enhancing VMMC uptake include difficulties reaching populations at higher risk for HIV infection and men 30 years and older; limitations to program and procedural quality and safety including variations in approaches used by programs; and lastly, sustainability with limited evidence-based practices. Considerations to address these gaps include the need for global guidance on estimating coverage, conducting additional research on specific sub-populations to improve VMMC uptake, implementation of responsive and comprehensive approaches to adverse event surveillance, and diversifying financing streams to progress towards sustainability. This report's findings may help establish a global VMMC research and programmatic agenda to inform policy, research, and capacity-building activities at the national and global levels.

    • Substance Use and Abuse
      1. Tobacco product use among middle and high school students - United States, 2022
        Park-Lee E, Ren C, Cooper M, Cornelius M, Jamal A, Cullen KA.
        MMWR Morb Mortal Wkly Rep. 2022 Nov 11;71(45):1429-1435.
        Tobacco use* is the leading cause of preventable disease, disability, and death among adults in the United States (1). Youth use of tobacco products in any form is unsafe, and nearly all tobacco use begins during youth and young adulthood (2). The Food and Drug Administration (FDA) and CDC analyzed data from the 2022 National Youth Tobacco Survey (NYTS) to estimate current (past 30-day) use of eight tobacco products among U.S. middle (grades 6-8) and high school (grades 9-12) students. In 2022, approximately 11.3% of all students (representing 3.08 million persons) reported currently using any tobacco product, including 16.5% of high school and 4.5% of middle school students (2.51 million and 530,000 persons, respectively). Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among high school (14.1%; 2.14 million) and middle school (3.3%; 380,000) students. Approximately 3.7% of all students (representing 1 million persons) reported currently smoking any combustible tobacco product. Current use of any tobacco product was higher among certain population groups, including 13.5% of non-Hispanic American Indian or Alaska Native (AI/AN)(†) students; 16.0% of students identifying as lesbian, gay, or bisexual (LGB); 16.6% of students identifying as transgender; 18.3% of students reporting severe psychological distress; 12.5% of students with low family affluence; and 27.2% of students with low academic achievement. Implementation of comprehensive evidence-based tobacco control strategies, combined with FDA regulation, is important for preventing and reducing youth tobacco product use (1,2).

    • Zoonotic and Vectorborne Diseases
      1. Evaluating the clinical and immune responses to spotted fever rickettsioses in the guinea pig-tick-Rickettsia system
        Stokes JV, Levin ML, Cross CE, Ross AL, Snellgrove AN, Willeford BV, Alugubelly N, Varela-Stokes AS.
        Curr Protoc. 2022 Nov;2(11):e584.
        The guinea pig was the original animal model developed for investigating spotted fever rickettsiosis (SFR). This model system has persisted on account of the guinea pig's conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig-tick-Rickettsia model for monitoring the course of infection and immune response to an infection by spotted fever group Rickettsia (SFGR) that can be studied at biosafety level 2 (BSL-2) and arthropod containment level 2 (ACL-2); adaptations must be made for BSL-3 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of Rickettsia to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick-borne pathogens. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Tick transmission of SFGR to guinea pigs Support Protocol 1: Laboratory infection of ticks by injection Alternate Protocol 1: Needle inoculation of SFGR to guinea pigs Basic Protocol 2: Monitoring the course of guinea pig rickettsial infection: clinical signs Basic Protocol 3: Monitoring the course of guinea pig rickettsial infection: collection of biological specimens Support Protocol 2: Guinea pig anesthesia Basic Protocol 4: Monitoring rickettsial burden in guinea pigs by multiplex qPCR Basic Protocol 5: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometry Basic Protocol 6: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometry Basic Protocol 7: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISA Support Protocol 4: Coating ELISA Plates Alternate Protocol 2: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay.

      2. Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 influenza a viruses with reduced reactivity to candidate vaccine virus antisera as measures of relative zoonotic risk
        Kimble JB, Souza CK, Anderson TK, Arendsee ZW, Hufnagel DE, Young KM, Lewis NS, Davis CT, Thor S, Vincent Baker AL.
        Viruses. 2022 Oct 29;14(11).
        During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm09) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population.


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