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Issue 15, April 12, 2022

CDC Science Clips: Volume 14, Issue 15, April 12, 2022

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. OBJECTIVE: To compare prevalence of hypertension and stage II hypertension assessed by two blood pressure observation protocols. METHODS: Participants aged 18 years and older (n = 4,689) in the National Health and Nutrition Examination Survey (NHANES 2017-2018) had their blood pressure (BP) measured following two protocols: the legacy auscultation protocol [AP] and oscillometric protocol [OP]. The order of protocols was randomly assigned. Prevalence estimates for hypertension (BP ≥130/80 mm Hg or use of medication for hypertension) and stage II hypertension (BP ≥140/90 mm Hg) were determined overall, by demographics, and by risk factors for each protocol. Ratios (OP% ÷ AP%) and Kappa statistics were calculated. RESULTS: Age-adjusted hypertension prevalence was 44.5% (95% CI: 41.1%-48.0%) using OP and 45.1% (95%CI: 41.5%-48.7%) using AP, prevalence ratio=0.99, (95% CI=0.94-1.04)). Age-adjusted Stage II hypertension prevalence was 15.8% (95% CI: 13.6%-18.2%) using AP and 17.1% (95% CI: 14.7%-19.7%) using OP, prevalence ratio=0.92, (95% CI=0.81-1.04)). For both hypertension and Stage II hypertension, the prevalence ratios by demographics and by risk factors all included unity in their 95% CI, except for Stage II hypertension in adults 60+ years (ratio: 0.88 (95% CI: 0.78-0.98)). Kappa for agreement between protocols for hypertension and stage II hypertension were 0.75 (95% CI=0.71-0.79) and 0.67 (95% CI=0.61-0.72), respectively. CONCLUSIONS: In adults and for nearly all subcategories there were no significant differences in prevalence of hypertension and stage II hypertension between protocols, indicating that protocol change may not affect the national prevalence estimates of hypertension and stage II hypertension.

      2. BK virus associated with small cell carcinoma of bladder in a patient with renal transplantexternal icon
        Loria SJ, Siddiqui NN, Gary JM, Bhatnagar J, Bollweg BC, Ahmed B, Berenson CS.
        BMJ Case Rep. 2022 Mar 29;15(3).
        A man in his 70s with a complex medical history, including cadaveric renal transplant, presented with recurrent urinary tract infections. Investigation revealed recurrent urinary pathogens, including Enterobacter cloacae and persistent BK viruria. Cystoscopy revealed a pedunculated mass in the right posterior-lateral wall, inferior to the transplant urethral orifice, and biopsy of this mass showed invasive small cell carcinoma with a prominent adenocarcinoma component. The tumour was treated with complete transurethral resection followed by carboplatin, etoposide and radiation. Laboratory analysis of biopsied samples showed immunostaining and molecular evidence of BK virus DNA in the cancer cells. Follow-up cystoscopies have shown no recurrence of the cancer.

      3. Associations between persistent symptoms after mild COVID-19 and long-term health status, quality of life, and psychological distressexternal icon
        Han JH, Womack KN, Tenforde MW, Files DC, Gibbs KW, Shapiro NI, Prekker ME, Erickson HL, Steingrub JS, Qadir N, Khan A, Hough CL, Johnson NJ, Ely EW, Rice TW, Casey JD, Lindsell CJ, Gong MN, Srinivasan V, Lewis NM, Patel MM, Self WH.
        Influenza Other Respir Viruses. 2022 Mar 28.
        BACKGROUND: We sought to assess whether persistent COVID-19 symptoms beyond 6 months (Long-COVID) among patients with mild COVID-19 is associated with poorer health status, quality of life, and psychological distress. METHODS: This was a multicenter prospective cohort study that included adult outpatients with acute COVID-19 from eight sites during 2-week sampling periods from April 1 and July 28, 2020. Participants were contacted 6-11 months after their first positive SARS-CoV-2 to complete a survey, which collected information on the severity of eight COVID-19 symptoms using a 4-point scale ranging from 0 (not present) to 3 (severe) at 1 month before COVID-19 (pre-illness) and at follow-up; the difference for each was calculated as an attributable persistent symptom severity score. A total attributable persistent COVID-19 symptom burden score was calculated by summing the attributable persistent severity scores for all eight symptoms. Outcomes measured at long-term follow-up comprised overall health status (EuroQol visual analogue scale), quality of life (EQ-5D-5L), and psychological distress (Patient Health Questionnaire-4). The association between the total attributable persistent COVID-19 burden score and each outcome was analyzed using multivariable proportional odds regression. RESULTS: Of the 2092 outpatients with COVID-19, 436 (21%) responded to the survey. The median (IQR) attributable persistent COVID-19 symptom burden score was 2 (0, 4); higher scores were associated with lower overall health status (aOR 0.63; 95% CI: 0.57-0.69), lower quality of life (aOR: 0.65; 95%CI: 0.59-0.72), and higher psychological distress (aOR: 1.40; 95%CI, 1.28-1.54) after adjusting for age, race, ethnicity, education, and income. CONCLUSIONS: In participants with mild acute COVID-19, the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress.

    • Communicable Diseases
      1. Post-validation survey in two districts of Morocco after the elimination of trachoma as a public health problemexternal icon
        Hammou J, Guagliardo SA, Obtel M, Razine R, Haroun AE, Youbi M, Bellefquih AM, White M, Gwyn S, Martin DL.
        Am J Trop Med Hyg. 2022 Mar 28.
        Trachoma is the leading infectious cause of blindness. In 2016, Morocco was validated by WHO as having eliminated trachoma as a public health problem. We evaluated two previously endemic districts in Morocco for trachomatous inflammation-follicular (TF), trachomatous trichiasis (TT), and antibodies against Chlamydia trachomatis, the causative agent of trachoma. Community-based cross-sectional surveys in the districts of Boumalene Dades and Agdez included 4,445 participants for whom both questionnaire and serology data were available; 58% were aged 1-9 years. Participants had eyes examined for TF and blood collected for analysis of antibodies to the C. trachomatis antigen Pgp3 by both a multiplex bead assay (MBA) and lateral flow assay (LFA). Seroconversion rates (SCR) per 100 people per year were used to estimate changes in the force of infection using Bayesian serocatalytic models. In Agdez, TF prevalence in 1-9-year-olds was 0.3%, seroprevalence ranged from 9.4% to 11.4%, and SCR estimates ranged from 2.4 to 3.0. In Boumalene Dades, TF prevalence in 1-9-year-olds was 0.07%, and modeling data from the different assays indicated a decrease in transmission between 20 and 24 years ago. The TF data support an absence of active trachoma in the two districts examined. However, seroprevalence and SCR in younger people were higher in Agdez than Boumalene Dades, showing that there can be differences in serology metrics in areas with similar TF prevalence. Data will be included in multicountry analyses to better understand potential thresholds for serological surveillance in trachoma.

      2. Comparative outcomes for mature T-cell and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomasexternal icon
        Koh MJ, Merrill MH, Koh MJ, Stuver R, Alonso CD, Foss FM, Mayor AM, Gill J, Epeldegui M, Cachay E, Thorne JE, Silverberg MJ, Horberg MA, Althoff KN, Nijhawan AE, McGinnis KA, Lee JS, Rabkin CS, Napravnik S, Li J, Castilho JL, Shen C, Jain S.
        Blood Adv. 2022 Mar 8;6(5):1420-1431.
        There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin's lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade.

      3. Mortuary and hospital-based HIV mortality surveillance among decedents in a low-resource setting: lessons from Western Kenyaexternal icon
        Nyakeriga E, Waruiru W, Opollo V, Waruru A, Kingwara L, Onyango D, Junghae M, Muuo S, Macharia T, Ngugi C, Mwangome M, Ali H.
        BMC Public Health. 2022 Mar 29;22(1):609.
        BACKGROUND: Lack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya. MAIN TEXT: We conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16-July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes. Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection. CONCLUSION: This study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.

      4. Factors associated with an outbreak of COVID-19 in oilfield workers, Kazakhstan, 2020external icon
        Nabirova D, Taubayeva R, Maratova A, Henderson A, Nassyrova S, Kalkanbayeva M, Alaverdyan S, Smagul M, Levy S, Yesmagambetova A, Singer D.
        Int J Environ Res Public Health. 2022 Mar 10;19(6).
        From March to May 2020, 1306 oilfield workers in Kazakhstan tested positive for SARS-CoV-2. We conducted a case-control study to assess factors associated with SARS-CoV-2 transmission. The cases were PCR-positive for SARS-CoV-2 during June-September 2020. Controls lived at the same camp and were randomly selected from the workers who were PCR-negative for SARS-CoV-2. Data was collected telephonically by interviewing the oil workers. The study had 296 cases and 536 controls with 627 (75%) men, and 527 (63%) were below 40 years of age. Individual factors were the main drivers of transmission, with little contribution by environmental factors. Of the twenty individual factors, rare hand sanitizer use, travel before shift work, and social interactions outside of work increased SARS-CoV-2 transmission. Of the twenty-two environmental factors, only working in air-conditioned spaces was associated with SARS-CoV-2 transmission. Communication messages may enhance workers' individual responsibility and responsibility for the safety of others to reduce SARS-CoV-2 transmission.

      5. Genome sequence of escherichia coli isolated from an adult in Kibera, an urban informal settlement in Nairobi, Kenyaexternal icon
        Kikwai GK, Juma B, Nindo F, Ochieng C, Wamola N, Mbogo K, Call DR, Hunsperger E.
        Microbiol Resour Announc. 2022 Mar 28:e0124121.
        An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id, bla(TEM-1B), and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.

      6. Tuberculosis - United States, 2021external icon
        Filardo TD, Feng PJ, Pratt RH, Price SF, Self JL.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 25;71(12):441-446.
        During 1993-2019, the incidence of tuberculosis (TB) in the United States decreased steadily; however, during the later years of that period the annual rate of decline slowed (1) until 2020 when a substantial decline (19.9%) was observed. This sharp decrease in TB incidence might have been related to multiple factors coinciding with the COVID-19 pandemic, including delayed or missed TB diagnoses or a true reduction in TB incidence related to pandemic mitigation efforts and changes in immigration and travel (2). During 2021, a total of 7,860 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC). National incidence of reported TB (cases per 100,000 persons) rose 9.4% during 2021 (2.37) compared with that in 2020 (2.16) but remained 12.6% lower than the rate during 2019 (2.71).* During 2021, TB incidence increased among both U.S.-born and non-U.S.-born persons. The increased TB incidence observed during 2021 compared with 2020 might be partially explained by delayed diagnosis of cases in persons with symptom onset during 2020; however, the continued, substantial reduction from prepandemic levels raises concern for ongoing underdiagnosis. TB control and prevention services, including early diagnosis and complete treatment of TB and latent TB infection, should be maintained and TB awareness promoted to achieve elimination in the United States.

      7. Lessons learned from programmatic gains in HIV service delivery during the COVID-19 pandemic - 41 PEPFAR-supported countries, 2020external icon
        Fisher KA, Patel SV, Mehta N, Stewart A, Medley A, Dokubo EK, Shang JD, Wright J, Rodas J, Balachandra S, Kitenge F, Mpingulu M, García MC, Bonilla L, Quaye S, Melchior M, Banchongphanith K, Phokhasawad K, Nkanaunena K, Maida A, Couto A, Mizela J, Ibrahim J, Charles OO, Malamba SS, Musoni C, Bolo A, Bunga S, Lolekha R, Kiatchanon W, Bhatia R, Nguyen C, Aberle-Grasse J.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 25;71(12):447-452.
        The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum(†) globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)(§) and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

      8. COVID-19-associated hospitalizations among adults during SARS-CoV-2 Delta and Omicron variant predominance, by race/ethnicity and vaccination status - COVID-NET, 14 states, July 2021-January 2022external icon
        Taylor CA, Whitaker M, Anglin O, Milucky J, Patel K, Pham H, Chai SJ, Alden NB, Yousey-Hindes K, Anderson EJ, Teno K, Reeg L, Como-Sabetti K, Bleecker M, Barney G, Bennett NM, Billing LM, Sutton M, Talbot HK, McCaffrey K, Havers FP.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 25;71(12):466-473.
        Beginning the week of December 19-25, 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant in the United States (i.e., accounted for >50% of sequenced isolates).* Information on the impact that booster or additional doses of COVID-19 vaccines have on preventing hospitalizations during Omicron predominance is limited. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET)(†) were analyzed to compare COVID-19-associated hospitalization rates among adults aged ≥18 years during B.1.617.2 (Delta; July 1-December 18, 2021) and Omicron (December 19, 2021-January 31, 2022) variant predominance, overall and by race/ethnicity and vaccination status. During the Omicron-predominant period, weekly COVID-19-associated hospitalization rates (hospitalizations per 100,000 adults) peaked at 38.4, compared with 15.5 during Delta predominance. Hospitalizations rates increased among all adults irrespective of vaccination status (unvaccinated, primary series only, or primary series plus a booster or additional dose). Hospitalization rates during peak Omicron circulation (January 2022) among unvaccinated adults remained 12 times the rates among vaccinated adults who received booster or additional doses and four times the rates among adults who received a primary series, but no booster or additional dose. The rate among adults who received a primary series, but no booster or additional dose, was three times the rate among adults who received a booster or additional dose. During the Omicron-predominant period, peak hospitalization rates among non-Hispanic Black (Black) adults were nearly four times the rate of non-Hispanic White (White) adults and was the highest rate observed among any racial and ethnic group during the pandemic. Compared with the Delta-predominant period, the proportion of unvaccinated hospitalized Black adults increased during the Omicron-predominant period. All adults should stay up to date (1) with COVID-19 vaccination to reduce their risk for COVID-19-associated hospitalization. Implementing strategies that result in the equitable receipt of COVID-19 vaccinations, through building vaccine confidence, raising awareness of the benefits of vaccination, and removing barriers to vaccination access among persons with disproportionately higher hospitalizations rates from COVID-19, including Black adults, is an urgent public health priority.

      9. Risk factors for invasive meningococcal disease belonging to a novel urethritis clade of Neisseria meningitidis-United States, 2013-2017external icon
        Oliver SE, Retchless AC, Blain AE, McNamara LA, Ahrabifard S, Farley M, Weiss D, Zaremski E, Wang X, Hariri S.
        Open Forum Infect Dis. 2022 Apr;9(4):ofac035.
        We describe cases of invasive meningococcal disease caused by nongroupable Neisseria meningitidis belonging to a novel phylogenetic clade associated with urethritis. Seven cases were identified, comprising 0.6% of sequenced invasive meningococcal disease isolates from 2013 to 2017. Five patients had a known or likely immunocompromising condition, including 2 with a complement deficiency.

    • Community Health Services
      1. Appreciative inquiry and the co-creation of an evaluation framework for Extension for Community Healthcare Outcomes (ECHO) implementation: A two-country experienceexternal icon
        Ghosh S, Struminger BB, Singla N, Roth BM, Kumar A, Anand S, Mtete E, Lusekelo J, Massawe I, Jarpe-Ratner E, Seweryn SM, Risley K, Moonan PK, Pinsker E.
        Eval Program Plann. 2022 Mar 10;92:102067.
        Persistent gaps exist in healthcare workers' capacity to address HIV and tuberculosis in Asia and Africa due to constraints in resources and knowledge. Project ECHO (Extension for Community Healthcare Outcomes) leverages video-enabled technology to build workforce capacity and promote collaboration through mentorship and case-based learning. To understand current perceptions of ECHO participants and develop a comprehensive evaluation framework for ECHO implementation, we utilized modified appreciative inquiry guided focus group discussions (FGD) in India and Tanzania and called it SCORE (Strengths, Challenges, Opportunities, Results, and Evaluation). Content and thematic analysis of transcripts from FGDs and key-informant interviews triangulated perceptions of diverse stakeholders about ECHO implementation and identified key elements for development of the framework. The perceived strengths (S) were capacity building and establishing communities of practice. The perceived challenges (C) included securing resources, engaging leadership, and building systems for monitoring impact. Improved internet connectivity, addressing logistical challenges, encouraging session interactivity, and having strategic scale-up plans were perceived opportunities (O). Additionally, gathering measurable results (R) led to development of a comprehensive evaluation (E) framework. Contextualizing and facilitating SCORE with qualitative analysis of findings 6-12 months post-ECHO implementation may serve as a best practice to assess mid-course corrections to improve ECHO implementation quality.

      2. Strengthening health system's capacity for pre-exposure prophylaxis for adolescent girls and young women and adolescent boys and young men in South Africa (SHeS'Cap-PrEP): Protocol for a mixed methods study in KwaZulu-Natal, South Africaexternal icon
        Nicol E, Ramraj T, Hlongwa M, Basera W, Jama N, Lombard C, McClinton-Appollis T, Govindasamy D, Pass D, Funani N, Aheron S, Paredes-Vincent A, Drummond J, Cheyip M, Dladla S, Bedford J, Mathews C.
        PLoS One. 2022 ;17(3):e0264808.
        INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an effective prevention intervention that can be used to control HIV incidence especially among people who are at increased risk for HIV such as adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM). In South Africa, various approaches of delivering PrEP have been adopted at different service delivery points (facility-based only, school-based only, community-based only and hybrid school-facility and community-facility models) to overcome challenges associated with individual, structural, and health systems related barriers that may hinder access to and uptake of PrEP among these populations. However, little is known about how to optimize PrEP implementation and operational strategies to achieve high sustained uptake of good quality services for AGYW and ABYM. This study aims to identify effective and feasible PrEP models of care for improving PrEP uptake, continuation, and adherence among AGYW and ABYM. METHODS AND ANALYSIS: A sequential explanatory mixed-methods study will be conducted in 22 service delivery points (SDPs) in uMgungundlovu district, KwaZulu-Natal, South Africa. We will recruit 600 HIV negative, sexually active, high risk, AGYW (aged 15-24 years) and ABYM (aged 15-35 years). Enrolled participants will be followed up at 1-, 4- and 7-months to determine continuation and adherence to PrEP. We will conduct two focus group discussions (with 8 participants in each group) across four groups (i. Initiated PrEP within 1 month, ii. Did not initiate PrEP within 1 month, iii. Continued PrEP at 4/7 months and iv. Did not continue PrEP at 4/7 months) and 48 in-depth interviews from each of the four groups (12 per group). Twelve key informant interviews with stakeholders working in HIV programs will also be conducted. Associations between demographic characteristics stratified by PrEP initiation and by various service-delivery models will be assessed using Chi-square/Fishers exact tests or t-test/Mann Whitney test. A general inductive approach will be used to analyze the qualitative data. ETHICS AND DISSEMINATION: The protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC051-11/2020). Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer-reviewed journal articles and research capacity building through research degrees.

      3. Barriers of linkage to HCV viremia testing among people who inject drugs in Georgiaexternal icon
        Butsashvili M, Abzianidze T, Kamkamidze G, Gulbiani L, Gvinjilia L, Kuchuloria T, Tskhomelidze I, Gogia M, Tsereteli M, Miollany V, Kikvidze T, Shadaker S, Nasrullah M, Averhoff F.
        Subst Abuse Treat Prev Policy. 2022 Mar 28;17(1):23.
        BACKGROUND: People who inject drugs (PWID) in Georgia have a high prevalence of hepatitis C virus antibody (anti-HCV). Access to care among PWID could be prioritized to meet the country's hepatitis C elimination goals. This study assesses barriers of linkage to HCV viremia testing among PWID in Georgia. METHODS: Study participants were enrolled from 13 harm reduction (HR) centers throughout Georgia. Anti-HCV positive PWID who were tested for viremia (complete diagnosis [CD]), were compared to those not tested for viremia within 90 days of screening anti-HCV positive (not complete diagnosis [NCD]). Convenience samples of CD and NCD individuals recorded at HR centers using beneficiaries' national ID were drawn from the National HCV Elimination Program database. Participants were interviewed about potential barriers to seeking care. RESULTS: A total of 500 PWID were enrolled, 245 CD and 255 NCD. CD and NCD were similar with respect to gender, age, employment status, education, knowledge of anti-HCV status, and confidence/trust in the elimination program (p > 0.05). More NCD (13.0%) than CD (7.4%) stated they were not sufficiently informed what to do after screening anti-HCV positive (p < 0.05). In multivariate analysis, HCV viremia testing was associated with perceived affordability of the elimination program (adjusted prevalence ratio = 8.53; 95% confidence interval: 4.14-17.62). CONCLUSIONS: Post testing counselling and making hepatitis C services affordable could help increase HCV viremia testing among PWID in Georgia.

    • Disease Reservoirs and Vectors
      1. Diel activity patterns of two distinct populations of Aedes aegypti in Miami, FL and Brownsville, TXexternal icon
        Mutebi JP, Wilke AB, Ostrum E, Vasquez C, Cardenas G, Carvajal A, Moreno M, Petrie WD, Rodriguez A, Presas H, Rodriguez J, Barnes F, Hamer GL, Juarez JG, Carbajal E, Vitek CJ, Estrada X, Rios T, Marshall J, Beier JC.
        Sci Rep. 2022 Mar 29;12(1):5315.
        The diel biting activity of Aedes (Stegomyia) aegypti (L) populations was extensively investigated in the early 1900s to gain more information on the biology of Ae. aegypti, and this information was used to devise effective approaches to controlling populations of this species and protect the human population from widespread arbovirus outbreaks. However, few contemporary studies are available regarding the diel activity patterns of Ae. aegypti. To assess the diel activity patterns of Ae. aegypti in southern Florida and Texas, we conducted 96-h uninterrupted mosquito collections once each month from May through November 2019 in Miami, Florida, and Brownsville, Texas, using BG-Sentinel 2 Traps. The overall diel activity pattern in both cities was bimodal with morning and evening peak activity between 7:00 and 8:00 and between 19:00 and 20:00. There were significant daily, monthly, seasonal, and site-specific differences in activity patterns, but these differences did not affect the overall peak activity times. These differences suggest daily, monthly, seasonal, and site-specific variations in human exposure to Ae. aegypti. Our observations can be used in planning and executing Ae. aegypti vector control activities in southern Florida and southern Texas, specifically those targeting the adult mosquito populations.

    • Environmental Health
      1. Arsenic in private well water and birth outcomes in the United Statesexternal icon
        Bulka CM, Scannell Bryan M, Lombard MA, Bartell SM, Jones DK, Bradley PM, Vieira VM, Silverman DT, Focazio M, Toccalino PL, Daniel J, Backer LC, Ayotte JD, Gribble MO, Argos M.
        Environ Int. 2022 Mar 26;163:107176.
        BACKGROUND: Prenatal exposure to drinking water with arsenic concentrations >50 μg/L is associated with adverse birth outcomes, with inconclusive evidence for concentrations ≤50 μg/L. In a collaborative effort by public health experts, hydrologists, and geologists, we used published machine learning model estimates to characterize arsenic concentrations in private wells-federally unregulated for drinking water contaminants-and evaluated associations with birth outcomes throughout the conterminous U.S. METHODS: Using several machine learning models, including boosted regression trees (BRT) and random forest classification (RFC), developed from measured groundwater arsenic concentrations of ∼20,000 private wells, we characterized the probability that arsenic concentrations occurred within specific ranges in groundwater. Probabilistic model estimates and private well usage data were linked by county to all live birth certificates from 2016 (n = 3.6 million). We evaluated associations with gestational age and term birth weight using mixed-effects models, adjusted for potential confounders and incorporated random intercepts for spatial clustering. RESULTS: We generally observed inverse associations with term birth weight. For instance, when using BRT estimates, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 5 μg/L was associated with a -1.83 g (95% CI: -3.30, -0.38) lower term birth weight after adjusting for covariates. Similarly, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 10 μg/L was associated with a -2.79 g (95% CI: -4.99, -0.58) lower term birth weight. Associations with gestational age were null. CONCLUSION: In this largest epidemiologic study of arsenic and birth outcomes to date, we did not observe associations of modeled arsenic estimates in private wells with gestational age and found modest inverse associations with term birth weight. Study limitations may have obscured true associations, including measurement error stemming from a lack of individual-level information on primary water sources, water arsenic concentrations, and water consumption patterns.

      2. Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO(2) & SiO(2)) in rats and an assessment of the impact of particle-generated oxidants on the dusts' toxicitiesexternal icon
        Lam CW, Castranova V, Zeidler-Erdely PC, Renne R, Hunter R, McCluskey R, Scully RR, Wallace WT, Zhang Y, Ryder VE, Cooper B, McKay D, McClellan RO, Driscoll KE, Gardner DE, Barger M, Meighan T, James JT.
        Inhal Toxicol. 2022 ;34(3-4):51-67.
        Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO(2). We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (•OH), showed that ground LDs > unground LD ≥ TiO(2) ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold •OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest •OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented.

      3. This first article in a series of three on land reuse highlights sustainable brownfields redevelopment in Europe. Sustainability is a key European concept. Europe's densely populated urban areas are facing specific challenges that include urban sprawl and environmental pollution. Redeveloping brownfields, or reusing the abandoned built landscape, can positively impact the economic, social, and environmental health security of cities. Many European Union (EU) cities benefit from policy and financial assistance in renovating their urban areas. This article reviews the EU's policy and funding frameworks that support sustainable brownfields redevelopment. Brownfield site problems are common to many countries in Europe and around the world, and this article aims to share knowledge and resources that support the transformation of these abandoned or underused areas into public or private uses.

      4. The article discusses the data modernization efforts in various U.S. states to increase the accessibility of environmental health services data. Also cited are the partnership between the Environmental Public Health Tracking Program and the Centers for Disease Control and Prevention's (CDC) Water, Food and Environmental Services Branch (WFEHSB) to advance modernization, and the focus on environmental health services like inspections, permits, and public inquiries.

    • Epidemiology and Surveillance
      1. Estimated COVID-19 cases and hospitalizations averted by case investigation and contact tracing in the USexternal icon
        Rainisch G, Jeon S, Pappas D, Spencer KD, Fischer LS, Adhikari BB, Taylor MM, Greening B, Moonan PK, Oeltmann JE, Kahn EB, Washington ML, Meltzer MI.
        JAMA Netw Open. 2022 Mar 1;5(3):e224042.
        IMPORTANCE: Evidence of the impact of COVID-19 case investigation and contact tracing (CICT) programs is lacking, but policy makers need this evidence to assess the value of such programs. OBJECTIVE: To estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs. DESIGN, SETTING, AND PARTICIPANTS: This decision analytical model study used combined data from US CICT programs (eg, proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model outcomes of CICT over a 60-day period (November 25, 2020, to January 23, 2021). The study estimated a range of outcomes by varying assumed compliance with isolation and quarantine recommendations. Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Data analysis was performed from July to September 2021. EXPOSURE: Public health case investigation and contact tracing. MAIN OUTCOMES AND MEASURES: The primary outcomes were numbers of cases and hospitalizations averted and the percentage of cases averted among cases not prevented by vaccination and other nonpharmaceutical interventions. RESULTS: In total, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (approximately 140 million persons), spanned all 4 US Census regions, and reported data that reflected all 59 federally funded CICT programs. This study estimated that 1.11 million cases and 27 231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33 527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across both scenarios and all jurisdictions, CICT averted an estimated median of 21.2% (range, 1.3%-65.8%) of the cases not prevented by vaccination and other nonpharmaceutical interventions. CONCLUSIONS AND RELEVANCE: These findings suggest that CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the 2020 to 2021 winter peak. Differences in outcomes across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs.

    • Food Safety
      1. PulseNet International Survey on the implementation of whole genome sequencing in low and middle-income countries for foodborne disease surveillanceexternal icon
        Davedow T, Carleton H, Kubota K, Palm D, Schroeder M, Gerner-Smidt P, Al-Jardani A, Chinen I, Kam KM, Smith AM, Nadon C.
        Foodborne Pathog Dis. 2022 Mar 21.
        PulseNet International (PNI) is a global network of 88 countries who work together through their regional and national public health laboratories to track foodborne disease around the world. The vision of PNI is to implement globally standardized surveillance using whole genome sequencing (WGS) for real-time identification and subtyping of foodborne pathogens to strengthen preparedness and response and lower the burden of disease. Several countries in North America and Europe have experienced significant benefits in disease mitigation after implementing WGS. To broaden the routine use of WGS around the world, challenges and barriers must be overcome. We conducted this study to determine the challenges and barriers countries are encountering in their attempts to implement WGS and to identify how PNI can provide support to improve and become a better integrated system overall. A survey was designed with a set of qualitative questions to capture the status, challenges, barriers, and successes of countries in the implementation of WGS and was administered to laboratories in Africa, Asia-Pacific, Latin America and the Caribbean, and Middle East. One-third of respondents do not use WGS, and only 8% reported using WGS for routine, real-time surveillance. The main barriers for implementation of WGS were lack of funding, gaps in expertise, and training, especially for data analysis and interpretation. Features of an ideal system to facilitate implementation and global surveillance were identified as an all-in-one software that is free, accessible, standardized and validated. This survey highlights the minimal use of WGS for foodborne disease surveillance outside the United States, Canada, and Europe to date. Although funding remains a major barrier to WGS-based surveillance, critical gaps in expertise and availability of tools must be overcome. Opportunities to seek sustainable funding, provide training, and identify solutions for a globally standardized surveillance platform will accelerate implementation of WGS worldwide.

    • Genetics and Genomics
      1. Enhancing meningococcal genomic surveillance in the meningitis belt using high-resolution culture-free whole genome sequencingexternal icon
        Itsko M, Topaz N, Ousmane S, Popoola M, Ouedraogo R, Gamougam K, Sadji AY, Abdul-Karim A, Lascols C, Wang X.
        J Infect Dis. 2022 Mar 24.
        Rollout of meningococcal serogroup A conjugate vaccine in Africa started in 2010, aiming to eliminate meningitis outbreaks, in meningitis belt countries. Since then, studies have been conducted, primarily using isolates, to assess the vaccine impact on the distribution of meningococcal strains in the region. Here, we implemented an innovative, culture-free whole genome sequencing approach on almost 400 clinical specimens collected between 2017-2019 from meningococcal meningitis cases in 6 African countries. About 50% of specimens provided high-quality whole genome sequence data for comprehensive molecular profiling of the meningococcal pathogen. Three major clonal complexes were identified: CC11 associated with serogroup W, CC181 associated with serogroup X and CC10217 associated with serogroup C, which continues to rise as a predominant clonal complex in the region. Genomic surveillance for meningococcal meningitis can be significantly improved using culture-free methods to increase data representativeness and monitor changes in epidemiological landscape, especially for countries with low culture rate.

    • Health Economics
      1. Economic burden of tuberculosis in Tanzania: a national survey of costs faced by tuberculosis-affected householdsexternal icon
        Kilale AM, Pantoja A, Jani B, Range N, Ngowi BJ, Makasi C, Majaha M, Manga CD, Haule S, Wilfred A, Hilary P, Mahamba V, Nkiligi E, Muhandiki W, Matechi E, Mutayoba B, Nishkiori N, Ershova J.
        BMC Public Health. 2022 Mar 29;22(1):600.
        BACKGROUND: Although tuberculosis (TB) care is free in Tanzania, TB-associated costs may compromise access to services and treatment adherence resulting in poor outcomes and increased risk of transmission in the community. TB can impact economically patients and their households. We assessed the economic burden of TB on patients and their households in Tanzania and identified cost drivers to inform policies and programs for potential interventions to mitigate costs. METHODS: We conducted a nationally representative cross-sectional survey using a standard methodology recommended by World Health Organization. TB patients of all ages and with all types of TB from 30 clusters across Tanzania were interviewed during July - September 2019. We used the human capital approach to assess the indirect costs and a threshold of 20% of the household annual expenditure to determine the proportion of TB-affected households experiencing catastrophic cost. We descriptively analyzed the cost data and fitted multivariable logistic regression models to identify potential predictors of catastrophic costs. RESULTS: Of the 777 TB-affected households, 44.9% faced catastrophic costs due to TB. This proportion was higher (80.0%) among households of patients with multi-drug resistant TB (MDR-TB). Overall, cost was driven by income loss while accessing TB services (33.7%), nutritional supplements (32.6%), and medical costs (15.1%). Most income loss was associated with hospitalization and time for picking up TB drugs. Most TB patients (85.9%) reported worsening financial situations due to TB, and over fifty percent (53.0%) borrowed money or sold assets to finance TB treatment. In multivariable analysis, the factors associated with catastrophic costs included hospitalization (adjusted odds ratio [aOR] = 34.9; 95% confidence interval (CI):12.5-146.17), living in semi-urban (aOR = 1.6; 95% CI:1.0-2.5) or rural areas (aOR = 2.6; 95% CI:1.8-3.7), having MDR-TB (aOR = 3.4; 95% CI:1.2-10.9), and facility-based directly-observed treatment (DOT) (aOR = 7.2; 95% CI:2.4-26.6). CONCLUSION: We found that the cost of TB care is catastrophic for almost half of the TB-affected households in Tanzania; our findings support the results from other surveys recently conducted in sub-Saharan Africa. Collaborative efforts across health, employment and social welfare sectors are imperative to minimize household costs due to TB disease and improve access to care, patient adherence and outcomes.

      2. The cost-effectiveness of hyperlipidemia medication in low- and middle-income countries: A reviewexternal icon
        Husain MJ, Spencer G, Nugent R, Kostova D, Richter P.
        Glob Heart. 2022 ;17(1):18.
        Hyperlipidemia is a risk factor for cardiovascular disease - the leading cause of death globally. Increased understanding of the cost-effectiveness of hyperlipidemia treatment in low- and middle-income countries can guide approaches to hyperlipidemia management in resource-limited environments. We conducted a systematic review of the evidence on the cost-effectiveness of hyperlipidemia medication treatment in low- and middle-income countries using studies published between January 2010 and April 2020. We abstracted study details, including study design, treatment setting, intervention type, health metrics, costs standardized to constant 2019 US dollars, and cost-effectiveness measures including average and incremental cost-effectiveness ratios. Comparisons across studies suggested that treatment via polypill is generally more cost-effective than statin-only therapy, and that primary prevention is more cost-effective than secondary prevention. Treating hyperlipidemia at a threshold of 5.7 mmol/l comes at a higher cost per disability-adjusted life-years averted than at a threshold of 6.2 mmol/l. Most pharmacological treatment strategies for hyperlipidemia were found to be cost-effective in most of the examined low- and middle-income countries.

      3. Economic burden of fungal diseases in the United Statesexternal icon
        Benedict K, Whitham HK, Jackson BR.
        Open Forum Infect Dis. 2022 Apr;9(4):ofac097.
        We conservatively estimated the US economic burden of fungal diseases as $11.5 billion in 2019: direct medical costs ($7.5 billion), productivity loss due to absenteeism ($870 million), and premature deaths ($3.2 billion). An alternative "value of statistical life" approach yielded >$48 billion. These are likely underestimates given underdiagnosis and underreporting.

    • Health Equity and Health Disparities
      1. Racial and ethnic disparities in adult vaccination: A review of the state of evidenceexternal icon
        Granade CJ, Lindley MC, Jatlaoui T, Asif AF, Jones-Jack N.
        Health Equity. 2022 ;6(1):206-223.
        Background: Adult vaccination coverage remains low in the United States, particularly among racial and ethnic minority populations. Objective: To conduct a comprehensive literature review of research studies assessing racial and ethnic disparities in adult vaccination. Search Methods: We conducted a search of PubMed, Cochrane Library, ClinicalTrials.gov, and reference lists of relevant articles. Selection Criteria: Research studies were eligible for inclusion if they met the following criteria: (1) study based in the United States, (2) evaluated receipt of routine immunizations in adult populations, (3) used within-study comparison of race/ethnic groups, and (4) eligible for at least one author-defined PICO (patient, intervention, comparison, and outcome) question. Data Collection and Analysis: Preliminary abstract review was conducted by two authors. Following complete abstraction of articles using a standardized template, abstraction notes and determinations were reviewed by all authors; disagreements regarding article inclusion/exclusion were resolved by majority rule. The Social Ecological Model framework was used to complete a narrative review of observational studies to summarize factors associated with disparities; a systematic review was used to evaluate eligible intervention studies. Results: Ninety-five studies were included in the final analysis and summarized qualitatively within two main topic areas: (1) factors associated with documented racial-ethnic disparities in adult vaccination and (2) interventions aimed to reduce disparities or to improve vaccination coverage among racial-ethnic minority groups. Of the 12 included intervention studies, only 3 studies provided direct evidence and were of Level II, fair quality; the remaining 9 studies met the criteria for indirect evidence (Level I or II, fair or poor quality). Conclusions: A considerable amount of observational research evaluating factors associated with racial and ethnic disparities in adult vaccination is available. However, intervention studies aimed at reducing these disparities are limited, are of poor quality, and insufficiently address known reasons for low vaccination uptake among racial and ethnic minority adults. © Charleigh J. Granade et al., 2022; Published by Mary Ann Liebert, Inc. 2022.

      2. Gay, bisexual, and other men who have sex with men (MSM) and transgender women, particularly those who are living with HIV, are disproportionately affected by human papillomavirus (HPV). For this narrative review of HPV health outcomes and vaccination for gay, bisexual, and other MSM and transgender women in the United States, we highlighted 71 publications regarding 1) burden of HPV infections and related diseases; 2) HPV vaccine efficacy; 3) HPV vaccination recommendations; 4) HPV vaccination coverage; 5) real-world vaccine effectiveness and health impacts; and 6) HPV vaccination acceptability. Vaccination is effective at reducing HPV infections among MSM; in the United States, routine HPV vaccination is recommended for all adolescents at age 11-12 years and for all persons through age 26 years. Efforts are ongoing to increase vaccination coverage and monitor health impacts of vaccination. Increasing vaccination coverage before sexual exposure to HPV is expected to reduce the burden of HPV-related disease.

    • Immune System Disorders
      1. A strong association between rubella virus (RuV) and chronic granulomas, in individuals with inborn errors of immunity, has been recently established. Both the RA27/3 vaccine and wild-type RuV strains were highly sensitive to a broad-spectrum antiviral drug, nitazoxanide (NTZ), in vitro. However, NTZ treatment, used as a salvage therapy, resulted in little or no improvements of RuV-associated cutaneous granulomas in patients. Here, we report investigations of possible causes of treatment failures in two ataxia-telangiectasia patients. Although a reduction in RuV RNA in skin lesions was detected by real-time RT-PCR, live immunodeficiency-related vaccine-derived rubella viruses (iVDRV) were recovered from granulomas, before and after the treatments. Tizoxanide, an active NTZ metabolite, inhibited replications of all iVDRVs in cultured A549 cells, but the 50% and 90% inhibitory concentrations were 10-40 times higher than those for the RA27/3 strain. There were no substantial differences in iVDRV sensitivities, neither before nor after treatments. Analysis of quasispecies in the E1 gene, a suspected NTZ target, showed no effect of NTZ treatments on quasispecies' complexity in lesions. Thus, failures of NTZ therapies were likely due to low sensitivities of iVDRVs to the drug, and not related to the emergence of resistance, following long-term NTZ treatments.

    • Immunity and Immunization
      1. School mandate and influenza vaccine uptake among prekindergartners in New York City, 2012-2019external icon
        Hong K, Lindley MC, Tsai Y, Zhou F.
        Am J Public Health. 2022 Mar 24:e1-e5.
        New York City (NYC) introduced a universal prekindergarten program in 2014 that mandated influenza vaccination for enrollment. We conducted a difference-in-difference-in-differences study to evaluate the program using 2012 to 2019 MarketScan claims data. After the introduction of the program, influenza vaccine uptake among four-year-old children in NYC during the subsequent seasons increased by 6.3 to 9.8 percentage points compared with the rest of New York State. (Am J Public Health. Published online ahead of print March 24, 2022: e1-e5. https://doi.org/10.2105/AJPH.2022.306765).

      2. COVID-19 vaccine effectiveness among healthcare workers in Albania (COVE-AL): protocol for a prospective cohort study and cohort baseline dataexternal icon
        Sridhar S, Fico A, Preza I, Hatibi I, Sulo J, Kissling E, Daja R, Ibrahim R, Lemos D, Rubin-Smith J, Schmid A, Vasili A, Valenciano M, Jorgensen P, Pebody R, Lafond KE, Katz MA, Bino S.
        BMJ Open. 2022 Mar 23;12(3):e057741.
        INTRODUCTION: Critical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in health workers (HWs) in Albania, an upper-middle-income country. METHODS AND ANALYSIS: In this 12-month prospective cohort study, we enrolled HWs at three hospitals in Albania. HWs are vaccinated through the routine COVID-19 vaccine campaign. Participants completed a baseline survey about demographics, clinical comorbidities, and infection risk behaviours. Baseline serology samples were also collected and tested against the SARS-CoV-2 spike protein, and respiratory swabs were collected and tested for SARS-CoV-2 by RT-PCR. Participants complete weekly symptom questionnaires and symptomatic participants have a respiratory swab collected, which is tested for SARS-CoV-2. At 3, 6, 9 months and 12 months of the study, serology will be collected and tested for antibodies against the SARS-CoV-2 nucleocapsid protein and spike protein. VE will be estimated using a piecewise proportional hazards model (VE=1-HR). BASELINE DATA: From February to May 2021, 1504 HWs were enrolled. The median age was 44 (range: 22-71) and 78% were female. At enrolment, 72% of participants were seropositive for SARS-CoV-2. 56% of participants were vaccinated with one dose, of whom 98% received their first shot within 4 days of enrolment. All HWs received the Pfizer BNT162b2 mRNA COVID-19 vaccine. ETHICS AND DISSEMINATION: The study protocol and procedures were reviewed and approved by the WHO Ethical Review Board, reference number CERC.0097A, and the Albanian Institute of Public Health Ethical Review Board, reference number 156. All participants have provided written informed consent to participate in this study. The primary results of this study will be published in a peer-reviewed journal at the time of completion. TRIAL REGISTRATION NUMBER: NCT04811391.

      3. Role of information sources in vaccination uptake: Insights from a cross-sectional household survey in Sierra Leone, 2019external icon
        Kulkarni S, Sengeh P, Eboh V, Jalloh MB, Conteh L, Sesay T, Ibrahim N, Manneh PO, Kaiser R, Jinnai Y, Wallace AS, Prybylski D, Jalloh MF.
        Glob Health Sci Pract. 2022 Feb 28;10(1).
        INTRODUCTION: There is limited understanding of the potential impact of information sources on vaccination attitudes and behaviors in low-income countries. We examined how exposure to immunization information sources may be associated with vaccination uptake in Sierra Leone. METHODS: In 2019, a household survey was conducted using multistage cluster sampling to randomly select 621 caregivers of children aged 12-23 months in 4 districts in Sierra Leone. We measured exposure to various sources of immunization information and 2 outcomes: (1) vaccination confidence using an aggregate score (from 12 Likert items, informed by previously validated scale) that was dichotomized into a binary variable; (2) uptake of the third dose of diphtheria-pertussis-tetanus-hepatitis B-Haemophilus influenzae type-b-pentavalent vaccine (penta-3) based on card record or through caregiver recall when card was unavailable. Associations between information sources and the outcomes were examined using modified Poisson regression with robust variance estimator. RESULTS: Weighted estimate for penta-3 uptake was 81% (75.2%-85.5%). The likelihood of uptake of penta-3 was significantly greater when caregiver received information from health facilities (adjusted prevalence ratio [aPR]=1.26, 95% confidence interval [CI]=1.1, 1.5), faith leaders (aPR=1.16, 95% CI=1.1, 1.3), and community health workers (aPR=1.13, 95% CI=1.003, 1.3). Exposure to greater number of information sources was associated with high penta-3 uptake (aPR=1.05, 95% CI=1.02, 1.1). DISCUSSION: Immunization information received during health facility visits and through engagement with religious leaders may enhance vaccination uptake. Assessments to understand context-specific information dynamics should be prioritized in optimizing immunization outcomes.

      4. Human papillomavirus vaccination coverage among young, gay, bisexual, and other men who have sex with men and transgender women - 3 U.S. cities, 2016-2018external icon
        Amiling R, Winer RL, Newcomb ME, Gorbach PM, Lin J, Crosby RA, Mustanski B, Markowitz LE, Meites E.
        Hum Vaccin Immunother. 2021 Dec 2;17(12):5407-5412.
        Gay, bisexual, and other men who have sex with men (MSM) and transgender women are disproportionately affected by human papillomavirus (HPV). HPV vaccination is routinely recommended for U.S. adolescents at age 11-12 years, with catch-up vaccination through age 26 years. We assessed HPV vaccination coverage and associated factors among young MSM and transgender women. The Vaccine Impact in Men study enrolled MSM aged 18-26 years from clinics in Seattle, Chicago, and Los Angeles, during February 2016-September 2018. Participants self-reported socio-demographic information and HPV vaccination status. Among 1416 participants, 673 (47.5%) reported ≥1 HPV vaccine dose. Among vaccinated participants, median age at first dose was 19 years and median age at first sex was 17 years; 493 (73.3%) reported that their age at first dose was older than their age at first sex. There were significant differences in HPV vaccination coverage by city (range 33%-62%), age, race/ethnicity, and gender identity. Coverage was highest in Seattle, where younger age was the only factor associated with vaccination. Differences in coverage by city may be due to variation in vaccination practices or enrollment at study sites. Increasing both routine and catch-up vaccination will improve coverage among MSM and transgender women.

      5. The clinical and economic impact of measles-mumps-rubella vaccinations to prevent measles importations from US pediatric travelers returning from abroadexternal icon
        Bangs AC, Gastañaduy P, Neilan AM, Fiebelkorn AP, Walker AT, Rao SR, Ryan ET, LaRocque RC, Walensky RP, Hyle EP.
        J Pediatric Infect Dis Soc. 2022 Mar 25.
        BACKGROUND: Pediatric international travelers account for nearly half of measles importations in the United States. Over one third of pediatric international travelers depart the United States without the recommended measles-mumps-rubella (MMR) vaccinations: 2 doses for travelers ≥12 months and 1 dose for travelers 6 to <12 months. METHODS: We developed a model to compare 2 strategies among a simulated cohort of international travelers (6 months to <6 years): (1) No pretravel health encounter (PHE): travelers depart with baseline MMR vaccination status; (2) PHE: MMR-eligible travelers are offered vaccination. All pediatric travelers experience a destination-specific risk of measles exposure (mean, 30 exposures/million travelers). If exposed to measles, travelers' age and MMR vaccination status determine the risk of infection (range, 3%-90%). We included costs of medical care, contact tracing, and lost wages from the societal perspective. We varied inputs in sensitivity analyses. Model outcomes included projected measles cases, costs, and incremental cost-effectiveness ratios ($/quality-adjusted life year [QALY], cost-effectiveness threshold ≤$100 000/QALY). RESULTS: Compared with no PHE, PHE would avert 57 measles cases at $9.2 million/QALY among infant travelers and 7 measles cases at $15.0 million/QALY among preschool-aged travelers. Clinical benefits of PHE would be greatest for infants but cost-effective only for travelers to destinations with higher risk for measles exposure (ie, ≥160 exposures/million travelers) or if more US-acquired cases resulted from an infected traveler, such as in communities with limited MMR coverage. CONCLUSIONS: Pretravel MMR vaccination provides the greatest clinical benefit for infant travelers and can be cost-effective before travel to destinations with high risk for measles exposure or from communities with low MMR vaccination coverage.

      6. Association of persistent rubella virus with idiopathic skin granulomas in clinically immunocompetent adultsexternal icon
        Wanat KA, Perelygina L, Chen MH, Hao L, Abernathy E, Bender NR, Shields BE, Wilson BD, Crosby D, Routes J, Samimi SS, Haun PL, Sokumbi O, Icenogle JP, Sullivan KE, Rosenbach M, Drolet BA.
        JAMA Dermatol. 2022 Mar 26.
        IMPORTANCE: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. OBJECTIVE: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. DESIGN, SETTING, AND PARTICIPANTS: This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed. MAIN OUTCOMES AND MEASURES: Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults. RESULTS: Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies. CONCLUSIONS AND RELEVANCE: The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV.

      7. BACKGROUND: HIV-1 vaccine efforts are primarily directed towards eliciting neutralizing antibodies (nAbs). However, vaccine trials and mother to child natural history cohort investigations indicate that antibody-dependent cellular cytotoxicity (ADCC), not nAbs, correlate with prevention. The ADCC characteristics associated with lack of HIV-1 acquisition remain unclear. METHODS: Here we examine ADCC and nAb properties in pre-transmission plasma from HIV-1 exposed infants and from the corresponding transmitting and non-transmitting mothers' breast milk and plasma. Breadth and potency (BP) is assessed against a panel of heterologous, non-maternal, variants. ADCC and neutralization sensitivity is estimated for the strains present in the infected mothers. RESULTS: Infants that eventually acquire HIV-1 and those that remain uninfected have similar pre-transmission ADCC BP. The viruses circulating in the transmitting and the non-transmitting mothers also have similar ADCC susceptibility. Infants with a combination of higher pre-transmission ADCC BP and exposure to more ADCC susceptible strains are less likely to acquire HIV-1. In contrast, higher pre-existing infant neutralization BP and greater maternal virus neutralization sensitivity does not associate with transmission. Infants have higher ADCC BP closer to birth and in the presence of high plasma IgG relative to IgA levels. Mothers with potent humoral responses against their autologous viruses harbor more ADCC sensitive strains. CONCLUSION: ADCC sensitivity of the exposure variants along with preexisting ADCC BP influence mother to child HIV-1 transmission during breastfeeding. Vaccination strategies that enhance ADCC responses are likely not sufficient to prevent HIV-1 transmission because strains present in chronically infected individuals can have low ADCC susceptibility. TRIAL REGISTRATION: NCT00164736 for BAN study.

      8. Effectiveness of mRNA vaccination in preventing COVID-19-associated invasive mechanical ventilation and death - United States, March 2021-January 2022external icon
        Tenforde MW, Self WH, Gaglani M, Ginde AA, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, McNeal T, Ghamande S, Gibbs KW, Files DC, Hager DN, Shehu A, Prekker ME, Frosch AE, Gong MN, Mohamed A, Johnson NJ, Srinivasan V, Steingrub JS, Peltan ID, Brown SM, Martin ET, Monto AS, Khan A, Hough CL, Busse LW, Duggal A, Wilson JG, Qadir N, Chang SY, Mallow C, Rivas C, Babcock HM, Kwon JH, Exline MC, Botros M, Lauring AS, Shapiro NI, Halasa N, Chappell JD, Grijalva CG, Rice TW, Jones ID, Stubblefield WB, Baughman A, Womack KN, Rhoads JP, Lindsell CJ, Hart KW, Zhu Y, Adams K, Surie D, McMorrow ML, Patel MM.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 25;71(12):459-465.
        COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).

      9. BNT162b2 protection against the Omicron variant in children and adolescentsexternal icon
        Price AM, Olson SM, Newhams MM, Halasa NB, Boom JA, Sahni LC, Pannaraj PS, Irby K, Bline KE, Maddux AB, Nofziger RA, Cameron MA, Walker TC, Schwartz SP, Mack EH, Smallcomb L, Schuster JE, Hobbs CV, Kamidani S, Tarquinio KM, Bradford TT, Levy ER, Chiotos K, Bhumbra SS, Cvijanovich NZ, Heidemann SM, Cullimore ML, Gertz SJ, Coates BM, Staat MA, Zinter MS, Kong M, Chatani BM, Hume JR, Typpo KV, Maamari M, Flori HR, Tenforde MW, Zambrano LD, Campbell AP, Patel MM, Randolph AG.
        N Engl J Med. 2022 Mar 30.
        BACKGROUND: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. METHODS: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. RESULTS: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). CONCLUSIONS: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.).

      10. Safety of live attenuated influenza vaccine in children with asthmaexternal icon
        Sokolow AG, Stallings AP, Kercsmar C, Harrington T, Jimenez-Truque N, Zhu Y, Sokolow K, Moody MA, Schlaudecker EP, Walter EB, Staat MA, Broder KR, Creech CB.
        Pediatrics. 2022 Mar 28.
        BACKGROUND AND OBJECTIVES: Asthma is considered a precaution for use of quadrivalent live attenuated influenza vaccine (LAIV4) in persons aged ≥5 years because of concerns for wheezing events. We evaluated the safety of LAIV4 in children with asthma, comparing the proportion of children with asthma exacerbations after LAIV4 or quadrivalent inactivated influenza vaccine (IIV4). METHODS: We enrolled 151 children with asthma, aged 5 to 17 years, during 2 influenza seasons. Participants were randomly assigned 1:1 to receive IIV4 or LAIV4 and monitored for asthma symptoms, exacerbations, changes in peak expiratory flow rate (PEFR), and changes in the asthma control test for 42 days after vaccination. RESULTS: We included 142 participants in the per-protocol analysis. Within 42 days postvaccination, 18 of 142 (13%) experienced an asthma exacerbation: 8 of 74 (11%) in the LAIV4 group versus 10 of 68 (15%) in the IIV4 group (LAIV4-IIV4 = -0.0390 [90% confidence interval -0.1453 to 0.0674]), meeting the bounds for noninferiority. When adjusted for asthma severity, LAIV4 remained noninferior to IIV4. There were no significant differences in the frequency of asthma symptoms, change in PEFR, or childhood asthma control test/asthma control test scores in the 14 days postvaccination between LAIV4 and IIV4 recipients. Vaccine reactogenicity was similar between groups, although sore throat (P = .051) and myalgia (P <.001) were more common in the IIV4 group. CONCLUSIONS: LAIV4 was not associated with increased frequency of asthma exacerbations, an increase in asthma-related symptoms, or a decrease in PEFR compared with IIV4 among children aged 5 to 17 years with asthma.

      11. Benefit conferred by "enhanced" influenza vaccines is often measured by relative vaccine effectiveness, (rVE), which compares disease risk among groups of people who received alternative vaccines. Differences in attenuation of illness severity by vaccine types could manifest as differences in rVE. Using a simulated VE study and cohort of adults aged ≥ 65 years, we examined how rVE varied with assumptions about attenuation of disease severity conferred by standard and enhanced vaccines and how this variation could lead to differing estimates of rVE for prevention of moderate (i.e., outpatient) versus severe (i.e., inpatient) influenza illness. We found that if enhanced vaccines attenuated severe illness more than moderate illness, then rVE observed against severe disease could be higher than rVE observed against moderate disease. Thus, if differences in disease attenuation by vaccine type occurs, estimates of rVE may vary for influenza outcomes of differing levels of severity.

      12. Concurrent outbreaks of circulating vaccine-derived poliovirus types 1 and 2 affecting the Republic of the Philippines and Malaysia, 2019-2021external icon
        Snider CJ, Boualam L, Tallis G, Takashima Y, Abeyasinghe R, Lo YR, Grabovac V, Avagyan T, Aslam SK, Eltayeb AO, Aung KD, Wang X, Shrestha A, Ante-Orozco C, Silva MW, Lapastora-Sucaldito N, Apostol LN, Jikal MB, Miraj W, Lodhi F, Kim HJ, Rusli N, Thorley BR, Kaye MB, Nishimura Y, Arita M, Sani JA, Rundi C, Feldon K.
        Vaccine. 2022 Mar 22.
        Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.

      13. Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccineexternal icon
        Voorman A, Lyons H, Bennette C, Kovacs S, Makam JK, Vertefeuille J, Tallis G.
        Vaccine. 2022 Mar 23.
        BACKGROUND: The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2). METHODS: We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016. We account for the changes in routine immunization schedules and varying implementation of preventive and outbreak response SIAs, assuming homogenous coverages of 50% and 80% for SIAs. RESULTS: In areas with strong routine immunization, the switch from tOPV to bOPV has likely resulted in gains in population immunity to types 1 and 3 poliovirus. However, we estimate that improved immunogenicity of new schedules has not compensated for declines in preventive SIAs in areas with weak routine immunization. For type 2 poliovirus, without tOPV in routine immunization or SIAs, mucosal immunity has declined nearly everywhere, while use of mOPV2 has created highly heterogeneous population immunity for which it is important to take into account when responding to cVDPV2 outbreaks. CONCLUSIONS: The withdrawal of tOPV and declining allocations of resources for preventive bOPV SIAs have resulted in reduced immunity in vulnerable areas to types 1 and 3 poliovirus and generally reduced immunity to type 2 poliovirus in the regions studied, assuming homogeneous coverages of 50% and 80% for SIAs. The very low mucosal immunity to type 2 poliovirus generates substantially greater risk for further spread of cVDPV2 outbreaks. Emerging gaps in immunity to all serotypes will require judicious targeting of limited resources to the most vulnerable populations by the Global Polio Eradication Initiative (GPEI).

      14. Effectiveness of monovalent rotavirus vaccine in Mozambique, a country with a high burden of chronic malnutritionexternal icon
        Chissaque A, Burke RM, Guimarães EL, Manjate F, Nhacolo A, Chilaúle J, Munlela B, Chirinda P, Langa JS, Cossa-Moiane I, Anapakala E, Bauhofer AF, Garrine M, João ED, Sambo J, Gonçalves L, Weldegebriel G, Shaba K, Bello IM, Mwenda JM, Parashar UD, Tate JE, Mandomando I, de Deus N.
        Vaccines (Basel). 2022 Mar 15;10(3).
        Mozambique introduced monovalent rotavirus vaccine (Rotarix(®)) in September 2015. We evaluated the effectiveness of Rotarix(®) under conditions of routine use in Mozambican children hospitalized with acute gastroenteritis (AGE). A test negative case-control analysis was performed on data collected during 2017-2019 from children &lt;5 years old, admitted with AGE in seven sentinel hospital sites in Mozambique. Adjusted VE was calculated for ≥1 dose of vaccine vs. zero doses using unconditional logistic regression, where VE = (1 - aOR) × 100%. VE estimates were stratified by age group, AGE severity, malnutrition, and genotype. Among 689 children eligible for analysis, 23.7% were rotavirus positive (cases) and 76.3% were negative (controls). The adjusted VE of ≥1 dose in children aged 6-11 months was 52.0% (95% CI, -11, 79), and -24.0% (95% CI, -459, 62) among children aged 12-23 months. Estimated VE was lower in stunted than non-stunted children (14% (95% CI, -138, 66) vs. 59% (95% CI, -125, 91)). Rotavirus vaccination appeared moderately effective against rotavirus gastroenteritis hospitalization in young Mozambican children. VE point estimates were lower in older and stunted children, although confidence intervals were wide and overlapped across strata. These findings provide additional evidence for other high-mortality countries considering rotavirus vaccine introduction.

    • Injury and Violence
      1. Intimate partner violence and health conditions among U.S. Adults-National Intimate Partner Violence Survey, 2010-2012external icon
        Gilbert LK, Zhang X, Basile KC, Breiding M, Kresnow MJ.
        J Interpers Violence. 2022 Mar 25:8862605221080147.
        INTRODUCTION: Few studies of intimate partner violence and health outcomes include multiple forms of intimate partner victimization, so this paper sought to examine health associations with intimate partner violence (IPV), including sexual, physical, stalking, and psychological forms, as well as polyvictimization. METHODS: Data are from the 2010-2012 National Intimate Partner and Sexual Violence Survey, an on-going national random-digit-dial telephone survey of U.S. adults. There were 41,174 respondents. Logistic regression was used to compute prevalence ratios for any IPV, adjusted for demographics and non-IPV victimization. For individual forms of IPV, prevalence ratios were further adjusted for other forms of IPV. Tests for linear trend in poly-victimization were performed. RESULTS: Any IPV was associated with all health conditions for both sexes with a few exceptions for males. Female penetrative sexual victimization and male stalking victimization were associated with the most health conditions. For each health condition, a significant linear trend indicated that as the number of forms of IPV experienced increased, prevalence of each health condition increased, with a few exceptions for males. CONCLUSIONS: It is important for service providers to screen for multiple forms of IPV, including psychological aggression, because individual forms or polyvictimization may have unique and cumulative health effects.

      2. Peer influence on IPV by young adult males: Investigating the case for a social norms approachexternal icon
        McKool M, Stephenson R, Winskell K, Teten Tharp A, Parrott D.
        J Interpers Violence. 2021 Jan;36(1-2):83-102.
        Nearly 32% of women report experiencing physical violence from an intimate partner and more than 8% report being raped by a significant other in their lifetime. Young people's perceptions that their peers perpetrate relationship violence have been shown to increase the odds of self-reported perpetration. Yet, limited research has been conducted on this relationship as individuals begin to age out of adolescence. The present study sought to examine the link between the perception of peer perpetration of intimate partner violence (IPV) and self-reported IPV perpetration among a sample of predominately young adult (21-35 years) males. This study also explored the discordance between the perception of peer IPV behavior and self-reported perpetration. Data from 101 male peer dyads (n = 202) were taken from a study on the effects of alcohol and bystander intervention in Atlanta, Georgia. Thirty-six percent (n = 73) of men reported perpetrating physical IPV and 67% (n = 135) reported perpetrating sexual IPV in the past 12 months. Nearly 35% (n = 55) of the sample reported that none of their peers had perpetrated physical IPV, which contradicted their friend's self-report of physical IPV perpetration. Similarly, 68% (n = 115) of the men perceived none of their peers to have perpetrated sexual IPV, which contradicted their friend's self-report of sexual IPV perpetration. Discordance variables were significantly associated with self-reported perpetration for both physical (χ(2) = 152.7, p < .01) and sexual (χ(2) = 164.4, p < .01) IPV. These results point to an underestimation of peer IPV perpetration among young adult males. Findings suggest a traditional social norms approach to IPV prevention, which seeks to persuade individuals that negative behaviors are less common than perceived, may not be the best approach given a significant number of men believed their friends were nonviolent when they had perpetrated violence.

    • Maternal and Child Health
      1. Group antenatal care for improving retention of adolescent and young pregnant women living with HIV in Kenyaexternal icon
        Teasdale CA, Odondi J, Kidiga C, Choy M, Fayorsey R, Ngeno B, Ochanda B, Langat A, Ngugi C, Callahan T, Modi S, Hawken M, Odera D, Abrams EJ.
        BMC Pregnancy Childbirth. 2022 Mar 15;22(1):208.
        BACKGROUND: Pregnant and breastfeeding adolescents and young women living with HIV (AYWLH) have lower retention in prevention of mother-to-child transmission (PMTCT) services compared to older women. METHODS: We evaluated a differentiated service model for pregnant and postnatal AYWLH at seven health facilities in western Kenya aimed at improving retention in antiretroviral treatment (ART) services. All pregnant AYWLH < 25 years presenting for antenatal care (ANC) were invited to participate in group ANC visits including self-care and peer-led support sessions conducted by health facility nurses per national guidelines. ART register data were used to assess loss to follow-up (LTFU) among newly-enrolled pregnant adolescent (< 20 years) and young women (20-24 years) living with HIV starting ART in the pre-period (January-December 2016) and post-period (during implementation; December 2017-January 2019). Poisson regression models compared LTFU incidence rate ratios (IRR) in the first six months after PMTCT enrollment and risk ratios compared uptake of six week testing for HIV-exposed infants (HEI) between the pre- and post-periods. RESULTS: In the pre-period, 223 (63.2%) of 353 pregnant AYWLH newly enrolled in ANC had ART data, while 320 (71.1%) of 450 in the post-period had ART data (p = 0.02). A higher proportion of women in the post-period (62.8%) had known HIV-positive status at first ANC visit compared to 49.3% in the pre-period (p < 0.001). Among pregnant AYWLH < 20 years, the incidence rate of LTFU in the first six months after enrollment in ANC services declined from 2.36 per 100 person months (95%CI 1.06-5.25) in the pre-period to 1.41 per 100 person months (95%CI 0.53-3.77) in the post-period. In both univariable and multivariable analysis, AYWLH < 20 years in the post-period were almost 40% less likely to be LTFU compared to the pre-period, although this finding did not meet the threshold for statistical significance (adjusted incidence rate ratio 0.62, 95%CI 0.38-1.01, p = 0.057). Testing for HEI was 10% higher overall in the post-period (adjusted risk ratio 1.10, 95%CI 1.01-1.21, p = 0.04). CONCLUSIONS: Interventions are urgently needed to improve outcomes among pregnant and postnatal AYWLH. We observed a trend towards increased retention among pregnant adolescents during our intervention and a statistically significant increase in uptake of six week HEI testing.

      2. Health needs and use of services among children with developmental disabilities - United States, 2014-2018external icon
        Cogswell ME, Coil E, Tian LH, Tinker SC, Ryerson AB, Maenner MJ, Rice CE, Peacock G.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 25;71(12):453-458.
        Developmental delays, disorders, or disabilities (DDs) manifest in infancy and childhood and can limit a person's function throughout life* (1-3). To guide strategies to optimize health for U.S. children with DDs, CDC analyzed data from 44,299 participants in the 2014-2018 National Health Interview Survey (NHIS). Parents reported on 10 DDs,(†) functional abilities, health needs, and use of services. Among the approximately one in six (17.3%) U.S. children and adolescents aged 3-17 years (hereafter children) with one or more DDs, 5.7% had limited ability to move or play, 4.7% needed help with personal care, 4.6% needed special equipment, and 2.4% received home health care, compared with ≤1% for each of these measures among children without DDs. Children with DDs were two to seven times as likely as those without DDs to have taken prescription medication for ≥3 months (41.6% versus 8.4%), seen a mental health professional (30.6% versus 4.5%), a medical specialist (26.0% versus 12.4%), or a special therapist, such as a physical, occupational, or speech therapist, (25.0% versus 4.5%) during the past year, and 18 times as likely to have received special education or early intervention services (EIS) (41.9% versus 2.4%). These percentages varied by type of disability and by sociodemographic subgroup. DDs are common, and children with DDs often need substantial health care and services. Policies and programs that promote early identification of children with developmental delays and facilitate increased access to intervention services can improve health and reduce the need for services later in life.(§) Sociodemographic inequities merit further investigation to guide public health action and ensure early and equitable access to needed care and services.

    • Nutritional Sciences
      1. Iron status and inflammation in women of reproductive age: A population-based biomarker survey and clinical studyexternal icon
        Finkelstein JL, Fothergill A, Guetterman HM, Johnson CB, Bose B, Qi YP, Rose CE, Williams JL, Mehta S, Kuriyan R, Bonam W, Crider KS.
        Clin Nutr ESPEN. 2022 .
        Background: Women of reproductive age (WRA) are at increased risk for anemia and iron deficiency. However, there is limited population-level data in India, which could help inform evidence-based recommendations and policy. Aims: To conduct a population-based biomarker survey of anemia, iron deficiency, and inflammation in WRA in Southern India. Methods: Participants were WRA (15-40 y) who were not pregnant or lactating. Blood samples (n = 979) were collected and analyzed for hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and alpha-1 acid glycoprotein (AGP). Anemia and severe anemia were defined as Hb < 12.0 and < 8.0 g/dL. Serum ferritin was adjusted for inflammation using BRINDA methods. Iron deficiency was defined as SF <15.0 μg/L, iron insufficiency was defined as SF < 20.0 and < 25.0 μg/L, and iron deficiency anemia was defined as Hb < 12.0 g/dL and SF < 15.0 μg/L. Inflammation was defined as CRP > 5.0 mg/L or AGP > 1.0 g/L. Restricted cubic spline regression models were also used to determine if alternative SF thresholds should be used t to classify iron deficiency. Results: A total of 41.5% of WRA had anemia, and 3.0% had severe anemia. Findings from spline analyses suggested a SF cut-off of < 15.0 μg/L, consistent with conventional cut-offs for iron deficiency. 46.3% of WRA had SF < 15.0 μg/L (BRINDA-adjusted: 61.5%), 55.0% had SF < 20.0 μg/L (72.7%), 61.8% had SF < 25.0 μg/L (81.0%), and 30.0% had IDA (34.5%). 17.3% of WRA had CRP > 5.0 mg/L and 22.2% had AGP > 1.0 g/L. The prevalence of ID (rural vs. urban: 49.1% vs. 34.9%; p = 0.0004), iron insufficiency (57.8% vs. 43.8%; p = 0.0005), and IDA (31.8% vs. 22.4%; p = 0.01) were significantly higher in rural areas, although CRP levels were lower and there were no differences in elevated CRP or AGP. Conclusions: The burden of anemia and iron deficiency in this population was substantial, and increased after adjusting for inflammation, suggesting potential to benefit from screening and interventions. Registration number: NCT04048330. © 2022 The Author(s)

      2. Impact of land use and food environment on risk of type 2 diabetes: A national study of veterans, 2008-2018external icon
        India-Aldana S, Kanchi R, Adhikari S, Lopez P, Schwartz MD, Elbel BD, Rummo PE, Meeker MA, Lovasi GS, Siegel KR, Chen Y, Thorpe LE.
        Environ Res. 2022 Mar 22:113146.
        BACKGROUND: Large-scale longitudinal studies evaluating influences of the built environment on risk for type 2 diabetes (T2D) are scarce, and findings have been inconsistent. OBJECTIVE: To evaluate whether land use environment (LUE), a proxy of neighborhood walkability, is associated with T2D risk across different US community types, and to assess whether the association is modified by food environment. METHODS: The Veteran's Administration Diabetes Risk (VADR) study is a retrospective cohort of diabetes-free US veteran patients enrolled in VA primary care facilities nationwide from January 1, 2008, to December 31, 2016, and followed longitudinally through December 31, 2018. A total of 4,096,629 patients had baseline addresses available in electronic health records that were geocoded and assigned a census tract-level LUE score. LUE scores were divided into quartiles, where a higher score indicated higher neighborhood walkability levels. New diagnoses for T2D were identified using a published computable phenotype. Adjusted time-to-event analyses using piecewise exponential models were fit within four strata of community types (higher-density urban, lower-density urban, suburban/small town, and rural). We also evaluated effect modification by tract-level food environment measures within each stratum. RESULTS: In adjusted analyses, higher LUE had a protective effect on T2D risk in rural and suburban/small town communities (linear quartile trend test p-value <0.001). However, in lower density urban communities, higher LUE increased T2D risk (linear quartile trend test p-value <0.001) and no association was found in higher density urban communities (linear quartile trend test p-value = 0.317). Particularly strong protective effects were observed for veterans living in suburban/small towns with more supermarkets and more walkable spaces (p-interaction = 0.001). CONCLUSION: Among veterans, LUE may influence T2D risk, particularly in rural and suburban communities. Food environment may modify the association between LUE and T2D.

    • Occupational Safety and Health
      1. Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panelexternal icon
        Visser M, Gosens I, Bard D, van Broekhuizen P, Janer G, Kuempel E, Riediker M, Vogel U, Dekkers S.
        NanoImpact. 2022 ;26.
        Unique physicochemical characteristics of engineered nanomaterials (ENMs) suggest the need for nanomaterial-specific occupational exposure limits (OELs). Setting these limits remains a challenge. Therefore, the aim of this study was to set out a framework to evaluate the feasibility of deriving advisory health-based occupational limit values for groups of ENMs, based on scientific knowledge. We have used an expert panel approach to address three questions: 1) What ENM-categories should be distinguished to derive advisory health-based occupational limit values (or health-based Nano Reference Values, HNRVs) for groups of ENMs? 2) What evidence would be needed to define values for these categories? And 3) How much effort would it take to achieve this? The panel experts distinguished six possible categories of HNRVs: A) WHO-fiber-like high aspect ratio ENMs (HARNs), B) Non-WHO-fiber-like HARNs and other non-spheroidal ENMs, C) readily soluble spheroidal ENMs, D) biopersistent spheroidal ENMs with unknown toxicity, E) biopersistent spheroidal ENMs with substance-specific toxicity and F) biopersistent spheroidal ENMs with relatively low substance-specific toxicity. For category A, the WHO-fiber-like HARNs, agreement was reached on criteria defining this category and the approach of using health-based risk estimates for asbestos to derive the HNRV. For category B, a quite heterogeneous category, more toxicity data are needed to set an HNRV. For category C, readily soluble spheroidal ENMs, using the OEL of their molecular or ionic counterpart would be a good starting point. For the biopersistent ENMs with unknown toxicity, HNRVs cannot be applied as case-by-case testing is required. For the other biopersistent ENMs in category E and F, we make several recommendations that can facilitate the derivation of these HNRVs. The proposed categories and recommendations as outlined by this expert panel can serve as a reference point for derivation of HNRVs when health-based OELs for ENMs are not yet available. © 2022

    • Occupational Safety and Health - Mining
      1. Pathology and mineralogy demonstrate respirable crystalline silica is a major cause of severe pneumoconiosis in US coal minersexternal icon
        Cohen RA, Rose CS, Go LH, Zell-Baran LM, Almberg KS, Sarver EA, Lowers HA, Iwaniuk C, Clingerman SM, Richardson DL, Abraham JL, Cool CD, Franko AD, Hubbs AF, Murray J, Orandle MS, Sanyal S, Vorajee NI, Petsonk EL, Zulfikar R, Green FH.
        Ann Am Thorac Soc. 2022 Mar 30.
        RATIONALE: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States (US) are not yet fully understood. OBJECTIVE: To compare the pathologic and mineralogic features of contemporary coal miners suffering severe pneumoconiosis to their historical counterparts. METHODS: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) to those born in or after 1930 (contemporary). RESULTS: We found a significantly higher proportion of silica-type PMF (57% vs. 18%, p<0.001) among contemporary miners compared to their historical counterparts. Mineral dust alveolar proteinosis (MDAP) was also more common in contemporary miners compared to their historical counterparts (70% vs. 37%, p<0.01). In situ mineralogic analysis showed the percentage (26.1% vs. 17.8%, p<0.01) and concentration (47.3 x 108 vs. 25.8 X 108 particles/cm3, p=0.036) of silica particles was significantly greater in specimens from contemporary miners compared to their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, MDAP, silicotic nodules, or immature silicotic nodules were present (p<0.05). CONCLUSIONS: Exposure to respirable crystalline silica appears causal in the unexpected surge in severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure in order to prevent the disabling and untreatable adverse health effects afflicting US coal miners. Primary Source of Funding: Alpha Foundation for the Improvement of Mine Safety and Health, Inc.

    • Parasitic Diseases
      1. Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug ad ministration surveillance in American Samoaexternal icon
        Cadavid Restrepo AM, Gass K, Won KY, Sheel M, Robinson K, Graves PM, Fuimaono S, Lau CL.
        Int J Infect Dis. 2022 Apr;117:378-386.
        BACKGROUND: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted 7 rounds of mass drug administration (MDA) between 2000 and 2006. The territory passed transmission assessment surveys (TASs) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Abs) may have provided a timelier indication of LF resurgence in American Samoa. METHODS: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, and Bm33 Ags at each TAS. Pearson chi-square test and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. RESULTS: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% confidence interval [CI] 1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33, or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). CONCLUSION: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in surveillance after MDA and decision making should be further investigated in other settings.

      2. Higher-dose primaquine to prevent relapse of plasmodium vivax malariaexternal icon
        Chamma-Siqueira NN, Negreiros SC, Ballard SB, Farias S, Silva SP, Chenet SM, Santos EJ, Pereira de Sena LW, Póvoa da Costa F, Cardoso-Mello AG, Marchesini PB, Peterka CR, Viana GM, Macedo de Oliveira A.
        N Engl J Med. 2022 Mar 31;386(13):1244-1253.
        BACKGROUND: In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. METHODS: In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. RESULTS: We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. CONCLUSIONS: The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).

    • Physical Activity
      1. BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

    • Public Health Leadership and Management

    • Reproductive Health
      1. Trends in emergency contraceptive use among adolescents and young adults, 2006-2017external icon
        Mehta SD, Kulkarni AD, Pazol K, Koumans EH.
        J Adolesc Health. 2022 Mar 26.
        PURPOSE: In 2013, age restrictions for adolescents on over-the-counter access were removed for "Plan B One-Step", a single oral medication option for emergency contraception use. Restrictions on generic options of the emergency contraceptive pill (ECP) were removed in 2014. METHODS: National Survey of Family Growth data were used to assess the prevalence of ever use of ECPs among sexually experienced female adolescents and young adults (AYA) aged 15-24 years (2015-2017 sample), and trends in indicators of ECP use and acquisition (2006-2017 samples). Prevalence estimates were obtained by age subgroups for 15-17, 18-19, and 20-24 years. Statistical significance was determined using an alpha of .05 and 95% confidence intervals calculated around the point estimates. RESULTS: The weighted estimate of sexually experienced female AYA in the United States ranged from 13.3 million in 2006-2008 to 12.7 million in 2015-2017. The prevalence of ever ECP use was 18.2% (95% CI 15.7-21.1) and 31.8% (95% CI 26.9-37.1) in 2006-2008 and 2015-2017, respectively. Ever use in 2015-2017 varied by age group, number of lifetime opposite-sex partners and abortions, and experience of nonconsensual sex. In 2008-2010, 46.1% (95% CI 36.0-56.5) of respondents last obtained ECPs at community health or family planning clinics, and 31.8% (95% CI 22.9-42.2) last obtained ECPs at a pharmacy compared to 18.1% (95% CI 12.0-26.4) and 70.1% (95% CI 60.6-78.1) respectively in 2015-2017. Prevalence of provider counseling about emergency contraception in female AYA regardless of prior sexual experience in the past 12 months remained at or below 5% from 2006 to 2017. CONCLUSION: Increasing access to ECPs over-the-counter may have contributed to notable increases in reported ever use of ECPs and in the receipts from a pharmacy among AYA between 2006 and 2017. AYA may benefit if pharmacists and healthcare providers increase reproductive health counseling.

      2. BACKGROUND: Little is known about trends in implementing skills-based instruction in US schools, specifically for sexual and reproductive health (SRH). We examined state-level trends in the percentage of US secondary schools teaching SRH skills in a required course in grades 6 to 8 and 9 to 12. METHODS: Representative data from 35 states participating across 6 cycles of School Health Profiles (2008-2018) was analyzed. The prevalence of teaching four SRH skills was assessed through lead health education teacher self-administered questionnaires. Logistic regression models examined linear trends in the percentages of schools teaching SRH skills in grades 6 to 8 and 9 to 12. Trends were calculated for states with weighted data (response rates ≥70%) for at least 3 cycles, including 2018. RESULTS: During 2008 to 2018, the median percentage of schools addressing each SRH skill ranged from 63.5% to 69.7% (grades 6-8) and 88.2% to 92.0% (grades 9-12). Linear decreases in SRH skills instruction were more common for grades 6 to 8 than grades 9 to 12; linear increases were comparable for both groups. Most states demonstrated no change in the percentage of schools teaching SRH skills in grades 6 to 8 and 9 to 12. CONCLUSIONS: Limited changes and decreases in SRH skills instruction in US secondary schools suggest efforts to strengthen SRH education are needed.

    • Sciences, General
      1. In a companion paper, we requested the Judicial Commission to correct the type strain of Aeromonas punctata from ATCC 15468(T) to NCMB 74(T) (=ATCC 23309(T)). Correction of this error on the 1980 Approved Lists by an Opinion of the Judicial Commission will remove the status of the name Aeromonas caviae as a junior objective synonym of A. punctata. This is important because the scientific community continues to use the name A. caviae almost exclusively instead of A. punctata. However, the corrective action of this Opinion will cause a new problem. A. punctata and A. eucrenophila will then become objective synonyms because both species will have the same type strain NCMB 74(T), and A. punctata would have priority because it was published first (1890 vs. 1987). Thus, A. punctata rather than A. eucrenophila would become the correct name for DNA hybridization group 6. A. punctata has had a very confusing history since it was first described as Bacillus punctatus by Zimmermann in 1890. It was without a type strain for over 50 years, and unfortunately, has had an incorrect type strain for some 40 years. The name A. punctata as a bacterial species has been used incorrectly in the literature very frequently, either based on the wrong type strain or with the wrong definition or circumscription. The name A. punctata is not accepted or used by most specialists who study and publish scientific papers and reviews on Aeromonas. Under the heading 'Rejection of Names' Rule 56a of the Bacterial Code states reasons why the Judicial Commission can reject a name, the first is: '(1) An ambiguous name (nomen ambiguum), i.e., a name which has been used with different meanings and thus has become a source of error'. Rule 56a gives the Judicial Commission authority to place names on the list of rejected names. Our analysis of its history leads us to state unequivocally that A. punctata currently is, and has been throughout the vast majority of its history, an ambiguous name. After considering all the possible alternatives and their consequences we request the Judicial Commission to go against the rules of priority; to invoke case (1) of Rule 56a, and issue an Opinion conserving A. eucrenophila over A. punctata; and to place the name A. punctata on the list of rejected names. We argue that these actions will give instant stability to a complex and confusing situation by making A. eucrenophila rather than A. punctata the correct name for 'Aeromonas DNA hybridization group 6', an association that is almost universally accepted by the scientific community as reflected in the literature.

    • Social and Behavioral Sciences
      1. An introduction to "discrete choice experiments" for behavior analystsexternal icon
        Friedel JE, Foreman AM, Wirth O.
        Behav Processes. 2022 Mar 27:104628.
        In this paper, we introduce discrete choice experiments (DCEs) and provide foundational knowledge on the topic. DCEs are one of the most popular methods within econometrics to study the distribution of choices within a population. DCEs are particularly useful when studying the effects of categorical variables on choice. Procedurally, a DCE involves recruiting a large sample of individuals exposed to a set of choice arrays. The factors that are suspected to affect choice are varied systematically across the choice arrays. Most commonly, DCE data are analyzed with a multinomial logit statistical model with a goal of determining the relative utility of each relevant factor. We also discuss DCEs in comparison with behavioral choice models, such as those based on the matching law, and we show an example of a DCE to illustrate how a DCE can be used to understand choice with behavioral, social, and organizational factors.

    • Substance Use and Abuse
      1. Association of prepregnancy substance use and substance use disorders with pregnancy timing and intentionexternal icon
        Coy KC, Ko JY, Ondersma SJ, Gilstad-Hayden K, Zapata LB, Chang G, Yonkers K.
        J Womens Health (Larchmt). 2022 Mar 23.
        Background: Limited research exists on the association between substance use disorders (SUDs) and dimensions of pregnancy intention. This study sought to examine the independent relationships between prepregnancy substance use and SUDs with pregnancy timing and intentions. Materials and Methods: Secondary analysis of data from three prenatal care sites in Connecticut, Massachusetts, and Michigan, 2016-2017. Associations were estimated using modified Poisson regression with robust error variance to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for relevant covariates. Results: The total sample size was 1115 women. Respectively, 61.1% and 15.5% of women used any substance in the 30 days prepregnancy or had any SUD in the past 12 months. After adjustment, any prepregnancy substance use was associated with a reduced likelihood of a well-timed (aPR 0.85; 95% CI: 0.77-0.93) and intended (aPR 0.80; 95% CI: 0.72-0.89) pregnancy; similarly, any SUD was associated with a reduced likelihood of a well-timed (aPR 0.66; 95% CI: 0.55-0.80) and intended (aPR 0.79; 95% CI: 0.67-0.93) pregnancy. Conclusions: Women with prepregnancy substance use or SUD have decreased prevalence of well-timed and intended pregnancies. Greater efforts are needed to address substance use and family planning in routine, well-woman, prenatal, and postpartum care.

      2. Variability in urinary nicotine exposure biomarker levels between waves 1 (2013-2014) and 2 (2014-2015) in the Population Assessment of Tobacco and Health Studyexternal icon
        Ashley DL, Zhu W, Wang L, Sosnoff C, Feng J, Del Valle-Pinero AY, Cheng YC, Chang CM, van Bemmel D, Borek N, Kimmel HL, Silveira ML, Blount BC.
        Nicotine Tob Res. 2022 Mar 25.
        INTRODUCTION: To date, no studies have evaluated the consistency of biomarker levels in people who smoke over a long-time period in real-world conditions with a large number of subjects and included use behavior and measures of nicotine metabolism. We evaluated the variability of biomarkers of nicotine exposure over approximately a 1-year period in people who exclusively smoke cigarettes, including intensity and recency of use and brand switching to assess impact on understanding associations with product characteristics. AIMS AND METHODS: Multivariate regression analysis of longitudinal repeated measures of urinary biomarkers of nicotine exposure from 916 adults in the Population Assessment of Tobacco and Health (PATH) Study with demographic characteristics and use behavior variables. Intraclass correlation coefficients (ICCs) were calculated to examine individual variation of nicotine biomarkers and the uncertainty of repeat measures at two time points (Waves 1 and 2). RESULTS: Age, race, and urinary creatinine were significant covariates of urinary cotinine. When including use behavior, recency, and intensity of use were highly significant and variance decreased to a higher extent between than within subjects. The ICC for urinary cotinine decreased from 0.7530 with no use behavior variables in the model to 0.5763 when included. Similar results were found for total nicotine equivalents. CONCLUSIONS: Urinary nicotine biomarkers in the PATH Study showed good consistency between Waves 1 and 2. Use behavior measures such as time since last smoked a cigarette and number of cigarettes smoked in the past 30 days are important to include when assessing factors that may influence biomarker concentrations. IMPLICATIONS: The results of this study show that the consistency of the nicotine biomarkers cotinine and total nicotine equivalents in spot urine samples from Waves 1 to 2 of the PATH Study is high enough that these data are useful to evaluate the association of cigarette characteristics with biomarkers of exposure under real-world use conditions.

      3. Urinary nicotine metabolites and self-reported tobacco use among adults in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014external icon
        Feng J, Sosnoff CS, Bernert JT, Blount BC, Li Y, Del Valle-Pinero AY, Kimmel HL, van Bemmel DM, Rutt SM, Crespo-Barreto J, Borek N, Edwards KC, Alexander R, Arnstein S, Lawrence C, Hyland A, Goniewicz ML, Rehmani I, Pine B, Pagnotti V, Wade E, Sandlin J, Luo Z, Piyankarage S, Hatsukami DK, Hecht SS, Conway KP, Wang L.
        Nicotine Tob Res. 2022 Mar 26;24(5):768-777.
        INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a longitudinal cohort study on tobacco use behavior, attitudes and beliefs, and tobacco-related health outcomes, including biomarkers of tobacco exposure in the U.S. population. In this report we provide a summary of urinary nicotine metabolite measurements among adult users and non-users of tobacco from Wave 1 (2013-2014) of the PATH Study. METHODS: Total nicotine and its metabolites including cotinine, trans-3'-hydroxycotinine (HCTT), and other minor metabolites were measured in more than 11 500 adult participants by liquid chromatography tandem mass spectrometry methods. Weighted geometric means (GM) and least square means from statistical modeling were calculated for non-users and users of various tobacco products. RESULTS: Among daily users, the highest GM concentrations of nicotine, cotinine and HCTT were found in exclusive smokeless tobacco users, and the lowest in exclusive e-cigarette users. Exclusive combustible product users had intermediate concentrations, similar to those found in users of multiple products (polyusers). Concentrations increased with age within the categories of tobacco users, and differences associated with gender, race/ethnicity and educational attainment were also noted among user categories. Recent (past 12 months) former users had GM cotinine concentrations that were more than threefold greater than never users. CONCLUSIONS: These urinary nicotine metabolite data provide quantification of nicotine exposure representative of the entire US adult population during 2013-2014 and may serve as a reference for similar analyses in future measurements within this study. IMPLICATIONS: Nicotine and its metabolites in urine provide perhaps the most fundamental biomarkers of recent nicotine exposure. This report, based on Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study, provides the first nationally representative data describing urinary nicotine biomarker concentrations in both non-users, and users of a variety of tobacco products including combustible, e-cigarette and smokeless products. These data provide a urinary biomarker concentration snapshot in time for the entire US population during 2013-2014, and will provide a basis for comparison with future results from continuing, periodic evaluations in the PATH Study.

      4. INTRODUCTION: Tobacco is the leading cause of preventable death in the world. Identification of factors associated with quit attempts and successful quitting can help strengthen tobacco cessation programs. In Ethiopia, no prior study of such factors exists. Our aim was to identify factors associated with quit attempts and successful quitting among adults who smoke tobacco in Ethiopia. METHODS: We used the Ethiopian 2016 Global Adult Tobacco Survey (GATS) data (n=10150). GATS is a nationally representative household survey that collects data on sociodemographic and tobacco-related characteristics. We calculated prevalence of reported past 12 months quit attempts and successful quitting and performed logistic regression to obtain prevalence ratios with 95% confidence intervals. A p<0.05 was considered statistically significant. RESULTS: Overall 42.0% of people who smoked tobacco made a quit attempt. Men were more likely (APR=3.9; 95% CI: 1.4-10.7) to make a quit attempt compared to women but were less likely to successfully quit (APR=0.6; 95% CI: 0.3-0.9). Those aware of the health harms of tobacco were 2.5 (95% CI: 1.1-5.5) and 3.9 (95% CI: 1.8-8.5) times as likely to make a quit attempt and successfully quit, respectively, than those unaware. Receiving healthcare provider advice to quit was not associated with quit attempts. CONCLUSIONS: More than 4 in 10 people smoking tobacco in Ethiopia are making attempts to quit. Receipt of healthcare provider advice to quit is not yet associated with quit attempts in Ethiopia; however, awareness of the health harms of tobacco is a powerful predictor of quit attempt and success in quitting. Improved access to cessation support and expanded awareness of the health harms of tobacco are urgently needed to enhance both quit attempts and success across Ethiopia.

    • Zoonotic and Vectorborne Diseases
      1. Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registryexternal icon
        Roth NM, Woodworth KR, Godfred-Cato S, Delaney AM, Olson SM, Nahabedian JF, Reynolds MR, Jones AM, Neelam V, Valencia-Prado M, Delgado-López C, Lee EH, Ellis EM, Lake-Burger H, Tonzel JL, Higgins CA, Chan RL, Tong VT, Gilboa SM, Cragan JD, Honein MA, Moore CA.
        Birth Defects Res. 2022 Mar 25.
        BACKGROUND: The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC). METHODS: We assessed birth and follow-up data from infants with birth HC measurements <3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly. We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and longitudinal HC measurements between 2 and 12 months of age. Two or more HC measurements were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was >3 cm/month in the first 3 months or HC was consistently >25th percentile during follow-up. RESULTS: Of 6,799 liveborn infants in USZPIR, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements <3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC <3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%. CONCLUSIONS: About one-third of infants in USZPIR with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in longitudinal studies can reduce misclassification of microcephaly.

      2. A country classification system to inform rabies prevention guidelines and regulationsexternal icon
        Henry RE, Blanton JD, Angelo KM, Pieracci EG, Stauffer K, Jentes ES, Allen J, Glynn M, Brown C, Friedman CR, Wallace R.
        J Travel Med. 2022 Mar 26.
        BACKGROUND: Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity, and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. METHODS: CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of Lyssaviruses (specifically canine or wildlife rabies virus variants or other bat Lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity, and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for postexposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate, or high. RESULTS: A total of 240 countries, territories, and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. CONCLUSIONS: We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country, and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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