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Issue 3, January 17, 2023

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CDC Science Clips: Volume 15, Issue 3, January 17, 2023

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. High level of pretreatment and Acquired Human Immunodeficiency Virus drug resistance in El Salvador: A nationally representative survey, 2018-2019
        Girón-Callejas A, García-Morales C, Mendizabal-Burastero R, Quezada A, Ruiz L, Arguera N, Sorto S, Nieto AI, Tapia-Trejo D, López-Sánchez DM, Pérez-García M, Cruz L, Andino R, Sajquim E, Juárez SI, Farach N, Ravasi G, Northbrook S, Reyes-Terán G, Ávila-Ríos S.
        Open Forum Infect Dis. 2022 Nov;9(11):ofac580.
        BACKGROUND: Human immunodeficiency virus drug resistance (HIVDR) can negatively impact the effectiveness of antiretroviral therapy (ART). We aimed to estimate the prevalence of pretreatment HIVDR (PDR) among ART initiators and the prevalence of viral load (VL) suppression and acquired HIVDR among individuals receiving ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in El Salvador. METHODS: Nationally representative cross-sectional PDR, ADR12 and ADR48 surveys were conducted among adults with HIV from October 2018 to August 2019, following World Health Organization-recommended methods. Demographic and clinic data and blood specimens were collected. RESULTS: Two hundred sixty participants were enrolled in the PDR survey, 230 in ADR12 and 425 in ADR48. Twenty-seven percent (95% confidence interval [CI], 17.1%-39.9%) of ART initiators had PDR to efavirenz or nevirapine. The prevalence of VL suppression was 88.8% (95% CI, 83.1%-92.8%) in ADR12 and 80.5% (95% CI, 76.6%-84.0%) in ADR48 surveys. Among people with HIV receiving a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens and with unsuppressed VL, the prevalence of ADR to efavirenz or nevirapine was 72.0% (95% CI, 32.3%-93.3%) and 95.0% (68.5%-99.4%) in the ADR12 and ADR28 surveys, respectively. ADR12 to boosted protease inhibitors (PI/r) or integrase strand transfer inhibitors (INSTIs) was not observed. ADR48 was 1.3% (95% CI, 0.2%-9.6%) and 2.1% (0.3%-13.7%), respectively. CONCLUSIONS: Programmatic improvements in ART delivery are urgently needed in El Salvador to address the high levels of resistance to efavirenz or nevirapine among ART initiators and the low VL suppression prevalence among individuals on treatment.

    • Chronic Diseases and Conditions
      1. DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

      2. Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2060: The SEARCH for Diabetes in Youth Study
        Tönnies T, Brinks R, Isom S, Dabelea D, Divers J, Mayer-Davis EJ, Lawrence JM, Pihoker C, Dolan L, Liese AD, Saydah SH, D'Agostino RB, Hoyer A, Imperatore G.
        Diabetes Care. 2022 Dec 16.
        OBJECTIVE: To project the prevalence and number of youths with diabetes and trends in racial and ethnic disparities in the U.S. through 2060. RESEARCH DESIGN AND METHODS: Based on a mathematical model and data from the SEARCH for Diabetes in Youth study for calendar years 2002-2017, we projected the future prevalence of type 1 and type 2 diabetes among youth aged <20 years while considering different scenarios of future trends in incidence. RESULTS: The number of youths with diabetes will increase from 213,000 (95% CI 209,000; 218,000) (type 1 diabetes 185,000, type 2 diabetes 28,000) in 2017 to 239,000 (95% CI 209,000; 282,000) (type 1 diabetes 191,000, type 2 diabetes 48,000) in 2060 if the incidence remains constant as observed in 2017. Corresponding relative increases were 3% (95% CI -9%; 21%) for type 1 diabetes and 69% (95% CI 43%; 109%) for type 2 diabetes. Assuming that increasing trends in incidence observed between 2002 and 2017 continue, the projected number of youths with diabetes will be 526,000 (95% CI 335,000; 893,000) (type 1 diabetes 306,000, type 2 diabetes 220,000). Corresponding relative increases would be 65% (95% CI 12%; 158%) for type 1 diabetes and 673% (95% CI 362%; 1,341%) for type 2 diabetes. In both scenarios, substantial widening of racial and ethnic disparities in type 2 diabetes prevalence are expected, with the highest prevalence among non-Hispanic Black youth. CONCLUSIONS: The number of youths with diabetes in the U.S. is likely to substantially increase in future decades, which emphasizes the need for prevention to attenuate this trend.

    • Communicable Diseases
      1. Prioritization of evidence-based and evidence-informed interventions for retention in medical care for persons with HIV
        Collins CB, Higa D, Taylor J, Wright C, Murray KH, Pitasi M, Greene Y, Lyles C, Edwards A, Andia J, Stallworth J, Alvarez J.
        AIDS Behav. 2022 Dec 29.
        Up to 50% of those diagnosed with HIV in the U.S. are not retained in medical care. Care retention provides opportunity to monitor benefits of HIV therapy and enable viral suppression. To increase retention, there is a need to prioritize best practices appropriate for translation and dissemination for real-world implementation. Eighteen interventions from CDC's Compendium of Evidence-Based Interventions were scored using the RE-AIM framework to determine those most suitable for dissemination. A CDC Division of HIV Prevention workgroup developed a RE-AIM scale with emphasis on the Implementation and Maintenance dimensions and less emphasis on the Efficacy dimension since all 18 interventions were already identified as evidence-based or evidence-informed. Raters referenced primary efficacy publications and scores were averaged for a ranked RE-AIM score for interventions. Of 18 interventions, four included care linkage and 7 included viral suppression outcomes. Interventions received between 20.6 and 35.3 points (45 maximum). Scores were converted into a percentage of the total possible with ranges between 45.8 and 78.4%. Top four interventions were ARTAS (78.4%); Routine Screening for HIV (RUSH) (73.2%); Optn4Life (67.4%) and Virology Fast Track (65.9%). All four scored high on Implementation and Maintenance dimensions. Select items within the scale were applicable to health equity, covering topics such as reaching under-served focus populations and acceptability to that population. Navigation-enhanced Case Management (NAV) scored highest on the health equity subscale. RE-AIM prioritization scores will inform dissemination and translation efforts, help clinical staff select feasible interventions for implementation, and support sustainability for those interventions.

      2. Measuring oral pre-exposure prophylaxis (PrEP) continuation through electronic health records during program scale-up among the general population in Zambia
        Heilmann E, Okuku J, Itoh M, Hines JZ, Prieto JT, Phiri M, Watala K, Nsofu C, Luhana-Phiri M, Vlahakis N, Kabongo M, Kaliki B, Minchella PA, Musonda B.
        AIDS Behav. 2022 Dec 31.
        HIV pre-exposure prophylaxis (PrEP) is being scaled-up in Zambia, but PrEP continuation data are limited by paper-based registers and aggregate reports. Utilization of Zambia's electronic health record (EHR) system, SmartCare, may address this gap. We analyzed individuals aged ≥ 15 years who initiated PrEP between October 2020 and September 2021 in four provinces in Zambia in SmartCare versus aggregate reports. We measured PrEP continuation using Kaplan-Meier survival analysis and Cox proportional hazards models. SmartCare captured 29% (16,791/58,010) of new PrEP clients; 49% of clients continued at one month, and 89% discontinued PrEP by February 2022. Women were less likely than men to discontinue PrEP (adjusted hazard ratio [aHR]: 0.89, 95% CI 0.86-0.92, z = - 6.99, p < 0.001), and PrEP clients aged ≥ 50 years were less likely to discontinue PrEP compared to clients 15-19 years (aHR: 0.53, 95% CI 0.48-0.58, z = - 13.04, p < 0.001). Zambia's EHR is a valuable resource for measuring individual-level PrEP continuation over time and can be used to inform HIV prevention programs.

      3. Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV-India
        Agarwal R, Agarwal U, Das C, Reddy RA, Pant R, Ho C, Kumar BR, Dabla V, Moonan PK, Nyendak M, Anand S, Puri AK, Mattoo SK, Sachdeva KS, Yeldandi VV, Sarin R.
        BMC Infect Dis. 2022 Dec 29;22(1):967.
        BACKGROUND: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc). METHODS: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc. RESULTS: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+ 8.6%; p = 0.025), and technical knowledge (+ 18.3%; p = 0.04) from baseline. Participating ARTc increased TB screening (+ 4.2%, p < 0.0001), TB diagnosis (+ 2.7%, p < 0.0001), ART initiation (+ 4.3%, p < 0.0001) and TB preventive treatment completion (+ 5.2%, p < 0.0001). CONCLUSION: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice.


      5. COVID-19 on the Nile: a cross-sectional investigation of COVID-19 among Nile River cruise travellers returning to the United States, February-march 2020
        Guagliardo SA, Quilter LA, Uehara A, White SB, Talarico S, Tong S, Paden CR, Zhang J, Li Y, Pray I, Novak RT, Fukunaga R, Rodriguez A, Medley AM, Wagner R, Weinberg M, Brown CM, Friedman CR.
        J Travel Med. 2022 Dec 29.
        BACKGROUND: Early in the pandemic, cruise travel exacerbated the global spread of SARS-CoV-2. We report epidemiologic and molecular findings from an investigation of a cluster of travelers with confirmed COVID-19 returning to the U.S. from Nile River cruises in Egypt. METHODS: State health departments reported data on real-time reverse transcription-polymerase chain reaction-confirmed COVID-19 cases with a history of Nile River cruise travel during February-March 2020 to the Centers for Disease Control and Prevention (CDC). Demographic and epidemiologic data were collected through routine surveillance channels. Sequences were obtained from either state health departments or from the Global Initiative on Sharing Avian Flu Data (GISAID). We conducted descriptive analyses of epidemiologic data and explored phylogenetic relationships between sequences. RESULTS: We identified 149 Nile River cruise travelers with confirmed COVID-19 who returned to 67 different U.S. counties in 27 states: among those with complete data, 4.7% (6/128) died and 28.1% (38/135) were hospitalized. These individuals traveled on 20 different Nile River cruise voyages (12 unique vessels). Fifteen community transmission events were identified in four states, with 73.3% (11/15) of these occurring in Wisconsin (as the result of a more detailed contact investigation in that state). Phylogenetic analyses supported the hypothesis that travelers were most likely infected in Egypt, with most sequences in Nextstrain clade 20A 93% (87/94). We observed genetic clustering by Nile River cruise voyage and vessel. CONCLUSIONS: Nile River cruise travelers with COVID-19 introduced SARS-CoV-2 over a very large geographic range, facilitating transmission across the United States early in the pandemic. Travelers who participate in cruises, even on small river vessels as investigated in this study, are at increased risk of SARS-CoV-2 exposure. Therefore, history of river cruise travel should be considered in contact tracing and outbreak investigations.

      6. Epidemiologic and clinical features of mpox in transgender and gender-diverse adults - United States, May-November 2022
        Blackburn D, Roth NM, Gold JA, Pao LZ, Olansky E, Torrone EA, McClung RP, Ellington SR, Delaney KP, Carnes N, Dawson P.
        MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1605-1609.
        As of November 9, 2022, a total of 28,730 cases of monkeypox (mpox) had been reported in the United States,* primarily among adult cisgender men reporting recent male-to-male sexual contact (1). Transgender and gender-diverse persons, who constitute an estimated 0.5% of the U.S. adult population,(†) face unique health disparities and barriers to care (2-4). However, data on the epidemiologic and clinical features of Monkeypox virus infections in this population are limited (5). CDC analyzed U.S. case surveillance data on mpox cases in transgender and gender-diverse adults reported during May 17-November 4, 2022. During this period, 466 mpox cases in transgender and gender-diverse adults were reported, accounting for 1.7% of reported cases among adults. Most were in transgender women (43.1%) or gender-diverse persons (42.1%); 14.8% were in transgender men. Among 374 (80.3%) mpox cases in transgender and gender-diverse adults with information available on sexual or close intimate contact, 276 (73.8%) reported sexual or close intimate contact with a cisgender male partner during the 3 weeks preceding symptom onset. During the ongoing outbreak, transgender and gender-diverse persons have been disproportionately affected by mpox. Members of this population frequently reported recent sexual or close intimate contact with cisgender men, who might be in sexual networks experiencing the highest incidence of mpox. These findings highlight the importance of tailoring public health prevention and outreach efforts to transgender and gender-diverse communities and could guide strategies to reduce mpox transmission.

      7. Notes from the field: Clinical and epidemiologic characteristics of mpox cases from the initial phase of the outbreak - New York city, May 19-July 15, 2022
        Kyaw NT, Kipperman N, Alroy KA, Baumgartner J, Crawley A, Peterson E, Ross A, Fowler RC, Ruiz VE, Leelawong M, Hughes S, Juste-Tranquille M, Lovingood K, Joe CD, Chase M, Shinall A, Ackelsberg J, Bergeron-Parent C, Badenhop B, Slavinski S, Reddy V, Lee EH.
        MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1631-1633.

      8. A focused multi-state model to estimate the pediatric and adolescent HIV epidemic in Thailand, 2005-2025
        Desmonde S, Lolekha R, Costantini S, Siraprapasiri T, Frank S, Bakkali T, Benjarattanaporn P, Hou T, Jantaramanee S, Kuttiparambil B, Sethaputra C, Ross J, Ciaranello A.
        PLoS One. 2022 ;17(11):e0276330.
        BACKGROUND: We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0-25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities. METHODS: We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population ("other"). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005-2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018-2025. RESULTS: The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were &lt;5 years, 21% were 5-14 years, and 71% were 15-25 years of age. By 2020, 94% were projected to be &gt;15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0-25 who were diagnosed and on ART increased from 37 to 60% over the 2005-2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and "other" youth. CONCLUSIONS: More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.

      9. Estimated incidence and prevalence of gonorrhea in the United States, 2006-2019
        Pollock ED, Clay PA, Kreisel KM, Spicknall IH.
        Sex Transm Dis. 2023 Jan 5.
        BACKGROUND: We extend recent work estimating incidence and prevalence of gonococcal infections among men and women aged 15-39 years in the US in 2018 by applying the same modeling framework to estimate gonococcal incidence and prevalence during 2006-2019. METHODS: The model is informed by cases from the Nationally Notifiable Disease Surveillance System, data from the National Survey of Family Growth, and data on other factors known to impact gonococcal incidence and prevalence. We use Monte Carlo simulation to account for uncertainty in input parameters. Results are reported as median annual per-capita incidence and prevalence; uncertainty intervals are characterized by the 25th and 75th simulated percentiles. RESULTS: 1,603,473 (1,467,801-1,767,779) incident cases of gonorrhea were estimated in 2019. Per-capita incidence increased 32%, from 1101 (1002-1221) to 1456 (1333-1605) infections per 100,000 persons. This trend in per-capita incidence had three phrases: an initial decline during 2006-2009, a plateau through 2013, and a rapid increase of 66% through 2019. Men aged 25-39 experienced the greatest increase in incidence (125%, 541 (467-651) to 1212 infections (1046-1458) per 100,000 men). Women aged 25-39 had the lowest incidence in 2019, with 1040 infections (882-1241) per 100,000 women. Prevalence increased more slowly among those aged 25-39 vs. 15-24. The incidence ratio comparing men to women aged 25-39 increased from 0.76 to 1.18. CONCLUSIONS: The burden of gonorrhea has increased among men and women aged 15-39 years since 2013. An increasing proportion of incident infections are among men. Additional biomedical and behavioral interventions are needed to control gonococcal transmission.

    • Community Health Services
      1. Findings from a scoping review: Presumptive treatment for chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in the USA, 2006-2021
        Allen KS, Hinrichs R, Heumann CL, Titus MK, Duszynski TJ, Valvi NR, Wiensch A, Tao G, Dixon BE.
        Sex Transm Dis. 2022 Dec 26.
        Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the two most common reported sexually transmitted infections in the USA. Current recommendations are to presumptively treat CT and/or GC in persons with symptoms or known contact. This review characterizes the literature around studies with presumptive treatment, including identifying rates of presumptive treatment and over- and under-treatment rates. Of the 18 articles that met our inclusion criteria, six pertained to outpatient settings. In the outpatient setting, presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 12% - 100%, and the percent positive of those presumptively treated ranged from 25% - 46%. Three studies also reported data on positive results in patients not presumptively treated, which ranged from 2% - 9%. Two studies reported median follow-up time for untreated, which was roughly nine days. The remaining 12 articles pertained to the emergency setting where presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 16% - 91%, the percent positive following presumptive treatment ranged from 14% - 59%. Positive results without presumptive treatment ranged from 4% - 52%. Two studies reported the percent positive without any treatment (6% and 32% respectively) and one reported follow-up time for untreated infections (median: 4.8 days). Rates of presumptive treatment, as well as rates of over- or under- treatment vary widely across studies and within care settings. Given large variability in presumptive treatment, the focus on urban settings, and minimal focus on social determinants of health, additional studies are needed to guide treatment practices for CT and GC in outpatient and emergency settings.

      2. The complexity of survey data and the availability of data from auxiliary sources motivate researchers to explore estimation methods that extend beyond traditional survey-based estimation. The U.S. Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System (BRFSS) collects a wide range of health information, including whether respondents have a personal doctor. While the BRFSS focuses on state-level estimation, there is demand for county-level estimation of health indicators using BRFSS data. A hierarchical Bayes small area estimation model is developed to combine county-level BRFSS survey data with county-level data from auxiliary sources, while accounting for various sources of error and nested geographical levels. To mitigate extreme proportions and unstable survey variances, a transformation is applied to the survey data. Model-based county-level predictions are constructed for prevalence of having a personal doctor for all the counties in the U.S., including those where BRFSS survey data were not available. An evaluation study using only the counties with large BRFSS sample sizes to fit the model versus using all the counties with BRFSS data to fit the model is also presented. © 2022, Springer-Verlag GmbH Germany, part of Springer Nature.

    • Disaster Preparedness and Emergency Services
      1. The measurement of uranium (U) isotope ratios in urine provides valuable information about the source of U exposure in humans and can be vitally important in a radiological emergency. This method provides rapid and accurate results for 235U/238U at 235U concentrations as low as 0.42 ng/L, which is equivalent to ~ 200 ng/L of total U for a depleted U (DU) at a 235U/238U ratio of ~ 0.002. The results are within 6% of Certified Reference Materials target values and agree with Department of Defense Armed Forces Institute of Pathology inter-laboratory comparison target values with a bias range of -6.9–7.6%. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

    • Disease Reservoirs and Vectors
      1. Spatial repellents: The current roadmap to global recommendation of spatial repellents for public health use
        Achee NL, Perkins TA, Moore SM, Liu F, Sagara I, Van Hulle S, Ochomo EO, Gimnig JE, Tissera HA, Harvey SA, Monroe A, Morrison AC, Scott TW, Reiner RC, Grieco JP.
        Curr Res Parasitol Vector Borne Dis. 2023 ;3:100107.
        Spatial repellent (SR) products are envisioned to complement existing vector control methods through the continual release of volatile active ingredients (AI) providing: (i) protection against day-time and early-evening biting; (ii) protection in enclosed/semi-enclosed and peri-domestic spaces; (iii) various formulations to fit context-specific applications; and (iv) increased coverage over traditional control methods. SR product AIs also have demonstrated effect against insecticide-resistant vectors linked to malaria and Aedes-borne virus (ABV) transmission. Over the past two decades, key stakeholders, including World Health Organization (WHO) representatives, have met to discuss the role of SRs in reducing arthropod-borne diseases based on existing evidence. A key focus has been to establish a critical development path for SRs, including scientific, regulatory and social parameters that would constitute an outline for a SR target product profile, i.e. optimum product characteristics. The principal gap is the lack of epidemiological data demonstrating SR public health impact across a range of different ecological and epidemiological settings, to inform a WHO policy recommendation. Here we describe in brief trials that are designed to fulfill evidence needs for WHO assessment and initial projections of SR cost-effectiveness against malaria and dengue.

    • Environmental Health
      1. Observations from the USA National Phenology Network can be leveraged to model airborne pollen
        Katz DS, Vogt E, Manangan A, Brown CL, Dalan D, Zhu K, Song Y, Crimmins TM.
        Aerobiologia (Bologna). 2022 .
        The USA National Phenology Network (USA-NPN) hosts the largest volunteer-contributed collection of plant phenology observations in the USA. The potential contributions of these spatially and temporally explicit observations of flowers and pollen cones to the field of aerobiology remain largely unexplored. Here, we introduce this freely available dataset and demonstrate its prospective applications for modeling airborne pollen in a case study. Specifically, we compare the timing of 4265 observations of flowering for oak (Quercus) trees in the eastern USA to winter–spring temperatures. We then use this relationship to predict the day of peak flowering at 15 pollen monitoring stations in 15 years and compare the predicted day of peak flowering to the peak day of measured pollen (n = 111 station-years). There was a strong association between winter–spring temperature and the presence of open flowers (r2 = 0.66, p &lt; 0.0001) and the predicted peak flowering was strongly correlated with peak airborne pollen concentrations (r2 = 0.81, p &lt; 0.0001). These results demonstrate the potential for the USA-NPN’s phenological observations to underpin source-based models of airborne pollen. We also highlight opportunities for leveraging and enhancing this near real-time dataset for aerobiological applications. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

      2. Associations of early life phthalate exposures with adolescent lipid levels and insulin resistance: The HOME Study
        Etzel TM, Kuiper JR, Wang X, Mueller NT, Calafat AM, Cecil KM, Chen A, Lanphear BP, Yolton K, Kalkwarf HJ, Braun JM, Buckley JP.
        Int J Hyg Environ Health. 2022 Dec 15;248:114102.
        BACKGROUND: Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. METHODS: Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. RESULTS: Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3 mg/dL (95% CI: 27.5, -3.13 mg/dL) and -11.8 mg/dL (-22.0, -1.51 mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0 mg/dL (95% CI: 7.11, 31.1 mg/dL) higher LDL levels in males and -30.4 mg/dL (95% CI: 50.9, -9.8 mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. CONCLUSIONS: Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

    • Genetics and Genomics
      1. Draft genome sequences of 20 clostridium botulinum type a isolates from foodborne botulism outbreaks
        Halpin JL, Gómez GA, Dykes JK, Lúquez C.
        Microbiol Resour Announc. 2023 Jan 4:e0086822.
        Here, we present 20 draft genome sequences of Clostridium botulinum type A isolates originating from foodborne outbreaks in the United States and Ethiopia. Publicly available genomes enhance our understanding of C. botulinum genomics and are an asset in bioterrorism preparedness.

    • Health Behavior and Risk
      1. Knowledge, attitude and practice of commercial sex workers regarding cervical cancer and its screening, Daulatdia Brothel, Rajbari District, Bangladesh, 2020-2021
        Qayum MO, Hassan MR, Henderson A, Billah MM, Nurunnahar M, Afser S, Shirin T.
        Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4085-4092.
        BACKGROUND: Cervical cancer is the second most common cancer in females in Bangladesh. This is caused by Human Papilloma Virus (HPV). Multiple sex partners, HIV infection, smoking, using birth control pills, and having more than three children are risk factors of cervical cancer. Hence, female sex workers have a high prevalence of infection with high risk HPV genotypes which eventually may causes cervical cancer. Unfortunately, the status of knowledge, attitude and practice among female sex workers regarding cervical cancer is mostly unknown. The aim of the study was to assess the knowledge, attitude and practice of women living in Daulatdia brothel regarding cervical cancer and its screening.  Methods: A cross-sectional knowledge-practice survey was conducted among 400 female sex workers in Daulatdia Brothel, Rajbari District, Bangladesh. The women's total score on knowledge, and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. RESULTS: Most sex workers (61%) were between 29 to 35 years, married at 13 to 15 years of age, and divorced (91%). Middle aged sex workers were more likely have a VIA test  than women in the 29 to 35 years group (18%, OR:5.2; CI: 2.0, 13.5). Less than half of the studied women (40%) had sufficient knowledge regarding cervical cancer and 12% knew that infection by HPV is a risk factor. Respondents with primary and secondary education were more likely to have sufficient knowledge than the illiterate (42%, OR: 1.32; CI: 0.82, 2.12). Practices to prevent cervical cancer were very poor. Nearly all women (99%) would recommend other women to have a VIA test. There were only 7% who had a VIA test and 2% were vaccinated against HPV. Unmarried sex workers were more likely to take action to prevent cervical cancer. Sex workers educated up to the primary level were more likely to have a VIA or other tests than the illiterate sex workers (10%, OR: 1.3; CI: 0.6, 3.2). CONCLUSION: Sex workers in Daulatdia brothel were less knowledgeable about cervical cancer and less likely to have a VIA test and poor practices towards preventing cervical cancer. The sex workers underutilized the VIA test and HPV vaccine. BACKGROUND: Cervical cancer is the second most common cancer in females in Bangladesh. This is caused by Human Papilloma Virus (HPV). Multiple sex partners, HIV infection, smoking, using birth control pills, and having more than three children are risk factors of cervical cancer. Hence, female sex workers have a high prevalence of infection with high risk HPV genotypes which eventually may causes cervical cancer. Unfortunately, the status of knowledge, attitude and practice among female sex workers regarding cervical cancer is mostly unknown. The aim of the study was to assess the knowledge, attitude and practice of women living in Daulatdia brothel regarding cervical cancer and its screening.  Methods: A cross-sectional knowledge-practice survey was conducted among 400 female sex workers in Daulatdia Brothel, Rajbari District, Bangladesh. The women's total score on knowledge, and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. RESULTS: Most sex workers (61%) were between 29 to 35 years, married at 13 to 15 years of age, and divorced (91%). Middle aged sex workers were more likely have a VIA test  than women in the 29 to 35 years group (18%, OR:5.2; CI: 2.0, 13.5). Less than half of the studied women (40%) had sufficient knowledge regarding cervical cancer and 12% knew that infection by HPV is a risk factor. Respondents with primary and secondary education were more likely to have sufficient knowledge than the illiterate (42%, OR: 1.32; CI: 0.82, 2.12). Practices to prevent cervical cancer were very poor. Nearly all women (99%) would recommend other women to have a VIA test. There were only 7% who had a VIA test and 2% were vaccinated against HPV. Unmarried sex workers were more likely to take action to prevent cervical cancer. Sex workers educated up to the primary level were more likely to have a VIA or other tests than the illiterate sex workers (10%, OR: 1.3; CI: 0.6, 3.2). CONCLUSION: Sex workers in Daulatdia brothel were less knowledgeable about cervical cancer and less likely to have a VIA test and poor practices towards preventing cervical cancer. The sex workers underutilized the VIA test and HPV vaccine. <br /><br />.

    • Health Communication and Education
      1. Cluster analysis of adults unvaccinated for COVID-19 based on behavioral and social factors, National Immunization Survey-Adult COVID Module, United States
        Meng L, Masters NB, Lu PJ, Singleton JA, Kriss JL, Zhou T, Weiss D, Black CL.
        Prev Med. 2022 Dec 31:107415.
        By the end of 2021, approximately 15% of U.S. adults remained unvaccinated against COVID-19, and vaccination initiation rates had stagnated. We used unsupervised machine learning (K-means clustering) to identify clusters of unvaccinated respondents based on Behavioral and Social Drivers (BeSD) of COVID-19 vaccination and compared these clusters to vaccinated participants to better understand social/behavioral factors of non-vaccination. The National Immunization Survey Adult COVID Module collects data on U.S. adults from September 26-December 31,2021 (n = 187,756). Among all participants, 51.6% were male, with a mean age of 61 years, and the majority were non-Hispanic White (62.2%), followed by Hispanic (17.2%), Black (11.9%), and others (8.7%). K-means clustering procedure was used to classify unvaccinated participants into three clusters based on 9 survey BeSD items, including items assessing COVID-19 risk perception, social norms, vaccine confidence, and practical issues. Among unvaccinated adults (N = 23,397), 3 clusters were identified: the "Reachable" (23%), "Less reachable" (27%), and the "Least reachable" (50%). The least reachable cluster reported the lowest concern about COVID-19, mask-wearing behavior, perceived vaccine confidence, and were more likely to be male, non-Hispanic White, with no health conditions, from rural counties, have previously had COVID-19, and have not received a COVID-19 vaccine recommendation from a healthcare provider. This study identified, described, and compared the characteristics of the three unvaccinated subgroups. Public health practitioners, healthcare providers and community leaders can use these characteristics to better tailor messaging for each sub-population. Our findings may also help inform decisionmakers exploring possible policy interventions.

    • Health Equity and Health Disparities
      1. Asian Americans (AAs) are the fastest-growing racial/ethnic minority group in the United States. While otherwise highly heterogeneous, AAs overall value filial piety and eldercare. This study compared the health and caregiving experiences of AA caregivers of older adults to AA non-caregivers and caregivers of older adults across racial/ethnic groups. We used 2015-2020 Behavioral Risk Factor Surveillance System data for 315 AA caregivers and 3822 AA non-caregivers, plus 395 American Indian/Alaska Native, 1883 Black, 1292 Hispanic, and 20,321 non-Hispanic White caregivers. Among AAs, 4.3% were caregivers, a lower proportion than in other racial/ethnic groups. Most AA caregivers were female (59%), married (71%), in excellent/very good/good health (76%), and with at least one chronic health condition (66%). Other than relationship to care recipients, caregivers' experiences were similar across racial/ethnic groups: most cared for <20 hours/week and provided household and personal care. Efforts to support AA caregivers should be attentive to cultural practices.

      2. OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

      3. National trends in gonorrhea rates may obscure informative local variations in morbidity. We used group-based trajectory models to identify groups of counties with similar gonorrhea rate trajectories among non-Hispanic White (NHW) and non-Hispanic Black (NHB) females using county-level data on gonorrhea cases in US females from 2003 to 2018. We assessed models with 1-15 groups and selected final models based on fit statistics and identification of divergent trajectory groups with distinct intercepts and/or slopes. We mapped counties by assigned trajectory group and examined the association of county characteristics with group membership. We identified 7 distinct gonorrhea trajectory groups for NHW females and 9 distinct trajectory groups for NHB females. All identified groups for NHW female morbidity experienced increasing gonorrhea rates with a limited range (11.6-183.3/100,000 NHW females in 2018); trajectories of NHB female morbidity varied widely in rates (146.6-966.0/1000 NHB females in 2018) and included 3 groups of counties that experienced a net decline in gonorrhea rates. Counties with higher NHW female morbidity had lower adult sex ratios, lower health insurance coverage, and lower marital rates among NHW adults. Counties with higher NHB female morbidity were more urban, experienced higher rates of poverty, and had lower rates of marriage among NHB adults. Morbidity patterns did not always follow geographic proximity, which could be explained by variation in social determinants of health. Our results demonstrated a highly heterogenous gonorrhea epidemic among NHW and NHB US females, which should prompt further analysis into the differential drivers of gonorrhea morbidity.

      4. Healthy community design, anti-displacement, and equity strategies in the USA: A scoping review
        Serrano N, Realmuto L, Graff KA, Hirsch JA, Andress L, Sami M, Rose K, Smith A, Irani K, McMahon J, Devlin HM.
        J Urban Health. 2022 Dec 29:1-30.
        Recent investments in built environment infrastructure to create healthy communities have highlighted the need for equity and environmental justice. Although the benefits of healthy community design (e.g., connecting transportation systems and land use changes) are well established, some reports suggest that these changes may increase property values. These increases can raise the risk of displacement for people with low incomes and/or who are from racial and ethnic minority groups, who would then miss out on benefits from changes in community design. This review scanned the literature for displacement mitigation and prevention measures, with the goal of providing a compilation of available strategies for a wide range of audiences including public health practitioners. A CDC librarian searched the Medline, EbscoHost, Scopus, and ProQuest Central databases, and we identified grey literature using Google and Google Scholar searches. The indexed literature search identified 6 articles, and the grey literature scan added 18 articles. From these 24 total articles, we identified 141 mitigation and prevention strategies for displacement and thematically characterized each by domain using an adapted existing typology. This work provides a well-categorized inventory for practitioners and sets the stage for future evaluation research on the implementation of strategies and practices to reduce displacement.

    • Immune System Disorders
      1. Refractory, fatal autoimmune hemolytic anemia due to ineffective thymic-derived T-cell reconstitution following allogeneic hematopoietic cell transplantation for hypomorphic RAG1 deficiency
        Yonkof JR, Basu A, Redmond MT, Dobbs AK, Perelygina L, Notarangelo LD, Abraham RS, Rangarajan HG.
        Pediatr Blood Cancer. 2022 Dec 30:e30183.

    • Immunity and Immunization
      1. SARS-CoV-2 infection history and antibody response to three COVID-19 mRNA vaccine doses
        Herring MK, Romine JK, Wesley MG, Ellingson KD, Yoon SK, Caban-Martinez AJ, Meece J, Gaglani M, Grant L, Olsho LE, Tyner HL, Naleway AL, Khan SM, Phillips AL, Schaefer Solle N, Rose S, Mak J, Fuller SB, Hunt A, Kuntz JL, Beitel S, Yoo YM, Zheng PQ, Arani G, Mayo Lamberte J, Edwards T, Thompson MG, Sprissler R, Thornburg NJ, Lowe AA, Pilishvili T, Uhrlaub JL, Lutrick K, Burgess JL, Fowlkes AL.
        Clin Infect Dis. 2022 Dec 29.
        BACKGROUND: Three doses of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines produce robust antibody responses, but data are limited among individuals previously infected with SARS-CoV-2. From a cohort of health care personnel (75.5%), first responders (4.6%), and other frontline workers (19.8%) in 6 US states, we longitudinally assessed antibody waning after dose-2, and response to dose-3, according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every three months, after SARS-CoV-2 infection, and after each COVID-19 vaccine dose. Sera were tested for antibodies and reported quantitatively as area under the serial dilution curve (AUC). Changes in the AUC values over time were compared as fold-changes using a linear mixed model. RESULTS: Analysis included 388 participants who received dose-3 by November 2021. Three comparison groups: (1) vaccine only with no known prior SARS-CoV-2 infection (n = 224); (2) infection prior to dose-1 (n = 123); and (3) infection after dose 2 and before dose-3 (n = 41). The interval from dose 2 and dose 3 was approximately 8-months. After dose-3, antibody levels rose 2.5-fold (95%CI = 2.2-3.0) in group 2, and 2.9-fold (95%CI = 2.6-3.3) in group 1. Those infected within 90 days before dose-3 (and median 233 days (IQR = 213-246) after dose-2) did not increase significantly after dose-3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection < 3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

      2. Demographic and clinical characteristics of mpox in persons who had previously received 1 dose of JYNNEOS vaccine and in unvaccinated persons - 29 U.S. Jurisdictions, May 22-September 3, 2022
        Farrar JL, Lewis NM, Houck K, Canning M, Fothergill A, Payne AB, Cohen AL, Vance J, Brassil B, Youngkin E, Glenn B, Mangla A, Kupferman N, Saunders K, Meza C, Nims D, Soliva S, Blouse B, Henderson T, Banerjee E, White B, Birn R, Stadelman AM, Abrego M, McLafferty M, Eberhart MG, Pietrowski M, De León SM, Creegan E, Diedhiou A, Wiedeman C, Murray-Thompson J, McCarty E, Marcinkevage J, Kocharian A, Torrone EA, Ray LC, Payne DC.
        MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1610-1615.
        As of November 14, 2022, monkeypox (mpox) cases had been reported from more than 110 countries, including 29,133 cases in the United States.* Among U.S. cases to date, 95% have occurred among males (1). After the first confirmed U.S. mpox case on May 17, 2022, limited supplies of JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) were made available to jurisdictions for persons exposed to mpox. JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.(†) On August 9, 2022, FDA issued an emergency use authorization to allow administration of JYNNEOS vaccine by intradermal injection (0.1 mL per dose) (2). A previous report on U.S. mpox cases during July 31-September 3, 2022, suggested that 1 dose of vaccine offers some protection against mpox (3). This report describes demographic and clinical characteristics of cases occurring ≥14 days after receipt of 1 dose of JYNNEOS vaccine and compares them with characteristics of cases among unvaccinated persons with mpox and with the vaccine-eligible vaccinated population in participating jurisdictions. During May 22-September 3, 2022, among 14,504 mpox cases reported from 29 participating U.S. jurisdictions,(§) 6,605 (45.5%) had available vaccination information and were included in the analysis. Among included cases, 276 (4.2%) were among persons who had received 1 dose of vaccine ≥14 days before illness onset. Mpox cases that occurred in these vaccinated persons were associated with lower percentage of hospitalization (2.1% versus 7.5%), fever, headache, malaise, myalgia, and chills, compared with cases in unvaccinated persons. Although 1 dose of JYNNEOS vaccine offers some protection from disease, mpox infection can occur after receipt of 1 dose, and the duration of protection conferred by 1 dose is unknown. Providers and public health officials should therefore encourage persons at risk for acquiring mpox to complete the 2-dose vaccination series and provide guidance and education regarding nonvaccine-related prevention strategies (4).

      3. Early estimates of bivalent mRNA vaccine effectiveness in preventing COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years - Ivy Network, 18 states, September 8-November 30, 2022
        Surie D, DeCuir J, Zhu Y, Gaglani M, Ginde AA, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, McNeal T, Ghamande S, Gibbs KW, Files DC, Hager DN, Ali H, Taghizadeh L, Gong MN, Mohamed A, Johnson NJ, Steingrub JS, Peltan ID, Brown SM, Martin ET, Khan A, Bender WS, Duggal A, Wilson JG, Qadir N, Chang SY, Mallow C, Kwon JH, Exline MC, Lauring AS, Shapiro NI, Columbus C, Halasa N, Chappell JD, Grijalva CG, Rice TW, Stubblefield WB, Baughman A, Womack KN, Rhoads JP, Hart KW, Swan SA, Lewis NM, McMorrow ML, Self WH.
        MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1625-1630.
        Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network(§) assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5).

      4. Early estimates of bivalent mRNA vaccine effectiveness in preventing COVID-19-associated emergency department or urgent care encounters and hospitalizations among immunocompetent adults - VISION Network, nine states, September-November 2022
        Tenforde MW, Weber ZA, Natarajan K, Klein NP, Kharbanda AB, Stenehjem E, Embi PJ, Reese SE, Naleway AL, Grannis SJ, DeSilva MB, Ong TC, Gaglani M, Han J, Dickerson M, Fireman B, Dascomb K, Irving SA, Vazquez-Benitez G, Rao S, Konatham D, Patel P, Schrader KE, Lewis N, Grisel N, McEvoy C, Murthy K, Griggs EP, Rowley EA, Zerbo O, Arndorfer J, Dunne MM, Goddard K, Ray C, Zhuang Y, Timbol J, Najdowski M, Yang DH, Hansen J, Ball SW, Link-Gelles R.
        MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1616-1624.
        During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.(†) VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

      5. A systematic review of COVID-19 vaccine antibody responses in people with HIV
        Chun HM, Milligan K, Agyemang E, Ford N, Rangaraj A, Desai S, Wilder-Smith A, Vitoria M, Zulu I.
        Open Forum Infect Dis. 2022 Nov;9(11):ofac579.
        HIV infection is a significant independent risk factor for severe coronavirus disease 2019 (COVID-19) disease and death. We summarize COVID-19 vaccine responses in people with HIV (PWH). A systematic literature review of studies from January 1, 2020, to March 31, 2022, of COVID-19 vaccine immunogenicity in PWH from multiple databases was performed. Twenty-eight studies from 12 countries were reviewed. While 22 (73%) studies reported high COVID-19 vaccine seroconversion rates in PWH, PWH with lower baseline CD4 counts, CD4/CD8 ratios, or higher baseline viral loads had lower seroconversion rates and immunologic titers. Data on vaccine-induced seroconversion in PWH are reassuring, but more research is needed to evaluate the durability of COVID-19 vaccine responses in PWH.

      6. Effectiveness of influenza vaccination of pregnant women for prevention of maternal and early infant influenza-associated hospitalizations in South Africa: A prospective test-negative study
        Nunes MC, Walaza S, Meiring S, Zar HJ, Reubenson G, McMorrow M, Tempia S, Rossi L, Itzikowitz R, Bishop K, Mathunjwa A, Wise A, Treurnicht FK, Hellferscee O, Laubscher M, Serafin N, Cutland CL, Madhi SA, Cohen C.
        Open Forum Infect Dis. 2022 Nov;9(11):ofac552.
        BACKGROUND: Influenza vaccination during pregnancy reduces influenza-associated illness in the women and their infants, but effectiveness estimates against influenza-associated hospitalization are limited and lacking from settings with high human immunodeficiency virus (HIV) infection prevalence. We assessed the effect of maternal vaccination in HIV-uninfected women and women with HIV in preventing influenza-associated hospitalizations in infants and the women. METHODS: During 2015-2018, influenza vaccination campaigns targeting pregnant women were augmented at selected antenatal clinics; these were coupled with prospective hospital-based surveillance for acute respiratory or febrile illness in infants aged <6 months and cardiorespiratory illness among pregnant or postpartum women. Vaccine effectiveness (VE) was assessed using a test-negative case-control study. RESULTS: Overall, 71 influenza-positive and 371 influenza-negative infants were included in the analysis; mothers of 26.8% of influenza-positive infants were vaccinated during pregnancy compared with 35.6% of influenza-negative infants, corresponding to an adjusted VE (aVE) of 29.0% (95% confidence interval [CI], -33.6% to 62.3%). When limited to vaccine-matched strains, aVE was 65.2% (95% CI, 11.7%-86.3%). For maternal hospitalizations, 56 influenza-positive and 345 influenza-negative women were included in the analysis, with 28.6% of influenza-positive women being vaccinated compared with 38.3% of influenza-negatives, for an aVE of 46.9% (95% CI, -2.8% to 72.5%). Analysis restricted to HIV-uninfected women resulted in 82.8% (95% CI, 40.7%-95.0%) aVE. No significant aVE (-32.5% [95% CI, -208.7% to 43.1%]) was detected among women with HIV. CONCLUSIONS: Influenza vaccination during pregnancy prevented influenza-associated hospitalizations among young infants when infected with vaccine strains and among HIV-uninfected women.

      7. Mild and asymptomatic influenza B virus infection among unvaccinated pregnant persons: Implication for effectiveness of non-pharmaceutical intervention and vaccination to prevent influenza
        Chen L, Levine MZ, Zhou S, Bai T, Pang Y, Bao L, Tan Y, Cui P, Zhang R, Millman AJ, Greene CM, Zhang Z, Wang Y, Zhang J.
        Vaccine. 2023 Jan 16;41(3):694-701.
        BACKGROUND: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication. METHODS: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance. RESULTS: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness. CONCLUSIONS: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission.

    • Informatics
      1. Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications
        Martin H, Falconer J, Addo-Yobo E, Aneja S, Arroyo LM, Asghar R, Awasthi S, Banajeh S, Bari A, Basnet S, Bavdekar A, Bhandari N, Bhatnagar S, Bhutta ZA, Brooks A, Chadha M, Chisaka N, Chou M, Clara AW, Colbourn T, Cutland C, D'Acremont V, Echavarria M, Gentile A, Gessner B, Gregory CJ, Hazir T, Hibberd PL, Hirve S, Hooli S, Iqbal I, Jeena P, Kartasasmita CB, King C, Libster R, Lodha R, Lozano JM, Lucero M, Lufesi N, MacLeod WB, Madhi SA, Mathew JL, Maulen-Radovan I, McCollum ED, Mino G, Mwansambo C, Neuman MI, Nguyen NT, Nunes MC, Nymadawa P, O'Grady KF, Pape JW, Paranhos-Baccala G, Patel A, Picot VS, Rakoto-Andrianarivelo M, Rasmussen Z, Rouzier V, Russomando G, Ruvinsky RO, Sadruddin S, Saha SK, Santosham M, Singhi S, Soofi S, Strand TA, Sylla M, Thamthitiwat S, Thea DM, Turner C, Vanhems P, Wadhwa N, Wang J, Zaman SM, Campbell H, Nair H, Qazi SA, Nisar YB.
        J Glob Health. 2022 Dec 29;12:04075.
        BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

      2. Natural language processing for improved characterization of COVID-19 symptoms: Observational study of 350,000 patients in a large integrated health care system
        Malden DE, Tartof SY, Ackerson BK, Hong V, Skarbinski J, Yau V, Qian L, Fischer H, Shaw SF, Caparosa S, Xie F.
        JMIR Public Health Surveill. 2022 Dec 30;8(12):e41529.
        BACKGROUND: Natural language processing (NLP) of unstructured text from electronic medical records (EMR) can improve the characterization of COVID-19 signs and symptoms, but large-scale studies demonstrating the real-world application and validation of NLP for this purpose are limited. OBJECTIVE: The aim of this paper is to assess the contribution of NLP when identifying COVID-19 signs and symptoms from EMR. METHODS: This study was conducted in Kaiser Permanente Southern California, a large integrated health care system using data from all patients with positive SARS-CoV-2 laboratory tests from March 2020 to May 2021. An NLP algorithm was developed to extract free text from EMR on 12 established signs and symptoms of COVID-19, including fever, cough, headache, fatigue, dyspnea, chills, sore throat, myalgia, anosmia, diarrhea, vomiting or nausea, and abdominal pain. The proportion of patients reporting each symptom and the corresponding onset dates were described before and after supplementing structured EMR data with NLP-extracted signs and symptoms. A random sample of 100 chart-reviewed and adjudicated SARS-CoV-2-positive cases were used to validate the algorithm performance. RESULTS: A total of 359,938 patients (mean age 40.4 [SD 19.2] years; 191,630/359,938, 53% female) with confirmed SARS-CoV-2 infection were identified over the study period. The most common signs and symptoms identified through NLP-supplemented analyses were cough (220,631/359,938, 61%), fever (185,618/359,938, 52%), myalgia (153,042/359,938, 43%), and headache (144,705/359,938, 40%). The NLP algorithm identified an additional 55,568 (15%) symptomatic cases that were previously defined as asymptomatic using structured data alone. The proportion of additional cases with each selected symptom identified in NLP-supplemented analysis varied across the selected symptoms, from 29% (63,742/220,631) of all records for cough to 64% (38,884/60,865) of all records with nausea or vomiting. Of the 295,305 symptomatic patients, the median time from symptom onset to testing was 3 days using structured data alone, whereas the NLP algorithm identified signs or symptoms approximately 1 day earlier. When validated against chart-reviewed cases, the NLP algorithm successfully identified signs and symptoms with consistently high sensitivity (ranging from 87% to 100%) and specificity (94% to 100%). CONCLUSIONS: These findings demonstrate that NLP can identify and characterize a broad set of COVID-19 signs and symptoms from unstructured EMR data with enhanced detail and timeliness compared with structured data alone.

    • Injury and Violence
      1. Morbidity and mortality of unintentional carbon monoxide poisoning: United States 2005 to 2018
        Shin M, Bronstein AC, Glidden E, Malone M, Chang A, Law R, Boehmer TK, Strosnider H, Yip F.
        Ann Emerg Med. 2022 Dec 28.
        STUDY OBJECTIVE: Centers for Disease Control and Prevention conducts case surveillance through the National Notifiable Diseases Surveillance System (NNDSS). This study aimed to provide surveillance report of unintentional carbon monoxide poisoning across multiple data sources to provide baseline data for the new NNDSS carbon monoxide poisoning surveillance. METHODS: For the period 2005 to 2018, we used 4 data sources to describe unintentional carbon monoxide poisoning: exposures reported by poison centers, emergency department (ED) visits, hospitalizations, and deaths. We conducted descriptive analyses by the cause of exposure (fire, nonfire, or unknown), age, sex, season, and US census region. Additional analyses were conducted using poison center exposure case data focusing on the reported signs and symptoms, management site, and medical outcome. RESULTS: Annually, we observed 39.5 poison center exposure calls (per 1 million, nationally), 56.5 ED visits (per 1 million, across 17 states), 7.3 hospitalizations (per 1 million, in 26 states), and 3.3 deaths (per 1 million, nationally) due to unintentional carbon monoxide poisoning. For 2005 to 2018, there was a decrease in the crude rate for non-fire-related carbon monoxide poisonings from hospital, and death data. Non-fire-related cases comprised 74.0% of ED visits data, 60.1% of hospitalizations, and 40.9% of deaths compared with other unintentional causes. Across all data sources, unintentional carbon monoxide poisonings were most often reported during the winter season, notably in January and December. Children aged 0 to 9 years had the highest reported rates in poison center exposure case data and ED visits (54.1 and 70.5 per 1 million, respectively); adults older than 80 years had the highest rates of hospitalization and deaths (20.2 and 9.9 per 1 million, respectively); and deaths occurred more often among men and in the Midwest region. Poison center exposure call data revealed that 45.9% of persons were treated at a health care facility. Headaches, nausea, and dizziness/vertigo were the most reported symptoms. CONCLUSION: The crude rates in non-fire-related carbon monoxide poisonings from hospitalizations, and mortality significantly decreased over the study period (ie, 2005 to 2018). This surveillance report provides trends and characteristics of unintentional carbon monoxide poisoning and the baseline morbidities and mortality data for the Centers for Disease Control and Prevention national surveillance system of carbon monoxide poisoning.

      2. Association between traumatic brain injury and suicidality using a mediation approach and MarketScan
        Miller GF, Zhou H, Peterson AB, Swedo E, Holland K, Kresnow MJ.
        Inj Prev. 2022 Dec 5.
        INTRODUCTION: Negative outcomes, including suicidal ideation/attempts, are a major public health concern, particularly among individuals who sustain a traumatic brain injury (TBI). TBI is associated with high rates of postinjury substance use, psychiatric disorders, post-traumatic stress disorder and sleep disturbances. This study examines the mediation effects of substance use, psychiatric disorder and sleep disorder on the associations between TBI and suicidal ideation/attempts. METHODS: A matched case-control study using data from MarketScan databases for private health insurance and Medicaid from October 2015 to December 2018 estimated the association between TBI and suicidal ideation/attempts using a mediation approach. Individuals less than 65 years of age were included. RESULTS: In the Medicaid sample, psychiatric disorders mediated 22.4% of the total effect between TBI and suicidal ideation/attempt, while substance use disorders other than opioid use disorder mediated 7.47%. In the private health insurance sample, psychiatric disorders mediated 3.97% of the total effect, opioid use disorders mediated 2.08% of the total effect and sleep disorder mediated 1.25% of the total effect. CONCLUSIONS: Mediators explained less than 30% of the relationship between TBI and suicidal ideation/attempt. Findings reinforce the importance of primary prevention of TBI and monitoring patients with a TBI for risk of suicide in the first 6-12 months following injury.

      3. Cost analysis of community-based violence prevention programs: Manhood 2.0 and job skills programs
        Tang S, Paglisotti TE, Ports KA, Abebe KZ, Jones KA, Levtov R, Kato-Wallace J, Miller E.
        J Fam Violence. 2022 .
        Purpose: Sexual violence (SV) and adolescent relationship abuse (ARA) are common in the U. S. and have strong associations with negative health and wellbeing outcomes. Manhood 2.0 is the first U.S. program designed for community settings to build bystander skills while also challenging harmful gender norms. A cluster-randomized trial comparing Manhood 2.0 to Job Skills, a job readiness training control condition, demonstrated that it is a promising strategy to prevent sexual violence and adolescent relationship abuse. Such community-based interventions may be particularly relevant in lower resource urban settings, and the costs of such prevention programs have not been considered previously. Methods: The aim of the present study is to perform systematic and standardized cost calculations associated with implementing Manhood 2.0 among adolescent males. In addition, this study provides detailed cost information of the community-based intervention program, as well as costs associated with implementing the Job Skills control program. Program implementation data were recorded throughout the study period (2015–2019) by the Manhood 2.0 study team. Results: The cost of implementing Manhood 2.0 is $4,771 per complete round of program delivery and $451 per participant, which is approximately the same cost as the control Job Skills program ($4,432 and $453 per participant). The marginal cost per additional round of Manhood 2.0 program is $3,682. Conclusion: Implementation of a community-based program requires substantial resources and collaborations with community partners especially in economically disadvantaged neighborhoods. This study provides a snapshot of the cost information of a community-based intervention program from the implementing agency’s perspective, which is essential in helping decision-makers understand the costs they will incur by implementing prevention programs and ensuring program feasibility and sustainability. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

      4. When traumatic brain injuries in children become chronic health conditions
        Kurowski BG, Haarbauer-Krupa J, Giza CC.
        J Head Trauma Rehabil. 2022 Dec 14.

    • Laboratory Sciences
      1. Meeting report: 35th international conference on antiviral research in Seattle, WA, USA - March 21-25, 2022
        Spengler JR, Welch SR, Deval J, Gentry BG, Brancale A, Carter K, Moffat J, Meier C, Seley-Radtke KL, Schang LM.
        Antiviral Res. 2022 Dec 31:105521.
        The 35th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Seattle, Washington, USA, on March 21-25, 2022 and concurrently through an interactive remote meeting platform. This report gives an overview of the conference on behalf of the society. It provides a general review of the meeting and awardees, summarizing the presentations and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. Through ICAR, leaders in the field of antiviral research were able to showcase their efforts, as participants learned about key advances in the field. The impact of these efforts was exemplified by many presentations on SARS-CoV-2 demonstrating the remarkable response to the ongoing pandemic, as well as future pandemic preparedness, by members of the antiviral research community. As we address ongoing outbreaks and seek to mitigate those in the future, this meeting continues to support outstanding opportunities for the exchange of knowledge and expertise while fostering cross-disciplinary collaborations in therapeutic and vaccine development. The 36th ICAR will be held in Lyon, France, March 13-17, 2023.

      2. Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages
        Xia H, Yeung J, Kalveram B, Bills CJ, Chen JY, Kurhade C, Zou J, Widen SG, Mann BR, Kondor R, Todd Davis C, Zhou B, Wentworth DE, Xie X, Shi PY.
        Emerg Microbes Infect. 2023 Jan 3:1-19.
        The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

      3. IPVS policy statement on HPV nucleic acid testing guidance for those utilising/considering HPV as primary precancer screening: Quality assurance and quality control issues
        Garland SM, Iftner T, Cuschieri K, Kaufmann AM, Arbyn M, de Sanjose S, Poljak M, Dillner J, Unger ER.
        J Clin Virol. 2022 Dec 8;159:105349.
        We advise that only clinically validated HPV assays which have fulfilled internationally accepted performance criteria be used for primary cervical screening. Further, assays should be demonstrated to be fit for purpose in the laboratory in which they will ultimately be performed, and quality materials manuals and frameworks will be helpful in this endeavor. Importantly, there is a fundamental shortage of well validated, low-cost, low complexity HPV tests that have demonstrated utility in a near-patient setting; representing a significant challenge and focus for future development in order to reach the WHO's goal of eliminating cervical cancer.

      4. Vulvovaginal candidiasis (VVC) is a common infection, and high-quality studies report that misdiagnosis is frequent, with diagnostic testing needed to distinguish it from other causes of vaginitis and avoid inappropriate empiric treatment. However, few recent studies have evaluated U.S. healthcare providers' testing practices for VVC in detail. We evaluated healthcare providers' self-reported testing practices for VVC and treatment outcomes as part of a nationwide online survey in order to identify potential opportunities for improving VVC testing and treatment in the United States. Among 1,503 providers surveyed, 21.3% reported "always" (7.4%) or "usually" (13.9%) ordering diagnostic testing for patients with suspected VVC; this proportion was higher among gynecologists (36.0%) compared with family practitioners (17.8%) and internists (15.8%). Most providers (91.2%) reported that patients' VVC "always" (6.4%) or "usually" (84.9%) responds to initial treatment. Whether the symptom resolution reported in this survey was truly related to VVC is unclear given high rates of misdiagnosis and known widespread empiric prescribing. With only about one-in-five providers reporting usually or always performing diagnostic testing for VVC despite guidelines recommending universal use, research is needed to address barriers to proper testing.

    • Maternal and Child Health
      1. Adverse maternal experiences and neonatal abstinence syndrome
        Hussaini KS, Yocher G.
        Matern Child Health J. 2023 Jan 2.
        OBJECTIVES: To propose a measure for adverse maternal experiences (AMEs) and examine if AMEs are independently associated with delivery of a neonatal abstinence syndrome (NAS) diagnosed infant. METHODS: Using the Pregnancy Risk Assessment Monitoring System (PRAMS) stressful life events questions, we constructed a composite measure of AMEs. We conducted a retrospective analysis of linked Birth Certificate Data, Hospital Discharge Data and PRAMS data for 2012-2018 using the composite measure. Our analytic sample included 6358 singleton deliveries. We calculated prevalence of NAS and AMEs and prevalence odds ratio (POR) for delivery of an NAS-diagnosed infant adjusting for maternal sociodemographic characteristics, pre-pregnancy depression, prescription medicine 12 months prior to pregnancy, and smoking during pregnancy. RESULTS: The overall prevalence of NAS in Delaware during 2012-2018 was 2.2% (95% CI 1.8-2.6); 9.5% (95% CI 8.7-10.2) of women reported AMEs. After adjustment, women with AMEs had 1.1 times greater odds (aPOR 2.1; 95% CI 1.3-3.3) to deliver a NAS-diagnosed infant as compared with women without AMEs. CONCLUSIONS: Although the cross-sectional nature of the study limits drawing any causal inferences, there are co-occurring factors that support plausibility of an association between AMEs and delivering NAS-diagnosed infants. Addressing AMEs, mental health and substance use screening and treatment as part of preconception and prenatal care may mitigate risks.

      2. PURPOSE AND OBJECTIVES: The objective of our study was to model the costs and benefits of 2 screening criteria for people with gestational diabetes. Because people with a history of gestational diabetes are at increased risk for type 2 diabetes, we modeled the effects of a postdelivery intervention based on the Diabetes Prevention Program, which is offered to all people with a history of gestational diabetes defined by either set of criteria. INTERVENTION APPROACH: We used a probabilistic decision tree model to compare the cost-effectiveness of the International Association of Diabetes in Pregnancy Study Group's (IADPSG's) screening criteria and the Carpenter-Coustan screening criteria for gestational diabetes through delivery and a follow-up period during which people might develop type 2 diabetes after pregnancy. EVALUATION METHODS: The model included perinatal outcomes for the infant and mother and a 10-year postdelivery period to model maternal progression to type 2 diabetes. The model assumed the health care system perspective. People with gestational diabetes received treatment for gestational diabetes during pregnancy, and we assumed that 10% would participate in a Diabetes Prevention Program-based postdelivery intervention to reduce the risk of type 2 diabetes. We estimated the cost-effectiveness of each screening strategy in quality-adjusted life-years (QALYs) in 2022 dollars. RESULTS: At 10% participation in a Diabetes Prevention Program-based postdelivery intervention, the Carpenter-Coustan criteria were cost-effective, compared with no screening ($66,085 per QALY). The IADPSG screening criteria were slightly less cost-effective, compared with no screening ($97,878 per QALY) or Carpenter-Coustan screening criteria ($122,279 per QALY). With participation rates of 23% or higher, the IADPSG screening criteria were highly cost-effective ($48,588 per QALY), compared with Carpenter-Coustan screening criteria. IMPLICATIONS FOR PUBLIC HEALTH: Diagnosing a larger proportion of pregnant people using the IADPSG screening criteria, compared with using Carpenter-Coustan screening criteria, is not cost-effective at low levels of participation. However, with moderate levels of participation (23%) in a Diabetes Prevention Program-based postdelivery intervention, the expanded IADPSG screening criteria are cost-effective and reach up to 4 times as many people as Carpenter-Coustan screening.

      3. Assessing the impact of hepatitis B immune globulin (HBIG) on responses to hepatitis B vaccine during co-administration
        Zubkova I, Zhao Y, Cui Q, Kachko A, Gimie Y, Chabot S, Murphy T, Schillie S, Major M.
        Vaccine. 2022 Dec 29.
        INTRODUCTION: A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered. METHODS: Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed. RESULTS: Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration CONCLUSION: Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site.

    • Nutritional Sciences
      1. Vitamin C status of US adults assessed as part of the National Health and Nutrition Examination Survey remained unchanged between 2003-2006 and 2017-2018
        Powers CD, Sternberg MR, Patel SB, Pfeiffer CM, Storandt RJ, Schleicher RL.
        J Appl Lab Med. 2023 Jan 2.
        BACKGROUND: We compared serum vitamin C (VIC) status of the adult (≥20 y) US population in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 with combined data from 2003-2004 and 2005-2006. METHODS: VIC was measured using HPLC with electrochemical detection. Mean data were stratified by age, sex, race/Hispanic origin, income, body mass index, dietary intake, supplement use, and smoking status. Prevalence of VIC deficiency (<11.4 μmol/L) was calculated. RESULTS: In NHANES 2017-2018, the mean VIC was 8 μmol/L higher in people ≥60 y compared with those 20-59 y of age, 10 μmol/L lower in men vs women, 8 μmol/L lower in low vs high income, 11 μmol/L lower in obese vs healthy weight, and 15 μmol/L lower in smokers vs nonsmokers. Differences in mean VIC across race/Hispanic origin groups ranged from 2 to 7 μmol/L. Mean VIC was 27 μmol/L higher with vitamin C-containing supplement use and positively associated (Spearman ρ = 0.33; P < 0.0001) with increasing dietary intake. The associations between mean VIC and the investigated covariates were generally consistent and the prevalence of deficiency was not significantly different between survey periods (6.8% vs 7.0%; P = 0.83). However, a few subgroups had double the risk. We found no significant survey differences in mean VIC (51.2 vs 54.0 μmol/L; P = 0.09). CONCLUSIONS: Overall VIC status of the US adult population has remained stable since last assessed in the NHANES 2005-2006 survey. Vitamin C deficiency remained high for those with low dietary intake and who smoke.

    • Occupational Safety and Health
      1. In practice, workers often handle the same chemical(s) of interest under different control measures (e.g. local ventilation, enclosed system) during a full shift. Stoffenmanager® allows users to predict either task-based or full-shift exposures. However, most previous studies evaluated the tool by comparing task-based exposures with measured exposures. Also, limited evaluation studies of the Advanced REACH Tool (ART) with the Bayesian approach (ART+B) are available, requiring additional evaluation studies. The performance of Stoffenmanager® and ART with and without the Bayesian approach was evaluated with measured full-shift exposures to volatile liquids in terms of accuracy, precision, and conservatism. Forty-two exposure situation scenarios (including 251 exposures), developed based on job tasks and chemicals handled during tasks from workplaces, were used to generate full-shift estimates. The estimates were then compared with measured exposures using various comparison methods. Overall, Stoffenmanager® appeared to be the most accurate among the testing tools, while ART+B was the most precise. The percentage of measured exposures exceeding the tools' 90th percentile estimates (%M>T) demonstrated that Stoffenmanager® (16%M>T) and ART+B (13%M>T) were more conservative than ART (41%M>T). When the 90% upper confidence limit of the 90th percentile estimate was considered, the level of conservatism changed from low (41%M>T) to medium (17%M>T) for ART and from medium (13%M>T) to high (0.8%M>T) for ART+B. The findings of this study indicate that no single tool would work for all ESs. Thus, it is recommended that users select a tool based on the performance results of three components (i.e. accuracy, precision, and conservatism), not depending on one or two components. The strength of this study is that the required tools' input parameters were obtained during the sample collection to minimize assumptions for many input parameters. In addition, unlike other previous studies, multiple subtasks, which happen often in workplaces, were incorporated in this study. Nevertheless, the present study did not cover all activities listed in the tools and was limited to volatile liquids, suggesting further studies cover other exposure categories (e.g. solid, metal) and diverse activities.

      2. Characterization of cleaning and disinfection product use, glove use, and skin disorders by healthcare occupations in a Midwestern healthcare facility
        Kobos L, Anderson K, Kurth L, Liang X, Groth CP, England L, Laney AS, Virji MA.
        Buildings. 2022 ;12(12).
        Healthcare facility staff use a wide variety of cleaning and disinfecting products during their daily operations, many of which are associated with respiratory or skin irritation or sensitization with repeated exposure. The objective of this study was to characterize the prevalence of cleaning and disinfection product use, glove use during cleaning and disinfection, and skin/allergy symptoms by occupation and identify the factors influencing glove use among the healthcare facility staff. A questionnaire was administered to the current employees at a midwestern Veterans Affairs healthcare facility that elicited information on cleaning and disinfection product use, glove use during cleaning and disinfection, skin/allergy symptoms, and other demographic characteristics, which were summarized by occupation. The central supply/environmental service workers (2% of the total survey population), nurses (26%,), nurse assistants (3%), and laboratory technicians (5%) had the highest prevalence of using cleaning or disinfecting products, specifically quaternary ammonium compounds, bleach, and alcohol. Glove use while using products was common in both patient care and non-patient care occupations. The factors associated with glove use included using bleach or quaternary ammonium compounds and using cleaning products 2–3 or 4–5 days per week. A high frequency of glove use (≥75%) was reported by workers in most occupations when using quaternary ammonium compounds or bleach. The use of alcohol, bleach, and quaternary ammonium compounds was associated with skin disorders (p < 0.05). These research findings indicate that although the workers from most occupations report a high frequency of glove use when using cleaning and disinfection products, there is room for improvement, especially among administrative, maintenance, and nursing workers. These groups may represent populations which could benefit from the implementation of workplace interventions and further training regarding the use of personal protective equipment and the potential health hazards of exposure to cleaning and disinfecting chemicals. © 2022 by the authors.

      3. The future of U.S. Agricultural injury surveillance needs collaboration
        Scott E, Weichelt B, Lincoln J.
        J Agromedicine. 2023 Jan;28(1):11-13.

    • Substance Use and Abuse
      1. Mouth level intake of nicotine from three brands of little filtered cigars with widely differing product characteristics among adult consumers
        Ashley DL, Zhu W, Watson CH, Bravo R, Ngac PK, Valentin-Blasini L, Pickworth WB, Kurti AN, Cunningham C, Blount BC.
        Chem Res Toxicol. 2023 Jan 4.
        Little filtered cigars are tobacco products with many cigarette-like characteristics. However, despite cigars falling under the U.S. Food and Drug Administration regulatory authority, characterizing flavors, which are still allowed in little filtered cigars, and filter design may influence how people use the products and the resulting exposure to harmful and potentially harmful constituents. We estimated nicotine mouth level intake (MLI) from analyses of little cigar filter butt solanesol levels, brand characteristics, carbon monoxide boost, and puff volume in 48 dual cigarette/cigar users during two repeat bouts of ad lib smoking of three little filtered cigar brands. Mean nicotine MLI for the three brands was significantly different with Swisher Sweets (0.1% ventilation) Cherry at 1.20 mg nicotine, Cheyenne Menthol (1.5%) at 0.63 mg, and Santa Fe unflavored (49%) at 0.94 mg. The association between nicotine MLI and puff volume was the same between Cheyenne Menthol and Santa Fe unflavored. However, these were different from Swisher Sweets Cherry. At least five main factors─flavor, ventilation, filter design, nicotine delivery related to tar, and user puff volume─may directly or indirectly impact MLI and its association with other measures. We found that users of little filtered cigars that have different filter ventilation and flavor draw dissimilar amounts of nicotine from the product, which may be accompanied by differences in exposure to other harmful smoke constituents.

      2. Trends in US e-cigarette sales and prices by nicotine strength, overall and by product and flavor type, 2017-2022
        Ali FR, Seaman EL, Crane E, Schillo B, King BA.
        Nicotine Tob Res. 2022 Dec 29.
        INTRODUCTION: The e-cigarette market has expanded considerably in recent years, resulting in changes in availability and use of e-cigarettes with varying characteristics. AIMS AND METHODS: This study assessed trends in sales and prices of e-cigarettes by nicotine strength level, including by product type and flavor, during January 2017-March 2022. US e-cigarette retail sales data were licensed from IRI company. Nicotine strength was categorized as: <1%; 1% to <2%; 2% to <3%; 3% to <4%; 4% to <5%; ≥5%. E-cigarette flavors were categorized as tobacco, menthol, mint, or other flavors. Product type was categorized as prefilled cartridge devices, disposable devices, or e-liquid bottles. Trend analyses were performed using Joinpoint Regression. RESULTS: During January 2017-March 2022, the unit share of products containing ≥5% nicotine strength increased by 1486.3%, while the dollar share increased by 1345.5%. By March 2022, 80.9% of total unit sales were composed of products containing ≥5% nicotine strength. By flavor, the percentage of units sold with ≥5% nicotine strength was 61.3% of tobacco-flavor sales, 79.3% of menthol sales, 87.4% of mint sales, and 96.1% of other flavor sales. By product type, the percentage of units sold with ≥5% nicotine strength was 90.6% of disposable e-cigarette sales and 74.2% of prefilled cartridge sales. During January 2017-March 2022, the price of low-nicotine strength e-cigarettes increased, while the price of high-nicotine products either decreased or did not change. CONCLUSIONS: Sales of high nicotine-strength e-cigarettes have dominated the US e-cigarette market. Limiting the nicotine strength of e-cigarettes could be considered as part of a comprehensive tobacco control strategy to reduce youth access to and use of these products. IMPLICATIONS: The findings from this study indicate that previously reported increases in e-cigarette nicotine strength during 2013-2018 have continued through 2022. The US e-cigarette market sales continue to be dominated by relatively high-nicotine products. Strategies to address factors that make these products, particularly appealing to youth, including flavors and product innovations, are critical. Such strategies are important-as part of a comprehensive approach alongside other evidence-based population-level actions-to address youth e-cigarette use. Importantly, actions to reduce e-cigarette use among youth are not mutually exclusive from actions to maximize the potential benefits of e-cigarettes for increasing smoking cessation among adults.

    • Veterinary Medicine
      1. Application of a universal parasite diagnostic test to biological specimens collected from animals
        Lane M, Kashani M, Barratt JL, Qvarnstrom Y, Yabsley MJ, Garrett KB, Bradbury RS.
        Int J Parasitol Parasites Wildl. 2023 Apr;20:20-30.
        A previously described universal parasite diagnostic (nUPDx) based on PCR amplification of the 18S rDNA and deep-amplicon sequencing, can detect human blood parasites with a sensitivity comparable to real-time PCR. To date, the efficacy of this assay has only been assessed on human blood. This study assessed the utility of nUPDx for the detection of parasitic infections in animals using blood, tissues, and other biological sample types from mammals, birds, and reptiles, known to be infected with helminth, apicomplexan, or pentastomid parasites (confirmed by microscopy or PCR), as well as negative samples. nUPDx confirmed apicomplexan and/or nematode infections in 24 of 32 parasite-positive mammals, while also identifying several undetected coinfections. nUPDx detected infections in 6 of 13 positive bird and 1 of 2 positive reptile samples. When applied to 10 whole parasite specimens (worms and arthropods), nUPDx identified all to the genus or family level, and detected one incorrect identification made by morphology. Babesia sp. infections were detected in 5 of the 13 samples that were negative by other diagnostic approaches. While nUPDx did not detect PCR/microscopy-confirmed trichomonads or amoebae in cloacal swabs/tissue from 8 birds and 2 reptiles due to primer template mismatches, 4 previously undetected apicomplexans were detected in these samples. Future efforts to improve the utility of the assay should focus on validation against a larger panel of tissue types and animal species. Overall, nUPDx shows promise for use in both veterinary diagnostics and wildlife surveillance, especially because species-specific PCRs can miss unknown or unexpected pathogens.

    • Zoonotic and Vectorborne Diseases
      1. Human biting mosquitoes and implications for West Nile virus transmission
        Uelmen JA, Lamcyzk B, Irwin P, Bartlett D, Stone C, Mackay A, Arsenault-Benoit A, Ryan SJ, Mutebi JP, Hamer GL, Fritz M, Smith RL.
        Parasit Vectors. 2023 Jan 2;16(1):2.
        BACKGROUND: West Nile virus (WNV), primarily vectored by mosquitoes of the genus Culex, is the most important mosquito-borne pathogen in North America, having infected thousands of humans and countless wildlife since its arrival in the USA in 1999. In locations with dedicated mosquito control programs, surveillance methods often rely on frequent testing of mosquitoes collected in a network of gravid traps (GTs) and CO(2)-baited light traps (LTs). Traps specifically targeting oviposition-seeking (e.g. GTs) and host-seeking (e.g. LTs) mosquitoes are vulnerable to trap bias, and captured specimens are often damaged, making morphological identification difficult. METHODS: This study leverages an alternative mosquito collection method, the human landing catch (HLC), as a means to compare sampling of potential WNV vectors to traditional trapping methods. Human collectors exposed one limb for 15 min at crepuscular periods (5:00-8:30 am and 6:00-9:30 pm daily, the time when Culex species are most actively host-seeking) at each of 55 study sites in suburban Chicago, Illinois, for two summers (2018 and 2019). RESULTS: A total of 223 human-seeking mosquitoes were caught by HLC, of which 46 (20.6%) were mosquitoes of genus Culex. Of these 46 collected Culex specimens, 34 (73.9%) were Cx. salinarius, a potential WNV vector species not thought to be highly abundant in upper Midwest USA. Per trapping effort, GTs and LTs collected > 7.5-fold the number of individual Culex specimens than HLC efforts. CONCLUSIONS: The less commonly used HLC method provides important insight into the complement of human-biting mosquitoes in a region with consistent WNV epidemics. This study underscores the value of the HLC collection method as a complementary tool for surveillance to aid in WNV vector species characterization. However, given the added risk to the collector, novel mitigation methods or alternative approaches must be explored to incorporate HLC collections safely and strategically into control programs.


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