Viral coinfections and their impact on long-term immunity represent an understudied area in disease ecology and infectious disease research. Coinfections can influence the host's susceptibility to future infections, alter host and pathogen population dynamics, modify infection and shedding patterns, impose evolutionary pressures, and affect the risk of zoonotic spillover. Egyptian rousette bats (ERB; Rousettus aegyptiacus; common name: Egyptian rousettes) are a natural reservoir host for Marburg virus (MARV) and Ravn virus (RAVV), as well as a vertebrate reservoir for Kasokero virus (KASV) and a putative reservoir for Sosuga virus (SOSV). Viral coinfections have been documented in numerous free-ranging bat species as well as ERBs, raising questions about how these interactions influence immune responses, viral shedding, and pathogen maintenance within the natural host population. This is particularly critical given the genetic diversity among co-circulating viral species (e.g., MARV and RAVV) and the potential implications for the development of protective immunity and subsequent viral inoculation outcomes. In this study, ERBs previously infected with MARV alone or KASV + MARV were inoculated approximately 8 months later with homotypic (MARV) or heterotypic (RAVV) orthomarburgvirus isolates. The results demonstrated no viral replication or shedding post-inoculation, and all bats displayed strong secondary immune responses consistent with sterilizing immunity. These findings suggest that both MARV monoinfection and KASV + MARV coinfection confer robust protection against reinfection, regardless of the viral isolate. This research enhances our understanding of immune responses during viral coinfections in bats and their potential role in mitigating zoonotic pathogen spillover.IMPORTANCELong-term immunity elicited in bats during coinfection (i.e., simultaneous infection) with viruses they naturally host is not well understood. These interactions could affect susceptibility to subsequent reinfection and pathogen spread. Egyptian rousette bats, natural hosts for several pathogenic zoonotic viruses, including Marburg and Kasokero viruses, can be found multiply infected in the wild, but the immune consequences of being coinfected remain unclear. Here, bats previously infected with either Marburg virus alone or with both Kasokero and Marburg viruses were later challenged with Marburg virus or the related Ravn virus. No reinoculated bats showed signs of virus replication, and all mounted strong immune responses. These results suggest that this coinfection combination still provides robust protection against reinfection, even with diverse orthomarburgviruses. This study helps improve our understanding of how bats manage viral coinfections and may inform how these interactions influence zoonotic spillover risk.

HIGHLIGHTS: Comprehensive view of occupational safety research: Prioritizing topics in robotics and autonomous machines. Barriers to safety research: Logistical, intellectual property, timeline, and funding challenges. Importance of surveillance or tracking system: Documenting fatalities, injuries, and near misses/good catches. Priority safety research needs: human-machine interaction, adoption of automation in the work setting, and surveillance/tracking. Collaboration with technology developers: Overcoming barriers and exploring emerging technologies and potential safety implications. ABSTRACT: In 2022, the SAfety for Emerging Robotics and Autonomous AGriculture (SAFER AG) Workshop was held to discuss and understand emerging challenges related to safety, occupational safety research needs, workforce implications, and other issues associated with robotics and autonomous machines in agriculture. This paper presents the major findings from the occupational safety research track of the workshop. This track identified existing hurdles to conducting occupational safety research including logistical barriers, intellectual property concerns, long timelines, and lack of funding. Considerations for developing a tracking or surveillance system for adverse events as well as exposure related to these technologies were also discussed, emphasizing the need for a comprehensive system. Finally, the priority occupational safety research needs identified during the session were related to human and non-human machine interaction, adoption of automation in the work setting, and event tracking/surveillance. To overcome barriers to research, collaboration between occupational safety researchers and technology developers is crucial. Enhancements to existing surveillance systems can facilitate better understanding of captured events. Additionally, prioritizing research on worker risk from robotics and autonomous machines in agriculture is essential. The integration of robotics and autonomous machines in agriculture has revolutionized the industry but requires evidence-based safety research, outreach, and education to ensure worker safety and health.

Background: In August 2023, the Centers for Disease Control and Prevention recommended nirsevimab, a long-acting monoclonal antibody, for all U.S. infants aged <8 months entering or born during their first respiratory syncytial virus (RSV) season. Our aim was to estimate nirsevimab effectiveness against RSV-associated emergency department (ED) encounters and hospitalisation among U.S. infants during the 2023–2024 RSV season. Methods: We conducted a test-negative analysis using electronic health record (EHR) data from 6 healthcare systems, including ED encounters and hospitalizations with a diagnosis of RSV-like illness (RLI) during October 8, 2023–March 31, 2024, among infants aged <8 months as of October 1, 2023, or born during the study period. Nirsevimab effectiveness was estimated by comparing children who received nirsevimab with those who did not among RSV-positive and RSV-negative encounters, adjusting for age, race and ethnicity, sex, calendar day, and geographic region and excluding infants whose mother received RSV vaccination during pregnancy. Findings: Among 5039 ED encounters with RLI among infants in their first RSV season, 2045 (41%) were RSV-positive and 446 (9%) received nirsevimab, with a median time since dose of 52 days (interquartile range [IQR]: 27–84 days). Among 1025 hospitalizations with RLI among infants in their first RSV season, 605 (59%) were RSV-positive and 95 (9%) received nirsevimab, with a median time since dose of 48 days (IQR: 24–82 days). Nirsevimab effectiveness was 77% (95% CI: 69%–83%) against RSV-associated ED encounters and 98% (95% CI: 95%–99%) against RSV-associated hospitalisation. Interpretation: Nirsevimab was effective in preventing RSV-associated ED encounters and hospitalisation among infants in their first RSV season, with greatest protection against hospitalisation. However, these estimates reflect a short interval from nirsevimab administration to RLI onset. Since nirsevimab is a passive immunization and concentration is expected to wane over time, it is important to continue monitoring effectiveness to assess effectiveness with increased time since dose. Funding: This work was supported by the Centers for Disease Control and Prevention (contracts 75D30121D12779 to Westat and 75D30123C18039 to Kaiser Foundation Hospitals). © 2025 Elsevier B.V., All rights reserved.

OBJECTIVES: Air medical services evacuation of patients with viral hemorrhagic fevers (VHFs) is a complex process. The United States National Emerging Special Pathogens Training and Education Center held an in-person tabletop exercise (TTX) in June 2023 to review and evaluate global processes and plans for long-range VHF air transportation capabilities. The TTX sought to test the coordination, prioritization, capacities, and plans for using VHF transportation capabilities when multiple countries simultaneously request support in air medical services evacuation of their sick or exposed citizens to a high-level isolation unit in their country for care. METHODS: Organizations invited to participate in the exercise (N = 16) were identified based on the TTX planning team's knowledge of their VHF transport capabilities. The TTX included a scenario involving a significant Sudan ebolavirus exposure event of an index case to 18 close contacts of diverse nationalities. Following the exercise, scribes' notes, evaluators' observations, and participant feedback forms were thematically analyzed to develop key findings and opportunities. The After Action Report was reviewed by all participants and finalized with their written approval. RESULTS: Representatives from 15 organizations in six countries participated in the TTX; the only organization unable to attend was the World Health Organization. Findings indicated many countries rely on the same organization for VHF air transportation resources that would be quickly exceeded in this scenario. There is a need to further define processes for determining global prioritization of transportation assets when requests exceed capacity. CONCLUSIONS: Reliance on the same limited global transportation assets has implications for health security and limits the global response to multiple patients or individuals needing repatriation simultaneously. This indicates the importance of prioritizing resources, enhancing multinational coordination, and highlights the need to elevate these findings and discussions to national and international policy levels to increase air transportation resources and expand global capacity for managing patients with VHFs.

Seasonal influenza causes 290,000-650,000 deaths annually, with vaccination efficacy ranging from 10 to 60%. The emergence of drug-resistant and highly pathogenic avian influenza viruses underscores the urgent need for novel protective strategies. Epidemiological observations have long suggested that certain vaccines, such as Bacillus Calmette-Guérin (BCG), can provide protection against diverse pathogens (S. Biering-Sørensen, P. Aaby, N. Lund, et al., Clin Infect Dis 65:1183-1190, 2017, https://doi.org/10.1093/cid/cix525; M.-L. Garly, C. L. Martins, C. Balé, et al., Vaccine 21:2782-2790, 2003, https://doi.org/10.1016/s0264-410x(03)00181-6; C. A. G. Timmermann, S. Biering-Sørensen, P. Aaby, et al., Trop Med Int Health 20:1733-1744, 2015, https://doi.org/10.1111/tmi.12614). While the cellular and molecular mechanisms underlying such protection remain incompletely understood, emerging research offers critical insights into innate immune system modulation (B. Cirovic, L. C. J. de Bree, L. Groh, et al., Cell Host Microbe 28:322-334, 2020, https://doi.org/10.1016/j.chom.2020.05.014; L. Kong, S. J. C. F. M. Moorlag, A. Lefkovith, et al., Cell Rep 37:110028, 2021, https://doi.org/10.1016/j.celrep.2021.110028; H. Mohammadi, N. Sharafkandi, M. Hemmatzadeh, et al., J Cell Physiol 233:4512-4529, 2018, https://doi.org/10.1002/jcp.26250; S. J. C. F. M. Moorlag, Y. A. Rodriguez-Rosales, J. Gillard, et al., Cell Rep 33:108387, 2021, https://doi.org/10.1016/j.celrep.2020.108387). We investigated whether a trained innate immune system with non-replicating adenoviruses could provide protection against diverse influenza virus strains. We demonstrated that replication-defective human adenoviruses can effectively train the innate immune system, conferring protective immunity in mice against multiple influenza virus strains, including H1N1, H3N2, H5N2, H7N9, and H9N2. In addition, bovine and chimpanzee adenoviruses can also activate human innate lymphoid cells (ILCs) and confer protection against challenge with influenza H3N2 virus in mice. Remarkably, this protection occurs in the complete absence of influenza-specific adaptive immune responses (influenza virus-specific hemagglutination-inhibiting antibodies, neutralizing antibodies, and influenza nucleoprotein-specific CD8 T cells). Key protective mechanisms include increased activation of ILC1, ILC2, and ILC3 populations, enhanced expression of interferon-stimulated genes (ISGs), upregulation of antiviral signaling pathways, and metabolic reprogramming of ILC subsets. Adoptive transfer experiments demonstrated that trained ILCs were sufficient to protect against influenza H1N1 infection in ILC-deficient mice. This research establishes a novel strategy for enhancing innate antiviral immunity, offering broad-spectrum protection against diverse influenza strains, a promising approach for not only pandemic preparedness but also against emerging infectious diseases. Training innate lymphoid cells through non-replicating adenoviral vectors represents a promising approach to enhancing broad-spectrum antiviral immunity, complementing traditional vaccination strategies.IMPORTANCEThe findings represent a potential game-changer for fighting influenza, which kills hundreds of thousands of people worldwide each year despite our best vaccination efforts. Current flu vaccines often provide limited protection because they must be reformulated annually to match circulating strains, and their effectiveness varies dramatically from year to year. The scientists discovered something remarkable: common adenoviruses (which typically cause mild cold-like symptoms) can essentially "train" our immune system's first line of defense to recognize and fight off multiple types of flu viruses simultaneously. This protection works through a completely different mechanism than traditional vaccines-it does not rely on creating specific antibodies against flu proteins. Instead, the treatment activates special immune cells called innate lymphoid cells (ILCs), which act like the body's rapid response team. These trained cells provide broad protection against various flu strains, including dangerous bird flu variants that could cause future pandemics. The significance lies in potentially creating a universal flu protection strategy that could work against unknown future flu strains, offering hope for better pandemic preparedness and reducing seasonal flu's devastating global impact.

BACKGROUND: Pneumonia causes high rates of hospitalization among adults living in long-term care (LTC) facilities and is a major cause of mortality in this population. Since 2014, pneumococcal conjugate vaccines (PCVs) have been recommended for U.S. adults aged ≥65 years; however, effectiveness of PCVs against all-cause pneumonia hospitalization among adults living in LTC remains unclear. METHODS: We used Medicare Fee-for-Service claims data to construct an open cohort of beneficiaries aged ≥65 years between September 2014 and December 2019. We estimated 13-valent PCV (PCV13) vaccine effectiveness (VE) by comparing rates of pneumonia hospitalization among PCV13-exposed and PCV13-unexposed time during LTC stays. Discrete-time logistic regression models with generalized estimating equations were used to estimate VE, incorporating time-varying exposures and covariates. RESULTS: Among 3,485,071 beneficiaries meeting the eligibility criteria, the proportion vaccinated with PCV13 increased from 1.1% to 52.7% during the study period. The characteristics of beneficiaries with shorter LTC stays differed from those with longer LTC stays: a lower proportion of beneficiaries aged ≥85 years (LTC stay ≤100 days vs >100 days: 38.5% vs. 48.2%), but a higher proportion with chronic medical conditions (71.4% vs 66.4%), immunocompromising conditions (36.6% vs. 25.2%), and recent hospitalizations (84.1% vs. 74.7%). VE of PCV13-only against all-cause pneumonia hospitalization was 3.8% (95% confidence interval 2.4%-5.2%) overall; 5.6% (3.9%-7.2%) for LTC stays ≤100 days and 0.3% (-2.1%- 2.77%) for LTC stays >100 days. CONCLUSIONS: PCV13 reduced the risk of pneumonia hospitalization among this population. Differences in beneficiary characteristics could explain differences in VE by length of LTC stay.

INTRODUCTION: There is high interest in long-acting injectable antiretroviral therapy (LAI-ART) among people with HIV (PWH), with many conveniences for uptake and persistence. However, both patients and clinicians have expressed important barriers to effective implementation, including concerns about frequent clinic visits and strain on clinic resources. Administration of LAI-ART by a trained layperson injector (such as family, friend or partner of the patient) can help mitigate some of these patient-identified and clinician-identified barriers. Alternative LAI-ART delivery methods have the potential to increase the PWH and layperson injector's confidence, empowerment, convenience, privacy and self-management skills and ultimately facilitate LAI-ART uptake and persistence. METHODS AND ANALYSIS: INVITE-Home (innovative administration of long-acting injectables for HIV treatment enhancement at home) will support the expansion of LAI-ART in non-clinical settings by developing, implementing and evaluating a comprehensive, theory-informed training to support the administration of LAI-ART by a trained layperson injector. First, INVITE-Home will design and develop an innovative, theory-based layperson injector training to improve acceptability and uptake of LAI-ART in home-based settings, grounded in qualitative evaluation of training barriers and needs of PWH, layperson injectors and clinicians to develop the training. In Aim 2, INVITE-Home will enhance understanding of home-based LAI-ART using the training, by examining implementation and effectiveness of home-based LAI-ART injections. ETHICS AND DISSEMINATION: This study and its protocols have been approved by the University of California, San Francisco (UCSF) Institutional Review Board and the scientific staff of HIV Research Branch, Division of HIV Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, at the Centers for Disease Control and Prevention. Study staff will disseminate findings locally (eg, to partnering clinics, via the UCSF Center for AIDS Prevention Studies' Community Engagement Core), statewide (eg, the California Department of Public Health's Office of AIDS) and nationally at conferences related to HIV. TRIAL REGISTRATION NUMBER: NCT06488846.

OBJECTIVE: On November 20, 2021, petroleum fuel contaminated the Red Hill well, which provides water to about 93 000 persons on Oahu, Hawaii. Initial investigations recommended further evaluations of long-term health effects of petroleum exposure in drinking water. We reviewed electronic health records of those potentially exposed to contaminated water to understand prevalence of conditions and symptoms. METHODS: A sample of persons potentially exposed during November 20, 2021-March 18, 2022 who sought care within the military health system through February 24, 2023 was identified. Abstracted records were categorized as worsening preexisting or persistent new for conditions and symptoms. RESULTS: Of 653 medical charts reviewed, 357 (55%) had worsening preexisting or persistent new conditions or symptoms. Most-documented conditions included worsening preexisting migraine (8%; 50/653) and chronic pain (4%; 26/653), and persistent new migraine (2%; 14/653) and adjustment disorder (2%; 13/653). Most-documented symptoms included worsening preexisting headache (8%; 49/653) and anxiety (6%; 42/653), and persistent new rash (7%; 46/653) and headache (5%; 34/653). CONCLUSIONS: Approximately half of the abstracted medical records demonstrated worsening preexisting or persistent new conditions or symptoms and might benefit from sustained access to physical, mental, and specialized health care support systems. Continued monitoring for long-term health outcomes is recommended.

Guidelines recommend children maintain a healthy body mass index (BMI) and do physical activity. No population-based estimates exist for elevated BMI or insufficient physical activity among children with congenital heart conditions (CHC). We estimated the national prevalence of elevated BMI and insufficient physical activity among children with and without CHC. We analyzed cross-sectional, nationally representative data on 57,080 children aged 6-17 years from the National Survey of Children's Health, 2021-2022. Among children with (N = 1135) and without (N = 55,945) CHC, we estimated prevalence and 95% confidence intervals (CI) for caregiver-reported elevated BMI (≥ 85th percentile for sex and age) and insufficient physical activity (< 60 min of physical activity < 7 days/week). Using multivariable Cox proportional hazards models adjusted for age, sex, ethnicity/race, federal poverty level, and caregiver education, we approximated adjusted prevalence ratios (aPR) and CI for each outcome by CHC status and, separately, by demographics among children with CHC. Children with CHC had a similar prevalence of elevated BMI (31.5%, aPR = 0.97, CI 0.82-1.14) and a slightly higher prevalence of insufficient physical activity (84.0%, aPR = 1.05, CI 1.00-1.09) compared to children without CHC. Among children with CHC, elevated BMI was 1.5-1.6 times higher for Hispanic compared to non-Hispanic White children, those with lower compared to higher household incomes, and those with caregivers with ≤ high school compared to ≥ college education; there were no demographic differences in insufficient physical activity. Pediatricians and cardiologists can support patients with CHC in meeting BMI and physical activity recommendations to improve their long-term cardiovascular outcomes.

Exposure to phthalates is common and difficult to avoid. However, intake of long-chain n-3 polyunsaturated fatty acids (n3PUFAs) may ameliorate negative effects on ovarian reserve by exposure to phthalates as both are involved in key processes of ovarian function. Among 139 women attending a fertility center in the Environment and Reproductive Health (EARTH) Study (2004-2017), we evaluated whether associations between urinary phthalate biomarkers and antral follicle count (AFC) were modified by tertiles of serum α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We used Poisson regression (for individual phthalate biomarkers) and quantile Q-computation (for mixtures) models adjusted for age, body mass index, prior smoking, number of urine samples and urinary specific gravity. We found that serum EPA + DHA levels modified the negative association of urinary phthalate biomarkers mixture with mean AFC (P for interaction = 0.23); sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) had the strongest effect modification (P interaction = 0.01). Specifically, phthalate biomarkers mixture and ∑DEHP were inversely related with AFC only among women in the low (P trend = 0.03 and < 0.001, respectively) and middle (P trend = 0.07 and 0.002) tertiles of serum EPA + DHA, but not among women in the high tertile (P trend = 0.56 and 0.93). No effect modifications were found by serum ALA. These findings suggest certain serum n3PUFAs may attenuate effects of phthalate exposure on ovarian reserve marker. Such interaction points toward select n3PUFAs as key modifiers of phthalate toxicity on ovarian health with potential implications for other women's reproductive health endpoints.

PURPOSE: The purpose of this study was to describe an exploratory partner approach to enrolling in the National Diabetes Prevention Program (National DPP), a proven 12-month lifestyle change program (LCP) for people at risk for developing type 2 diabetes. FHI360 and the University of Maryland Horowitz Center for Health Literacy created a "partner approach" to investigate whether people at risk for developing diabetes might be willing to join, complete, and be successful in the LCP if they intentionally go through the program with a partner who influences their lifestyle choices. METHODS: The research team analyzed aggregated participant self-reported weight and physical activity data, participant survey and focus group data, and lifestyle coach in-depth interview data to assess the retention, motivation, and acceptability of the partner approach. RESULTS: Across sites, retention of participants at risk of developing type 2 diabetes at the end of the year-long program was at 79%. Participants at the partner approach sites reported being motivated and successful. Lifestyle coaches reported that participants stayed in the program longer and adapted their lifestyle more than participants at other sites that did not offer the partner approach. CONCLUSIONS: People at risk of developing type 2 diabetes may respond positively to participating in a National DPP LCP when they can join with engaged partners. Based on study results, the partner approach may be a way to attract people at risk for type 2 diabetes who are more comfortable joining with a partner.

BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC. METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as ≥3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage. RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics. CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S. METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data. RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings. CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research. POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.

BACKGROUND: Mozambique implemented a phased roll-out of COVID-19 vaccination in 2021. This study aimed to evaluate COVID-19 vaccine acceptability among higher-risk populations in Zambézia Province. METHODS: A mixed-methods study in Zambézia Province assessed knowledge, perceptions, and acceptability of COVID-19 vaccination. Structured questionnaire-based surveys among community health workers/volunteers, taxi drivers, and persons with HIV; and focus group discussions using semi-structured guides with community/religious leaders, adults aged 18-49 years and adults aged 50+ years were conducted in August-September 2021. Surveys were captured using tablets; group discussions were recorded. Univariate analyses were performed for quantitative data; qualitative data were analyzed thematically. RESULTS: A total of 731 individuals participated (539 survey respondents; 192 discussion respondents); 53% male (n = 386) and 74% urban (n = 544) residents. Most had heard about COVID-19 vaccines, mainly through television and/or radio. Trustworthy information sources mentioned were community leaders and healthcare providers. Among survey respondents, 249/539 (46%) reported having received at least 1 vaccine dose. Motivators for vaccination mentioned by survey respondents were "belief that vaccines protect themselves" (72%), "belief it would protect their family" (17%). Myths and beliefs, misinformation, and long queues were main barriers for vaccination mentioned in group discussions. Participants suggested that campaigns should focus on communication talks led by health professionals, in partnership with community or church leaders and/or community health workers/volunteers. CONCLUSIONS: This study showed that information on COVID-19 vaccination had successfully reached the vast majority of study participants, mainly via radio and television. Targeted campaigns specific for rural and urban contexts can increase awareness and uptake of vaccination.

IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics. OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status. DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months. SETTING: Participants were recruited across eight US sites. PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey. EXPOSURE: SARS-CoV-2 index status and employment type (essential healthcare worker [HCW], essential non-HCW, and non-essential worker ["general worker"]). MAIN OUTCOMES AND MEASURES: PROMIS-29 (mental and physical health summary) and PROMIS Cognitive SF-CF 8a (cognitive function) scores were assessed at baseline, short-term (3-months), and long-term (12-18 months) timepoints using GEE modeling. RESULTS: Of the 1,463 participants: 53.5% were essential workers (51.4% HCWs, 48.6% non-HCWs) and 46.5% were general workers. Most associations between outcomes and employment type became non-significant after adjusting for sociodemographics, comorbidities, COVID-19 vaccination, and SARS-CoV-2 variant period. However, among COVID-negative participants, essential HCWs had higher cognitive scores at baseline (β: 3.91, 95% CI [1.32, 6.50]), short term: (β: 3.49, 95% CI: [0.80, 6.18]) and long-term: (β: 3.72, 95% CI: [0.98, 6.46]) compared to general workers. Among COVID-positive participants, essential non-HCWs had significantly worse long-term physical health summary scores (β:-1.22, 95% CI: [-2.35, -0.09]) compared to general workers. CONCLUSIONS AND RELEVANCE: Differences in outcomes by worker status were largely explained by baseline characteristics. However, compared to general workers, essential HCW status had higher cognitive function in the absence of SARS-CoV-2 infection at all timepoints, while essential non-HCWs were most vulnerable to poor recovery in long-term physical health following SARS-CoV-2 infection. Preparation efforts for future pandemics may consider enhanced protection and post-infection resources for frontline workers.

Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other poorly understood post-acute infection syndromes (PAIS) can present with unexplained symptoms or conditions that may be misunderstood by healthcare providers, causing delays in diagnosis and care. To address these issues, the Centers for Disease Control and Prevention (CDC) funded the Long COVID and Fatiguing Illness Recovery Program (LC&FIRP), initiated as a pilot project to assess whether providing tele-mentoring and other online education for primary care providers could help them improve the quality of life and support the recovery of their patients with these conditions. The LC&FIRP multi-disciplinary team-based care approach is built on the Extension for Community Healthcare Outcomes (ECHO) learning model, which is an evidence-based virtual learning framework developed by the University of New Mexico and designed to disseminate and implement best practices, especially in under-resourced areas. A distinctive feature of LC&FIRP was the inclusion of lived-experience experts. To explore the influence of lived-experience experts on the care patients received, we collected the educational recommendations provided by the lived-experience experts during webinar sessions (January 2022-March 2024) and grouped these by themes. The major themes that emerged included validation of patients' illness experience; attitudes and beliefs about Long COVID, ME/CFS, and PAIS; understanding patients' challenges and communicating with empathy; navigating referrals; recognizing and supporting disability; and supporting self-care. Investigators also interviewed patients of the Family Health Centers of San Diego (FHCSD) about their experiences receiving care from participating primary care providers and employed content analysis methods to code interview transcripts to identify themes among patients' perspectives. Positive comments from the patients about topics emphasized by the lived-experience experts provided evidence of providers' uptake and application of the experts' recommendations and support the value of involving lived-experience experts in medical education to improve health services.

In the years following the COVID-19 pandemic, immunization coverage has declined among frontline post-acute and long-term care (PALTC) staff, such as nurses, certified nursing assistants, and kitchen staff. We took a novel approach to addressing these declines by engaging frontline staff in design of immunization-focused professional development by surveying a convenience sample of 200 frontline PALTC staff to understand their attitudes toward immunization and preferences for job-related education and training. Frontline staff reported being motivated to protect themselves and residents from illness but were skeptical about the ability of vaccines to do so. Many felt strongly that immunization is a personal choice and wanted objective and reliable information on vaccines. We used this learning to design a 45-minute in-service for frontline staff that presented information on the benefits and risks of recommended immunization for PALTC residents and staff in a neutral way that respected staff autonomy. Accompanying brief online training prepared supervisors to deliver the in-service and answer staff questions. To evaluate the training, we surveyed a separate convenience sample of supervisors at 3 PALTC facilities, and all positively evaluated the in-service materials and training. The core focus of this innovative approach is centered on trusted messengers sharing reliable and relevant vaccine information in respectful ways.

OBJECTIVE: To develop a U.S.-based microsimulation model for assessing the cost-effectiveness of interventions to manage type 1 diabetes. RESEARCH DESIGN AND METHODS: We developed risk equations for 14 diabetes-related complications and mortality, 12 risk factor progression equations, and one equation for utilities associated with 14 complications using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) studies and the Epidemiology of Diabetes Complications (EDC) study. We integrated all equations into a simulation model. We conducted internal and external validation and demonstrated the utility of the model using a real-world example. Main model-generated outcomes included cumulative incidence of diabetes-related complications, life years, quality-adjusted life years, medical costs, and incremental cost-effectiveness ratios. RESULTS: The model generates long-term clinical and economic outcomes from changes in risk factors of type 1 diabetes complications. Internal validation comparing modeled outcomes to observed data used to develop the model yielded good prediction accuracy, with mean absolute percentage error across all complications of 9% and correlation of cumulative failure rates above 0.9. External validation results were mixed, with occurrence of slight under- or overprediction across complications and studies. We illustrated the model with a case study estimating the effects of expanding the use of an insulin pump with continuous glucose monitoring to all people with type 1 diabetes. CONCLUSIONS: Our new comprehensive type 1 diabetes simulation model can generate valid and accurate results for assessing the long-term cost-effectiveness of interventions to manage type 1 diabetes in the U.S.

BACKGROUND: The CDC's Colorectal Cancer Control Program (CRCCP) partners with health system clinics to implement evidence-based interventions (EBIs) to increase colorectal cancer (CRC) screening prevalence. The sustainability of those EBIs is critical for the long-term success and impact of the CRCCP. This paper examines various aspects of the sustainability of these EBIs, including the factors associated with sustainability. METHOD: We used Clinic Data collected by CDC for program evaluation. The study employed two definitions of sustainability and conducted a comprehensive analysis including all available information on sustainability in the Clinic Data. Our descriptive analysis included comparing frequencies and means of the outcome variable as defined in the study. Logistic regression methods were used to explore the association of multiple explanatory factors with EBI sustainability. RESULTS: The results highlighted significant variations in the sustainability of different EBIs. Provider reminders were reported as sustainable by 82.0% of the clinics, while reducing structural barriers were reported as sustainable by 55.6% of the clinics. The percentage of clinics able to sustain each of the four EBIs trended upwards over time, ranging from 13 to 34 percentage points increase. Clinics that had implemented EBIs before CRCCP involvement, those that integrated multiple interventions, and those with dedicated screening champions were more likely to sustain EBIs in the long term. CONCLUSIONS: We found substantial improvement in the sustainability of EBIs over the 5-year program period, although results varied by EBIs and room for improvement remains. The findings offer valuable insights for future implementation and sustainability of EBIs.

INTRODUCTION: The antiretroviral therapy (ART) initiation policy in Uganda recommends that ART is initiated on the same day of HIV diagnosis to those who do not have contraindications. We assessed determinants of retention in ART care at the first follow-up (FFU) after same-day ART initiation and retention in long-term care beyond the FFU visit. METHODS: We conducted a retrospective longitudinal analysis among persons living with HIV aged ≥18 years who initiated ART during April 2016-February 2021 after the inception of Uganda's Test-and-Treat ART policy, which states that 'all individuals diagnosed with HIV should initiate ART regardless of clinical stage CD4 count'. Missing the FFU after ART initiation (missing FFU) was defined as not returning for FFU within 1 month of ART initiation; loss to follow-up long-term (LTFU-LT) was defined as delaying more than 3 months to return for a scheduled ART drug refill after the FFU appointment. LTFU-LT time was defined as the time from the FFU visit date to the last follow-up visit date during the study period. We used log-binomial distributions to estimate unadjusted and adjusted relative risks (adjRRs) of missing FFU, and we used Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (adjHRs) for LTFU-LT. RESULTS: Overall, 8332 clients initiated ART on the same day of HIV diagnosis. Most were female (55%), aged 25-34 years (44%), resided in the semi-urban or rural district (41% and 41%, respectively) and had a median age of 25 years (IQR = 24-35). Overall, missing FFU was 15.1%. Increased likelihood/risk of missing FFU was seen in clients who initiated ART at outreach health service centres versus health facilities (adjRRs = 1.79, 95% CI = 1.6-2.0), in younger clients aged 18-24 years and 25-34 years versus ≥45 years [(adjRRs = 1.65, 95% CI = 1.3-2.0) and (adjRRs = 1.31, 95% CI = 1.1-1.6), respectively], and clients residing in agrarian districts versus fishing districts (adjRRs = 1.24, 95% CI = 1.1-1.4). Overall, the LTFU-LT rate was 25 clients/100 pys (95% CI = 23.9-25.9) and was associated with younger age (18-34 years versus ≥45 years, adjHRs = 1.77, 95% CI = 1.5-2.1), residence in semi-urban (adjHRs = 1.33, 95% CI = 1.2-1.5) or agrarian district (adjHRs = 1.30, 95% CI = 1.2-1.5) versus fishing-community district. CONCLUSION: Retention-strengthening strategies in tandem with same-day ART initiation efforts for younger clients and clients initiated on ART from mobile and outreach health service settings might improve HIV treatment retention. Best practices for retaining fishing-community clients might improve health outcomes if applied to agrarian and semi-urban communities.

IMPORTANCE: West Nile virus (WNV), a neurotropic flavivirus spread by Culex species mosquitoes, is the leading cause of mosquito-borne disease in the contiguous US. From 2014 to 2023, a mean of 1298 WNV neuroinvasive disease cases and 129 deaths were reported annually in the US. OBSERVATIONS: Almost all WNV infection occurs via mosquito bites, but transmission can rarely occur via blood transfusion, organ transplantation, and transplacental, perinatal, breastmilk, percutaneous, and conjunctival exposure. Since 2018, large WNV outbreaks have been reported in Europe, Tunisia, Israel, and the US. In 2021, the largest county-level US outbreak occurred in Arizona, with 1487 disease cases and 101 deaths reported. Based on seroprevalence surveys, approximately 80% of human WNV infections are asymptomatic, 20% cause a febrile illness (West Nile fever), and less than 1% cause neuroinvasive disease (eg, meningitis, encephalitis, acute flaccid myelitis). Mortality of patients with neuroinvasive disease is approximately 10% overall but is 20% in individuals 70 years or older and 30% to 40% in patients with hematologic malignancies, solid organ transplants, and those receiving B-cell-depleting monoclonal antibodies. Among patients hospitalized for WNV disease, 30% to 40% are discharged to long-term care facilities, and more than 50% have long-term sequelae such as fatigue, weakness, myalgia, memory loss, and depression. WNV transmission during solid organ transplantation was identified in 14 clusters in the US and Italy from 2002 to 2023. Since WNV screening of the US blood supply began in 2003, 14 cases of WNV transmission through blood transfusion have been reported. For patients with fever or neurologic symptoms during summer and fall months, WNV should be considered; IgM testing of serum and/or cerebrospinal fluid is recommended, followed by confirmatory neutralizing antibody testing in cases of possible exposure to cross-reacting flaviviruses, atypical presentation or death, or suspected unusual transmission modes such as organ transplantation. Reverse transcription-polymerase chain reaction testing is often more sensitive than IgM testing in patients with severe immunocompromise. There are no evidence-based therapies or human vaccines for WNV disease. Preventive methods include personal protective behaviors, such as using Environmental Protection Agency-registered mosquito repellents, wearing protective clothing, and limiting outdoor exposure from dusk to dawn, and community mosquito control measures. CONCLUSIONS AND RELEVANCE: WNV causes more than 1200 neuroinvasive disease cases and 120 deaths annually in the US. People who are older or immunocompromised are at higher risk of severe disease and death. Since there are no therapies or human vaccines, prevention relies on personal protective measures, WNV surveillance, and mosquito control interventions.

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV infection in the United States, especially Black MSM (BMSM) and Hispanic/Latino MSM (HLMSM). Long-acting preexposure prophylaxis (LA PrEP) is effective in preventing HIV; however, medical mistrust may contribute to barriers in uptake among BMSM and HLMSM. We assessed the role of medical mistrust in BMSM and HLMSM's unwillingness to use LA PrEP. BMSM and HLMSM aged ≥18 years without a previous HIV diagnosis or current PrEP use were recruited through dating and general interest websites/apps. Using Poisson regression with robust standard errors, we conducted multivariate analyses to assess the association between medical mistrust and willingness to use LA PrEP (i.e., injection or rod implanted in the arm) separately for each racial/ethnic group. Over 90% of the 1,126 BMSM and 924 HLMSM in this study were willing to use some form of PrEP; however, only 74% of BMSM and 81% of HLMSM were willing to use PrEP injections, and significantly fewer BMSM (30%) were willing to receive a PrEP implant compared with 44% of HLMSM. After controlling for sociodemographic, behavioral, and clinical covariates, medical mistrust was associated with lower willingness to use LA PrEP for BMSM, but not for HLMSM. Addressing and reducing medical mistrust among BMSM is important to increase the use of LA PrEP as an effective HIV prevention strategy. Addressing structural barriers and building trust within healthcare systems are crucial steps in reducing disparities in HIV infection among BMSM and HLMSM.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, many of which exhibit low in vivo clearance rates. The long-chain PFAS (≥6 perfluorinated carbons), due to low clearance rates, are often perceived to exert a higher toll on human health than short-chain PFAS. However, a comprehensive toxicological and epidemiological comparison of long- and short-chain PFAS is overdue, leaving significant data gaps and limitations. For the first time, this study investigated the quantitative relationship between overall PFAS fluorine structure (C-F bond), which includes the alkyl chain length as one component, and PFAS doses that trigger changes in rat blood-based clinical markers. Fifteen markers published by the National Toxicology Program (NTP) after 28-day exposure to 7 PFAS with both long- and short-chain perfluorinated alkyl structures were examined. The aim of this study was to (1) determine PFAS doses that trigger changes in the marker levels for hepatic, renal, cardiovascular, and metabolic systems and (2) use these doses in multiple linear regression models to examine relationship to variables describing PFAS chemical structures. Our findings showed a log-linear dependence of alterations in marker levels on PFAS fluorine structure, as measured in the number of alkyl carbon-fluorine (C-F) bonds. Each C-F bond affected the marker effect levels by 0.45 ± 0.01 mmol/kg-day. The variety of studied clinical markers suggests that PFAS exposures led to deviations in multiple biological pathways in the rat animal model, which may inform future research and regulatory decisions. | Perfluorinated carboxylic or sulfonic acids with linear chains of 4 to 10 carbons, known as perfluoroalkyl acids (PFAA)s, are types of PFAS commonly found in the environment.In a 28-day study by NTP, these PFAAs had dose-response effects in a panel of blood-based clinical markers in rats at specific doses.In regression models for individual clinical markers or a joint regression for all markers, these doses were strongly correlated with the number of carbon-fluorine bonds in the PFAAs.The resulting multiple linear regression (MLR) models provide a simple estimation tool for PFAAs’ exposure levels on blood-based clinical marker responses in rats. | eng

INTRODUCTION: Gulf War Illness is a chronic multisymptomatic disorder that affects as many as 25-35% of the military personnel who were sent to the Persian Gulf war in 1991. The illness has many debilitating symptoms, including cognitive problems, gastrointestinal symptoms, and musculoskeletal pain. Those so afflicted have been sick for more than 30 years and, therefore, it has become imperative to understand the etiology of Gulf War Illness and then produce treatments to ease the symptoms. We hypothesized that the length of the disease was reflected in epigenetic modification of possibly several genes related to the symptoms. METHODS: We subjected male and female mice from 11 BXD strains to combined corticosterone and the sarin surrogate, diisopropylfluorophosphate, to emulate the physiological stress of war and the potential exposures to organophosphate pesticides and nerve agent in theater. Three hundred days after treatment, we used Methyl-CpG-binding domain sequencing (MBD-seq) to assay genome-wide methylation. RESULTS: The analysis revealed 20 methylated genes, notably Eif2b5, that regulates myelin production. DISCUSSION: Loss of myelin with accompanying musculoskeletal pain is a major symptom of Gulf War Illness. Our work demonstrates multiple genes were methylated by exposure to organophosphates and glucocorticoids. These genes point to biochemical mechanisms that may be targets for therapeutic intervention.

INTRODUCTION: We examined the association of pre-exposure prophylaxis (PrEP) programme retention with the use of daily, event-driven (ED) or regimen switching reported during follow-up at any point prior to discontinuation among men who have sex with men (MSM) in Hanoi, Vietnam. METHODS: Between April 2020 and February 2023, we collected data from PrEP clients at Hanoi Medical University Sexual Health Promotion clinic who were prescribed either ED or daily PrEP at the initial visit; at subsequent visits, clients reported the regimen used since the prior visit. We defined three categories of PrEP use: ED-PrEP exclusively, daily PrEP exclusively and switching regimens. The primary outcome was time to discontinuation in the PrEP programme during the study period, defined as missing a scheduled visit by > 30 days. We performed survival analysis using Kaplan-Meier curves. RESULTS: In total, 2107 people were included: 61.1% (n = 1288) reported exclusive use of daily PrEP, 10.4% (n = 220) reported exclusive use of ED-PrEP and 28.4% (n = 599) reported switching PrEP regimens. Among switchers, 29.40% (n = 176) switched more than once. Furthermore, 82.5% switched from daily to ED-PrEP and 17.5% switched from ED to daily PrEP. The median time to discontinuation in the PrEP programme was 105 days (IQR: 52-182) among those reporting exclusive use of ED-PrEP, 104 days (IQR: 56-274) among those reporting exclusive use of daily PrEP and 163 days (IQR: 101-308) among those who switched. Among switchers, those who switched more than once had a median time to discontinuation in the PrEP programme of 231 days (IQR: 137-380) in comparison to 133 days (IQR: 90-274) for those who switched once. CONCLUSIONS: We provide real-world data from MSM in an HIV PrEP programme in Vietnam that those who switched had longer periods of retention during the study period. Our findings suggest that offering flexible PrEP regimen options may improve engagement and long-term adherence among this population.

OBJECTIVES: Understanding of long-term lung cancer risks from radon decay products (RDP) exposure derives largely from studies of uranium miners. We aimed to compare mortality for lung and other cancers to the general population, to estimate excess absolute rate (EAR) and excess relative rate (ERR) from RDP exposure, and to estimate the joint effects of RDP and cigarette smoking in extended follow-up of a cohort of 4137 male uranium miners from the US Colorado Plateau. METHODS: We extended mortality follow-up through 2016 and re-evaluated RDP exposure against original work history and mine records. We calculated standardised mortality ratios (SMRs) compared with a regional population, evaluated EAR of lung cancer mortality using standardised rate ratios and modelled ERR using Cox proportional hazards regression. We evaluated interactions of RDP with smoking pack-years, attained age (AA) and time-since-exposure (TSE). RESULTS: There were 695 lung cancer deaths, including 146 among never-smokers and light smokers. The overall SMR was >4; the EAR per unit RDP exposure increased substantially with smoking pack-years and decades of follow-up. Lung cancer ERR decreased with AA and TSE. ERR attenuation at high exposure rates was smaller than observed elsewhere. Joint effects of RDP and smoking were submultiplicative but greater-than-additive, appearing closer to multiplicative at lower RDP exposures. Pancreas was the only other site showing a significantly positive ERR per unit exposure. CONCLUSIONS: Excess rates of lung cancer mortality persist throughout the lifespan among this cohort of uranium miners. Information about RDP-smoking interactions is of interest for occupational and general population exposure.

Attractive targeted sugar baits (ATSBs) are a novel malaria control tool designed to target mosquitoes outdoors. We conducted a cluster-randomised trial to evaluate the impact of ATSBs on malaria indicators in Kenya. Seventy clusters (≥100 households/cluster) in Siaya county were randomly assigned (1:1) to intervention or control. Pyrethroid-only long-lasting insecticidal nets were distributed to all clusters, aiming for universal coverage. Two ATSBs containing dinotefuran were hung outside household structures in intervention clusters. ATSBs were monitored every two months and replaced every six months over two years. Three consecutive cohorts of randomly selected children (1- < 15 years) were enrolled, aiming to accrue 1,260 person-years over two years of follow-up. Incidence of clinical malaria (fever with a positive malaria test) was the primary outcome. A multilevel Poisson regression model was applied, with clusters as a random intercept and study arm as a fixed effect. Secondary outcomes were malaria prevalence in community residents (≥1 month), and parity of mosquitos captured through human landing catches. In March 2022, ATSBs were delivered to 33,180 of 33,419 (99.3%) household structures in intervention clusters. Overall, 268,268 ATSBs were deployed over two years. Of 2,962 cohort children enrolled (intervention = 1,497; control = 1,465), 2,869 (96.9%) were included in the primary analysis (intervention = 1,461; control = 1,408), contributing 1,445 person-years of follow-up. Malaria incidence was 1.32 episodes per person-years in the intervention arm versus 1.20 in the control (unadjusted incidence rate ratio 1.11; 95% CI: 0.75-1.65; p = 0.598). Of 7,488 community residents surveyed (intervention = 3,760; control = 3,728), 1,474 (39.2%) intervention and 1,461 (39.2%) control participants tested positive for malaria (unadjusted odds ratio [OR] 0.98; 95% CI: 0.60-1.59; p = 0.93). Of 6,457 female anopheles mosquitoes collected (intervention = 4,058; control = 2,399), 3,579 (88.2%) intervention and 1,973 (82.2%) control mosquitoes were parous (OR 1.34; 95% CI: 0.91-1.99; p = 0.14). In Kenya, we found no evidence that ATSBs reduced clinical malaria incidence, malaria prevalence, or vector parity. Trial registration Clinicaltrials.gov (NCT05219565), 22 January 2022.

West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood-brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration.