Journal of Travel Medicine

Background. Climate change is intensifying extreme weather events (EWEs) with potentially profound consequences for zoonotic disease dynamics, yet the mechanisms linking EWEs to highly pathogenic avian influenza (HPAI) H5N1 outbreaks remain poorly characterized. The ongoing H5N1 panzootic, responsible for infection in over 500 avian and mammalian species, as well as nearly 1000 human cases and 477 deaths worldwide, provides a critical opportunity to evaluate how climate conditions shape spillover risk at landscape scales. Methods. We compiled a county-month dataset of confirmed H5N1 detections across the contiguous United States from 2022 to 2024 and integrated it with satellite-derived climate metrics, storm event data, and wild bird activity data. We trained and validated a gradient boosting machine classifier to predict outbreak risk and characterize predictor relationships. Results. Our model achieved strong discriminative performance (AUC-ROC = 0.856; AUC-PR = 0.237, representing a 7-fold improvement over chance) and high recall (0.726), supporting its utility as an early warning tool. Human population and temperature-related variables were the most influential predictors: cold temperature shocks and prolonged low temperatures were consistently associated with elevated outbreak risk, likely through enhanced environmental viral persistence, wild bird habitat compression, and allostatic stress-driven immunosuppression in reservoir hosts. Among storm variables, high wind coverage elevated risk, potentially via aerosol dispersal of contaminated particulates, while tornado activity showed an inverse relationship, consistent with documented avoidant behavior in migratory birds. Wild bird reservoir density showed a strong positive monotonic relationship with outbreak risk. Conclusions. Our analyses demonstrate that routinely available environmental and infection data can be used to predict HPAI outbreak risk at fine spatiotemporal scales. These findings demonstrate the divergent roles of short- versus long-term environmental exposures in HPAI spillover dynamics, as well as the potential for machine learning-based surveillance tools to inform targeted biosecurity interventions and early warning systems.

This novel study detected persistent low level infections of Elephant Endotheliotropic Herpesviruses (EEHV), that can cause highly pathogenic Elephant Hemorrhagic Disease (EHD) in Loxodonta and Elephas, and co-infection of presumed less pathogenic Elephant Gammaherpesviruses (EGHV), in skin nodule biopsies, saliva and tissues collected from 43 wild L. africana (savannah elephant) in Botswana, Kenya, South Africa and Zimbabwe; in saliva from 25 wild L. cyclotis (forest elephant) in Gabon; and in saliva collected over seven years from 7 wild-born L.africana at Six Flags Safari Park, USA; and in saliva, blood and tissues from an additional 200 L. africana in USA zoos. DNA from these samples was extracted in our USA laboratories and amplified by conventional polymerase chain reaction using three-round nested primer sets designed specifically to screen for known EEHV and EGHV genes loci and to discover new species and subtypes. Sanger sequencing of purified DNA from nearly all samples yielded unambiguous positive genetic matches to previously known Loxodonta-associated EEHV2, EEHV3A, EEHV3B, EEHV6, EEHV7A, and EGHV1B, EGHV2, EGHV3B, EGHV4B, EGHV5B and discovered novel types EEHV3C-H and EEHV7B and the prototype EGHV1B. Many of the primer sets used could also have detected known Elephas-associated EEHV1A, EEHV1B, EEHV4, and EEHV5 if present in these samples, but they did not. Our extensive library of EEHV and EGHV sequences from wild and zoo Loxodonta, (as well as from 100 zoo Elephas maximus not discussed in this review), is a significant contribution to the elephant virology community, particularly for comparing subtypes types of EEHV found in pathogenic cases of EHD in zoos as well as determining and comparing species and subtypes of EEHV present in existing zoo herds, and in individual elephants being transported between zoos, and for importation of wild elephants into existing zoo herds.

Influenza viruses present a significant public health risk, causing substantial illness and death in humans each year. Seasonal flu vaccines must be updated regularly, and their effectiveness often decreases due to mismatches with circulating strains. Furthermore, inactivated vaccines do not provide protection against shifted influenza viruses that have the potential to cause a pandemic. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b is prevalent among wild birds worldwide and is causing a multi-state outbreak affecting poultry and dairy cows in the United States (US) since March 2024. In this study, we have generated a NS1 deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1, namely LPhTXdNS1, and validated its safety, immunogenicity, and protection efficacy in a prime vaccination regimen against wild-type (WT) A/Texas/37/2024 H5N1. The attenuation of LPhTXdNS1 in vitro was confirmed by its reduced replication in cultured cells and inability to control IFN{beta} promoter activation. In C57BL/6J mice, LPhTXdNS1 has reduced viral replication and pathogenicity compared to WT A/Texas/37/2024 H5N1. Notably, LPhTXdNS1 vaccinated mice exhibited high immunogenicity that reach its peak at weeks 3 and 4 post-immunization, leading to robust protection against subsequent lethal challenge with WT A/Texas/37/2024 H5N1. Altogether, we demonstrate that a single dose vaccination with LPhTXdNS1 is safe and able to induce protective immune responses against H5N1. Both safety profile and protection immunity suggest that LPhTXdNS1 holds promise as a potential solution to address the urgent need for an effective vaccine in the event of a pandemic for the treatment of infected animals and humans.

Zoos may serve as sentinel sites for zoonotic vector-borne diseases. West Nile virus (WNV) and Usutu virus (USUV) are closely related orthoflaviviruses transmitted between Culex mosquitoes and a bird reservoir. Both viruses can also infect mammals, including humans, where they may cause symptoms and, more rarely, hospitalization and death. However, serological cross-reactivity between WNV and USUV complicates their differential diagnosis. Here, we aimed to reconstruct the dynamics of emergence of WNV in a zoo located in a newly affected area in Europe, using ELISA and Virus Neutralization Test (VNT) serological analysis of 1707 animal sera collected between 2015 and 2024. Combining this data in a model accounting for cross-reactivity with USUV, we estimated yearly forces of infection (FOI) by both viruses, and thus found that WNV likely circulated in the area one year prior to the first cases reported to the passive surveillance system. Our results also showed that, in the zoo, mammals and reptiles had a lower risk of infection than birds (relative risk of 0.14 [0.05; 0.28]), and that the exposure of birds to water (aquatic lifestyle or proximity to stagnant water) affected the risk. Finally, we estimated diagnosis parameters, including the sensitivity of the VNT (80.4% [76.5%; 84.3%]), the expected VNT titer value, and the level of serological cross-reactivity between viruses during the VNT. To conclude, our modelling framework allowed to disentangle the co-circulation of two closely related viruses, a crucial point in ensuring the reliable sentinel surveillance of these vector-borne zoonotic pathogens.

Toxoplasma gondii is a globally prevalent zoonotic parasite with multiple life stages and transmission routes, including ingestion and transplacental transmission. It is a major cause of abortion in sheep, goats and pigs, among other production animals, worldwide. While Type II strains are common in livestock in North America and Europe, non-archetypal, non-clonal genotypes are highly prevalent in South America. This study aimed to determine the molecular epidemiology of T. gondii strains causing sheep abortion in Uruguay. Phylogenomic analyses confirmed significant divergence among typed strains and revealed similarities with genotypes previously detected in the human population. Two novel strains, were isolated and characterized, uncovering the connection between their genetic makeup and phenotypes. Differences in virulence could be correlated to differences in gene copy number of the pseudo kinase ROP5 - further highlighting this virulence factor as relevant in wild strains. Whole-genome sequencing further confirmed the divergence among Uruguayan isolates, uncovering at least three distinct evolutionary origins. Overall, our findings highlight the circulation of virulent non-clonal lineages with links to human infections and underscore the importance of furthering genomic surveillance in South America to better understand Toxoplasmas transmission dynamics, pathogenic potential, and zoonotic risk.

Background and ObjectivesPatient portals have become essential infrastructure for healthcare delivery following the 21st Century Cures Act, yet adoption remains inequitable. Understanding demographic and geographic determinants of portal activation is critical for addressing digital health disparities, particularly among neurology patients who face unique access barriers. We examined the demographic, geographic, and neighborhood-level factors associated with patient portal activation among neurology patients at multiple geographic scales in the Washington, DC metropolitan area. MethodsWe conducted a retrospective cohort study of 72,417 adult neurology patients seen at two academic medical centers sharing an electronic health record in Washington, DC (February 2021-February 2026). We examined portal activation using multivariable logistic regression and geographic analysis at four nested scales: the metropolitan catchment area, DCs eight wards, individual census tracts (via geocoded patient addresses), and individual DC residents. ResultsPortal activation was 64.7% overall. Activation varied by race/ethnicity (Non-Hispanic White 76.1%, Non-Hispanic Black 57.0%, Non-Hispanic Asian 57.6%, Hispanic 55.0%) and geography (DC Ward 2: 82.0% vs. Ward 7: 48.0%). Ward-level educational attainment (r = 0.948), broadband access (r = 0.889), and income (r = 0.811) were strongly correlated with activation. Within individual wards, Non-Hispanic White patients activated at 84-91% while Non-Hispanic Black patients activated at 48-64%, demonstrating that neighborhood resources alone do not explain disparities. DiscussionPatient portal activation is shaped by demographic, socioeconomic, and geographic factors operating at multiple levels. Persistent within-ward racial disparities indicate that geographically targeted interventions must be paired with culturally tailored approaches to achieve digital health equity.

This study evaluates the feasibility of implementing artificial intelligence (AI)-driven disease surveillance systems at Julius Nyerere International Airport (JNIA) in Tanzania, a key hub for regional and international travel. Through a mixed-methods approach combining qualitative interviews and quantitative surveys, the research assesses the infrastructure, human resource capacity, and regulatory frameworks necessary for AI integration. Findings indicate that while Port Health Officers are strongly optimistic about AIs potential to enhance disease detection, the airport faces significant barriers, including outdated infrastructure, insufficient technical resources, and a lack of trained personnel. Ethical and privacy concerns, particularly surrounding data security, also emerged as key challenges, compounded by limited public awareness and the socio-cultural acceptability of AI systems. Furthermore, the study identifies gaps in national policies and inter-agency coordination that hinder the effective implementation of AI technologies. The research concludes that while current conditions render AI adoption infeasible, strategic investments in infrastructure, workforce training, and policy development could pave the way for future integration, enhancing public health surveillance at JNIA and potentially other airports in low- and middle-income countries. This study contributes critical insights into the barriers and opportunities for AI-driven disease surveillance in low-resource settings, specifically focusing on a high-priority transit point, international airports. It emphasizes the importance of region-specific solutions to enhance health security in East Africa and supports the broader global health agenda by advocating for international collaboration and the development of scalable disease surveillance systems. Future research should explore pilot AI implementations at other airports to evaluate real-world challenges and refine AI systems for broader applicability, including cost-effectiveness analyses and integration of public perspectives on AI.

Typhoid fever remains a significant public health challenge in low- and middle-income countries. In 2018, The World Health Organization recommended a single dose typhoid conjugate vaccine (TCV) for routine immunization in endemic settings; however, evidence guiding booster doses remains limited. Homologous TCV booster doses have demonstrated immune boosting. This study assessed the immunogenicity and safety of a heterologous booster using a Vi capsular polysaccharide-CRM197 TCV (Vi-CRM) administered 5-6 years after primary vaccination with a Vi capsular polysaccharide tetanus toxoid TCV (Vi-TT) in children. Children previously enrolled in a Phase 2 trial were recruited. Participants who had received TCV at 9-11 or 15-23 months were given a Vi-CRM booster at 6-7 years of age (Booster-TCV group), and controls received their first TCV dose at the same age (1st-TCV group). Serum anti-Vi IgG concentrations were measured at baseline and 28 days post-vaccination. Solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) were recorded. Among 147 children enrolled, 87 received a second and 60 received a first TCV dose. Baseline anti-Vi IgG geometric mean titers (GMT) were higher in the Booster-TCV group (21.5 EU/mL; 95% CI: 17.2-26.8) than in the 1st-TCV group (5.5 EU/mL; 95% CI: 4.5-6.7). At day 28, GMTs rose markedly in both groups: 5140.0 EU/mL (95% CI: 4302.0-6141.3) in the Booster-TCV group and 2084.8 EU/mL (95% CI: 1724.4-2520.5) in the 1st-TCV group. Local reactions and systemic AEs were mild. No SAEs were observed. Vi-TT-induced immunity persisted for at least 5-6 years, and a heterologous booster triggered a strong immune response with universal seroconversion. These findings support heterologous prime-boost strategies to maintain protection in school-age children and inform optimization of TCV schedules in endemic regions.

Background: Dengue emerged as a new public health threat in the Rohingya refugee camps in Coxs Bazar, Bangladesh, in 2021 and expanded into large-scale upsurges in subsequent years. Evidence on dengue epidemiology and clinical presentation in protracted refugee settings remains limited, despite the need for stronger outbreak preparedness and case management in these contexts. Objectives: To describe the epidemiological, clinical, and diagnostic characteristics of the dengue upsurge among Rohingya refugees and surrounding host communities in Coxs Bazar, Bangladesh, and to identify predictors of inpatient admission and diagnostic positivity patterns. Methods: This retrospective observational study used anonymized surveillance data from the International Organization for Migration (IOM) dengue patient database. Rapid diagnostic test (RDT)-confirmed dengue cases identified across 36 IOM-supported health facilities in Ukhiya and Teknaf between 1 October 2021 and 31 December 2024 were included. Demographic, epidemiological, clinical, and laboratory variables were summarized using descriptive statistics. Weekly incidence was aggregated by epidemiological week and calendar year, and epidemic growth and decay phases were modelled using phase-specific Poisson regression. Multivariable logistic regression was used to identify predictors of inpatient admission and to examine associations between delay in presentation and RDT positivity patterns, adjusting for age and sex. Results: A total of 35,581 RDT-confirmed dengue cases were reported, of which 90.2% occurred among Rohingya refugees. The median age was 17 years (IQR 7-30), and 46.0% of cases were among children aged 0-14 years. Annual caseload increased from 1,011 in 2021 to 11,752 in 2022, 10,669 in 2023 and 12,149 in 2024, with seasonal peaks during the monsoon period and progressively later peaks and longer epidemic tails over time. Poisson models showed decreasing growth rates across years (r=0.449 in 2021 to r=0.091 in 2024) with increasing doubling times, while decay rates remained broadly comparable (halving time ~4.4-6.0 weeks). Overall, 8.0% of cases required inpatient admission, 1.3% were referred, and four deaths were reported (case fatality <0.1%). In multivariable analysis, inpatient admission was associated with older age ([&ge;]60 vs 0-14: aOR 2.31), delayed presentation (aOR 1.06 per day), refugee status (aOR 1.39), presence of any World Health Organization (WHO) warning sign (aOR 26.60), low systolic BP (aOR 2.84) and chronic co-morbidity (aOR 6.07). In addition, males had lower odds of admission than females (aOR 0.88). NS1 antigen alone was positive in 62.1% of cases, IgM alone in 33.6%, and dual positivity in 4.3%. Longer delay from symptom onset to presentation was strongly associated with IgM-only positivity compared with NS1-only positivity (adjusted models controlling for age and sex). Conclusion: Sustained dengue preparedness is required in Coxs Bazar, including strengthened surveillance, community-based early referral, targeted monitoring of high-risk groups, environmental vector control, and phase-appropriate use of NS1 and IgM/IgG diagnostics to reduce missed diagnoses and prevent progression to severe disease. These findings highlight the need for a policy shift from episodic outbreak response toward sustained dengue preparedness in humanitarian settings, including strengthened surveillance systems, integrated diagnostic strategies, community-based early referral, and coordinated vector control interventions.

BackgroundDuring 2021-2022, high pathogenicity avian influenza (HPAI) caused mass mortality in wild birds across Europe, with Northern Gannets (Morus bassanus) among the most affected. Following the outbreak, unusual alterations in the species characteristic pale iris were observed in some individuals. MethodsOpportunistically captured gannets on Bass Rock (n=52), selected to represent a range of iris pigmentation, were examined. Slit-lamp biomicroscopy, indirect ophthalmoscopy, rebound tonometry and photography were performed. Iris pigmentation was classified as normal, mottled or black. Eleven birds underwent avian influenza virus (AIV) serology. Histopathology was performed on two eyes. ResultsAbnormal iris pigmentation was found in 74% of adult and immature gannets, with 61% affected bilaterally. Additional signs consistent with uveitis were present in 77% of affected birds. Iris pigmentation abnormalities were positively associated with AIV H5 seropositivity (Fishers exact test, P=0.018). Histopathology from affected eyes showed increased melanin deposition and disorganisation, including loss of a distinct anterior layer of melanocytic cells and hypertrophy of melanocytes within the iris stroma. LimitationsField conditions limited uniform lighting and concurrent serology. ConclusionsIris pigmentation changes were associated with prior HPAI exposure and frequently accompanied by signs of uveitis, suggesting iris alterations may indicate past infection and potential chronic sequelae.

Background: Although the hemagglutination inhibition (HAI) titer remains the gold standard correlate of protection against influenza, it does not fully capture the broader antibody responses that contribute to immunity. Methods: We analyzed immune responses in paired pre-infection and convalescent sera from 306 RT-PCR-confirmed A/H3N2 infections from two household studies (2014-18) in Managua, Nicaragua. Antibody responses were measured by HAI and enzyme-linked immunosorbent assays (ELISAs) against full-length hemagglutinin (HA), the HA stalk, and neuraminidase (NA). Participants were classified as HAI responders ([&ge;]4-fold HAI rise), alternate responders (no HAI rise but [&ge;]4-fold boost in [&ge;]1 ELISA), or no-response individuals (no [&ge;]4-fold rise in any assay). We compared demographic, clinical, and pre-infection antibody characteristics across these groups. We also analyzed predictors of an NA response. Results: Overall, 77% of participants had HAI seroconversion or a 4-fold rise. Among the 23% HAI non-responders, 62% had alternate antibody responses. No-response individuals had the highest pre-infection HAI and full-length HA titers (p < 0.0001), the lowest viral loads, and the fewest fever or influenza like illness (ILI) symptoms (p < 0.01). An NA response was more common among symptomatic individuals (p = 0.0483) and those with low or high baseline NA titers. Conclusions: High baseline HAI titers can limit detectable 4-fold rises and are associated with milder illness. Evaluating additional immune responses may capture a more complete picture of the host response to infection, thereby improving surveillance and informing vaccine development. Keywords: Influenza A/H3N2; Hemagglutination inhibition (HAI); Neuraminidase antibodies; symptomatic vs asymptomatic infection; correlates of protection.

Background: Dengue is rapidly emerging in parts of Europe. How households value vector control attributes, and whether inferences depend on decision models or message framing, is unclear. Methods: We conducted a split-ballot online experiment among adults in Italy and France, as well as a hotspot subsample from Marche, Italy. National samples included 1,505 respondents in Italy and 1,501 in France; 183 respondents were recruited in Marche. Participants were randomised to a discrete choice experiment (random utility maximisation) or a regret-based choice experiment (random regret minimisation) and to one of three pre-task messages (control, loss aversion, community values). Each respondent completed 12 choice tasks comparing two dengue control programmes and an opt-out. We estimated mixed logit and mixed random-regret models with random parameters and treatment effects. Results: Across frameworks, nearby cases and high mosquito prevalence were the dominant drivers of programme uptake, whereas cost and operational burden were secondary. In pooled analyses, loss-aversion messaging increased the weight on high mosquito prevalence in both models (from 0.483 to 0.547 in the utility model; from 0.478 to 0.557 in the regret model). Cost effects were small nationally but larger in the hotspot subsample. Conclusions: Risk salience dominates preferences for dengue vector control in these European settings. Random utility and random regret models yield consistent rankings of attributes but differ in behavioural interpretation and some secondary effects; messaging effects were modest and context dependent.

Background and aimTrauma healing with low-intensity ultrasound is effective for different types of injuries affecting both soft tissues and bones. The work aimed to disclose the healing potential of a new type of ultrasound, ultra-wideband low-intensity mechanical waves (UMUS), and to compare its effects with those of low-intensity pulsed ultrasound (LIPUS) in a model of trauma. Material and methodsThe work was performed on 2-to 3-month-old male Wistar rats. The model of tail amputation was created, and a transducer emitting UMUS (1-7 MHz, 0.22 mW/cm2) was applied daily for 10 days to the surface of the trauma site in animals that were timely immobilized. LIPUS (1.5 mHz, 30.0 mW/cm2) was used in a separate group of animals. Sham-stimulated rats were used as a control. The intensity of collagen expression in the subdermal tissue was assessed in van Gieson-stained sections, whereas in the UMUS group, expression of CD31, CD34, VEGF, and Ki67 was analyzed. ResultsStarting on the 20th day after trauma, UMUS-treated animals demonstrated a statistically significant decrease in the surface area of the traumatic zone compared to the control, whereas LIPUS-treated rats showed this difference on the 30th day of observation. Starting from the 30th day, a significantly greater reduction in the surface of trauma was observed in UMUS, with complete closure achieved in 6 out of 9 rats (P=0.019 vs control), whereas in LIPUS-treated animals, a similar result was observed in 2 out of 8 rats (P>0.05). In UMUS-treated rats, heightened expression of collagen in animals with LIPUS exceeded control data by 7.84% (P=0.034), while the expression in rats with UMUS exceeded data in LIPUS-treated rats by 14.71% (P=0.013). Increased expression of CD31, CD34, VEGF, and Ki67 was observed in UMUS-treated rats. ConclusionsUMUS treatment accelerated healing and reduced wound size, and increased the expression of collagen, CD31, VEGF, CD34, and Ki67, supporting angiogenesis and collagen formation. Effects are more pronounced compared to LIPUS treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/717366v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@1b82f66org.highwire.dtl.DTLVardef@12ffd81org.highwire.dtl.DTLVardef@1ac385aorg.highwire.dtl.DTLVardef@1a7da17_HPS_FORMAT_FIGEXP M_FIG C_FIG

Equine asthma (EA) is a highly prevalent, chronic, inflammatory disease of the lower airways ranging from mild-to-moderate to severe clinical presentations. Diagnosis currently relies on bronchoalveolar lavage fluid (BALF) cytology, an invasive method associated with interobserver variability, which highlights the need for more reproducible approaches. MicroRNAs (miRNAs) are small noncoding RNAs involved in post-transcriptional gene regulation. They are stable and readily detectable in body fluids and have shown promising results as biomarkers in human asthma. The aim of this study was to characterize miRNA abundance profiles in BALF and serum from horses with distinct EA endotypes to evaluate their biomarker potential and explore their involvement in disease pathogenesis. A total of 43 horses were included and classified as either EA (n=32) or controls (n=11), based on clinical examination and BALF cytology. The EA horses were further divided into three endotypes based on BALF inflammatory cell composition: neutrophilic asthma (n=10), mastocytic asthma (n=15), and mixed asthma (n=7). RNA was isolated from both serum and BALF samples and analyzed by quantitative real-time PCR (qPCR) targeting 103 miRNAs linked to asthma and pulmonary inflammation in humans. Differential miRNA abundance was analyzed across EA endotypes. The most significantly differentially abundant miRNAs were used for in silico target prediction and pathway enrichment analyses. Horses with mixed EA had significantly lower levels of eca-miR-125a-3p and eca-miR-125b-5p in BALF compared to controls. Additionally, eca-miR-146a-5p abundance was significantly increased in BALF from horses with neutrophilic EA compared to mastocytic EA. Target and pathway enrichment analyses for eca-miR-146a-5p identified immune-relevant pathways, such as MAPK and T-cell receptor signaling, supporting its involvement in inflammatory processes associated with asthma. This study identified three promising candidates, eca-miR-125a-3p, eca-miR-125b-5p, and eca-miR-146a-5p, as potential biomarkers associated with different EA endotypes. These miRNAs are interesting candidates for further investigation in an independent cohort.

Importance Missed outpatient appointments, including no-shows and cancellations, may disrupt continuity of care and be associated with worse outcomes, but long-term system-wide patterns and clinical implications are not well characterized. Objective To characterize variation in missed appointment rates in the Veterans Health Administration (VHA) over time and by geographic location, visit modality, and preexisting conditions, and to evaluate associations between missed appointment rates and adverse outcomes among veterans with posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI). Design Cohort study using VHA Corporate Data Warehouse outpatient appointment data from January 1, 2000, through December 31, 2024. Setting National integrated health care system of the VHA. Participants System analysis includes all scheduled outpatient appointments with a valid status, and outcome analysis includes veterans with PTSD (n = 1 429 890) or TBI (n = 554 553), diagnosed before 2023. Exposures For system -level analyses, missed appointment rates were calculated. In outcome analyses, 2023 missed appointment rates were categorized into tertiles within the cohort and appointment type. Main Outcomes and Measures One year risks of all-cause hospitalization, all-cause mortality, and hospitalization or death beginning January 1, 2024. Results Among 2,162,520,880 outpatient appointments from 2000 to 2024, 6.5% were no-shows and 25.4% were canceled. Across facilities, no-show rates ranged from 3.5% to 14.1%, patient-initiated cancellation rates from 9.7% to 26.0%, and clinic-initiated cancellation rates from 8.5% to 17.9%. In 2023, veterans with amputation, Parkinson disease, PTSD, or TBI had higher missed appointment rates than veterans without these conditions. Among veterans with PTSD, the highest no-show tertile, compared with none, was associated with higher mortality (HR, 1.91; 95% CI, 1.84-1.98) and hospitalization or death (HR, 1.07; 95% CI, 1.05-1.08). Among veterans with TBI, the highest no-show tertile was associated with hospitalization or death (HR, 1.65; 95% CI, 1.61-1.69). Conclusions and Relevance Missed outpatient appointments were common in the VHA and varied substantially across facilities and over time. Among veterans with PTSD or TBI, higher missed appointment rates, particularly no-shows, were associated with increased risks of hospitalization and mortality, suggesting that these patterns may help identify high-risk veterans for targeted outreach.

Background Tuberculosis (TB) remains a critical public health challenge, with two-thirds of the global TB burden in ten Asian countries. Social vulnerabilities, comorbidities, health inequity, multi-dimensional poverty, malnutrition, and barriers to healthcare access continue to fuel TB epidemic. Inability to detect asymptomatic and sub-clinical TB, combined with passive approach in service delivery and overreliance on smear microscopy, leads to delayed diagnosis, a substantial burden of undetected cases, and continuing TB transmission in the communities. In such a context, the introduction and scale-up of active case-finding approaches - including community-based TB screening using highly sensitive screening tools and novel rapid diagnostics - becomes a strategic priority to interrupt transmission. The growing availability of multiple screening and diagnostic options makes evidence-based decision-making increasingly complex. Methods To estimate the potential epidemiological impact and cost implications of scaling up TB diagnostics and community-based screening in ten high-burden Asian countries, we constructed a mathematical model and evaluated multiple intervention scenarios. We then assessed and compared four service delivery models: 1) digital ultraportable chest x-ray (UPCXR) & Xpert/Truenat in community, 2) digital UPCXR in community and Xpert/Truenat at health facilities, 3) digital UPCXR in community and near point of care (nPOC) at health facilities, 4) nPOC in community & Xpert/Truenat at health facilities - for total investment required and projected health benefits for their cost-effectiveness. Results and conclusions The modelling study indicated that strengthening health facility capacity (with enhanced TB screening, expanded molecular diagnostics, reduced loss to follow-up, private sector standard of care, leading to increased treatment coverage & quality of active disease treatment and reduced post-treatment relapse, scale-up of TB preventive treatment (TPT), and provision of nutritional support to 80% of TB patients and their household contacts) can significantly reduce TB incidence and mortality; however, community-wide mass screening remains essential to achieving TB elimination targets . Targeted screening of vulnerable populations demonstrated greater cost-effectiveness than untargeted screening approaches. Achieving the End TB goals will ultimately require an effective TB vaccine with high population-level coverage. AI-enabled digital UPCXR-based screening combined with Xpert/Truenat testing at the community level demonstrated maximum epidemiological impact potential, while the most cost-efficient model is Digital UPCXR in the community combined with nPOC testing at health facilities. An investment of USD 12.7 billion over the next five years in community-level implementation of digital UPCXR and molecular diagnostics could avert an additional 9.8 million TB cases and 1.9 million deaths across ten Asian countries over a ten-year horizon.

For millions of immunocompromised individuals, vaccines may not elicit adequate protection from infections, so alternative strategies for pre-exposure prophylaxis are essential. There is only one non-vaccine product authorized in the U.S. as pre-exposure prophylaxis against COVID-19: the monoclonal antibody pemivibart. We previously showed that pemivibart had lower neutralizing activity in vitro against many recent dominant SARS-CoV-2 variants, such as KP.3.1.1, NB.1.8.1, and LP.8.1.1, than it had against JN.1, which was dominant when the antibody was first authorized. The manufacturer of pemivibart (Invivyd) recently initated clinical testing of a new monoclonal antibody derived from pemivibart, VYD2311, but there are no available studies of the activity of VYD2311 against dominant and emerging SARS-CoV-2 variants. Here, using pseudovirus neutralization assays, we measured the neutralizing activity of laboratory-synthesized VYD2311 and pemivibart against dominant and emerging SARS-CoV-2 variants, including XFG, NB.1.8.1, and the genetically distant BA.3.2.2. We found that VYD2311 potently neutralized all tested variants in vitro, dramatically more so than pemivibart. Combined with interpretation of earlier clinical trials of a parental antibody product, we conclude that VYD2311 is a promising candidate for passive immunoprophylaxis against COVID-19, particularly for those who do not respond well to vaccination.

Introduction: Modeling when influenza epidemics typically occur can help countries optimize surveillance, time clinical and public health interventions, and reduce the burden of influenza. Methods: We used influenza virus detections reported during 2011-2024 by 180 countries to the Global Influenza Surveillance and Response System, excluding COVID-19 pandemic impacted years (2020-2023). We analyzed data by calendar year (week 1-52) or shifted year (week 30-29) time windows, based on when most influenza detections occurred in each country. For countries with sufficient data, we computed generalized additive models (GAMs) of each country's weekly influenza-positive tests to smooth and impute time series distributions. From these GAMs, we calculated each country's normalized weekly influenza burden. Country-specific normalized time series were grouped using hierarchical k-means clustering reducing the Euclidean distance between time series within clusters. We calculated cluster-specific GAMs to estimate average seasonal timing. Countries without sufficient data were assigned to a cluster based on population-weighted latitudinal distance to a cluster's mean latitude. Results: We identified five clusters, or epidemic zones, from 111 countries with sufficient data. The influenza burden in epidemic zones A and B was consistent with a northern hemisphere pattern, with most influenza detections occurring during October-April (A) and September-March (B), while epidemic zones D and E were characterized by southern hemisphere-like seasonal timing, with most influenza burden occurring during May-November. Epidemic zone C had most influenza burden occurring during September-March; most countries assigned to this cluster were in the tropics. Conclusion: Epidemic zones may serve as a useful tool to strengthen and optimize influenza surveillance for global health decision-making (e.g., during vaccine strain composition discussions) and to guide country preparedness efforts for seasonal influenza epidemics, including the timing of enhanced surveillance, as well as the procurement and delivery of vaccines and antivirals.

Background: Rectal cancer (RC) is traditionally grouped within colorectal cancer (CRC), despite growing evidence of distinct epidemiologic features. However, global comparative assessments of lifetime risks of RC relative to CRC remain limited. We aimed to estimate lifetime risks of developing and dying from RC and CRC worldwide and to examine geographic, socioeconomic, and temporal variations in the proportional contribution of RC within CRC. Methods: Age-specific incidence and mortality estimates for RC and CRC across 185 countries were obtained from GLOBOCAN 2022, together with population and all-cause mortality data from the United Nations. Lifetime risks of incidence (LRI) and mortality (LRM) were calculated using the adjusted-for-multiple-primaries (AMP) method by sex, country, region, and Human Development Index (HDI). The RC-to-CRC lifetime risk ratio quantified the proportional contribution of RC. Temporal trends were assessed in 42 countries using Cancer Incidence in Five Continents Plus (CI5plus) data and average annual percent change (AAPC). Results: In 2022, the global lifetime risk of developing RC was 1.61% and dying from RC was 0.95%, accounting for approximately 35% of the corresponding CRC lifetime burden (4.61% and 2.68%). Absolute lifetime risks of both RC and CRC increased with HDI. In contrast, the proportional contribution of RC varied markedly, peaking at 41%-43% in Central and South-Eastern Asia but falling below 20% in the Caribbean and Central America, and showed a negative association with HDI. The LRI/LRM ratio increased with socioeconomic development. Temporal analyses showed increasing LRI trends in 17 of 42 countries for CRC versus 9 for RC, while declines occurred in 14 countries for RC and 11 for CRC. Conclusions: RC constitutes a substantial yet epidemiologically distinct component of the global CRC burden. Its proportional contribution varies across regions and does not parallel absolute risk patterns, supporting the need for subsite-specific surveillance and prevention strategies.

Methods: Using Global Burden of Disease (GBD) data, we analyzed prevalence, incidence, mortality, and disability-adjusted life years (DALYs) rates across global and 21 GBD regions from 1990-2023. Joinpoint regression identified temporal trends, age-period-cohort models analyzed effect contributions, Das Gupta decomposition quantified demographic and epidemiological impacts, inequality indices assessed health equity, and Bayesian models projected 2024-2038 trends. Results: In 2023, the global number of children and adolescents with asthma reached 131 million, with an age-standardized prevalence rate (ASPR) of 1,789.9 per 100,000. From 1990 to 2023, the global ASPR and age-standardized incidence rate (ASIR) of asthma in children and adolescents showed an upward trend, while the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate (ASDR) exhibited a downward trend. Among the 0-14 age group, the disease burden was greater in males than in females, whereas in the 15-19 age group, males had a lower disease burden than females. Projections indicate that over the next 15 years, the overall disease burden will continue to decline; however, female mortality rates and DALYs rates are projected to show an upward trend. Conclusions: The increasing prevalence and incidence rates, coupled with declining mortality and DALYs rates of asthma among children and adolescents globally, underscore the necessity for targeted public health interventions. These findings provide crucial insights for early diagnosis, treatment optimization, and global health policy formulation.