BACKGROUND: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings. METHODS: A retrospective cross-sectional study was conducted for encounters from four large, integrated health systems participating in the VISION network of adult patients presenting with acute respiratory illness to urgent cares or emergency departments and with positive influenza virus test results during the 2023-2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics. RESULTS: A total of 10,700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (N=5,231), 58% (range across sites: 47-64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (N=3,050), 80% (range across sites: 75-91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (0.57 [95% CI: 0.42-0.78]) and lower odds of same-day dispensing (0.58 [95% CI: 0.36-0.94]) compared to those 18-49 years. CONCLUSIONS: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.

Many strategies have been applied to increase seasonal influenza vaccination; however, gaps in coverage remain. We synthesized the evidence on effectiveness of implementation strategies to increase seasonal influenza vaccination among U.S. adults. Studies performed from February 2010-August 2023 in the United States, focused on seasonal influenza vaccination, and measuring uptake and coverage were included. Guidance from Cochrane was followed. Interventions were mapped to Expert Recommendations for Implementing Change strategies. A total of 1,585 non-duplicate records were identified, full-text screening was performed for 353 records, and 51 studies met inclusion criteria. Among these studies, implementation strategies included those that engaged consumers, trained and educated stakeholders, and supported providers. Considerable heterogeneity was found in the study setting, populations, design, and methods. Substantial study variation limits the ability to conclude which strategies are most effective at increasing influenza vaccination uptake and coverage in U.S. adults.

CONTEXT: Many people living in the 5 inhabited US territories experience high rates of natural hazard exposure and social vulnerability to disaster impacts. Public health workforce development and evidence-based, culturally competent approaches to disaster preparedness, response, and recovery are needed in these regions. PROGRAM: In 2020, the Natural Hazards Center established the Public Health Disaster Research Award Program with funding from the Centers for Disease Control and Prevention. The program's goal is to advance public health disaster research and practice by funding, training, mentoring, and connecting researchers, students, and practitioners in historically underserved areas with high natural hazard risk. Between 2020 and 2022, 26 research teams received up to $50 000 each to investigate public health disasters in 1 or more US territories. The program also supported awardees by providing individual consultations, online trainings, feedback on report drafts, and a virtual group workshop on the public health implications of research. Awardees authored final reports and presented at a public webinar. EVALUATION: In 2023, the Natural Hazards Center developed and distributed an online survey to all principal investigators. The survey evaluated how awardees advanced knowledge about public health disasters in the US territories; what skills, resources, and connections they acquired; and how they translated their research into public health applications and otherwise disseminated their findings. DISCUSSION: Our evaluation showed that the program is advancing knowledge of understudied hazard contexts and socially vulnerable populations in the US territories and supports awardees in sharing their findings with academics, policymakers, and practitioners. Moreover, it expanded the public health disaster workforce by bringing professionals from a diverse range of disciplines and institutions into the field, and by investing in students, early career scholars, and investigators based in US territories. Researchers are working with local partners to apply their findings to practice.

Domestic ferrets (Mustela putorius furo) are important for modeling human respiratory diseases. However, ferret B and T cell receptors have not been completely identified or annotated, limiting immune repertoire studies. Here, we performed long-read transcriptome sequencing of ferret splenocyte and lymph node samples to obtain over 120,000 high-quality full-length immunoglobin (Ig) and T cell receptor (TCR) transcripts. We constructed a complete reference set of the constant regions of ferret Ig and TCR isotypes and chain types. We also systematically annotated germline Ig and TCR variable (V), diversity (D), joining (J), and constant (C) genes on a recent ferret reference genome assembly. We designed new ferret-specific immune repertoire profiling assays by targeting positions in constant regions without allelic diversity across 11 ferret genome assemblies and experimentally validated them using a commercially compatible single-cell-based platform. These improved resources and assays will enable future studies to fully capture ferret immune repertoire diversity.IMPORTANCEDomestic ferrets (Mustela putorius furo) are an increasingly common model organism to study human respiratory diseases such as influenza infections. However, researchers lack ferret-specific reagents and resources to study the immune system and immune response in ferrets. In this study, we developed comprehensive ferret immune repertoire reference resources and assays, which will enable more accurate analyses of the ferret immune system in the future.

BACKGROUND: Understanding virus-virus interactions is important for evaluating disease transmission and severity. Positive interactions suggest concurrent circulation, while negative interactions indicate reduced transmission of one virus when another is prevalent. This study examines interactions among seven respiratory viruses using a Bayesian approach that accounts for seasonality and long-term trends. METHODS: We analyzed data from 43,385 acute febrile illness cases in the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2013-2023). Viruses studied included influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), human parainfluenza viruses 1 and 3 (HPIV-1, HPIV-3), human adenovirus (HAdV), and human metapneumovirus (HMPV). Wavelet coherence analysis investigated synchronous or asynchronous viral co-variation, while a Bayesian hierarchical model estimated pairwise interactions. RESULTS: Among 43,385 participants, 26.0% tested positive for at least one virus, with IAV (9.5%), HAdV (4.1%), RSV (3.6%), and IBV (3.6%) being most frequent. Coinfections occurred in 0.5% of cases, often involving HAdV. Wavelet coherence identified significant synchronization among RSV/HMPV, HPIV-1/HMPV, and other virus pairs, with minimal coherence during the COVID-19 pandemic. Bayesian modeling suggested five virus-virus associations: four positive (RSV/HPIV-3, HMPV/HPIV-1, IBV/HAdV, IBV/HMPV) and one negative (IAV/HAdV). However, when restricting the analysis to the pre-pandemic period, fewer associations remained statistically credible. CONCLUSIONS: Respiratory viruses in Puerto Rico demonstrate patterns of co-circulation that may reflect complex interactions, but these associations appear context-dependent. Findings highlight the need for continued surveillance to better understand virus-virus dynamics and their implications for public health interventions.

PURPOSE: Type 1 hereditary hemochromatosis (HH) can result in iron overload and liver disease if not detected and treated early. Most cases are found among people homozygous for HFE p.Cys282Tyr variants. Compound heterozygosity with the HFE p.His63Asp variant is associated with disease to a lesser degree. We sought to examine the association of HFE variation with HH-related phenotypes and assess the prevalence of testing and diagnosis of HH using All of Us data. METHODS: We used data from 133,978 participants with genetic information linked to medical records. For different HFE genotypes, we examined the prevalence of HH diagnosis codes and related biochemical and clinical phenotypes. RESULTS: Among participants who were p.Cys282Tyr homozygotes, the prevalence of HH diagnosis codes was 22.6% among males and 15.6% among females. Serum transferrin-iron saturation measures were available only for 31.4% of males and 21.1% of females who were p.Cys282Tyr homozygotes. Liver disease, including cirrhosis or hepatocellular carcinoma, was present more among males who were p.Cys282Tyr homozygotes compared with males with no p.Cys282Tyr or p.His63Asp variants (15.5% vs 8.5%, P = .0001). Of the 71 participants who were p.Cys282Tyr homozygotes with indication of liver disease, 32 (45.1%) did not have a serum transferrin-iron saturation measure, and 37 (52.1%) did not have diagnosis codes for HH. CONCLUSION: Limited serum transferrin-iron saturation measures or HH diagnosis codes among p.Cys282Tyr homozygotes, even those with liver disease, suggests potential undertesting and underdiagnosis of type 1 HH in clinical practice and a need for improved awareness, education, and testing around HH.

Human ehrlichiosis is a potentially fatal tickborne disease caused by 3 species: Ehrlichia chaffeensis, E. ewingii, and E. muris eauclairensis. In the United States, 234 confirmed cases of E. ewingii ehrlichiosis were reported to the Centers for Disease Control and Prevention through the National Notifiable Diseases Surveillance System during 2013-2021; average annual incidence was 0.08 cases/1 million population. E. ewingii ehrlichiosis was reported more commonly among older, White, non-Hispanic, and male patients. Incidence and case counts generally increased yearly, except for 2020 and 2021. The highest number of cases were reported from Missouri and Arkansas. We report the geographic expansion of E. ewingii ehrlichiosis and the continued public health challenge of clarifying clinical manifestations of this infection. Clinician education will be essential to implement molecular assays to properly diagnose E. ewingii infection in patients and gain a better understanding of the epidemiology of this emerging disease.

Dengue, a mosquitoborne viral infection, is a public health threat in Puerto Rico, where multiple dengue virus (DENV) serotypes circulate. Dengue causes an acute febrile illness that can progress to severe disease or death. The last outbreak declared by the Puerto Rico Department of Health occurred during 2013. In January 2024, the number of dengue cases in Puerto Rico surpassed the epidemic threshold and remained elevated, prompting the Puerto Rico Department of Health to declare a public health emergency in March 2024. In collaboration with CDC, a dengue outbreak response was initiated to monitor the outbreak and implement vector-control measures alongside public health campaigns to raise awareness about increasing dengue case numbers and strategies to prevent mosquito bites. During 2024, a total of 6,291 confirmed dengue cases were reported; the highest numbers of cases were reported in the municipalities of San Juan (1,200; 17.3%), Carolina (354; 5.1%), and Rincón (252; 3.6%). DENV serotype 3 predominated, accounting for 59.2% of cases with known serotype. Approximately one half of ill patients (52.3%) required hospitalization, with the highest percentages of hospitalizations (33.9%) and severe dengue cases (28.4%) occurring among persons aged 10-19 years. Overall, severe dengue was identified in 4.2% of cases, with 11 reported fatalities (0.2%). Transmission remains elevated in multiple regions, underscoring the need for tailored public health measures, including vaccination among eligible populations, vector management, community outreach, and provider education to facilitate improved outcomes. To reduce the risk for mosquito bites, residents of and visitors to Puerto Rico should consider using repellents, wearing protective clothing, and staying in places with door and window screens.

BACKGROUND: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized. METHODS: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multistate population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality. RESULTS: A total of 26 233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median, 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted odds ratio for death was 1.14 (95% confidence interval [CI], 1.01-1.27) in those starting treatment on day 1 and 1.40 (95% CI, 1.17-1.66) in those starting on days 2-5. CONCLUSIONS: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.

OBJECTIVES: To determine the impact of increased long-acting injectable antiretroviral therapy (Cabotegravir-rilpivirine [CAB/RPV]) use among persons with diagnosed HIV (PWDH) with viral suppression (VLS), per 2021 US Food and Drug Administration (FDA) guidelines, on HIV incidence and levels of VLS in the US. METHODS: We used the HOPE compartmental model to simulate CAB/RPV use during 2023-2035. We first simulated a baseline scenario (no CAB/RPV), in which 69% of PWDH had VLS. We then introduced CAB/RPV in 2023 under two scenarios: (1) where CAB/RPV improved the duration of VLS post-cessation of ART use compared to oral ART; (2) where CAB/RPV additionally improved adherence. We compared cumulative 2023-35 incidence and percentage of PWDH with VLS at year-end 2035 to baseline. RESULTS: When CAB/RPV increased the duration of VLS only, cumulative incidence was reduced up to 9%, and VLS increased up to 4%. When CAB/RPV also improved ART adherence, incidence was reduced up to 19.5%, and VLS increased up to 9%. CONCLUSIONS: CAB/RPV, even if only used among PWDH with VLS, may reduce HIV incidence and increase VLS, due to longer-lasting VLS post-cessation of usage. If CAB/RPV also improves ART adherence, incidence is further reduced. Improved clinical efficacy of CAB/RPV may translate to improved population-level outcomes, even in limited use cases.

Mosquito-transmitted viruses such as dengue are a global and growing public health challenge. Without widely available vaccines, mosquito control is the primary tool for fighting the spread of these viruses. New mosquito control technologies are needed to complement existing methods, given current challenges with scalability, acceptability, and effectiveness. A field trial was conducted in collaboration with the Communities Organized to Prevent Arboviruses project in Ponce, Puerto Rico, to measure entomological and epidemiological effects of reducing Aedes aegypti populations using Wolbachia incompatible insect technique. We packed and shipped Wolbachia-males from California and released them into 19 treatment clusters from September 2020 to December 2020. Preliminary evaluation revealed sub-optimal Wolbachia-male densities and impact on the wild-type population. In 2021, we shifted to a phased release strategy starting in four clusters, reducing the mosquito population by 49% (CI 29-63%). We describe the investigation into male quality and other factors that may have limited the impact of Wolbachia-male releases. Laboratory assays showed a small but significant impact of packing and shipping on male fitness. However, mark-release-recapture assessments suggest that male daily survival rates in the field may have been significantly impacted. We compared induced-sterility levels and suppression of the wild population and found patterns consistent with mosquito population compensation in response to our intervention. Analysis of epidemiological impact was not possible due to very low viral transmission rates during the intervention period. Our entomological impact data provide evidence that Wolbachia incompatible-male releases reduced Ae. aegypti populations, although efficacy will be maximized when releases are part of an integrated control program. With improvement of shipping vessels and shipped male fitness, packing and shipping male mosquitoes could provide a key solution for expanding access to this technology. Our project underscores the challenges involved in large and complex field effectiveness assessments of novel vector control methods.

OBJECTIVES: Evidence indicates that people living with HIV (PLHIV) are more impacted by COVID-19. The burden of SARS-CoV-2 infection among PLHIV is unknown in Nigeria. METHODS: We conducted repeated cross-sectional SARS-CoV-2 serosurveys in 14 states and the Federal Capital Territory in Nigeria among PLHIV who had an HIV viral load (VL) test during April 2022 to January 2023. Evidence of SARS-CoV-2 immunoglobulin G (IgG) antibodies was assessed using a multiplex bead assay to measure IgG to spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins to identify potential infection and/or vaccination status. RESULTS: Between April 2022 and January 2023, 47,614 remnant VL samples were included and tested for SARS-CoV-2 antibodies. Seroprevalence of SARS-CoV-2 infection, defined as IgG antibodies to spike and RBD591 [S+] and nucleocapsid [N+], (S+N+), ranged between 21.1% (95% confidence intervals [CI]: 11.4-31.8) in Ekiti State in January 2023 to 71.4% (95% CI 71.9-81.9) in Gombe State in November 2022, with overall steady trends within and between states over time, across age and sex. CONCLUSION: High rates of SARS-CoV-2 antibody seroprevalence among PLHIV in Nigeria were observed. This underscores the need to understand the association between HIV and SARS-CoV-2 to inform strategies to reduce the threat posed by COVID-19.

Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

BACKGROUND: Serology for dengue viruses (DENV) and Zika virus (ZIKV) has been hindered by antibody cross-reactivity, which limits the utility of these tests for surveillance and assessment of sero-status. Our aim was to develop a multiplexed IgG-based assay with increased accuracy to assess the history of previous DENV and ZIKV infections. METHODS: We developed and assessed the analytical performance of a sample-sparing, multiplexed, microsphere-based serological assay using domain III of the envelope protein (EDIII) of DENV serotypes 1-4 and ZIKV, the most variable region between each virus. We used a reference panel of well-characterised serum samples from US-based travellers or residents of southeast Asia, central America, or Puerto Rico, who were naive or immune to either or both DENV and ZIKV, to develop an algorithm for detecting previous exposure to DENV and ZIKV and identify optimal positivity cutoffs to maximise assay performance. To independently confirm the performance of the assay and algorithm, we used a second test set of previously collected samples from healthy children (aged 9-16 years) living in Puerto Rico, whose DENV and ZIKV serostatus had been defined using the gold-standard virus neutralisation assay. We evaluated the performance of the multiplex assay compared with the gold-standard assay by estimating sensitivity and specificity for identification of past exposure to ZIKV and DENV. FINDINGS: The multiplexed EDIII assay showed reproducible results over different days and a linearity range from μg to pg levels for various EDIII antigens. Using a reference panel of serum samples from individuals who were DENV naive (n=136), DENV immune (n=38), ZIKV naive (n=67), and ZIKV immune (n=28), we optimised the assay and developed a testing algorithm that was 94·9% (95% CI 83·1-99·1) sensitive and 97·1% (92·7-98·9) specific for identifying previous exposure to DENV, and 100% (95% CI 88·0-100) sensitive and 97·0% (89·8-99·5) specific for identifying previous exposure to ZIKV. In an analysis with an independent test set of 389 samples, the assay and algorithm had 94·2% (89·9-97·1) sensitivity and 92·9% (87·3-96·5) specificity for DENV, and 94·1% (88·7-97·4) sensitivity and 95·0% (90·0-98·0) specificity for ZIKV. INTERPRETATION: The multiplexed EDIII serology assay can accurately identify the history of previous infection with either DENV or ZIKV. This high-throughput and sample-sparing assay is a promising new tool for supporting flavivirus surveillance, epidemiological and clinical studies, and serological testing for dengue vaccine eligibility. Further studies are needed to reduce the cost of the assay, eliminate high background in some samples, and to assess performance in DENV-endemic and ZIKV-endemic countries. FUNDING: US National Institutes of Health.

BACKGROUND: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses. METHODS: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness (ARI) who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter). RESULTS: Overall, 74,000 encounters in children and adolescents aged 6 months - 17 years (3,479 hospitalizations, 70,521 ED/UC encounters) and 267,606 in adults aged ≥18 years (66,828 hospitalizations, 200,778 ED/UC encounters) were included. Across care settings, among children and adolescents 15% (2,758/17,833) of cases versus 32% (18,240/56,167) of controls had received vaccination. Among adults, 25% (11,632/46,614) of cases versus 44% (97,811/220,992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI]: 44-69%) against hospitalization and 58% (95% CI: 56-60%) against ED/UC encounters for children and adolescents, and 39% (95% CI: 35-43) against hospitalization and 47% (95% CI: 46-49%) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A. CONCLUSIONS: Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023-2024 influenza season.

Dengue is a mosquitoborne viral illness that can cause acute febrile illness, severe disease, or death. Worldwide, the number of dengue cases is increasing. During the last dengue outbreaks in Puerto Rico throughout 2010-2013, dengue virus (DENV) serotype 1 (DENV-1) predominated, and the largest proportion of cases occurred among adolescents and young adults aged 10-19 years. Dengue case data from January 1, 2010-November 4, 2024, were obtained from the Puerto Rico Department of Health. Bivariate analyses were conducted to evaluate the distribution of cases by patient age, DENV serotype, and hospitalization status during three periods: 2010-2019, 2020-2022, and 2023-2024. During 2023-2024, the median age of dengue cases increased to 26 years (95% CI = 25-27 years) compared with that during 2020-2022 (17 years; 95% CI = 17-18 years) and 2010-2019 (19 years; 95% CI = 19-19 years). After >10 years of DENV-1 predominance, the proportions of DENV serotypes 2 (DENV-2) and 3 (DENV-3) increased significantly during 2023-2024, with DENV-3 replacing DENV-1 as the predominant serotype. In addition, the proportion of dengue patients who were hospitalized increased from 35.7% (2010-2019) to 53.5% (2023-2024). The current dengue outbreak in Puerto Rico marks a shift in serotype predominance to DENV-3 and increasing percentages of cases in older age groups (61.7% in adults aged ≥20 years), although a high proportion of cases still occur among adolescents aged 10-19 years (29.5%). The current dengue outbreak also has a higher rate of hospitalizations than those in previous years. Understanding the changing epidemiology of dengue is crucial to guiding public health strategies for dengue control, including clinical management, surveillance and health care system resilience, and public outreach and education.

IMPORTANCE: Seasonal influenza is associated with substantial disease burden. The relationship between census tract-based social vulnerability and clinical outcomes among patients with influenza remains unknown. OBJECTIVE: To characterize associations between social vulnerability and outcomes among patients hospitalized with influenza and to evaluate seasonal influenza vaccine and influenza antiviral utilization patterns across levels of social vulnerability. DESIGN, SETTING, AND PARTICIPANTS: This retrospective repeated cross-sectional study was conducted among adults with laboratory-confirmed influenza-associated hospitalizations from the 2014 to 2015 through the 2018 to 2019 influenza seasons. Data were from a population-based surveillance network of counties within 13 states. Data analysis was conducted in December 2023. EXPOSURE: Census tract-based social vulnerability. MAIN OUTCOMES AND MEASURES: Associations between census tract-based social vulnerability and influenza outcomes (intensive care unit admission, invasive mechanical ventilation and/or extracorporeal membrane oxygenation support, and 30-day mortality) were estimated using modified Poisson regression as adjusted prevalence ratios. Seasonal influenza vaccine and influenza antiviral utilization were also characterized across levels of social vulnerability. RESULTS: Among 57 964 sampled cases, the median (IQR) age was 71 (58-82) years; 55.5% (95% CI, 51.5%-56.0%) were female; 5.2% (5.0%-5.4%) were Asian or Pacific Islander, 18.3% (95% CI, 18.0%-18.6%) were Black or African American, and 64.6% (95% CI, 64.2%-65.0%) were White; and 6.6% (95% CI, 6.4%-68%) were Hispanic or Latino and 74.7% (95% CI, 74.3%-75.0%) were non-Hispanic or Latino. High social vulnerability was associated with higher prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support (931 of 13 563 unweighted cases; adjusted prevalence ratio [aPR], 1.25 [95% CI, 1.13-1.39]), primarily due to socioeconomic status (790 of 11 255; aPR, 1.31 [95% CI, 1.17-1.47]) and household composition and disability (773 of 11 256; aPR, 1.20 [95% CI, 1.09-1.32]). Vaccination status, presence of underlying medical conditions, and respiratory symptoms partially mediated all significant associations. As social vulnerability increased, the proportion of patients receiving seasonal influenza vaccination declined (-19.4% relative change across quartiles; P < .001) as did the proportion vaccinated by October 31 (-6.8%; P < .001). No differences based on social vulnerability were found in in-hospital antiviral receipt, but early in-hospital antiviral initiation (-1.0%; P = .01) and prehospital antiviral receipt (-17.3%; P < .001) declined as social vulnerability increased. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, social vulnerability was associated with a modestly increased prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support among patients hospitalized with influenza. Contributing factors may have included worsened baseline respiratory health and reduced receipt of influenza prevention and prehospital or early in-hospital treatment interventions among persons residing in low socioeconomic areas.

OBJECTIVE: Pet ownership among people experiencing homelessness (PEH) is common, but access to shelter, veterinary care, and flea-preventative products for PEH who own pets in the US is not well described. We sought to evaluate current knowledge of fleas and flea-borne diseases and characterize practices around pets and service animals among staff at homeless shelters and outreach organizations. METHODS: In-person surveys were administered to staff at homeless shelters and on outreach teams in 7 states from August 2022 to April 2023 to evaluate knowledge, attitudes, and practices and to assess homeless shelter/organizational characteristics. RESULTS: Surveys were administered to 333 staff members at 60 homeless shelters and among 29 outreach teams. Seventy-eight percent of homeless shelters allowed pets or service animals. Only 2% of homeless shelters and 7% of outreach teams provided veterinary care; 15% of homeless shelters and 7% of outreach teams provided flea preventatives. Nearly three-quarters of surveyed homeless shelter staff responded that no steps were taken to treat fleas at their shelters. CONCLUSIONS: Veterinary care and availability of flea-preventative products are limited in homeless shelter and outreach organizations serving people experiencing homelessness. CLINICAL RELEVANCE: Pets of PEH might be at an increased risk of flea infestation and flea-borne diseases because of limited access to veterinary care and preventatives. Improving knowledge and access to flea prevention, screening, and treatment are critical to ensure PEH and their pets can consistently access homeless shelters or outreach services, and to prevent flea-borne disease transmission.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

CONTEXT: Adverse childhood experiences (ACEs), substance use disorders (SUDs), and overdose are interconnected issues impacting individuals and communities at multiple levels of the social ecology and across generations. Few studies describe approaches that intentionally and simultaneously address these issues. PROGRAM: This paper examines activities of 15 sites across the country that were designed to simultaneously prevent ACEs, SUD, and overdose. This paper describes the work at the intersection as well as gaps and opportunities. Describing ways to implement intersectional programming may assist other organizations in taking similar steps in their communities. IMPLEMENTATION: From December 2020 through July 15, 2023, funded sites received technical assistance from the National Association of County and City Health Officials and the Centers for Disease Control and Prevention for 18 months to support the implementation, adaptation, and/or expansion of evidence-based programs to address ACEs, SUD, and overdose. EVALUATION: Activities were coded to identify intersectional interventions that addressed ACEs, SUD, and overdose. Most of the ACEs prevention strategies and overdose prevention priority areas/guiding principles from which communities could choose were represented. Most activities were implemented with caregivers and families and addressed ACEs through interventions to lessen harm or to promote social norms. Primary prevention and coordination of resources were the most used overdose prevention priority area/guiding principle. DISCUSSION: It is possible to address the intersection of ACEs, SUD, and overdose on a local level. Opportunities to further address the intersection include incorporating more secondary and tertiary prevention strategies, expanding economic supports, and increasing the work focused on equity.

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs.

A survey of US infectious disease physicians indicated that few regularly reviewed wastewater surveillance (WWS) data but many reported examples of how WWS has affected or could affect their clinical practice. WWS data can be useful for physicians, but increased communication between public health professionals and physicians regarding WWS could improve its utility.

During the 2023-2024 influenza season, the Republic of Moldova, a lower-middle income country seeking accession into the European Union, independently financed their influenza vaccine supply transitioning from external support from the Partnership for International Vaccine Initiatives, a collaboration conceived in 2015. As part of this transition, a mixed-methods evaluation was conducted from May 2023 - January 2024 to identify current strengths and weaknesses of the influenza vaccination program. A total of 157 interviews were conducted: one with the National Immunization Program (NIP), six with district health officers, 18 at health facilities, 18 with caregivers/parents, 34 with healthcare workers, 43 with adults with chronic diseases, 19 with pregnant women, and 13 vaccine observation sessions; further five expert interviews with an international organization, the insurance company, senior government officials in public health and within the ministry of health, and those involved with COVID-19 were conducted. The Republic of Moldova's NIP has benefited from decades of experience, internal commitments to progress, and contributions from external partners. Despite this progress, the evaluation recognized four areas for improvement. Recommendations from the evaluation assessment included: 1) develop a national strategy for immunization, including the establishment of national goals in consultation with the national immunization technical advisory group (NITAG); 2) expand immunization communications and advocacy initiatives, particularly to adults and pregnant individuals; 3) leverage trusted patient-doctor relationships and encourage vaccination as a healthcare norm with physician specialists; and 4) conduct operations research to better understand vaccine hesitancy in populations such as pregnant individuals. Additional thematic findings emphasized the importance of ensuring timely receipt of vaccine doses into the country no later than September, as medical providers reported difficulty administering doses when vaccines were delivered after September. Our findings outline ways to further strengthen the Republic of Moldova's self-sustained annual influenza vaccination program.

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.

Leptospirosis, an acute bacterial zoonotic disease, is endemic in Puerto Rico. Infection in approximately 10%-15% of patients with clinical disease progresses to severe, potentially fatal illness. Increased incidence has been associated with flooding in endemic areas around the world. In 2022, Hurricane Fiona, a Category 1 hurricane, made landfall and inundated Puerto Rico with heavy rainfall and severe flooding, increasing the risk for a leptospirosis outbreak. In response, the Puerto Rico Department of Health (PRDH) changed guidelines to make leptospirosis cases reportable within 24 hours, centralized the case investigation management system, and provided training and messaging to health care providers. To evaluate changes in risk for leptospirosis after Hurricane Fiona to that before the storm, the increase in cases was quantified, and patient characteristics and geographic distribution were compared. During the 15 weeks after Hurricane Fiona, 156 patients experienced signs and symptoms of leptospirosis and had a specimen with a positive laboratory result reported to PRDH. The mean weekly number of cases during this period was 10.4, which is 3.6 as high as the weekly number of cases during the previous 37 weeks (2.9). After Hurricane Fiona, the proportion of cases indicating exposure to potentially contaminated water increased from 11% to 35%, and the number of persons receiving testing increased; these factors likely led to the resulting overall surge in reported cases. Robust surveillance combined with outreach to health care providers after flooding events can improve leptospirosis case identification, inform clinicians considering early initiation of treatment, and guide public messaging to avoid wading, swimming, or any contact with potentially contaminated floodwaters.

Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for seven tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the five best-performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9- to 16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the four best-performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity in detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to the Zika virus. For the detection of previous DENV infections, the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation. IMPORTANCE: The Advisory Committee on Immunization Practices (ACIP) has set forth recommendations that dengue pre-vaccination screening tests must exhibit at least 98% specificity and 75% sensitivity. Our research rigorously assesses the performance of various commercial tests against these benchmarks using well-characterized specimens from Puerto Rico. The findings from our study are particularly relevant given FDA approval and ACIP recommendation of Sanofi Pasteur's Dengvaxia vaccine, highlighting the need for accurate pre-vaccination screening tools.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.