IMPORTANCE: Evidence is needed on the economic favorability of a 2023-2024 COVID-19 vaccination program to support policy decisions on recommendations for COVID-19 vaccination. OBJECTIVE: To measure the cost-effectiveness of vaccination with a 2023-2024 COVID-19 mRNA vaccine in adults aged 18 years or older compared with no updated vaccination (with a 2023-2024 vaccine). DESIGN, SETTING, AND PARTICIPANTS: This decision analytic modeling study used a simulation model to compare outcomes for hypothetical cohorts of vaccinated and unvaccinated, immunocompetent adults stratified by age (18-49 years, 50-64 years, and >/=65 years). Parameters were drawn from primary and published data to represent characteristics of the US adult population. The interventions included vaccination with a 2023-2024 mRNA vaccine against COVID-19-associated illness compared with no updated vaccination (with a 2023-2024 vaccine) using a 1-year analytic time frame. A phase 2 analysis also considered an intervention strategy of vaccination with an additional dose of 2023-2024 COVID-19 mRNA vaccine. MAIN OUTCOME AND MEASURE: The incremental cost-effectiveness ratio as reported in 2023 US dollars per quality-adjusted life-year. RESULTS: Vaccination averted substantial numbers of cases, hospitalizations, intensive care unit stays, and deaths across age groups. For adults aged 18 to 49 years and 50 to 64 years, vaccination yielded incremental cost-effectiveness ratios of $115 588 and $25 787 per quality-adjusted life-year gained, respectively. For individuals aged 65 years or older, vaccination was cost saving. Sensitivity analyses indicated that the results were most sensitive to the cost per vaccine dose, vaccine effectiveness, and probability of hospitalization. In phase 2 analyses, an additional dose strategy was only economically favorable in higher-risk scenarios for individuals aged 65 years or older. CONCLUSIONS AND RELEVANCE: In this modeling study, economic favorability of COVID-19 vaccination varied by age. Cost-effectiveness results for individuals in the 2 older age groups were favorable and generally robust to changes in parameter inputs, while results for the younger age group were sensitive to parameter input changes. As the evidence base for COVID-19 vaccination and burden of illness evolves, it may be important to continue to update and revise the economic evaluation of vaccination. The Advisory Committee on Immunization Practices considered these results in its decision to recommend vaccination with the 2023 to 2024 COVID-19 mRNA vaccines.

Surveillance of enteric organisms can identify outbreaks and support control measures. The BIOFIRE FilmArray Gastrointestinal Panel (FilmArray GI) is the most common culture-independent diagnostic test (CIDT) used in Wisconsin to diagnose enteric infections. State clinical laboratories have raised concerns about inaccurate Campylobacter detection with the FilmArray GI. The Wisconsin State Laboratory of Hygiene (WSLH) evaluated the percentage of positivity and culture confirmations stratified by CIDT for Campylobacter, Salmonella, and STEC from 2018 to 2024. We further analyzed the transport time of Campylobacter specimens and the melt curves of specimens that tested positive by FilmArray GI. Campylobacter, Salmonella, and STEC specimens tested on the FilmArray GI had increases in percentage of positivity compared to those tested on other CIDTs. Salmonella and STEC specimens positive by FilmArray GI, compared to other CIDTs, had no significant culture confirmation differences. However, Campylobacter specimens positive by FilmArray GI had significantly lower culture confirmations than positive specimens from other CIDTs (62% vs. 78%; P < 0.05). Campylobacter culture confirmations were lower for FilmArray GI specimens, compared to other CIDTs, regardless of how many days the specimen spent in transport in 2023. Additionally, we found atypical melt curves among specimens positive by FilmArray GI with cultures that did not grow Campylobacter. Taken together, the higher percentage of positivity, the lower percentage of culture confirmation, and the atypical melt curves suggest that the FilmArray GI might yield false-positive Campylobacter results. These findings emphasize the importance of public health surveillance to identify potential issues with commercially available diagnostic tests.IMPORTANCEEnteric pathogens cause ~9.4 million illnesses annually in the United States. Clinical laboratories rely on culture-independent diagnostic testing platforms (CIDTs) for rapid and accurate diagnosis of enteric pathogens. Campylobacter, Salmonella, and Shiga-toxin-producing Escherichia coli (STEC) are three of the most identified enteric bacterial infections in Wisconsin. The BioFire FilmArray Gastrointestinal panel (FilmArray GI) is currently the most common CIDT used by Wisconsin clinical laboratories to diagnose Campylobacter, Salmonella, and STEC infections. However, the FilmArray GI has had notable issues and recalls in the past. Here, we used public health surveillance data to assess platform performance for these organisms. We analyzed percent positivity and culture confirmations based on testing platforms. Through our analysis, we identified potential false-positive Campylobacter results from the FilmArray GI, which were associated with atypical melt curve profiles on the BioFire platform. Public health surveillance can help identify potential issues with diagnostic platforms.

INTRODUCTION: Community-acquired pneumonia (CAP) is an important cause of hospitalisation among older adults. Assessing costs of CAP hospitalisation aids in economic evaluation of preventive interventions and guides policy decisions. METHODS: We estimated resource utilisation rates and costs from a societal perspective among adults aged >60 years admitted with CAP in eight public and eight private hospitals in four Indian cities (ie, National Capital Region-Delhi, Kolkata, Pune and Chennai) from December 2018 to March 2020. We interviewed patients, reviewed medical records and bills to estimate resources used, direct medical cost of diagnosis and treatment; direct non-medical cost of travel, lodging and food; and indirect cost of patients and caregivers' lost income from admission to discharge. Mean costs with SD by hospital type, age group, chronic condition, critical care (intensive care unit, ICU) and virus detection are presented in US dollars (US$). Linear regression after log transformation was conducted to identify determinants of total cost. RESULTS: We analysed data from 1009 CAP patients in private (63%) and public (37%) hospitals with a median age of 68 (IQR: 63-75) years. Influenza was detected in 121 (12%) and respiratory syncytial virus (RSV) in 21 (2%). Mean length of stay was 6.2 (SD 4.8) days; 37% required ICU admission. Antibiotics and antivirals were used in 96% and 23% of admissions, respectively. Mean (SD) CAP hospitalisation cost was US$305 (244) in public and US$1210 (1019) in private hospitals; US$1024 (1095) in influenza and US$943 (778) in RSV-associated CAP. Regression analysis showed that cost was higher in hospitalisation in private hospitals, those requiring ICU care and among persons with comorbid conditions. CONCLUSIONS: Substantial resources were used, and costs were incurred during CAP hospitalisation among older adults. The findings could aid in cost-benefit analyses of interventions to reduce pneumonia burden, including influenza, RSV or pneumococcal vaccination in older adults.

Foodborne botulism is a rare and potentially fatal illness caused by ingestion of food containing botulinum neurotoxin produced by the bacterium Clostridium botulinum or other neurotoxigenic Clostridium species. C. botulinum can grow in improperly prepared or stored food items such as home-canned or home-preserved vegetables. On June 25, 2024, the Fresno County Department of Public Health and California Department of Public Health, in collaboration with CDC and two local hospitals, initiated an investigation of a foodborne botulism outbreak linked to two related family gatherings in Fresno County, California. A total of 31 persons attended one or both gatherings. Eight attendees had symptoms compatible with botulism and received botulism antitoxin; five of eight had botulinum neurotoxin type A (BoNT/A) detected in serum. Patients had hospital stays ranging from 2 to 42 days, six patients were admitted to an intensive care unit, and two required invasive mechanical ventilation; all survived. Epidemiologic investigation identified home-preserved prickly pear cactus pads (nopales) included in a homemade salad and served at both events as a food item of interest; laboratory testing confirmed the nopales salad as the source of BoNT/A. This foodborne botulism outbreak is the first reported to be linked to home canning of nopales, a popular vegetable used in traditional Mexican cuisine. Rapid public health coordination is essential for responses to foodborne botulism outbreaks. Enhancing community and clinician awareness of foodborne botulism by increasing access to culturally and linguistically accessible home food preservation and canning guidelines might help prevent future outbreaks.

The rapid global expansion of Aedes aegypti-borne diseases such as dengue, chikungunya, and Zika has positioned this mosquito as a key target for vector control programs. These programs rely heavily on insecticide use, leading to the widespread emergence of insecticide resistance. Understanding the molecular basis of resistance is essential for developing effective management strategies. In this study, we employed a whole-transcriptome (RNA-seq) approach to analyze gene expression in three Ae. aegypti populations from Mexico that underwent four generations of laboratory selection with deltamethrin. Several cytochrome P450 genes (CYP6AG4, CYP6M5, CYP307A1) and a chitin-binding peritrophin-like gene (Ae-Aper50) were significantly overexpressed following selection, supporting roles for both detoxification and midgut protection. We also observed a consistent downregulation of cuticular protein genes in deltamethrin-selected groups relative to the baseline populations, suggesting their involvement in baseline tolerance rather than induced resistance. Additionally, the overexpression of immune- and stress-related genes, including the RNA helicase MOV-10, indicates that insecticide selection may trigger broader physiological responses. These findings highlight complex, multi-pathway transcriptomic changes associated with resistance development in Ae. aegypti.

Mpox emerged on the global scale in 2022 and predominately affected gay, bisexual, and other men who have sex with men (GBMSM). Stigma related to mpox is a potential harm for individuals experiencing multiple levels of marginalization who may already be discriminated against in family, health care, and other social domains. To understand perceived mpox stigma among cisgender GBMSM in the United States, we conducted a study within the American Men's Internet Survey with 824 cisgender GBMSM >= 15 years from August 5 to 15, 2022. Perceived mpox stigma was most prevalent among non-Hispanic Black individuals (13.9%) compared to non-Hispanic White individuals (6.0%) and particularly among men aged 25-29 (15.1%) compared to men aged 40+ (5.6%). In adjusted logistic regression models, mpox stigma was significantly associated with knowing someone who tested for mpox (adjusted odds ratio (aOR) = 4.3 95% confidence interval, CI [2.1, 9.0]), knowing someone who was vaccinated for mpox (aOR = 2.1; 95% CI [1.2, 3.7]), or having an unexplained rash in the 3 months prior to survey completion (aOR = 3.6; 95% CI [1.9, 7.0]). These initial findings suggested people who were more connected to mpox-affected social networks and also those who had symptoms consistent with mpox were more likely to experience stigma. Taken together, these data suggest the potential harmful impact of mpox-related stigma by affecting those who would most benefit from services. Moreover, these data suggest the importance of real-time stigma measurement and mitigation for both rapidly emergent and chronic infectious diseases to improve equity, reduce fear and misinformation, and optimize the impact of public health responses. (PsycInfo Database Record (c) 2025 APA, all rights reserved) Impact Statement Stigma can have far-reaching consequences. It can exacerbate health disparities, influence social networks, and discourage individuals from seeking preventative health care, including vaccination. This study's findings highlight that, even if not widespread, stigma can concentrate in marginalized groups and drastically affect individuals' lives. By acknowledging and addressing stigma, public health agencies and providers can foster inclusivity, limit fear, promote trust in health care systems, and improve the overall health and resilience of communities. (PsycInfo Database Record (c) 2025 APA, all rights reserved)

The Centers for Disease Control and Prevention (CDC) funds tuberculosis (TB) Centers of Excellence (COEs) that support TB control and prevention efforts in the United States. In 2018, the TB COEs conducted a multiphased assessment among U.S. staff involved in TB service delivery to identify needs related to TB training, resources, and medical consultation. Representatives from each TB COE and CDC's Division of TB Elimination formed a workgroup to guide the design of the needs assessment. The group used an online survey for data collection. Participants were staff working in some capacity on TB within the United States, Puerto Rico, and the U.S. Virgin Islands. Staff could be in non-public health (e.g., community health center, hospital, laboratory, private practice) or public health (state or local health department staff responsible for TB) settings and did not have to be a clinical health care provider (N = 1,482). We identified four priority areas for future TB training and education efforts. These areas include (1) focus on key topics; (2) tailor training and products to different professions, settings, and skill levels; (3) keep learners updated on the latest resources and best practices; and (4) use a mix of training methods and formats. The findings highlighted future priorities for TB training and education and were shared with health department TB programs throughout the United States.

Since the worldwide eradication of smallpox in 1980, orthopoxvirus vaccines had been used nearly exclusively by persons at risk for occupational exposure to orthopoxviruses, including Monkeypox virus, the virus that causes mpox. However, during recent years, the epidemiology of mpox has been changing in countries where the animal reservoirs are believed to live and where endemic transmission has been known to occur for decades. CDC issues outbreak-specific vaccination recommendations based on the epidemiology at the time specific cases or clusters are identified; however, because of the increased risk for U.S. mpox outbreaks, the Advisory Committee on Immunization Practices (ACIP) reviewed results from a previously performed modified Grading of Recommendations Assessment, Development, and Evaluation of the 2-dose JYNNEOS (smallpox and mpox vaccine, live, nonreplicating) vaccination series and an Evidence to Recommendations (EtR) framework addressing multiple domains (e.g., benefits, harms, and target population values and preferences). Based on this assessment, ACIP recommended the use of JYNNEOS (a live, replication-deficient vaccinia virus vaccine) for persons aged ≥18 years at risk for mpox during an mpox outbreak (irrespective of clade). Because the cause of future mpox outbreaks and the populations affected by these outbreaks remain uncertain, public health authorities will continue to issue outbreak-specific vaccination guidance when outbreaks occur. A clade IIb mpox outbreak that began in 2022 continued to cause substantial morbidity and mortality >1 year later. Although CDC had issued outbreak-specific vaccination guidance, it was anticipated that the outbreak would be protracted. For this reason, ACIP reviewed a second EtR framework about outbreaks and in 2023 recommended JYNNEOS for persons aged ≥18 years at risk for acquiring mpox during the multinational clade IIb outbreak. As of 2025, cases continue to occur; however, the future need for the recommendation will be reassessed as the outbreak evolves. Mpox vaccination is not routinely recommended for health care personnel during mpox outbreaks, including during the ongoing clade IIb outbreak.

Several oxylipins are potent lipid mediators that regulate diverse aspects of health and disease and whose quantitative analysis by liquid chromatography-mass spectrometry (LC-MS) presents substantial technical challenges. As members of the lipidomics community, we developed technical recommendations to ensure best practices when quantifying oxylipins by LC-MS.

Maternal respiratory syncytial virus (RSV) vaccine and nirsevimab, a long-acting monoclonal antibody for infants aged 0-7 months and children aged 8-19 months who are at increased risk for severe RSV disease, became widely available for prevention of severe RSV disease among infants and young children during the 2024-25 RSV season. To evaluate the association between availability of these products and infant and child RSV-associated hospitalization rates, the rates among children aged <5 years were compared for the 2024-25 and 2018-20 RSV seasons using data from the RSV-Associated Hospitalization Surveillance Network (RSV-NET) and New Vaccine Surveillance Network (NVSN). Among infants aged 0-7 months (eligible for protection with maternal vaccination or nirsevimab), 2024-25 RSV-associated hospitalization rates were lower compared with 2018-20 pooled rates (estimated relative rate reductions of 43% [RSV-NET: 95% CI = 40%-46%] and 28% [NVSN: 95% CI = 18%-36%]). The largest estimated rate reduction was observed among infants aged 0-2 months (RSV-NET: 52%, 95% CI = 49%-56%; NVSN: 45%, 95% CI = 32%-57%) and during peak hospitalization periods (December-February). These findings support Advisory Committee on Immunization Practices' recommendations for maternal vaccination or nirsevimab to protect against severe RSV disease in infants and highlight the importance of implementing the recommendations to protect infants as early in the RSV season as possible, before peak transmission, and for infants born during the RSV season, within the first week of life, ideally during the birth hospitalization.

Nirsevimab is a long-acting monoclonal antibody that protects infants and young children against severe respiratory syncytial virus (RSV) disease. Children are eligible for one 50 mg dose, one 100 mg dose, or two 100 mg doses of nirsevimab based on age, weight, time of year, maternal vaccination, and risk of severe disease. In winter 2023/2024, we developed a model to project the number of nirsevimab doses needed to immunize all eligible U.S. children during the 2024/2025 season. We grouped all births from March 2023 through March 2025 into weekly cohorts, partitioned those cohorts based on eligibility criteria, and computed eligibility for each partition. In the absence of maternal RSV vaccination, we estimated U.S. children would be eligible to receive 4.3 million nirsevimab doses in 2024/2025, of which 48% would be 100 mg doses. Projections of total eligibility can be used to inform production goals and avoid shortages of nirsevimab.

BACKGROUND: Influenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of "PIVOT," a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment. METHODS: 14-20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018. RESULTS: In year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2. CONCLUSIONS: The results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults. CLINICAL TRIALS REGISTRATION: NCT03330132.

Antimicrobial resistance (AMR) is an urgent threat to public health, but gaps in surveillance limit the detection of emergent novel threats and knowledge about the global distribution of AMR genes. International travelers frequently acquire AMR organisms, and thus may provide a window into AMR dynamics in otherwise poorly monitored regions and environments. To assess the utility of travelers as global AMR sentinels, we collected pre- and post-travel stool samples from 608 travelers, which were screened for the presence of extended-spectrum beta-lactamase producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales. A total of 307 distinct AMR organisms were sequenced in order to determine genotypic patterns and their association with travel region and behavior. Travel-associated AMR organisms were overwhelmingly E. coli, which exhibited considerable phylogenetic diversity regardless of travel region. However, the prevalence of resistance genes varied by region, with bla (CTX-M-55) and bla (CTX-M-27) significantly more common in travelers returning from South America and South-Eastern Asia, respectively. Hybrid assembly and plasmid reconstruction revealed the genomic neighborhood of bla (CTX-M-55) frequently matched a motif previously linked to animal populations. Contact with animals was also associated with virulence factors in acquired AMR organisms, including carriage of the ColV plasmid, a driver of avian pathogenic E. coli. We identified novel variants of the mcr-1 gene in strains acquired from Western Africa, highlighting the potential for traveler surveillance to detect emerging clinical threats. Ongoing efforts to track travel-acquired organisms could complement existing global AMR surveillance frameworks.

A Rocky Mountain spotted fever (RMSF) epidemic has spread through the state of Baja California, Mexico over the last decade and a half, beginning in Mexicali, and subsequently to Tijuana and to Ensenada by 2018. In October of 2022, we surveyed dogs and homes in randomly selected Áreas Geoestadisticas Básicas (AGEBs) with and without reported human cases. Brown dog ticks (Rhipicephalus sanguineus sensu lato) were found on 33.9% of dogs and in the yards of 23.6% of homes. Homes from AGEBs with cases had over a 6-fold increased odds of ticks being present in the yard than AGEBs without reported cases. Both dogs that were permitted to roam and the presence of roaming dogs in the neighborhood were strongly associated with tick infestation of dogs and homes. No ticks or blood samples were polymerase chain reaction-positive for Rickettsia (R.) rickettsii, the causative agent of RMSF, although 54.6% of dogs were seropositive for spotted fever group rickettsiae, and 17.4% were seropositive for typhus group rickettsiae. R. massiliae and R. felis were detected in eight (1.3%) and 29 (4.8%) ticks, respectively; and R. felis was also detected in eight (4.6%) dog blood samples. Although the pathogenic potential of these other rickettsial species and their role in RMSF transmission remains unclear, our data on tick burdens in dogs and homes as risk factors for RMSF exposure provide further support to the pivotal need to reduce tick burdens and the numbers of roaming dogs to successfully manage the RMSF epidemic in northern Mexico.

BACKGROUND: The 2022 mpox outbreak in the United States disproportionately affected gay, bisexual, and other men who have sex with men (GBMSM). Uptake of mpox testing may be related to symptomology, sociodemographic characteristics, and behavioral characteristics. OBJECTIVE: This study aimed to describe suspected mpox symptoms and testing uptake among a sample of GBMSM recruited via the internet in the United States in August 2022. METHODS: We conducted a rapid internet-based mpox survey from August 5 to 15, 2022, among cisgender men 15 years and older who had previously participated in the 2021 American Men's Internet Survey. We estimated the prevalence of suspected mpox symptoms (fever or rash or sores with unknown cause in the last 3 mo) and uptake of mpox testing. We calculated adjusted prevalence ratios (aPRs) and 95% CIs for associations between participant characteristics and suspected mpox symptoms and summarized characteristics of GBMSM reporting mpox testing. Among symptomatic GBMSM who did not receive mpox testing, we described testing self-efficacy, barriers, and facilitators. RESULTS: Of 824 GBMSM, 126 (15.3%) reported at least 1 mpox symptom in the last 3 months; 58/126 (46%) with rash or sores, 57 (45.2%) with fever, and 11 (8.7%) with both. Increased prevalence of suspected mpox symptoms was associated with condomless anal sex (CAS; aPR 1.53, 95% CI 1.06-2.20). Mpox testing was reported by 9/824 GBMSM (1%), including 5 with symptoms. Most GBMSM reporting mpox testing were non-Hispanic White men (7/9 vs 1 Black and 1 Hispanic or Latino man), and all 9 lived in urban areas. Most reported having an sexually transmitted infections test (8/9), 2 or more partners (8/9), CAS (7/9), and group sex (6/9) in the last 3 months. Of those tested, 3 reported living with HIV and all were on treatment, whereas the remaining 6 men without HIV reported current pre-exposure prophylaxis (PrEP) use. Of symptomatic GBMSM who did not report mpox testing, 47/105 (44.8%) had low mpox testing self-efficacy. Among those with low self-efficacy, the most common barriers to testing were not knowing where to get tested (40/47, 85.1%) and difficulty getting appointments (23/47, 48.9%). Among those with high testing self-efficacy (58/105, 55.2%), the most common facilitators to testing were knowing where to test (52/58, 89.7%), convenient site hours (40/58, 69%), and low-cost testing (38/58, 65.5%). CONCLUSIONS: While all GBMSM who reported testing for mpox were linked to HIV treatment or PrEP, those with symptoms but no mpox testing reported fewer such links. This suggests targeted outreach is needed to reduce structural barriers to mpox services among GBMSM in rural areas, Black and Hispanic or Latino GBMSM, and GBMSM living with HIV. Sustaining and scaling community-tailored messaging to promote testing and vaccination represent critical interventions for mpox control among GBMSM in the United States.

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.

BACKGROUND: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease. METHODS: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and study participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients. RESULTS: We enrolled a total of 15,833 participants, of whom 3,308 (21%) were positive for DENV infection. Of 2,644 cases with serotype result by RT-PCR, 559 corresponded to DENV1, 1,002 to DENV2, 760 to DENV3 and 323 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock. CONCLUSIONS: These findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.

We assessed mpox vaccine communication and sexual behavior among U.S. MSM during the 2022 mpox outbreak. Less than 40% of respondents asked a new male sex partner about their mpox vaccination status. Mpox vaccine communication was positively associated with condomless anal sex and group sex. Mpox vaccine communication is low but may inform and sexual behaviors among MSM.

OBJECTIVE: To determine whether differences exist in antibiotic prescribing for respiratory infections in pediatric urgent cares (PUCs) by patient race/ethnicity, insurance, and language. DESIGN: Multi-center cohort study. SETTING: Nine organizations (92 locations) from 22 states and Washington, DC. PARTICIPANTS: Patients ages 6 months-18 years evaluated April 2022-April 2023, with acute viral respiratory infections, otitis media with effusion (OME), acute otitis media (AOM), pharyngitis, community-acquired pneumonia (CAP), and sinusitis. METHODS: We compared the use of first-line (FL) therapy as defined by published guidelines. We used race/ethnicity, insurance, and language as exposures. Multivariable logistic regression models estimated the odds of FL therapy by group. RESULTS: We evaluated 396,340 ARI encounters. Among all encounters, 351,930 (88.8%) received FL therapy (98% for viral respiratory infections, 85.4% for AOM, 96.0% for streptococcal pharyngitis, 83.6% for sinusitis). OME and CAP had the lowest rates of FL therapy (49.9% and 60.7%, respectively). Adjusted odds of receiving FL therapy were higher in Black Non-Hispanic (NH) (adjusted odds ratio [aOR] 1.53 [1.47, 1.59]), Asian NH (aOR 1.46 [1.40, 1.53], and Hispanic children (aOR 1.37 [1.33, 1.41]), compared to White NH. Additionally, odds of receiving FL therapy were higher in children with Medicaid/Medicare (aOR 1.21 [1.18-1.24]) and self-pay (aOR 1.18 [1.1-1.27]) compared to those with commercial insurance. CONCLUSIONS: This multicenter collaborative showed lower rates of FL therapy for children of the White NH race and those with commercial insurance compared to other groups. Exploring these differences through a health equity lens is important for developing mitigating strategies.

OBJECTIVE: The 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed to evaluate its utility as a predictor for mortality and hospitalisation and to derive and validate an ominosity score based on the SLE classification criteria set. METHODS: Incident patients with SLE in a population-based cohort were included. The association between the 2019 EULAR/ACR SLE score and mortality and hospitalisation was assessed using Cox regression adjusted for age, sex and calendar year. An ominosity score for mortality was developed based on the SLE criteria set. The least absolute shrinkage and selection operator method was used to estimate model coefficients. Concordance and calibration were assessed by cross-validation and by plotting the observed event rates against the deciles of predicted probabilities. RESULTS: Among 374 patients with incident SLE, a EULAR/ACR score ≥20 points was not associated with an increased risk of mortality (HR 1.17, 95% CI 0.67 to 2.03) or first hospitalisation (HR 1.14, 95% CI 0.79 to 1.64) compared with a score ≤19 points. The derived ominosity score for mortality included age, sex, thrombocytopaenia, neuropsychiatric manifestations, subacute cutaneous or discoid lupus, non-scarring alopecia, inflammatory arthritis, renal involvement, antiphospholipid antibodies and hypocomplementaemia. This model demonstrated a concordance=0.76 with adequate calibration. Age and sex were the main predictors, as seen in the model including just age, sex and year (concordance=0.77). CONCLUSION: The 2019 EULAR/ACR SLE criteria score was not associated with mortality and hospitalisation. The derived ominosity score for mortality presented good prediction for mortality but was not better than age and sex alone.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) causes substantial hospitalization in US infants. The Advisory Committee on Immunization Practices recommended nirsevimab in infants younger than 8 months born during or entering their first RSV season and for children aged 8 to 19 months at increased risk of RSV hospitalization in their second season. This study's objective was to evaluate the cost-effectiveness of nirsevimab in all infants in their first RSV season and in high-risk children in their second season. METHODS: We simulated healthcare utilization and deaths from RSV with and without nirsevimab among infants aged 0 to 7 months and those 8 to 19 months old over a single RSV season. Data came from published literature, US Food and Drug Administration approval documents, and epidemiologic surveillance data. We evaluated societal outcomes over a lifetime discounting at 3% and reporting in 2022 US dollars. Sensitivity and scenario analyses identified influential variables. RESULTS: We estimated that 107 253 outpatient visits, 38 204 emergency department visits, and 14 341 hospitalizations could be averted each year if half of the US birth cohort receives nirsevimab. This would cost $153 517 per quality-adjusted life year (QALY) saved. Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved. CONCLUSIONS: Nirsevimab for infants may be cost-effective, particularly among those with higher risks and costs of RSV.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) commonly causes hospitalization among US infants. A maternal vaccine preventing RSV in infants, RSV bivalent prefusion F maternal vaccine (RSVpreF), was approved by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices. Our objective was to evaluate the health benefits and cost-effectiveness of vaccinating pregnant persons in the United States using RSVpreF. METHODS: We simulated RSV infection and disease with and without seasonal RSVpreF vaccination in half of the pregnant persons in the annual US birth cohort during weeks 32 through 36 of gestation. Model inputs came from peer-reviewed literature, Food and Drug Administration records, and epidemiological surveillance databases. The results are reported using a societal perspective in 2022 US dollars for a 1-year time frame, discounting future health outcomes and costs at 3%. Sensitivity and scenario analyses were performed. RESULTS: Year-round maternal vaccination with RSVpreF would prevent 45 693 outpatient visits, 15 866 ED visits, and 7571 hospitalizations among infants each year. Vaccination had a societal incremental cost of $396 280 per quality-adjusted life-year (QALY) saved. Vaccination from September through January cost $163 513 per QALY saved. The most influential inputs were QALYs lost from RSV disease, the cost of the vaccine, and RSV-associated hospitalization costs; changes in these inputs yielded outcomes ranging from cost-saving to $800 000 per QALY saved. CONCLUSIONS: Seasonal maternal RSV vaccination designed to prevent RSV lower respiratory tract infection in infants may be cost-effective, particularly if administered to pregnant persons immediately before or at the beginning of the RSV season.

Rocky Mountain spotted fever (RMSF) is an ongoing public health crisis in Mexico, particularly in states bordering the United States. The national highest incidence and mortality of RMSF occur in this region, resulting in a case-fatality rate that ranges annually between 10% and 50%, primarily affecting vulnerable groups such as children, elderly adults, and persons living in poverty. Multiple biological, environmental, and social determinants can explain its growing presence throughout the country and how it challenges the health system and society. It is necessary to integrate resources and capacities from health authorities, research centers, and society to succeed in dealing with this problem. Through a scientific symposium, a group of academicians, U.S. health officials, and Mexican health authorities met on November 8-10, 2023, in Hermosillo, Mexico, to discuss the current situation of RMSF across the country and the challenges associated with its occurrence. An urgent call for action to improve national capacity against RMSF in the aspects of epidemiological and acarological surveillance, diagnosis, medical care, case and outbreak prevention, health promotion, and research was urged by the experts. The One Health approach is a proven multidisciplinary strategy to integrate policies and interventions to mitigate and prevent the burden of cases, deaths, and suffering caused by RMSF in Mexico.

OBJECTIVE: To characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. METHODS: We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity (SLEDAI-2k), and SLICC/ACR damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. RESULTS: The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 months (95% confidence interval [CI] 0.9-1.5); time to diagnosis 30.6 months (95% CI 18.9-48.1), and time to treatment initiation 4.7 months (95% CI 3.9-8.4). Approximately 25% (93/373) of patients experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (<2 SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, while hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). CONCLUSIONS: Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with damage. Fewer manifestations, hematologic, or antiphospholipid antibodies were associated with delays.

BACKGROUND: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications. METHODS: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes. FINDINGS: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile. INTERPRETATION: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens. FUNDING: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).

INTRODUCTION: This research aims to characterize disparities in mpox- and vaccine-related knowledge in gay, bisexual, and other men who have sex with men in the U.S. METHODS: The authors conducted a study using the American Men's Internet Survey, which includes 823 cisgender (defined as their gender identity matching their sex assigned at birth) males aged ≥15 years from August 5 to 15, 2022. The authors evaluated sociodemographic and behavioral factors associated with mpox knowledge, including race/ethnicity, region, age group, and HIV pre-exposure prophylaxis use using chi-square tests. RESULTS: The authors identified knowledge gaps, with many participants unsure about whether individuals need 2 doses of the vaccine (34.4%) and whether the vaccine confers immediate protection (27.2%). The authors observed racial and regional disparities (p<0.01), with 24.4% of non-Hispanic Black men and 18.1% of men living in the South reporting little to no mpox awareness. Among the 707 self-reported HIV-negative participants, people who used pre-exposure prophylaxis within the past year were more likely to exhibit high awareness about mpox than people who did not use pre-exposure prophylaxis. CONCLUSIONS: Findings suggest the potential to leverage existing networks (i.e., sexually transmitted infection or general health care services with pre-exposure prophylaxis use) for future targeted health service programming or education campaigns for mpox vaccination among gay, bisexual, and other men who have sex with men.

INTRODUCTION: We evaluated internet platforms for distributing HIV self-tests (HIVSTs) to Black or African American (Black) and Hispanic or Latino men who have sex with men (MSM) and transgender women (TGW). METHODS: We recruited MSM and TGW from general interest, dating, and lesbian, gay, bisexual, and transgender platforms. Two HIVSTs were mailed to all MSM and TGW. Surveys (screening, baseline, 4-month, and results reporting) were completed online. After 4 months, participants were mailed another HIVST and a dried blood spot card. All HIVST interpretations and images of HIVST devices were reported online. RESULTS: Of 2093 MSM and 102 TGW, most were recruited through general interest and dating platforms. Over 50% were 18-29 years old, most identified as gay or bisexual. Overall, 45% had not tested for HIV in the past 12 months, and 9.1% of MSM reported a positive (reactive for HIV antibodies) HIVST result, with the highest percentage among Black MSM (11.5%). Dating platforms recruited higher percentages of MSM who recorded positive results compared with MSM from general interest platforms during the intervention period (11.9% vs 5.5% (P < 0.0001)), and MSM who had never tested for HIV reported a greater percentage of positive HIVST results compared with MSM who had been tested for HIV before enrollment (16.1% vs. 7.1%; P < 0.0001). MSM were able to correctly interpret and report HIVST results. Of TGW, 7% reported a positive HIVST result. CONCLUSIONS: Internet dating and general interest platforms can be key to increasing awareness of infection among BMSM, HMSM, and TGW persons, including those who do not use existing HIV services. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT04219878.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two subunit RSV vaccines (Arexvy [GSK] and Abrysvo [Pfizer]) received approval from the U.S. Food and Drug Administration (FDA). In June 2023, ACIP recommended that adults aged ≥60 years may receive a single dose of RSV vaccine, using shared clinical decision-making. In support of development of this policy, our objective was to assess the cost-effectiveness of RSV vaccination in the general population in this age group. We used a decision-analytical model of RSV over a two-year timeframe using data from published literature, FDA documents, epidemiological databases, and manufacturer data. We tracked RSV-associated outpatient, emergency department, inpatient healthcare utilization, RSV-attributable deaths, quality-adjusted life-years lost (QALYs), and societal costs. The societal cost per QALY saved from RSV vaccination depended on age group and product: adults aged ≥60 years, $196,842 for GSK's vaccine and $176,557 for Pfizer's vaccine; adults ≥65 years, $162,138 for GSK and $146,543 for Pfizer; adults 60- <65 years, $385,829 for GSK and $331,486 for Pfizer. Vaccine efficacy, incidence of RSV hospitalization, and vaccine cost had the greatest influence on cost per QALY. Cost per QALY saved decreased as the age of those vaccinated increased. Inputs such as long-term efficacy are uncertain. RSV vaccination in adults aged ≥60 years may be cost-effective, particularly in those of more advanced age. Lower vaccine acquisition costs and persistent efficacy beyond two RSV seasons would render RSV vaccination more cost-effective for a broader target population. PRIMARY FUNDING SOURCE: US Centers for Disease Control and Prevention.

BACKGROUND: Better understanding differences associated with antibiotic prescribing for acute sinusitis can help inform antibiotic stewardship strategies. We characterized antibiotic prescribing patterns for acute sinusitis among commercially insured adults and explored differences by patient- and prescriber-level factors. METHODS: Outpatient encounters among adults aged 18 to 64 years diagnosed with sinusitis between 2016 and 2020 were identified by national administrative claims data. We classified antibiotic agents-first-line (amoxicillin-clavulanate or amoxicillin) and second-line (doxycycline, levofloxacin, or moxifloxacin)-and ≤7-day durations as guideline concordant based on clinical practice guidelines. Modified Poisson regression was used to examine the association between patient- and prescriber-level factors and guideline-concordant antibiotic prescribing. RESULTS: Among 4 689 850 sinusitis encounters, 53% resulted in a guideline-concordant agent, 30% in a guideline-discordant agent, and 17% in no antibiotic prescription. About 75% of first-line agents and 63% of second-line agents were prescribed for >7 days, exceeding the length of therapy recommended by clinical guidelines. Adults with sinusitis living in a rural area were less likely to receive a prescription with guideline-concordant antibiotic selection (adjusted risk ratio [aRR], 0.92; 95% CI, .92-.92) and duration (aRR, 0.77; 95% CI, .76-.77). When compared with encounters in an office setting, urgent care encounters were less likely to result in a prescription with a guideline-concordant duration (aRR, 0.76; 95% CI, .75-.76). CONCLUSIONS: Opportunities still exist to optimize antibiotic agent selection and treatment duration for adults with acute sinusitis, especially in rural areas and urgent care settings. Recognizing specific patient- and prescriber-level factors associated with antibiotic prescribing can help inform antibiotic stewardship interventions.