BACKGROUND: On January 30, 2020, the World Health Organization declared COVID-19 a Public Health Emergency of International Concern (PHIEC). On March 11, 2020, it was characterized as a pandemic, prompting the Government of Sierra Leone to implement response plans. The first case in the country was reported on March 31, 2020. To build resilient public health systems after the Ebola crisis, the Sierra Leone Field Epidemiology Training Program (SLFETP) was launched in 2016 with funding from the U.S. CDC in collaboration with the Ministry of Health and the African Field Epidemiology Network (AFENET). The program started at the FETP Frontline level, a 3-month in-service training program, followed by the FETP Intermediate, a 9-month in-service training program launched in 2017. Both levels adopted the CDC curriculum to the local context. The curriculum consists of classroom modules focusing on surveillance, outbreak investigation, and field projects. The SLFETP graduates and trainees were deployed to assist in COVID-19 response efforts. While reports indicate the SLFETP's contributions to COVID-19 preparedness and response, the specific roles of its graduates and trainees remain undocumented. This paper outlines their crucial involvement during the pandemic in Sierra Leone. METHODS: We reviewed 12 documents from the SLFETP, including work plans, outbreak investigation reports, and success stories, to assess the FETP's contributions during the COVID-19 pandemic. We interviewed graduates and trainees about their roles and conducted discussions with stakeholders and FETP staff to explore the FETP's role during the pandemic's preparedness and response phases. A thematic analysis was performed. RESULTS: The SLFETP played a critical role during the preparedness and response phase of the COVID-19 pandemic. The trainees and graduates enhanced the surveillance system and led key response pillars, such as coordination, surveillance, and quarantine. SLFETP supported districts by building their capacity, especially in the district surveillance pillar, to conduct case investigations, contact tracing, quarantine monitoring, and data management. CONCLUSIONS: The graduates and trainees reportedly played critical roles in key response pillars across the country in the preparedness and response phase of the COVID-19 pandemic. These gains should be maintained and scaled up to build a strong and resilient public health workforce in Sierra Leone, which is crucial for preparedness and response to future outbreaks.

BACKGROUND: Uganda reported a significant reduction in the mortality rate of children under 5 years of age, from 146/1,000 live births in 2000-42/1,000 live births in 2021. With the rollout of Option B+, the vertical transmission rate of HIV decreased from 13.0% (2012) to 6.0% (2019). However, its impact on the mortality rate among children is not well documented. We determined the mortality rate and associated risk factors among infants exposed and not exposed to HIV attending immunization clinics in Uganda. METHODS: We conducted an observational prospective cohort study of mother-infant pairs (MIPs) with infants exposed or unexposed to HIV. We enrolled infants aged 4-12 weeks. The inclusion criteria were biological mothers attending health facilities that provide routine immunization for children and/or postnatal care visits who were able to provide signed written informed consent; mothers or infants who were not severely ill; and those who consented to have their infants tested for HIV antibodies at baseline and follow-up visits every 3 months until the children were aged 18 months. Child-HIV infection and death were censored events. Children lost to follow-up or withdrawn from the study were censored from analyses at the last documented study visit. The outcome of interest was child mortality, and the independent variables were mother's age; infant HIV exposure status; infant sex; family socioeconomic status; marital status; education level; malaria during pregnancy; birth attendee; mother's ART initiation; mode of transport to health facilities; breastfeeding pattern; 4 or more ANC visits; and mother's baseline viral load nonsuppression and place of delivery. We used Kaplan-Meier survival curves to estimate cumulative mortality probability and the Wilcoxon log-rank test to compare differences in cumulative survival functions. We used multivariate Weibull proportional hazards and Weibull accelerated failure time (AFT) regression models with 95% confidence intervals (CIs) to identify factors associated with child death. RESULTS: Among the 16,718 MIPs identified, 11,519 (68.9%) mothers consented to study follow-up. At the 18-month follow-up, 0.7% (79/11,519) of the infants had died, 40.5% (32/79) of whom were exposed to HIV. The overall child mortality rate per 1,000 person-years was 5.0 (95% CI: 4.0--6.2) and was significantly greater among the infants exposed to HIV (14.2; 95% CI: 10.0--20.0) than among the infants not exposed to HIV (3.5; 95% CI: 2.6--4.6). In the adjusted model, the mortality risk factors were HIV exposure status (aHR5.6 95% CI: 3.5--9.4), maternal age < 25 years (aHR1.8; 95% CI: 1.1--2.9), living without a partner (aHR1.8; 95% CI: 1.1--2.9), and delivery at home (aHR2.2; 95% CI: 1.3--4.0). CONCLUSION: Single young mothers living with HIV delivering at home increased the risk of child mortality. Identifying mothers with risk factors early for support could reduce the risk of child mortality.

Jurisdictional health departments use public health information systems (PHIS) to maintain and transmit their surveillance data for national surveillance. We investigated if changes to a PHIS had an impact on sexually transmitted infection case-based surveillance data and document short-term issues that resulted in decreased data quality.

PROBLEM/CONDITION: Candidemia, a bloodstream infection caused by Candida spp., is a common cause of health care-associated bloodstream infections in the United States. Candidemia is associated with substantial health care costs, morbidity, and mortality. PERIOD COVERED: 2017-2021. DESCRIPTION OF SYSTEM: CDC's Emerging Infections Program (EIP), a collaboration among CDC, state health departments, and academic partners, was used to conduct active, population-based laboratory surveillance for candidemia at city or county sites located in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee), representing a combined population of approximately 21.5 million persons, or 7% of the U.S. population in 2019. Connecticut began reporting cases on January 1, 2019, and conducts statewide surveillance. Although candidemia is not a nationally notifiable condition, cases of Candida auris infection are nationally notifiable, and cases of candidemia caused by C. auris could be included in both national case counts and EIP surveillance. A culture-confirmed candidemia case is defined as a positive blood culture for any Candida sp. from a resident in the surveillance catchment area. Subsequent positive blood cultures for Candida within 30 days of the initial positive culture (index date) in the same patient are considered part of the same case. Clinical laboratories serving each catchment area report candidemia cases, and trained surveillance officers abstract information from medical charts for all cases. Corresponding isolates are sent to CDC for species confirmation and antifungal susceptibility testing. RESULTS: A total of 7,381 candidemia cases were identified during the surveillance period (2017-2021). The overall incidence was 7.4 cases per 100,000 population. Across age groups, sexes, racial and ethnic groups, and surveillance sites, incidence was generally stable or increased slightly from 2017 to 2021, with the lowest overall incidence in 2019 (6.8) and the highest in 2021 (7.9). In 2021, candidemia incidence was highest in patients aged ≥65 years (22.7) and infants (aged <1 year) (8.0). Incidence was higher in males (8.7) compared with females (7.0) and higher in non-Hispanic Black or African American (Black) patients (12.8) compared with non-Black patients (5.6). Incidence was highest in Maryland (14.5), followed by Tennessee (10.1) and Georgia (10.0); incidence was lowest in Oregon (4.8). Increases occurred in the percentage of cases classified as health care onset (52.2% in 2017 to 58.0% in 2021). Overall, among 7,381 cases (in 6,235 patients), 63.7% occurred in patients who had a central venous catheter, 80.7% involved recent systemic antibiotic receipt, and 9.0% occurred in patients who had a history of injection drug use. The percentage of cases with a positive SARS-CoV-2 test during the 90 days before or after the index date increased from 10.4% in 2020 to 17.7% in 2021. From 2017 to 2021, the percentage of cases involving an intensive care unit stay before the index date increased from 38.3% to 44.9%. Echinocandins (e.g., micafungin) were used as treatment in 49.8% of cases, and azoles were used in 47.7%. The all-cause in-hospital mortality rate was 32.6%; this increased from 26.8% in 2019 to 36.1% in 2021. Overall, Candida albicans accounted for 37.1% of cases, followed by Candida glabrata (30.4%) and Candida parapsilosis (13.5%); however, C. glabrata was the most frequent species in California (38.4%) and Maryland (32.9%). Candida auris infections accounted for 0.4% of cases. Among 6,576 Candida isolates for which interpretive breakpoints exist and isolates were available for testing, 5.6% were fluconazole resistant, and <1% were echinocandin resistant. Antifungal resistance was stable for all antifungals tested across years. INTERPRETATION: Candidemia remains an important health care-associated infection. The disproportionate incidence among older adults, males, and Black patients is consistent with previous reports, and the overall incidence of candidemia has not changed substantially compared with previous EIP findings based on data collected during 2012-2016 (8.7 per 100,000 population). The higher mortality rate associated with candidemia during 2020-2021 likely reflects consequences of the COVID-19 pandemic, including strained health care systems and an increased population of patients who were susceptible to candidemia because of COVID-19-related critical illness. PUBLIC HEALTH ACTION: Strict implementation of measures to prevent health care-associated bloodstream infections is important to help prevent candidemia cases. Health care officials and providers should be vigilant for candidemia as a complication of critical illness. Continued surveillance is needed to monitor for emerging populations at risk for candidemia and changes in antifungal resistance patterns, which can help guide antifungal treatment selection.

BACKGROUND: SARS-CoV-2 pandemic has caused a continuing health crisis affecting the public health system globally. Population-based serological surveys are a highly valuable and recommended method to measure population exposure and spread of pandemic, given the existence of asymptomatic cases and little access to diagnostic testing. This national population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in all parts of Ethiopia and determine potential risk factors and burden of infection. METHODS: A nationwide seroprevalence survey was done among 12,756 households (HHs) across the country using three-stage stratified sampling technique from April 15, 2021 to May 16, 2021 among population of Ethiopia above 15 years of age. One member of each of the selected HHs, who fulfilled the eligibility criteria, was randomly selected. We captured data using interviews and finger prick blood samples to test for anti-SARS-CoV-2 antibodies using high specificity rapid diagnostic tests (RDTs). A questionnaire was used to capture all necessary data on demographics, social exposure, and history of vaccination for SARS-CoV-2, symptoms compatible with SARS-CoV-2, and any known medical conditions. The data were collected using an open data kits (ODK) software and imported into STATA version 17 for analysis. Descriptive statistics (frequencies and proportions) were used to summarize data on the study variables. Forest plots and maps were used to visualize the seroprevalence of SARS-CoV-2 across various individual and environmental factors. The study sample was weighted, and the survey set command in Stata (svy) was used in the analyses to account for the survey design. Adjusted Odd ratio (AOR) was used to determine higher risk factors of having been infected at least once, 95% confidence interval to assess precision of the estimates, and a P value ≤  0.05 to determine statistically significant. RESULT AND DISCUSSION: This study indicated the overall national prevalence of seropositivity was 9.3% that suggests nearly one in ten individuals in Ethiopia was exposed to SARS-CoV-2 infection by May 2021. All regional states in the country are affected with SARS-CoV-2 infection although infection was more common in densely populated regions. Seroprevalence was significantly higher among, individual, aged 35-44, 55-64 and 65 and over years had more odds of being infected by SARS-CoV-2 compared with those aged 15-24 years. The seroprevalence is also high among professional/technical occupations, and among those having at least one comorbidity. The participants who had seven and more members had higher odds of infection compared with those who had two or less members. The odds of infection among respondents, who reported having ever tested for COVID-19 and being sick since March 2020, were higher compared with their counterparts. Among the environmental factors, the odds of SARS-CoV-2 infection in urban residents were higher than in the rural setting. In relation to geographic administration boundaries, participants from Harari Region, Addis Ababa, and Benishangul Gumuz had higher odds of infection compared to those from Afar Regions respective. CONCLUSION AND RECOMMENDATIONS: This study reveals the overall seroprevalence of SARS CoV-2 antibodies in Ethiopia was 10.0% as of May 2021. The seroprevalence of IgG antibodies against COVID-19 is higher than that of IgM antibodies, indicating a past infection. SARS-CoV-2 antibody seroprevalence was varied by regional state, sex, residence area, age, and occupational status. It also suggests that the majority of Ethiopia's have inadequate knowledge of understanding about SARS-CoV-2 antibodies, we recommend strengthening public health and social measures to mitigate the spread of COVID-19 diseases, including increased vaccination coverage and testing capability. All responsible authorities and stakeholders working locally, nationally, and globally need to support strengthening health systems and be prepared to combat morbidity and mortality and to encourage ongoing vaccination efforts. Periodic seroprevalence surveys will aid in monitoring the status and progress of the COVID-19 pandemic.

Disease burden studies commonly use data from electronic health records (EHRs) or community surveys. Quantitative bias assessments of these study designs are needed. We compared two studies on acute gastroenteritis (AGE) burden conducted in an integrated healthcare system in Oregon and Washington, USA. EHRs were used to identify AGE patients who sought care during July 2014 - June 2016 and determine the incidence of medically attended AGE (MAAGE). Members from the same health care system were surveyed during September 2016 - September 2017 to estimate community AGE incidence. MAAGE incidence was calculated using the rate of reported healthcare seeking among survey respondents and compared to the estimate derived from the EHR study. Survey respondents' EHR data were used to conduct a bias analysis. MAAGE incidence from survey respondents was 6.1 times higher than the EHR derived MAAGE estimate. Among survey respondents who self-reported contacting KPNW for an AGE episode, 36.3% had an AGE-coded encounter in the EHR during the same timeframe, and among those who reported no contact (either no AGE or AGE without medical attention), 2.6% did have an AGE-coded encounter. Potential noninfectious explanations for symptoms were reported by 35% of ill survey respondents. We quantify misclassification bias in both studies and discuss other potential sources of bias. Researchers should consider these biases when designing disease burden studies and consider including sensitivity analyses in published work.

A 45-year-old woman presented to urgent care suspecting an allergic reaction to foods that were consumed the previous evening. Her condition rapidly deteriorated to include cranial nerve palsies followed by a descending symmetric muscle weakness requiring mechanical ventilation. Botulism was suspected, and after consultation with public health experts at the state health department and Centers for Disease Control and Prevention, treatment with botulism antitoxin was initiated. The patient required prolonged ventilation and rehabilitation but achieved near-complete recovery after several weeks. Botulinum neurotoxin type F was detected in the patient's serum. Serial testing of the patient's clinical specimens was not performed. The patient's rapid progression to severe paralysis with a relatively swift recovery resembles previously described botulism type F cases. Public health investigations were unable to determine whether the patient had foodborne or adult intestinal colonization botulism.

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.

BACKGROUND: While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. METHODS: Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively. RESULTS: In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial. CONCLUSIONS: Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease. TRIAL REGISTRATION: The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).

BACKGROUND: Risk factors for severe respiratory syncytial virus (RSV) illness include early infancy, premature birth, and underlying medical conditions. However, the clinical significance of respiratory viral co-detection is unclear. We compared the clinical outcomes of young children with RSV-only detection and those with RSV viral co-detection. METHODS: We conducted active, population-based surveillance of children with medically attended fever or respiratory symptoms at 7 US medical centers (1 December 2016-31 March 2020). Demographic and clinical data were collected through parental interviews and chart abstractions. Nasal swabs, with or without throat swabs, were systematically tested for RSV and 6 other common respiratory virus groups. We compared clinical outcomes, including hospitalization, and among those hospitalized, length of stay, intensive care unit admission, supplemental oxygen use, and intubation, between children aged <2 years with RSV-only detection and those with RSV co-detection. RESULTS: We enrolled 18 008 children aged <2 years. Of 17 841 (99.1%) tested for RSV, 5099 (28.6%) were positive. RSV was singly detected in 3927 children (77.0%) and co-detected in 1172 (23.0%). RSV co-detection with parainfluenza virus or adenovirus was associated with significantly lower odds of hospitalization (adjusted odds ratio, 0.56; 95% confidence interval [CI]: .33-.95; P = .031) and supplemental oxygen use (adjusted odds ratio, 0.66; 95% CI: .46-.95; P = .026), respectively, than RSV-only detection. For all other comparisons, we did not identify a significant association between RSV co-detection and worse clinical outcomes. CONCLUSIONS: Co-detection of RSV with another respiratory virus was not significantly associated with worse clinical outcomes compared with RSV-only detection.

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain. OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 testing periods (July to October 2017, July to November 2018, July to November 2020, and July 2021 to December 2022). Included children were aged younger than 18 years, reported 1 or more qualifying ARI symptoms, with a symptom duration less than 14 days at enrollment. Data were analyzed from in October 2024. EXPOSURES: Laboratory-confirmed EV-D68 infection, including overall infections or those without viral codetection. MAIN OUTCOMES AND MEASURES: Trends and characteristics of EV-D68, including demographics, underlying conditions, and clinical severity by health care setting, were explored. Among hospitalized children with EV-D68-positive results without viral codetection, multivariable logistic regression was used to examine factors associated with receipt of (1) supplemental oxygen or (2) intensive care. RESULTS: From 2017 to 2022, 976 children with EV-D68-positive results were identified (median [IQR] age, 47 [18-63] months; 391 [40.1%] female); most were enrolled in 2018 (382 children) and 2022 (533 children). Among these, 856 had no viral codetection, of which 320 were discharged home from the ED (median [IQR] age, 33 [16-59] months; 180 male [56.3%]; 237 [74.1%] with no reported underlying conditions) and 536 were hospitalized (median [IQR] age, 40 [19-69] months; 330 male [61.6%]; 268 [50.0%] with no reported underlying conditions). Among those hospitalized, 199 (37.1%) reported a history of asthma or reactive airway disease (RAD) and 77 (14.4%) reported a condition other than asthma or RAD. Having an underlying condition other than asthma or RAD was associated with increased odds of receiving supplemental oxygen (adjusted odds ratio, 2.72; 95% CI, 1.43-5.18) or intensive care admission (adjusted odds ratio, 3.09; 95% CI, 1.72-5.56); neither age group nor history of asthma or RAD were associated with oxygen receipt or intensive care admission. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of children with medically attended EV-D68 infections, EV-D68 was associated with severe disease in otherwise healthy children of all ages, and children with nonasthma or RAD comorbidities were at higher risk for severe outcomes when hospitalized.

BACKGROUND: While acute gastroenteritis (AGE) occurs year-round, norovirus has a winter seasonality in the United States. OBJECTIVE: We analyzed norovirus seasonality within a US integrated healthcare delivery system from 2016-2019. METHODS: Electronic medical records were collected for acute gastroenteritis (AGE) encounters with specific ICD-9/10 codes or clinical stool testing. Norovirus percent positivity was calculated as the 8-week centered rolling average. Temperature and absolute humidity data were measured via weather station. The relationship between these factors and weekly norovirus episodes were modeled via negative binomial models. RESULTS: From 2016-2019, there were 198,181 AGE episodes reported; among the 18,998 episodes tested, 892 (5%) were norovirus positive. Norovirus percent positivity peaked in epidemiologic week 7 at 9%. Two negative binomial models showed significant inverse relationships between weekly number of norovirus episodes and both temperature and absolute humidity. CONCLUSION: Norovirus AGE exhibited winter seasonality from 2016-2019, associated with lower temperatures and humidity. Understanding this seasonality may help predict peak transmission periods and their impact on healthcare resources.

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.

In May 2023, the Shelby County Health Department identified a legionellosis outbreak among attendees of the same church. Epidemiologic, environmental, and laboratory investigations were initiated. Laboratory-based surveillance identified persons with a positive Legionella test result. Church attendees were surveyed about attendance, symptoms of legionellosis, and water exposures. Environmental assessment of the church included asking about recent water management practices and collecting samples from water sources for culture. The health department identified 16 church attendees who had legionellosis symptoms. Of these, 9 (56%) had positive laboratory test results for Legionella pneumophila, 7 were hospitalized, and none died. Our investigation revealed that recent changes in water management practices at the church included renewed operation of a large, jetted baptismal font. In all, 17 environmental samples were collected; of these samples, 5 (including 4 from the baptismal font) had L. pneumophila serogroup 1 isolated by culture. Environmental sampling was crucial in identifying the baptismal font as the likely source of L. pneumophila. Education about water management and remediation recommendations were provided to staff at the church.

The occupation of firefighting is classified as a Group 1 carcinogen. Increased cancer risk among firefighters may be partly attributable to increased occupational exposure to a range of chemicals, including per- and polyfluoroalkyl substances (PFAS). Some PFAS are known and suspect human carcinogens. Investigating epigenetic response to these PFAS exposures in firefighters may help to identify biological pathways of specific cancers, and previously unidentified health outcomes that are associated with PFAS. We therefore investigated the associations of serum PFAS concentrations with miRNA expression in firefighters. Serum samples collected from 303 firefighters from 6 sites across the USA were analyzed for 9 PFAS along with miRNA expression. Covariate-adjusted linear regression was used to estimate associations between log PFAS and miRNA expression, with false discovery rate (FDR) set to 0.05 for significance, and an exploratory cutoff of FDR q<0.20. Gene set enrichment analysis (GSEA) was performed using miRTarBase's miRWalk pathways. Age, race-ethnicity, BMI, fire department, and sex were controlled for in all models. At FDR<0.05, the linear isomer of perfluorooctane sulfonic acid (PFOS) was inversely associated with miR-128-1-5p expression (Beta = -0.146, 95% CI -0.216, -0.076). At a relaxed FDR of 0.20, we observed inverse associations for the sum of branched isomers of PFOS (Sm-PFOS) with 5 miRNAs (let-7d-5p, let-7a-5p, miR-423-5p, let-7b-5p, miR-629-5p). Several pathways were enriched for multiple PFAS, including those correlated with certain cancers, blood diseases, thyroid disorders, autoimmune disorders, and neurological outcomes. Some PFAS in firefighters were found to be associated with alteration of miRNA consistent with increased risk for a range of chronic diseases.

Nail polishes contain over a dozen chemical compounds, including chemicals that can cause adverse reproductive outcomes and pose a risk to the high proportion of nail salon workers who are women of childbearing age. Consumer demand has resulted in a shift toward more natural products, with manufacturers attempting to remove harmful ingredients (n-free products). Many products that claim to have eliminated toluene, formaldehyde, and dibutyl phthalate (DBP) are labeled as "3-free"; however, studies have found these products often contain higher concentrations of toluene and DBP compared to products with no such claims. Products used only at salons are not required to list ingredients, leading to uncertainties as to the exact chemical composition and potential exposures. A better understanding of chemical exposures associated with nail polish products is necessary to understand potential worker exposures and develop effective control options. This study evaluated chemical exposures generated while painting nails with 20 n-free polishes using real-time and time-integrated air sampling. Total volatile organic compounds (TVOCs, PID, ION Science Inc.) and 22 individual compounds (FTIR, Gasmet Technologies) were measured in the breathing zone of the manicurist while two coats of polish were applied to artificial nails on a manikin in an exposure chamber and for 2 hr afterwards. Formaldehyde and toluene were measured in all polishes using the real-time FTIR, despite all claiming to be 3-free. Normalized geometric mean (GM) formaldehyde exposures from the FTIR ranged from 0.021 to 0.273 ppm/g, GM toluene exposures ranged from 0.068 to 0.534 ppm/g, and GM benzene exposures ranged from 0.076 to 0.752 ppm/g. Notably, formaldehyde, toluene, and benzene exposures did not significantly differ between different products. Neither DBP nor triphenyl phosphate (TPhP) was detected in any of the polishes. This study highlights that despite industry claims, n-free polishes may still contain chemicals associated with negative health effects and that more studies are necessary to understand the true chemical exposures of nail salon workers.

Racial misclassification on death certificates leads to inaccurate mortality data for American Indian and Alaska Native (AI/AN) populations. We describe methods for correcting for racial misclassification among non-Hispanic AI/AN (NH-AI/AN) populations using data from the year 2020. We linked National Death Index (NDI) records with the Indian Health Service (IHS) patient registration database to identify AI/AN decedents. Matches were then linked to the National Vital Statistics System (NVSS) mortality data to identify AI/AN individuals that had been misclassified as another race on their death certificates. Analyses were limited to NH-AI/AN and purchased/referred care delivery areas (PRCDA) or urban areas. We compared death rates and counts pre- and post- linkage and calculated sensitivity and classification ratios by region, sex, age, cause of death (COD) and urban area. Racial misclassification on death certificates among NH-AI/AN varied by geographic region. Some of the highest racial misclassification occurred in the Southern Plains and Pacific Coast. Death rates for NH-AI/AN people and differences between NH-AI/AN and Non-Hispanic White (NHW) people were larger using the linked data. Improving AI/AN mortality data using linkages between vital statistics data and IHS strengthens data quality and can help address health disparities through public health planning efforts.

SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. Here we combine daily longitudinal sampling of individuals with replicate sequencing to increase the accuracy of and lower the threshold for variant calling. We sequenced 577 specimens from 105 individuals in a household cohort during the BA.1/BA.2 variant period. Individuals exhibited extremely low viral diversity, and we estimated a low within-host evolutionary rate. Within-host dynamics were dominated by genetic drift and purifying selection. Positive selection was rare but highly concentrated in spike. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 14 loci with 7 in spike, including S:448 and S:339. This detectable immune-mediated selection is unusual in acute respiratory infections and may be caused by the relatively narrow antibody repertoire in individuals during the early Omicron phase of the SARS-CoV-2 pandemic.

BACKGROUND: Patients hospitalised with influenza have heterogeneous clinical presentations and disease severity, which may complicate epidemiologic study design or interpretation. We applied latent class analysis to identify clinically distinct subgroups of adults hospitalised with influenza. METHODS: We analysed cross-sectional study data on adults (≥18 years) hospitalised with laboratory-confirmed influenza from the population-based U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET) including 13 states during 2017-2018 and 2018-2019 influenza seasons (October 1 through April 30). Adults were included if they were residents of the FluSurv-NET catchment area, hospitalised with laboratory-confirmed influenza during these two seasons, and had both the main case report form and the supplemental disease severity case report form completed. We constructed a latent class model to identify subgroups from multiple observed variables including baseline characteristics (age and comorbidities) and clinical course (symptoms at admission, respiratory support requirement, and development of new complications and exacerbations of underlying conditions). FINDINGS: Among the 43,811 influenza-associated hospitalizations reported during the 2017-2018 and 2018-2019 influenza seasons, 15,873 (36.2%) were included in our analytic population: among them, 7069 (44.5%) were male and 8804 (55.5%) were female. We identified five subgroups. Subgroup A included persons of all ages with few comorbidities and 87.9% (255/290) of pregnant women. Subgroup B included older adults with comorbidities (cardiovascular disease (79.7% [3650/4581]) and diabetes (50.6% [2320/4581])). Almost all patients in subgroups C and D had asthma or chronic lung disease and high proportions with exacerbations of underlying conditions (59.7% [889/1489] and 65.1% [2274/3496], respectively). Subgroup E had the highest proportion with new complications (90.3% [1383/1531]). Subgroups D and E had the highest proportions with severe disease indicators: 21.0% (733/3496) and 50.4% (771/1531) required ICU admission, 7.2% (253/3496) and 28.0% (428/1531) required invasive mechanical ventilation, and 3.3% (116/3496) and 11.4% (174/1531) died in-hospital, respectively. INTERPRETATION: The five identified subgroups of adults hospitalised with influenza had varying distributions of age, comorbid conditions, and clinical courses characterized by new complications versus exacerbations of existing conditions. Stratifying by these subgroups may strengthen analyses that assess the impact of influenza vaccination and antiviral treatment on risk of severe disease. Limitations included that results were based on a convenience sample within FluSurv-NET sites and were likely not representative of all adults hospitalised with influenza in the United States. Influenza testing was also clinician-driven, likely leading to under-ascertainment. FUNDING: Centers for Disease Control and Prevention.

BACKGROUND: The Michigan Polybrominated Biphenyl (PBB) registry, followed since 1976, was created after a 1973 chemical manufacturing mistake. The flame retardant PBB was accidentally mixed into animal feed and distributed to Michigan farms for nearly a year, exposing farm residents and animal product consumers. OBJECTIVE: We synthesize knowledge to date on health effects of PBB exposure within the Michigan PBB Registry, and describe research findings in the context of literature on other persistent organic pollutants (POPs) and endocrine disrupting chemicals (EDCs). METHODS: We reviewed literature published from 1973-2025 on human health effects of PBB following the Michigan contamination using PubMed and Thompson Reuters (ISI) Web of Science databases. We excluded studies not in English; on exposures besides PBB; animal studies; reviews, abstracts, or letters to the editor; studies without a health outcome; and studies outside of Michigan or unrelated to the 1973 contamination. For each article, two researchers performed title and abstract screening, full article review, and data extraction. RESULTS: We included 79 publications out of 601 identified and screened. Early studies did not find many health outcomes associated with PBB, possibly because of methodological limitations. More recent studies on long-term and multigenerational impacts found an increased breast cancer risk, accelerated pubertal development and earlier menarche for girls exposed in utero, urogenital problems and slower pubertal development in boys exposed in utero, lower estrone 3-glucuronide and follicle-stimulating hormone among women exposed in childhood, and increased miscarriage risk among daughters of exposed women. Epigenetic and metabolomic research reported altered pathways related to estrogenic effects and immune function, and epigenetic alterations of spermatogenic cells. DISCUSSION: This unique community-academic partnership has produced insights into multigenerational consequences of EDC/POP exposures across the lifecourse. The findings from this cohort underscore the broader relevance of critical windows of vulnerability, particularly during fetal development and childhood.. https://doi.org/10.1289/EHP15012.

Macrophages are major innate immune cells for the clearance of inhaled nanoparticles but may undergo cell death upon phagocytosis of certain nanoparticles due to their resistance to lysosomal degradation and high toxicity to the cell. Here we investigated the pyroptotic effect of exposure to fibrogenic multiwalled carbon nanotubes (MWCNTs) on macrophages, an inflammatory form of cell death. We first evaluated MWCNT-induced cell death in M1 and M2 macrophages that mediate the temporal inflammatory response to MWCNTs in mammalian lungs. Macrophages were differentiated from human monocytic THP-1 cells, followed by polarization to M1 or M2 cells. MWCNTs caused concentration- and time-dependent cytotoxicity in M1 and, to a lesser extent, M2 cells. Carbon black, an amorphous carbonous material control for CNTs, did not cause apparent toxicity in the cells. MWCNTs increased the production and secretion of IL-1β, accompanied by activation of caspase-1, in M1, but not M2, cells. Moreover, MWCNTs induced the formation of apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain specks and the release of cathepsin B in M1 cells, revealing activation of the nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via lysosomal damage. MWCNTs induced the cleavage of gasdermin D (GSDMD) to form the 31 kDa N-terminal fragment (GSDMD-N), the pore-forming peptide causing pyroptotic cell death. Increased IL-1β release was completely suppressed by AC-YVAD-CMK (a caspase-1 inhibitor), MCC-950 (an NLRP3 inflammasome inhibitor), or CA-074 Me (a cathepsin B inhibitor), alongside the blockage of MWCNT-induced cleavage of GSDMD. The study demonstrates that MWCNTs trigger pyroptosis in M1 macrophages and boost sterile inflammation by activating the NLRP3 inflammasome pathway. SIGNIFICANCE STATEMENT: The nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 inflammasome mediates the inflammatory response to fibrogenic nanoparticles in the lung via multiple means. The current study uncovers the induction of pyroptotic death of macrophages as a major means of nanotoxicity and sterile inflammation via the nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 pathway by nanoparticles.

BACKGROUND: A multistate outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) occurred in 2019. Because of EVALI's novelty and severity, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) prospectively assessed sequelae among NYC residents who received an EVALI diagnosis in 2019. METHODS: Using existing NYC EVALI surveillance data, DOHMH attempted contact with all living residents who received an EVALI diagnosis in 2019 and conducted 3 waves of telephone interviews during April 2020-March 2021. Interview questions were adapted from the Centers for Disease Control and Prevention's EVALI case report form and validated surveys. Baseline differences between respondents and nonrespondents were assessed with Chi-square and Fisher's exact tests; clinical and behavioral characteristics and open-ended responses were summarized. RESULTS: In 2019, 53 NYC residents received an EVALI diagnosis; 33 (67%), 14 (29%), and 18 (37%) of 49 living residents participated in the first, second, and third interviews, respectively. Interviews occurred after outpatient diagnosis (6%) or hospital discharge (94%), at a median of 8, 11, and 17 months for each wave. Respondents (N = 33) and nonrespondents (N = 16) did not differ by sex, age, hospitalization status or length. Respondents were mostly male (70%), had a median age of 23 years (range: 16-63 years), and all reported using vaping or e-cigarette products (vaping) with tetrahydrocannabinol (88%), nicotine (49%), or cannabidiol (9%) before diagnosis. Respiratory (first and second interviews) and gastrointestinal (third interviews) symptoms were most commonly reported. Sixteen respondents (49%) reported any new diagnosis during follow-up. Fifteen to 29% of respondents reported vaping at each interview; 58%-93% reported recent non-vaped cannabinoid use. CONCLUSION: NYC residents with EVALI reported symptoms throughout the follow-up period, and approximately half reported newly diagnosed health conditions. Further studies are needed to understand EVALI's relationship with symptoms and health conditions.

BACKGROUND: West Nile virus (WNV) is the most common cause of mosquito-borne disease in the continental USA, with an average of ~1200 severe, neuroinvasive cases reported annually from 2005 to 2021 (range 386-2873). Despite this burden, efforts to forecast WNV disease to inform public health measures to reduce disease incidence have had limited success. Here, we analyze forecasts submitted to the 2022 WNV Forecasting Challenge, a follow-up to the 2020 WNV Forecasting Challenge. METHODS: Forecasting teams submitted probabilistic forecasts of annual West Nile virus neuroinvasive disease (WNND) cases for each county in the continental USA for the 2022 WNV season. We assessed the skill of team-specific forecasts, baseline forecasts, and an ensemble created from team-specific forecasts. We then characterized the impact of model characteristics and county-specific contextual factors (e.g., population) on forecast skill. RESULTS: Ensemble forecasts for 2022 anticipated a season at or below median long-term WNND incidence for nearly all (> 99%) counties. More counties reported higher case numbers than anticipated by the ensemble forecast median, but national caseload (826) was well below the 10-year median (1386). Forecast skill was highest for the ensemble forecast, though the historical negative binomial baseline model and several team-submitted forecasts had similar forecast skill. Forecasts utilizing regression-based frameworks tended to have more skill than those that did not and models using climate, mosquito surveillance, demographic, or avian data had less skill than those that did not, potentially due to overfitting. County-contextual analysis showed strong relationships with the number of years that WNND had been reported and permutation entropy (historical variability). Evaluations based on weighted interval score and logarithmic scoring metrics produced similar results. CONCLUSIONS: The relative success of the ensemble forecast, the best forecast for 2022, suggests potential gains in community ability to forecast WNV, an improvement from the 2020 Challenge. Similar to the previous challenge, however, our results indicate that skill was still limited with general underprediction despite a relative low incidence year. Potential opportunities for improvement include refining mechanistic approaches, integrating additional data sources, and considering different approaches for areas with and without previous cases.

BACKGROUND: Marburg virus disease (MVD) is a severe viral infection caused by the Marburg marburgvirus species. In February 2023, Equatorial Guinea declared its first outbreak. This case series describes the natural history of MVD in five laboratory confirmed patients. METHODS: Patients with confirmed MVD admitted to the national treatment center in Bata, Equatorial Guinea, were monitored for vital signs and symptoms. Comprehensive clinical data was collected to understand the progression and outcome of the disease. RESULTS: Five patients were confirmed to have MVD. Three male healthcare workers were diagnosed early in their disease and subsequently survived. The other two patients, both females, were admitted later in their disease progression and died within 24 hours of admission. Four patients received remdesivir under a protocol for the Monitored Emergency Use of Unregistered and Experimental Interventions. The early symptoms were non-specific, with rapid progression to more severe conditions in the later stages of the disease. Early treatment with remdesivir showed the drug to be well tolerated. CONCLUSIONS: Contrary to some reports and the recommended case definition for MVD, our patients presented with a rash but did not exhibit vomiting or diarrhea. Hemorrhagic signs were solely observed in the terminal stage, preceding demise. Despite the limited sample size, these findings emphasize the importance of tailoring the case definition to the specific outbreak. Further evidence on the efficacy and safety of therapeutics for MVD, including remdesivir, should be gathered through well-designed trials during future epidemic responses.

BACKGROUND: Firefighters are at an increased risk of cancer and other health conditions compared with the general population. However, the specific exposures and mechanisms contributing to these risks are not fully understood. This information is critical to formulate and test protective interventions. OBJECTIVE: The purpose of the Fire Fighter Cancer Cohort Study (FFCCS) is to conduct community-engaged research with the fire service to advance the evaluation and reduction of firefighter exposures, along with understanding and mitigating effects leading to an increased risk of cancer and other health conditions. This involves establishing a long-term (>30 years) firefighter multicenter prospective cohort study. METHODS: The structure of the FFCCS includes a fire service oversight and planning board to provide guidance and foster communication between researchers and fire organizations; a data coordinating center overseeing survey data collection and data management; an exposure assessment center working with quantitative exposure data to construct a firefighter job exposure matrix; and a biomarker analysis center, including a biorepository. Together, the centers evaluate the association between firefighter exposures and toxic health effects. Firefighter research liaisons are involved in all phases of the research. The FFCCS research design primarily uses a set of core and project-specific survey questions accompanied by a collection of biological samples (blood and urine) for the analysis of biomarkers of exposure and effect. Data and samples are collected upon entry into the study, with subsequent collection after eligible exposures, and at intervals (eg, 1-2 years) after enrollment. FFCCS data collection and analysis have been developed to evaluate unique exposures for specific firefighter groups; cancer risks; and end points in addition to cancer, such as reproductive outcomes. Recruitment is carried out with coordination from partnering fire departments and eligible participants, including active career and volunteer firefighters in the United States. RESULTS: The FFCCS protocol development was first funded by the US Federal Emergency Management Agency in 2016, with enrollment beginning in February 2018. As of September 2024, >6200 participants from >275 departments across 31 states have enrolled, including recruit and incumbent firefighters. Biological samples have been analyzed for measures of exposure and effect. Specific groups enrolled in the FFCCS include career and volunteer structural firefighters, women firefighters, trainers, fire investigators, wildland firefighters, firefighters responding to wildland-urban interface fires, and airport firefighters. Peer-reviewed published results include measurement of exposures and the toxic effects of firefighting exposure. Whenever possible, research results are provided back to individual participants. CONCLUSIONS: The FFCCS is a unique, community-engaged, multicenter prospective cohort study focused on the fire service. Study results contribute to the evaluation of exposures, effects, and preventive interventions across multiple sectors of the US fire service, with broad implications nationally. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/70522.

INTRODUCTION: E-cigarette unit sales have been estimated using the number of items typically available in a package to standardize unit sales of each product type. However, recent market changes, such as increases in e-liquid volume and nicotine concentration, challenge the validity of assessing sales according to item count without accounting for product attributes. This study measured nicotine content (mg) in e-cigarettes sold as a function of e-liquid volume (mL) and nicotine concentration (mg/mL), compared with e-cigarette unit sales standardized by item count. METHODS: U.S. e-cigarette retail sales data from Circana (February 2019 to June 2024) were analyzed. Trends in mg nicotine sold were compared with standardized unit sales. Additionally, sales-weighted average e-liquid volume, nicotine concentration, and price per milligram of nicotine were measured by product type. Trends were assessed using Joinpoint regression. Analyses were conducted in 2024. RESULTS: From February 2020 to June 2024, monthly milligrams of nicotine content sold increased by 249.2% (p<0.001)-an increase 7.2 times greater than the 34.7% increase in standardized unit sales. Disposable e-cigarettes experienced the greatest increase in mg nicotine sold, which was largely driven by the rise in e-liquid volume. By June 2024, a disposable device contained 9.0 times more e-liquid than a prefilled cartridge. However, the price per milligram of nicotine in prefilled cartridges was 3.7 times greater than that of disposable devices. CONCLUSIONS: Nicotine is an addictive drug added to most e-cigarettes. Measuring e-cigarette sales in milligrams of nicotine content sold could better account for rapid changes in product attributes and inform policy strategies.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in children less than 5 years of age worldwide. In the United States, RSV commonly causes hospitalization in young children and is the leading cause of hospitalizations in infants. As new RSV immunizations become available, burden estimates are critical to guide the implementation of recommendations and quantify impact. METHODS: We estimated RSV-associated hospitalization rates at a large US pediatric medical center during an 8-year period using five approaches, namely, estimation directly from active and passive surveillance systems, both a crude and stratified capture-recapture analysis of data from both systems, and estimation based on discharge diagnosis codes. The stratified analysis was performed to ensure adherence with the capture-recapture methodology assumption that samples are independent and participants have an equal probability of being observed within each system. RESULTS: Overall, estimated RSV-associated hospitalization rates per 1000 children were 4.0 (2.5, 6.1) based on adjusted estimates from active surveillance, 1.7 (2.1, 4.4) from passive surveillance, 7.9 (5.7, 13.0) from crude capture-recapture analysis, 5.0 (3.8, 7.2) from the stratified capture-recapture, and 4.4 (4.0, 4.9) from discharge diagnosis codes. CONCLUSIONS: Each method has limitations and inherent biases that may impact the estimation of the burden of RSV. Capture-recapture analysis may be a useful tool to estimate the burden of RSV, but needs to be adjusted to account for possible violation of the assumptions of independence and equal probability of capture to ensure accurate approximation of disease burden and avoid over estimation.

BACKGROUND: Powered equipment for patient handling was designed to alleviate Emergency Medical Service (EMS) clinician injuries while lifting patients. This project evaluated the organizational rationale for purchasing powered equipment and the outcomes from equipment use. METHODS: This project analyzed secondary data obtained via an insurance Safety Intervention Grant (SIG) program in Ohio USA. These data were primarily in reports from EMS organizations. Investigators applied a mixed-methods approach, analyzing quantitative data from 297 grants and qualitative data from a sample of 64 grants. Analysts abstracted data related to: work-related injuries or risk of musculoskeletal-disorders (MSD), employee feedback regarding acceptance or rejection, and impact on quality, productivity, staffing, and cost. RESULTS: A total of $16.67 million (2018 adjusted USD) was spent from 2005 through 2018 for powered cots, powered loading systems, powered stair chairs, and non-patient handling equipment (eg, chest compression system, powered roller). Organizations purchased equipment to accommodate staff demographics (height, age, sex) and patient characteristics (weight, impairments). Grantees were fire departments (n = 254) and public (n = 19) and private (n = 24) EMS organizations consisting of career (45%), volunteer (20%), and a combination of career and volunteer (35%) staff. Powered equipment reduced reported musculoskeletal injuries, and organizations reported it improved EMS clinicians' safety. Organization feedback was mostly positive, and no organization indicated outright rejection of the purchased equipment. Analyst-identified design advantages for powered cots included increased patient weight capacity and hydraulic features, but the greater weight of the powered cot was a disadvantage. The locking mechanism to hold the cot during transportation was reported as an advantage, but it was a disadvantage for older cots without a compatibility conversion kit. Around one-half of organizations described a positive impact on quality of care and patient safety resulting from the new equipment. CONCLUSION: Overall, organizations reported improved EMS clinicians' safety but noted that not all safety concerns were addressed by the new equipment.