Rotavirus (RV) remains a significant cause of infantile morbidity and mortality, while oral RV vaccines offer inconsistent protection. This study investigates whether gut microbiota influence immune responses to orally and intramuscularly (IM) administered RV strains. Using murine models, we identified microbiota constituents, including segmented filamentous bacteria, reducing oral RV infection and RV antibody generation. Such blockade of RV-induced responses was associated with elevated expression of intestinal Reg3β and Reg3γ and was recapitulated by intraperitoneal administration of cognate recombinant proteins. IM administration following oral RV inoculations enhanced antibody production and defense against RV challenge. We further showed microbiota composition also influenced the efficacy of a single IM RV inoculation. Antibiotic-induced microbiota depletion boosted IM RV efficacy in poorly responding animals. Such enhancement of IM RV-induced immunity appeared to be associated with increased expression of serum RANTES and Eotaxin. The phenotype was recapitulated by directly adjuvating these chemokines to the IM inoculum.

BACKGROUND: Rural adolescents in the United States lag behind their urban counterparts in the uptake of the human papillomavirus (HPV) vaccine. However, a systematic assessment of factors associated with rural-urban disparities in HPV vaccination coverage to inform potential vaccination promotion interventions is lacking in the literature. Prioritizing HPV vaccination for rural adolescents is necessary for increasing overall HPV vaccination coverage for adolescents and for reducing the incidence of HPV infections and future HPV-related cancers. METHODS: We conducted a cross-sectional survey of caregivers of adolescents aged 9-17 years from 13 states located in the southern United States. Participants were recruited from a nationally representative online survey panel and self-administered the survey from December 2019 to January 2020. The survey assessed HPV vaccination initiation and series completion for rural and urban adolescents, and sought to systematically identify modifiable factors (eg, caregiver knowledge and attitudes about HPV/HPV vaccine, health care access) and nonmodifiable factors (eg, sociodemographic characteristics) that may be associated with rural-urban disparities in adolescent HPV vaccination. Rural versus urban residence status of respondents was determined using the US Census definition and Federal Information Processing System (FIPS) codes. RESULTS: Among 2,262 sampled caregivers, data from 987 respondents (43.6%) were included in the analysis; 193 respondents (19.6%) were from rural areas and 794 (80.4%) were from urban areas. Overall, 333 (33.7%) adolescents had received at least 1 dose of HPV vaccination and 259 (26.3%) adolescents had completed HPV vaccination. In comparison to urban adolescents, fewer rural adolescents had initiated (-7.7 percentage points) or completed (-14.9 percentage points) HPV vaccination. Uptake of tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal (MenACWY), and influenza vaccines was similar between urban and rural adolescents. Caregiver attitudes, but not their knowledge about HPV infection or the HPV vaccine, were associated with disparities in HPV vaccination initiation. Rural caregivers were more likely to report concerns with the HPV vaccine, lower access to a pediatric primary care provider, longer travel times to reach health care providers, and HPV vaccination at age 11 years or older compared with age 9 or 10 years. When compared with urban caregivers, fewer rural caregivers reported discussing HPV vaccination with their adolescent's provider although difference in the receipt of a provider recommendation was not statistically significant between rural and urban adolescents. CONCLUSIONS: Our findings confirm rural-urban disparities in HPV vaccination coverage for adolescents living in the 13 southern US states. Future research efforts to reduce rural-urban disparities in HPV vaccination should evaluate the impacts of interventions that increase positive caregiver attitudes about HPV vaccination, expand access to vaccination services and pediatricians for rural adolescents, enable strong provider recommendations, and increase the window of HPV vaccination by promoting vaccination initiation at younger ages (9-10 years). While this analysis focused on rural-urban disparities, lower rates of HPV vaccination overall suggest that interventions in rural areas be implemented alongside broader efforts to promote adolescent HPV vaccination coverage in the southern United States.

IMPORTANCE: Clostridioides difficile is among the most prevalent health care-associated pathogens worldwide. Controlling it remains a critical challenge, due in part to spore viability on surfaces. OBJECTIVE: To quantify transmission of C difficile within health care facilities and evaluate the roles of environmental surfaces and health care personnel (HCP) hands in C difficile movement. DESIGN, SETTING, AND PARTICIPANTS: In 2018, a 13-week longitudinal, observational study was conducted in 2 intensive care units (ICUs) in Utah with daily culture-based sampling of patient body sites, room environmental surfaces, HCP hands, and shared environmental surfaces. Both toxigenic and nontoxigenic C difficile strains were selected for whole genome sequencing and included in the analysis. Data were analyzed from September 2021 to September 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was the identification of transmission clusters based on genomic relatedness between isolates from patients, environmental surfaces, and HCP hands. Clusters were defined as isolates with 2 or fewer single nucleotide variants between them. RESULTS: Of the 278 unique ICU admissions, 177 patients consented to body site sampling and were sampled. Along with these, environment surfaces and HCP hands were sampled daily for all occupied rooms, leading to 7000 total samples. Sampling patients, their environment, and HCP hands revealed that nearly 8% of all patients had C difficile linked to other admissions and 57% of transmission clusters bridged nonoverlapping patient-stays. Including environmental surfaces and HCP hands, a 3.6-fold higher C difficile movement was identified than with patient sampling alone, highlighting environmental surfaces as reservoirs. CONCLUSIONS AND RELEVANCE: These results challenge the idea that nosocomial transmission is not a primary source of acquisition and underscore the importance of hand hygiene and environmental decontamination. This study reinforces the need to include environmental surfaces and HCP hands in future work characterizing the burden of nosocomial transmission. Understanding the transmission pathways of C difficile within health care facilities, particularly the roles of environmental surfaces and HCP hands, is critical to improving infection control measures.

AIMS: To examine the national trend in per-capita medical expenditures among U.S. adults with diabetes from 2000 to 2022. METHODS: We analyzed data from the Medical Expenditure Panel Survey in U.S. adults aged ≥18 years with self-reported diabetes. We calculated the expenditure in total and by component, including outpatient services, inpatient services, emergency room (ER) visits, prescription drugs, and other medical services. We used joinpoint regression to identify changes in trends. RESULTS: Estimated total per-capita expenditure increased 66 %, from $9,700 (95 % CI $8,736-$10,663) in 2000 to $16,067 (95 % CI $15,049-$17,086) in 2022. Specifically, spending on prescription drugs, outpatient, ER, and other medical services increased by 144 %, 96 %, 122 %, and 135 %, respectively, while inpatient spending decreased by 28 %. Two significant upward trend periods (2000-2004 and 2011-2018) were identified for total expenditure. Spending trends by component varied, with an accelerated increase in prescription drug spending after 2012; by 2022, prescription drugs accounted for the largest share (39 %) of total expenditures. CONCLUSIONS: The economic burden of diabetes on the national health care system has been increasing, with spending changes varying by medical service category. Interventions to prevent diabetes and its complications may help mitigate this growing economic burden.

BACKGROUND: Community-level social vulnerabilities may affect HIV outcomes. This analysis assessed the association between county-level social vulnerability and Centers for Disease Control and Prevention (CDC)-funded HIV testing program outcomes. SETTING: HIV testing data from 60 state and local health departments and 119 community-based organizations were submitted to CDC during 2020-2022. METHODS: HIV testing data were combined with the county-level Minority Health Social Vulnerability Index, which measures economic, medical, and social vulnerability. We calculated absolute and relative disparity measures for HIV testing program outcomes (ie, HIV positivity, linkage to HIV medical care, interview for partner services, referral to preexposure prophylaxis providers) between high and low social vulnerability counties. We compared differences in HIV testing program outcomes by demographic factors and test site type. RESULTS: The majority (85.8%) of the 4.9 million tests were conducted in high social vulnerability counties. HIV positivity (1.1%) and linkage to medical care after a new diagnosis (77.5%) were higher in high social vulnerability counties. However, interview for partner services after a new diagnosis (72.1%) and referrals to preexposure prophylaxis providers among eligible HIV-negative persons (48.1%) were lower in high social vulnerability counties. Additionally, the relative disparity in HIV testing program outcomes varied by demographic factors and test site type. CONCLUSIONS: CDC-funded HIV testing programs reach the most vulnerable communities. However, testing outcomes vary by community vulnerability, demographic factors, and test site type. Continued monitoring of the relationship between county-level social vulnerability and HIV testing program outcomes would guide HIV testing efforts and allocate resources effectively to achieve the national goal of ending the HIV epidemic.

In the United States, New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) are frequently associated with healthcare encounters. From September 2021 to September 2022, 21 patients with NDM-CRE identified from urine and without healthcare exposure were reported to the Centers for Disease Control and Prevention. Isolates were genetically similar to healthcare-associated strains.

BACKGROUND: Phthalate exposure during pregnancy has been associated with preterm birth, but mechanisms of action may depend on the timing of exposure. OBJECTIVE: Investigate critical periods of susceptibility during pregnancy for associations between urinary phthalate metabolite concentrations and preterm birth. METHODS: Individual-level data were pooled from 16 US cohorts (N = 6045, n = 539 preterm births). We examined trimester-averaged urinary phthalate metabolite concentrations. Most phthalate metabolites had 2248, 3703, and 3172 observations in the first, second, and third trimesters, respectively. Our primary analysis used logistic regression models with generalized estimating equations (GEE) under a multiple informant approach to estimate trimester-specific odds ratios (ORs) of preterm birth and significant (p < 0.20) heterogeneity in effect estimates by trimester. Adjusted models included interactions between each covariate and trimester. RESULTS: Differences in trimester-specific associations between phthalate metabolites and preterm birth were most evident for di-2-ethylhexyl phthalate (DEHP) metabolites. For example, an interquartile range increase in mono (2-ethylhexyl) phthalate (MEHP) during the first and second trimesters was associated with ORs of 1.15 (95 % confidence interval [CI]: 0.99, 1.33) and 1.11 (95 % CI: 0.97, 1.28) for preterm birth, respectively, but this association was null in the third trimester (OR = 0.91 [95 % CI: 0.76, 1.09]) (p-heterogeneity = 0.03). CONCLUSION: The association of preterm birth with gestational biomarkers of DEHP exposure, but not other phthalate metabolites, differed by the timing of exposure. First and second trimester exposures demonstrated the greatest associations. Our study also highlights methodological considerations for critical periods of susceptibility analyses in pooled studies.

People who inject drugs (PWID) account for the majority of hepatitis C virus (HCV) infections in the United States. The injection-equipment-sharing network likely plays an important role in shaping the dynamics of HCV transmission. Recognizing the emerging HCV epidemic in rural communities, we developed an agent-based network simulation model of HCV transmission via injection-equipment-sharing and used data on rural PWID networks to inform model parameterization and calibration. We then simulated an array of networks that varied key network properties to understand their impact on the magnitude and distribution of HCV incidence. The results show substantial heterogeneity in HCV acquisition risks across the network, summarized using the Ghyaini coefficient. In addition, although PWID with fewer injection partners had lower incidence, they collectively acquired more infections due to their larger population size. Higher prevalence, average number of partners, and homophily in HCV infection were associated with lower heterogeneity in infection risk across the network and higher overall incidence; other network properties including population size did not have a substantial impact. Our findings illustrate the heterogeneity of HCV transmission among PWID and suggest key network properties that could be measured, evaluated, or considered in the design of interventions for PWID in future studies.

Per- and polyfluoroalkyl substances (PFAS) have been associated with increased risk of hypertensive disorders of pregnancy, but whether PFAS influence blood pressure (BP) trajectories among normotensive pregnant women is unknown. We examined associations between PFAS mixtures and BP trajectories during pregnancy among normotensive women. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in plasma collected at ∼28 gestational weeks among pregnant women enrolled in the New Hampshire Birth Cohort Study (2009-2018). Systolic BP (SBP) and diastolic BP (DBP) were abstracted from pregnancy medical records. We identified BP trajectories using latent class trajectory modeling and evaluated associations between PFAS mixtures and BP trajectories using probit Bayesian kernel machine regression and multinomial quantile g-computation. We used linear mixed models to examine individual PFAS and BP changes during the third trimester. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, and gestational week of blood sample collection. During late pregnancy, plasma PFOS was associated with greater increases in SBP and PFHxS was associated with greater increases in DBP. Over the third trimester, each doubling in plasma PFOS was associated with 0.07 mmHg (95% CI: -0.01, 0.14) increase per week in SBP, and each doubling in plasma PFHxS was associated with 0.07 mmHg (95% CI: 0.02, 0.12) increase per week in DBP. Our study provides additional evidence suggesting that PFAS may adversely influence blood pressure even among normotensive women.

BACKGROUND: Incidence data on pediatric chronic kidney disease (CKD) is incomplete. We developed electronic health record (EHR)-based algorithms (e-phenotypes) to identify cases and provide incidence estimates of 5 leading causes of pediatric CKD. METHODS: E-Phenotypes using common standardized clinical terminology were built and contained utilization, diagnostic, procedural, age, and time-period inclusion and exclusion criteria for autosomal dominant polycystic kidney disease (ADPKD), Alport Syndrome (AS), congenital anomalies of the kidney and urinary tract (CAKUT), lupus nephritis (LN), and primary childhood nephrotic syndrome (NS). Cases diagnosed between 2014 and 2023 were identified from a pediatric healthcare system that is the sole pediatric nephrology provider serving the Atlanta Metropolitan Statistical Area (MSA). The performance of the e-phenotypes was tested using a cohort of 1,000 pediatric patients. Cases identified were used to estimate incidences using population information from the Georgia Department of Health. RESULTS: The e-phenotypes demonstrated sensitivity ranging from 0.83 to 0.95, specificity 0.96 to 1.00, PPV 0.81 to 1.00, and NPV 0.98 to 1.00. All positive likelihood ratios (LR) were >20 and negative LR < 0.20. The 6,814 combined cases of ADPKD (n=107), AS (n=31), CAKUT (n=6,120), LN (n=161), and NS (n=395) had an annual incidence of 47.07 (95% CI 45.96-48.20) per 100,000 children. Annual incidence per 100,000 children (95% CI) for each condition was: ADPKD 0.74 (0.61- 0.89), AS 0.21 (0.15-0.30), CAKUT 42.28 (41.22-43.35), LN 1.11 (0.95-1.30), and NS 2.73 (2.47-3.01). CONCLUSIONS: Our incidence estimates suggest CKD conditions are common among children. The e-phenotypes require validation for use at other institutions but offer opportunities to examine determinants of CKD detection, management, and outcomes.

Background: Although short-term outcomes of Long COVID have been described, longer-term physical and mental health outcomes of Long COVID are less well-established. This study sought to assess differences in long-term physical and mental health outcomes extending up to three years among those with current, resolved, and no Long COVID, as well as duration of Long COVID and vaccination status. Methods: This was a prospective, multisite, study of participants with SARS-CoV-2 infection from 12/7/2020-8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by Long COVID status (never-had, resolved, current), Long COVID duration and vaccination status. Findings: Of 3663 participants, 2604 (71.1%) never had Long COVID, 994 (27.1%) reported current Long COVID, and 65 (1.8%) reported resolved Long COVID. Compared to never having Long COVID, current Long COVID had lower/worse scores for Patient-Reported Outcomes Measurement Information System (PROMIS) version 29 Physical (7.8; 95% confidence interval [CI] 7.3–8.3) and Mental Health (9.4; 95% CI 8.8–10.1) and higher likelihood of moderate-to-high stress (adjusted odds ratio [aOR]: 2.0; 95% CI 1.6–2.4), moderate-to-high loneliness (aOR: 1.6; 95% CI 1.4–2.0), moderate-to-severe fatigue (aOR: 3.0; 95% CI 2.5–3.7), insufficient activity (aOR for Speedy Nutrition and Physical Activity Assessment ≤4: 0.6; 95% CI 0.5–0.7; aOR for Exercise Vital Sign ≤150 min/week: 0.7, 95% CI 0.6–1.0), and worse dyspnea (aOR: 5.0; 95% CI 4.3–5.8). Resolved Long COVID had lower scores for PROMIS Physical by 2.0 (95% CI 0.2–3.8) and Mental Health by 2.3 (95% CI 0.2–4.4) than the never-had-Long COVID cohort. Number of COVID-19 vaccinations was associated with better outcomes across all measures. Interpretation: Among participants followed up to 3 years after initial infection, those with current Long COVID had worse physical and mental health outcomes. The majority of those with Long COVID did not resolve, with less than 2% having resolved Long COVID. The resolved Long COVID cohort had moderately worse physical and mental health compared with those never-having-Long COVID. COVID-19 vaccination was associated with better outcomes. Funding: Centers for Disease Control and Prevention. © 2025 The Author(s)

INTRODUCTION: There is limited information about vaccine-preventable disease (VPD) surveillance cost. To address this gap, retrospective micro-costing studies of pre-COVID-19 pandemic VPD surveillance were conducted in Nepal and Ethiopia. Based on these evaluations-the sole cost evaluations on comprehensive VPD surveillance-this article provides methodological considerations and recommendations for other countries planning to conduct VPD surveillance costing studies to inform planning and budgeting. METHODS: The methods used for each study were systematically compared by key themes: costing perspective, cost categories, costing approach, allocation of shared costs, sampling criteria, extrapolation strategies, data collection, and analytic adjustments. For each theme, investigators identified methodologic challenges and potential strategies to address them, compared study methodologies to surveillance costing guidelines, and recommended practices for future such studies. RESULTS: The studies used similar perspectives and VPD inclusion criteria. Costs in Nepal were collected and analyzed by a subset of surveillance core and support functions, whereas the Ethiopia study categorized costs using surveillance support functions from the Global Strategy on Comprehensive VPD Surveillance. A mix of random and purposive sampling of surveillance sites was used in both studies. Surveillance sites were selected considering the strata of interest at each administrative level. Results from both studies were extrapolated country-wide using sampling weights and assumptions about the representativeness of purposively sampled units. DISCUSSION: The review highlighted potential methodologic tradeoffs in utility and precision of results based on the lessons learned from two country VPD surveillance cost studies. The advantages of collecting and using cost estimates by VPD surveillance core versus support function for program budgeting for varied audiences should be explored in future studies. Sampling strategies should be developed with consideration for the precision needed for the intended use of costing results. The resulting recommendations can improve and standardize the conduct and interpretation of future such studies.

Anemia is an important cause of child morbidity and mortality. Postmortem point-of-care hemoglobin testing is a potential method for assessing anemia at death, but its reliability has not been extensively studied. We aimed to assess the feasibility and validity of postmortem point-of-care hemoglobin assessment using HemoCue in the setting of a child mortality surveillance program in South Africa.In a pilot cohort study, 44 children under five years of age who died in an academic hospital in South Africa were enrolled. Hemoglobin levels were measured from venous blood antemortem using standard hematology analyzers and postmortem using the HemoCue 201 from blood collected within 72 hours of death (either by needle aspiration or from whole blood collected in an EDTA tube). Updated World Health Organization hemoglobin cutoffs to define anemia were used. Wilcoxon signed-rank tests, equivalence tests, and regression models assessed the concordance between antemortem and postmortem hemoglobin concentrations. Postmortem testing showed a significant decrease in hemoglobin concentrations compared to antemortem levels. However, no significant differences were found between hemoglobin measurements from needle aspiration and those from EDTA tubes postmortem. The prevalence of anemia increased from 52% antemortem to 73-77% postmortem, with the most notable rises in moderate and severe anemia. Bland-Altman analysis confirmed a systematic, not random, decrease in postmortem hemoglobin measurements. Upon applying a fixed adjustment of 2.5 g/dL, the sensitivity and specificity of postmortem hemoglobin testing to diagnose anemia were 69.6% and 61.9%, respectively. Postmortem point-of-care hemoglobin testing using HemoCue is feasible and offers a potentially valid reflection of antemortem anemia status in deceased children, despite consistently lower measured values postmortem. These findings support the utility of postmortem hemoglobin assessments in determining the presence and severity of anemia at the time of death.

IMPORTANCE: The degree that in-home cannabis smoking can be detected in the urine of resident children is unclear. OBJECTIVE: Test association of in-home cannabis smoking with urinary cannabinoids in children living at home. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from Project Fresh Air, a 2012-2016 randomized clinical trial to reduce fine particulate matter levels. Eligible participants were recruited from households in San Diego County, California, with children under age 14 years and an adult tobacco smoker in residence. Children's urine samples were analyzed in 2022. EXPOSURES: In-home cannabis smoking, measured by: parent or guardian report of in-home cannabis smoking; number of daily nonspecific smoking events computed via an air particle count algorithm; and number of daily cannabis smoking events ascertained by residualization, adjusting for air nicotine, tobacco smoking, and other air particle generating or ventilating activities. MAIN OUTCOMES AND MEASURES: Levels of the cannabis biomarker Δ9-tetrahydrocannabinol (THC) and its major metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Biomarker molar equivalents were summed to represent total THC equivalents (TTE) in urine. Logistic regression assessed whether in-home smoking was associated with cannabis biomarker detection. For children with detectable urinary cannabinoids, linear regression assessed in-home smoking association with quantity of urinary TTE. RESULTS: A total of 275 children were included in analysis (mean [SD] age, 3.6 [3.6] years; 144 male [52.4%]; 38 Black [13.8%], 132 Hispanic [48.0%], and 52 White [18.9%]). Twenty-nine households (10.6%) reported in-home cannabis smoking in the past 7 days; 75 children [27.3%] had detectable urinary cannabinoids. Odds of detectable TTE in children's urine were significantly higher in households with reported in-home cannabis smoking than households without (odds ratio [OR], 5.0; 95% CI, 2.4-10.4) and with each additional ascertained daily cannabis smoking event (OR, 2.5; 95% CI, 1.6-3.9). Although the point estimate for TTE levels was higher among children with detectable urinary cannabinoids and exposure to more daily cannabis smoking events (increase per event, 35.68%; 95% CI, -7.12% to 98.21%), the difference was not statistically significant. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, in-home cannabis smoking was associated with significantly increased odds of child exposure to cannabis smoke, as assessed by urinary cannabinoid biomarkers. As young children spend most of their time at home, reducing in-home cannabis smoking could substantially reduce their exposure to the toxic and carcinogenic chemicals found in cannabis smoke.

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses.

INTRODUCTION: Population risk for neural tube defects (NTDs) can be determined using red blood cell (RBC) folate. However, a paucity of biomarker and surveillance data among non-lactating, non-pregnant women of reproductive age (NPWRA) from Africa limits accurate assessment. Our study assessed folate and vitamin B12 status among non-lactating NPWRA and predicted population risk of NTDs in Tanzania. METHODS: A cross-sectional biomarker survey of non-lactating NPWRA (15-49 years) in the Morogoro region, Tanzania was conducted during June-October 2019. Questionnaire interview responses and non-fasting blood samples were collected. Folate was assessed using the CDC microbiologic assay kit and vitamin B12 was measured using an electrochemiluminescence immunoassay. Complex survey design analyses were conducted using SAS-callable SUDAAN (v11.0.1). RESULTS: Of the 761 participating non-lactating NPWRA, 294 (39.8%) had RBC folate insufficiency (<748 mol/L). The prevalence of RBC folate insufficiency was lower among non-lactating NPWRA living in urban than rural areas (PR: 0.72, 95% CI: 0.52-0.99) but did not differ by age or household wealth index. Vitamin B12 insufficiency was uncommon (< 221 pmol/L, 2.7%). The estimated NTD risk was 10.5 (95% uncertainty interval: 8.1-13.3) per 10,000 births. DISCUSSION: Elevated NTD risk was predicted in the Morogoro region of Tanzania, where ∼ 40% of non-lactating NPWRA had RBC folate insufficiency and < 3% had vitamin B12 insufficiency. The NTD risk is consistent with surveillance data for the area, limited folic acid fortification of staple foods, and low vitamin B12 insufficiency. Further studies are needed to better understand the context of these findings, especially the impact of micronutrient fortification in Tanzania.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.91 million children (4.2% of children) had in their lifetime experienced prevalent orphanhood and caregiver death combined, with incidence increasing by 49.5% and prevalence by 7.9% since 2000. Populations disproportionately affected by orphanhood included 5.2% of all adolescents; 6.4% and 4.7%, respectively, of non-Hispanic American Indian or Alaska Native, and non-Hispanic Black children; and children in southern and eastern states. In 2021, drug overdose was the leading cause of orphanhood among non-Hispanic white children, but not among minoritized subgroups. Effective policies and programs to support nearly three million bereaved children are needed to reduce the acute and long-term negative effects of orphanhood.

Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials(®) (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D(2) [25(OH)D(2)] and 25-hydroxyvitamin D(3) [25(OH)D(3)], was assessed through an interlaboratory study. The following SRMs were assessed: (1) SRM 2969 Vitamin D Metabolites in Frozen Human Serum (Total 25-Hydroxyvitamin D Low Level), (2) SRM 2970 Vitamin D Metabolites in Frozen Human Serum (25-Hydroxyvitamin D(2) High Level), and (3) SRM 1949 Frozen Human Prenatal Serum. These SRMs represent three clinically relevant situations including (1) low levels of total 25(OH)D, (2) high level of 25(OH)D(2), and (3) 25(OH)D levels in nonpregnant women and women during each of the three trimesters of pregnancy with changing concentrations of vitamin D-binding protein (VDBP). Twelve laboratories using 17 different ligand binding assays and eight laboratories using nine commercial and custom liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays provided results in this study. Commutability of the SRMs with patient samples was assessed using the Clinical and Laboratory Standards Institute (CLSI) approach based on 95% prediction intervals or a pre-set commutability criterion and the recently introduced International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approach based on differences in bias for the clinical and reference material samples using a commutability criterion of 8.8%. All three SRMs were deemed as commutable with all LC-MS/MS assays using both CLSI and IFCC approaches. SRM 2969 and SRM 2970 were deemed noncommutable for three and seven different ligand binding assays, respectively, when using the IFCC approach. Except for two assays, one or more of the three pregnancy levels of SRM 1949 were deemed noncommutable or inconclusive using different ligand binding assays and the commutability criterion of 8.8%. Overall, a noncommutable assessment for ligand binding assays is determined for these SRMs primarily due to a lack of assay selectivity related to 25(OH)D(2) or an increasing VDBP in pregnancy trimester materials rather than the quality of the SRMs. With results from 17 different ligand binding and nine LC-MS/MS assays, this study provides valuable knowledge for clinical laboratories to inform SRM selection when assessing 25(OH)D status in patient populations, particularly in subpopulations with low levels of 25(OH)D, high levels of 25(OH)D(2), women only, or women who are pregnant.

Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals. Copyright © 2025 by the American Thoracic Society.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring. METHODS: We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002. We examined associations of maternal prenatal (median: 9.6 weeks gestation) plasma concentrations of six PFAS (log2 transformed) with PCOS and related characteristics among daughters during mid-to-late adolescence. We estimated the associations of single PFAS and PFAS as a mixture with each outcome, using logistic regression and quantile g-computation, respectively, adjusting for parity, and maternal sociodemographic and other lifestyle/health factors. RESULTS: Among the 322 mother-daughter pairs, the majority of mothers identified as non-Hispanic White and had a college degree, and 13% of daughters had either self-reported PCOS or probable PCOS based on irregular menstrual cycles and clinical or biochemical markers of hyperandrogenism. Among all daughters, there were 27% with irregular menstrual cycles, 34% with hirsutism, and 6% with moderate-to-severe acne. When fully adjusted for confounders, per doubling of maternal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) concentration was associated with higher odds of self-reported PCOS [OR (95% CI) = 2.66 (1.18, 5.99)], and per doubling of maternal perfluorononanoate (PFNA) concentration was associated with higher odds of moderate-to-severe acne [OR (95% CI) = 2.33 (1.09, 4.99)] in daughters with or without irregular menstrual cycles. We found no associations of the mixture of six PFAS with PCOS or related traits. CONCLUSION: Our findings suggest a positive association between maternal concentrations of EtFOSAA and PCOS in their daughters during mid-to-late adolescence, although future studies with larger sample size and extended follow-up across the reproductive life-course are needed.

INTRODUCTION: Despite progress in systemic lupus erythematosus (SLE) treatment, challenges persist in medication adherence due to side effects and costs. Precision nutrition, particularly adjusting fatty acid intake, offers a cost-effective strategy for enhancing SLE management. Prior research, including our own, indicates that increased consumption of omega-3 polyunsaturated fatty acids (PUFAs) correlates with improved outcomes in SLE patients. Here we build upon these findings by investigating associations between serum fatty acids-grouped as PUFAs, monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs)-and lupus activity, pain, and sleep disturbance. METHODS: Using data from 418 participants with SLE in the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, we examined associations between serum levels of 25 fatty acids determined by GC-MS and patient-reported outcomes. Disease activity, pain, and sleep quality were assessed using standardized questionnaires. Generalized additive models and partial residual plots were utilized to examine the linearity of fatty acid effects. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO), followed by multiple linear regression adjusting for sociodemographic factors. RESULTS: Findings indicated favorable associations between ω-3 PUFAs-and, to a lesser extent, ω-6 PUFAs-and patient-reported outcomes, while MUFAs and SFAs showed unfavorable associations. Docosahexaenoic acid (DHA), an omega-3 PUFA, exhibited the most robust favorable associations across all outcomes. Additionally, the omega-3 α-linolenic acid (ALA) was linked to reduced pain, whereas eicosapentaenoic acid (EPA), another omega-3, was associated with worsened disease activity and pain. Among omega-6 PUFAs, dihomo-γ-linolenic acid (DGLA) was favorably associated with disease activity, while the omega-9 PUFA Mead acid was linked to increased pain. DISCUSSION: These findings underscore the prospect that increased tissue levels of long-chain omega-3 PUFAs, particularly DHA, are favorably associated with SLE outcomes. Although further research is needed to establish causal relationships, existing evidence supports the role of omega-3 PUFAs in managing cardiovascular and chronic kidney disease, common SLE comorbidities. Most study participants exhibited low omega-3 PUFA status, suggesting substantial potential for improvement through targeted dietary interventions and supplementation. This study supports a potential role for precision nutrition in comprehensive SLE management, considering the impact of PUFAs, SFAs and MUFAs.

BACKGROUND: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections. METHODS: The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health. RESULTS: We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants. CONCLUSION: Here, we present the Consortium's formation and overarching study design. IMPACT: The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies.

Inhalation exposure to respirable crystalline silica (RCS) during the fabrication of engineered stone-based kitchen countertops has been on the rise in recent years and has become a significant occupational health problem in the United States and globally. Little is known about the presence of nanocrystalline silica (NCS), i.e., particles below 100 nm. We present a methodology to quantify the crystalline silica content in the sub-100 nm size fraction of the aerosol released during engineered stone fabrication using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Aerosol was generated in a test chamber designed per EN 1093-3 and sampled using cascade impactors. XRD and FTIR analysis showed the presence of both α-quartz (15-60%) and cristobalite (10-50%) polymorphs in all size fractions. With increasing particle size, the cristobalite content increased. Seventy percent of the total aerosol mass in the sub-100 nm fraction was found to be crystalline silica, qualitatively confirmed by electron diffraction and electron energy loss spectroscopy. The presence of other minerals was detected in all size fractions; no polymeric resin binder was detected in the sub-100 nm fraction. Although the sub-100 nm fraction was about 1% of the aerosol mass, it accounted for 4-24% of the aerosol surface area based on the total lung deposition. If the surface area is a more relevant exposure metric, the assessment of the efficacy of current engineering control systems using mass as an exposure metric may not provide adequate protection.

BACKGROUND: Tuberculosis (TB) Building and Strengthening Infection Control Strategies (TB BASICS) aimed to achieve improvements in TB infection prevention and control (IPC) through structured training and mentorship. METHODS: TB BASICS was implemented in six Chinese provinces from 2017-2019. Standardized, facility-based risk assessments tailored to inpatient, laboratory, and outpatient departments were conducted quarterly for 18 months. Knowledge, attitudes, and practices surveys were administered to healthcare workers (HCW) at nine participating facilities during the first and last assessments. Kruskal-Wallis rank sum test assessed score differences between departments (alpha = 0.05). RESULTS: Fifty-seven departments received risk assessments. IPC policies and practices improved substantially during follow up. Facility-based assessment scores were significantly lower in outpatient departments than other departments (p <0.05). All indicators achieved at least partial implementation by the final assessment. Low scores persisted for implementing isolation protocols, while personal protective equipment use among staff was consistent among all departments. Overall, we observed minimal change in IPC knowledge among HCW. In general, HCW had favorable views of their own IPC capabilities, but reported limited agency to improve institutional IPC. CONCLUSIONS: TB BASICS demonstrated improvements in TB IPC implementation. Structured training and mentorship engaged HCW to maintain confidence and competency for TB prevention.

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.

BACKGROUND: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response. METHODS: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins. FINDINGS: During September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies. INTERPRETATION: Although all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses. FUNDING: Centers for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation.

OBJECTIVES: To examine if point-of-care urine tenofovir testing-informed counseling could be used to improve virologic suppression (VS) among participants with virologic failure (VF) after ≥1 prior round of enhanced adherence counseling (EAC). METHODS: Participants were enrolled from 42 clinics across Namibia. At each monthly medication pick-up, participants completed the point-of-care urine test and received EAC informed by this testing (EAC+). If VS was not achieved after 3 months of EAC+, up to 3 additional rounds of EAC+ were provided, with resistance testing at month (M)9. RESULTS: Of 310 potentially-eligible participants across 42 clinics in Namibia, we enrolled 211 participants with VF (median age 33 years, 61% female); 195 reached M3 defined as receiving EAC+ and follow-up viral load testing; 169 achieved VS within M3 (87%, p<0(.)001) and 97% by M9 (181/186) compared to 40% (22/55) prior to the intervention (p<0.001). Resistance testing was performed in five remaining participants with VF at M9, of whom 1/5 (20%) developed dolutegravir resistance. CONCLUSIONS: The urine tenofovir assay when incorporated into adherence counseling has potential to be a cost-effective intervention among participants failing tenofovir-based regimens, increasing VS to 97% in those failing TLD. Encouraging results of this pre-post intervention will be rigorously tested in a randomized trial.