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

INTRODUCTION: Although preventable, dental caries remains highly prevalent. Many children do not receive preventive dental services routinely in clinical settings. This review examined the effectiveness of school (preschool through high school) fluoride varnish delivery programs (SFVDP) in preventing caries. METHODS: Community Guide systematic review methods were followed. In 2024, databases were searched for studies published through December 2023 on SFVDP effectiveness in increasing fluoride varnish (FV) receipt and decreasing caries. Included studies had to be written in English, published in peer-reviewed journals, and conducted in upper-middle or high-income countries. Data synthesis conducted in 2024 used median RR and interquartile interval (IQI) to summarize findings across studies. RESULTS: Of 31 included studies with 60,780 students, 25 were randomized controlled trials-20 with good quality of execution. Most studies were conducted in low socioeconomic status (SES) areas among students at elevated caries risk. SFVDP reduced caries initiation by 32% (IQI: 21%, 37%) in permanent teeth (19 studies, 25,826 students) and by 25% (IQI: 4%, 37%) in primary teeth (12 studies, 4,304 students). Stratified assessments indicated findings were largely applicable to different settings, populations, and intervention characteristics. Two studies found SFVDP significantly increased the number of annual FV applications and two found that SFVDP effectiveness was inversely related to SES. DISCUSSION: About 30% of states report having no SFVDPs. Possible barriers to implementation include that Medicaid in some states only reimburses dental and medical professionals and does not reimburse non-dental providers for FV delivered to children older than 6 years.

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023-February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season. METHODS: During September 1, 2023-May 31, 2024, a multistate sentinel surveillance network of 24 medical centers in 20 U.S. states enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI). Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and SARS-CoV-2. Vaccine effectiveness (VE) against influenza-associated hospitalization was calculated as (1 - adjusted odds ratio for vaccination) × 100%. RESULTS: Among 7690 patients, including 1170 influenza cases (33% vaccinated) and 6520 controls, VE was 40% (95% CI: 31%-48%) with varying estimates by age (18-49 years: 53% [34%-67%]; 50-64 years: 47% [31%-60%]; ≥65 years: 31% [16%-43%]). Protection was similar among immunocompetent patients (40% [30%-49%]) and immunocompromised patients (32% [7-50%]). VE was statistically significant against influenza B (67% [35%-84%]) and A(H1N1) (36% [21%-48%]) and crossed the null against A(H3N2) (19% [-8%-39%]). VE was higher for patients 14-60 days from vaccination (54% [40%-65%]) than >120 days (18% [-1%-33%]). CONCLUSIONS: During 2023-2024, influenza vaccination reduced the risk of influenza A(H1N1)- and influenza B-associated hospitalizations among adults; effectiveness was lower in patients vaccinated >120 days prior to illness onset compared with those vaccinated 14-60 days prior.

OBJECTIVES: Buprenorphine can decrease opioid use disorder and mortality risk but remains underutilized. This study evaluates changes in monthly buprenorphine dispensing associated with federal policy changes in the United States from 2018 to 2023. METHODS: This study used interrupted time series analysis comparing the monthly rate of patients dispensed buprenorphine after the implementation of telehealth flexibilities in March 2020, relaxation of training requirements in April 2021, and removal of waiver requirements in December 2022. Buprenorphine formulated for opioid use disorder was included from the IQVIA Total Patient Tracker. RESULTS: Before March 2020, the monthly rate of individuals dispensed buprenorphine was increasing. The rate of increase slowed after each policy change: -0.69 (95% CI=-1.00 to -0.39) after telehealth flexibilities were initiated, -0.60 (95% CI=-0.92 to -0.27) after relaxing training requirements, and -0.49 (95% CI=-0.73 to -0.24) after waiver elimination. After the elimination of the waiver, declines were observed across several specialty groups, including pain medicine, emergency medicine, and primary care, while the rate increased among addiction medicine specialists. CONCLUSIONS: After each policy change, the rate of individuals dispensed buprenorphine increased at a slower rate than before each policy change. These findings suggest that the removal of the waiver, while important, may not be sufficient on its own to meaningfully expand buprenorphine prescribing. Individual and systems-level strategies may be needed to fully optimize the impact of these policy changes focusing on reducing patient, clinician, and institutional stigma, addressing clinician barriers, implementing systems-level improvements, and strengthening payment policies that incentivize prescribing.

Vaccination is an effective preventive strategy against influenza. Kyrgyzstan introduced a comprehensive influenza vaccination program in 2013 and has collaborated with the Task Force for Global Health since 2017 to expand vaccination coverage. In 2023, an influenza vaccine post-introduction evaluation was conducted to identify strengths and weaknesses in the influenza vaccination program and to identify measures for improvement. Site visits were conducted across six regions of the country and interviews were conducted with national, regional and district staff, health facility staff, and individuals from priority populations for influenza vaccination using standardized questionnaires. Two major challenges identified in this evaluation were the inadequate supply of influenza vaccine to cover the priority groups and the low acceptance and uptake of influenza vaccine among pregnant people. These findings are important as they can inform targeted strategies and policy updates to increase influenza vaccine implementation and uptake in Kyrgyzstan.

OBJECTIVES: Serologic testing is a useful adjunct for the diagnosis of Lyme disease, a major public health problem in certain US regions. We aimed to determine whether Lyme disease serologic testing and results differed by sex and age group. METHODS: We identified 2 cohorts of individuals across all ages who underwent serologic testing for Lyme disease at a national reference laboratory in 2019 (cohort 1) and 2022 (cohort 2). If an individual had multiple tests in the same year, we included only the first test. We excluded individuals who had been tested in the previous 5 years. RESULTS: Cohorts 1 and 2 consisted of 578 052 and 550 674 people, respectively. Fewer males than females were tested in cohort 1 (42.7% vs 57.3%) and cohort 2 (42.3% vs 57.7%), although similar numbers were tested for both sexes among nonadults. More males than females had a positive test result in cohort 1 (53.9% more males) and cohort 2 (52.9% more males). The odds ratio of receiving a positive test result among males versus females was 2.09 (95% CI, 2.01-2.17) in cohort 1 and 2.12 (95% CI, 2.05-2.19) in cohort 2. Among people with positive test results, females (except children) were more likely than males to have positive immunoglobulin M and negative immunoglobulin G results, which can serve as a marker of early infection (odds ratio = 1.43 [95% CI, 1.31-1.55] in cohort 1 and 1.38 [95% CI, 1.29-1.47] in cohort 2). CONCLUSIONS: Further studies are needed to understand whether the observed differences in Lyme disease testing and positivity result from sex- and age-associated disparities in social behavior, health care seeking, clinical practice, or other factors.

OBJECTIVE: We investigated associations between per- and polyfluoroalkyl substances (PFAS) and changes in diabetes indicators from pregnancy to 12 years after delivery among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Eighty Hispanic women with GDM history were followed from the third trimester of pregnancy to 12 years after delivery. Oral and intravenous glucose tolerance tests were conducted during follow-up. Plasma PFAS concentrations were measured at the third trimester of pregnancy and first postpartum visit. A linear mixed-effects model was used to analyze associations between PFAS and trajectories of diabetes indicators, adjusted for age, breastfeeding status, daily total calorie intake, and body fat percentage. RESULTS: Increased 2-(N-methyl-perfluorooctane sulfonamido) acetate level was associated with faster increase in concentrations of fasting glucose (P = 0.003). Increased perfluorononanoate (PFNA) and linear perfluorooctanoate (n-PFOA) concentrations were associated with faster increase in fasting insulin concentrations (P = 0.04 for PFNA; P = 0.02 for n-PFOA) and faster decrease in acute insulin response to glucose (P = 0.04 for PFNA; P = 0.02 for n-PFOA). CONCLUSIONS: PFAS exposure is associated with glucose intolerance, insulin resistance, and β-cell dysfunction, thus increasing type 2 diabetes risk.

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.

We assessed the impact of pneumococcal conjugate vaccines on pneumococcal otitis media (OM) among children living in Navajo and White Mountain Apache Tribal lands. During the PCV7 era (2000-2009), the proportion of vaccine-type OM declined. However, vaccine-type OM (predominantly 3, 19A, and 19F) persisted in the PCV13 era (2010-2019).

BACKGROUND: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi. METHODS: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice. The intervention, tailored for each setting, included a diagnostic and management algorithm, a lumbar puncture pack, a testing panel, and staff training. We used multivariable logistic regression and interrupted time series analysis to compare the coprimary outcomes-the percentage of patients achieving a syndromic diagnosis and the percentage achieving a microbiological diagnosis before and after the intervention. The study was registered at ClinicalTrials.gov (NCT04190303) and is complete. FINDINGS: Between Jan 5, 2021, and Nov 30, 2022, we screened 10 462 patients and enrolled a total of 2233 patients at 13 hospital sites connected to the four study centres in Brazil, India, and Malawi. 1376 (62%) were recruited before the intervention and 857 (38%) were recruited after the intervention. 2154 patients (96%) had assessment of the primary outcome (1330 [62%] patients recruited pre-intervention and 824 [38%] recruited post-intervention). The median age across centres was 23 years (IQR 6-44), with 1276 (59%) being adults aged 16 years or older and 888 (41%) children aged between 29 days and 15 years; 1264 (59%) patients were male and 890 (41%) were female. Data on race and ethnicity were not recorded. 1020 (77%) of 1320 patients received a syndromic diagnosis before the intervention, rising to 701 (86%) of 813 after the intervention (adjusted odds ratio [aOR] 1·81 [95% CI 1·40-2·34]; p<0·0001). A microbiological diagnosis was made in 294 (22%) of 1330 patients pre-intervention, increasing to 250 (30%) of 824 patients post-intervention (aOR 1·46 [95% CI 1·18-1·79]; p=0·00040). Interrupted time series analysis confirmed that these increases exceeded a modest underlying trend of improvement over time. The percentage receiving a lumbar puncture, time to appropriate therapy, and functional outcome also improved. INTERPRETATION: Diagnosis and management of patients with suspected acute brain infections improved following introduction of a simple intervention package across a diverse range of hospitals on three continents. The intervention is now being implemented in other settings as part of the WHO Meningitis Roadmap and encephalitis control initiatives. FUNDING: UK National Institute for Health and Care Research.

IMPORTANCE: Stimulants are increasingly prescribed for US adults. Whether such prescribing is associated with misuse and prescription stimulant use disorder (PSUD) is less understood. OBJECTIVES: To examine (1) sex- and age-specific trends in the number of persons dispensed stimulants and trends in dispensed prescription stimulants by prescriber specialty in 2019 through 2022; (2) prevalence of misuse and PSUD by use of prescription amphetamine-type stimulants (hereafter referred to as amphetamines) and methylphenidate; and (3) PSUD prevalence and sociodemographic and behavioral health correlates among persons using prescription stimulants with and without prescription stimulant misuse. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study used the 2019-2022 IQVIA Total Patient Tracker and National Prescription Audit New to Brand databases and the 2021-2022 National Surveys on Drug Use and Health (NSDUH) (community-dwelling 18- to 64-year-old individuals). Data analysis was performed from March to April 2024. EXPOSURE: Past-year use of prescription stimulants. MAIN OUTCOMES AND MEASURES: PSUD using DSM-5 criteria. RESULTS: Of the sampled 83 762 adults aged 18 to 64 years, 33.8% (unweighted) were aged 18 to 25 years, 53.0% (unweighted) were aged 26 to 49 years, and 56.0% (unweighted) were women. Among those using prescription stimulants, 25.3% (95% CI, 23.8%-26.8%) reported misuse, and 9.0% (95% CI, 8.0%-10.0%) had PSUD. Among those with PSUD, 72.9% (95% CI, 68.3%-77.6%) solely used their own prescribed stimulants, 87.1% (95% CI, 82.3%-90.8%) used amphetamines, 42.5% (95% CI, 36.6%-48.5%) reported no misuse, and 63.6% (95% CI, 56.8%-69.8%) had mild PSUD. Individuals using amphetamines, compared with those using methylphenidate, had higher prevalence ratios of misuse (3.1 [95% CI, 2.2-4.3]) and PSUD (2.2 [95% CI, 1.3-3.8]). The largest increase in the number of individuals dispensed prescription stimulants was among women aged 35 to 64 years, from 1.2 million in quarter 1 of 2019 to 1.7 million in quarter 4 of 2022 (average quarterly percentage change, 2.6% [95% CI, 2.1%-3.1%]). The prevalence of prescription stimulant misuse was lower among women aged 35 to 64 years using these medications (13.7% [95% CI, 11.1%-16.8%]) than other sex- and age-specific subgroups (ranging from 22.0% [95% CI, 17.9%-26.7%] for men aged 35-64 years to 36.8% [95% CI, 32.6%-41.2%] for women aged 18-25 years). CONCLUSIONS AND RELEVANCE: High prevalence of prescription stimulant misuse and PSUD (regardless of misuse status) suggests the importance of ensuring clinically appropriate use and of screening for and treating PSUD among all adults prescribed stimulants, especially those using amphetamines. Findings may suggest potential progress in addressing the mental health care gap for middle-aged women and the need for evidence-based clinical guidance and training on benefits and risks of prescription stimulants for adults.

American Indian (AI) communities in the Southwest have a high burden of invasive pneumococcal disease (IPD) and COVID-19. Through laboratory-based surveillance, the impact of the pandemic on IPD incidence and serotype distribution was evaluated in two AI communities. IPD rates were lower during the pandemic (21.8 vs. 39.0/100 000 pre-pandemic). Rates increased in 2021 compared to 2020 but not to pre-pandemic levels. Cases with SARS-CoV-2 co-infection had a higher case fatality rate (45.2% vs. 17.6% without co-infection). No significant change in serotype distribution was observed. Continued surveillance in these communities is critical to understand the changing IPD burden as the pandemic evolves.

Krabbe disease (KD), which affects 0.3-2.6 per 100 000 live births, is an autosomal recessive lysosomal disorder caused by variants in the GALC gene that reduce galactosylceramidase (GALC) activity, leading to psychosine accumulation, cerebral white matter degeneration, and peripheral neuropathy. The most common form, infantile KD (IKD), has onset by 12 months with irritability, feeding difficulty, neurologic regression, and, when untreated, death in early childhood. Hematopoietic stem cell transplantation (HSCT) for IKD approximately 1 month after birth can improve long-term survival but has about a 10% risk of mortality within 100 days, and affected individuals can still have significant functional impairment. Newborn screening for KD is based on low GALC levels in dried-blood spots. Second-tier testing to assess whether an elevated psychosine concentration is present in the same dried-blood spot improves the specificity of screening for IKD. Without newborn screening, diagnosis of IKD is generally made after significant clinical symptoms develop, past when HSCT can be effective. The benefit of newborn detection of later-onset phenotypes of KD is uncertain. In 2024, the US Secretary of Health and Human Services added IKD to the Recommended Uniform Screening Panel after a recommendation by the Advisory Committee on Heritable Disorders in Newborns and Children. For IKD newborn screening to be as effective as possible, it is important to have systems in place to support families in making challenging decisions soon after diagnosis about whether to pursue HSCT and to ensure rapid access to HSCT if chosen.

We describe the epidemiology of invasive group B streptococcal (GBS) disease among non-pregnant Alaska adults using statewide surveillance data. During 2004-2023, 880 cases of invasive GBS disease were reported for an age-adjusted annual incidence of 9.1 (95% CI, 8.5-9.7) cases per 100,000 adults. Incidence increased 1.9-fold (95% CI, 1.6-2.2) between 2004-2013 and 2014-2023. Adults aged ≥65 years had a 4.4-fold higher risk of invasive disease compared to younger adults, and 47% of adults with invasive GBS had diabetes. Healthcare providers should be aware of populations at increased risk, potentially allowing for more prompt treatment.

Numerous studies have investigated vaccine-induced correlates of protection (CoP) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, but data on infection-induced CoP are limited. Given differences between vaccine- and infection-induced immune responses, in conjunction with low vaccination in many US populations, a better understanding of infection-induced CoP is needed. We used residual sera from a mid-2020 Rhode Island serosurvey of healthcare professionals (HCP) and corresponding state-collected SARS-CoV-2 testing data through February 2021 to generate an analytic cohort of HCP with a first SARS-CoV-2 infection prior to serosurvey blood collection and multiple viral tests after blood collection to assess for reinfection (defined as a positive viral test ≥90 days after their first positive). We tested sera for levels of IgG and IgA targeting ancestral spike (S), receptor-binding domain (RBD), or nucleocapsid (N). We used adjusted Cox proportional hazard ratios to assess the association between categorical antibody level and the risk of subsequent reinfection. Among 170 HCP included in this analysis (median age = 47 years; interquartile range: 35-55 years), 30 were reinfected during the analytic period. Adjusted Cox proportional hazard ratios indicated that higher levels of anti-S or anti-RBD IgG were significantly associated with a lower risk of reinfection. These findings support the use of anti-S or anti-RBD IgG levels as markers of immunologic protection, such as in population serosurveys, or immune-bridging studies in settings of high prevalence of prior infection.  IMPORTANCEThe measurement of antibodies in blood is a relatively simple process and commonly used to estimate overall levels of past infection in populations. But, if someone has antibodies, does this mean that they are protected from being infected again? And are people with higher levels of antibody better protected? There are good data in the literature exploring how antibodies from the coronavirus disease 2019 (COVID-19) vaccination are associated with protection. But, there is still a lot to learn about protection conferred by antibodies that develop after a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In our study, we measure the levels of six different antibody types developed after infection and compare levels to the risk of subsequent infection to better understand which antibody types are best associated with protection. Our data are important for improving studies that use antibodies as proxies for protection, such as population immunity estimates, or those assessing new prevention products.

OBJECTIVES/BACKGROUND: We evaluated patterns of serum concentrations of endocrine disrupting chemicals (EDCs), namely polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), in a U.S. military sample by race/ethnicity (R/E) and sex. METHODS: Twenty-three EDCs were measured in stored serum samples obtained between 1995 and 2010 for 708 service members from the Department of Defense Serum Repository. For each EDC, geometric means (GM) were estimated using log-transformed concentrations in a linear regression model, for eight combined R/E/sex groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), non-Hispanic Asian (NHA), and Hispanic men and women, adjusted for age and service branch and stratified by age tertile ("younger age": 17-23, "middle age": 24-30, and "older age": 31-52 years). Comparisons were made between our military sample and the National Health and Nutrition Examination Survey (NHANES) 2003-2004 data for NHW and NHB groups. RESULTS: Within our military sample, the highest PCB concentrations were among older age NHB men and women and highest OCP concentrations among older age NHB women and NHA men. PBDE concentrations were generally highest in middle age Hispanic women and NHA men, though based on small sample size. Generally, NHB men and women had higher concentrations of EDCs in both the military and NHANES. CONCLUSIONS: We found patterns of elevated EDC concentrations among NHB, NHA, and Hispanic groups in the military sample and for NHB men and women in NHANES. There were no consistent patterns of higher or lower EDCs comparing the military to NHANES. Future studies of EDCs and health outcomes should stratify by R/E/sex to account for potential disparities in EDC concentrations.

Objective: Schools’ ability to implement recommended hygiene-related activities is critical in preventing the spread of gastrointestinal and respiratory illness. We conducted this study to improve understanding of perceived barriers to, and responsibility for implementing recommended activities related to hand hygiene, cleaning, and disinfection. Methods: We recruited a convenience sample of adults affiliated with the National Parent Teacher Association during July-August 2020. Questions focused on barriers to implementing recommended hygiene-related, cleaning, and disinfection activities. Results: Overall, 1173 participants completed the survey. Among caregivers, the main barriers to conducting hand hygiene were educators’ ability to monitor students (72%), lack of time (66%), and limited funding for hygiene supplies (65%). Among educators, the main barriers to conducting hand hygiene were access to needed supplies (75%), ability to monitor students (75%), and lack of time (72%). The top barriers reported by both groups relating to cleaning and disinfection activities were similar, with both groups reporting limited staff capacity (61% vs 75%), lack of time/scheduling difficulties (64% vs 75%), and lack of funds to purchase supplies (64% vs 70%). Conclusions: Our results clarify stakeholder concerns around implementation and main barriers. To implement recommended activities, schools need support (funding, staff, and supplies) and guidance for hygiene-related activities. © 2024, Paris Scholar Publishing. All rights reserved.

Antimalarial therapeutic efficacy studies are vital for monitoring drug efficacy in malaria-endemic regions. The WHO recommends genotyping polymorphic markers including msp-1, msp-2, and glurp for distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with microsatellites (Poly-α, PfPK2, TA1). However, suitable combinations with msp-1 and msp-2, as well as the performance of different algorithms for classifying recrudescence, have not been systematically assessed. This study investigated various microsatellites alongside msp-1 and msp-2 for molecular correction and compared different genotyping algorithms across three sites in Uganda. Microsatellites 313, Poly-α, and 383 exhibited the highest diversity, while PfPK2 and Poly-α revealed elevated multiplicity of infection (MOI) across all sites. The 3/3 match-counting algorithm classified significantly fewer recrudescences than both the ≥ 2/3 and Bayesian algorithms at probability cutoffs of ≥ 0.7 and ≥ 0.8 (P < 0.05). The msp-1/msp-2/2490 combination identified more recrudescences using the ≥ 2/3 and 3/3 algorithms in the artemether-lumefantrine (AL) treatment arm, while msp-1/msp-2/glurp combination classified more cases of recrudescence using the ≥ 2/3 in the dihydroartemisinin-piperaquine (DP) arm. Microsatellites PfPK2 and Poly-α, potentially sensitive to detecting minority clones, are promising replacements for glurp. Discrepancies in recrudescence classification between match-counting and Bayesian algorithms highlight the need for standardized PCR correction practices.

BACKGROUND: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery. METHODS: This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways. RESULTS: We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways. CONCLUSION: Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

BACKGROUND: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance. METHODS: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]). RESULTS: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods. CONCLUSIONS: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups.

People with immunocompromising conditions (IC) are at increased risk of severe COVID-19 and death. These individuals show weaker immunogenicity following vaccination than individuals without IC, yet immunogenicity after SARS-CoV-2 infection is poorly understood. To address this gap, the presence of infection-induced antibodies in sera following a positive COVID-19 test result was compared between patients with and without IC. A commercial laboratory provided patient data gathered during July 2020-February 2022 on COVID-19 viral test results and antibody assay results, which included infection-induced (anti-N) antibody presence. Participants were categorized into having or not having IC based on if there was an indicative diagnostic code on their health record for a five-year period prior to the study period. Anti-N presence in sera from people with a positive COVID-19 test result was compared by IC status for four post-infection periods: 14-90, 91-180, 181-365, and 365+ days. A longitudinal, logistic regression produced adjusted odds ratios comparing anti-N prevalence among specimens with and without associated IC, adjusted for age, sex, residence in a metro area, and social vulnerability index (SVI) tertile. Data included 17,025 anti-N test results from 14,690 patients, 1,424 (9.7%) of which had at least one IC on record. In an adjusted comparison to patients without IC, patients with any IC were 0.61 times as likely to have infection-induced antibodies (99% CI: 0.40-0.93), during the 14-90 days following infection. Similar patterns were found when comparing people with two specific types of IC to people without any IC: (1) solid malignancies and (2) other intrinsic immune conditions. These findings stress the importance of prevention measures for people with IC, such as additional vaccination doses and consistent mask use before and after a documented infection.

During 2023, the Centers for Disease Control and Prevention (CDC) recommended the first respiratory syncytial virus (RSV) immunizations intended for widespread use in the United States to prevent severe RSV illness in infants and older adults. CDC, in collaboration with federal, public health, and academic partners, is conducting evaluations of real-world effectiveness of recommended RSV immunization products in the United States. Similar frameworks for evaluation are being applied to RSV vaccines and nirsevimab, a long-acting preventative monoclonal antibody, to estimate product effectiveness. The overall goal of CDC's RSV immunization effectiveness program is to generate timely and robust evidence through observational studies to inform immunization product policy decisions and other measures related to RSV prevention and control. CDC is evaluating effectiveness through high-quality, well-controlled observational studies leveraging a variety of platforms that provide robust data to inform policy decisions.

Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell culture collection-deposited control reference strains (Philadelphia-1 and Knoxville-1) as well as two accessible reference strains with moderately (lpeAB-carrying) and markedly (23S rRNA mutation-carrying) elevated azithromycin minimum inhibitory concentration (MIC). The defined protocol enables up to eight L. pneumophila strains to be set up on a single 96-well plate per antimicrobial tested. Initial ranges to routinely capture an MIC for these reference strains using clinically relevant antimicrobials azithromycin (0.01-0.25 mg/L), levofloxacin (0.008-0.03 mg/L), lefamulin (0.01-2 mg/L), rifampicin (0.0002-0.0008 mg/L) and doxycycline (0.25-16 mg/L) following incubation for 48 h at 37 °C in a shaking incubator have been empirically determined. Establishment of this internationally agreed protocol sets the scene for the next step: validation and comparison of antimicrobial ranges between international Legionella reference laboratories to establish putative resistance cut-off thresholds for these clinically relevant antimicrobials.

BACKGROUND: Previous studies have demonstrated associations of persistent organic pollutants (POPs) with sex-related hormones; however, findings were inconsistent. Sex-specific impacts and pathways through which adiposity influences associations are not completely understood. We sought to evaluate sex-specific associations of POPs serum concentration with sex-related hormones and to explore pathways through which adiposity may modify associations. METHODS: We studied 1,073 men and 716 postmenopausal women participating in the "Persistent Organic Pollutants, Endogenous Hormones, and Diabetes in Latinos" ancillary study which is a subcohort of the "Hispanic Community Health Study/Study of Latinos." We use baseline examination data collected from 2008-2011 to investigate associations between eight organochlorine pesticides (OCPs), five polychlorinated biphenyls (PCB) groups, sum of polybrominated diphenyl ethers and polybrominated biphenyl 153 on sex hormone binding globulin (SHBG) and various sex-related hormone levels. We examined associations cross-sectionally using linear and logistic regression models adjusted for complex survey design and confounders. RESULTS: PCBs and select OCPs were associated with increased SHBG in women and decreased estradiol (E2) and/or bioavailable E2 in men. For instance, per quartile increase in serum concentrations of ∑PCBs and oxychlordane were associated with decreased levels of E2 (β=-6.36 pmol/L; 95% CI:-10.7,-2.02 and β=-5.08 pmol/L; 95% CI:-8.11,-2.05) and bioavailable E2 (β=-4.48 pmol/L; 95% CI:-7.22,-1.73 and β=-4.23 pmol/L; 95% CI:-6.17,-2.28), respectively, in men, and increased levels of SHBG (β=7.25 nmol/L; 95% CI:2.02,12.8 and β=9.42 nmol/L; 95% CI:4.08,15.0), respectively, in women. p,p'-DDT and β-HCCH, and o,p'-DDT were also associated with decreased testosterone (T) and bioavailable T (ng/dL) levels in men. Adiposity modified associations in men, revealing stronger inverse associations of PCBs, PBDEs, and several OCPs with LH, SHBG, E2, bioavailable E2, T, and the ratios of LH to FSH and E2 to T in those with below median body mass index and waist-to-hip ratio. CONCLUSION: Distinct patterns of hormone dysregulation with increasing POPs serum concentration were identified in men and post-menopausal women. In men but less so in postmenopausal women, adiposity modified associations of POPs serum concentration with sex-related hormones.

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

For this narrative review, we describe recent high-profile and severe outbreaks of emerging fungal infections, emphasizing lessons learned and opportunities to improve future prevention and response efforts. Several themes and challenges remain consistent across a diverse array of fungal outbreaks, including the multidisciplinary need for improved diagnostic testing to determine species and perform antifungal susceptibility testing, clinical awareness, and optimization of antifungal use. Recent outbreaks exemplify the growing promise of non-culture-based tools in identifying fungal outbreaks and improving responses, although access remains limited. Culture-based tools remain critical for performing antifungal-susceptibility to guide therapy.

BACKGROUND: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. RESULTS: A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). CONCLUSION: Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.

BACKGROUND: The Federal Retail Pharmacy Program (FRPP) integrated pharmacies as partners in the national effort to maximize vaccination during the COVID-19 public health emergency. OBJECTIVES: The objective of this study was to quantify the contribution of pharmacies participating in FRPP to COVID-19 vaccination efforts during December 2020-September 2023 across sociodemographic groups in the United States. METHODS: Data on COVID-19 vaccine doses administered reported to CDC by FRPP and jurisdictional immunization information systems (IIS) of all 50 states, the District of Columbia, and U.S. territories were analyzed to estimate FRPP contributions. RESULTS: Approximately 314.9 million COVID-19 vaccine doses were administered by FRPP throughout this period, constituting 48.9% of all COVID-19 vaccine doses administered. FRPP contributions to COVID-19 vaccination ranged from 12.9% to 56.8% for persons aged 6 months-4 years and 12-17 years, respectively. FRPP made the highest contribution to administering COVID-19 doses to Non-Hispanic Asian (48.7%) and Hispanic/Latino (49.8%) persons. The proportion of COVID-19 doses given by FRPP pharmacies was found to be higher in urban areas (57%) compared with rural areas (45%). CONCLUSION: FRPP administered a substantial proportion of COVID-19 vaccine doses in the United States and provided vaccine access for persons across a wide range of groups. Pharmacies can complement vaccination efforts during public health emergency situations and in routine vaccination programs.

The Department of Defense (DoD) remains committed to mitigating harmful behaviors that harm personnel and hinder military readiness. DoD's Sexual Assault Prevention and Response Office (SAPRO) and the Division of Violence Prevention (DVP) within the Centers for Disease Control and Prevention (CDC) established a partnership to build capacity for primary prevention though a wide-ranging training and technical assistance (TTA) system, The Integrated Prevention Technical Assistance Center (IPTAC). The system serves as a support system within the Interactive Systems Framework (ISF). The goal for IPTAC's TTA support is to build capacity for integrated primary prevention and build sustainability for prevention in complex military environments. To assess the effectiveness of IPTAC, the system is evaluated on what TTA is delivered, the skills and knowledge increase in TTA participants, participant satisfaction with TTA received, and participant application or intent for application of skills. Early results are positive; however, these results could be improved partly through ensuring a larger focus on tailoring to military contexts within all TTA activities. This article describes the creation of IPTAC, the role of the ISF in the implementation of TTA, and the evaluation of IPTAC. Implications for TTA delivery in the military and civilian sectors are discussed.