Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Background: Inequities in stroke outcomes have existed for decades, and the COVID-19 pandemic amplified these inequities. Objectives: This study examined the association between social vulnerability and all-cause mortality among Medicare beneficiaries hospitalized with acute ischemic stroke (AIS) during COVID-19 pandemic periods. Methods: We analyzed data on Medicare fee-for-service beneficiaries aged ≥65 years hospitalized with AIS between April 1, 2020, and December 31, 2021 (followed until December 31, 2023) merged with county-level data from the 2020 Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry's Social Vulnerability Index (SVI). We used a Cox proportional hazard model to examine the association between SVI quartile and all-cause mortality. Results: Among 176,123 Medicare fee-for-service beneficiaries with AIS, 29.9% resided in the most vulnerable counties (SVI quartile 4), while 14.9% resided in counties with least social vulnerability (SVI quartile 1). AIS Medicare beneficiaries living in the most vulnerable counties had the highest proportions of adults aged 65 to 74 years, non-Hispanic Black or Hispanic, severe stroke at admission, a history of COVID-19, and more prevalent comorbidities. Compared to those living in least vulnerable counties, AIS Medicare beneficiaries living in most vulnerable counties had significantly higher all-cause mortality (adjusted HR: 1.11, 95% CI: 1.08-1.14). The pattern of association was largely consistent in subgroup analyses by age group, sex, and race and ethnicity. Conclusions: Higher social vulnerability levels were associated with increased all-cause mortality among AIS Medicare beneficiaries. To improve outcomes and address disparities, it may be important to focus efforts toward addressing social vulnerability. © 2024

IMPORTANCE: Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. OBJECTIVE: To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. EXPOSURE: History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. MAIN OUTCOMES AND MEASURES: The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. RESULTS: Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

IMPORTANCE: Uncontrolled hypertension is a major contributor to cardiovascular disease (CVD) in the US. OBJECTIVE: To determine the prevalence of hypertension control cascade outcomes (hypertension awareness, treatment recommendations, and medication use) among individuals with uncontrolled hypertension to inform action across cascade levels. DESIGN, SETTING, AND PARTICIPANTS: This weighted cross-sectional study used January 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) data from noninstitutionalized adults aged 18 years or older in the US with uncontrolled hypertension. Data analysis occurred from January to February 2024. EXPOSURE: Calendar year of response to the NHANES survey. MAIN OUTCOMES AND MEASURES: Mean blood pressure (BP) was computed using up to 3 measurements. Uncontrolled hypertension was defined as systolic BP of 130 mm Hg or greater or diastolic BP of 80 mm Hg or greater, regardless of medication use. Outcomes included patient awareness of hypertension, treatment recommendations, and medication use. To estimate population totals by subgroup, the age-standardized proportion of each outcome was multiplied by the estimated number of adults with uncontrolled hypertension. RESULTS: The study included 3129 US adults with uncontrolled hypertension (1675 male [weighted percentage, 52.3%]; 775 aged 18 to 44 years [weighted percentage, 29.4%]; 1306 aged 45 to 64 years [weighted percentage, 41.4%]; 1048 aged 65 years or older [weighted percentage, 29.2%]), resulting in a population estimate of 100.4 million adults (weighted percentage, 83.7%) with uncontrolled hypertension. More than one-half of study participants (57.8 million adults [weighted percentage, 57.6%]) were unaware that they had hypertension, and of the 35.0 million who were aware and met criteria for antihypertensive medication, 24.8 million (weighted percentage, 70.8%) took the medication but had hypertension that remained uncontrolled. These negative outcomes in the hypertension control cascade occurred across demographic groups, with notably high prevalence among younger adults and individuals engaged in health care. Among an estimated 30.1 million adults aged 18 to 44 years with hypertension, 10.4 of 11.3 million females (weighted percentage, 91.8%) and 17.7 million of 18.8 million males (weighted percentage, 94.3%) had uncontrolled hypertension. Of the 10.4 million females, 7.2 million (weighted percentage, 68.8%) were unaware of their hypertension status, and of the 17.7 million males, 12.0 million (weighted percentage, 68.1%) were unaware. Additionally, 9.9 of 13.0 million adults with uncontrolled hypertension (weighted percentage, 75.7%) reported no health care visits in the past year and were unaware. Conversely, among 70.6 million adults with uncontrolled hypertension reporting 2 or more health care visits, approximately one-half (36.6 million [weighted percentage, 51.8%]) were unaware. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, more than 50% of adults with uncontrolled hypertension in the US were unaware of their hypertension and were untreated, and 70.8% of those who were treated had hypertension that remained uncontrolled. These findings have serious implications for the nation's overall health given the association of hypertension with increased risk for CVD.

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

BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

BACKGROUND: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. METHODS: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques. FINDINGS: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. INTERPRETATION: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence. FUNDING: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO.

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

Mycetoma is a debilitating neglected tropical disease that affects individuals worldwide, particularly in regions where there is poverty and limited health care access. The Mycetoma Research Center (MRC), based in Khartoum, Sudan, provides a sustainable, holistic approach to patient care as the only World Health Organization collaborating center for mycetoma. We describe MRC activities that align with the United Nations' Sustainable Development Goals to control mycetoma in Sudan and globally.

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

The global disruption caused by the SARS-CoV-2 pandemic profoundly affected healthcare systems, particularly impacting People Living with Human Immunodeficiency Virus (PLHIV). This study investigated the repercussions of SARS-CoV-2 infection on access to human immunodeficiency virus (HIV) care and antiretroviral therapy (ARV) in Malawi, emphasizing the critical need to sustain uninterrupted HIV services during health crises. Employing mobile phone-based syndromic surveillance, this study assessed the influence of SARS-CoV-2 on healthcare access for PLHIV across nine districts supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). Telephone-based interviews were conducted to analyze demographic factors, challenges encountered in accessing HIV services, and adherence to ARV medication, illuminating the pandemic's effects on ARV uptake. The findings revealed that approximately 3.9% (n = 852) of 21981 participants faced obstacles in accessing crucial HIV services during the pandemic, resulting in approximately 1.2% (n = 270) reporting multiple missed doses of ARV medication in a particular month. After adjusting for various variables, males exhibited a higher likelihood of service inaccessibility than females (Adjusted Odds Ratio [AOR] = 1.39, 95% CI: 1.20-1.60, p < 0.001). Age also played a significant role, with individuals aged 35-49 years and those aged 50 years or older demonstrating reduced odds of service failure compared with the reference group aged 18-34 years. Only a small proportion of PLHIV reported disruption in HIV care access, which may be because Malawi did not initiate stringent travel restrictions during the SARS-CoV-2 pandemic. Nonetheless, enduring challenges have been observed in retaining younger PLHIV and men in HIV-care settings. Thus, targeted strategies are imperative for effectively engaging and sustaining these populations in HIV care during and after health crises.

We searched for evidence of knockdown resistance (kdr) mutations in the voltage-gated sodium channel gene of Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) mosquitoes from Panama. Conventional PCR was performed on 469 Ae. aegypti and 349 Ae. albopictus. We did not discover kdr mutations in Ae. albopictus, but 2 nonsynonymous kdr mutations, V1016I (found in 101 mosquitoes) and F1534C (found in 29 of the mosquitoes with the V1016I), were detected in Ae. aegypti. These kdr mutations were present in all specimens that were successfully sequenced for both IIS5-S6 and IIIS6 regions, which included samples collected from 8 of the 10 provinces of Panama. No other kdr mutations were found in Ae. aegypti, including V1016G, which has already been reported in Panama. Findings suggest that the V1016I-F1534C variant is prevalent in Panama, which might be related to the introduction and passive movement of mosquitoes as part of the used-tire trade. However, we cannot rule out the possibility that selection on de novo replacement of kdr mutations also partially explains the widespread distribution pattern of these mutations. These 2 ecological and evolutionary processes are not mutually exclusive, though, as they can occur in tandem. Research in Panama needs to calculate the genotypic and allelic frequencies of kdr alleles in local Ae. aegypti populations and to test whether some combinations confer phenotypic resistance or not. Finally, future studies will have to track the introduction and spreading of new kdr mutations in both Aedes species.

BACKGROUND: Organophosphate esters (OPEs), flame retardants and plasticizers found widely in consumer products, may impact vascularization processes in pregnancy. Yet, the association between maternal exposure to OPEs and both preeclampsia and blood pressure during pregnancy remains understudied. METHODS: Within the LIFECODES Fetal Growth Study (N = 900), we quantified 8 OPE metabolites from maternal urine collected at up to 3 time points during pregnancy and created within-subject geometric means. Outcomes included diagnosis of preeclampsia and longitudinal systolic (SBP) and diastolic (DBP) blood pressure measurements (mean = 14 per participant). Cox proportional hazards models were used to estimate associations between OPE metabolites and preeclampsia. Associations between average OPE metabolite concentrations and repeated blood pressure measurements were estimated using generalized estimating equations. RESULTS: Five OPE metabolites were detected in at least 60% of samples; 3 metabolites detected less frequently (5-39%) were examined in an exploratory analysis as ever vs. never detectable in pregnancy. There were 46 cases of preeclampsia in our study population. Associations between OPE metabolites and preeclampsia were null. We noted several divergent associations between OPE metabolites and longitudinal blood pressure measurements. An interquartile range (IQR) difference in average bis(2-chloroethyl) phosphate concentrations was associated with a decrease in SBP (-0.81 mmHg, 95% confidence interval [CI]: -1.62, 0.00), and, conversely, bis(1-chloro-2-propyl) phosphate was associated with a slight increase in SBP (0.94 mmHg, 95% CI: 0.28, 1.61). We also noted a decrease in SBP in association with several metabolites with low detection frequency. CONCLUSIONS: We observed null associations between OPE metabolites and preeclampsia, but some positive and some inverse associations with blood pressure in pregnancy. While our study was well-designed to assess associations with blood pressure, future studies with a larger number of preeclampsia cases may be better poised to investigate the association between OPE metabolites and phenotypes of this heterogenous hypertensive disorder of pregnancy.

CONTEXT: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity. OBJECTIVE: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife. METHODS: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture. CONCLUSION: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health.

In April 2023, an outbreak of acute hepatitis was reported in the Nazareth internally displaced persons camp in South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis.

This case study describes the design, implementation, and evaluation of an initiative to increase COVID-19 vaccine confidence and uptake among refugee and immigrant women in Clarkston, Georgia. Applying the principles and practices of human-centered design, Mothers x Mothers was co-created by Refugee Women's Network and IDEO.org as a series of gatherings for refugee and immigrant mothers to discuss health issues, beginning with the COVID-19 vaccine. The gatherings included both vaccinated and unvaccinated mothers and used a peer support model, with facilitation focused on creating a trusting environment and supporting mothers to make their own health decisions. The facilitators for Mothers x Mothers gatherings were community health workers (CHWs) recruited and trained by Refugee Women's Network. Notably, these CHWs were active in every phase of the initiative, from design to implementation to evaluation, and the CHWs' professional development was specifically included among the initiative's goals. These elements and others contributed to an effective public health intervention for community members who, for a variety of reasons, did not get sufficient or appropriate COVID-19 vaccine information through other channels. Over the course of 8 Mothers x Mothers gatherings with 7 distinct linguistic/ethnic groups, 75% of the unvaccinated participants decided to get the COVID-19 vaccine and secured a vaccine referral.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya. METHODS: A structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019-2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness. RESULTS: We enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251-408 ) in Kilifi and USD 527 (95% CI: 405- 649) in Siaya. Household costs were USD 67 (95% CI: 54-80) and USD 172 (95% CI: 131- 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10-12) and USD 67 (95% CI: 51-83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration. CONCLUSIONS: RSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses.

BACKGROUND: There are no recent estimates for hypertension-associated medical expenditures. This study aims to estimate hypertension-associated incremental medical expenditures among privately insured US adults. METHODS: We conducted a retrospective cohort study using IQVIA's Ambulatory Electronic Medical Records-US data set linked with PharMetrics Plus claims data. Among privately insured adults aged 18 to 64 years, hypertension was identified as having ≥1 diagnosis code or ≥2 blood pressure measurements of ≥140/90 mm Hg, or ≥1 antihypertensive medication in 2021. Annual total expenditures (in 2021 $US) were estimated using a generalized linear model with gamma distribution and log-link function adjusting for demographic characteristics and cooccurring conditions. Out-of-pocket expenditures were estimated using a 2-part model that included logistic and generalized linear model regression. Overlap propensity score weights from logistic regression were used to obtain a balanced sample on hypertension status. RESULTS: Among the 393 018 adults, 156 556 (40%) were identified with hypertension. Compared with individuals without hypertension, those with hypertension had $2926 (95% CI, $2681-$3170) higher total expenditures and $328 (95% CI, $300-$355) higher out-of-pocket expenditures. Adults with hypertension had higher total inpatient ($3272 [95% CI, $1458-$5086]) and outpatient ($2189 [95% CI, $2009-$2369]) expenditures when compared with those without hypertension. Hypertension-associated incremental total expenditures were higher for women ($3242 [95% CI, $2915-$3569]) than for men ($2521 [95% CI, $2139-$2904]). CONCLUSIONS: Among privately insured US adults, hypertension was associated with higher medical expenditures, including higher inpatient and out-of-pocket expenditures. These findings may help assess the economic value of interventions effective in preventing hypertension.

Public health disease surveillance can guide a range of decisions related to the protection of populations. Economic analysis can be used to assess how surveillance for specific diseases can substitute for or complement other public health interventions and how to structure surveillance most efficiently. Assessing the value and costs of different disease surveillance options as part of broader disease prevention and control efforts is important for both using available resources efficiently to protect populations and communicating the need for additional resources as appropriate.

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

BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVE: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services. DESIGN: Cohort study using electronic health record data from adult patients hospitalized on medical services at four academic medical centers between 2016 and 2019. PARTICIPANTS: Among 111,550 admissions not on intermediate or full-dose anticoagulation, 48,520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. MAIN MEASURES: Candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission. KEY RESULTS: After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest two tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (1(st)) tertile (OR 0.84, 95% CI [0.81, 0.86] for 2(nd) tertile, OR 0.95, 95% CI [0.92, 0.98] for 3(rd) tertile). CONCLUSIONS: Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first two hospital days was lower in patients with higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with higher predicted risk could not be assessed.

IMPORTANCE: Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US. OBJECTIVE: To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035. DESIGN, SETTING, AND PARTICIPANTS: Generalized additive regression models projecting trends in TB incidence and case-fatality rates from 2023 to 2035 were fit based on national TB surveillance data for 2010 to 2019 in the 50 US states and the District of Columbia among US-born persons. This baseline scenario was compared with alternative scenarios in which racial and ethnic disparities in age- and sex-adjusted incidence and case-fatality rates were eliminated by setting rates for each race and ethnicity to goal values. Additional scenarios were created examining the potential outcomes of delayed reduction of racial and ethnic disparities. The potential benefits of eliminating disparities from differences between baseline and alternative scenario outcomes were quantified. Data were analyzed from January 2010 to December 2019. EXPOSURES: Non-Hispanic American Indian or Alaska Native, non-Hispanic Asian, non-Hispanic Black, Hispanic, non-Hispanic Native Hawaiian or Other Pacific Islander, or non-Hispanic White race and ethnicity. MAIN OUTCOMES AND MEASURES: TB cases and deaths averted, quality-adjusted life years gained, and associated costs from a societal perspective. RESULTS: The study included 31 811 persons with reported TB from 2010 to 2019 (mean [SD] age, 47 [24] years; 20 504 [64%] male; 1179 [4%] American Indian or Alaska Native persons; 1332 [4%] Asian persons; 12 152 [38%] Black persons; 6595 [21%] Hispanic persons; 299 [1%] Native Hawaiian or Other Pacific Islander persons; and 10 254 [32%] White persons). There were 3722 persons with a reported TB death. Persistent racial and ethnic disparities were associated with an estimated 11 901 of 26 203 TB cases among US-born persons (45%; 95% uncertainty interval [UI], 44%-47%), 1421 of 3264 TB deaths among US-born persons (44%; 95% UI, 39%-48%), and an economic cost of $914 (95% UI, $675-$1147) million from 2023 to 2035. Delayed goal attainment reduced the estimated avertable TB outcomes by 505 (95% UI, 495-518) TB cases, 55 (95% UI, 51-59) TB deaths, and $32 (95% UI, $24-$40) million in societal costs annually. CONCLUSIONS AND RELEVANCE: In this modeling study of racial and ethnic disparities of TB, these disparities were associated with substantial future health and economic outcomes of TB among US-born persons without interventions beyond current efforts. Actions to eliminate disparities may reduce the excess TB burden among these persons and may contribute to accelerating TB elimination within the US.

BACKGROUND: There are known disparities in U.S. COVID-19 vaccination but there is limited information on national vaccine uptake in a large, racially diverse, all-age population. Here, we describe COVID-19 vaccination coverage in a large U.S. population accessing care in OCHIN (not an acronym), a national network of community-based healthcare organizations. METHODS: Within OCHIN, we identified patients aged 6 months and older with ≥1 completed clinical encounter since becoming age-eligible for the COVID-19 vaccine between December 13, 2020 and December 31, 2022. Patients' COVID-19 vaccination status was assessed from OCHIN's Epic® electronic health record which includes data from state immunization information systems. Patients were considered vaccinated if they received ≥1 dose of a monovalent vaccine product; coverage was categorized by age groups (6 months-4 years; 5-11 years, 12-15 years, 16+ years). Multivariate analyses assessed factors associated with COVID-19 vaccination across age groups. RESULTS: The cohort included 3.3 million Hispanic (37 %), non-Hispanic (NH) White (31 %), NH Black (15 %), and NH Asian (7 %) patients; 45 % of whom were Medicaid-enrolled, 19 % uninsured, and 53 % with a household income below 100 % of the federal poverty level. The proportion with ≥1 COVID-19 vaccine dose increased with age, from 11.7 % (6 months through 4 years) to 72.3 % (65 years and older). The only factors associated with significantly higher COVID-19 vaccine coverage across age groups were prior receipt of an influenza vaccine and having private insurance. In adjusted modeling, when compared to NH whites, COVID-19 vaccine coverage was significantly higher among Hispanic, NH Asian, and NH multiple-race patients aged ≥5 years and significantly lower among NH Black and NH Native Hawaiian/Other Pacific Islander patients aged 6 months-4 years old. CONCLUSIONS: We identified disparities in primary series COVID-19 vaccine coverage by age, race and ethnicity, household income, insurance status, and prior influenza vaccination within this large, diverse population accessing care in community-based healthcare organizations.

BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

BACKGROUND: Outer membrane vesicle (OMV) meningococcal serogroup B (MenB) vaccines might be protective against gonorrhea. We evaluated the effectiveness of MenB-4C, an OMV MenB vaccine, against gonorrhea. METHODS: We identified gonococcal mono-infections, chlamydial mono-infections, and gonococcal/chlamydial co-infections among persons aged 15-30 years in the electronic health records of Kaiser Permanente Northern California during 2016-2021. We determined MenB-4C vaccination status (vaccinated [≥1 MenB-4C vaccine dose] or unvaccinated [MenB-4C vaccine naïve]) at each infection. We used log-binomial regression with generalized estimating equations to calculate adjusted prevalence ratios (APR) and 95 % confidence intervals (CI) to determine if MenB-4C vaccination was protective against gonococcal mono-infections compared to chlamydial mono-infection. We also evaluated if MenB-4C vaccination was protective against gonococcal/chlamydial co-infections. Because of concerns with small sample size of vaccinated persons, we estimated effects using a limited model (adjusting for race/ethnicity only) and an expanded model (adjusting for additional potential confounders). RESULTS: Of 68,454 persons, we identified 558 (0.8 %) MenB-4C vaccinated persons and 85,393 infections (13,000 gonococcal mono-infections, 68,008 chlamydial mono-infections, and 4385 gonococcal/chlamydial co-infections). After adjusting for race/ethnicity, MenB-4C vaccination was 23 % protective against gonococcal mono-infection compared to chlamydial mono-infection (APR = 0.77, 95 % CI = 0.64-0.99) in the limited model but not in the expanded model. CONCLUSION: MenB-4C vaccination was protective against gonococcal mono-infection, independent of race/ethnicity. This protective effect was not observed when other potential confounders were included in the analysis. Protection against gonococcal/chlamydial co-infection was not observed. Efficacy data from clinical trials are needed.

BACKGROUND: Monovalent rotavirus vaccine substantially reduced rotavirus disease burden after introduction (May 2014) in Madagascar. We examined the effectiveness and long-term impact on acute watery diarrhea and rotavirus-related hospitalizations among children <5 years old at two hospitals in Antananarivo, Madagascar (2010-2022). METHODS: We used a test-negative case-control design to estimate monovalent rotavirus vaccine effectiveness (VE) against laboratory-confirmed rotavirus hospitalizations among children age 6-23 months with documented vaccination status adjusted for year of symptom onset, rotavirus season, age group, nutritional status, and clinical severity. To evaluate the impact, we expanded to children age 0-59 months with acute watery diarrhea. First, we used admission logbook data to compare the proportion of all hospitalizations attributed to diarrhea in the pre-vaccine (January 2010-December 2013), transition period (January 2014-December 2014), and post-vaccine (January 2015-December 2022) periods. Second, we used active surveillance data (June 2013-May 2022) to describe rotavirus positivity and detected genotypes by vaccine introduction period and surveillance year (1 June-31 May). RESULT: Adjusted VE of at least one dose against hospitalization due to rotavirus diarrhea among children age 6-23 months was 61 % (95 % CI: -39 %-89 %). The annual median proportion of hospitalizations attributed to diarrhea declined from 28 % in the pre-vaccine to 10 % in the post-vaccine period. Rotavirus positivity among hospitalized children age 0-59 months with acute watery diarrhea was substantially higher during the pre-vaccine (59 %) than the post-vaccine (23 %) period. In the pre-vaccine period, G3P[8] (76 %) and G2P[4] (12 %) were the dominant genotypes detected. Although genotypes varied by surveillance year, G1P[8] and G2P[4] represented >50 % of the genotypes detected post-introduction. CONCLUSIONS: Rotavirus vaccine has been successfully implemented in Madagascar's routine childhood immunization program and had a large impact on rotavirus disease burden, supporting continued use of rotavirus vaccines in Madagascar.

Vasovagal syncope, or fainting, can be triggered by various stimuli, including medical procedures. Syncope after vaccination has been reported, most commonly among adolescents, and can result in injuries. Using the Vaccine Adverse Event Reporting System (VAERS), we reviewed and summarized reports of syncope after live attenuated influenza vaccine, intranasal (LAIV) administered as the sole vaccine (i.e., no concomitant injections). From June 17, 2003 (date of LAIV licensure in the US) through May 31, 2024, VAERS received 50 reports of syncope after LAIV. Nearly half (23; 46 %) pertained to individuals 10-19 years of age. While the vast majority of reports (35; 70 %) did not describe any injuries, 15 people (30 %) were injured, most commonly by falling and hitting their head or face. Twenty-two people (44 %) required evaluation in the emergency department or doctor's office, including an individual who lost consciousness while he was driving home from the vaccination appointment. He did not report any injuries, but the car was severely damaged. Nearly three-quarters of people (37; 74 %) developed syncope within 15 min after vaccination, but fewer than half of reports (24; 48 %) stated that the patient had waited in the observation area for at 15 min. Based on approximately 111.9 million doses of LAIV distributed in the US during the same time period, the reporting rate is approximately 0.4 per million doses, suggesting that syncope following LAIV is rare. The information summarized here may enable clinicians, patients, and caregivers to make a more informed decision regarding preventing injuries that may occur following LAIV-related syncope.

OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8,856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future.

Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.

BACKGROUND: The Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms are designed to help obstetric practices address perinatal depression. The PRogram in Support of Moms includes the statewide Massachusetts Child Psychiatry Access Program for Moms program, plus proactive implementation support. OBJECTIVE: The goal of this study was to understand the impact of these programs on perinatal generalized anxiety disorder and posttraumatic stress disorder symptoms among individuals screening positive for depression. STUDY DESIGN: We conducted a secondary analysis of 2017-2022 data from a cluster randomized controlled trial of Massachusetts Child Psychiatry Access Program for Moms vs PRogram In Support of Moms. We included participants completing a generalized anxiety disorder or posttraumatic stress disorder screen at baseline (n=254) with antenatal Edinburgh Postnatal Depression Scale scores ≥10. We assessed changes in generalized anxiety disorder and posttraumatic stress disorder symptoms from pregnancy (4-25 weeks of gestational age or 32-40 weeks of gestational age), 4-12 weeks postpartum, and 11-13 months postpartum. We conducted a difference-in-difference analysis to compare symptom change from pregnancy to postpartum. We used adjusted linear mixed models with repeated measures to examine the impact of the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms on changes in the Generalized Anxiety Disorder 7 and the Posttraumatic Stress Disorder Checklist. RESULTS: Mean Generalized Anxiety Disorder 7 scores decreased by 3.6 (Massachusetts Child Psychiatry Access Program for Moms) and 6.3 (PRogram In Support of Moms) points from pregnancy to 4-12 weeks postpartum. Mean Posttraumatic Stress Disorder Checklist scores decreased by 6.2 and 10.0 points, respectively, at 4-12 weeks postpartum among individuals scree ning positive on the Generalized Anxiety Disorder 7 (n=83) or Posttraumatic Stress Disorder Checklist (n=58) in pregnancy. Generalized Anxiety Disorder 7 and Posttraumatic Stress Disorder Checklist scores decreased among both groups at 11-13 months postpartum. These changes were clinically meaningful. PRogram In Support of Moms conferred a statistically significant greater decrease (2.7 points) on the Generalized Anxiety Disorder 7 than the Massachusetts Child Psychiatry Access Program for Moms at 4-12 weeks postpartum. No differences were found between the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms in Posttraumatic Stress Disorder Checklist or Generalized Anxiety Disorder 7 change at 11-13 months, although both were associated with a reduction in generalized anxiety disorder and posttraumatic stress disorder symptoms at 4-12 weeks and 11-13 months postpartum. CONCLUSION: Both the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms could help to improve symptoms for individuals experiencing co-occurring symptoms of depression, generalized anxiety disorder, or posttraumatic stress disorder. PRogram In Support of Moms may confer additional benefits in the early postpartum period, although this difference was not clinically significant.

Congenital transmission of Toxoplasma gondii can occur when a woman becomes infected for the first time during or just before pregnancy. Toxoplasma gondii in the fetus can lead to miscarriage, stillbirth, ocular or neurological abnormalities at birth, or progressive visual, hearing, motor, and cognitive deficiencies. The national seroprevalence of T. gondii infection in Nigeria was previously unknown. The 2018 Nigeria HIV/AIDS Indicator and Impact Survey collected demographic, socioeconomic, and HIV-related data and stored blood specimens with consent for future analysis for other pathogens of public health importance. We evaluated toxoplasmosis seropositivity and risk factors in a sample of 44,269 women of reproductive age (WRA) between 15 and 44 years. The national T. gondii seroprevalence among WRA was 26.8% (95% CI: 25.8-27.7%). We found that WRA from all 36 states and the Federal Capital Territory had T. gondii exposure. Seroprevalence was higher in 25- to 44-year-olds than in 15- to 24-year-olds. A similar proportion of pregnant and nonpregnant women were seropositive. Increased odds of seropositivity were associated with unimproved toilet facilities and drinking water sources, being in a higher wealth quintile, and primary and secondary education compared with no education. Decreased odds of seropositivity were associated with living in an urban area and owning livestock. This study provides the first-ever national seroprevalence estimate for WRA in Nigeria. Although information on known risk factors for toxoplasmosis (e.g., consumption of undercooked meat, cat ownership) was not collected, future studies could further investigate potential risk factors to inform the development of effective toxoplasmosis prevention measures.

BACKGROUND: Critical congenital heart defects (CCHDs) are associated with considerable morbidity and mortality. This study estimated survival of children with nonsyndromic CCHDs and evaluated relationships between exposures of interest and survival by CCHD severity (univentricular or biventricular function). METHODS: This analysis included 4380 infants with CCHDs (cases) born during 1999-2011 and enrolled in the National Birth Defects Prevention Study, a multisite, population-based case-control study of major birth defects. Cases were linked to state death files. Nonparametric Kaplan-Meier survival functions were used to estimate 1- and 5-year survival probabilities overall and by severity group (univentricular/biventricular) stratified by demographic and clinical exposure variables of interest. The log-rank test was used to determine whether stratified survival curves were equivalent. Survival and 95% confidence intervals (CIs) were also estimated using Cox proportional hazards modeling adjusted for maternal age, education, race/ethnicity, study site, and birth year. RESULTS: One- and five-year survival rates were 85.8% (CI 84.7-86.8) and 83.7% (CI 82.5-84.9), respectively. Univentricular 5-year survival was lower than biventricular case survival [65.3% (CI 61.7-68.5) vs. 89.0% (CI 87.8-90.1; p < 0.001)]. Clinical factors (e.g. preterm birth, low birthweight, and complex/multiple defects) were associated with lower survival in each severity group. Sociodemographic factors (non-Hispanic Black race/ethnicity, <high school education, smoking, and lower household income) were only associated with survival among biventricular cases. CONCLUSIONS: Mortality among children with CCHDs occurred primarily in the first year of life. Survival was lower for those with univentricular defects, and social determinants of health were most important in predicting survival for those with biventricular defects.

BACKGROUND: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. METHODS: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. RESULTS: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. CONCLUSIONS: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

OBJECTIVE: To describe volunteer firefighters' perspectives on how firefighter- and fire department-level factors influence their physical activity and fitness. METHODS: Firefighters (n = 28) were interviewed, stratified by their years of firefighting, using an interview guide. Thematic analysis and systematic coding were employed to analyze the interview transcripts. RESULTS: Five themes were identified: (1) health and firefighting performance; (2) firefighter time and availability; (3) responsibility of the fire department to support volunteer members' physical fitness; (4) fire training drills as a form of functional physical activity, and (5) fitness initiatives at the department. Interviewing by years of experience showed varied perspectives which converged towards similar conclusions. CONCLUSIONS: Incorporating fitness discussions into department meetings and trainings, and identifying fitness advocates within the department, may contribute to overcoming barriers to physical fitness among volunteer firefighters.

Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched.Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA.Gene expression, proteomics, and informatics tools were utilized to characterize changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH).RT-qPCR analysis using a panel of 39 candidate primers demonstrated 9 candidate genes upregulated and 30 unchanged.HPLC-MS/MS analysis of HEKa cell lysate identified 18,540 proteins across all samples Sixty proteins demonstrate statistically significant differential expression in exposed cells, some of which suggest activation of immune and inflammatory pathways.The results support the hypothesis that dermal exposures have the potential to play an important role in the development of MDI-OA. Furthermore, proteomic and gene expression data suggest multiple immune (adaptive and innate) and inflammatory pathways may be involved in the development of MDI-OA.

CONTEXT: In response to the COVID-19 pandemic, Congress passed the American Rescue Plan Act of 2021 (ARPA) that included a historic investment in the public health workforce. PROGRAM: Charged with implementing this investment, the U.S. Centers for Disease Control and Prevention (CDC) launched the Public Health Infrastructure Grant (PHIG). PHIG builds on CDC's experience working with state, local, and territorial public health departments and represents a new approach to strengthening the public health workforce. IMPLEMENTATION: Specifically, PHIG incorporates features that allow these public health departments to prioritize and tailor the funding to meet their communities' needs: 1) focus on workforce as core infrastructure, 2) streamlined programmatic and administrative requirements, 3) more equitable funding approach, and 4) enhanced support from national partners and CDC. DISCUSSION: The goal is to optimize the unprecedented opportunity afforded by ARPA and lead to a stronger public health workforce and infrastructure across the United States.

CONTEXT: Schools vary in their capacity to implement recommended strategies to prevent infectious diseases, such as COVID-19. Professional development (PD) and technical assistance (TA) are well-established tools used to strengthen school capacity and infrastructure for healthier school environments. OBJECTIVE: The authors examined the relationship between PD and TA received by districts and schools and their implementation of COVID-19 prevention strategies during the 2020-2021 school year. DESIGN AND SETTING: We conducted a descriptive analysis of survey responses collected during Spring 2021 from selected districts and schools in 9 participating states. The survey assessed the implementation of 10 COVID-19 prevention strategies recommended by the Centers for Disease Control and Prevention and whether district or school staff received PD and/or TA on topics related to COVID-19 during the same year. PARTICIPANTS: Survey responses were received from designated contacts in 310 districts and 931 schools across 9 states. MAIN OUTCOME MEASURES: The dependent variable was the number of COVID-19 prevention strategies that were reported as "in place" by each district and school ranging from 0 to 10. RESULTS: On average, districts and schools reported implementing 7 of 10 recommended COVID-19 prevention strategies during the 2020-2021 school year. Schools that received PD on at least 1 of 12 topics reported implementing 7.61 COVID-19 prevention strategies, whereas schools that did not receive PD reported implementing 6.34 strategies. Similarly, schools that received TA on at least 1 topic reported higher COVID-19 implementation scores (7.51) than schools that did not receive any TA (7.20). CONCLUSIONS: Findings reveal a positive relationship between receiving PD and/or TA and implementation of COVID-19 prevention strategies in school settings.

Current e-cigarette use among U.S. youth has declined considerably since 2019*; however, approximately 2.13 million youths used e-cigarettes in 2023 (1). As sales of nicotine pouches (small, dissolvable, flavored pouches containing nicotine derived from tobacco that users place in the mouth between the lip and gum)(†) have continued to rise nationally since 2016, their use among U.S. youths has become concerning (2,3). All pouches and most e-cigarettes contain nicotine,(§) which is highly addictive and can harm the developing adolescent brain (4,5).

BACKGROUND: Following California's statewide law prohibiting the sale of flavoured tobacco products, some cigarette brands introduced new variants advertised as non-menthol, yet featuring design and text commonly found in menthol cigarette marketing. METHODS: Data are from the February-May 2023 wave of the Tobacco Epidemic Evaluation Network (TEEN+) national probability-based survey (aged 13-25 years). Respondents (N=10 217) were shown images of two (of four) 'new non-menthol' brand ads or packaging and two comparators ('classic' non-menthol and menthol cigarette brands). Respondents reported expected taste of each (no or any minty/menthol taste; 'don't know'). Multinomial regression models tested associations between predictors (age, gender identity, race and ethnicity, perceived financial situation, smoking status) and expectation of minty/menthol taste. RESULTS: Younger age was associated with expectations of minty/menthol taste, controlling for covariates. Respondents aged 13-17 years had greater odds of expecting minty/menthol taste than no minty/menthol taste for all tested new non-menthol brands (Camel Crush Oasis adjusted OR (aOR): 1.30, p<0.05; Camel Crisp aOR: 1.47, p<0.001; Kool Non-Menthol Blue aOR: 1.27, p<0.05; Kool Non-Menthol Green aOR: 1.43, p<0.01), compared to respondents aged 21 and older. Respondents aged 18-20 years had greater odds of reporting minty/menthol expectancies than no minty/menthol expectancies for Camel Crush Oasis (aOR: 1.35, p<0.05) and Kool Non-Menthol Green (aOR: 1.29, p<0.05) compared to those aged 21-25 years. Compared to non-Hispanic white respondents, non-Hispanic Asian respondents had greater odds of expecting minty/menthol taste than no minty/menthol taste for Camel Crush Oasis (aOR: 1.89, p<0.01), Kool Non-Menthol Blue (aOR: 1.88, p<0.01) and Kool Non-Menthol Green (aOR: 1.72, p<0.05). DISCUSSION: Younger age was associated with expectations of new non-menthol cigarettes having a minty/menthol taste. Results raise concerns regarding the potential appeal of these products to youth and young adults.

Deaths associated with COVID-19 in the United States are currently estimated to be over 1.2 million, but the true burden of mortality due to the SARS-CoV-2 virus is unknown. Methods for identifying and reporting deaths related to COVID-19 differ between jurisdictions, and concerns about overreporting and underreporting exist. Excess death estimates for the pandemic period, based on data from the National Center for Health Statistics, may be used to approximate the number of COVID-19-associated deaths. In this analysis, we first describe the process by which the New Jersey Department of Health identified, classified, and reported COVID-19-associated deaths from January 2020 through December 2022. The National Center for Health Statistics' excess deaths estimates are first compared with New Jersey's reported COVID-19-associated deaths, and then with the observed COVID-19-associated deaths in the entire United States, by month, from January 2020 through December 2022. New Jersey's reported COVID-19-associated deaths (n = 35,555) accounted for (and slightly exceeded) the state's excess deaths estimated by the National Center for Health Statistics for 2020-2022 (n = 30,365). However, the overall number of United States observed COVID-19 deaths for 2020-2022 (n = 1,094,230) for the study period did not account for all estimated excess deaths in the nation for the same period (n = 1,233,366). The general congruence of New Jersey's reported COVID-19 deaths and the National Center for Health Statistics' excess death estimates may be due in part to New Jersey's early detailed classification system for identifying and reporting deaths associated with COVID-19, leading to more accurate COVID-19 death reporting by the state.

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

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

BACKGROUND: Anopheles stephensi is an invasive malaria vector in Africa that threatens to put an additional 126 million people at risk of malaria if it continues to spread. The island nation of Mauritius is highly connected to Asia and Africa and is at risk of introduction due to this connectivity. For early detection of An. stephensi, the Vector Biology and Control Division under the Ministry of Health in Mauritius, leveraged a well-established Aedes program, as An. stephensi is known to share Aedes habitats. These efforts triggered multisectoral coordination and cascading benefits of integrated vector and One Health approaches. METHODS: Beginning June 2021, entomological surveys were conducted at points of entry (seaport, airport) and on ships transporting livestock in collaboration with the Civil Aviation Department, the Mauritian Port Authority and National Veterinary Services. A total of 18, 39, 723 mosquito larval surveys were respectively conducted in the airport, seaport, and other localities in Mauritius while two, 20, and 26 adult mosquito surveys were respectively conducted in the airport, seaport, and twenty-six animal assembly points. Alongside adult mosquito surveys, surveillance of vectors of veterinary importance (e.g.- Culicoides spp.) was also carried out in collaboration with National Parks and Conservation Service and land owners. RESULTS: A total of 8,428 adult mosquitoes were collected and 1,844 larval habitats were positive for mosquitoes. All collected mosquitoes were morphologically identified and 151 Anopheles and 339 Aedes mosquitoes were also molecularly characterized. Mosquito species detected were Aedes albopictus, Anopheles arabiensis, An. coustani, An. merus, Culex quinquefasciatus, Cx. thalassius and Lutzia tigripes. Anopheles stephensi was not detected. The One Health approach was shared with the French Agricultural Research Centre for International Development (CIRAD), strengthening collaboration between Mauritius and Réunion Island on vector surveillance at entry points and insecticide resistance monitoring. The Indian Ocean Commission (IOC) was also alerted to the risk of An. stephensi, leading to regional efforts supporting trainings and development of a response strategy to An. stephensi bringing together stakeholders from Comoros, Madagascar, Mauritius, Réunion Island and Seychelles. CONCLUSIONS: Mauritius is a model system showing how existing public health entomology capabilities can be used to enhance vector surveillance and control and create multisectoral networks to respond to any emerging public and veterinary health vector-borne disease threat.

INTRODUCTION: In March 2023, a Marburg Virus Disease (MVD) outbreak was declared in Kagera region, Northwestern Tanzania. This was the first MVD outbreak in the country. We describe the epidemiological characteristics of MVD cases and contacts. METHODS: The Ministry of Health activated an outbreak response team. Outbreak investigation methods were applied to cases identified through MVD standard case definitions and confirmed through reverse-transcriptase polymerase chain reaction (RT PCR). All identified case contacts were added into the contact listing form and followed up in-person daily for any signs or symptoms for 21 days. Data collected from various forms was managed and analyzed using Excel and QGIS software for mapping. RESULTS: A total of nine MVD cases were reported with eight laboratory-confirmed and one probable. Two of the reported cases were frontline healthcare workers and seven were family related members. Cases were children and adults between 1-59 years of age with a median age of 34 years. Six were males. Six cases died equivalent to a case fatality rate (CFR) of 66.7%. A total of 212 individuals were identified as contacts and two (2) became cases. The outbreak was localized in two geo-administrative wards (Maruku and Kanyangereko) of Bukoba District Council. CONCLUSION: Transmission during this outbreak occurred among family members and healthcare workers who provided care to the cases. The delay in detection aggravated the spread and possibly the consequent fatality but once confirmed the swift response stemmed further transmission containing the disease at the epicenter wards. The outbreak lasted for 72 days but as the origin is still unknown, further research is required to explore the source of this outbreak.