Addressing antimicrobial resistance requires multi-disciplinary action, including from the clinical laboratory. Cascade reporting of the antimicrobial susceptibility test (AST) is a strategy used by some laboratories to nudge clinicians toward the use of more narrow-spectrum antimicrobials. Cascade reporting involves suppression of broader-spectrum antimicrobials if the narrower-spectrum first-line antimicrobials show in-vitro susceptibility. Studies have shown that cascade reporting can reduce use of broad-spectrum antimicrobials and reduce antimicrobial resistance rates. However, implementing cascade reporting can be complex, and some question the effectiveness on impacting long-term prescribing behaviors. Furthermore, there are concerns surrounding compliance and the possible negative impact on public health surveillance for antimicrobial resistance. In this article, experts weigh in on the benefits and risks associated with implementing AST cascade reporting. General consensus is that cascade reporting is a benefit to antimicrobial stewardship, but protocols need careful implementation to minimize risk to patients and public health.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is critical to the end TB strategy. There is limited evidence on its long-term protective effect among people living with HIV (PLWH) receiving antiretroviral therapy (ART) in high-burden programmatic settings. METHODS: This observational cohort study included PLWH who initiated a single TPT course from March 2017 to September 2018 at 14 ART centres in Andhra Pradesh, India (TB prevalence: 274/100,000). We followed PLWH for 6 years and censored person-time at TB diagnosis, loss to follow-up, or death. We calculated TB incidence rates (IR) and mortality rates (MR) per 100 person-years (PY) stratified by TPT completion and effective ART (viral load<1000 copies/ml). Cox-proportional hazards models estimated adjusted hazard ratios (aHR) with 95% confidence limits (95% CL) for TB and mortality. FINDINGS: We followed 4,706 PLWH for 23,414 PY. TB was diagnosed in 135 PLWH (2.9%)-122 among 4,454 PLWH who completed TPT (IR: 0.55/100PY, 95% CL: 0.46-0.66), and 13 among 252 PLWH who did not (IR: 1.06/100PY, 95% CL: 0.56-1.81). There were 553 all-cause deaths (11.8%)-MR: 2.2/100PY (95% CL: 2.0-2.4) among those who completed TPT compared to 13.5/100PY (95% CL: 11.1-16.3) among those who did not. TPT, combined with effective ART, was associated with an 87% reduction in TB (aHR: 0.13; 95% CL: 0.05-0.37) and a 94% reduction in all-cause mortality (aHR: 0.06; 95% CL: 0.04-0.10). CONCLUSION: A single TPT course combined with effective ART conferred durable protection against TB and significantly reduced mortality among PLWH in a high-burden TB setting.

Background: Antifungal therapeutic drug monitoring (TDM) is critical for individualized, precision treatment and prevention of fungal infections, but previous research has highlighted low TDM utilization rates, potentially reflecting long turnaround times, complex testing logistics, results interpretation, and cost. Objectives: To inform strategies to increase antifungal TDM use, we assessed TDM-related knowledge, attitudes, and practices among infectious disease (ID) physicians and pharmacists. Methods: We summarized findings from three structured focus group discussions (FGD)—two with six ID physicians each and one with six pharmacists—during March 2024. Open-ended discussions were held regarding awareness of and experiences with fungal infections and TDM, perceptions of antifungal TDM such as potential benefits, barriers, and challenges to conducting antifungal TDM, and information needs about antifungal TDM. We conducted qualitative transcription-based analysis to identify themes. Results: Six themes emerged from FGDs: (1) variable knowledge and experience with antifungal TDM among participants, (2) the importance of close collaboration between physicians and pharmacists during the TDM process, (3) the main motivators driving TDM use were improving treatment outcomes, preventing toxicity, and addressing pharmacokinetic variability, (4) the perception that antifungal resistance was unrelated to TDM, (5) key barriers were a lack of comprehensive clinical guidelines, long lab testing turnaround times, complex testing logistics, and high costs, and (6) a need for additional clinical data on TDM's impact on outcomes. Conclusions: Our findings can inform efforts to increase TDM use by addressing barriers to practice. Development of evidence-based clinical guidelines and improvements in testing infrastructure across practice settings could increase antifungal TDM use. Published 2025. This article is a U.S. Government work and is in the public domain in the USA.

BACKGROUND: School professionals, including classroom teachers, school administrators, psychologists, teachers' aides, and nurses, often interact with students with concussions. To ensure they have the knowledge to identify and manage concussions, the U.S. Centers of Disease Control and Prevention developed the HEADS UP to Schools online training. METHODS: The HEADS UP to Schools training includes a pre-test and post-test consisting of 16 knowledge questions in three areas (symptom recognition, school support and accommodation, and guidance and recommendations for school staff) and five self-efficacy questions. Pre- and post-test responses of 8750 individuals were compared and analyzed to evaluate the effectiveness of the training. RESULTS: Respondent scores significantly improved between pre- and post-test responses for all knowledge questions and self-efficacy questions. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Schools and school districts may consider offering this training to staff to help ensure that at least one person at each school is trained on concussion and to increase awareness of evidence-based practices. CONCLUSIONS: Knowledge and self-efficacy on concussion identification and management improved among school professionals who completed the HEADS UP to Schools training. Future research to assess whether concussion knowledge and self-efficacy are maintained long term may be beneficial.

BACKGROUND: Training and education may benefit nurses whose nonstandard work hours put them at risk of poor sleep, fatigue, and ensuing adverse health and safety outcomes. The National Institute for Occupational Safety and Health (NIOSH) published "Training for Nurses on Shift Work and Long Work Hours" in 2015 as a free online resource which remains one of the few trainings available on this topic. However, the extent to which nurses have completed the program and the characteristics of current learners have not been examined. OBJECTIVE: We aimed to describe the potential reach of the NIOSH Training for Nurses between May 2015 through December 2020. METHODS: Data were obtained on learners who received continuing education credits upon completion of the NIOSH Training for Nurses. We applied a widely used implementation and evaluation framework, RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance), to describe the potential reach of the nurses' training and provide descriptive statistics of learners. RESULTS: From 2015 to 2020, 7899 learners from different occupations received continuing education credits for completing the training. Approximately 60% of learners were nurses and 30% were students. Among nurses, most were Registered Nurses (93%), with few Licensed Practical Nurses (6%) and Advanced Practice Nurses (2%). In 2020, the number of learners who were nurses represented only 0.09% of all licensed US nurses. CONCLUSION: A renewed dissemination plan may help extend training reach to the larger population of licensed US nurses. The NIOSH training remains a seminal, freely available, online resource for nurses, filling a critical gap in training to manage work-related fatigue.

INTRODUCTION: Urinary biomarkers are useful in characterizing exposure to harmful and potentially harmful constituents (HPHCs) of tobacco products and linking exposure to health outcomes. However, the consistency/reproducibility of many urinary biomarkers over long periods is unknown. METHODS: Among people who exclusively used cigarettes in the Population Assessment of Tobacco and Health Study Waves 1, 2, 4, and 5 (ranging from 746 to 1361 subjects), we used weighted models to estimate variance components and intra-class correlation coefficients (ICC) for 15 biomarkers of exposure for urine samples collected 3-5 years apart, creatinine-only-adjusted and also adjusted for demographic and behavioral predictors. RESULTS: In models adjusted only for creatinine, ICC values of biomarkers ranged from 0.41 (95% confidence interval (CI): 0.32, 0.49) (N-acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.73 (95% CI: 0.65, 0.81) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), varying within each chemical class. For models adjusted for predictors, associations between biomarkers and predictors were similar for samples collected 3-5 years and 1 year apart. Predictor-adjusted ICCs for samples collected 3-5 years apart ranged from 0.29 (95% CI: 0.17, 0.40) (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.63 (95% CI: 0.56, 0.69) (N-Acetyl-S-(2-hydroxyethyl)-L-cysteine) and appeared not different from those for samples collected 1 year apart. CONCLUSIONS: Even for 3 or 5 years between urine sample collection, unadjusted biomarkers of exposure showed fair to excellent reproducibility. Similar consistency between 1 year and 3-5 years between collections was found when including predictors in the model. IMPLICATIONS: These biomarkers may be useful to characterize long-term exposures to HPHCs from cigarettes with different characteristics for those who smoke cigarettes exclusively.

BACKGROUND: Comparing the characteristics of patients with long COVID to those with other post-acute infection syndromes (PAIS) could potentially provide clues to common underlying disease processes that may affect patient recovery. METHODS: We identified records of patients who had documented SARS-CoV-2 tests in the University of Washington Medicine electronic health record (EHR) database from January 1, 2019, through January 31, 2022 (n = 139,472). Patients were classified into three groups: 1) long COVID defined by a positive SARS-CoV-2 test and a long COVID-related diagnosis code (n = 580); 2) recovered COVID defined by a positive test and no long COVID associated diagnosis codes (n = 7,437); and 3) non-COVID PAIS defined by a negative test, non-SARS-CoV-2 related PAIS diagnosis codes, and no COVID related codes (n = 106). Using multivariate logistic regression, we compared the clinical characteristics of these groups at three timeframes to address preclinical, acute and post-acute diagnoses: before index SARS-CoV-2 test, within 30 days of index test, and > 30 days after index test. RESULTS: The long COVID group had a higher Charlson comorbidity index [median (IQR), 2 (0-4)] than the other two patient groups [median (IQR), 1 (0-3) and 1 (0-3)]. The long COVID and non-COVID PAIS patients were older and had greater smoking exposure than the recovered COVID group. Compared to the recovered COVID control group, the long COVID group had more health problems prior to the infection, including respiratory and metabolic as well as more severe infections and comorbidities based on the ICD codes found in the acute phase records. In the post-acute timeframe, many symptoms were more likely to be associated with long COVID than recovered patients with COVID-19 including abnormalities of heart beat [OR (95% CI), 5.31 (3.96-7.13)], cognition, perception, or emotional state symptoms [OR (95% CI), 5.14 (3.81-6.92)], malaise and fatigue [OR (95% CI), 4.20 (3.13-5.63)], and sleep disorders [OR (95% CI), 2.47, (1.79-3.43)], all p < 0.05. In contrast, the non-COVID PAIS group shared many similarities with the long COVID group across all three timeframes. CONCLUSIONS: Patients diagnosed with long COVID were more similar to patients with a non-COVID-related PAIS than to recovered patients with COVID-19. This suggests risk factors for PAIS may be similar and independent of the infectious agent.

INTRODUCTION: Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID. METHODS: We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25-54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019). RESULTS: The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed. CONCLUSIONS: The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.

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

We conducted retrospective analysis of the emergence of the SARS-CoV-2 JN.1 variant in US wastewater during November 2023-July 2024 using Aquascope, a bioinformatics pipeline for the National Wastewater Surveillance System. This study highlights the value of open-source bioinformatics tools in tracking pathogen variants for public health monitoring.

BACKGROUND: Hypertension is a major risk factor for cardiovascular and renal diseases, significantly contributing to morbidity and mortality. The COVID-19 pandemic has heightened concerns about the impact of hypertension on severe COVID-19 outcomes. METHODS: We analyzed 2020-2021 data from the MarketScan Commercial and Health and Productivity Management databases, focusing on adults aged 18-64 years with continuous employer-sponsored private insurance, excluding pregnancy or capitated plans. We compared medical costs, healthcare utilization (emergency department [ED] visits, inpatient admissions, outpatient visits, and outpatient prescription drugs), and productivity losses (sick absences, short-term disability [STD], and long-term disability [LTD]) between individuals with and without hypertension, stratified by COVID-19 diagnosis. We used multivariable regression models, including an interaction term for hypertension and COVID-19 diagnosis, to estimate differences in outcomes, adjusting for demographics and comorbidities. RESULTS: Among 1,296,596 adults, 21% had hypertension. Those with hypertension were older, less likely female, less likely urban residents, and had more comorbidities. Excess medical costs associated with hypertension were $8,572 per patient over the two-year period (95% CI $8,182-$8,962). Patients with versus without hypertension had 0.200 (95% CI, 0.195-0.205) more ED visits, 0.081 (95% CI, 0.077-0.085) more inpatient admissions, 5.984 (95% CI, 5.892-6.075) more outpatient visits, and 20.25 (95% CI, 20.09-20.41) more prescriptions per patient over the two-year period. They also had more sick absences (1.13 days; 95% CI 0.93-1.34) and STD occurrences (3.88 days; 95% CI 3.56-4.20) per patient. Among those with hypertension, individuals with versus without COVID-19 had $3,495 (95% CI, $2,135-$4,856) higher medical costs and 2.588 (95% CI, 1.112-4.065) more STD days per patient over the two-year period. CONCLUSIONS: Hypertension was associated with higher medical costs, healthcare utilization, and productivity losses, exacerbated by COVID-19.

For detection of viral RNA in blood or tissue, samples are often collected into lysis buffers prior to downstream molecular analysis. Immediate sample processing and cold storage are not always possible during large-scale or field studies, or in facilities lacking a stable electrical supply. Additionally, samples may need to be transported significant distances before processing. Here, using Peptidylprolyl Isomerase A (Ppia), a stably expressed gene in rodent tissues, we investigate the long-term stability and detection of RNA in guinea pig tissues stored for up to 52 weeks and in hamster blood stored for up to 12 weeks in MagMAX Lysis/Binding Solution Concentrate at -80°C, 4°C, 21°C, and 32°C.

Nonoccupational postexposure prophylaxis (nPEP) for HIV is recommended when a nonoccupational (e.g., sexual, needle, or other) exposure to nonintact skin or mucous membranes that presents a substantial risk for HIV transmission has occurred, and the source has HIV without sustained viral suppression or their viral suppression information is not known. A rapid HIV test (also referred to as point-of-care) or laboratory-based antigen/antibody combination HIV test is recommended before nPEP initiation. Health care professionals should ensure the first dose of nPEP is provided as soon as possible, and ideally within 24 hours, but no later than 72 hours after exposure. The initial nPEP dose should not be delayed due to pending results of any laboratory-based testing, and the recommended length of nPEP course is 28 days. The recommendations in these guidelines update the 2016 nPEP guidelines (CDC. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. Atlanta, GA: US Department of Health and Human Services, CDC; 2017). These 2025 nPEP guidelines update recommendations and considerations for use of HIV nPEP in the United States to include newer antiretroviral (ARV) agents, updated nPEP indication considerations, and emerging nPEP implementation strategies. The guidelines also include considerations for testing and nPEP regimens for persons exposed who have received long-acting injectable ARVs in the past. Lastly, testing recommendations for persons who experienced sexual assault were updated to align with the most recent CDC sexually transmitted infection treatment guidelines. These guidelines are divided into two sections: Recommendations and CDC Guidance. The preferred regimens for most adults and adolescents are now bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine). However, the regimen can be tailored to the clinical circumstances. Medical follow-up for persons prescribed nPEP also should be tailored to the clinical situation; recommended follow-up includes a visit at 24 hours (remote or in person) with a medical provider, and clinical follow-up 4-6 weeks and 12 weeks after exposure for laboratory testing. Persons initiating nPEP should be informed that pre-exposure prophylaxis for HIV (PrEP) can reduce their risk for acquiring HIV if they will have repeat or continuing exposure to HIV after the end of the nPEP course. Health care professionals should offer PrEP options to persons with ongoing indications for PrEP and create an nPEP-to-PrEP transition plan for persons who accept PrEP.

BACKGROUND: Phthalate exposures are ubiquitous and have been associated with pregnancy complications. Interaction between serum long-chain n-3 polyunsaturated fatty acids (n3PUFA) and phthalate biomarkers is biologically plausible because both can bind to human peroxisome proliferator-activated receptors (PPARs) which are involved in placenta development. However, evidence of this interaction in humans is lacking. OBJECTIVE: To evaluate whether serum n3PUFA modifies the associations of biomarkers of phthalate exposure on pregnancy outcomes. METHODS: Among 351 women undergoing in vitro fertilization in the Environment and Reproductive Health study (2004-2017), we evaluated the effect modification of eicosapentaenoic acid (EPA) and serum docosahexaenoic acid (DHA) on the association of pregnancy outcomes with the mixture of urinary concentrations of phthalate biomarkers by quantile g-computation. All models were adjusted for age, body mass index, prior smoking, infertility diagnosis, treatment year, and urinary specific gravity. RESULTS: Concentrations of the phthalate biomarkers mixture were associated with higher adjusted probabilities of pregnancy loss and lower estimated probabilities of live birth among women with serum EPA+DHA in the lowest tertile (< 2.66% of total fatty acids), but not among women with middle-to-high serum EPA+DHA (p interactions = 0.06 and 0.15, respectively). Among women in the lowest tertile of serum EPA+DHA, the adjusted probability [95% confidence interval (CI)] of pregnancy loss for women in the lowest and highest quartile of phthalates mixtures was 5% (2%, 16%) and 44% (23%, 85%), respectively (p trend = 0.01). The corresponding estimates were 14% (5%, 41%) and 11% (3%, 42%) among women with serum EPA+DHA in the highest tertile (⩾ 3.78% of total fatty acids) (p trend = 0.81). Similar trends were observed for live birth but not for implantation and clinical pregnancy. CONCLUSIONS: This study suggests adverse effects of phthalate exposure on pregnancy loss and live birth may be attenuated by intakes of n3PUFA. These results, if replicated, could inform clinical practice reducing the burden of infertility by phthalate exposure among the general population and improving pregnancy outcomes among subfertile couples.. https://doi.org/10.1289/EHP15942.

Rocky Mountain spotted fever (RMSF) is a deadly tick-borne disease caused by the bacterium Rickettsia rickettsii. An ongoing epidemic of RMSF is affecting tribal communities in Arizona, with nearly 500 cases and 28 deaths since 2003. The San Carlos Apache Tribe has been consistently working to prevent RMSF using tick collars on dogs, pesticide treatments around homes, and increasing education for nearly a decade. Besides monitoring human disease levels and tick burden on dogs, we have little understanding of the long-term impact of prevention practices on tick abundance and infection rates in the peridomestic environment. We evaluated risk factors associated for tick infestation at home sites across the San Carlos Indian Reservation as well as R. rickettsii and Rickettsia massiliae prevalence in off-host ticks. Although the presence of fencing appears protective, the number of nearby structures is the most important risk factor associated with increased adult and nymphal tick abundance, highlighting the impact of a free-roaming dog population.

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

Genomic surveillance of SARS-CoV-2 is crucial for detecting emerging variants and informing public health responses. Various sequencing technologies are used for whole genome sequencing of SARS-CoV-2. This cross-platform benchmark study applied established bioinformatics tools to assess and improve the performance of Illumina NovaSeq, Oxford Nanopore Technologies MinION, and Pacific Biosciences Sequel II sequencing platforms in identifying SARS-CoV-2 variants and lineage assignment. NovaSeq produced the highest number of reads and bases, depth of coverage, completeness of consensus genomes, stable mapping coverage across open reading frames in the genome, and consistent lineage assignments. The long-read sequencing platforms had lower yields, sequencing depth, and mapping coverage, limiting the number of qualified sequences for lineage assignment and variant identification. However, implementing proper quality controls on sequence data overcame these limitations and achieved consistent SARS-CoV-2 lineage assignments across all three sequencing platforms. The advancements in library preparation and technology for long-read sequencing are likely to enhance sequence quality and expand genome coverage, effectively addressing current limitations in genome analysis. By merging the unique advantages of both short- and long-read methods, we can significantly improve SARS-CoV-2 genomic surveillance and provide insights into sequencing strategies for other RNA viruses, pending further validation. This may lead to precise tracking of viral evolution and support public health policy decisions.

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

BACKGROUND: In the United States, 2 doses of measles-mumps-rubella (MMR)-containing vaccines are recommended routinely during childhood; a third dose may be given under certain circumstances. We present observed seroprotection rates and estimate long-term dynamics of measles, mumps, and rubella neutralizing antibody (nAb) levels among 2- and 3-dose MMR (MMR2 and MMR3, respectively) vaccinees. METHODS: Persons who received MMR2 at age 4-12 years or MMR3 at age 18-31 years were enrolled in 1994-1995 and 2009-2010, respectively. Per cohort, sera were collected before vaccination (baseline) and at various intervals ranging from 1 month to 10 years postvaccination to assess nAb levels. Annual changes in nAb levels per virus and cohort were estimated through 10 years postvaccination using generalized estimating equations. Models were stratified by baseline nAb levels. RESULTS: Among MMR2 participants (n = 621), 93.7%, 73.4%, and 83.9% had protective nAb levels against measles, mumps, and rubella, respectively, at the 10-year visit; among MMR3 participants (n = 665), 90.5%, 69.1%, and 100% had protective nAb levels, respectively, at the 9-11-year visit. Estimated nAb levels declined annually across both cohorts, all viruses, and baseline nAb strata, though patterns and magnitude varied. More than one-quarter of participants had mumps nAb levels below the presumed seroprotection threshold at the terminal visits. CONCLUSIONS: These findings indicate that even when MMR antibodies wane, protection against disease is largely retained. Waning of mumps antibodies was greater than for measles and rubella in both 2- and 3-dose vaccinees, likely because a greater proportion failed to mount a robust initial response.

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

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.

OBJECTIVE: Promoting health during adolescence can support long-term well-being, especially for teens diagnosed with attention-deficit/hyperactivity disorder (ADHD), who face increased risks due to the disorder's impact on development and health behaviors. ADHD is often associated with difficulties in social interactions, a higher likelihood of bullying involvement, and co-occurring mental health conditions. These factors may also be influenced by health factors such as physical activity, sleep quality, and screen time usage. Nationally representative teen self-reports provide a novel perspective on ADHD-related health outcomes compared with relying on parent reports. METHOD: We used nationally representative data from the National Health Interview Survey (NHIS) and NHIS-Teen from July 2021 to December 2022, to examine teen-reported health and well-being factors, stratified by parent-reported ADHD diagnoses among teens aged 12 to 17 years. Weighted prevalence estimates and adjusted prevalence ratios (aPR) adjusting for teen age, sex, and family income, all with 95% confidence intervals (CIs), were calculated. RESULTS: Just over 10% of teens had ADHD and they reported higher prevalence of bullying victimization (aPR = 1.64, CI = 1.27-2.11), difficulties making friends (aPR = 1.83, CI = 1.15-2.90), difficulty getting out of bed (aPR = 1.29, CI = 1.02-1.64), irregular wake times (aPR = 2.17, CI = 1.45-3.25), and >4 hours daily screen time (aPR = 1.26, CI = 1.05-1.52) than teens without ADHD; teens with ADHD reported a lower prevalence of lacking peer support (aPR = 0.70, CI = 0.51-0.96). CONCLUSION: Teens with ADHD face distinct challenges related to social-emotional well-being and health behaviors that support overall wellness. Findings may inform opportunities for health promotion among teens with ADHD.

Over 10 years, the reported incidence of primary and secondary syphilis increased among women at 6 times the rate compared with men (636% vs. 103%). Untreated syphilis can lead to life-altering complications including permanent vision and hearing loss, congenital syphilis, and increased HIV acquisition. Syphilis diagnosis and staging require current and prior laboratory results, physical examination, and history. The preferred treatment for syphilis is long-acting penicillin G benzathine. Partner testing and treatment are critical to prevent re-infection and further community transmission. Innovative strategies are needed to prevent and treat syphilis among women, especially those without regular access to health care.

IMPORTANCE: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden. OBJECTIVE: To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022. DESIGN, SETTING, AND PARTICIPANTS: Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.9 million persons across 10 US states. A case was defined as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis or streptococcal toxic shock syndrome between January 1, 2013, and December 31, 2022. Demographic and clinical data were collected from medical record review. From 2013 to 2014, available isolates were emm typed and antimicrobial susceptibilities determined using conventional methods; from 2015 onward, whole-genome sequencing was used. MAIN OUTCOMES AND MEASURES: Incidence rates by sex, age, race, and selected risk factors; clinical syndromes, outcomes, and underlying patient conditions; and isolate characteristics, including antimicrobial susceptibility. RESULTS: Surveillance in 10 US states identified 21 312 cases of invasive GAS from 2013 through 2022, including 1981 deaths. The majority of cases (57.5%) were in males. Among case-patients, 1272 (6.0%) were aged 0 to 17 years, 13 565 (63.7%) were aged 18 to 64 years, and 6474 (30.4%) were 65 years or older; 5.5% were American Indian or Alaska Native, 14.3% were Black, and 67.1% were White. Incidence rose from 3.6 per 100 000 persons in 2013 to 8.2 per 100 000 persons in 2022 (P < .001 for trend). Incidence was highest among persons 65 years or older; however, the relative increase over time was greatest among adults aged 18 to 64 years (3.2 to 8.7 per 100 000 persons). Incidence was higher among American Indian or Alaska Native persons than in other racial and ethnic groups. People experiencing homelessness, people who inject drugs, and residents of long-term care facilities had substantially elevated GAS incidence rates. Among tested isolates, those nonsusceptible to macrolides and clindamycin increased from 12.7% in 2013 to 33.1% in 2022. CONCLUSIONS: Invasive GAS infections increased substantially in 10 US states during a surveillance period from 2013 to 2022. Accelerated efforts to prevent and control GAS are needed, especially among groups at highest risk of infection.

Human metapneumovirus (hMPV) infections cause acute respiratory illness and lower respiratory tract disease. Respiratory syncytial virus (RSV) is a closely related virus within the Pneumoviridae family, and hMPV and RSV infections are associated with similar clinical manifestations. Although no specific antiviral therapies or vaccines exist for hMPV, vaccines and monoclonal antibody products are available to protect against severe RSV disease. This report summarizes hMPV circulation relative to the timing of RSV epidemics before, during, and after the COVID-19 pandemic. Polymerase chain reaction testing results reported to the National Respiratory and Enteric Virus Surveillance System during July 2014-June 2024, were analyzed. Before the COVID-19 pandemic, the median hMPV season onset, peak, and offset occurred in early January, late March, and early June, respectively (median duration = 21 weeks). The 2021-22 season was atypically long (35 weeks); seasonality reverted to more typical patterns during the 2022-23 and 2023-24 seasons. In the two COVID-19 pandemic seasons (2021-22 and 2022-23) and one postpandemic season (2023-24), RSV offsets occurred earlier in January (2021-22 and 2022-23) or March (2023-24) than before the pandemic, when the median offsets occurred in April. The annual interval from peak RSV to peak hMPV circulation increased from a prepandemic median of 11.5 weeks (range = 2-17 weeks) to 19 weeks (range = 19-20 weeks) during and after the pandemic. Fewer than 5 weeks of cocirculation of RSV and hMPV occurred in most regions during the 2022-23 and 2023-24 seasons. Real-time surveillance of RSV and hMPV co-circulation patterns can help guide clinician-directed testing and supportive care, optimize the use of prevention products, prompt detection of and response to outbreaks, and help ensure health care system preparedness for seasonal increases in illnesses.

HIV cross-sectional surveys require multi-layered testing with several tests to estimate HIV prevalence and HIV-1 incidence. We evaluated the performance and accuracy of the newly developed HIV Triplex assay to diagnose HIV-1 and HIV-2 and detect HIV-1 recent infections using plasma samples from the 2018 Nigeria AIDS Indicator and Impact Survey (NAIIS). Plasma samples from consenting HIV-positive (n=2,773) and a subset of HIV-negative samples (n=7,196), as determined by the national rapid testing algorithm, followed by Bio-Rad Geenius HIV-1/2 Supplemental Assay and Western Blot, aged 18 months - 64 years, were tested using the Luminex-based HIV Triplex assay. The assay classified specimens as HIV-1 positive, HIV-2 positive, dual (HIV-1 & 2) infections, or HIV-seronegative. All HIV-1 and dual infections were further classified as either HIV-1 recent (<6 months) or long-term (LT) based on mean fluorescent intensities and compared with the LAg-Avidity EIA as the reference. Multiplex results were analyzed and compared with the final NAIIS survey data for unweighted HIV prevalence and HIV-1 incidence. The diagnostic sensitivity and specificity of the HIV Triplex assay was 99.71% and 99.37%, respectively, with a kappa of 0.987 when compared to NAIIS survey results. Percent agreement between the HIV Triplex assay and the LAg-Avidity EIA for recent and LT classification was 98.86% with a kappa of 0.80 [CI: 0.71-0.89] and a Spearman-ranked correlation (ρ) of 0.689. A small number (n=45; 0.63%) of the subset of negatives tested were classified by the multiplex assay as either HIV-1 positive (n=35) or HIV-2 positive (n=10). Nevertheless, the HIV Triplex assay agreed with NAIIS HIV-negative survey results (99.37%). Using these results as they were, unweighted estimates of HIV prevalence for both HIV Triplex assay and NAIIS test results were similar (1.62% [95% CI: 1.56-1.68] and 1.60% [95% CI: 1.54-1.66], respectively) with overlapping confidence. After adjusting for viral load and anti-retroviral therapy, HIV-1 unweighted incidence for ages ≥15 years, using HIV Triplex assay data, was 0.70 per 1,000 [95% CI: 0.40-0.90]. This is similar to the unweighted incidence using the LAg-based RITA (recent infection testing algorithm) of 0.80 per 1,000 [95% CI: 0.60-1.10]. The HIV Triplex assay combines several assays in one, providing highly accurate results for estimating HIV prevalence and HIV-1 incidence in surveys. This assay has the potential to simplify cross-sectional surveys making them less expensive, easier, and quicker.

BACKGROUND: People who use long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) can have ambiguous HIV test results if HIV is acquired during its use. The 2021 CDC PrEP guidelines recommend both HIV antigen/antibody (Ag/Ab) and RNA testing at CAB-LA initiation and follow-up. METHODS: We conducted a cohort study using the HealthVerity database to evaluate the utilization of HIV testing among people who use CAB-LA PrEP. We identified and adjudicated HIV Ag/Ab and RNA tests with a positive result, and estimated the incidence of breakthrough HIV infection or long-acting early viral inhibition (LEVI) syndrome. Testing agreement, false positive test rates, and positive predictive value were explored. RESULTS: Among 384 people who use CAB-LA PrEP with both HIV Ag/Ab and RNA testing with a median follow-up time of 4.2 months, we found one discordant pair with Ag/Ab(-) and RNA(+), and one with Ag/Ab(+) and RNA(-). Among four users with a positive Ag/Ab or RNA test, we identified one who acquired HIV before CAB-LA initiation with both Ag/Ab(+) and RNA(+), one likely false RNA(+), one likely false Ag/Ab(+), and one inconclusive Ag/Ab(+) due to insufficient follow-up. We identified no persons with confirmed breakthrough HIV infection or LEVI syndrome, or with RNA testing resulting in an earlier HIV diagnosis compared with Ag/Ab testing alone. INTERPRETATION: The frequency of breakthrough HIV infection or LEVI syndrome in this real-world cohort was low during initial three to seven months of injectable PrEP use. Ongoing assessment of the added value of HIV RNA testing for monitoring during CAB-LA PrEP use is warranted.