BACKGROUND: Rotavirus gastroenteritis is one of major causes of death in infants, particularly in sub-Saharan Africa. In the Central African Republic (CAR), sentinel surveillance of rotavirus gastroenteritis was established in 2011. In this study, we assessed the burden of rotavirus gastroenteritis and identified rotavirus strains circulating in CAR during 2011-2021. METHODS: Stool samples were collected from < 5-year-old children with diarrhoea according to WHO criteria, at the sentinel site in Bangui, CAR. Samples were screened for group A rotavirus antigen by EIA. RNA was extracted from all EIA-positive samples which were subjected to genotyping using a semi nested RT-PCR assay. RESULTS: From 2011 to 2021, 1855 stool samples were collected and 854 (46.0%) were positive for rotavirus by EIA. Genotypes were obtained from 77.3% (660/854) EIA positive samples. Of these 660 samples, genotypes funds were: G1 (35.4%) and G2 (26.6%) for VP7, and P[6] (42.7%) and P[8] (35.6%) for the VP4 gene. The most frequent genotype combinations were G1P[8], 19.3% and G1P[6], 15.0%. CONCLUSION: This study reports the prevalence of rotavirus genotypes that circulated for ten years, providing a pre-vaccine baseline data genotype estimate for rotavirus gastroenteritis sentinel surveillance in the Central African Republic. CLINICAL TRIAL NUMBER: Not applicable.

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.

BACKGROUND: The advanced disease management (ADM) package, which aims to reduce morbidity and mortality in people with Advanced HIV disease (AHD, WHO stage III/IV and/or CD4 count < 200 cells/mm(3) or age < 5 years), is not fully implemented in India. We assessed the feasibility of implementing the full WHO ADM package as part of routine HIV care under the programmatic setting in antiretroviral therapy centers of Mumbai. METHODS: We implemented the ADM package (screening, treatment, and prophylaxis for major opportunistic infections, rapid ART initiation, and ART adherence support) in 17 ART centers from October 2020 to December 2021. Treatment naïve and experienced persons with AHD, including children, were enrolled. We assessed the feasibility through coverage of ADM package components and reported the proportion of rapid ART initiation (≤ 7 days), cotrimoxazole prophylaxis, TB preventive treatment (TPT) for those eligible [(excluded active TB disease (n = 280) and those completed TPT prior to enrolment (n = 1,186)], TB-LAM screening (excluded current TB disease), and cryptococcal antigen (CrAg) assay (excluded children < 10 years of age). We used a point of care test for TB (LAM) and cryptococcus (CrAg) screening. We followed the prospective cohort for one year (through 31 July 2022) to document outcomes for survival and lost to follow- up (LTFU). RESULTS: We identified 4,334 PLHIV with AHD and provided the full ADM package to 64% (2,779/4,334); 297 did not receive ADM (146 died, 151 LTFU), and 1,258 received routine standard of care (587 had TB, 366 were at decentralized sites, and 305 LAM/CrAg kits were not available) with existing ART center staff. Nearly 78% (385/494) of treatment naïve were rapidly initiated on ART. Nearly 82% (1,129/1,383) and 99% (2,751/2,779) received TPT and cotrimoxazole prophylaxis, respectively. Of the eligible, 99% (2,508/2,524) and 98% (2,715/2,758) were screened for TB and cryptococcal infection, respectively. At the end of 12 months, 88% (2,458/2,779) were alive, 8% (210/2,779) died, and 4% (111/2,779) were LTFU. Mean survival time was significantly (p < 0.001) higher among treatment experienced people; 11.6 months (95% CI: 11.5,11.7) compared to treatment naïve people 10.8 months (95% CI: 10.5,11.0). CONCLUSION: With careful anticipatory planning, stakeholder engagement, and training, implementing the full ADM package is feasible in a routine program setting with existing human resources. Additional intensive case management may be necessary for the reduction of mortality among treatment naïve PLHIV.

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

BACKGROUND: This report represents a collaborative effort by the major cancer surveillance organizations to present the definitive US statistics for cancer incidence and mortality. METHODS: Cancer incidence data were obtained from population-based cancer registries funded by the Centers for Disease Control and Prevention and the National Cancer Institute and compiled by the North American Association of Central Cancer Registries. Cancer death data were obtained from the National Center for Health Statistics' National Vital Statistics System. Statistics are reported by cancer type, sex, race and ethnicity, and age. The potential impact of the coronavirus disease 2019 (COVID-19) pandemic on incidence was assessed by using state-level changes compared with previous years, the stringency of COVID-19 policy restrictions, the magnitude of COVID-19 death rates, and changes in the use of mammography. RESULTS: Overall cancer incidence rates per 100,000 were 500 among males and 437 among females. Excluding 2020, cancer incidence rates remained stable (2013-2021) among males and increased 0.3% per year on average (2003-2021) among females. The overall cancer death rate per 100,000 was 173 among males and 126 among females. Cancer death rates decreased by 1.5% per year (2018-2022), slowing from a previous 2.1% decline. Cancer incidence in 2020 declined from prepandemic levels for all demographic groups examined. However, the magnitude of decline was not strongly associated with the study's proxies for health care capacity, health care access, or COVID-19 policies. CONCLUSIONS: Overall cancer mortality declined over 20 years, even during the COVID-19 pandemic. Disruptions in health care use early in the pandemic resulted in incidence declines in 2020, but 2021 incidence returned to prepandemic levels.

INTRODUCTION: Chronic conditions are costly and major causes of death and disability. Addressing conditions earlier in adulthood can slow disease progression and improve well-being across the lifespan. We estimated, by life stage, 10-year trends among US adults in the prevalence of 1 or more chronic conditions, multiple chronic conditions (MCC; ≥2 conditions), and 12 selected chronic conditions. METHODS: We analyzed data from the 2013-2023 (odd years) Behavioral Risk Factor Surveillance System (N = 2,673,529). We estimated the prevalence of 1 or more conditions, MCC, and each of 12 conditions, by life stage: young (18-34 y), midlife (35-64 y), and older (≥65 y) adults. We used polynomial contrasts to analyze 10-year trends. RESULTS: In 2023, 76.4% (representing 194 million) of US adults reported 1 or more chronic conditions, including 59.5%, 78.4%, and 93.0% of young, midlife, and older adults, respectively. Moreover, 51.4% (representing 130 million) of US adults reported MCC, including 27.1%, 52.7%, and 78.8% of young, midlife, and older adults, respectively. Among young adults, from 2013 to 2023, prevalence increased significantly from 52.5% to 59.5% for 1 or more conditions and from 21.8% to 27.1% for MCC. CONCLUSION: Approximately 6 in 10 young, 8 in 10 midlife, and 9 in 10 older US adults report 1 or more chronic conditions. Trends in conditions worsened among young adults during 2013-2023. Recognizing the burden of chronic disease throughout life stages, especially earlier in life, practitioners and partners may consider prevention and management approaches critical for addressing costs, care, and health outcomes. Practitioners may also consider tailoring these approaches to unique roles, transitions, and challenges in different life stages.

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus, is an important reservoir of Leptospira spp. in urban settings. We investigated the presence of Leptospira spp. among brown rats in Boston, Massachusetts and hypothesized that rat population dynamics in this urban setting influence the transportation, persistence, and diversity of Leptospira spp. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira spp. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira spp. isolates obtained from frozen and fresh tissue from some of the 59 positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional Leptospira spp. genomes from rats. We also generated an enriched Leptospira spp. genome from a 2018 human case in Boston. We found evidence of high genetic structure among rat populations that is likely influenced by major roads and/or other dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats that were tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and its transportation is influenced by rat population dynamics. Finally, our genomic analyses of the Leptospira spp. detected in the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other similar urban settings.

OBJECTIVES: This study examines the prevalence of health conditions for which miners enrolled in a state-funded insurance program sought care. METHODS: We conducted a retrospective analysis of claims data submitted to the Wyoming Miner's Hospital during 2014-2023. Using International Classification of Diseases codes and identifiers unique to each miner, we calculated the number of unique miners with claims submitted for major disease categories and common diagnoses within each category. RESULTS: Musculoskeletal disorders (MSDs) and diseases of the endocrine and cardiovascular systems were the most prevalent conditions, affecting 72.7%, 34.2%, and 31.1% of enrolled miners, respectively. CONCLUSIONS: This population of miners has a substantial burden of health conditions that can adversely impact health and well-being. Mine safety and health professionals can use analyses of claims data to identify priorities for improving miner health and well-being.

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

Seismic monitoring of underground longwall mines can provide valuable information for managing coal burst risks and understanding the ground response to extraction. However, the underground longwall mine environment poses major challenges for traditional in-mine microseismic sensors including the restricted use of electronics due to potentially explosive atmospheres, the need to frequently and quickly relocate sensors as rapid mining progresses, and source parameter errors associated with complex time-dependent velocity structure. Distributed acoustic sensing (DAS), a technology that uses rapid laser pulses to measure strain along fiber-optic cables, shows potential to alleviate these shortcomings and improve seismic monitoring in coal mines when used in conjunction with traditional monitoring systems. Moreover, because DAS can acquire measurements that are not possible to record with traditional seismic sensors, it also enables entirely new monitoring approaches. This work demonstrates several DAS deployment strategies such as deploying fiber on the mine floor, in boreholes drilled from the surface and from mine level, on the longwall mining equipment, and wrapped around secondary support cans. Although there are several data processing and deployment improvements needed before DAS-based monitoring can become routine in underground longwall mines, the findings presented here can aid decision makers in assessing the potential of DAS to meet their needs and help guide future deployment designs. © 2025

Work-related injuries from overexertion, particularly lifting, are a major concern in occupational safety. Traditional assessment tools, such as the Revised NIOSH Lifting Equation (RNLE), require significant training and practice for deployment. This study presents an approach that integrates tactile gloves with computer vision (CV) to enhance the assessment of lifting-related injury risks, addressing the limitations of existing single-modality methods. Thirty-one participants performed 2747 lifting tasks across three lifting risk categories (LI < 1, 1 ≤ LI ≤ 2, LI > 2). Features including hand pressure measured by tactile gloves during each lift and 3D body poses estimated using CV algorithms from video recordings were combined and used to develop prediction models. The Convolutional Neural Network (CNN) model achieved an overall accuracy of 89 % in predicting the three lifting risk categories. The results highlight the potential for a real-time, non-intrusive risk assessment tool to assist ergonomic practitioners in mitigating musculoskeletal injury risks in workplace environments.

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

BACKGROUND: Human parainfluenza viruses (PIV) are a major cause of acute respiratory infection (ARI) leading to hospitalization in young children. In order to quantify the burden of PIV hospitalizations and to evaluate the characteristics of children hospitalized with PIV by virus type, we used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective population-based surveillance network, enrolling children hospitalized for ARI (defined as fever and/or respiratory symptoms) at 7 U.S. children's hospitals. METHODS: The study period included December 1, 2016 through March 31, 2020. Data captured included demographic characteristics, clinical presentation, underlying medical conditions, discharge diagnoses, and virus detection by RT-PCR. Linear and logistic regression were used to compare descriptive and clinical characteristics among children. Population-based PIV-associated hospitalization rates were calculated by age group and PIV-type. RESULTS: Of the 16,791 enrolled children with PIV virologic testing, 10,488 had only one respiratory virus detected, among whom 702 (7%) had positive testing for PIV without a co-detected virus (mean age [SD], 2.2 [3.2] years). Of these 702 children, 340 (48%) had underlying comorbidities, 139 (20%) had a history of prematurity, 121 (17%) were admitted to the ICU, and 23 (3%) required intubation. Overall, PIV hospitalization rates were highest in children aged 0-5 months (1.91 hospitalizations per 1,000 children per year [95% CI, 1.61-2.23], with PIV-3 contributing to the highest rates in that age group, followed by PIV-1 and PIV-4: 1.08 [0.84-1.21], 0.42 [0.28-0.58] and 0.25 [0.15-0.37] per 1,000 children per year, respectively. Seasonal distribution of PIV-associated hospitalizations varied by type. CONCLUSIONS: PIV infection was associated with a substantial number of ARI hospitalizations in children aged 0-5 months. Results suggest that future PIV prevention strategies in the US that focus on younger children and protection against PIV-3, PIV-1, and PIV-4 might have the greatest impact on reducing PIV hospitalization burden.

Estimating the number of illnesses caused by foodborne pathogens is critical for allocating resources and prioritizing interventions. We estimated the number of illnesses, hospitalizations, and deaths in the United States caused by 7 major foodborne pathogens by using surveillance data and other sources, adjusted for underreporting and underdiagnosis. Campylobacter spp., Clostridium perfringens, invasive Listeria monocytogenes, norovirus, nontyphoidal Salmonella serotypes, and Shiga toxin-producing Escherichia coli caused ≈9.9 million (90% credible interval [CrI] 5.9-15.4 million) domestically acquired foodborne illnesses in 2019. Together with Toxoplasma gondii, those pathogens caused 53,300 (90% CrI 35,700-74,500) hospitalizations and 931 (90% CrI 530‒1,460) deaths. Norovirus caused most illnesses (≈5.5 million illnesses, 22,400 hospitalizations), followed by Campylobacter spp. (1.9 million illnesses, 13,000 hospitalizations) and nontyphoidal Salmonella serotypes (1.3 million illnesses, 12,500 hospitalizations). Salmonella infection was the leading cause of death (n = 238). Foodborne illness estimates can inform policy and direct food safety interventions that reduce those illnesses.

BACKGROUND: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria before treatment. The use of nucleic-acid amplification (NAAT) for detection of Plasmodium spp. has expanded rapidly in recent years, for epidemiological research globally and clinical care in high-resource settings. Data from NAATs are frequently used to inform policy decisions, so quality control is essential to ensure results are reliable and comparable. Therefore, robust quality control, including an external quality assessment (EQA) scheme targeting malaria NAATs, is essential. The WHO Global Malaria Programme and the UK National External Quality Assessment Service (UK NEQAS) have collaborated since 2017 to implement a global malaria NAAT EQA scheme. METHODS: Panels of specimens containing five major species of human-infecting Plasmodium at various parasite concentrations and negative samples were created in lyophilized blood (LB) and dried blood spot (DBS) formats. Two distributions per year were sent, containing five LB and five DBS specimens. Samples were validated by expert referee laboratories prior to distribution. Between 37 and 51 laboratories participated in each distribution and submitted results online. Participants were scored based on their laboratory's stated capacity to identify Plasmodium species, and individual laboratory reports were sent which included performance comparison with anonymized peers. Change in performance over time was calculated using a generalized mixed model with a logit link function. RESULTS: Participating laboratories were located in 42 countries. Sample format (DBS or LB) and parasite density were found to significantly affect performance, while referee labs performed better at identifying P. falciparum samples than non-referee labs. Performance of laboratories improved significantly over time, especially for lower density and P. falciparum samples. CONCLUSIONS: Results from the first eleven distributions indicate that the EQA scheme has facilitated improved performance of laboratories over time, highlighting the value of implementing such programmes. EQA schemes are critical to safeguarding the reliability of data and diagnoses, especially in situations where NAAT methodologies and protocols are used. In future, funders should make participation in an EQA scheme a requirement for laboratories, and countries can take initiatives to embed such schemes into their own national assessment programmes.

IMPORTANCE: Antimicrobial resistance is a major public health problem in the US. Estimating national rates of antimicrobial-resistant infections commonly associated with health care can aid in targeted public health efforts. OBJECTIVE: To determine the national incidence rates of 6 pathogens over time: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp (excluding Klebsiella aerogenes) (ESCR-EK), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter spp (CRAsp), and multidrug-resistant (MDR) Pseudomonas aeruginosa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2012 to 2022 on inpatient hospitalizations, clinical cultures, and facility-level characteristics. Hospital-months were included in the dynamic cohort if the hospital reported at least 1 culture with microbial growth accompanied by antimicrobial susceptibility testing (AST) results in the month. Data from the PINC-AI and Becton Dickinson Insights databases were used, and cases were defined as incident nonsurveillance cultures yielding an organism of interest with sufficient AST results for a phenotype of interest. Data were collected from January 2012 to December 2022 and analyzed from April 2023 to June 2024. EXPOSURE: Inpatient hospitalizations with a discharge date in an included hospital month. MAIN OUTCOMES AND MEASURES: National annual antimicrobial-resistant cases per 10 000 hospitalizations were obtained using weights based on facility-level characteristics. Cases were defined as community-onset if collected on or before day 3 of hospitalization and hospital-onset if obtained on day 4 or later. RESULTS: This study cohort included 332 to 606 hospitals per year between 2012 to 2022 and 7 158 139 cultures. Antimicrobial-resistant pathogens accounted for an estimated 569 749 (95% CI, 475 949-663 548) cases and 179.6 (95% CI, 163.1-196.1) cases per 10 000 hospitalizations in 2022. Of these cases, 77% (437 657; 95% CI, 364 529-510 785) were community-onset and 23% (132 092; 95% CI, 108 241-155 943) were hospital-onset. MRSA (44% [251 854; 95% CI, 209 558-294 150]) and ESCR-EK (35% [200 884; 95% CI, 163 692-238 077]) made up the largest proportions of total infections in 2022, respectively. Rates of hospital-onset MRSA, VRE, CRE, CRAsp, and MDR P aeruginosa had periods of decline from 2012 to 2019; however, all pathogens experienced an increase in hospital-onset rates in 2020 and 2021. Community-onset ESCR-EK rates increased from 2012 to 2022, while community-onset rates of MRSA, VRE, and MDR P aeruginosa declined. CONCLUSIONS AND RELEVANCE: While antimicrobial resistance rates have experienced uneven declines in the US from 2012 to 2022, the burden of resistance remains substantial. These findings suggest that more effective strategies to reduce antimicrobial resistance are needed.

BACKGROUND: Nanomedicine offers a number of innovative strategies to address major public health burdens, including complex respiratory illnesses. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation for the treatment of influenza, SARS-CoV-2, and their co-infections. METHODS: The SARS-CoV-2 antiviral, remdesivir; the influenza antiviral, baloxavir marboxil; and the anti-inflammatory, dexamethasone, were co-crystalized and then ablated in aqueous media using a femtosecond pulsed laser and subsequently surface modified with the cationic polymer, chitosan, or poly-d-lysine. Physical and chemical properties were then characterized using multiple complimentary techniques. Finally, a clinically relevant in vitro primary mouse trachea epithelial cell-air-liquid interface culture model was used to analyze the antiviral effect of our nanoparticles against Influenza Virus A. RESULTS: Our final nanoparticle exhibited a positive zeta potential with a diameter of ~73 nm. Remdesivir, baloxavir marboxil, and dexamethasone were all present in the nanoparticle suspension at a 1:1:1 ratio. Notably, these particles exhibited a potent anti-influenza effect, decreasing the viral titer by ≈ 4 logs in comparison to vehicle controls. CONCLUSION: Overall, these findings demonstrate great promise both for the use of laser ablation to generate multi-drug nanoparticles and for the anti-viral effects of our nanoformulation against respiratory illness.

Road traffic deaths are preventable but remain a major public health problem. Crashes cause more than 40,000 deaths annually in the United States, and traffic-related pedestrian deaths have increased rapidly. To examine change in pedestrian and overall traffic death rates (deaths per 100,000 population) within an international context, CDC analyzed 2013-2022 data from the United States and 27 other high-income countries in the International Road Traffic and Accident Database, as well as early 2023 U.S. estimates. Between 2013 and 2022, U.S. pedestrian death rates increased 50% (from 1.55 to 2.33 per 100,000 population), while other countries generally experienced decreases (median decrease = 24.7%). During this period, overall U.S. traffic death rates increased 22.5% (from 10.41 to 12.76), but decreased by a median of 19.4% in 27 other high-income countries. Among all countries examined, the United States had the highest pedestrian death rates overall and among persons aged 15-24 and 25-64 years. Projected 2023 U.S. estimates suggest a potential decline in pedestrian (2%) and overall traffic (4%) deaths, compared with those in 2022. Accelerated adoption of a Safe System approach, focused on creating safer roadways and vehicles, establishing safer speeds, supporting safer road users, and improving post-crash care, can help reduce U.S. pedestrian and overall traffic deaths.

Relapsing fever Borrelia (RFB) employs antigenic variation to alter its surface protein structure in response to host immune pressure. This process occurs by the single translocation of archived variable major protein (Vmp) pseudogenes into a vmp expression locus. Borrelia miyamotoi, phylogenetically grouped with RFB, has the genetic makeup for antigenic variation, but it has not been determined whether B. miyamotoi can create new variant serotypes in vivo. We inoculated mice with a non-clonal parental B. miyamotoi CT13-2396 strain with a known Vmp majority serotype with spirochete isolation at various days post-infection. The vmp that determined the reisolated variant serotype was identified by PCR of the expression locus followed by DNA sequencing of the amplified product. For each mouse reisolate, new variants replaced the parent majority serotype. Moreover, some mice produced additional variant reisolates days apart, indicative of the presentation seen in relapsing fever infections. Infection of mice with a clonal population resulted in the elimination of the inoculated serotype and isolation of new variants. Mouse serum obtained following infection revealed IgM antibodies reactive to the parent Vmp serotype, suggesting that the immune response eliminated or greatly reduced the majority population. These results demonstrated that B. miyamotoi reisolated from infected mice exhibited serotype populations differing from the inoculated strain, indicating the spirochetes underwent antigenic variation to evade the host's immune response. However, whether the observed variation occurred by way of outgrowth of minority populations or by translocation of archived pseudogenes to the expression locus creating new variants awaits further study.

BACKGROUND: Noroviruses are the leading cause of acute gastroenteritis worldwide with GII.4 Sydney viruses responsible for the majority of infections until 2023. METHODS: To study the evolutionary dynamics of GII.4 noroviruses in the US (2011-2023), we sequenced and analyzed 406 VP1 and 335 RdRp sequences submitted to CaliciNet. RESULTS: Time-scale analysis showed the average evolutionary rate of GII.4 strains was 5.56 x 10-3 substitutions/site/year and the emergence of a new cluster within GII.4 Sydney every 4 years starting with GII.4 Sydney[P31] from 2011-2015 followed by GII.4 Sydney[P16] from 2016-2020, and the most recent GII.4 Sydney[P16]-2020 from 2021-to date. Since 2017, based on amino acids in VP1, we observed the emergence of three novel GII.4 clusters (GII.4 San Francisco, GII.4 Allegany and GII.4 Wichita). GII.4 Sydney was identified with 4 P-types (P4, P12, P16, and P31). GII.4 San Francisco and GII.4 Allegany had a P31 RdRp, whereas GII.4 Wichita strains had P4. GII.4 Allegany and GII.4 Wichita exhibited major amino acid substitutions in epitopes A-E, G, and H, while GII.4 San Francisco viruses have an alanine insertion in epitope A. Both GII.4 Allegany and GII.4 Wichita VLPs bound porcine gastric mucin at a similar level as GII.4 New Orleans and GII.4 Sydney. However, blocking of binding to VLPs by human serum pools demonstrated their antigenicity was significantly different. CONCLUSION: We identified three new emerging GII.4 noroviruses co-circulating with GII.4 Sydney. Early detection of new strains will aid in tracking their spread and assessing their pandemic potential.

Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.4 VP1 capsid-encoding adenoviral vaccine. Two participants were specifically selected on the basis of the breadth of serum neutralization responses either across GII.4 variants (participant A) or across GII genotypes (participant B). In participant A, vaccination back-boosted highly abundant serum antibody clonotypes targeting epitopes conserved among rapidly evolving GII.4 variants spanning from a strain identified in 1987 to a strain identified in 2019. In participant B, we identified a recall response consisting of broadly neutralizing monoclonal antibodies with remarkable cross-GII ligand-binding blockade (blocking ≥ seven GII genotypes) and virus neutralization breadth. The cocrystal structure of one of these antibodies, VX22, in complex with the VP1 capsid protruding (P) domain revealed a highly conserved epitope (residues 479 to 484 and 509 to 513) within two lateral loops of the P1 subdomain. Antibody evolutionary trajectory analysis further revealed that VX22 had originally evolved from an early heterologous infection, likely by a GII.12 strain. Together, our study demonstrates that norovirus human monoclonal antibodies with broad GII.4 potency and cross-GII breadth can be boosted in serum after immunization with an adenoviral vector-based vaccine, findings that may guide the design of immunogens for broadly protective norovirus vaccines.

BACKGROUND: Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide. Data of the associations between specific volatile organic compounds (VOCs), a major component of air pollution and tobacco smoke, and subsequent CRD mortality in the general population are scarce. METHODS: In a case-cohort analysis within the population-based Golestan cohort study (n = 50045, aged 40-75 years, 58% women, enrollment: 2004-2008, northeastern Iran), we included all participants who died from CRD during follow-up through 2018 (n = 242) as cases and stratified them into 16 strata defined by age, sex, residence, and tobacco smoking. Subcohort participants (n = 610) were randomly selected from all eligible cohort participants in each stratum, and sampling fractions were calculated. Baseline urine samples were used to measure 20 VOCs using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. After excluding participants with previous history of CRDs, we used stratified Cox regression models weighted by the inverse sampling fractions (i.e. inverse probability weighting) adjusted for potential confounders, including urinary cotinine and pack-years of smoking, to calculate hazard ratios (HR) for the associations between biomarker tertiles and CRD mortality. RESULTS: Data from 545 non-case, sub-cohort participants and 149 cases (69.1% chronic obstructive pulmonary disease, 13.4% asthma, 17.5% other CRDs) were assessed in this study. During a follow-up of 10.5 years, associations [2nd and 3rd vs. 1st tertiles, HR (95% confidence interval), p for trend] were observed between metabolites of acrolein [1.56 (0.64,3.79), 3.53 (1.53,8.16), 0.002] and styrene/ethylbenzene [1.17 (0.53,2.60), 3.24 (1.37,7.66), 0.005] and CRD mortality, which persisted after excluding the first four years of follow-up. CONCLUSION: Our findings support prior research suggesting respiratory toxicity of VOCs. Further investigation and monitoring of these compounds, especially acrolein and styrene/ethylbenzene, as CRD risk factors, are recommended.

In the era of genomic characterization of strains for public health microbiology, whole genome sequencing (WGS)-enabled subtyping of Salmonella provides superior discrimination of strains compared to traditional methods such as serotyping. Nonetheless, serotypes are still very useful; they maintain historical continuity and facilitate clear communication. Genetic determination of serotypes from WGS data is now routine. Genetic determination of rarer serotypes can be problematic due to a lack of sequences for rare antigen types and alleles, a lack of understanding of the genetic basis for some antigens, or some inconsistencies in the White-Kauffmann-Le Minor (WKL) Scheme for Salmonella serotype designation. Here, we present a simplified interpretation of serotypes to address the shortcomings of genetic methods, which will allow the streamlined integration of serotype determination into the WGS workflow. The simplification represents a consensus perspective among major U.S. public health agencies and serves as a WGS-oriented interpretation of the WKL Scheme. We also present SeqSero2S, a bioinformatics tool for WGS-based serotype prediction using the simplified interpretation.IMPORTANCEThe utility of Salmonella serotyping has evolved from a primary subtyping method, where the need for strain discrimination justified its complexity, to a supplemental subtyping scheme and nomenclature convention, where clarity and simplicity in communication have become important for its continued use. Compared to phenotypic methods like serotyping, whole genome sequencing (WGS)-based subtyping methods excel in recognizing natural populations, which avoids grouping together strains from different genetic backgrounds or splitting genetically related strains into different groups. This simplified interpretation of serotypes addresses a shortcoming of the original scheme by combining some serotypes that are known to be genetically related. Our simplified interpretation of the White-Kauffmann-Le Minor (WKL) Scheme facilitates a complete and smooth transition of serotyping's role, especially from the public health perspective that has been shaped by the routine use of WGS.

This study demonstrated that workers' compensation claims data can provide insights into federal employees' workplace injuries and illnesses. Employing agencies, safety staff, and occupational clinicians can use these data to direct efforts to improve conditions to prevent injuries/illnesses, optimize programs for injured worker treatment, rehabilitation, accommodation, and stay-at-work or return-to-work programs. Objective: The purpose of this study was to understand federal workplace injury/illness trends. Methods: Over 1.5 million federal and Postal Service employee workers' compensation (WC) claims from 2007 to 2022 were linked to employment data and analyzed. Results: From 2007 to 2019, falls, slips, trips represented the highest proportion of claims (30.7%), followed by overexertion and bodily reaction (24.4%), unclassified (16.4%), contact with objects and equipment (13.1%), violence and other injuries by persons or animals (8.8%), transportation incidents (4.0%), exposure to harmful substances or environments (2.5%), and fires and explosions (0.24%). From 2020 to 2022, COVID-19 drove a major shift to exposure to harmful substances or environments representing the highest proportion of claims (44.3%). Conclusions: Claims data represent a potentially rich data source that employing agencies can use to focus prevention and treatment of injury/illness.

To assess the prevalence of several parasitic infections in Kiribati, dried blood spots collected during trachoma prevalence surveys in the two major population centers in 2015, 2016, and 2019 were tested using multiplex bead-based serologic assays to detect IgG antibodies against four pathogens of public health interest: Toxoplasma gondii (T. gondii), Taenia solium (T. solium), Strongyloides stercoralis (S. stercoralis), and Toxocara canis (T. canis). In Kiritimati Island, the seroprevalences of T. solium recombinant antigen for detection of cysticercosis antibodies (T24H) and recombinant antigen for detection of taeniasis antibodies (ES33) were ≤4% in both surveys, whereas in Tarawa, the T24H seroprevalence was 2% (2016) and 7% (2019) and the ES33 seroprevalence was ≤3% in both surveys. At both sites, the seropositivity of S. stercoralis recombinant antigen for detection of Strongyloides was 0-4%, and for T. canis, the C-type lectin-1 antigen was 0-1% in all surveys. For T. gondii, the surface antigen glycoprotein 2A antigen seroprevalences on Kiritimati Island were 41% (2015) and 36% (2019), and in Tarawa, they were 36% (2016) and 22% (2019), suggesting that T. gondii infections are common in Kiribati, whereas the other pathogens are not.

BACKGROUND: Globally, opioid use remains a major public health problem. In 2019, 480,000 deaths were related to opioid use. Locally, mortality from opioid-involved overdose is high among Illinois residents, with 83 % of ∼4000 overdose deaths during 2022 involving opioids. Treatment for opioid use disorder with buprenorphine, methadone, and naltrexone is approved, safe, and effective. However, significant barriers to treatment remain for many persons. METHODS: In response to new prescribing policy flexibilities, in May 2022, the Chicago Department of Public Health and the Substance Use Prevention and Recovery Division of the Illinois Department of Human Services partnered with a statewide opioid treatment provider, Family Guidance Centers. The partnership started an immediate opioid use disorder treatment helpline program. We performed a descriptive analysis using aggregate data from all calls for assistance with substance use received by the Illinois Helpline during May 9, 2022-March 7, 2024. RESULTS: A total of 2649 unique calls were made to the helpline from persons seeking assistance with substance use, and 1698 unique callers were connected to Family Guidance Centers for treatment initiation. Most callers were prescribed buprenorphine by telemedicine, followed by methadone during in-person treatment. In total, 1515 (89.2 %) of 1698 callers with opioid use disorder were initiated on buprenorphine or methadone through the program. CONCLUSION: A state-wide low-barrier access to medications by telemedicine program is an effective treatment model for the initiation of medications for opioid use disorder.

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

Antimicrobial resistance continues to be a growing threat globally, specifically in health-care settings in which antimicrobial-resistant pathogens cause a substantial proportion of health-care-associated infections (HAIs). Next-generation sequencing (NGS) and the analysis of the data produced therein (ie, bioinformatics) represent an opportunity to enhance our capacity to address these threats. The 3rd Geneva Infection Prevention and Control Think Tank brought together experts to identify gaps, propose solutions, and set priorities for the use of NGS for HAIs and antimicrobial-resistant pathogens. The major deliverable recommendation from this meeting was a proposed framework for implementing the sequencing of HAI pathogens, specifically those harbouring antimicrobial-resistance mechanisms. The key components of the proposed framework relate to wet laboratory quality, sequence data quality, database and tool selection, bioinformatic analyses, data sharing, and NGS data integration, to support public health and actions for infection prevention and control. In this Personal View we detail and discuss the framework in the context of global implementation, specifically in low-income and middle-income countries.

Beginning with the 2020 decennial census and the 2020 American Community Survey (ACS), the U.S. Census Bureau implemented changes in question design, data processing, and coding procedures for the race and ethnicity data they collect that appear to have resulted in major data discontinuity. However, the Census Bureau has not released nor plans to release research showing the impact of these changes. We explore the impact of the Census Bureau's procedural changes on the racial and ethnic distributions of the Hispanic (generally and by country of origin) and the American Indian and Alaska Native populations, the two populations most impacted by these changes. We use the 2019 and 2021 one-year ACS public-use microdata and 2019 and 2021 NCHS mortality data to compare racial distributions and estimate and compare select demographic and socioeconomic characteristics, and mortality measures across the two years. Our results show that changes the Census Bureau implemented beginning with the 2020 decennial census and ACS appear to have had a significant impact on the comparability of Census Bureau race and ethnicity data. We find a significant data discontinuity impacting a wide variety of demographic, socioeconomic, and mortality statistics and analyses that rely on U.S. Census Bureau data as input for calculations. To mitigate these effects, methods that bridge race and ethnicity data between pre- and post-2020 census data are needed. Our research brings new attention and clarity to the race and ethnicity data discontinuity in Census Bureau data that started in 2020. © 2025

Structural variants of the synthetic opioid fentanyl are a major threat to public health. Following an investigation showing that many derivatives are poorly detected by commercial lateral flow and related assays, we created hapten conjugate vaccines using an immunogenic virus-like particle carrier and eight synthetic fentanyl derivatives designed to mimic the structural features of several of the more dangerous analogues. Immunization of mice elicited strong antihapten humoral responses, allowing the screening of hundreds of hapten-specific hybridomas for binding strength and specificity. A panel of 13 monoclonal IgG antibodies were selected, each showing a different pattern of recognition of fentanyl structural variations, and all proving to be highly efficient at capturing parent fentanyl compounds in competition ELISA experiments. These results provide antibody reagents for assay development as well as a demonstration of the power of the immune system to create binding agents capable of both broad and specific recognition of small-molecule targets.