OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

INTRODUCTION: The association between various disparity factors and cardiovascular disease (CVD) prevalence among older US adults with diabetes has not been comprehensively explored. We examined disparities in CVD prevalence among Medicare beneficiaries with diabetes. METHODS: Data were from the 2015-2019 Medicare Current Beneficiary Survey. Diabetes and CVD conditions - myocardial infarction (MI), stroke, and heart failure - were self-reported. We estimated the adjusted prevalence ratios (APRs) of CVD by race and ethnicity, education, income-to-poverty ratio (IPR), urbanicity, food insecurity, and social vulnerability using logistic regressions that controlled for these factors as well as age and sex. RESULTS: Annually, an estimated 9.2 million Medicare beneficiaries aged 65 years or older had diabetes. Among them, 16.7% had MI, 13.7% had stroke, and 12.5% had heart failure. Beneficiaries who were food insecure, socially vulnerable, with an IPR less than or equal to 135%, and residing in rural areas had a higher crude CVD prevalence. After controlling for other factors, low IPR and food insecurity were linked to a higher prevalence of CVD. Hispanic beneficiaries had lower stroke and heart failure prevalence than non-Hispanic (NH) White and NH Black beneficiaries. NH Black beneficiaries had lower MI prevalence but higher heart failure prevalence compared with NH White beneficiaries. Female respondents with an IPR less than or equal to 135% had higher MI and stroke prevalence; this was not seen in male respondents. CONCLUSION: Low IPR and food insecurity were associated with higher MI, stroke, and heart failure prevalence among Medicare beneficiaries with diabetes. Our findings can inform targeted interventions to reduce CVD disparities in these populations.

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced -2.43 (95% CI: -3.76, -1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced -2.79 (95% CI: -4.99, -0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

Conducting persistence studies of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces may require a biosafety level 3 (BSL-3) laboratory. We aimed to compare the environmental persistence of BSL-2 level human coronaviruses (229E, NL63, and OC43) and bovine coronavirus (BoCoV) with three SARS-CoV-2 variants (WA-1, Delta, and Omicron). OC43 (1.8 TCID(50)/mL) and BoCoV (1.0 TCID(50)/mL) had lower detection thresholds in cell culture assays compared to 229E (150 TCID(50)/mL) and NL63 (2,670 TCID(50)/mL) and were used for persistence tests at room temperature. Viable OC43 became undetectable (>5.2log(10)) after 48 hours on stainless steel and plastic coupons but exhibited extended persistence up to 72 hours on touchscreen glass coupons. In contrast, BoCoV remained viable for up to 120 hours with <1.8 log(10) infectivity loss. Both OC43 and BoCoV showed a reduction of >5 log(10) on vinyl coupons after 48 hours. On stainless steel coupons, the viability of all three SARS-CoV-2 variants became undetectable (>2.3 log(10) reduction) after 48 hours, with minor differences in reduction levels at 24 hours, whereas on touchscreen glass coupons, the viable virus could be detected for up to 48 hours for WA-1 and Omicron and 72 hours for the Delta variant. Regardless of coupon or virus type, viral RNA titers increased <4.5 Ct values after 120 hours. Our data demonstrate distinct persistence characteristics between BoCoV and OC43, with neither fully mimicking SARS-CoV-2 variants. This variability along with the impact of surface types on viral persistence underscores the need for caution when using these viruses as surrogates for SARS-CoV-2.IMPORTANCEIn this study, we evaluated three human seasonal coronaviruses (OC43, NL63, and 229E) and one bovine coronavirus (BoCoV) as potential surrogate viruses for SARS-CoV-2. Our data suggest that among the four surrogate viruses tested, OC43 and BoCoV were the most promising candidates due to their assay sensitivity, ease of handling, and high genetic similarity to SARS-CoV-2. However, neither BoCoV nor OC43 fully mimicked the environmental persistence characteristics of SARS-CoV-2 variants highlighting the potential limitations of using surrogate viruses.

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.

In 2006, human papillomavirus (HPV) vaccine was first recommended in the United States to prevent cancers and other diseases caused by HPV; vaccination coverage increased steadily through 2021, and increasing numbers of young women had received HPV vaccine as children or adolescents. Since 2008, CDC has monitored incidence of precancerous lesions (cervical intraepithelial neoplasia [CIN] grades 2-3 and adenocarcinoma in situ [AIS], collectively CIN2+), which are detected through cervical cancer screening and can be used as an intermediate outcome for monitoring vaccination impact, via the five-site Human Papillomavirus Vaccine Impact Monitoring Project. This analysis describes trends in incidence of CIN2+ and CIN3+ (i.e., CIN grade 3 and AIS) lesions during 2008-2022. Among women aged 20-24 years who were screened for cervical cancer, rates during 2008-2022 decreased for CIN2+ by 79%, and for CIN3+ by 80%. In the same period, CIN3+ rates among screened women aged 25-29 years decreased by 37%. These data are consistent with considerable impact of HPV vaccination for preventing cervical precancers among women in the age groups most likely to have been vaccinated, and support existing recommendations to vaccinate children at the routinely recommended ages as a cancer prevention measure.

Our understanding of how exposure to school microbiota affects the respiratory health of staff and students in schools is limited. We examined the associations between exposure to school microbiota and respiratory and gastrointestinal infections. We performed an epidemiologic analysis of 1,529 school employees in the U.S. A questionnaire was administered to school staff to collect health information, and floor dust was vacuumed from 500 classrooms in 50 schools. Fungal internal transcribed spacer region and bacterial 16S amplicon sequencing were performed with extracted genomic DNA using Illumina Mi-Seq platform. The resulting DNA sequences were clustered into operational taxonomic units (OTUs). Staff were assigned the school-building-specific floor average number of bacterial or fungal OTUs from the same floor as their exposure. We used logistic regression models to estimate adjusted odds ratios of reported respiratory and gastrointestinal infections in the last 12 months. Exposure to the highest quartile in number of OTUs (Q4, highest richness) of the bacterial phyla Firmicutes or Actinobacteria was associated with 28–61 % lower odds of upper or lower respiratory infections compared to the lower three quartiles (Q123). Higher Firmicutes diversity was more strongly associated with upper respiratory infections, while greater Actinobacteria diversity showed a stronger association with lower respiratory infections. Fungal diversity was not associated with any type of infection, and neither bacterial nor fungal diversity was associated with gastrointestinal infections. Our study suggests that exposure to a highly diverse bacterial microbiota in school environments may play an important role in protecting school staff against respiratory infections. © 2025

In the United States, typhoid vaccination is recommended for international travelers to areas with a recognized risk of typhoid exposure. Using MarketScan® Commercial Database from 2016 through 2022, we estimated typhoid vaccination costs by route (injectable vs. oral) and provider setting (clinic vs. pharmacy). Of 165,930 vaccinated individuals, 99,471 received injectable and 66,459 received oral typhoid vaccines, with 88% and 17% respectively administered at clinics. Average costs for injectable vaccination were $132.91 per person [95% confidence interval (CI): $132.68-$133.13], with clinic and pharmacy costs at $136.38 [95% CI: $136.14-$136.63], and $107.45 [95% CI: $107.13-$107.77] respectively. Oral vaccination costs averaged $81.23 per person [95% CI: $81.14-$81.33], encompassing $86.61 [95% CI: $86.13-$87.10] at clinics and $80.14 [95% CI: $80.09-$80.19] at pharmacies. Out-of-pocket costs comprised 21% and 33% of total costs for injectable and oral vaccinations. These findings may inform clinical decision-making to protect international travelers' health.

Background: Uganda's Integrated Child Health Day (ICHD) initiative aims to improve children's access to vaccinations. Although widely used as a catch-up vaccination strategy, the effectiveness of the ICHD program in increasing immunization coverage, especially among vulnerable populations, has not been recently evaluated. This study assessed the reach and uptake of ICHD for immunizations in Uganda. Methods: A mixed-methods evaluation was conducted in three districts (Rakai, Kayunga, and Bukedea) where ICHDs occurred. The data collection included a cross-sectional household survey using validated WHO-adapted questionnaires of 1432 caregivers of children under five years old, key informant interviews with 42 health managers and workers, and nine focus group discussions with caregivers between October and December 2022. The vaccines assessed were Bacillus Calmette-Guerin, oral polio, Pentavalent, pneumococcal conjugate, rotavirus (RV), and measles-rubella (MR). Results: The immunization coverage based on child health cards was over 90% for all vaccines except for the second dose of RV (88.3%) and MR (16.2%). Among the children, 2.3% had received no Pentavalent vaccine, and 69.4% were fully vaccinated for their age. Of the 631 children who attended ICHDs, 79.4% received at least one vaccine during the event. Village Health Teams (49%), health workers (18.3%), and megaphone outreach (17.9%) were the primary information sources. Key informants cited challenges with coordination, vaccine delivery, and mobilization. Conclusions: Despite operational challenges, ICHDs appear to have contributed to routine childhood vaccinations. Further research is needed to assess the sustainability and cost-effectiveness of the program.

BACKGROUND: Frequent consumption of sugar-sweetened beverages (SSB) is associated with an increased risk of some health outcomes. OBJECTIVE: We investigated the relationships between knowledge of health risks related to SSB and SSB intake among adults. METHODS: This cross-sectional study utilized data from the 2021 SummerStyles survey. There were 4022 US adult participants (≥18 years). The outcome variable was SSB intake (none, >0 to <1, 1 to <2, or ≥2 times/day). The exposure variables were knowledge of the association between SSB and seven health conditions. Statistical analyses included seven multinomial regressions to estimate adjusted odds ratios (AOR) for the consumption of SSB according to knowledge of SSB-related health risks after controlling for sociodemographics. RESULTS: Overall, about 30% of adults consumed SSB ≥ 2 times/day. While most adults identified SSB-related conditions such as weight gain (84.0%), diabetes (78.4%), and cavities (74.2%) as being related to drinking SSB, fewer adults recognized related conditions, such as some cancers (23.9%), high cholesterol (28.4%), heart disease (33.5%), and high blood pressure (37.8%). Knowledge of any of the health conditions was not significantly associated with consuming SSB ≥ 2 times/day compared to non-SSB consumers. CONCLUSIONS: Knowledge of SSB-related health conditions varied by sociodemographics but was not associated with high SSB intake. Future studies could explore other factors beyond knowledge that may influence adults' high SSB intake.

Blastomycosis is a fungal disease caused by inhalation of Blastomyces spores from the environment that can result in severe pulmonary illness and high hospitalization rates. In early March 2023, Public Health Delta and Menominee Counties (Michigan) reported a cluster of blastomycosis cases among paper mill workers to the Michigan Department of Health and Human Services (MDHHS). MDHHS subsequently notified CDC. On March 17, paper mill management requested a health hazard evaluation (HHE) from CDC&#8217;s National Institute for Occupational Safety and Health (NIOSH) to investigate potential workplace exposures to Blastomyces and recommend prevention and control measures at the mill. The workplace epidemiologic investigation combined a NIOSH HHE medical survey consisting of a questionnaire on work and health with Blastomyces urine antigen testing of specimens obtained from workers to assist in case finding, with additional case information from MDHHS blastomycosis surveillance data. Assessment of 645 mill workers identified 162 cases of blastomycosis with illness onset during November 1, 2022-May 15, 2023, with the weekly case count peaking at 21 cases in early March 2023. HHE environmental sampling in and around the mill did not identify the source of workers' Blastomyces exposure in the mill. This outbreak was the largest documented blastomycosis outbreak in the United States, and the first associated with a paper mill or an industrial setting. A coordinated public health response facilitated swift prevention measures with recommendations focused on reducing workers' exposure to Blastomyces, including hazard communication, respiratory protection, mill cleaning, and ventilation system improvements.

BACKGROUND: The Centers for Disease Control and Prevention's Drug Overdose Surveillance and Epidemiology (DOSE) system captures non-fatal overdose data from health departments' emergency department (ED) and inpatient hospitalisation discharge data; however, these data have not been compared with other established state-level surveillance systems, which may lag by several years depending on the state. This analysis compared non-fatal overdose rates from DOSE discharge data with rates from the Healthcare Cost and Utilization Project (HCUP) in order to compare DOSE data against an established dataset. METHODS: DOSE discharge data case definitions (ie, International Classification of Diseases, 10th revision, Clinical Modification codes) for non-fatal unintentional/undetermined intent all drug, all opioid-involved, heroin-involved and stimulant-involved overdoses were applied to HCUP's 2018-2020 State Emergency Department Databases (SEDD) and State Inpatient Databases (SID). Quarterly crude rates (per 100 000 population) and rate differences of four overdose categories were calculated for ED and inpatient data sources across 18 states included in DOSE and HCUP datasets for at least 2 consecutive years. Joinpoint regression models examined trends from 2018 through 2020, estimating average quarterly percentage change (AQPC) and 95% CIs. RESULTS: Quarterly crude rate differences between DOSE ED and SEDD data (across 12 states) and DOSE inpatient and SID data (across 16 states) indicated that 82% and 93% of rates, respectively, were within ±0.5 non-fatal overdoses per 100 000 population of each other. AQPC across states and drug categories were similar between the two data sources for both ED and inpatient data. DISCUSSION: Non-fatal overdose surveillance through DOSE discharge data may be a valid and timely source for estimating non-fatal overdoses at the state level.

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

Hurricane Ida, a Category 4 hurricane, made landfall in southern Louisiana in August of 2021, causing widespread wind damage and flooding. The objective of this study was to investigate knowledge, attitudes, and practices related to post-hurricane mold exposure and cleanup among residents and workers in areas of Louisiana affected by Hurricane Ida and assess changes in knowledge, attitudes, and practices that have occurred over the past 16 years since Hurricane Katrina. We conducted in-person interviews with 238 residents and 68 mold-remediation workers in areas in and around New Orleans to ask about their mold cleanup knowledge and practices, personal protective equipment use, and risk perceptions related to mold. Knowledge of recommended safety measures increased since the post-Katrina survey but adherence to recommended safety measures did not. Many residents and some workers reported using insufficient personal protective equipment when cleaning up mold despite awareness of the potential negative health effects of mold exposure.

BACKGROUND: With accumulating evidence of single-dose human papillomavirus (HPV) vaccine efficacy in young women, we conducted a community vaccine effectiveness study comparing HPV single-dose and 2-dose regimens (0 and 6 months) of a bivalent HPV vaccine among grade 8 schoolgirls (aged 13-14 years) in Thailand. METHODS: In 2018, eligible grade 8 schoolgirls in Udon Thani (single dose) and Buri Ram (2 doses) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey for measuring baseline HPV prevalence was conducted in grade 10 (n = 2600) and grade 12 unvaccinated schoolgirls (n = 2000) in each province. HPV infection was assessed in first-void urine samples, tested by DNA polymerase chain reaction on the cobas 4800 system (Roche Molecular Diagnostics, Pleasanton, CA). All samples positive on the cobas system and an equal number of negative samples were also tested by Anyplex II HPV28 Detection (Seegene, Seoul, South Korea). The surveys were repeated in 2020 and 2022, when vaccinated grade 8 schoolgirls reached grade 10, and then subsequently grade 12, respectively. Vaccine effectiveness was estimated by comparing the weighted prevalence of HPV-16 or HPV-18 between grade-matched unvaccinated schoolgirls on the baseline survey (2018) and vaccinated schoolgirls in the year-2 (2020) and year-4 (2022) surveys. Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the noncontemporaneous comparison. RESULTS: The prevalence of HPV-16 and HPV-18 on the baseline survey among unvaccinated grade 10/grade 12 schoolgirls was 2.90% (95% confidence interval [CI] = 2.54% to 3.31%)/3.98% (95% CI = 3.52% to 4.49%) for Udon Thani and 3.87% (95% CI = 3.46% to 4.34%)/6.13% (95% CI = 5.56% to 6.75%) for Buri Ram. On the year-2 survey, the prevalence among vaccinated grade 10 schoolgirls was 0.57% (95% CI = 0.42% to 0.77%) for Udon Thani and 0.31% (95% CI = 0.21% to 0.47%) for Buri Ram. The 2-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 80.4% (95% CI = 73.9% to 86.9%), and for the 2-dose regimen at 91.9% (95% CI = 88.5% to 95.4%). On the year-4 survey, the prevalence among vaccinated grade 12 schoolgirls was 0.37% (95% CI = 0.25% to 0.56%) for Udon Thani and 0.28% (95% CI = 0.18% to 0.45%) for Buri Ram. Four-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 90.6% (95% CI = 86.6% to 94.6%) and for the 2-dose regimen was estimated at 95.4% (95% CI = 93.2% to 97.6%). All adjustment methods minimally affected vaccine effectiveness for the single-dose and 2-dose regimens. At 4 years after vaccination, the difference in crude vaccine effectiveness between the single-dose and 2-dose regimens was ‒4.79% (95% CI = ‒9.32% to ‒0.25%), meeting the study's noninferiority criteria. CONCLUSIONS: Our study demonstrated that both single-dose and 2-dose HPV vaccination significantly decreased HPV-16/18 point prevalence 2 years and 4 years after vaccination. Crude vaccine effectiveness at 4 years after vaccination was greater than 90% for both the single-dose and 2-dose regimens; the single-dose regimen was not inferior to the 2-dose regimen. These data show that a single dose of HPV vaccine provides high levels of protection when administered to schoolgirls younger than 15 years of age.

BACKGROUND: Physical activity is an adjunctive therapy that improves symptoms in people living with systemic lupus erythematosus (SLE), yet the mechanisms underlying this benefit remain unclear. METHODS: We carried out a cohort study of 123 patients with SLE enrolled in the California Lupus Epidemiology Study (CLUES). The primary predictor variable was self-reported physical activity, which was measured using a previously validated instrument. We analyzed peripheral blood mononuclear cell (PBMC) single-cell RNA sequencing (scRNA-seq) data available from the cohort. From the scRNA-seq data, we compared immune cell frequencies, cell-specific gene expression, biological signalling pathways, and upstream cytokine activation states between physically active and inactive patients, adjusting for age, sex and race. FINDINGS: We found that physical activity influenced immune cell frequencies, with sedentary patients most notably demonstrating greater CD4+ T cell lymphopenia (P(adj) = 0.028). Differential gene expression analysis identified a transcriptional signature of physical inactivity across five cell types. In CD4+ and CD8+ T cells, this signature was characterized by 686 and 445 differentially expressed genes (P(adj) < 0.1). Gene set enrichment analysis demonstrated enrichment of proinflammatory genes in the TNF-α signalling through NF-kB, interferon-γ (IFN-γ), IL2/STAT5, and IL6/JAK/STAT3 signalling pathways. Computational prediction of upstream cytokine activation states suggested CD4+ T cells from physically inactive patients exhibited increased activation of TNF-α, IFN-γ, IL1Β, and other proinflammatory cytokines. Network analysis demonstrated interconnectivity of genes driving the proinflammatory state of sedentary patients. Findings were consistent in sensitivity analyses adjusting for corticosteroid treatment and physical function. INTERPRETATION: Taken together, our findings suggest a mechanistic explanation for the observed benefits of physical activity in patients with SLE. Specifically, we find that physical inactivity is associated with altered frequencies and transcriptional profiles of immune cell populations and may exacerbate pathologic inflammatory signalling via CD4+ and CD8+ T cells. FUNDING: This work was supported by the US National Institutes of Health (NIH) (R01 AR069616, K23HL138461-01A1, K23AT011768) the US CDC (U01DP0670), and the CZ Biohub.

Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

A very small proportion of all chemicals in commerce have occupational exposure limits (OELs) based on quantitative risk assessments which require estimates of exposure-response relationships (XRs). For only 18 of the 94 chemicals declared by NIOSH to be carcinogens were human XRs reported in or calculable from published reports. For the 18 carcinogens, 96 such XRs could be derived (corresponding to chemicals with multiple associated cancer end-points and/or multiple source studies). Twenty-four of 96 XR estimates came directly from reported statistical models (on continuous cumulative exposure), 45 were derived from summary study-population attributes, and 27 came from categorical analyses. Using the 96 XRs, OEL conferring one-per-thousand excess lifetime risk were calculated. OSHA's OEL, permissible exposure limits (PEL) were then compared to OEL derived from the 96 XRs. For 88 of the 96 calculated OELs (for which a corresponding PEL exists) all but 10 fell below the current PEL. Thirty-four OEL estimates were 10- to 100-fold below the PEL and 21 were greater than 100-fold below the PEL. This same pattern was observed using the different methods for deriving XRs. These findings can guide priorities in setting standards and the method is not limited to carcinogens.

BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

Use of tobacco products in any form is unsafe, and nearly all tobacco product use begins during adolescence. CDC and the Food and Drug Administration (FDA) analyzed data from the 2024 National Youth Tobacco Survey to determine tobacco product use among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2024, current (previous 30-day) use of any tobacco product was reported by 10.1% of high school students (representing 1.58 million students) and 5.4% of middle school students (representing 640,000 students). Among all students, e-cigarettes were the most commonly reported tobacco product currently used (5.9%), followed by nicotine pouches (1.8%), cigarettes (1.4%), cigars (1.2%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), heated tobacco products (0.8%), hookahs (0.7%), and pipe tobacco (0.5%). During 2023-2024, among all students, the estimated number who reported current use of any tobacco product decreased from 2.80 to 2.25 million students; e-cigarette use decreased (from 2.13 to 1.63 million students); and hookah use decreased (from 290,000 to 190,000 students). Among high school students, current use of any tobacco product decreased from 12.6% to 10.1% of students, and e-cigarette use decreased from 10.0% to 7.8%. Among middle school students, no statistically significant changes occurred. Evidence-based strategies can help prevent initiation and promote cessation of tobacco product use among U.S. youths.

Mumps outbreaks among fully vaccinated young adults have raised questions about potential waning of immunity over time and need for a third dose of the measles, mumps, rubella (MMR) vaccine. However, there are currently limited data on real-life effectiveness of the third-dose MMR vaccine in preventing mumps. Here, we used a deterministic compartmental model to infer the effectiveness of the third-dose MMR vaccine in preventing mumps cases by analyzing the mumps outbreak that occurred at the University of Iowa between August 24, 2015, and May 13, 2016. The modeling approach further allowed us to evaluate the population-level impact of vaccination by different timing in relation to the start of the outbreak and varied coverage levels, and to account for potential sources of bias in estimating vaccine effectiveness. We found large uncertainty in vaccine effectiveness estimates; however, our models showed that early introduction of a third dose of MMR vaccine during a mumps outbreak can be effective in preventing transmission. School holidays, such as the winter break, likely played important roles in preventing mumps transmission.

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

mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Filtering facepiece respirators (FFRs) are manufactured in discrete sizes, with some models being limited in accommodating the fit of some sex and race combinations. This study presents the development of a custom-fit respiratory protective device (RPD) which conforms to a user's facial features and flexes and moves with facial movements during use. Our design also integrates a pressure-sensing network, which continuously monitors fit and will alert the user when the fit is compromised. In this Part II of the three-part series, we design and incorporate a continuous fit monitoring system in the RPD designed in Part I to enhance its role in protecting users from inhalation hazards in an effective manner during its use. The fit monitoring system comprises a fabric-based sensor network integrated into the RPD and an Android-based App designed to alert the user when the pressure at the faceseal falls below a given threshold established during the initial configuration of the RPD for the user. We also develop algorithms for the incorporation of the sensor slots and data buses into the custom-fit RPD using the Taxonomy of Landmarks defined in Part I. We enhance the structure developed in Part I to secure the sensor network during the use of the RPD. We develop algorithms for customizing a fastening hub to suit the head profiles of individuals to enable them to don the RPD quickly, easily, effectively, and in a repeatable manner. We demonstrate the successful application of the total design methodology by creating digital prototypes for three individuals with different facial profiles and make further advances to our goal of ensuring equitable respiratory protection for all including children, for whom RPDs are currently limited.

Information on microorganisms in indoor air of various institutional and commercial buildings has significant value in a public health management perspective. However, there is a lack of prior research comparing indoor airborne microbiota across different categories of those buildings. We characterized indoor airborne bacteria in 10 buildings (two for each of five categories: train station, parking garage, mart, public library, and daycare center) during summer and winter. The 16S rRNA gene in the bacterial gDNA extracted from samples was quantified using quantitative real-time polymerase chain reaction and sequenced with the Illumina MiSeq™ platform for characterizing community composition. We collected information on temperature, relative humidity, CO2 concentration, and particulate matter (PM) concentrations by particle size (<1 µm, 1–2.5 µm, 2.5–10 µm) indoors. We performed a multivariate regression analysis to identify factors influencing bacterial quantity and Permutational Multivariate Analysis of Variance (PERMANOVA) to determine factors affecting cluster dissimilarity. We found that bacterial concentration was significantly (p-values < 0.05) associated with season and CO2 concentration. The PERMANOVA analyses showed the significant (p-values < 0.05) associations of bacterial cluster dissimilarity with season, building category, and CO2. Our study indicated that the season, and CO2 concentrations may be important factors associated with the indoor airborne bacterial concentration and composition. Building category and usage appeared to significantly influence the bacterial community composition but not the concentration. Our study may provide basic data on bacterial community composition and their concentration that are needed for properly managing microbial exposures in occupants or customers of the studied institutional and commercial buildings. Copyright © 2024 American Association for Aerosol Research. © 2024 American Association for Aerosol Research.

Mortality surveillance systems can have limitations, including reporting delays, incomplete reporting, missing data, and insufficient detail on important risk or sociodemographic factors that can impact the accuracy of estimates of current trends, disease severity, and related disparities across subpopulations. The Centers for Disease Control and Prevention used multiple data systems during the COVID-19 emergency response-line-level case‒death surveillance, aggregate death surveillance, and the National Vital Statistics System-to collectively provide more comprehensive and timely information on COVID-19‒associated mortality necessary for informed decisions. This article will review in detail the line-level, aggregate, and National Vital Statistics System surveillance systems and the purpose and use of each. This retrospective review of the hybrid surveillance systems strategy may serve as an example for adaptive informational approaches needed over the course of future public health emergencies. (Am J Public Health. Published online ahead of print July 25, 2024:e1-e10. https://doi.org/10.2105/AJPH.2024.307743).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with Trichinella spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat. In July 2022, a hospitalized patient with suspected trichinellosis was reported to the Minnesota Department of Health. One week before symptom onset, the patient and eight other persons shared a meal that included bear meat that had been frozen for 45 days before being grilled and served rare with vegetables that had been cooked with the meat. Investigation identified six trichinellosis cases, including two in persons who consumed only the vegetables. Motile Trichinella larvae were found in remaining bear meat that had been frozen for >15 weeks. Molecular testing identified larvae from the bear meat as Trichinella nativa, a freeze-resistant species. Persons who consume meat from wild game animals should be aware that that adequate cooking is the only reliable way to kill Trichinella parasites and that infected meat can cross-contaminate other foods.