Colorectal cancer (CRC) screening allows for early detection and prevention through removal of polyps. In 2021, the US Preventive Services Task Force updated recommendations to screen adults aged 45 to 75 years. We analyzed 2022 Behavioral Risk Factor Surveillance System data to establish baseline prevalence estimates for those eligible for screening aged 45 to 75, including those aged 45 to 49 years who are newly eligible. Only 61.4% of adults aged 45 to 75 were up to date with CRC screening, below the Healthy People 2030 target (72.8%). Public health and clinical systems can prioritize identifying and screening adults not up to date on screening to reduce CRC risk.

BACKGROUND: Nipah virus (NiV) causes deadly outbreaks in Bangladesh, with fatality rate of 71%. Two sublineages, NiV-BD 1 and NiV-BD 2, have been identified. This study aimed to characterize their epidemiological and clinical diversity. METHODS: This study analyzed 21 new (2016-2023) and 17 previously (2012-2015) reported NiV genome sequences and compared sublineages using descriptive and bivariate analysis. RESULTS: Median age of sequenced cases was 17 years (IQR: 9-30); with 66% male. Raw date palm sap consumption was main transmission pathway (92%). NiV-BD 2 showed broader geographic distribution, including southern region. The sublineages did not differ significantly in age, sex, or transmission modes. Both sublineages presented with fever, altered mental status, and unconsciousness. Respiratory distress was more frequent in NiV-BD 2 (23/29 cases), while hospitalization was longer for NiV-BD 1 (median: 3 days; IQR: 1-23). Overall mortality was 84%, with no significant difference between sublineages. Phylogenetic analysis demonstrated that NiV-BD 1 and NiV-BD 2 formed distinct clusters with 98.72%-99.25% nucleotide and 99.98%-99.99% amino acid identity. The structural nucleoprotein (N) and matrix (M) proteins remained conserved across sublineages. CONCLUSION: This study highlights genetic, spatio-temporal and clinical variation between sublineages, emphasizing continuous genomic surveillance to inform future vaccine and therapeutic strategies.

Rabies vaccine failures in domestic animals can have severe public health consequences and are not consistently publicized. This study describes trends in rabies vaccine failures among dogs and cats in the US reported to the CDC's National Rabies Surveillance System between 2002 and 2022 to characterize the efficacy of rabies vaccines and evaluate the economic and public health burdens of nonvaccination. Thirty-nine of 1,525 rabid dogs (2.56%) and 30 of 5,530 rabid cats (0.54%) were documented as having a history of rabies vaccination, and 15 true vaccine failures (11 dogs and 4 cats) were identified among these during the study period. Dogs and cats with up-to-date vaccination were 130.8 and 93.6 times less likely, respectively, to contract rabies than nonvaccinated counterparts. Current rabies vaccination practices will likely prevent $166 million in public health- and healthcare-related costs over the following 10 years; high rates of rabies vaccination in dogs and cats in the US greatly reduce medical costs for the human health sector. Effective coordination between local and national surveillance is essential for assessing epidemiological patterns in animal rabies cases, including vaccination failures. The companion Currents in One Health by Payette-Stroman et al, AJVR, October 2025, addresses patterns of domestic rabies burden in livestock.

BACKGROUND: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in U.S. patients who received epidural anesthesia in Matamoros, Mexico. METHODS: Early epidemiological information suggested U.S. patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in two Matamoros clinics. U.S. patients known to have received surgery at these clinics during January 1-May 13, 2023, (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, including use of the experimental antifungal fosmanogepix. Whole genome sequencing was conducted on outbreak isolates. RESULTS: U.S. public health officials attempted to contact 233 potentially exposed U.S. residents who underwent surgeries, mostly cosmetic, in Mexico, reaching 170 (73%). Of those, 104 (61%) reported receiving epidural anesthesia and were therefore considered potentially at risk for fungal meningitis. At least 30/104 (29%) at-risk patients received a diagnostic lumbar puncture; 24 (23 women, 17 Hispanic or Latino) were diagnosed with fungal meningitis, and six were not. Twelve (50%) with fungal meningitis died. All cases involved epidural anesthesia administered by the same anesthesiologist in Mexico. Whole genome sequencing showed that patient isolates of Fusarium from the two implicated clinics in Matamoros, Mexico, were genetically closely related. CONCLUSIONS: Clinicians should maintain suspicion for fungal meningitis in patients with negative bacterial culture, viral culture and molecular testing with a history of epidural anesthesia for any reason.

BACKGROUND: This study aimed to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific binding and neutralizing antibody responses in healthcare workers (HCWs) who received coronavirus disease 2019 (COVID-19) vaccines, with or without postvaccination infections. METHODS: We conducted a prospective, observational cohort study of HCW in 2 hospitals in Manaus, Brazil. From 31 March through 31 May 2021, HCWs had nasal swabs collected and questionnaires administered weekly for 4 visits. Nasal swabs were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR). Blood specimens were obtained at visits 1 and 4 unless the HCW was found to be infected. If infected, a blood specimen was collected on days 14 and 28 after symptom onset or date of positive specimen, if asymptomatic. COVID-19 vaccination cards, state immunization records, and self-reported history of previous SARS-CoV-2 infection were obtained. Fully vaccinated HCWs who tested SARS-CoV-2 rRT-PCR positive were classified as postvaccination infections. RESULTS: A total of 771 HCWs were enrolled, with 73.7% (568/771) fully vaccinated. Anti-SARS-CoV-2 S1 immunoglobulin G and neutralizing antibody levels showed steep decay within the first 50 days after COVID-19 vaccination. HCWs with prior SARS-CoV-2 infection had slower visible decay after 50 days compared with those without prior infection. We identified 12 postvaccination infections of 16 HCWs who were SARS-CoV-2 rRT-PCR+, including 4 who also reported previous infection. Those positive for SARS-CoV-2 had lower baseline neutralizing antibody levels against Gamma and Delta variants preinfection (median log10 titers [interquartile range]: Gamma, 1.5 [3]; Delta: 0 [0.25]) compared to those who remained rRT-PCR negative (median log10 titers [interquartile range]: Gamma, 3 [2]; Delta, 1 [2]). CONCLUSIONS: Our findings highlight the importance of routine antibody surveillance, targeted boosters, and hybrid immunity in low and middle income countries. Timely booster doses for HCWs and the development of new vaccines against emerging variants can help sustain immunity and prevent workforce shortages, strengthening healthcare resilience in resource-limited settings.

OBJECTIVES: In August 2024, the U.S. Centers for Disease Control and Prevention updated U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC), which provides recommendations for safe use of contraception for women with certain characteristics and medical conditions. This paper provides a summary of the evidence and context for new and updated U.S. MEC recommendations. STUDY DESIGN: The 2024 U.S. MEC was updated through a rigorous, multi-year process of determining priorities that would have high impact on clinical care, conducting systematic reviews of the evidence, and considering perspectives of health care providers and patients on how the evidence could best support updated recommendations. RESULTS: New U.S. MEC recommendations were added for chronic kidney disease, specifically for three subconditions: current nephrotic syndrome, hemodialysis, and peritoneal dialysis. Revisions were made to several existing recommendations, such as those for sickle cell disease, anticoagulant therapy use, various thrombogenic conditions, cirrhosis, liver tumors, solid organ transplantation, and intrauterine device placement in the postpartum period. Updated recommendations include those that reflect decreased safety concerns for some medical conditions (e.g., progestin-only contraception and some liver diseases) and increased safety concerns for others (e.g., combined hormonal contraception and depot medroxyprogesterone acetate for women with sickle cell disease). Recommendations for new contraceptive methods were added. CONCLUSIONS: Evidence-based clinical guidelines can be used by health care providers to support patient-centered contraceptive counseling and services and remove unnecessary barriers to accessing and using contraception. Provider tools including a mobile app are available to help with implementation of the updated recommendations. IMPLICATIONS: Keeping U.S. MEC up-to-date is critical for supporting contraceptive decision-making and improving access to contraception and reproductive health care. This includes new research to address current evidence gaps, rigorous methodology for continuous evidence identification and synthesis, state-of-the-art methods for guideline development, and a broad range of dissemination and implementation strategies.

INTRODUCTION: The antiretroviral therapy (ART) initiation policy in Uganda recommends that ART is initiated on the same day of HIV diagnosis to those who do not have contraindications. We assessed determinants of retention in ART care at the first follow-up (FFU) after same-day ART initiation and retention in long-term care beyond the FFU visit. METHODS: We conducted a retrospective longitudinal analysis among persons living with HIV aged ≥18 years who initiated ART during April 2016-February 2021 after the inception of Uganda's Test-and-Treat ART policy, which states that 'all individuals diagnosed with HIV should initiate ART regardless of clinical stage CD4 count'. Missing the FFU after ART initiation (missing FFU) was defined as not returning for FFU within 1 month of ART initiation; loss to follow-up long-term (LTFU-LT) was defined as delaying more than 3 months to return for a scheduled ART drug refill after the FFU appointment. LTFU-LT time was defined as the time from the FFU visit date to the last follow-up visit date during the study period. We used log-binomial distributions to estimate unadjusted and adjusted relative risks (adjRRs) of missing FFU, and we used Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (adjHRs) for LTFU-LT. RESULTS: Overall, 8332 clients initiated ART on the same day of HIV diagnosis. Most were female (55%), aged 25-34 years (44%), resided in the semi-urban or rural district (41% and 41%, respectively) and had a median age of 25 years (IQR = 24-35). Overall, missing FFU was 15.1%. Increased likelihood/risk of missing FFU was seen in clients who initiated ART at outreach health service centres versus health facilities (adjRRs = 1.79, 95% CI = 1.6-2.0), in younger clients aged 18-24 years and 25-34 years versus ≥45 years [(adjRRs = 1.65, 95% CI = 1.3-2.0) and (adjRRs = 1.31, 95% CI = 1.1-1.6), respectively], and clients residing in agrarian districts versus fishing districts (adjRRs = 1.24, 95% CI = 1.1-1.4). Overall, the LTFU-LT rate was 25 clients/100 pys (95% CI = 23.9-25.9) and was associated with younger age (18-34 years versus ≥45 years, adjHRs = 1.77, 95% CI = 1.5-2.1), residence in semi-urban (adjHRs = 1.33, 95% CI = 1.2-1.5) or agrarian district (adjHRs = 1.30, 95% CI = 1.2-1.5) versus fishing-community district. CONCLUSION: Retention-strengthening strategies in tandem with same-day ART initiation efforts for younger clients and clients initiated on ART from mobile and outreach health service settings might improve HIV treatment retention. Best practices for retaining fishing-community clients might improve health outcomes if applied to agrarian and semi-urban communities.

OBJECTIVES: We assessed characteristics associated with pediatric COVID-19 hospitalizations and risk factors for severe disease among hospitalized children ≥6 months. METHODS: Using data from COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) during October 1, 2022-April 30, 2024, we described demographic characteristics, underlying medical conditions, COVID-19 vaccination status, and clinical outcomes, including severe disease (ICU admission, mechanical ventilation, extracorporeal membrane oxygenation, in-hospital death), of hospitalized children 6 months-17 years residing in the COVID-NET catchment area with laboratory-confirmed SARS-CoV-2 infection. Multivariable log-linked Poisson generalized estimating equations were conducted to assess risk factors for severe disease among children 6-23 months and 2-17 years. RESULTS: Of 2,490 children hospitalized for COVID-19, 1114 (44.7%) were 6-23 months; 1358 (54.1%) were male. Overall, 1464 (58.9%) had ≥1 underlying conditions: 471 (41.8%) of children 6-23 months, 290 (61.6%) 2-4 years, 383 (79.2%) 5-11 years, and 320 (77.0%) 12-17 years. 100 (3.8%) were up-to-date with recommended COVID-19 vaccination. Among children 6-23 months, severe disease was associated with underlying chronic lung (adjusted risk ratio [aRR] 1.5, 95% CI: 1.2-1.8) and cardiovascular disease (aRR: 1.4, 95% CI: 1.1-1.7). Among children ≥2 years, severity was associated with chronic lung disease (aRR: 1.9, 95% CI: 1.5-2.3), diabetes (aRR: 1.5, 95% CI: 1.2-1.8), and neurologic disorders (aRR: 1.4, 95% CI: 1.2-1.6). CONCLUSION: Most hospitalized children ≥6 months had ≥1 underlying conditions and <5% were up-to-date with COVID-19 vaccination. Specific conditions were associated with increased risk of severe illness. Increasing COVID-19 vaccination, particularly among children with high-risk conditions, may reduce pediatric COVID-19 hospitalizations and severe outcomes.

BACKGROUND: Updated benchmark data on invasive fungal disease (IFD) in solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) recipients are necessary to increase clinical recognition and inform treatment and prevention strategies. We estimated IFD incidence and potential risk factors in transplant recipients in a large US commercial health insurance database. METHODS: We observed patients who received SOT or HCT during 2018-2022 until IFD development, disenrollment, or database end date (July 31, 2023). We calculated incidence (per 1000 person-years) and time to IFD development, comparing demographic features and underlying conditions for IFD versus non-IFD patients. RESULTS: Overall, 9143 patients received an SOT (5667 kidney, 2025 liver, 759 heart, 650 lung, 39 pancreas, 3 intestine), and 5693 patients received an HCT (3519 autologous, 2114 allogeneic, 60 unspecified type). Among SOT patients, 360 developed an IFD (incidence: 21.0 [per 1000 person-years]). Mold infections had the highest incidence (7.1), followed by unspecified mycoses (3.9) and endemic mycoses (3.3). Among HCT patients, 292 developed an IFD (incidence: 28.5), with higher incidence among allogeneic (58.4) versus autologous (12.8) HCT recipients; among all HCT recipients, unspecified mycoses had the highest incidence (8.3), then pneumocystosis (7.6), and mold infections (6.7). Median time to IFD was 173.5 days for SOT recipients and 197.5 days for HCT recipients. IFD risk varied substantially by transplant type, region, and certain underlying conditions. CONCLUSION: Our results suggest that IFDs remain an important cause of infection among SOT and HCT recipients, particularly later in the posttransplant period, and highlight the need for prevention strategies.

Nipah virus (NiV) causes severe diseases in humans with a high case fatality rate. The primary risk factors for NiV infection in Bangladesh are drinking raw date palm sap (DPS) contaminated with Pteropus fruit bat secretions/excretions or close contact with or exposure to the body fluid of an individual with NiV infection. During the 2023 NiV outbreak investigation in Bangladesh, the breast milk of a NiV-infected nursing mother was tested by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for detection of NiV-RNA. The newborn was also tested as a suspected NiV-infected subject. NiV, specifically NiV RNA, was detected in the breast milk sample. Through the investigation, it was determined that the mother consumed raw DPS 9 days before the delivery. The newborn was also confirmed as NiV positive and had exposure to maternal bodily fluid while breastfeeding, and was in prolonged maternal contact during caregiving. Although the detection of NiV RNA in breast milk does not equate to viability and transmissibility of the virus, this finding provides preliminary evidence that warrants further investigation into the potential role of breast milk in postnatal transmission of NiV. Our findings advocate incorporating breast milk testing into NiV diagnostic protocols for symptomatic mothers. This advancement will broaden our understanding of postnatal transmission of NiV and pave the way for more effective containment strategies.

To date, the primary focus of chronic kidney disease (CKD) care has been on managing disease progression, complications, and kidney failure. In contrast, maintaining kidney health and preventing CKD have received limited attention, despite their potential to save millions of lives, reduce health care costs, and lessen environmental burdens. The cardiovascular-kidney-metabolic (CKM) concept frames CKD as part of a complex, high-risk syndrome requiring global risk assessment and multifactorial intervention. CKD incidence along with CKM risk factors may be reduced by a healthy diet, physical activity, and a supportive environment. However, risk for CKD does extend beyond the cardiovascular-metabolic component, and residual risk persists despite healthy lifestyles and treatment of risk factors. Post hoc analyses of clinical trials suggest pharmacological interventions, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, may help to prevent or regress CKD in individuals with type 2 diabetes or obesity. Clinical trials are needed to validate these findings in broader high-risk populations. Personalized strategies to improve kidney health should include CKD risk prediction via targeted testing, genetic or biomarker assessments, shared decision-making, cost considerations, selection of therapeutics, and the potential for adverse effects. The overall goals of CKD prevention should prioritize a lifespan approach to risk evaluation along with safe, efficacious, and accessible interventions to maintain kidney health.

The Coalition for Global Hepatitis Elimination's National Hepatitis Elimination Profiles assess the status of national data, policy, and programme development for the elimination of viral hepatitis. To date, profiles from 33 countries and territories have been developed. These profiles reveal that 30 (91%) countries and territories have hepatitis C national action plans, 11 (33%) have systems to monitor hepatitis C-related mortality, 16 (48%) have systems to monitor hepatitis C incidence, and 18 (55%) have systems to track the number of people tested and treated. Some countries and territories continue to uphold barriers to hepatitis C treatment, with 12 (36%) still having partial or full restrictions on prescribing authority for non-specialists. Ten (30%) countries and territories have met the WHO 2025 diagnosis coverage target of 60%, five (15%) have met the treatment target of 50%, and seven (21%) have met the needle and syringe exchange target. Although there are examples of countries and territories across the income spectrum meeting these targets, policy development in low-income and middle-income countries and territories generally lags behind that in high-income countries and territories.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV). Antiretroviral therapy (ART) initiation lowers the risk of HIV-associated TB. Earlier studies have shown TB incidence to be high in the first year of ART. We undertook a study to (1) assess the incidence of TB and (2) associated factors among persons initiating ART in a rural cohort. METHODS: We conducted a retrospective cohort analysis study among PLHIV aged ≥ 18 years, initiated on ART from January 1, 2012, to December 31, 2019, and TB disease-free at the time of ART initiation, at Kalisizo ART clinic. TB disease incidence was calculated by dividing the number of new TB cases by the total follow-up time expressed per 100 person-years among persons followed up until the date of incident TB disease, loss to follow-up, transfer out, death or censored at the end of the study; whichever occurred first. Factors associated with TB disease incidence were assessed in the multivariable analysis by Poisson regression analysis at 5% significance level. RESULTS: For the period 2012 to 2019, 2,589 PLHIV were initiated on ART; 57% (1,470/2,589) were female. Females were more likely to be aged below 35 years while males were more likely to be aged 25-44 years (p < 0.001). Eighty-seven per cent (1,269/1,470) of females compared to 78% (866/1,119) of males were in WHO clinical stage 1 (p < 0.001). Sixty-one TB disease events were observed in 7,363 person-years. The overall TB disease incidence was 0.83 (95% CI: 0.63-1.06) per 100 person-years. Males were more likely than females to develop TB disease, adjusted incidence rate ratio (adj IRR) 2.13 (95% CI: 1.27-3.57) per 100 person-years, p = 0.004. Compared to using ART for 0-5 months, time on ART was associated with a lower TB incidence rate at 6-12 months, 13-24 months, > 24 months (adj IRR 0.20 (95% CI: 0.09-0.46), 0.14 (95% CI: 0.06-0.33), 0.16 (95% CI: 0.08-0.31) p < 0.001 respectively). CONCLUSIONS AND RECOMMENDATIONS: Incidence of TB among PLHIV on ART was low in this rural population. Clinicians offering care to people with HIV in the rural setting should have a heightened index of suspicion for TB disease.

PROBLEM/CONDITION: Candidemia, a bloodstream infection caused by Candida spp., is a common cause of health care-associated bloodstream infections in the United States. Candidemia is associated with substantial health care costs, morbidity, and mortality. PERIOD COVERED: 2017-2021. DESCRIPTION OF SYSTEM: CDC's Emerging Infections Program (EIP), a collaboration among CDC, state health departments, and academic partners, was used to conduct active, population-based laboratory surveillance for candidemia at city or county sites located in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee), representing a combined population of approximately 21.5 million persons, or 7% of the U.S. population in 2019. Connecticut began reporting cases on January 1, 2019, and conducts statewide surveillance. Although candidemia is not a nationally notifiable condition, cases of Candida auris infection are nationally notifiable, and cases of candidemia caused by C. auris could be included in both national case counts and EIP surveillance. A culture-confirmed candidemia case is defined as a positive blood culture for any Candida sp. from a resident in the surveillance catchment area. Subsequent positive blood cultures for Candida within 30 days of the initial positive culture (index date) in the same patient are considered part of the same case. Clinical laboratories serving each catchment area report candidemia cases, and trained surveillance officers abstract information from medical charts for all cases. Corresponding isolates are sent to CDC for species confirmation and antifungal susceptibility testing. RESULTS: A total of 7,381 candidemia cases were identified during the surveillance period (2017-2021). The overall incidence was 7.4 cases per 100,000 population. Across age groups, sexes, racial and ethnic groups, and surveillance sites, incidence was generally stable or increased slightly from 2017 to 2021, with the lowest overall incidence in 2019 (6.8) and the highest in 2021 (7.9). In 2021, candidemia incidence was highest in patients aged ≥65 years (22.7) and infants (aged <1 year) (8.0). Incidence was higher in males (8.7) compared with females (7.0) and higher in non-Hispanic Black or African American (Black) patients (12.8) compared with non-Black patients (5.6). Incidence was highest in Maryland (14.5), followed by Tennessee (10.1) and Georgia (10.0); incidence was lowest in Oregon (4.8). Increases occurred in the percentage of cases classified as health care onset (52.2% in 2017 to 58.0% in 2021). Overall, among 7,381 cases (in 6,235 patients), 63.7% occurred in patients who had a central venous catheter, 80.7% involved recent systemic antibiotic receipt, and 9.0% occurred in patients who had a history of injection drug use. The percentage of cases with a positive SARS-CoV-2 test during the 90 days before or after the index date increased from 10.4% in 2020 to 17.7% in 2021. From 2017 to 2021, the percentage of cases involving an intensive care unit stay before the index date increased from 38.3% to 44.9%. Echinocandins (e.g., micafungin) were used as treatment in 49.8% of cases, and azoles were used in 47.7%. The all-cause in-hospital mortality rate was 32.6%; this increased from 26.8% in 2019 to 36.1% in 2021. Overall, Candida albicans accounted for 37.1% of cases, followed by Candida glabrata (30.4%) and Candida parapsilosis (13.5%); however, C. glabrata was the most frequent species in California (38.4%) and Maryland (32.9%). Candida auris infections accounted for 0.4% of cases. Among 6,576 Candida isolates for which interpretive breakpoints exist and isolates were available for testing, 5.6% were fluconazole resistant, and <1% were echinocandin resistant. Antifungal resistance was stable for all antifungals tested across years. INTERPRETATION: Candidemia remains an important health care-associated infection. The disproportionate incidence among older adults, males, and Black patients is consistent with previous reports, and the overall incidence of candidemia has not changed substantially compared with previous EIP findings based on data collected during 2012-2016 (8.7 per 100,000 population). The higher mortality rate associated with candidemia during 2020-2021 likely reflects consequences of the COVID-19 pandemic, including strained health care systems and an increased population of patients who were susceptible to candidemia because of COVID-19-related critical illness. PUBLIC HEALTH ACTION: Strict implementation of measures to prevent health care-associated bloodstream infections is important to help prevent candidemia cases. Health care officials and providers should be vigilant for candidemia as a complication of critical illness. Continued surveillance is needed to monitor for emerging populations at risk for candidemia and changes in antifungal resistance patterns, which can help guide antifungal treatment selection.

BACKGROUND: High-grade Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in east and southern Africa has prompted trials evaluating intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. We aimed to provide an updated and comprehensive review of trials conducted in areas of high P. falciparum resistance that compared the efficacy of two types of IPTp regimens on maternal, birth, and infant outcomes. METHODS: We conducted two-stage, individual participant data meta-analyses of randomised trials comparing IPTp with dihydroartemisinin-piperaquine to sulfadoxine-pyrimethamine on maternal, birth, and infant outcomes. We searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.Gov, PubMed, and the Malaria in Pregnancy Consortium Library, on July 30, 2020 (updated on September 24, 2024), without restrictions by publication date, peer-review status, or language. Eligible trials enrolled HIV-uninfected pregnant women, followed participants to delivery, included participants with no prior IPTp use during the current pregnancy, and were conducted in areas with high-level parasite resistance to sulfadoxine-pyrimethamine (i.e., PfDHPS 540E ≥ 90% and/or 581G>0%). Only singleton pregnancies were analysed. The primary endpoint was a composite measure of any adverse pregnancy outcome defined as fetal or neonatal loss, small-for-gestational age, low birthweight, or preterm birth. Summary estimates were generated using a random-effects model. Gravidity subgroup analyses were performed. Causal mediation analyses were used to investigate the maternal mechanisms underlying the effect of IPTp regimens on birth outcomes. The meta-analysis is registered in PROSPERO (CRD42020196127). FINDINGS: Of 85 screened records, six trials (one multi-country trial) from Kenya, Malawi, Uganda and Tanzania contributed data on 6646 pregnancies. Compared to sulfadoxine-pyrimethamine, dihydroarteminsinin-piperaquine was associated with a 69% [95% CI: 45%-82%] lower incidence of clinical malaria during pregnancy, a 62% [37%-77%] lower risk of placental parasitaemia, and a 17% [0%-31%] lower incidence of moderate maternal anaemia. In contrast, sulfadoxine-pyrimethamine was associated with higher mean maternal weight gain (34 g/week [17-51]). There were no statistically significant differences in the composite adverse pregnancy outcome (RR = 1.05 [0.92-1.19]; I (2) = 48%). Individual components of the primary outcome showed no statistically significant differences in the risks of fetal loss (RR = 0.94 [0.61-1.46]), preterm birth (RR = 0.93 [0.76-1.14]), low birthweight (RR = 1.09 [0.83-1.43]), or neonatal loss (RR = 0.73 [0.42-1.26]), though findings may have been underpowered. Small-for-gestational-age risk was 15% (3%-24%) lower in the sulfadoxine-pyrimethamine arm, particularly among multigravidae (a 22% reduction vs 9% in primigravidae). Among multigravidae, infant stunting and underweight by two months was 20% [8%-30%] and 35% [17%-49%] lower in the sulfadoxine-pyrimethamine arm compared to dihydroartemisinin-piperaquine. Compared to dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine was associated with higher mean newborn birthweight (mean difference (MD) = 50 g [95% CI: 13-88]; p = 0.0090, I(2) = 61%) and BWGA z-scores (MD = 0.12 [95% CI: 0.05-0.20]; p = 0.0012, I(2) = 51%), but not gestational age at birth (MD = 0 weeks [95% CI: -0.11 to 0.12]; p = 0.94; I(2) = 42%). Infant wasting by two months was 13% [3%-22%] lower in the sulfadoxine-pyrimethamine arm, regardless of gravidity. Mediation analyses indicated that 15% [0%-19%] of sulfadoxine-pyrimethamine's superior effect on small-for-gestational-age risk was mediated by its greater impact on gestational weight gain. INTERPRETATION: In areas with high P. falciparum sulfadoxine-pyrimethamine resistance, dihydroartemisinin-piperaquine offers superior antimalarial efficacy than sulfadoxine-pyrimethamine. However, replacing sulfadoxine-pyrimethamine with dihydroartemisinin-piperaquine alone may not lead to improved maternal and infant health outcomes. Instead, it could result in slightly reduced gestational weight gain and a modest increase in the risk of small-for-gestational age births, and poor infant growth by two months of age. Future research evaluating alternative strategies for IPTp are needed. FUNDING: This work was supported by the Bill and Melinda Gates Foundation and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

BACKGROUND: Mandatory public health reporting of influenza laboratory results and vaccine doses administered in the state of California can provide estimates of seasonal influenza vaccine effectiveness (VE). METHODS: We analyzed linked influenza immunization registry and laboratory reporting data among California residents aged ≥6 months tested for influenza during the 2023-24 influenza season (October 2023-June 2024). Individually linked laboratory reporting included influenza molecular or viral culture test result. Odds Ratios (OR) and 95% confidence intervals (CI) contrasted odds of documented 2023-2024 vaccination among persons with influenza-positive tests versus persons with negative influenza tests. VE was calculated as (1 - adjusted OR) x 100 using logistic regression, adjusting for patient age, race, ethnicity, week of specimen collection, and county of residence. RESULTS: Among 1,382,142 laboratory reports, 129,253 persons (9%) (129,253) had a positive influenza test result, of whom 415,390 (30%) had documented influenza vaccination ≥14 days before test date. VE against laboratory-confirmed influenza was 41% (95% CI, 40%-42%). VE was 32% (95% CI, 31%-33%) against influenza A, 68% (95% CI, 66%-69%) against influenza B, and 26% (95% CI, 24%-29%) among adults aged ≥65 years. CONCLUSIONS: Influenza vaccination was associated with prevention of laboratory-confirmed influenza. Results demonstrated feasibility of assessing seasonal influenza vaccine effectiveness using linked immunization and laboratory data from public health surveillance systems.

Reliance on traditional vector control methods, such as insecticides and "clean-up" source reduction efforts for reducing mosquito breeding sites, has proven increasingly ineffective and costly in the battle against dengue. The Wolbachia-based mosquito replacement strategy, which replaces wild mosquitoes with mosquitoes trans-infected with Wolbachia bacteria, preventing up to 77% dengue transmission, represents an advancement in prevention. Integrating this approach into current routine dengue control efforts could reduce dengue incidence. However, challenges such as implementation costs, the need for country ownership, alignment of released mosquitoes with local mosquito populations, increased education and sensitization for government authorities and the public on the benefits of Wolbachia, identifying international funding partners, and recognizing areas where the strategy may be less effective due to environmental or socio-political factors, must be addressed. Furthermore, Wolbachia replacement must focus in areas with high population density and high dengue incidence since it is not feasible to cover all endemic areas. Establishing robust surveillance systems to monitor efficacy against different dengue serotypes is also critical. Despite these challenges, the Wolbachia strategy is the one of the most promising developments in dengue prevention to date. By complementing this approach with effective vaccines, we have the unprecedented opportunity to significantly reduce dengue.

Whilst a quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis, it is unknown whether TB infection (TBI) increases the risk of severe COVID-19, which is relevant in TB-endemic settings, especially where HIV co-infection is also common. A convenience cohort of symptomatic and asymptomatic COVID-19 patients aged 8-80 years in western Kenya was followed daily for 14 days to assess disease progression using the validated inFLUenza-Patient-Reported-Outcome Plus signs and symptom tool. Nasal swabbing for SARS-CoV-2 was conducted to confirm the virus using polymerase chain reaction. QuantiFERON-TB Gold Plus was used to diagnose TBI. HIV status was based on self-reports. Between January 3, 2021, and January 20, 2022, 373 out of 387 participants had conclusive QuantiFERON results. At baseline, 5.9% (22/373) had self-reported severe COVID-19, 33.2% (124/373) had TBI, and 11.1% (38/341) reported being HIV-infected. Median follow-up of the cohort was 105 days (range 0-368). Self-reported severe COVID-19 was experienced by 10 of 124 (8.1%) participants compared with 12 of 249 (4.8%) without TBI (odds ratio [OR] 1.73, 95% CI 0.73-4.12, p = 0.21). HIV was not associated with self-reported severe COVID-19 (OR 3.13, 0.96-8.77, p = 0.039, adjusted OR 2.77, 95%CI 0.84-7.93, p = 0.070), but age ≥ 50 years was associated with self-reported severe COVID-19 (OR 3.73, 1.47-9.07, p = 0.004, adjusted OR 2.91, 95%CI 1.02-7.69, p = 0.035). One participant died of COVID-19 three days after diagnosis, and another participant developed active TB 128 days after his COVID-19 diagnosis and was successfully treated. Both were QuantiFERON positive. Self-reported severe COVID-19 was associated with older age and not TBI. Our finding that increased age was associated with self-reported severe COVID-19 is consistent with findings in multiple settings around the world.

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

Purpose of Review: This review summarizes current literature about the disability burden of the fungal neglected tropical diseases (NTDs) sporotrichosis, chromoblastomycosis, eumycetoma, and paracoccidioidomycosis. The review highlights current knowledge gaps in global settings and describes available tools that could be adopted to fill these gaps. Recent Findings: Sporotrichosis, chromoblastomycosis, and eumycetoma often present initially as skin lesions that can become progressively disfiguring, lead to stigmatization, and cause various sequalae affecting health and function. Chronic paracoccidioidomycosis can have systemic involvement and commonly results in impaired pulmonary function, which can limit activities of daily living and employment capacity. Use of standardized tools to quantify disability with fungal NTDs has been limited to date. Standardized tools to measure the impacts on quality of life and mental health are available and have been used for similar patient populations, including persons with other fungal diseases and persons with non-fungal skin NTDs. Summary: Fungal NTDs can be disabling. Improved understanding of the quality of life and mental health consequences might lead to greater awareness of the burden of fungal NTDs and enhance health planning to address the health and rehabilitation needs of persons affected by these diseases. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.

BACKGROUND: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings. METHODS: A retrospective cross-sectional study was conducted for encounters from four large, integrated health systems participating in the VISION network of adult patients presenting with acute respiratory illness to urgent cares or emergency departments and with positive influenza virus test results during the 2023-2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics. RESULTS: A total of 10,700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (N=5,231), 58% (range across sites: 47-64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (N=3,050), 80% (range across sites: 75-91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (0.57 [95% CI: 0.42-0.78]) and lower odds of same-day dispensing (0.58 [95% CI: 0.36-0.94]) compared to those 18-49 years. CONCLUSIONS: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.

During the 2023-2024 respiratory syncytial virus (RSV) season, vaccination was recommended for adults ≥60 years based on shared clinical decision-making with their healthcare providers. We examined RSV vaccine uptake and characteristics associated with uptake among age-eligible Kaiser Permanente Southern California (KPSC) patients. Our study cohort included all patients ≥60 years from September 23, 2023 (i.e., date RSV vaccination first became available at KPSC; N = 1,003,132) to April 9, 2024 (i.e., end of local RSV season). To identify sociodemographic and clinical characteristics associated with RSV vaccination, we used multivariable robust Poisson regression to estimate the adjusted relative risk (aRR) and 95 % CI. Overall, 7.6 % of patients were vaccinated for RSV. In multivariable regression analyses, those aged 70-79.9 years (aRR: 1.36; 95 % CI: 1.34-1.39) and aged ≥80 years (aRR: 1.35; 95 % CI: 1.32-1.38) were more likely to be vaccinated, compared with those aged 60-69.9 years. Compared with Non-Hispanic White patients, Asian (aRR: 0.95; 95 % CI: 0.93-0.97), Hispanic (aRR: 0.52; 95 % CI: 0.51-0.54), Non-Hispanic Black (aRR: 0.69; 95 % CI: 0.67-0.71), Pacific Islander (aRR: 0.91; 95 % CI: 0.84-0.98), and Native American or Alaska Native (aRR: 0.80; 95 % CI: 0.70-0.92) patients were less likely to be vaccinated. Those in higher neighborhood deprivation quartiles were less likely to be vaccinated (Q2: aRR: 0.86; 95 % CI: 0.85-0.88; Q3: aRR: 0.77; 95 % CI: 0.76-0.79; and Q4: aRR: 0.67; 95 % CI: 0.65-0.68), compared with those in the lowest deprivation quartile. We found low vaccination uptake and identified disparities in vaccination that might exacerbate existing disparities in RSV infection and severe RSV disease among certain populations. CDC's ACIP recently updated their recommendations for all adults 75+ years, and this might begin to address these disparities.

Persons who work closely with dairy cows, poultry, or other animals with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) viruses are at increased risk for infection. In September 2024, the California Department of Public Health was notified of the first human case of HPAI A(H5N1) in California through monitoring of workers on farms with infected cows. During September 30-December 24, 2024, a total of 38 persons received positive test results for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows, and one was a child aged <18 years with an undetermined exposure, the first pediatric HPAI A(H5N1) case reported in the United States. All patients had mild illness. The identification of cases associated with occupational exposure to HPAI A(H5N1) viruses on dairy farms highlights the continued risk for persons who work with infected animals. The pediatric case was identified through routine surveillance. Given recent increases in the prevalence of HPAI A(H5N1) viruses among some animal populations, public health agencies should continue to investigate cases of HPAI A(H5N1) in humans as part of control measures, pandemic preparedness, to identify concerning genetic changes, and to prevent and detect potential human-to-human transmission of the virus. To date, no human-to-human transmission of HPAI A(H5N1) virus has been identified in the United States.

To help achieve the End TB Strategy target of a 90% reduction in tuberculosis (TB) incidence by 2030, member states of the United Nations High-Level Meetings on TB called for improving provision of TB preventive treatment (TPT) for household contacts of persons with TB, who are at increased risk for infection and disease. However, TPT use among household contacts worldwide remained at 21% in 2023. The International Union Against Tuberculosis and Lung Disease, the Uganda Ministry of Health, and CDC piloted a comprehensive approach for increasing case finding and TPT coverage among household contacts of persons with TB. During November 1, 2023-September 30, 2024, a total of 521 index patients with TB disease were registered at six health facilities in Uganda. Home visits to index patients identified 1,913 household contacts, 1,739 (91.0%) of whom underwent TB symptom screening at home; 321 (18.5%) reported TB symptoms. Of 309 (96.3%) persons with TB symptoms who were further evaluated, 284 (91.9%) provided a sputum specimen for laboratory testing, including 270 (84.1% of those with symptoms) who did so during the home visit; 214 (69.3%) underwent chest radiography. Overall, 80 TB cases were diagnosed; in 61 (76.3%) persons, the diagnosis was based on radiographic findings. Among 1,496 HHCs eligible for TPT, 1,239 (82.8%) initiated treatment and 1,178 (95.1%) completed it. Global scale-up of this approach might help reach global TB elimination goals.

BACKGROUND: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown. METHODS: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen's kappa statistic. RESULTS: Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56-0.66). CONCLUSION: ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.

Regulations, accreditation standards, and professional guidance require laboratories to use reference materials for assay development, validation, quality control, and proficiency testing of clinical genetic tests. There are, however, few publicly available reference materials for most genetic tests. To address this issue, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Program (GeT-RM), the Coriell Institute for Medical Research, and the genetic testing community have conducted 19 studies, including nine for pharmacogenetic (PGx) and Human Leukocyte Antigen (HLA) testing, to create characterized, renewable, and publicly available DNA samples for use as reference materials. Because new PGx alleles are frequently identified, and allele designations change over time, many samples were reanalyzed for the same gene(s) in subsequent GeT-RM studies. These studies utilized more comprehensive and sensitive methods and panels that examined additional single nucleotide variants (SNVs) and/or star alleles to expand and update the consensus genotypes. Up to date information is available in two newly established resources: the GeT-RM Consolidated PGx and HLA Table and the GeT-RM PGx Search Tool. These resources contain all available PGx and HLA genotypes for 363 publicly available samples characterized during nine GeT-RM PGx or HLA studies for 34 genes/loci in a consolidated and searchable format.

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: The tick-borne pathogens, Bourbon virus (BRBV) and Heartland virus (HRTV) are the cause of febrile illnesses that may progress to severe and fatal diseases. Materials and Methods: As a preliminary effort to determine if these viruses were enzootic in Texas, ticks and blood samples were collected from feral swine (Sus scrofa) and white-tailed deer (Odocoileus virginianus) (WTD) killed by gunning as part of an abatement program during 2019-2021 in Travis County, Texas. Ticks were collected from these animals by hand and blood samples were obtained by cardiac puncture using 22-gauge needles and 5 mL syringes. Information was recorded for each animal, including date, sex, and location. The species of ticks were identified morphologically using a taxonomic key, and serum samples were tested for neutralizing antibodies to BRBV and HRTV. Results: A total of 83 Ixodes scapularis and 58 Amblyomma americanum ticks were collected from feral swine, and 196 I. scapularis and 11 Dermacentor albipictus from WTD. Although A. americanum, the implicated vector of both viruses was collected from feral swine, neutralizing antibody was not detected to BRBV, but 12% (9/75) had antibody to HRTV as evidence of a previous infection. Of the serum samples obtained from WTD, all were negative for BRBV neutralizing antibody, but 6.6%% (5/75) were positive for HRTV antibody. Conclusion: These preliminary results indicated that HRTV was enzootic in Travis, County, Texas and further studies are warranted to determine the specific tick vectors and the possible role of WTD and feral swine in the maintenance and transmission cycle of this virus.

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.

BACKGROUND: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized. METHODS: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multistate population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality. RESULTS: A total of 26 233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median, 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted odds ratio for death was 1.14 (95% confidence interval [CI], 1.01-1.27) in those starting treatment on day 1 and 1.40 (95% CI, 1.17-1.66) in those starting on days 2-5. CONCLUSIONS: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.