In 2022, uptake of all seven Core Elements of Antibiotic Stewardship were reported by 83% of US long-term care facilities. Though 98% of facilities reported access to an electronic health record, less than one-third utilized it for tracking antibiotic use, suggesting opportunities to leverage electronic data for automated reporting.

We identified 34 patients with Coxiella burnetii infection using PCR; 31 (86%) cases were diagnosed from cardiac specimens. Nearly half (15/31, 48%) of those cases were not reported to any channel of national disease surveillance, indicating substantial underreporting for diseases identified using molecular methods at noncommercial laboratories.

Stigma toward homosexuality plays an important role in the increased risk of acquiring or transmitting HIV among men who have sex with men (MSM). This study describes associations between three dimensions of homosexuality-related stigma (enacted, perceived and internalized) and HIV risk behaviors among HIV-negative MSM in Hanoi, Vietnam. A total of 1675 HIV-negative MSM were recruited from the baseline of a cohort study from 2017 to 2019 through respondent-driven, time-location and internet-based sampling strategies. Stigma was measured by a locally validated instrument, with a higher score indicated a higher level of stigma (from 1 to 4). Enacted stigma (mean = 2.10), perceived stigma (mean = 2.62) and internalized stigma (mean = 2.55) were found. About 25% of participants reported group sex and 6.3% reported drug use before or during group sex in the last 6 months. Enacted stigma was significantly associated with group sex (adjusted OR = 1.48; 95% CI 1.20-1.84) and drug use before or during group sex (adjusted OR = 1.68; 95% CI 1.19-2.36). Internalized stigma was significantly associated with group sex (adjusted OR = 1.27; 95% CI 1.05-1.53) and drug use before or during group sex (adjusted OR = 1.44; 95% CI 1.04-1.99). The results highlight the need for multifaced interventions at a multiple socio-ecological levels to reduce stigma toward homosexuality.

BACKGROUND: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI. METHODS: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS). RESULTS: Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS. CONCLUSIONS: CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

Novichok nerve agents, such as A-230, A-232, and A-234, were classified as Schedule 1 chemicals under the Chemical Weapons Convention (CWC) by the Organisation for the Prohibition of Chemical Weapons (OPCW) following poisoning incidents in 2018. As a result, the production, storage, and use of these chemicals are strictly prohibited by CWC signatory nations. The identification of biomarkers indicating Novichok exposure in humans is crucial for prompt detection and response to potential incidents involving these banned chemical weapons. In this study, BChE was isolated from human serum samples exposed to Novichok nerve agents in vitro using immunomagnetic capture, followed by enzymatic digestion with Pronase or proteinase K to generate new peptide biomarkers indicative of exposure. We identified nine previously unpublished Novichok-adducted peptides generated through enzymatic digestion with proteinase K and Pronase using liquid chromatography-high-resolution mass spectrometry. Two peptides, [Agent]-serine-alanine for proteinase K digestion and [Agent]-serine-alanine-glycine for Pronase digestion, were selected for optimization due to their abundance. The analysis was subsequently transferred to an LC-triple quadrupole system to enhance throughput and detect these new biomarkers at the limits of detection corresponding to BChE inhibition levels of 3.90% or less. These additional biomarkers can improve laboratory preparedness for OPCW-designated biomedical testing laboratories as well as other clinical and investigative laboratories tasked with responding to emergencies involving these highly toxic chemicals.

The objective of this study is to evaluate the impact of low blood lead levels (BLLs) on the red blood cell folate concentrations in U.S. children aged 2-17 years. All data were obtained from the National Health and Nutrition Examination Survey (NHANES) over six consecutive cycles from 2007-2008 to 2017-2018. A total of 12,739 children with BLLs lower than 10 µg/dL (geometric mean: 0.66 µg/dL) were included in the dataset. BLLs were categorized into three tertiles (tertile 1: <0.55 µg/dL; tertile 2: 0.55-0.95 µg/dL; and tertile 3: ≥0.95 µg/dL). The multivariate linear regression model analysis indicates a negative relationship between BLLs and red blood cell folate concentrations. After adjusting for potential confounding factors, red blood cell folate concentrations were lower in children in the BLL tertile 2 (β-coefficient = -0.0450; 95% CI: -0.0676, -0.0224) and BLL tertile 3 groups (β-coefficient = -0.0775; 95% CI: -0.1032, -0.0517) compared to children in the BLL tertile 1 group. When stratified by age, gender, and race/Hispanic origin, the subgroup analysis consistently revealed a negative relationship between BLLs and red blood cell folate concentrations, with red blood cell folate concentrations being lower (p < 0.05) in children in the BLL tertile 3 group compared to children in the tertile 1 group. Further investigation is needed to explore the mechanism underlying the potential relationship between BLLs and red blood cell folate concentrations and determine whether folate plays an active role beneficial for preventing the harmful effects of lead on children.

BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).

BACKGROUND: Prolonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice. METHODS: C57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O(2)) conditions for 6 days. Control, low (5 ng/neonate) and high (25 ng/neonate) doses of VitD were administered daily beginning at day 2 via oral gavage. Lung tissue was analyzed for edema, changes in pulmonary structure and function, and inflammatory cytokine expression. RESULTS: Neonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant changes in cytokine expression were observed between untreated and VitD neonates. While changes in surfactant protein mRNA expression were impacted by hyperoxia and VitD administration, no significant changes in alveolar type II cell percentages were observed. At 3 weeks, mice in hyperoxia treated with VitD had greater lung compliance, diminished airway reactivity and improved weight gain. CONCLUSIONS: High dose VitD significantly limited harmful effects of HALI. These results suggest that supplementation of VitD to neonatal mice during hyperoxia exposure provides both short-term and long-term protective benefits against HALI.

Lead's neurotoxic properties and potential harmful effects to humans, particularly young children, have been recognized for decades, influencing public health policies to reduce its admixture in house paint and passenger car gasoline. We signal 3 emergent trends: firearm proliferation, complex international food supply chains, and equally complex product marketing strategies, which have opened opportunities for lead exposure to children from guns and ammunition, and lead contamination in children's food and consumer goods. Readers will also be apprised of Childhood Lead Poisoning Prevention Program and education strategies cultivated and advanced by the Centers for Disease Control and Prevention and its lead prevention partners. A national governmental policy update is included, as are future considerations.

BACKGROUND: Limited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS). METHODS: School KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten-12th grade) in Kansas City, Missouri. During the 2022-2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs. RESULTS: From 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys. CONCLUSION: Respiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures.

The first dengue "endgame" summit was held in Syracuse, NY over August 9 and 10, 2023. Organized and hosted by the Institute for Global Health and Translational Sciences at SUNY Upstate Medical University, the gathering brought together researchers, clinicians, drug and vaccine developers, government officials, and other key stakeholders in the dengue field for a highly collaborative and discussion-oriented event. The objective of the gathering was to discuss the current state of dengue around the world, what dengue "control" might look like, and what a potential roadmap might look like to achieve functional dengue control. Over the course of 7 sessions, speakers with a diverse array of expertise highlighted both current and historic challenges associated with dengue control, the state of dengue countermeasure development and deployment, as well as fundamental virologic, immunologic, and medical barriers to achieving dengue control. While sustained eradication of dengue was considered challenging, attendees were optimistic that significant reduction in the burden of dengue can be achieved by integration of vector control with effective application of therapeutics and vaccines.

OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program.

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.

Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and mortality caused by RVA. From 2016 to 21, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 20. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 21 were mapped using next-generation sequencing. From 2016 to 21, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P[8], G3P[8] and G8P[8]. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019-2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2-99.9% and 99.1-99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.

Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.

BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. METHODS: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. FINDINGS: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. INTERPRETATION: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. FUNDING: Bill & Melinda Gates Foundation.

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients aged 8 months to <5 years with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. RESULTS: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. CONCLUSIONS: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.

Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided.

This report updates the 2012 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccines for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2012;61:613-8). Routine annual influenza vaccination is recommended for all persons aged ≥ 6 months. For the 2013-14 influenza season, it is expected that trivalent live attenuated influenza vaccine (LAIV3) will be replaced by a quadrivalent LAIV formulation (LAIV4). Inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Vaccine virus strains included in the 2013-14 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional influenza B virus strain, a B/Brisbane/60/2008-like virus, intended to ensure that both influenza B virus antigenic lineages (Victoria and Yamagata) are included in the vaccine. This report describes recently approved vaccines, including LAIV4, IIV4, trivalent cell culture-based inactivated influenza vaccine (ccIIV3), and trivalent recombinant influenza vaccine (RIV3). No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates also will be found at this website. Vaccination and health-care providers should check the CDC influenza website periodically for additional information.

At its October 2012 meeting, the Advisory Committee on Immunization Practices (ACIP) voted to recommend vaccination against meningococcal serogroups C and Y for children aged 6 weeks through 18 months at increased risk for meningococcal disease. Meningococcal groups C and Y and Haemophilus b tetanus toxoid conjugate vaccine (Hib-MenCY-TT [MenHibrix, GlaxoSmithKline Biologicals]) is licensed for active immunization for prevention of invasive disease caused by Haemophilus influenzae type b (Hib) and meningococcal serogroups C and Y. Hib-MenCY-TT is not indicated for prevention of disease caused by meningococcal serogroup B, the most common serogroup causing disease in infants, or serogroups W135 or A, which are represented in quadrivalent meningococcal vaccines. Before licensure of Hib-MenCY-TT, no meningococcal conjugate vaccine was licensed for infants aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is licensed as a 2-dose series for infants and toddlers aged 9 through 23 months, and MenACWY-D and MenACWY-CRM (Menveo, Novartis Vaccines) are licensed for persons aged 2 through 55 years as a single dose. These vaccines are recommended routinely for persons aged 11 through 18 years and persons aged 2 through 55 years at increased risk for meningococcal disease (and persons aged 9 months through 55 years for MenACWY-D). This report summarizes the deliberations of ACIP, the rationale for its decision, and recommendations for use of Hib-MenCY-TT in infants at increased risk for meningococcal disease.

Baseline trachoma surveys in Côte d'Ivoire (2019) identified seven evaluation units (EUs) with a trachomatous inflammation-follicular (TF) prevalence ≥10%, but a trachomatous trichiasis (TT) prevalence in individuals ≥15 y of age below the elimination threshold (0.2%). Two of these EUs, Bondoukou 1 and Bangolo 2, were selected for a follow-up survey to understand the epidemiology of trachoma using additional indicators of Chlamydia trachomatis infection (DNA from conjunctival swabs) and exposure (anti-Pgp3 and Ct694 antibodies from dried blood spots [DBSs]). A two-stage cluster sampling methodology was used to select villages and households. All individuals 1-9 y of age from each selected household were recruited, graded for trachoma and had a conjunctival swab and DBS collected. Conjunctival swabs and DBSs were tested using Cepheid GeneXpert and a multiplex bead assay, respectively. The age-adjusted TF and infection prevalence in 1- to 9-year-olds was <1% and <0.3% in both EUs. Age-adjusted seroprevalence was 5.3% (95% confidence interval [CI] 1.5 to 15.6) in Bondoukou 1 and 8.2% (95% CI 4.3 to 13.7) in Bangolo 2. The seroconversion rate for Pgp3 was low, at 1.23 seroconversions/100 children/year (95% CI 0.78 to 1.75) in Bondoukou 1 and 1.91 (95% CI 1.58 to 2.24) in Bangolo 2. Similar results were seen for CT694. These infection, antibody and clinical data provide strong evidence that trachoma is not a public health problem in either EU.

Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones.

Despite the improvements in HIV care outcomes in the United States (US), non-US-born persons continue to be disproportionately affected by HIV. We analyzed National HIV Surveillance System (NHSS) data on HIV diagnoses, stage 3 (AIDS) at diagnosis, linkage to medical care, and viral suppression for non-US-born persons by region of birth (RoB) reported to the (NHSS) in 2020 to determine care outcomes among this population. Overall, a larger proportion of non-US-born persons received a late-stage diagnosis [stage 3 (AIDS)] classification. Among all non-US-born persons, African-born males, Asian-born females, and persons aged 55 + years had the highest proportions of late-stage diagnosis. Despite a late-stage of diagnosis, a higher proportion of non-US-born persons were linked to medical care and were virally suppressed compared to US-born persons. HIV care outcomes varied by RoB and selected characteristics. Knowing the RoB of non-US-born persons is necessary to identify culturally sensitive approaches for prevention planning and increasing testing activities to ultimately increase early diagnosis in this population.

INTRODUCTION: Dog-mediated rabies is enzootic in Vietnam, resulting in at least 70 reported human deaths and 500,000 human rabies exposures annually. In 2016, an integrated bite cases management (IBCM) based surveillance program was developed to improve knowledge of the dog-mediated rabies burden in Phu Tho Province of Vietnam. METHODS: The Vietnam Animal Rabies Surveillance Program (VARSP) was established in four stages: (1) Laboratory development, (2) Training of community One Health workers, (3) Paper-based-reporting (VARSP 1.0), and (4) Electronic case reporting (VARSP 2.0). Investigation and diagnostic data collected from March 2016 to December 2019 were compared with historical records of animal rabies cases dating back to January 2012. A risk analysis was conducted to evaluate the probability of a rabies exposure resulting in death after a dog bite, based on data collected over the course of an IBCM investigation. RESULTS: Prior to the implementation of VARSP, between 2012 and 2015, there was an average of one rabies investigation per year, resulting in two confirmed and two probable animal rabies cases. During the 46 months that VARSP was operational (2016 - 2019), 1048 animal investigations were conducted, which identified 79 (8%) laboratory-confirmed rabies cases and 233 (22%) clinically-confirmed(probable) cases. VARSP produced a 78-fold increase in annual animal rabies case detection (one cases detected per year pre-VARSP vs 78 cases per year under VARSP). The risk of succumbing to rabies for bite victims of apparently healthy dogs available for home quarantine, was three deaths for every 10,000 untreated exposures. DISCUSSION: A pilot IBCM model used in Phu Tho Province showed promising results for improving rabies surveillance, with a 26-fold increase in annual case detection after implementation of a One Health model. The risk for a person bitten by an apparently healthy dog to develop rabies in the absence of rabies PEP was very low, which supports the WHO recommendations to delay PEP for this category of bite victims, when trained animal assessors are available and routinely communicate with the medical sector. Recent adoption of an electronic IBCM system is likely to expedite adoption of VARSP 2.0 to other Provinces and improve accuracy of field decisions and data collection.