BACKGROUND: Of the 43 mpox cases reported by the WHO in South East Asia between January 2022 and March 2023, 24 (56%) were from India. OBJECTIVES: We describe the clinical and epidemiological profile of cases identified through India's hospital case-based surveillance. MATERIALS AND METHODS: We identified mpox cases as a positive result for mpox virus polymerase-chain-reaction assay, reported through surveillance from July 1, 2022 to January 7, 2023. Cases and clinicians were interviewed, and data were abstracted from the medical records. We conducted contact tracing among family, close social networks, and healthcare personnel staff for the first 17 cases. We collected the data on sociodemographics, clinical findings, and behavior, and described data using summary statistics. RESULTS: We identified 24 laboratory-confirmed cases (42% females, median age 30 years, range 22-38), including one death (case fatality rate 4.2%). We collected clinical and behavioural data from 21 of 24 cases. All had rashes with vesicles and genital lesions; 7 (33%) reported genital lesions as the first symptom; and 3 (13%) reported complications. Among the 21 cases, all were sexually active, none self-identified as men having sex with men (MSM), and 6 (29%) reported multiple sex partners. We identified 51 contacts of the first 17 reported cases, none reported symptoms suggestive of mpox. CONCLUSION: The clinical and behavioral characteristics of mpox cases in India are consistent with the global 2022 outbreak, with the exception that no cases in India reported MSM. Most were sexually active young adult economic migrants and developed genital lesions.

BACKGROUND: There are no recent estimates for hypertension-associated medical expenditures. This study aims to estimate hypertension-associated incremental medical expenditures among privately insured US adults. METHODS: We conducted a retrospective cohort study using IQVIA's Ambulatory Electronic Medical Records-US data set linked with PharMetrics Plus claims data. Among privately insured adults aged 18 to 64 years, hypertension was identified as having ≥1 diagnosis code or ≥2 blood pressure measurements of ≥140/90 mm Hg, or ≥1 antihypertensive medication in 2021. Annual total expenditures (in 2021 $US) were estimated using a generalized linear model with gamma distribution and log-link function adjusting for demographic characteristics and cooccurring conditions. Out-of-pocket expenditures were estimated using a 2-part model that included logistic and generalized linear model regression. Overlap propensity score weights from logistic regression were used to obtain a balanced sample on hypertension status. RESULTS: Among the 393 018 adults, 156 556 (40%) were identified with hypertension. Compared with individuals without hypertension, those with hypertension had $2926 (95% CI, $2681-$3170) higher total expenditures and $328 (95% CI, $300-$355) higher out-of-pocket expenditures. Adults with hypertension had higher total inpatient ($3272 [95% CI, $1458-$5086]) and outpatient ($2189 [95% CI, $2009-$2369]) expenditures when compared with those without hypertension. Hypertension-associated incremental total expenditures were higher for women ($3242 [95% CI, $2915-$3569]) than for men ($2521 [95% CI, $2139-$2904]). CONCLUSIONS: Among privately insured US adults, hypertension was associated with higher medical expenditures, including higher inpatient and out-of-pocket expenditures. These findings may help assess the economic value of interventions effective in preventing hypertension.

Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8(+) T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8(+) T cells. Our results indicate that both CD8(+) T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8(+) T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8(+) T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8(+) T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8(+) T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer. IMPORTANCE: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer.

The study aims were (1) to explore whether "periodontal treatment" consisting of surgical therapy (flap, resective, or regenerative) or scaling and root planing treatment with long-term periodontal maintenance treatment, is cost-effective in terms of preventing periodontitis-attributable tooth extraction and replacement by implant-supported crowns ("extraction/replacement"); (2) to assess the effect of cigarette smoking on this cost-effectiveness. Data for this observational retrospective study were collected from dental charts of patients who had received periodontal therapy and at least annual follow-up visits for >10 years were analyzed by linear regression generalized estimating equations and generalized linear models. Among 399 adults (199 males, 200 females), those with the least mean annual treatment cost experienced the greatest mean annual costs for extraction/replacement, indicating general cost-effectiveness. Cigarette smoking adversely impacted this cost-effectiveness, with current heavy smokers experiencing no cost-effectiveness. Former smokers with Grade C periodontitis benefitted most, whereas smoking did not influence cost-effectiveness for Grade B periodontitis. Assessed by mean annual costs of "extraction/replacement," periodontal treatment was cost-effective, which decreased in a dose-response manner by former and current smoking intensity. Cigarette smoking should be factored into treatment planning and cost-effective analyses of periodontal treatment. Smoking cessation should be encouraged.

IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES: To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN: Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING: Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS: Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS: Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE: We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

INTRODUCTION: This study seeks to estimate health care expenditures and use associated with hypertension, focusing on differences among racial and ethnic groups. METHODS: Data were from the 2019 Medical Expenditure Panel Survey, analyzed in 2023. The study sample included noninstitutionalized U.S. adults aged ≥18 years. Outcome variables were health care expenditures and events. Hypertension was determined by a self-reported diagnosis or diagnoses codes. Race and ethnicity were self-reported. A 2-part model was used to estimate expenditures associated with hypertension. A zero-inflated negative binomial model was used to estimate events associated with hypertension. Sampling designs were applied to generate nationally representative estimates. RESULTS: Hypertension was associated with $2,759 (95% confidence interval [CI]: $2,039, $3,479) in health care expenditures and 10.3 (95% CI: 9.3, 11.3) health care events, including prescriptions filled, in 2019 per person. Compared with non-Hispanic White adults, hypertension-associated health care expenditures were significantly lower among Hispanic adults (difference: -$1,877; 95% CI: -$3,389, -$364) and Asian adults (difference: -$2,452; 95% CI: -$4,093, -$811), and hypertension-associated health care events were significantly lower among Hispanic adults (difference: -3.8; 95% CI: -6.1, -1.6) and non-Hispanic Asian adults (difference: -4.1; 95% CI: -6.9, -1.2). Differences between non-Hispanic White adults and non-Hispanic Black adults were not statistically significant in health care expenditures (difference: -$954; 95% CI: -$2,849, $941) and events (difference: 0.3; 95% CI: -2.1, 2.8). CONCLUSIONS: This study reveals differences in health care expenditures and use associated with hypertension among racial and ethnic groups. Future studies are needed to examine potential drivers of these differences.

Measles is a highly infectious, vaccine-preventable disease that can cause severe illness, hospitalization, and death. A measles outbreak associated with a migrant shelter in Chicago occurred during February-April 2024, in which a total of 57 confirmed cases were identified, including 52 among shelter residents, three among staff members, and two among community members with a known link to the shelter. CDC simulated a measles outbreak among shelter residents using a dynamic disease model, updated in real time as additional cases were identified, to produce outbreak forecasts and assess the impact of public health interventions. As of April 8, the model forecasted a median final outbreak size of 58 cases (IQR = 56-60 cases); model fit and prediction range improved as more case data became available. Counterfactual analysis of different intervention scenarios demonstrated the importance of early deployment of public health interventions in Chicago, with a 69% chance of an outbreak of 100 or more cases had there been no mass vaccination or active case-finding compared with only a 1% chance when those interventions were deployed. This analysis highlights the value of using real-time, dynamic models to aid public health response, set expectations about outbreak size and duration, and quantify the impact of interventions. The model shows that prompt mass vaccination and active case-finding likely substantially reduced the chance of a large (100 or more cases) outbreak in Chicago.

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests. RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.

Natural planned exposure (NPE) remains one of the most common methods in swine herds to boost lactogenic immunity against rotaviruses. However, the efficacy of NPE protocols in generating lactogenic immunity has not been investigated before. A longitudinal study was conducted to investigate the dynamics of genotype-specific antibody responses to different doses (3, 2 and 1) of Rotavirus A (RVA) NPE (genotypes G4, G5, P[7] and P[23]) in gilts and the transfer of lactogenic immunity to their piglets. Group 1 gilts received three doses of NPE at 5, 4 and 3 weeks pre-farrow (WPF), group 2 received two doses at 5 and 3 WPF, group 3 received one dose at 5 WPF, and group 4 received no NPE (control group). VP7 (G4 and G5) and truncated VP4* (P[7] and P[23]) antigens of RVA were expressed in mammalian and bacterial expression systems, respectively, and used to optimize indirect ELISAs to determine antibody levels against RVA in gilts and piglets. In day-0 colostrum samples, group 1 had significantly higher IgG titers compared to the control group for all four antigens, and either significantly or numerically higher IgG titers than groups 2 and 3. Group 1 also had significantly higher colostrum IgA levels than the control group for all antigens (except G4), and either significantly or numerically higher IgA levels compared to groups 2 and 3. In piglet serum, group 1 piglets had higher IgG titers for all four antigens at day 0 than the other groups. Importantly, RVA NPE stimulated antibodies in all groups regardless of the treatment doses and prevented G4, G5, P[7] and P[23] RVA fecal shedding prior to weaning in piglets in the absence of viral challenge. The G11 and P[34] RVA genotypes detected from pre-weaning piglets differed at multiple amino acid positions with parent NPE strains. In conclusion, the results of this study suggest that the group 1 NPE regimen (three doses of NPE) resulted in the highest anti-RVA antibody (IgG and IgA) levels in the colostrum/milk, and the highest IgG levels in piglet serum.

INTRODUCTION: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. METHODS: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. RESULTS: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. CONCLUSION: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

BACKGROUND: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan. METHODS: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates. RESULTS: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively. CONCLUSION: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes.

BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

BACKGROUND: Antimicrobial resistance poses a significant threat to public health globally. We studied the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and colistin-resistant Enterobacterales (Col-RE) in hospitals and the surrounding community in South India. METHODS: Adults from 2 hospitals and the catchment community who consented to provide stool specimens were enrolled. Stools were plated on CHROMagar selective for ESCrE, CRE, and Col-RE. Bacterial identification and antibiotic susceptibility testing were done using Vitek 2 Compact and disc diffusion testing. Colistin broth microdilution was performed for a subset of isolates. Prevalence estimates were calculated with 95% confidence intervals (CIs), and differences were compared across populations using the Pearson χ(2) or Fisher exact test. RESULTS: Between November 2020 and March 2022, 757 adults in the community and 556 hospitalized adults were enrolled. ESCrE colonization prevalence was 71.5% (95% CI, 68.1%–74.6%) in the community and 81.8% (95% CI, 78.4%–84.8%) in the hospital, whereas CRE colonization prevalence was 15.1% (95% CI, 12.7%–17.8%) in the community and 22.7% (95% CI, 19.4%–26.3%) in the hospital. Col-RE colonization prevalence was estimated to be 1.1% (95% CI, .5%–2.1%) in the community and 0.5% (95% CI, .2%–1.6%) in the hospital. ESCrE and CRE colonization in hospital participants was significantly higher compared with community participants (P < .001 for both). CONCLUSIONS: High levels of colonization with antibiotic-resistant Enterobacterales were found in both community and hospital settings. This study highlights the importance of surveillance of colonization in these settings for understanding the burden of antimicrobial resistance.

Implementing infection prevention and control (IPC) programmes in line with the World Health Organization's (WHO) eight core components has been challenging in Sierra Leone. In 2021, a baseline study found that IPC compliance in three tertiary hospitals was sub-optimal. We aimed to measure the change in IPC compliance and describe recommended actions at these hospitals in 2023. This was a 'before and after' observational study using two routine cross-sectional assessments of IPC compliance using the WHO IPC Assessment Framework tool. IPC compliance was graded as inadequate (0-200), basic (201-400), intermediate (401-600), and advanced (601-800). The overall compliance scores for each hospital showed an improvement from 'Basic' in 2021 to 'Intermediate' in 2023, with a percentage increase in scores of 16.9%, 18.7%, and 26.9% in these hospitals. There was improved compliance in all core components, with the majority in the 'Intermediate' level for each hospital IPC programme. Recommended actions including the training of healthcare workers and revision of IPC guidelines were undertaken, but a dedicated IPC budget and healthcare-associated infection surveillance remained as gaps in 2023. Operational research is valuable in monitoring and improving IPC programme implementation. To reach the 'Advanced' level, these hospitals should establish a dedicated IPC budget and develop long-term implementation plans.

Introduction Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (KLK10, a secreted serine protease) as a flow-sensitive gene in arterial endothelial cells, but its role in endothelial biology and atherosclerosis was unknown.Methods and Results Here, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo mouse models and in vitro studies with cultured endothelial cells (ECs). Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated KLK10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced inflammation and permeability dysfunction in human artery ECs (HAECs). Further, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of KLK10-expressing plasmids inhibited atherosclerosis in ApoE-/- mice. Studies using pharmacological inhibitors and siRNAs revealed that the anti-inflammatory effects of KLK10 were mediated by a Protease Activated Receptors (PAR1/2)-dependent manner. However, unexpectedly, KLK10 did not cleave the PARs. Through a proteomics study, we identified HTRA1 (High-temperature requirement A serine peptidase 1), which bound and cleaved KLK10. Further, siRNA knockdown of HTRA1 prevented KLK10’s anti-inflammatory and barrier protective function in HAECs, suggesting that HTRA1 regulates KLK10 function. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques.Conclusion KLK10 is a flow-sensitive endothelial protein and, in collaboration with HTRA1, serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor.Competing Interest StatementThe authors have declared no competing interest.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

This Research Topic has focused on subjects such as tracking emerging SARS-CoV-2 variants, detection, isolation, and genomic characterization of emerging variants, transmission, pathogenesis, clinical effects of variants, assessment of COVID-19 vaccination and treatment effectiveness, comparative analysis of SARS-CoV-2 genomic data, and other public health intervention measures. The Research Topic featured 27 articles highlighting the emergence of Omicron variants and their sub-lineages across the globe and their clinical presentations, specifically asymptomatic infections, COVID-19-associated liver injury, and comorbidities such as hypertension, diabetes, and bronchitis. Additionally, a few studies have reported the efficacy of therapeutic drugs in reducing viral load and the significance of vaccination and a booster dose against Omicron variants. Furthermore, the studies on genomic surveillance and evolutionary analysis have demonstrated the emergence of Omicron and its sub-lineages and their characteristic mutations. All these in-depth studies have explored various elements of Omicron, resulting in a comprehensive understanding of this variant.

BACKGROUND: We present post-vaccination nasal shedding findings from the phase IV, community-based, triple-blinded RCT conducted to assess efficacy of trivalent LAIV and inactivated influenza vaccines in rural north India. METHODS: Children aged 2-10 years received LAIV or intranasal placebo across 2015 and 2016, as per initial allocation. On days 2 and 4 post-vaccination, trained study nurses collected nasal swabs from randomly selected subset of trial participants based on operational feasibility, accounting for 10.0% and 11.4% of enrolled participants in 2015 and 2016, respectively. Swabs were collected in viral transport medium and transported under cold chain to laboratory for testing by reverse transcriptase real-time polymerase chain reaction. RESULTS: In year 1, on day 2 post-vaccination, 71.2% (74/104) of LAIV recipients shed at least one of vaccine virus strains compared to 42.3% (44/104) on day 4. During year 1, on day 2 post-vaccination, LAIV-A(H1N1)pdm09 was detected in nasal swabs of 12% LAIV recipients, LAIV-A(H3N2) in 41%, and LAIV-B in 59%. In year 2, virus shedding was substantially lower; 29.6% (32/108) of LAIV recipients shed one of the vaccine virus strains on day 2 compared to 21.3% on day 4 (23/108). CONCLUSION: At day 2 post-vaccination in year 1, two-thirds of LAIV recipients were shedding vaccine viruses. Shedding of vaccine viruses varied between strains and was lower in year 2. More research is needed to determine the reason for lower virus shedding and vaccine efficacy for LAIV-A(H1N1)pdm09.

In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other than methadone, principally illicitly manufactured fentanyls (IMFs) (1). Xylazine, a nonopioid sedative not approved for human use and with no known antidote, has been increasingly detected in IMF products in the U.S. drug supply* and in IMF-involved overdose deaths (2). Limited studies suggest xylazine can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans (3,4); chronic use might lead to severe withdrawal symptoms(†) as well as skin ulcerations (4). This report uses data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS) to describe IMF-involved(§) overdose deaths with and without xylazine detected that occurred during January 2019-June 2022. Among 21 jurisdictions, which included 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%. Among IMF-involved deaths during January 2021-June 2022 in 32 jurisdictions, xylazine was detected in a higher percentage of jurisdictions in the Northeast U.S. Census Bureau region; listing detected xylazine as a cause of death varied across jurisdictions. Expanded postmortem and illicit drug product testing for xylazine is needed to clarify prevalence in drug supplies; further investigation of xylazine's effects on humans is necessary to characterize morbidity and overdose risk. It is important for overdose prevention and response messages to highlight the potential presence of xylazine in IMF products and emphasize the need for respiratory and cardiovascular support to address the sedative effects of xylazine.

IMPORTANCE: Nearly 40% of US youth aged 2 to 19 years do not have a body mass index (BMI) in the healthy weight category. However, there are no recent estimates for BMI-associated expenditures using clinical or claims data. OBJECTIVE: To estimate medical expenditures among US youth across all BMI categories along with sex and age groups. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study used IQVIA's ambulatory electronic medical records (AEMR) data set linked with IQVIA's PharMetrics Plus Claims database from January 2018 through December 2018. Analysis was performed from March 25, 2022, through June 20, 2022. It included a convenience sample of a geographically diverse patient population from AEMR and PharMetrics Plus. The study sample included privately insured individuals with a BMI measurement in 2018 and excluded patients with pregnancy-related visits. EXPOSURE: BMI categories. MAIN OUTCOMES AND MEASURES: Total medical expenditures were estimated using generalized linear model regression with γ distribution and log-link function. For out-of-pocket (OOP) expenditures, a 2-part model was used that included logistic regression to estimate the probability of positive expenditures followed by generalized linear model. Estimates were shown with and without accounting for sex, race and ethnicity, payer type, geographic region, age interacted with sex and BMI categories, and confounding conditions. RESULTS: The sample included 20 876 individuals aged 2 to 19 years; 104 066 were male (50.5%) and the median age was 12 years. Compared with those with healthy weight, total and OOP expenditures were higher for all other BMI categories. Differences in total expenditures were highest for those with severe obesity ($909; 95% CI, $600-$1218) followed by underweight ($671; 95% CI, $286-$1055) compared with healthy weight. Differences in OOP expenditures were highest for those with severe obesity ($121; 95% CI, $86-$155) followed by underweight ($117; 95% CI, $78-$157) compared with healthy weight. Having underweight was associated with higher total expenditures at ages 2 to 5 years and 6 to 11 years by $679 (95% CI, $228-$1129) and $1166 (95% CI, $632-$1700), respectively; having severe obesity was associated with higher total expenditures at ages 2 to 5 years, 6 to 11 years, and 12 to 17 years by $1035 (95% CI, $208-$1863), $821 (95% CI, $414-$1227), and $1088 (95% CI, $594-$1582), respectively. CONCLUSIONS AND RELEVANCE: The study team found medical expenditures to be higher for all BMI categories when compared with those with healthy weight. These findings may indicate potential economic value of interventions or treatments aimed at reducing BMI-associated health risks.

IMPORTANCE: Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. OBJECTIVE: To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493 724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. INTERVENTIONS: Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. RESULTS: The baseline period included 207 047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183 893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. CONCLUSIONS AND RELEVANCE: The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

BACKGROUND: Nucleic acid amplification (NAA) tests rapidly detect Mycobacterium tuberculosis complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis. METHODS: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017. RESULTS: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.9%) were reported as not having an NAA test performed; the proportion without NAA testing declined annually, from 60.5% in 2011 to 33.6% in 2017. Of 67082 verified cases, 27912 (41.6%) had positive, 8215 (12.2%) had negative, and 135 (0.2%) had indeterminate NAA test results. Among the 33937 cases with an acid-fast bacilli (AFB) smear-positive result, 24093 (70.9%) had an NAA test performed; 11490 of the 30244 (38.0%) with an AFB smear-negative result had an NAA test performed. Although sputum was the most common specimen type tested, 79.8% (7023/8804) of nonsputum specimen types had a positive NAA test result. Overall, 63.7% of cases with laboratory testing had NAA test results reported <6 days following specimen collection; for 13891 cases not yet on treatment, median time to treatment after the laboratory report date was 2 days. CONCLUSIONS: Our analyses demonstrate increased NAA test utilization between 2011 and 2017. However, a large proportion of cases did not have an NAA test performed, reflecting challenges in broader uptake, suggesting an opportunity to expand use of this diagnostic methodology.

Acute encephalopathy syndrome (AES) is characterized by sudden onset of seizures and altered sensorium of infectious or non-infectious origin. Seasonal outbreaks of fatal hypoglycaemic AES in children, associated with eating fruit from the Sapindaceae family (e.g., ackee, litchi), have been reported globally [1,2]. Since 1995, AES outbreaks have been reported during the litchi-harvesting season from May–July in Muzaffarpur, the largest commercial litchi-producing district of Bihar, India [3]. An AES outbreak investigation in Muzaffarpur in 2014 linked known toxins hypoglycin A and α-methylene cyclopropyl glycine (MCPG) in litchi fruit to hypoglycaemic AES in children [3]. Following the 2014 outbreak, the Government of Bihar implemented community-based interventions to prevent hypoglycemia in children. They also strengthened the clinical management of hypoglycaemic seizures in public health facilities [4]. The number of AES cases and deaths declined from 2015–18, suggesting that the interventions were effective. However, in May–June 2019, AES cases increased. We conducted a descriptive epidemiological analysis of the AES cases. | | Methods | | We identified AES cases from established hospital-based surveillance in the two tertiary referral hospitals in Muzaffarpur. We defined a suspected AES case as seizures or altered sensorium in a child aged ≤15 years admitted from 1 May to 2nd July 2019. We excluded patients aged six months to 6 years who were admitted for fever and a single generalized convulsion of <15 minutes in duration and recovered consciousness within 60 minutes of seizure. We conducted a review of medical records and abstracted data using a structured tool for socio-demographics, clinical history, duration of hospitalization, treatment, and laboratory profile. We also assembled a prospective cohort of probable cases admitted to the hospital during the investigation. We defined a probable AES case as new-onset seizures or altered sensorium of <7 days duration in a child aged ≤15 years admitted t from 1 May to 2 July 2019. For the cohort of probable cases, we interviewed the caregivers using a structured clinical-epidemiological questionnaire for socio-demographics, anthropometry, illness characteristics, treatment-seeking behavior, meal assessment, exposure to litchi fruit, and exposure to health messages. For anthropometry, we calculated Z-scores using the World Health Organization 2006 standardized growth tables [5]. | | Results | | Of the 655 suspected and probable AES cases identified, the case fatality rate (CFR) was 21% (139 deaths). The median age was four years (interquartile range: 3 months–14 years), and 58% (378) were females. The first case was reported on 5 May 2019, cases peaked on 15 June, and the last case on 2 July (Figure 1). Among cases with available data, 75% (389/518) had blood glucose levels of <70 mg/dL upon hospital admission, and 75% (476/638) were residents of Muzaffarpur district. We identified cases from 15 (94%) of 16 blocks in the Muzaffarpur district and calculated a district incidence of 22 per 100,000 children ≤15 years old. | | The prospective cohort comprised 94 probable AES cases; CFR was 26%. Among probable cases, 63% (49/78) of caregivers were wage workers, and 34% (31/91) were of low socioeconomic status. Symptoms were reported in the early morning (3 am to 8 am) for 67% (62/93) of cases, and 97% (90/93) presented with seizures. Among probable cases with anthropometry data, 62% (43/69) were underweight (i.e., weight-for-age Z score <-2), 44% (25/57) stunted (i.e., height-for-age Z score <-2), and 43% (10/23) wasted (i.e., weight-for-height Z score <-2). Primary health facilities referred 46% (43/93) of probable cases to the two tertiary hospitals for admission. Among cases referred, only 30% (13/43) received hypoglycemia and seizure management at the primary health facility. | | Eating litchis in the 24 hours and seven days before illness onset was reported by 57% (54/94) and 87% (59/68) of caregivers, respectively. Skipping any meal and skipping the evening meal in the 24 hours before illness onset was reported by 55% (48/88) and 44% (28/63) of caregivers, respectively. Among probable cases, 45% (27/60) of caregivers reported Government Supplementary Nutrition (GSN) programme enrollment. Sixty percent (50/83) of caregivers said a visit by health workers in the week before illness. Still, only 8% (7/83) reported receiving messages on AES prevention and early treatment by health workers in the past month. | | Conclusions | | The 2019 AES outbreak in Muzaffarpur district, Bihar, occurred among young children with hypoglycemia upon hospital admission and had high associated mortality. Although the Government of Bihar implemented community and clinical measures to prevent AES cases after the 2014 outbreak, a large proportion of the AES cases did not benefit from the prevention measures based on our investigation [4]. New state and district health leadership, turnover of community and facility-level healthcare workers, lack of ongoing training and focused community outreach, and competing health priorities might have been factors responsible for the resurgence. To prevent future AES cases, we recommended prompt emergency management of hypoglycemia and seizures at primary health facilities before referral. We recommend enrollment of all eligible children to GSN and enhanced community health communications to reinforce the importance of an evening meal for children and limiting the eating of litchi fruit during the harvesting season from May to July

We used 2016-2017 administrative claims data to calculate the direct medical cost and productivity loss per diagnosed case of chlamydia and gonorrhea treatment. In 2018 US dollars, the direct cost per diagnosed case was $151 for chlamydia (n = 9180) and $85 for gonorrhea (n = 3048); productivity loss was $206 (n = 31) and $246 (n = 7), respectively, among those missing work seeking care.

We used 2016-2018 outpatient claims data to calculate direct outpatient medical costs per case of trichomoniasis in 2019 US dollars. The outpatient, drug, and total costs per treated case of trichomoniasis were $174, $39, and $213, respectively. Total costs were higher for female patients ($220) than for male patients ($158).