INTRODUCTION: Community-acquired pneumonia (CAP) is an important cause of hospitalisation among older adults. Assessing costs of CAP hospitalisation aids in economic evaluation of preventive interventions and guides policy decisions. METHODS: We estimated resource utilisation rates and costs from a societal perspective among adults aged >60 years admitted with CAP in eight public and eight private hospitals in four Indian cities (ie, National Capital Region-Delhi, Kolkata, Pune and Chennai) from December 2018 to March 2020. We interviewed patients, reviewed medical records and bills to estimate resources used, direct medical cost of diagnosis and treatment; direct non-medical cost of travel, lodging and food; and indirect cost of patients and caregivers' lost income from admission to discharge. Mean costs with SD by hospital type, age group, chronic condition, critical care (intensive care unit, ICU) and virus detection are presented in US dollars (US$). Linear regression after log transformation was conducted to identify determinants of total cost. RESULTS: We analysed data from 1009 CAP patients in private (63%) and public (37%) hospitals with a median age of 68 (IQR: 63-75) years. Influenza was detected in 121 (12%) and respiratory syncytial virus (RSV) in 21 (2%). Mean length of stay was 6.2 (SD 4.8) days; 37% required ICU admission. Antibiotics and antivirals were used in 96% and 23% of admissions, respectively. Mean (SD) CAP hospitalisation cost was US$305 (244) in public and US$1210 (1019) in private hospitals; US$1024 (1095) in influenza and US$943 (778) in RSV-associated CAP. Regression analysis showed that cost was higher in hospitalisation in private hospitals, those requiring ICU care and among persons with comorbid conditions. CONCLUSIONS: Substantial resources were used, and costs were incurred during CAP hospitalisation among older adults. The findings could aid in cost-benefit analyses of interventions to reduce pneumonia burden, including influenza, RSV or pneumococcal vaccination in older adults.

Foodborne botulism is a rare and potentially fatal illness caused by ingestion of food containing botulinum neurotoxin produced by the bacterium Clostridium botulinum or other neurotoxigenic Clostridium species. C. botulinum can grow in improperly prepared or stored food items such as home-canned or home-preserved vegetables. On June 25, 2024, the Fresno County Department of Public Health and California Department of Public Health, in collaboration with CDC and two local hospitals, initiated an investigation of a foodborne botulism outbreak linked to two related family gatherings in Fresno County, California. A total of 31 persons attended one or both gatherings. Eight attendees had symptoms compatible with botulism and received botulism antitoxin; five of eight had botulinum neurotoxin type A (BoNT/A) detected in serum. Patients had hospital stays ranging from 2 to 42 days, six patients were admitted to an intensive care unit, and two required invasive mechanical ventilation; all survived. Epidemiologic investigation identified home-preserved prickly pear cactus pads (nopales) included in a homemade salad and served at both events as a food item of interest; laboratory testing confirmed the nopales salad as the source of BoNT/A. This foodborne botulism outbreak is the first reported to be linked to home canning of nopales, a popular vegetable used in traditional Mexican cuisine. Rapid public health coordination is essential for responses to foodborne botulism outbreaks. Enhancing community and clinician awareness of foodborne botulism by increasing access to culturally and linguistically accessible home food preservation and canning guidelines might help prevent future outbreaks.

The recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek(®) 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0-99). Colonization with ESCrE in hospitals was high in all sites (range 34-84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.

Introduction: There are no national estimates for blood pressure–lowering prescription trends among the U.S. pediatric population. This study describes trends in blood pressure–lowering prescription fills among individuals aged 3–17 years by sex and age group. Methods: Data were obtained from IQVIA's Total Patient Tracker database covering 94% of all outpatient retail prescription fills in the U.S. The key outcome was blood pressure–lowering prescription fills during 2017–2023, utilizing a list of 113 generic medications from 21 drug classes. In addition, a subset of 20 medications recommended in the 2017 American Academy of Pediatrics guideline was examined. Annual population percentage and percentage change compared with 2017 were reported, and average annual percentage change was estimated using Joinpoint regression. Results: From 2017 to 2023, blood pressure–lowering prescription fills among those aged 3–17 years increased slightly from 1.93% (95% CI=1.88%, 1.98%) to 2.09% (95% CI=2.04%, 2.14%). Among males, blood pressure–lowering prescription fills remained stable (between 2.32% and 2.38%; average annual percentage change= −0.3%; p=0.545), whereas fills among females increased by 23.9% (from 1.49% to 1.84%; average annual percentage change=4.16%; p<0.001). The sharpest increase occurred among females aged 13–17 years (from 2.26% to 3.17%; average annual percentage change=6.3%; p<0.001). Prescription fills for guideline-recommended medications either remained stable or declined, with some variation by sex and age group. Conclusions: Results indicate growth in blood pressure–lowering prescription fills, especially among females aged 13–17 years. Increases were driven by medications not included in the 2017 American Academy of Pediatrics guideline, suggesting that blood pressure–lowering medications may be increasingly prescribed for conditions other than pediatric hypertension. © 2025

Egg-free influenza vaccines, specifically cell culture-based inactivated influenza vaccine (ccIIV) and recombinant influenza vaccine (RIV), represent a significant advancement over traditional egg-based inactivated influenza vaccines (IIV), particularly for populations with extensive vaccination histories. This comprehensive immunological study investigated the comparative efficacy of ccIIV, IIV, and RIV in healthcare personnel (HCP) with repeated vaccination histories, examining both cellular and humoral immune responses through multiple analytical approaches. Our investigation employed a multi-faceted analytical framework, combining serological assessments via hemagglutination inhibition (HI) and microneutralization (MN) assays with detailed cellular immune response analysis. We utilized advanced flow cytometry techniques with recombinant hemagglutinin (HA) probes to evaluate both circulating T follicular helper cells (cTfh) and HA-specific B cells, providing a comprehensive view of vaccine-induced immune responses. The results revealed RIV's superior immunogenicity profile, demonstrating significantly elevated levels of both cTfh and HA-specific B cells compared to ccIIV and IIV. RIV's enhanced performance was particularly evident in its response to influenza A components, with notably higher immunogenicity against both A(H3N2) and A(H1N1) strains. This superiority was reflected in elevated HI titers and markedly increased HA-specific B cell induction. While RIV also demonstrated enhanced HA-specific B cell responses against influenza B components compared to ccIIV, interestingly, HI titers remained comparable across all vaccine groups for these strains. These findings underscore the critical importance of comprehensive immune response evaluation in vaccine assessment. The disparity between cellular and serological responses, particularly for influenza HA-specific B cells, highlights that traditional serological measures alone may not fully capture the breadth and depth of vaccine-induced immunity. This study provides compelling evidence for the inclusion of cellular immunity assessments in vaccine evaluation protocols, offering crucial insights into vaccine immunogenicity that may be missed by conventional serological analysis alone.

The Centers for Disease Control and Prevention (CDC) funds tuberculosis (TB) Centers of Excellence (COEs) that support TB control and prevention efforts in the United States. In 2018, the TB COEs conducted a multiphased assessment among U.S. staff involved in TB service delivery to identify needs related to TB training, resources, and medical consultation. Representatives from each TB COE and CDC's Division of TB Elimination formed a workgroup to guide the design of the needs assessment. The group used an online survey for data collection. Participants were staff working in some capacity on TB within the United States, Puerto Rico, and the U.S. Virgin Islands. Staff could be in non-public health (e.g., community health center, hospital, laboratory, private practice) or public health (state or local health department staff responsible for TB) settings and did not have to be a clinical health care provider (N = 1,482). We identified four priority areas for future TB training and education efforts. These areas include (1) focus on key topics; (2) tailor training and products to different professions, settings, and skill levels; (3) keep learners updated on the latest resources and best practices; and (4) use a mix of training methods and formats. The findings highlighted future priorities for TB training and education and were shared with health department TB programs throughout the United States.

OBJECTIVES: To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment. SUBJECTS AND METHODS: Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6. RESULTS: We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log(10) cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log(10) cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific Inhibin Subunit Alpha (inhA) gene mutations. CONCLUSIONS: The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.

Data-driven approaches to clinical research are necessary for understanding and effectively treating infectious diseases. However, challenges such as issues with data validity, lack of collaboration, and difficult-to-treat infectious diseases (e.g., those that are rare or newly emerging) hinder research. Prioritizing innovative methods to facilitate the continued use of data generated during routine clinical care for research, but in an organized, accelerated, and shared manner, is crucial. This study investigates the potential of CURE ID, an open-source platform to accelerate drug-repurposing research for difficult-to-treat diseases, with COVID-19 as a use case. Data from eight US health systems were analyzed using least absolute shrinkage and selection operator (LASSO) regression to identify key predictors of 28-day all-cause mortality in COVID-19 patients, including demographics, comorbidities, treatments, and laboratory measurements captured during the first two days of hospitalization. Key findings indicate that age, laboratory measures, severity of illness indicators, oxygen support administration, and comorbidities significantly influenced all-cause 28-day mortality, aligning with previous studies. This work underscores the value of collaborative repositories like CURE ID in providing robust datasets for prognostic research and the importance of factor selection in identifying key variables, helping to streamline future research and drug-repurposing efforts.

BACKGROUND: Hypertension is a major risk factor for cardiovascular and renal diseases, significantly contributing to morbidity and mortality. The COVID-19 pandemic has heightened concerns about the impact of hypertension on severe COVID-19 outcomes. METHODS: We analyzed 2020-2021 data from the MarketScan Commercial and Health and Productivity Management databases, focusing on adults aged 18-64 years with continuous employer-sponsored private insurance, excluding pregnancy or capitated plans. We compared medical costs, healthcare utilization (emergency department [ED] visits, inpatient admissions, outpatient visits, and outpatient prescription drugs), and productivity losses (sick absences, short-term disability [STD], and long-term disability [LTD]) between individuals with and without hypertension, stratified by COVID-19 diagnosis. We used multivariable regression models, including an interaction term for hypertension and COVID-19 diagnosis, to estimate differences in outcomes, adjusting for demographics and comorbidities. RESULTS: Among 1,296,596 adults, 21% had hypertension. Those with hypertension were older, less likely female, less likely urban residents, and had more comorbidities. Excess medical costs associated with hypertension were $8,572 per patient over the two-year period (95% CI $8,182-$8,962). Patients with versus without hypertension had 0.200 (95% CI, 0.195-0.205) more ED visits, 0.081 (95% CI, 0.077-0.085) more inpatient admissions, 5.984 (95% CI, 5.892-6.075) more outpatient visits, and 20.25 (95% CI, 20.09-20.41) more prescriptions per patient over the two-year period. They also had more sick absences (1.13 days; 95% CI 0.93-1.34) and STD occurrences (3.88 days; 95% CI 3.56-4.20) per patient. Among those with hypertension, individuals with versus without COVID-19 had $3,495 (95% CI, $2,135-$4,856) higher medical costs and 2.588 (95% CI, 1.112-4.065) more STD days per patient over the two-year period. CONCLUSIONS: Hypertension was associated with higher medical costs, healthcare utilization, and productivity losses, exacerbated by COVID-19.

BACKGROUND: Many medications can have blood pressure (BP)-elevating effects, which might negatively impact BP control among people with hypertension. This study examines trends in prescription fills for BP-elevating and antihypertensive medications, individually and concurrently, among US individuals. METHODS: Quarterly trends of concurrent and individual fills for BP-elevating and antihypertensive medications were reported using the nationwide sample from IQVIA's Total Patient Tracker database, covering 94% of all retail prescription fills in the United States. We identified 1387 products containing BP-elevating medications and 240 products containing antihypertensive medications. Percentage change from Q1/2017 and average quarterly percent change from the joinpoint regression were used to present trends overall and by sex and age group (0-17, 18-44, 45-64, 65-74, and ≥75 years). RESULTS: From 2017 to 2023, fills remained stable for BP-elevating medications alone and increased for antihypertensive medications alone (9.5% increase; from 10.1% to 11.0%; P<0.001). Concurrent fills for antihypertensive and BP-elevating medications increased by 15.9% (from 5.4% to 6.2%; P<0.001). Fills for BP-elevating medications were higher among adult women compared with men; among women aged 18 to 44 years, this was primarily due to the use of combined oral contraceptives. In Q4/2023, fills for BP-elevating medications were most common among those aged 65 to 74 years (females=30.7%; males=20.4%). CONCLUSIONS: These results provide the first nationwide trends in concurrent prescription fills for BP-elevating and antihypertensive medications, indicating an increasing trend. Our findings might inform clinician decision-making regarding medication selection for patients with hypertension.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

Pyrazinamide (PZA) is a key first-line antituberculosis drug that plays an important role in eradicating persister Mycobacterium tuberculosis (TB) bacilli and shortening the duration of tuberculosis treatment. However, PZA-resistance is on the rise, particularly among persons with multidrug-resistant (MDR) tuberculosis. This nationwide study was conducted to explore the prevalence of mutations conferring PZA resistance, catalogue mutation diversity, investigate the associations of PZA resistance with specific lineages, examine co-resistance to 13 first- and second-line drugs, and evaluate the diagnostic accuracy of sequencing pncA and panD genes for predicting PZA resistance. Whole genome sequencing was performed on 2,207 M. tuberculosis isolates from 25 States and 4 Union Territories of India. The majority of phenotypically PZA-resistant isolates (77%) harbored 171 distinct mutations in pncA; however, a small number of mutations in panD, rpsA and clpC1 were also observed. A set of novel mutations associated PZA resistance was uncovered, along with an additional 143 PZA resistance-conferring mutations in pncA based on application of WHO-endorsed grading rules. PZA resistance was predominately observed in Lineage 2 and eight lineage-specific resistance markers were identified. Mutations distributed across pncA correlate to 94% of PZA resistance and were the predominant drivers of phenotypic resistance; evidence generated herein substantiates sequencing the entire gene and promoter for comprehensive genotypic-based prediction of PZA resistance. This work provides key insights into the scope of PZA-resistance in India, a high drug-resistant TB burden country, and can support the effectiveness of TB prevention and control efforts.

We studied the relationship of frailty and acute lower respiratory infection (ALRI) among a multi-site cohort of community-dwelling older adults aged ≥60 years in India. During January 2019‒January 2020, participants completed the Edmonton Frail Scale (EFS) at baseline and every 3 months at four sites in India, with each participant completing a maximum of four surveys. Participants were categorized as non-frail (0-5 points), vulnerable (6-7 points), and frail (≥8 points) based on EFS score. Project nurses made weekly home visits to identify ALRI episodes with onset during past 7 days. We estimated adjusted hazard ratios (aHR) for having an ALRI episode within 90 days after EFS by frailty category. We also assessed risk of deterioration of frailty during 7-100 days after ALRI episode onset in terms of an increased EFS score by ≥1 point and change of frailty category. Among 5801 participants (median age 65 years, 41% males), 3568 (61·5%) were non-frail, 1507 (26%) vulnerable, and 726 (12·5%) frail at enrolment. Compared with non-frail participants, the hazard of an ALRI episode was higher among vulnerable (aHR: 1·6, (95%CI 1·3-2.0) and frail participants (aHR: 1·7, 95%CI 1·3-2·2). Participants having ALRI within the past 7-100 days were at increased risk of worsening frailty category (aOR: 1.9, 95%CI 1·3-2.8) compared to participants without an ALRI episode during the same period. The association between ALRIs and worsened frailty suggests prevention of ALRIs through vaccination and other strategies may have broad reaching health benefits for older adults.

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

Bartonella quintana infection can cause severe disease that includes clinical manifestations such as endocarditis, chronic bacteremia, and vasoproliferative lesions of the skin and viscera. B. quintana bacteria is transmitted by the human body louse (Pediculus humanus corporis) and is associated with homelessness and limited access to hygienic services. We report B. quintana infection in 2 kidney transplant recipients in the United States from an organ donor who was experiencing homelessness. One infection manifested atypically, and the other was minimally symptomatic; with rapid detection, both recipients received timely treatment and recovered. B. quintana was identified retrospectively in an archived donor hematoma specimen, confirming the transmission link. Information about the organ donor's housing status was critical to this investigation. Evaluation for B. quintana infection should be considered for solid organ transplant recipients who receive organs from donors with a history of homelessness or of body lice infestation.

BACKGROUND: Hypertension affects nearly half of US adults yet remains inadequately controlled in over three-quarters of these cases. This study aimed to assess the association between adherence to antihypertensive medications and total medical costs, health care use, and productivity-related outcomes. METHODS AND RESULTS: We conducted cross-sectional analyses using MarketScan databases, which included individuals aged 18 to 64 years with noncapitated health insurance plans in 2019. Adherence was defined as ≥80% medication possession ratio for prescribed antihypertensive medications. We used a generalized linear model to estimate total medical costs, a negative binomial model to estimate health care use (emergency department visits and inpatient admissions), an exponential hurdle model to estimate productivity-related outcomes (number of sick absences, short-term disability, long-term disability), and a 2-part model to estimate productivity-related costs in 2019 US dollars. All models were adjusted for age, sex, urbanicity, census region, and comorbidities. We reported average marginal effects for outcomes related to antihypertensive medication adherence. Among 379 503 individuals with hypertension in 2019, 54.4% adhered to antihypertensives. Per person, antihypertensive medication adherence was associated with $1441 lower total medical costs, $11 lower sick absence costs, $291 lower short-term disability costs, and $69 lower long-term disability costs. Per 1000 individuals, medication adherence was associated with lower health care use, including 200 fewer emergency department visits and 90 fewer inpatient admissions, and productivity-related outcomes, including 20 fewer sick absence days and 442 fewer short-term disability days. CONCLUSIONS: Adherence to antihypertensives was consistently associated with lower total medical costs, reduced health care use, and improved productivity-related outcomes.

BACKGROUND: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. METHODS: In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. RESULTS: The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06-2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05-2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% - 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% - 24.1%) had the highest population attributable fraction for intussusception. CONCLUSION: Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Monoclonal antibodies are powerful therapeutic, diagnostic, and research tools. Methods utilized to generate monoclonal antibodies are evolving rapidly. We created a transfectable linear antibody expression cassette from a 2-h high-fidelity overlapping PCR reaction from synthesized DNA fragments. We coupled heavy and light chains into a single linear sequence with a promoter, self-cleaving peptide, and poly(A) signal to increase the flexibility of swapping variable regions from any sequence available in silico. Transfection of the linear cassette tended to generate similar levels to the two-plasmid system and generated an average of 47 μg (14-98 μg) after 5 days in 2 mL cultures with 15 unique antibody sequences. The levels of antibodies produced were sufficient for most downstream applications in less than a week. The method presented here reduces the time, cost, and complexity of cloning steps.

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.