INTRODUCTION: Since 2016, the US Food and Drug Administration (FDA) has required e-cigarette packaging and advertising to bear the warning: "WARNING: THIS PRODUCT CONTAINS NICOTINE. NICOTINE IS AN ADDICTIVE CHEMICAL." Nicotine has numerous adverse consequences besides addiction, including increased anxiety and depression symptoms that arise from nicotine withdrawal. We tested the effects of exposure to text-only e-cigarette package labels about the psychological consequences of nicotine withdrawal. AIMS AND METHODS: We randomized 1919 US young adults aged 18-24 years to view one of four warning label conditions: a no-message control, the current FDA warning, a message that "nicotine addiction can worsen depression and anxiety symptoms," and a message that "nicotine addiction is a source of stress." We explored associations between condition and intentions to use or quit e-cigarettes and perceived message effectiveness. RESULTS: Label condition was not associated with intentions to use or quit e-cigarettes. Intentions were equivalent among those who viewed the FDA label and those who viewed the no-message control. Compared with the FDA label, the depression/anxiety label and the stress label produced greater agreement among participants that the message "makes me concerned about nicotine addiction" after adjustment for sociodemographic characteristics; those who viewed the depression/anxiety label had greater agreement that the message "discourages me from wanting to use nicotine." CONCLUSIONS: While brief exposure to the warnings tested may not impact young adults' intentions to use or quit vaping, messages about stress, depression, and anxiety arising from nicotine addiction had higher perceived effectiveness among young adults than the FDA's current message about addictiveness. IMPLICATIONS: Findings from this randomized controlled experiment among US young adults suggest that warnings about the mental health consequences of nicotine addiction might be one type of message to consider including in a suite of required e-cigarette warnings and as part of a comprehensive effort to educate the public about the risks of commercial tobacco products.

Background: Bacterial meningitis is a severe syndrome with dynamic epidemiology, but assessments of current trends are limited. We aimed to describe changing epidemiologic patterns among common bacterial causes of meningitis in the United States. Methods: We analyzed data on bacterial meningitis cases caused by Streptococcus pneumoniae, group B Streptococcus (GBS), Haemophilus influenzae, Neisseria meningitidis, and Listeria monocytogenes in 10 U.S. surveillance sites. We compared incidence (cases per 100,000) across four epidemiologic periods: 2008–2009, 2010–2019, 2020–2021, and 2022–2023. Findings: We identified 5,032 bacterial meningitis cases; among those with outcome data, 11% (573/5028) died. S. pneumoniae was the dominant pathogen (59% [2922/5032]) throughout. However, GBS predominated among infants aged 0–2 months (85% [660/775]), the age group with the highest incidence. Between 2008–2009 and 2010–2019, overall bacterial meningitis incidence declined from 1.3 to 1.1, driven by decreases in S. pneumoniae meningitis caused by serotypes contained in the 13-valent pneumococcal conjugate vaccine (PCV13) and N. meningitidis meningitis. Meningitis caused by non-b H. influenzae strains increased during this period. During 2020–2021, incidence declined to 0.7, driven by decreases in S. pneumoniae, H. influenzae, and N. meningitidis meningitis, regardless of organism subtype. During 2022–2023, incidence increased to 1.0, driven by increases in S. pneumoniae and H. influenzae meningitis. Case fatality ratios remained stable throughout. Interpretation: Bacterial meningitis incidence rates have declined since 2008, with a notable low during 2020–2021, followed by a resurgence during 2022–2023. Case fatality remains high. Strategies that provide effective and broader pneumococcal and H. influenzae serotype protection and prevent infant GBS meningitis could reduce residual meningitis burden. Funding: U.S. Centers for Disease Control and Prevention. © 2025

The COVID-19 pandemic has been marked by continuous emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which those variants establish themselves in new geographic areas. We performed a discrete phylogeographic analysis on 18,529 sequences of the SARS-CoV-2 Omicron BA.5 sublineage sampled during February-June 2022 to elucidate emergence of that sublineage in different regions of the United States. The earliest BA.5 sublineage introductions came from Africa, the putative variant origin, but most were from Europe, matching a high volume of air travelers. In addition, we discovered extensive domestic transmission between different US regions, driven by population size and cross-country transmission between key hotspots. We found most BA.5 virus transmission within the United States occurred between 3 regions in the southwestern, southeastern, and northeastern parts of the country. Our results form a framework for analyzing emergence of novel SARS-CoV-2 variants and other pathogens in the United States.

OBJECTIVES: To evaluate the cost-effectiveness of testing and treatment for Mycobacterium tuberculosis (Mtb) infection among Asian and Hispanic persons with diagnosed diabetes in the United States. METHODS: We estimated population size and Mtb infection prevalence for Asian and Hispanic persons aged ≥15 years with diagnosed, non-gestational diabetes, by age and US-born-status. We assumed a one-time test for Mtb infection intervention, with positive-testing persons offered treatment. Using a deterministic, transmission-dynamic model of TB in the United States, we estimated costs, TB cases and deaths averted, and quality-adjusted life-years (QALY) gained under the intervention compared to no-intervention. We estimated incremental cost-effectiveness ratios (ICERs), calculated as costs per QALY-gained, from a TB health services perspective, including diagnosis and treatment for TB infection and disease. We also assessed health services and societal perspectives. We estimated 95% uncertainty intervals via probabilistic sensitivity analysis. RESULTS: TB cases averted per 100,000 persons tested ranged from 7.5 (95% uncertainty interval: 6.9-8.1) among US-born Hispanic persons to 238.9 (225.2-254.3) among non-US-born Asian persons. TB deaths averted per 100,000 persons tested ranged from 1.3 (1.2-1.4) among US-born Hispanic persons to 53.7 (51.4-56.1) among non-US-born Asian persons. ICERs for US-born Asian and Hispanic populations were $856,671 ($533,506-$1,234,032) and $1,081,646 ($673,142-$1,551,264), respectively. ICERs for non-US-born Asian and Hispanic populations were lower: $66,664 ($41,456-$93,625) and $68,749 ($43,136-$97,044), respectively. ICERs were 2-19% higher under a societal perspective. CONCLUSIONS: While the intervention produced health benefits for all populations assessed, health benefits were greater-and ICERs more favorable-for non-US-born Asian and Hispanic populations with diagnosed-diabetes.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

BACKGROUND: Centers for Disease Control and Prevention recommends test-of-cure (TOC) for persons with pharyngeal gonorrhea (GC) 7-14 days after treatment. We investigated the yield and feasibility of routine pharyngeal GC TOC to detect treatment failures. METHODS: During May 2021-July 2022, four U.S. STD clinics implemented pharyngeal GC TOC. Sites collected demographic, clinical, and behavioral data on all treated pharyngeal GC and positive TOC cases. Cases were dispositioned with the suspected reason for positive TOC. To assess perceived feasibility, sites participated in qualitative interviews. RESULTS: During the study period, 1,968 pharyngeal GC infections were diagnosed. Among 1,829 treated cases, 97.3% (n = 1,777) received ceftriaxone and 45.7% (n = 836) returned for TOC, varying by site (range: 35.5%- 70.8%). Among those with TOC, 4.7% (n = 39) were positive by NAAT. Of these, 48.7% had culture attempted; six positive TOC (15.4%) were also positive by culture. Most positive TOC (66.7%) were attributed to re-infection (n = 13) or false-positive results (n = 13). Six (15.4%) were treatment failures. Four failed recommended treatment and had a positive culture: two were susceptible to ceftriaxone and two did not have antimicrobial susceptibility results. Seven positive TOC (17.9%) had insufficient data to disposition. Sites perceived TOC to be feasible, though substantial resources were required.ConclusionRoutine pharyngeal GC TOC yielded 5% positivity, though treatment failure was rare (<1%), and no cases of cephalosporin-resistant GC were identified. Low TOC return rates, limited culture collection, and limited culture yield highlight challenges to determining the cause of a positive TOC and the limitations of TOC in identifying cephalosporin resistance.

BACKGROUND: Tuberculosis (TB) notifications and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends. METHODS: We identified four mechanisms potentially contributing to observed TB trends during 2020-2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons experiencing TB disease. We employed a Bayesian approach to synthesize evidence on how these mechanisms changed during the pandemic and how they might have combined to produce observed 2020-2023 TB data, using a transmission-dynamic model to link mechanisms to TB outcomes. We also simulated a no-pandemic-counterfactual scenario that assumed mechanisms followed pre-pandemic trends. We estimated TB outcomes associated with the pandemic until 2035 to capture lagged effects. We evaluated additional scenarios to estimate the individual effect of each mechanism. RESULTS: Over 2020-2035, we estimate an additional 2,784 (95% uncertainty interval: 2,164-3,461) TB notifications and 1,138 (1,076-1,201) TB deaths in the United States associated with changes occurring during the COVID-19 pandemic. Mechanisms had offsetting effects - decreases in TB diagnosis rates led to more TB deaths and notifications, while reductions in contact rates reduced TB deaths and notifications. Immigration changes initially reduced TB deaths, but increased deaths and notifications over time. Higher TB mortality rates increased TB deaths, but decreased TB notifications. CONCLUSIONS: While direct impacts of the COVID-19 pandemic occurred between 2020-2023, these changes may continue to influence TB incidence and mortality in future years.

BACKGROUND: Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both are important for developing improved vaccines. We estimated influenza infection incidence and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. METHODS: We conducted a prospective cohort study among children aged 6 to 23 months from May to October 2022. Study nurses collected symptom and temperature data and midturbinate nasal swabs twice weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza with polymerase chain reaction. RESULTS: Of 230 healthy screened children, 93 were enrolled, of whom 87 (94%) completed 6-month follow-up. In total, 95% (4245/4476) of scheduled nurses, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections, and 67% (9245/13 768) of scheduled symptom diaries were completed. Polymerase chain reaction-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 episodes and 1 (2%) had 3. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (IQR, 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregivers' diaries of reported and measured fever were 19% (25/73, 34%) and 11% (15/73, 21%) higher than nurse-reported (11/73, 15%) and nurse-measured (7/73, 10%) fever, respectively. CONCLUSIONS: The incidence of influenza infection was high and mainly symptomatic, suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

RATIONALE: Individuals surviving TB disease may experience chronic sequelae that reduce survival and quality-of-life. These post-TB sequalae are not generally considered in estimates of the health impact of TB disease. OBJECTIVES: To estimate the TB-attributable reductions in life expectancy and quality-adjusted life expectancy for individuals developing TB disease in the United States, including post-TB sequelae. METHODS: We extracted national surveillance data on individuals diagnosed with TB during 2015-2019, including demographics, vital status at diagnosis, treatment duration, treatment outcome, and co-prevalent conditions. Using a mathematical model we simulated life expectancy and quality-adjusted life-years (QALYs) for the TB cohort, as compared to a no-TB counterfactual (same distribution of age, sex, race/ethnicity, and co-prevalent conditions as the TB cohort but without TB-attributable mortality and disutility). We disaggregated results to report the proportion due to post-TB sequelae, and stratified outcomes by age, sex, and race. MEASUREMENTS AND MAIN RESULTS: Estimated life expectancy after TB diagnosis was 30.3 (95% uncertainty interval: 29.9, 30.7) years for the TB cohort versus 32.3 (31.9, 32.7) without TB, a difference of 2.03 (1.84, 2.21) years and 1.93 (1.69, 2.18) QALYs. Life-years lost were greatest for 65-74-year-olds versus other age groups, for men versus women, and for American Indian or Alaska Native individuals versus persons from other race/ethnicities. Overall, 41% (35, 46) of life-years and 48% (42, 54) of QALYs lost were estimated to result from post-TB sequelae. CONCLUSIONS: In the United States, a substantial fraction of the life-years and QALYs lost from TB are attributable to post-TB sequelae. Evidence is needed on approaches to prevent and repair post-TB lung damage, in the context of frequent co-prevalent health conditions.

BACKGROUND: In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB). OBJECTIVE: To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population. DESIGN: Model-based cost-effectiveness analysis. DATA SOURCES: Nationally representative surveys and published evidence. TARGET POPULATION: Medicare-eligible persons aged 65 years or older with at least 1 of 15 factors associated with elevated TB risk, as identified by guidelines from the U.S. Preventive Services Task Force (USPSTF) and other organizations. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time offer of LTBI testing and treatment versus no intervention. OUTCOME MEASURES: Lifetime TB cases and deaths averted, quality-adjusted life-years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: In 2022, there were an estimated 29.9 million Medicare-eligible persons (95% uncertainty interval [UI], 28.4 to 31.6 million persons) aged 65 years or older with elevated TB risks, including 14.7 million (95% UI, 13.4 to 16.0 million) with USPSTF-recommended factors. In the target population, 4.9 million persons (95% UI, 4.0 to 5.8 million persons) (16.4% [95% UI, 13.9% to 19.1%]) were estimated to have LTBI. Testing and treatment of LTBI was estimated to prevent 10 946 TB cases (95% UI, 4684 to 20 579 cases) and 2579 TB deaths (95% UI, 1106 to 4882 deaths), with 13 234 lifetime QALYs (95% UI, 5343 to 25 519 lifetime QALYs) gained. For the overall target population and for persons with USPSTF-recommended factors, ICERs were $192 000 (95% UI, $92 000 to $503 000) and $155 000 (95% UI, $77 000 to $393 000) per QALY gained, respectively. RESULTS OF SENSITIVITY ANALYSIS: The ICER was $109 000 (95% UI, $49 000 to $285 000) per QALY gained for 65-year-olds newly eligible for Medicare. LIMITATION: Health benefits from averted post-TB sequelae were not estimated. CONCLUSION: Medicare-eligible persons represent approximately one third of all U.S. persons with LTBI. Testing and treatment of LTBI in this population could lead to substantial reductions in TB and TB-related mortality, particularly among 65-year-olds newly eligible for Medicare. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4-6 months. sCJD in younger individuals is extremely rare. Here, we present a 21-year-old female who died with a sporadic prion disease. She presented with psychiatric symptoms followed by a rapidly progressive neurocognitive and motor decline. EEG was negative for periodic sharp wave complexes; however, brain MRI was suggestive of prion disease. The cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) assay was indeterminate. Neuropathologic examination at autopsy revealed severe neuronal loss and gliosis with secondary white matter degeneration but minimal spongiform changes and PrP deposits in the cerebellum and neocortex by immunohistochemistry. Absence of pathogenic mutations and methionine/valine heterozygosity at codon 129 of the prion protein gene (PRNP), atypical type 1 protease-resistant PrP that lacks or shows underrepresentation of the diglycosylated PrP isoform by western blot analysis, and no acquired prion disease risk factors resulted in a final diagnosis of atypical sCJD. Very young onset sCJD often has atypical clinical presentations and disease progression, neuropathological examination results, and/or laboratory test results that may confound diagnosis. It is critical to perform thorough, comprehensive evaluations to make an accurate diagnosis, which includes autopsy confirmation with histology, prion protein typing and prion gene sequencing.

IMPORTANCE: Health information technology, such as electronic health records (EHRs), has been widely adopted, yet accessing and exchanging data in the fragmented US health care system remains challenging. To unlock the potential of EHR data to improve patient health, public health, and health care, it is essential to streamline the exchange of health data. As leaders across the US Department of Health and Human Services (DHHS), we describe how DHHS has implemented fundamental building blocks to achieve this vision. OBSERVATIONS: Across DHHS, we have implemented 3 foundational building blocks called for by the 2016 21st Century Cures Act to create a unified approach for secure, high-quality, and timely exchange of health data across the health care system. The United States Core Data for Interoperability provides a minimum baseline for data elements that must be available in federally regulated health information technology systems such as certified EHRs. These data elements now must be accessible using Fast Healthcare Interoperability Resources-a secure, flexible, and open-industry standard for health data exchange. The Trusted Exchange Framework and Common Agreement provides a network to securely exchange health data across the country. The 3 building blocks of United States Core Data for Interoperability, Fast Healthcare Interoperability Resources, and Trusted Exchange Framework and Common Agreement are now in place thanks to diligent public and private sector work over 2 administrations. Across DHHS, we are working to refine these building blocks and increase their adoption through regulatory authorities, grants, and public-private partnerships. CONCLUSIONS AND RELEVANCE: The technological building blocks described in this article are creating a unified approach to health data exchange for patient access, clinical care, quality improvement, scientific research, public health, and other uses of health data. Collaborations between the public, nonprofit, and private sectors are needed to maximize their potential. By unlocking the potential of health data, these building blocks are the foundation of a 21st-century digital health care system that will improve the experience of patients and clinicians and result in better health outcomes.

BACKGROUND: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative. METHODS AND FINDINGS: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available. CONCLUSIONS: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

BACKGROUND: Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata. METHODS: We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection. We calculated the COI by household income strata and calculated the out-of-pocket (OOP) cost as a proportion of household income. RESULTS: We included 11 studies representing 11 LMICs. OOP expenses, as a proportion of annual household income, were highest among the lowest income quintile in 10 of 11 studies: in 4/4 studies among the general population, in 6/7 studies among children, 2/2 studies among older adults, and in the sole study for adults with chronic medical conditions. COI was generally higher for hospitalizations compared with outpatient illnesses; median OOP costs for hospitalizations exceeded 10% of annual household income among the general population and children in Kenya, as well as for older adults and adults with chronic medical conditions in China. CONCLUSIONS: The findings indicate that influenza and acute respiratory infections pose a considerable economic burden, particularly from hospitalizations, on the lowest income households in LMICs. Future evaluations could investigate specific drivers of COI in low-income household and identify interventions that may address these, including exploring household coping mechanisms. Cost-effectiveness analyses could incorporate health inequity analyses, in pursuit of health equity.

Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination.

Before October 2024, the Advisory Committee on Immunization Practices (ACIP) recommended use of a pneumococcal conjugate vaccine (PCV) for all adults aged ≥65 years, as well as for those aged 19-64 years with risk conditions for pneumococcal disease who have not received a PCV or whose vaccination history is unknown. Options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals) or 21-valent PCV (PCV21; CAPVAXIVE; Merck Sharp & Dohme) alone or 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme). There are additional recommendations for use of PCV20 or PCV21 for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on expanding the age-based PCV recommendation to include adults aged 50-64 years. On October 23, 2024, ACIP recommended a single dose of PCV for all PCV-naïve adults aged ≥50 years. Recommendations for PCVs among adults aged 19-49 years with risk conditions and PCV13-vaccinated adults have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides updated clinical guidance for use of PCV.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Legionnaires disease is a serious pneumonia caused by Legionella bacteria. During November 2022-June 2024, CDC was notified of 12 cases of Legionnaires disease among travelers on two cruise ships; eight on cruise ship A and four on cruise ship B. CDC, in collaboration with the cruise lines, initiated investigations to ascertain the potential sources of on-board exposure after notification of the second potentially associated case for each ship. Epidemiologic data collected from patient interviews and environmental assessment and sampling results identified private hot tubs on selected cabin balconies as the most likely exposure source. To minimize Legionella growth, both cruise lines modified the operation and maintenance of these devices by removing the heating elements, draining water between uses, and increasing the frequency of hyperchlorination and cleaning. Hot tubs offer favorable conditions for Legionella growth and transmission when maintained and operated inadequately, regardless of location. Private hot tubs on cruise ships are not subject to the same maintenance requirements as are public hot tubs in common areas. Given the range of hot tub-type devices offered as amenities across the cruise industry, to reduce risk for Legionella growth and transmission, it is important for cruise ship water management program staff members to inventory and assess private balcony hot tubs and adapt public hot tub maintenance and operations protocols for use on private outdoor hot tubs.

We evaluated HIV DNA levels in individuals who received long-acting cabotegravir (CAB-LA) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis in the HPTN 083 and 084 trials and had HIV DNA testing performed to help determine HIV status. HIV DNA testing was performed using peripheral blood mononuclear cell (PBMC) samples collected after a reactive HIV test was obtained at a study site. DNA was quantified using droplet digital PCR (lower limit of detection [LLOD]: 4.09 copies/million PBMCs). Final HIV status and the timing of the first HIV-positive visit were determined by an independent adjudication committee based on HIV test results from real-time site testing and retrospective testing at a centralized laboratory. HIV DNA testing was performed for 133 participants [21 HIV-positive (7 CAB-LA arm, 14 TDF/FTC arm) and 112 HIV-negative; 1-6 tests/person]. For persons with HIV, the time between the first HIV-positive visit and collection of the first sample for DNA testing was a median of 81 days for those receiving CAB-LA (range 41-246) and 11 days for those receiving TDF/FTC (range 3-127). Four (57.1%) of the seven CAB-LA cases with infection had a low initial DNA result [three detected <LLOD; one near the LLOD (4.2 copies/10(6) PBMCs); in 2/4 cases, the DNA level was still <10 copies/10(6) PBMCs ≥40 weeks after the first HIV-positive visit. In contrast, only 3/14 (21.4%) of the TDF/FTC cases had a low or negative initial DNA test result (one not detected; two <10 copies/10(6) PBMCs). In this study, the time between the first HIV-positive visit and the first DNA test was longer in the CAB-LA cases than the TDF/FTC cases. Despite this difference, low or undetectable DNA levels were more frequently observed in the CAB-LA cases. This suggests that CAB-LA exposure may limit seeding of the HIV reservoir in early infection.

INTRODUCTION: Exposure to unfavorable environmental conditions during pregnancy, such as extreme heat and air pollution, has been linked to increased risk of stillbirth, defined as fetal mortality at or after 20 weeks' gestation, however no studies have examined its association with social vulnerability. We examined associations between county-level stillbirth rates, environmental risk factors for stillbirth, and social vulnerability in the United States. METHODS: This ecologic study linked county-level data from three nationwide datasets on stillbirths (National Vital Statistics System), environmental conditions (North American Land Data Assimilation System and Environmental Protection Agency), and social vulnerability (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index). Poisson and negative binomial models were fit to the variables and produced rate ratios to estimate associations among stillbirth rates, environmental risk factors, and social vulnerability. RESULTS: Social vulnerability was positively associated withn stillbirth rates, annual average number of extreme heat days, and ambient concentration of particulate matter ≤ 2.5 μm in diameter (PM2.5). The average number of days that ozone and PM2.5 each exceeded regulatory standards were not associated with stillbirth rates or social vulnerability. A positive association between average annual PM2.5 concentration and stillbirth rates was detected; no other significant associations between environmental risk factors and stillbirth rates were observed. DISCUSSION: We found evidence of associations between social vulnerability and stillbirth rates, and between social vulnerability and environmental risk factors for stillbirth at the county level. Further research could inform understanding of how social vulnerability impacts the relationship between environmental exposures and stillbirth risk.

Despite advances in HIV care and treatment in the U.S., disparities in outcomes along the HIV care continuum persist. The widespread replication of effective and sustainable interventions that prioritize the engagement of underserved populations has been identified as a promising path to ending the HIV epidemic in the U.S. Intervention dissemination products, however, rarely provide the comprehensive and accessible information needed to replicate interventions within community settings. To bridge the divide between research and community-based implementation, the Using Evidence-informed Interventions to Improve Health Outcomes among People Living with HIV (E2i) initiative-grounded in the HIV/AIDS Bureau Implementation Science Framework-created a suite of tools to promote the rapid replication of interventions focused on transgender women, Black men who have sex with men, behavioral health integration, and identifying and addressing trauma. The resulting dissemination products are detailed and digestible multimedia toolkits that follow adult learning theory principles and align with the Template for Intervention Description and Replication criteria for adapting non-pharmacological interventions. Each E2i toolkit consists of five components: implementation guides, narrative videos of site implementation, best practice demonstration videos, interactive learning modules, and recruitment posters and brochures. Over 2 years (2022-2024), the E2i toolkit webpages amassed 7703 unique users and 17,666 pageviews. These toolkits can serve as a blueprint for designing comprehensive and accessible dissemination products for replication of HIV interventions in care settings. Dissemination products that bridge the gap between intervention research and replication in community settings are a crucial missing tool for ending the HIV epidemic.

BACKGROUND: Identifying risk factors for respiratory syncytial virus (RSV)-associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions. METHODS: Using surveillance data from South Africa (2012-2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis. RESULTS: RSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2-4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5-125.8), malnutrition (aOR 1.9; 95% CI 1.2-3.2), prematurity (aOR 2.4; 95% CI 1.3-4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9-174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5-24 years (aOR 10.7; 95% CI 1.1-107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1-6.3), underlying illness (aOR 2.7; 95% CI 1.5-26.1) and LWH (aOR 16.8, 95% CI: 4.8-58.2). CONCLUSION: Individuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions. CLINICAL TRIAL NUMBER: Not applicable, this is not a clinical trial.

Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations.

BACKGROUND: COVID-19 vaccine effectiveness (VE) studies leveraging systematic surveillance in sub-Saharan Africa are limited. We assessed the effectiveness of two vaccines (Pfizer BNT162b2 and Johnson & Johnson Ad26.COV2.S) against SARS-CoV-2-associated hospitalization in South African adults aged ≥18 years. METHODS: We conducted a test-negative case-control study using pneumonia surveillance data in South Africa. Inpatients with physician-diagnosed lower respiratory tract infection or suspected COVID-19, testing SARS-CoV-2 positive or negative from June 2021-March 2022, were cases or controls, respectively. Fully vaccinated individuals received one Ad26.COV2.S dose or two BNT162b2 doses ≥14-days before enrollment. VE was estimated using multivariable logistic regression for Delta- and Omicron BA.1/BA.2-predominant periods, stratified by age and HIV status. RESULTS: The study included 925 cases and 1890 controls; 38 (4%) cases and 186 (10%) controls were fully vaccinated with BNT162b2, and 30 (3%) cases and 94 (5%) controls with Ad26.COV2.S. The vaccine effectiveness of BNT162b2 against SARS-CoV-2-associated hospitalization over Delta and Omicron BA.1/BA.2 periods was 91% (95% CI: 52%, 98%) and 33% (-16%, 86%), respectively. The vaccine effectiveness of Ad26.COV2.S against hospitalization over Delta and Omicron BA.1/BA.2 periods was 72% (-36% ,94%), and -19% (-130%, 39%), respectively. The vaccine effectiveness of BNT162b2 against hospitalization over the Delta period was 94% (50%, 99%) and 89% (27%, 98%) among adults aged ≥60 years and HIV-uninfected, respectively. CONCLUSIONS: The BNT162b2 vaccine was effective against SARS-CoV-2-associated hospitalization during the Delta period for adults aged ≥18 years, ≥60 years and those HIV-uninfected. VE for Ad26.COV2.S was inconclusive, potentially due to limited sample size or residual confounding. These findings highlight the utility of sentinel surveillance for estimating VE.