INTRODUCTION: Significant differences exist in the risk of diabetes and diabetes-related complications by income level in the United States. We assessed 1) to what extent medical expenditures in total and by health service type differ by income levels, and 2) how demographic and socioeconomic factors and health status are associated with these differences. METHODS: Data from the 2017 through 2021 Medical Expenditure Panel Survey were analyzed to estimate annual per-person medical expenditures for adults with diabetes. These expenditures were categorized by service type (inpatient, outpatient, prescription, home health care services, emergency department, or other) and compared across income groups based on the federal poverty level (FPL): poor (<125% FPL), low (125% to <200% FPL), middle (200% to <400% FPL), and high (>/=400% FPL). One-way analysis of variance was used to test group differences, and a regression-based decomposition identified factors driving expenditure disparities. All expenditures were adjusted to 2021 US dollars. RESULTS: Mean total medical expenditures were significantly higher for the poor-income group compared with the low-income, middle-income, and high-income groups, though no significant differences were observed among the latter 3 groups. Prescription drugs and home health care services in the poor-income group accounted for most of this difference. Key factors associated with the higher expenditures in this group included elevated disability rates, poorer physical health status, and dual Medicaid-Medicare coverage. CONCLUSION: Adults with diabetes from the poorest households incurred the highest medical expenditures, largely driven by poor physical health and higher rates of disability. Reducing disability and improving health outcomes for this group may help lower their medical expenses.

BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are genetically related viruses and major causes of medically attended acute respiratory illness in children. Research comparing the severity of illnesses resulting from these infections lacks consensus. METHODS: Children younger than 18 years with acute respiratory illness were enrolled through active, prospective surveillance from 2016 to 2020 at 7 US pediatric hospitals and emergency departments (EDs). Clinical information was obtained from parent interviews and medical records. Midturbinate nasal swabs were collected and tested for RSV and HMPV using molecular diagnostic assays at each site. We compared descriptive and clinical features of children with RSV or HMPV and calculated adjusted odds ratios (aOR) for severe outcomes comparing RSV with HMPV. Risk factors for severe outcomes were assessed in children with RSV or HMPV using logistic regression models. RESULTS: A total of 5329 children hospitalized with RSV (n = 4398) or HMPV (n = 931) and 3276 children with RSV-associated (n = 2371) or HMPV-associated (n = 905) ED visits were enrolled. The median age of children hospitalized with RSV was lower than that of children with HMPV (7 months vs 16 months, P < .0001). Children presenting to the ED with RSV-associated acute respiratory illness had higher odds of being hospitalized than children with HMPV (aOR, 1.68; 95% CI, 1.50-1.87), with the highest odds in infants younger than 6 months (aOR, 3.27; 95% CI, 2.53-4.23). Underlying conditions were more than twice as common among infants hospitalized with HMPV (26%) than those with RSV (11%). CONCLUSIONS: Children with HMPV-associated hospitalization tend to be older and more likely to have underlying medical conditions compared with children with RSV-associated hospitalization.

Seasonal influenza causes 290,000-650,000 deaths annually, with vaccination efficacy ranging from 10 to 60%. The emergence of drug-resistant and highly pathogenic avian influenza viruses underscores the urgent need for novel protective strategies. Epidemiological observations have long suggested that certain vaccines, such as Bacillus Calmette-Guérin (BCG), can provide protection against diverse pathogens (S. Biering-Sørensen, P. Aaby, N. Lund, et al., Clin Infect Dis 65:1183-1190, 2017, https://doi.org/10.1093/cid/cix525; M.-L. Garly, C. L. Martins, C. Balé, et al., Vaccine 21:2782-2790, 2003, https://doi.org/10.1016/s0264-410x(03)00181-6; C. A. G. Timmermann, S. Biering-Sørensen, P. Aaby, et al., Trop Med Int Health 20:1733-1744, 2015, https://doi.org/10.1111/tmi.12614). While the cellular and molecular mechanisms underlying such protection remain incompletely understood, emerging research offers critical insights into innate immune system modulation (B. Cirovic, L. C. J. de Bree, L. Groh, et al., Cell Host Microbe 28:322-334, 2020, https://doi.org/10.1016/j.chom.2020.05.014; L. Kong, S. J. C. F. M. Moorlag, A. Lefkovith, et al., Cell Rep 37:110028, 2021, https://doi.org/10.1016/j.celrep.2021.110028; H. Mohammadi, N. Sharafkandi, M. Hemmatzadeh, et al., J Cell Physiol 233:4512-4529, 2018, https://doi.org/10.1002/jcp.26250; S. J. C. F. M. Moorlag, Y. A. Rodriguez-Rosales, J. Gillard, et al., Cell Rep 33:108387, 2021, https://doi.org/10.1016/j.celrep.2020.108387). We investigated whether a trained innate immune system with non-replicating adenoviruses could provide protection against diverse influenza virus strains. We demonstrated that replication-defective human adenoviruses can effectively train the innate immune system, conferring protective immunity in mice against multiple influenza virus strains, including H1N1, H3N2, H5N2, H7N9, and H9N2. In addition, bovine and chimpanzee adenoviruses can also activate human innate lymphoid cells (ILCs) and confer protection against challenge with influenza H3N2 virus in mice. Remarkably, this protection occurs in the complete absence of influenza-specific adaptive immune responses (influenza virus-specific hemagglutination-inhibiting antibodies, neutralizing antibodies, and influenza nucleoprotein-specific CD8 T cells). Key protective mechanisms include increased activation of ILC1, ILC2, and ILC3 populations, enhanced expression of interferon-stimulated genes (ISGs), upregulation of antiviral signaling pathways, and metabolic reprogramming of ILC subsets. Adoptive transfer experiments demonstrated that trained ILCs were sufficient to protect against influenza H1N1 infection in ILC-deficient mice. This research establishes a novel strategy for enhancing innate antiviral immunity, offering broad-spectrum protection against diverse influenza strains, a promising approach for not only pandemic preparedness but also against emerging infectious diseases. Training innate lymphoid cells through non-replicating adenoviral vectors represents a promising approach to enhancing broad-spectrum antiviral immunity, complementing traditional vaccination strategies.IMPORTANCEThe findings represent a potential game-changer for fighting influenza, which kills hundreds of thousands of people worldwide each year despite our best vaccination efforts. Current flu vaccines often provide limited protection because they must be reformulated annually to match circulating strains, and their effectiveness varies dramatically from year to year. The scientists discovered something remarkable: common adenoviruses (which typically cause mild cold-like symptoms) can essentially "train" our immune system's first line of defense to recognize and fight off multiple types of flu viruses simultaneously. This protection works through a completely different mechanism than traditional vaccines-it does not rely on creating specific antibodies against flu proteins. Instead, the treatment activates special immune cells called innate lymphoid cells (ILCs), which act like the body's rapid response team. These trained cells provide broad protection against various flu strains, including dangerous bird flu variants that could cause future pandemics. The significance lies in potentially creating a universal flu protection strategy that could work against unknown future flu strains, offering hope for better pandemic preparedness and reducing seasonal flu's devastating global impact.

Researchers need enhanced analytical techniques to profile and characterize tissue and cellular proteomes in studying nanogram scale peptide samples. To meet this demand, nanoflow liquid chromatography (nLC) and mass spectrometry (MS) work has focused on method development, while improvements are made in new cell sorting and isolation instrumentation. In this article, we describe improvements in peptide and protein identifications using simple, cost-effective changes to common mass spectrometry procedures. We focused on procedures that used an Orbitrap instrument to analyze 1 nanogram of peptide material or less. We found protein identifications increased over 40% when applying lowered precursor intensity thresholds in data-dependent selection. We also demonstrate improvements in identifying late-eluting peptides using sample diluents containing n-dodecyl-β-D-maltoside (DDM). We also show lower nLC flow rates can enhance protein identifications over 20%. Finally, we report improvements of 18% in peptide identifications when multiple high-field asymmetric waveform ion mobility spectrometry (FAIMS) compensation voltages (CV) are applied within a single method. These simple modifications provide researchers with options to improve peptide detection in very limited or low concentration samples.

BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC. METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as ≥3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage. RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics. CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.

Pertussis is a respiratory disease caused by the bacterium Bordetella pertussis. Acellular pertussis (aP) vaccines replaced more reactogenic whole-cell pertussis (wP) vaccines in the United States in the 1990s. Despite high rates of vaccination, a slow but consistent increase in the number of U.S. pertussis cases was observed starting in the 1980s that accelerated following the introduction of aP vaccines. Most aP vaccines contain pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN), and some contain fimbriae (FIM 2/3). Countries that transitioned into aP vaccines have observed increasing rates of pertactin-negative (PRN(NEG)) clinical isolates, exceeding 85% in some countries. This outcome suggests B. pertussis does not require PRN, and immune responses against PRN may impact B. pertussis circulation. With the high prevalence of PRN(NEG) strains circulating in the United States, we sought to identify an acceptable PRN(NEG) strain for use in baboon challenge studies and controlled human infection model (CHIM) studies. Baboons were challenged with the PRN-positive (PRN(POS)) strain D420 or one of three PRN(NEG) strains selected to represent the genetic diversity of B. pertussis strains circulating in the United States. Despite comparable levels of colonization between the animals infected with the PRN(NEG) strains and D420, there was variability between the three PRN(NEG) strains with respect to virulence, and two of the three strains appeared reduced in one or more measures of virulence. These findings suggest that some PRN(NEG) clinical isolates may be less virulent than D420 and suggest care should be taken when selecting strains for baboon and CHIM studies.IMPORTANCEWith the increased circulation of Bordetella pertussis PRN(NEG) strains in countries using acellular pertussis (aP) vaccines, understanding the epidemiology and pathogenesis of PRN(NEG) strains is critical. Our results suggest that virulence varies between circulating PRN(NEG) strains, with some strains appearing to be less virulent than PRN(POS) strains. These results tell us that care should be taken when selecting PRN(NEG) pertussis strains for baboon and CHIM studies. Our results may also support the continued use of PRN in aP vaccines. If PRN(NEG) strains are less virulent and induce less severe disease than PRN(POS) strains, maintaining vaccine selective pressure against PRN(POS) strains may be beneficial.

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S. METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data. RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings. CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research. POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.

BACKGROUND: High and increasing syphilis rates among American Indian/Alaska Native (AI/AN) communities and particularly among AI/AN women and infants call for immediate interventions to reach and offer syphilis testing to sexually active populations paired with timely treatment. METHODS: The Great Plains Tribal Epidemiology Center within the Great Plains Tribal Leaders Health Board (GPTLHB) partnered with a local non-tribal healthcare facility to offer free community-based syphilis testing in Rapid City, South Dakota, starting in December 2022 through June 2024. Participants received cash incentive cards for undergoing testing for syphilis, human immunodeficiency virus (HIV) and hepatitis C (HCV). RESULTS: Fifteen community testing events were conducted. Laboratory-based syphilis testing was performed on 1434 unique individuals, average age 38.8 years. Seventy-six (76) people were diagnosed with syphilis that had previously not been identified (prevalence 5.3% (76/1434); 51 (67.1%) were female. Treatment was provided to 80.3% of people with syphilis (61/76) within an average of 36 days. In total, the 15 events cost $158,019 ($75,000 administrative staff time + $5,100 laboratory staff time + $24,009 lab tests + $ 53,910 incentives) or $88 per test performed ($158,019/1797). The cost to identify a previously unidentified case was $$2,079 ($158,019/76 newly identified infected persons). CONCLUSIONS: This community-based screening event revealed high prevalence of undiagnosed syphilis. Incentives supported community members to access screening services. Collaborations between clinical, tribal, and public health entities to bring diagnosis and treatment services to patients using a community-based approach have clear benefits but need ongoing supportive resources to be maintained.

OBJECTIVE: During the COVID-19 pandemic, the United States Centers for Disease Control and Prevention provided strategies, such as extended use and reuse, to preserve N95 filtering facepiece respirators (FFR). We aimed to assess the prevalence of N95 FFR contamination with SARS-CoV-2 among healthcare personnel (HCP) in the Emergency Department (ED). DESIGN: Real-world, prospective, multicenter cohort study. N95 FFR contamination (primary outcome) was measured by real-time quantitative polymerase chain reaction. Multiple logistic regression was used to assess factors associated with contamination. SETTING: Six academic medical centers. PARTICIPANTS: ED HCP who practiced N95 FFR reuse and extended use during the COVID-19 pandemic between April 2021 and July 2022. PRIMARY EXPOSURE: Total number of COVID-19-positive patients treated. RESULTS: Two-hundred forty-five N95 FFRs were tested. Forty-four N95 FFRs (18.0%, 95% CI 13.4, 23.3) were contaminated with SARS-CoV-2 RNA. The number of patients seen with COVID-19 was associated with N95 FFR contamination (adjusted odds ratio, 2.3 [95% CI 1.5, 3.6]). Wearing either surgical masks or face shields over FFRs was not associated with FFR contamination, and FFR contamination prevalence was high when using these adjuncts [face shields: 25% (16/64), surgical masks: 22% (23/107)]. CONCLUSIONS: Exposure to patients with known COVID-19 was independently associated with N95 FFR contamination. Face shields and overlying surgical masks were not associated with N95 FFR contamination. N95 FFR reuse and extended use should be avoided due to the increased risk of contact exposure from contaminated FFRs.

INTRODUCTION: Nationally representative estimates of mental health symptoms and services in adults with kidney disease are limited. The objective of this study was to examine the mental health status and use of health care among adults with and without kidney disease. METHODS: We used data from the 2021 National Health Interview Survey. Diagnosed kidney disease is based on adults who reported ever being told by a doctor or other health professional that they had weak or failing kidneys. The survey question captures data on adults who are aware of having kidney disease and most likely have advanced kidney disease. Mental health measures examined were serious psychological distress (SPD), current symptoms of anxiety and depression, diagnosed anxiety and depressive disorder, prescription medication use for these disorders, and receipt of counseling. We used logistic regression models, with predicted marginal proportions, to calculate unadjusted and adjusted prevalence ratios, controlling for sociodemographic and health characteristics. RESULTS: About 2.9% of adults reported having a diagnosis of kidney disease; prevalence varied by sociodemographic and health characteristics. The prevalence of SPD; current symptoms of anxiety or depression or both; history of diagnosed anxiety or depression or both; and receiving counseling and prescription use for these disorders were higher among adults with kidney disease than among adults without kidney disease. In multivariable models adjusted for sociodemographic and health characteristics, adults with diagnosed kidney disease remained more likely than adults not diagnosed with kidney disease to experience mental health conditions and receive counseling. CONCLUSION: A survey of the US population found a higher prevalence of poor mental health and receipt of mental health care among people diagnosed with kidney disease than among people not diagnosed with kidney disease.

BACKGROUND: Hypoxaemia predicts mortality at all levels of care, and appropriate management can reduce preventable deaths. However, pulse oximetry and oxygen therapy remain inaccessible in many primary care health facilities. We aimed to develop and validate a simple risk score comprising commonly evaluated clinical features to predict hypoxaemia in 2-59-month-old children with pneumonia. METHODS: Data from seven studies conducted in five countries from the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) dataset were included. Readily available clinical features and demographic variables were used to develop a multivariable logistic regression model to predict hypoxemia (oxygen saturation <90%) at presentation to care. The adjusted log coefficients were transformed to derive the PREPARE hypoxemia risk score and its diagnostic value was assessed in a held-out, temporal validation dataset. The model and risk score were analysed by evaluating the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: We included 14 509 children in the analysis; 9.8% (n=2515) were hypoxemic at presentation. The multivariable regression model to predict hypoxemia included age, sex, respiratory distress (nasal flaring, grunting and/or head nodding), lower chest indrawing, respiratory rate, body temperature and weight-for-age z-score. The model showed fair discrimination (AUC 0.70, 95% CI 0.67 to 0.73) and calibration in the validation dataset. The simplified PREPARE hypoxaemia risk score includes five variables: age, respiratory distress, lower chest indrawing, respiratory rate and weight-for-age z-score. CONCLUSION: The PREPARE hypoxemia risk score, comprising five easily available characteristics, has the potential to be used to identify hypoxemia in children with pneumonia with a fair degree of certainty for use in health facilities without pulse oximetry. Its implementation would require careful consideration to limit the burden of inappropriate referrals on patients and the health system. Further external validation in community settings in low- and middle-income countries is required.

Tobacco cigarette smoking is the leading cause of preventable diseases and death in the US. Exposure to secondhand smoke (SHS) can also cause heart disease, lung cancer, and respiratory illness. Cotinine (COT) and trans-3'-hydroxycotinine (HCT) are the primary metabolites of nicotine, the main addictive alkaloid in tobacco products. For many years, we have measured serum levels of COT and HCT in National Health and Nutritional Examination Survey (NHANES) participants to monitor exposure of the U.S. population to active smoking and SHS. As exposure to SHS is decreasing, a more sensitive analytical method is needed to detect the lower levels of these biomarkers for SHS assessment. We developed and validated a new automated method for the detection of COT and HCT in human serum. We implemented a new liquid handling automation system to aliquot and prepare samples using supported liquid extraction. Samples were analyzed by liquid chromatography-tandem mass spectrometry. The new automated sample preparation method increases sample throughput by reducing sample cleanup time to 2 hours for preparing a 96-well plate. The method has excellent sensitivity, specificity, precision (<10%), and accuracy (±15%). We were able to lower the estimated limit of detection (LOD) for COT by 33% and HCT by 73% from our previous LOD. The new LODs for COT and HCT are 0.010 ng/mL and 0.004 ng/mL, respectively. These lower LODs would enable better detection of SHS in future NHANES surveys.

Antiviral susceptibility of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Response System. This study describes a global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs, oseltamivir, zanamivir, peramivir, laninamivir) and the cap-dependent endonuclease inhibitor (CENI, baloxavir) for three periods (May to May for 2020-2021, 2021-2022 and 2022-2023). In particular, global influenza activity declined significantly in 2020-2021 and 2021-2022 when compared to the pre-pandemic period of COVID-19. Combined phenotypic and NA sequence-based analysis revealed that the global frequency of seasonal influenza viruses with reduced or highly reduced inhibition (RI/HRI) by NAIs remained low, 0.09% (2/2224), 0.12% (27/23465) and 0.23% (124/53917) for 2020-2021, 2021-2022 and 2022-2023, respectively. As in previous years, NA-H275Y in A(H1N1)pdm09 viruses was the most frequent substitution causing HRI by oseltamivir and peramivir. Sequence-based analysis of polymerase acidic (PA) protein supplemented with phenotypic testing revealed low global frequencies of seasonal influenza viruses with reduced susceptibility (RS) to baloxavir, 0.07% (1/1376), 0.05% (9/18380) and 0.12% (48/39945) for 2020-2021, 2021-2022 and 2022-2023, respectively; commonly associated substitutions were PA-I38T/M/L. In Japan, the rate was 3.3% (16/488) during 2022-2023, with 11 A(H3N2) viruses having PA-I38T/M substitutions. For zoonotic viruses, 2.7% (3/111) contained substitutions, one each NA-H275Y, NA-S247N and NA-N295S, associated with RI/HRI NAI phenotypes, and none contained PA substitutions associated with RS to baloxavir. In conclusion, the great majority of seasonal and zoonotic influenza viruses remained susceptible to NAIs and CENI baloxavir.

The purpose of this study was to determine the feasibility of facility-level wastewater surveillance in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in skilled nursing facility (SNF) wastewater using three concentration methods, as well as a proof-of-concept for antimicrobial resistance (AR) genes/organisms detection. Wastewater effluent samples were collected from an SNF over an 8-week period. Wastewater was concentrated using electronegative membrane filtration (enMF), polyethylene glycol precipitation, and Nanotrap(®) magnetic virus particles (NP). Quantification of the genome copy concentration from SARS-CoV-2 and bovine respiratory syncytial virus (BRSV), a SARS-CoV-2 surrogate spiked into all samples, was performed with droplet digital polymerase chain reaction (ddPCR). Wastewater sample aliquots were also enriched in microbiological culture media and screened for organisms with AR phenotypes on selective and differential agars. Multiplex real-time PCR was used to detect a broad array of carbapenem resistance genes. SARS-CoV-2 was detected and quantified from a single enMF-concentrated wastewater sample. The highest concentration of BRSV came from enMF-concentrated samples. Klebsiella, Enterobacter, Citrobacter, and Escherichia coli exhibiting AR phenotypes were successfully detected using culture-dependent approaches. Culture-independent, multiplex PCR indicated that bla(KPC) was the main carbapenemase gene detected in wastewater samples. Facility-level wastewater surveillance could be a useful strategy for SNFs.

Current seasonal influenza vaccines offer strain-specific protection and, thus, are less effective against mismatched strains. A broadly protective influenza vaccine is desirable to provide comprehensive protection against a wide range of influenza viruses for seasonal and pandemic influenza preparedness. Here, we evaluated the vaccine candidates based on bovine adenoviral (BAd) vectors expressing nucleoprotein (NP) of influenza A (BAd-C5-NP/A) and B (BAd-C5-NP/B) viruses linked to the autophagy-inducing peptide C5 (AIP-C5 or C5) to develop a predominantly T-cell-based vaccine. Robust cellular immune responses and humoral responses were elicited in mice with a single intranasal inoculation. Mice immunized with the BAd Bivalent (BAd-C5-NP/A + BAd-C5-NP/B) vaccine formulation exhibited protective immunity, providing protection against a broad panel of homosubtypic and heterosubtypic influenza A and B viruses, as evidenced by the absence of morbidity and mortality, along with significant reductions in lung viral titers. Protective immunity against seasonal influenza viruses was observed in ferrets following the BAd Bivalent vaccine immunization. These findings support further investigation of the potential of a unique Ad vaccine platform for mucosal immunization expressing NP linked to AIP-C5 as a broadly protective influenza vaccine. © 2025 The Author(s)

Background: Malaria is a mosquito borne disease caused by parasites of the genus Plasmodium. In 2023, the United States (US) experienced nine cases of autochthonous Plasmodium vivax malaria transmission; seven in Florida, one in Texas, and another in Arkansas. These were the first autochthonous cases since 2003 when a cluster was identified in Florida. The aim of this study was to genetically characterize the implicated P. vivax isolates in order to complement epidemiologic investigations of these cases. Methods: A custom Illumina AmpliSeq sequencing panel capturing 495 amplicons was designed. This panel was used to ascertain whether these 2023 cases were related, and assess if they were associated with a single or separate introduction events. Sequence data were hierarchically clustered and a Naïve Bayes classification approach was used to assign genotypes to a probable geographic origin based on 113 ‘geo-informative’ SNPs captured by the panel. Genotypes associated with the 2023 Arkansas, Texas, and Florida cases were clustered alongside those sequenced from archived blood samples from the 2003 Florida case-patients, a set of reference strains, and other travel-associated specimens. Microsatellite analysis was performed on a subset of samples from these autochthonous cases to complement the AmpliSeq analysis. Findings: The 2023 autochthonous Florida cases were genetically linked as were the 2003 Florida cases. The 2023 and 2003 Florida clusters were genetically distinct, and the two Florida clusters were distinct from the 2023 Texas and Arkansas cases, which were also distinct from each other. These genotypes classified to the Central or South American region using the Naïve Bayes classifier, including those from the 2003 cluster. Interpretation: These data support that at least three distinct P. vivax introduction events in the US in 2023, involving parasites possessing genetic signatures consistent with Central or South America. Funding: This work was supported by the National Center for Emerging and Zoonotic Infectious Diseases at the US Centers for Disease Control and Prevention. © 2025

INTRODUCTION: Given the increasing usage of vaping during pregnancy and limited longitudinal health-related data, there is an urgent need to assess the potential risks of vaping. AIMS AND METHODS: A cross-sectional study was conducted among pregnant UK adults (n = 140). Five study groups were purposively recruited: exclusive-smokers (n = 38), exclusive-vapers (former smokers) (n = 35), dual users of smoking and vaping (n = 25), dual users of smoking and nicotine replacement therapy (n = 10), and "never-users" of nicotine or tobacco products (n = 32). Sociodemographic, smoking, and vaping characteristics were assessed. Participants' urine samples were analyzed for biomarkers of exposure to tobacco alkaloids, and toxicants, including 14 volatile organic compounds (VOCs), tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), heavy metals (cadmium, lead, chromium, nickel, copper, and tin) and a polycyclic aromatic hydrocarbon (2-naphthol). Regression analysis was used to compare biomarkers by group. RESULTS: Nicotine levels varied across product users, but not significantly. After controlling for confounders, for most VOCs, biomarker levels were similar for exclusive-vapers and never-users and significantly lower than for exclusive-smokers and any dual users. There were generally no significant differences between groups for 2-naphthol or heavy metals. For NNAL, cadmium and chromium, a high percentage of values were below the limit of detection, making analyses unreliable. CONCLUSIONS: During pregnancy, former smokers who are established exclusive vapers, but not dual users, had levels of selected VOCs that were substantially lower than those for exclusive smokers and comparable with those who have never used nicotine or tobacco products. IMPLICATIONS: Based on the biomarkers assessed in this study, during pregnancy, on average, exclusive-vapers are likely to have similar levels of exposure to selected VOCs as never-users and far lower levels than exclusive-smokers or dual-users (although dual-vaping and smoking may result in less exposure than exclusive-smoking). This provides preliminary information about exposure to vaping during pregnancy and suggests that, for some biomarkers, exclusive vaping is likely to result in lower exposures than exclusive smoking or dual-use. There may be exposure to other vaping toxicants that were not explored in this study. Studies are needed to assess pregnancy and birth outcomes as well as early life effects.

Monitoring the zoonotic potential of emerging SARS-CoV-2 variants in animals is a critical tool to protect public health. We conducted a longitudinal study in 47 households reporting people with COVID-19 in Texas from January to July 2022, during the first Omicron wave. We evaluated 105 people and 100 of their companion animals for SARS-CoV-2 infection at three sequential sampling events, starting 0-5 days after the first reported diagnosis of COVID-19 in the house. SARS-CoV-2 RNA was detected in 68% of people from 43 households; 95.5% of people had antibodies to SARS-CoV-2. Dogs were the only animal species positive by RT-qPCR (5.4%; 3/55), and their viral loads were consistently lower compared with those from household members. Additionally, infected dogs did not yield infectious virus. Clusters of Omicron BA.1.1, BA.2.3.4, and BA.5.1.1 in people, dogs, and a dog food bowl confirmed human-to-dog transmission within households, with no evidence of onward transmission from the infected dogs. Eleven dogs (n = 55) and two cats (n = 26) had neutralizing antibodies against SARS-CoV-2. Overall, infection was not associated with clinical signs in pets; only two animals that tested negative for SARS-CoV-2 were reported to be sick. Nearly one-third (30.2%) of households with active COVID-19 had pets exposed to SARS-CoV-2, similar to our pre-Omicron studies; however, the incidence of infection in cats was lower compared with pre-Omicron. These differences suggest that the zoonotic transmission dynamics in households may differ based on variants.IMPORTANCESARS-CoV-2 infects a broad diversity of mammals, with companion dogs and cats at risk of infection via close contact with infectious owners. Longitudinal studies sampling pets and their owners over time are essential to understanding within-household SARS-CoV-2 transmission dynamics. Our repeated sampling in households with people reporting COVID-19 found that 68% of the people in 43 households had active SARS-CoV-2 infection during at least one of the three sampling events. Although none of the 27 cats were positive, 3/55 dogs had active infections. Household clusters of three different Omicron subvariants were involved in these human-to-dog transmission events, and our data suggest reduced infection in pets during Omicron transmission compared with pre-Omicron waves. Protecting pets from SARS-CoV-2 infection remains important, as viral evolution can be accompanied by changes in the infectiousness of different hosts.

One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mechanisms of bacterial infection in the dissemination of lung cancer cells. A series of studies have indicated that certain Gram-negative bacteria are able to hijack antigen-presenting cells (APCs) via interaction with DC-SIGN (CD209) receptors to facilitate the dissemination of pathogens, including viruses, bacteria, fungi, and parasites. Therefore, in the present work, it was hypothesized that bacterial infection may promote the dissemination of cancer cells via the utilization of a similar mechanism. It was first discovered that human lung cancer tissues contain a very high diversity of bacterial DNAs, indicating the co-existence of lung cancer tissues and microbial organisms. It was then found that lung cancer tissues express DC-SIGN, leading to binding with a Gram-negative bacterium, Shigella sonnei. Further, this bacterium was found to be able not only to induce the expression of DC-SIGN on macrophages but also to enhance the migration ability of lung cancer cells in vitro. The in vivo experiments supported these observations, showing that in wild-type (WT) mice, Shigella sonnei infection significantly increased tumor size, weight, and metastatic nodules compared to SIGNR1 knockout (KO) mice. These observations were associated with increasing DC-SIGN expression in WT mice. Finally, these results suggest that bacterial infections could play a significant role in promoting lung cancer progression and metastasis via DC-SIGN-mediated mechanisms.

In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

INTRODUCTION: Urinary biomarkers are useful in characterizing exposure to harmful and potentially harmful constituents (HPHCs) of tobacco products and linking exposure to health outcomes. However, the consistency/reproducibility of many urinary biomarkers over long periods is unknown. METHODS: Among people who exclusively used cigarettes in the Population Assessment of Tobacco and Health Study Waves 1, 2, 4, and 5 (ranging from 746 to 1361 subjects), we used weighted models to estimate variance components and intra-class correlation coefficients (ICC) for 15 biomarkers of exposure for urine samples collected 3-5 years apart, creatinine-only-adjusted and also adjusted for demographic and behavioral predictors. RESULTS: In models adjusted only for creatinine, ICC values of biomarkers ranged from 0.41 (95% confidence interval (CI): 0.32, 0.49) (N-acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.73 (95% CI: 0.65, 0.81) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), varying within each chemical class. For models adjusted for predictors, associations between biomarkers and predictors were similar for samples collected 3-5 years and 1 year apart. Predictor-adjusted ICCs for samples collected 3-5 years apart ranged from 0.29 (95% CI: 0.17, 0.40) (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.63 (95% CI: 0.56, 0.69) (N-Acetyl-S-(2-hydroxyethyl)-L-cysteine) and appeared not different from those for samples collected 1 year apart. CONCLUSIONS: Even for 3 or 5 years between urine sample collection, unadjusted biomarkers of exposure showed fair to excellent reproducibility. Similar consistency between 1 year and 3-5 years between collections was found when including predictors in the model. IMPLICATIONS: These biomarkers may be useful to characterize long-term exposures to HPHCs from cigarettes with different characteristics for those who smoke cigarettes exclusively.

BACKGROUND: It is not recommended to perform tuberculin skin tests (TSTs) or interferon-γ release assays (IGRAs) in the 4 weeks following live-virus vaccination because these vaccines are thought to increase the risk of false-negative results. METHODS: We retrospectively analyzed TST and IGRA results for 158 484 US-bound immigrant and refugee children aged 2-14 years who received a required medical examination and live-virus vaccines (measles, mumps, rubella; oral polio; or varicella) overseas during 2014-2022. We created logistic regression models to assess the association between test positivity and vaccination during the critical interval (1-28 days after live-virus vaccination) versus after or before, adjusting for sex, age group, country of examination, and other factors. RESULTS: The percentage of positive results and the adjusted odds of a positive IGRA result were higher for children tested during the critical interval (4.6%) than for those tested after (3.5%) (adjusted odds ratio, 1.27 [95% confidence interval, 1.13-1.43) or before (3.3%) (1.26 [1.13-1.41]). The percentage of positive results and the adjusted odds of a positive TST were also higher for children tested during the critical interval (15.7%) than for those tested after (7.2%) (adjusted odds ratio, 2.40 [95% confidence interval, 1.79-3.22]) or before (6.6%) (3.81 [2.80--5.18]). CONCLUSIONS: The concern that recent administration of live-virus vaccines leads to false-negative TST and IGRA results is not supported by these findings. Instead, we observed a modest increase in positive results among children tested during the critical postvaccination interval, challenging the need for the testing delay.

BACKGROUND: SARS-CoV-2 pandemic has caused a continuing health crisis affecting the public health system globally. Population-based serological surveys are a highly valuable and recommended method to measure population exposure and spread of pandemic, given the existence of asymptomatic cases and little access to diagnostic testing. This national population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in all parts of Ethiopia and determine potential risk factors and burden of infection. METHODS: A nationwide seroprevalence survey was done among 12,756 households (HHs) across the country using three-stage stratified sampling technique from April 15, 2021 to May 16, 2021 among population of Ethiopia above 15 years of age. One member of each of the selected HHs, who fulfilled the eligibility criteria, was randomly selected. We captured data using interviews and finger prick blood samples to test for anti-SARS-CoV-2 antibodies using high specificity rapid diagnostic tests (RDTs). A questionnaire was used to capture all necessary data on demographics, social exposure, and history of vaccination for SARS-CoV-2, symptoms compatible with SARS-CoV-2, and any known medical conditions. The data were collected using an open data kits (ODK) software and imported into STATA version 17 for analysis. Descriptive statistics (frequencies and proportions) were used to summarize data on the study variables. Forest plots and maps were used to visualize the seroprevalence of SARS-CoV-2 across various individual and environmental factors. The study sample was weighted, and the survey set command in Stata (svy) was used in the analyses to account for the survey design. Adjusted Odd ratio (AOR) was used to determine higher risk factors of having been infected at least once, 95% confidence interval to assess precision of the estimates, and a P value ≤  0.05 to determine statistically significant. RESULT AND DISCUSSION: This study indicated the overall national prevalence of seropositivity was 9.3% that suggests nearly one in ten individuals in Ethiopia was exposed to SARS-CoV-2 infection by May 2021. All regional states in the country are affected with SARS-CoV-2 infection although infection was more common in densely populated regions. Seroprevalence was significantly higher among, individual, aged 35-44, 55-64 and 65 and over years had more odds of being infected by SARS-CoV-2 compared with those aged 15-24 years. The seroprevalence is also high among professional/technical occupations, and among those having at least one comorbidity. The participants who had seven and more members had higher odds of infection compared with those who had two or less members. The odds of infection among respondents, who reported having ever tested for COVID-19 and being sick since March 2020, were higher compared with their counterparts. Among the environmental factors, the odds of SARS-CoV-2 infection in urban residents were higher than in the rural setting. In relation to geographic administration boundaries, participants from Harari Region, Addis Ababa, and Benishangul Gumuz had higher odds of infection compared to those from Afar Regions respective. CONCLUSION AND RECOMMENDATIONS: This study reveals the overall seroprevalence of SARS CoV-2 antibodies in Ethiopia was 10.0% as of May 2021. The seroprevalence of IgG antibodies against COVID-19 is higher than that of IgM antibodies, indicating a past infection. SARS-CoV-2 antibody seroprevalence was varied by regional state, sex, residence area, age, and occupational status. It also suggests that the majority of Ethiopia's have inadequate knowledge of understanding about SARS-CoV-2 antibodies, we recommend strengthening public health and social measures to mitigate the spread of COVID-19 diseases, including increased vaccination coverage and testing capability. All responsible authorities and stakeholders working locally, nationally, and globally need to support strengthening health systems and be prepared to combat morbidity and mortality and to encourage ongoing vaccination efforts. Periodic seroprevalence surveys will aid in monitoring the status and progress of the COVID-19 pandemic.

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.

During August-October 2020, United States federal, state, and Canadian partners investigated an outbreak of Salmonella Enteritidis infections, in the U.S. and Canada, linked to fresh, whole peaches packed and supplied by a grower and packer with multiple orchards (Farm A). In the U.S., a total of 101 ill people and 28 hospitalizations were reported in 17 states, while in Canada, 57 ill people and 12 hospitalizations were reported in two Canadian provinces. The U.S. traceback investigation included 14 points of service (POS), representing 18 illnesses in eight states. Multiple distributors, packinghouses, and orchards supplied bagged and loose peaches during the timeframe of interest to identified POS, with peaches and packinghouses linked to Farm A being the primary source. Orchards of interest were identified for peach fruit, orchard tree leaf, and soil-drag swab sample collection using traceback and geospatial analysis. Geospatial analyses showed that several orchards were in proximity to animal operations. While none of the Salmonella isolates recovered matched the outbreak strain, Salmonella Alachua was recovered from peaches and leaf samples, and Salmonella Montevideo was recovered from orchard tree leaves. Whole genome sequencing indicated that these Salmonella isolates were closely related to historical poultry and cattle isolates. Farm A voluntarily recalled loose peaches sold from June 1 to August 3, 2020, and bagged Brand A conventional and organic peaches sold from June 1 to August 19, 2020. Recalled products were likely distributed to at least 14 different countries. Findings suggest that adjacent animal operations may be a potential contributing factor to Salmonella contamination of peaches, with windborne or fugitive dust as a possible route. The findings from this first reported international outbreak of Salmonella linked to peaches grown in the U.S. highlight the importance of grower awareness of adjacent land use.

Rotavirus (RV) remains a significant cause of infantile morbidity and mortality, while oral RV vaccines offer inconsistent protection. This study investigates whether gut microbiota influence immune responses to orally and intramuscularly (IM) administered RV strains. Using murine models, we identified microbiota constituents, including segmented filamentous bacteria, reducing oral RV infection and RV antibody generation. Such blockade of RV-induced responses was associated with elevated expression of intestinal Reg3β and Reg3γ and was recapitulated by intraperitoneal administration of cognate recombinant proteins. IM administration following oral RV inoculations enhanced antibody production and defense against RV challenge. We further showed microbiota composition also influenced the efficacy of a single IM RV inoculation. Antibiotic-induced microbiota depletion boosted IM RV efficacy in poorly responding animals. Such enhancement of IM RV-induced immunity appeared to be associated with increased expression of serum RANTES and Eotaxin. The phenotype was recapitulated by directly adjuvating these chemokines to the IM inoculum.

BACKGROUND: Rural adolescents in the United States lag behind their urban counterparts in the uptake of the human papillomavirus (HPV) vaccine. However, a systematic assessment of factors associated with rural-urban disparities in HPV vaccination coverage to inform potential vaccination promotion interventions is lacking in the literature. Prioritizing HPV vaccination for rural adolescents is necessary for increasing overall HPV vaccination coverage for adolescents and for reducing the incidence of HPV infections and future HPV-related cancers. METHODS: We conducted a cross-sectional survey of caregivers of adolescents aged 9-17 years from 13 states located in the southern United States. Participants were recruited from a nationally representative online survey panel and self-administered the survey from December 2019 to January 2020. The survey assessed HPV vaccination initiation and series completion for rural and urban adolescents, and sought to systematically identify modifiable factors (eg, caregiver knowledge and attitudes about HPV/HPV vaccine, health care access) and nonmodifiable factors (eg, sociodemographic characteristics) that may be associated with rural-urban disparities in adolescent HPV vaccination. Rural versus urban residence status of respondents was determined using the US Census definition and Federal Information Processing System (FIPS) codes. RESULTS: Among 2,262 sampled caregivers, data from 987 respondents (43.6%) were included in the analysis; 193 respondents (19.6%) were from rural areas and 794 (80.4%) were from urban areas. Overall, 333 (33.7%) adolescents had received at least 1 dose of HPV vaccination and 259 (26.3%) adolescents had completed HPV vaccination. In comparison to urban adolescents, fewer rural adolescents had initiated (-7.7 percentage points) or completed (-14.9 percentage points) HPV vaccination. Uptake of tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal (MenACWY), and influenza vaccines was similar between urban and rural adolescents. Caregiver attitudes, but not their knowledge about HPV infection or the HPV vaccine, were associated with disparities in HPV vaccination initiation. Rural caregivers were more likely to report concerns with the HPV vaccine, lower access to a pediatric primary care provider, longer travel times to reach health care providers, and HPV vaccination at age 11 years or older compared with age 9 or 10 years. When compared with urban caregivers, fewer rural caregivers reported discussing HPV vaccination with their adolescent's provider although difference in the receipt of a provider recommendation was not statistically significant between rural and urban adolescents. CONCLUSIONS: Our findings confirm rural-urban disparities in HPV vaccination coverage for adolescents living in the 13 southern US states. Future research efforts to reduce rural-urban disparities in HPV vaccination should evaluate the impacts of interventions that increase positive caregiver attitudes about HPV vaccination, expand access to vaccination services and pediatricians for rural adolescents, enable strong provider recommendations, and increase the window of HPV vaccination by promoting vaccination initiation at younger ages (9-10 years). While this analysis focused on rural-urban disparities, lower rates of HPV vaccination overall suggest that interventions in rural areas be implemented alongside broader efforts to promote adolescent HPV vaccination coverage in the southern United States.

IMPORTANCE: Clostridioides difficile is among the most prevalent health care-associated pathogens worldwide. Controlling it remains a critical challenge, due in part to spore viability on surfaces. OBJECTIVE: To quantify transmission of C difficile within health care facilities and evaluate the roles of environmental surfaces and health care personnel (HCP) hands in C difficile movement. DESIGN, SETTING, AND PARTICIPANTS: In 2018, a 13-week longitudinal, observational study was conducted in 2 intensive care units (ICUs) in Utah with daily culture-based sampling of patient body sites, room environmental surfaces, HCP hands, and shared environmental surfaces. Both toxigenic and nontoxigenic C difficile strains were selected for whole genome sequencing and included in the analysis. Data were analyzed from September 2021 to September 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was the identification of transmission clusters based on genomic relatedness between isolates from patients, environmental surfaces, and HCP hands. Clusters were defined as isolates with 2 or fewer single nucleotide variants between them. RESULTS: Of the 278 unique ICU admissions, 177 patients consented to body site sampling and were sampled. Along with these, environment surfaces and HCP hands were sampled daily for all occupied rooms, leading to 7000 total samples. Sampling patients, their environment, and HCP hands revealed that nearly 8% of all patients had C difficile linked to other admissions and 57% of transmission clusters bridged nonoverlapping patient-stays. Including environmental surfaces and HCP hands, a 3.6-fold higher C difficile movement was identified than with patient sampling alone, highlighting environmental surfaces as reservoirs. CONCLUSIONS AND RELEVANCE: These results challenge the idea that nosocomial transmission is not a primary source of acquisition and underscore the importance of hand hygiene and environmental decontamination. This study reinforces the need to include environmental surfaces and HCP hands in future work characterizing the burden of nosocomial transmission. Understanding the transmission pathways of C difficile within health care facilities, particularly the roles of environmental surfaces and HCP hands, is critical to improving infection control measures.

AIMS: To examine the national trend in per-capita medical expenditures among U.S. adults with diabetes from 2000 to 2022. METHODS: We analyzed data from the Medical Expenditure Panel Survey in U.S. adults aged ≥18 years with self-reported diabetes. We calculated the expenditure in total and by component, including outpatient services, inpatient services, emergency room (ER) visits, prescription drugs, and other medical services. We used joinpoint regression to identify changes in trends. RESULTS: Estimated total per-capita expenditure increased 66 %, from $9,700 (95 % CI $8,736-$10,663) in 2000 to $16,067 (95 % CI $15,049-$17,086) in 2022. Specifically, spending on prescription drugs, outpatient, ER, and other medical services increased by 144 %, 96 %, 122 %, and 135 %, respectively, while inpatient spending decreased by 28 %. Two significant upward trend periods (2000-2004 and 2011-2018) were identified for total expenditure. Spending trends by component varied, with an accelerated increase in prescription drug spending after 2012; by 2022, prescription drugs accounted for the largest share (39 %) of total expenditures. CONCLUSIONS: The economic burden of diabetes on the national health care system has been increasing, with spending changes varying by medical service category. Interventions to prevent diabetes and its complications may help mitigate this growing economic burden.