BMC Infectious Diseases

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells primarily through the angiotensin-converting enzyme 2 (ACE2) receptor. Genetic variation in the ACE2 gene may influence host inflammatory responses and clinical outcomes during COVID-19. Tuberculosis (TB) on the other hand increases the level of ACE2 expression through interferon stimulation. The objective of this study was to investigate the association between specific single-nucleotide polymorphism (SNP) in the ACE2 gene and their impact on susceptibility to and severity of SARS-CoV-2 and Mycobacterium tuberculosis Co-infection. Methods: This retrospective cross-sectional study included 120 symptomatic individuals recruited between September 2020 and December 2023 from four hospitals in Yaounde, Cameroon. Participants were classified into four groups: COVID-19, TB, TB/COVID-19 co-infection, and infection-negative controls. Diagnoses were confirmed using RT-PCR and standard microbiological methods. Serum biochemical markers and cytokines were quantified, and genotyping of ACE2 polymorphisms was performed using TaqMan assays. Results: Statistical analysis showed a significant association between ACE2 expression and inflammatory or biochemical markers, particularly for rs147311723. Several ACE2 polymorphisms (rs6632677, rs147311723, rs4646140, rs2285666, and rs4646142) were significantly associated with increased pro-inflammatory cytokine levels. Selected biochemical parameters demonstrated suggestive associations with ACE2 variants, including creatinine (rs147311723, p = 0.0522), AST (rs2285666, p = 0.0536), and ALT (rs4646142, p = 0.0582), indicating potential renal and hepatic involvement. Principal component analysis identified distinct immunometabolic profiles across patient groups, with co-infected individuals exhibiting heightened inflammatory and metabolic perturbations. Conclusions: These findings suggest that ACE2 genetic variability is associated with modulation of inflammatory responses and may contribute to organ-specific dysfunction in COVID-19 and TB across different populations. This highlights the potential role of host genetics in shaping disease severity and underscore the need for larger studies to validate these associations in diverse populations. Keywords: ACE2 polymorphisms; COVID-19; tuberculosis; co-infection; cytokines; biomarkers; genetic susceptibility;

Introduction: This study compared the health and economic impact of the 21-valent pneumococcal conjugate vaccine (aPCV21) vs the 20-valent pneumococcal conjugate vaccine (PCV20) on invasive pneumococcal disease (IPD) and post-meningitis sequelae (PMS) among adults aged 65 years and older in the United Kingdom (UK). Methods: A published Markov model was used to simulate a single-cohort of vaccine-naive adults who became eligible for age-based vaccination at age 65 years, with uptake occurring over time. The cohort was followed until a maximum age of 100 years. Model inputs were derived from publicly available national health data and published reports. Outcomes were discounted at 3.5% annually, and costs were adjusted to the 2024 Great Britain Pound ({pound}). Additional analyses explored the impact of changing the age-based recommendation from 65 years to 75 years. Scenarios involving instantaneous vaccine uptake rates were included as part of the sensitivity analyses. A deterministic sensitivity analysis was performed on the incremental direct medical costs between vaccinating with aPCV21 vs PCV20 under the age-based recommendation of 65 years. Results: Using an age-based recommendation of 65 years, aPCV21 led to fewer cases, deaths, and costs than PCV20. Compared with PCV20, aPCV21 averted an additional 138 IPD cases, 1 PMS case, and 22 IPD deaths, saving {pound}1.2 million in direct medical costs. Raising the age-based recommendation from 65 to 75 years and using aPCV21 (or PCV20, respectively), resulted in 120 (92) additional IPD cases, 2 (1) additional PMS case(s), 19 (14) additional IPD death(s), and an extra {pound}1.1 ({pound}0.8) million in direct medical costs. The deterministic sensitivity analysis showed that aPCV21 reduced direct medical costs across all parameter ranges. Conclusions: Compared with PCV20, aPCV21 prevented more IPD cases, IPD deaths, and direct medical costs among older adults in the UK. Changing the age-based recommendation from age 65 to 75 resulted in worse health and economic outcomes. Key words. Pneumococcal infections; pneumococcal vaccines; vaccines, conjugate; serotype; United Kingdom; health costs

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Objectives: To evaluate the epidemiological evolution of unique pneumococcal serotypes covered by either PCV20 or PCV21, common serotypes by both vaccines and non-vaccine serotypes in adults. Methods: We characterized all national IPD clinical isolates from January 2009 to June 2026. Results: The highest burden of IPD was caused by serotypes shared between PCV20 and PCV21 with serotypes 3 and 8 the most prevalent in adults of all ages. During the pre-pandemic period, IPD caused by unique-PCV20 serotypes declined probably due to herd protection by paediatric vaccination with PCVs. In contrast, unique-PCV21 serotypes increased in incidence accounting for more cases than unique-PCV20 serotypes. However, after the COVID-19 pandemic, a different pattern was observed with unique-PCV20 serotypes increasing in incidence due a marked rise in IPD caused by serotypes 4 and 14 that has progressively reduced the gap in disease coverage. In adults aged 18-64 years, the fraction of disease that could be prevented with PCV20/PCV21 changed from 5% in favour of PCV21 (years 2022/2023) to 15% in favour of PCV20 (year 2026) whereas in adults [≥]65 years the vaccine contribution declined from 20% in favour of PCV21 (year 2022) to 8% in 2026. Conclusions: IPD trends in adults have changed after the COVID-19 pandemic, especially in recent years. Our study emphasizes the rapid re-emergence of infections caused by traditional PCV7 serotypes especially serotypes 4 and 14 and reinforce the idea that the use of broader PCVs must be accompanied by an increase in the uptake rates in adults of all ages.

Background: The biological mechanism linking rainfall with leptospirosis transmission is well established, but rigorous quantitative evidence for the insular Caribbean remains scarce, limited mostly to descriptive reports of post-hurricane outbreaks. We aimed to quantify the association between rainfall and leptospirosis incidence in the Dominican Republic, where leptospirosis is endemic, between 2012 and 2026 using a distributed-lag approach. Methods: We conducted an ecological time-series study complemented by a province panel with fixed effects. Case data (5,412 valid cases) were obtained from the national surveillance system (SIP-0276FA51); rainfall data were obtained from 15 INDOMET rain gauge stations across 13 provinces (2000 to 2026). We calculated the cross-correlation function between lagged monthly rainfall (0 to 6 months) and case counts, fitted a negative binomial distributed-lag regression model (lags 0 to 3 months) adjusted for seasonality and trend, triangulated findings with a 13-province fixed-effects panel, compared four rainfall exposure metrics, assessed extreme-rainfall threshold sensitivity, and estimated the population attributable fraction (PAF) with a parametric bootstrap. Results: The rainfall-case association peaked at a 1-month lag (r = 0.551; 95 % CI 0.437-0.647; p < 0.001) and remained significant through 3 months. In the distributed-lag model, all four lags were independently significant, with the 1-month lag showing the strongest effect (incidence rate ratio [IRR] = 1.156 per additional 50mm; 95 % CI 1.090-1.226; p < 0.001). The province panel yielded an almost identical 1-month lag effect (IRR = 1.147; 95 % CI 1.127-1.167). Rainfall above the historical 90th percentile increased case risk the following month (rate ratio = 1.95), with effect magnitude increasing monotonically with threshold stringency. An estimated 28.2 % (95 % CI 19.0-36.6 %) of cases were attributable to rainfall above the recorded historical minimum. Conclusions: Rainfall is a robust, consistent predictor of leptospirosis incidence in the Dominican Republic, with the strongest association observed at a 1-month lag and a lag pattern broadly consistent with findings from distributed-lag studies in Thailand and the Philippines. These findings, which to our knowledge constitute the first formal quantification of this association for the insular Caribbean, provide an evidence base for rainfall-linked early-warning systems, with the strongest signal at approximately one month and elevated risk extending through three months after rainfall.

The African meningitis belt, spanning 26 countries, experiences regular seasonal outbreaks of bacterial meningitis. Outbreaks predominantly occur during the October-April dry season, characterised by low humidity, high temperatures, and increased dust levels driven by the movement of the Harmattan winds. Whilst many studies have examined the relationship between bacterial meningitis outbreaks and climate across Africa, this has rarely been examined on a continental level. Additionally, previous continental analyses have been unable to account for spatiotemporal changes in bacterial meningitis epidemiology. We developed a district-level Bayesian spatiotemporal model to estimate monthly meningitis risk across Africa using climatic variables. For district-months between 2003-2022 we generated a Boolean variable to identify districts affected by meningitis outbreaks, defined as an incidence of [&ge;]10 suspected cases per 100,000 population per week. Covariates included rainfall, humidity, windspeed and direction, MenAfriVac campaign status, population density, aerosol optical depth (AOD), temperature and land cover type. We used a Bayesian Integrated Nested Laplace Approximation (INLA) model to account for spatial and temporal heterogeneity. Covariate inclusion was decided using the Watanabe Akaike Information Criterion (WAIC), the Deviance Information Criterion (DIC), as well as considering variable epidemiological relevance. Our final model included linear effects for humidity, AOD, zonal wind strength and direction, an interaction term between zonal wind direction and AOD, and a non-linear temperature effect. Zonal wind strength had a statistically significant positive relationship with outbreaks whilst humidity had a negative association. The interaction term between zonal wind direction and AOD had a highly positive association with outbreak occurrence. When zonal wind moved westwards, higher AOD levels increased the likelihood of outbreak occurrence. Furthermore, whilst the log odds of meningitis outbreak occurrence remained low at cooler temperatures, the effect peaked between 37-38{degrees}C before beginning to plateau. The non-linear association between meningitis incidence and temperature is suggestive of an optimal temperature for bacterial transmission. Additionally, the significance of the AOD and wind direction interaction highlights the role of the Harmattan winds in exacerbating meningitis risk, rather than outbreaks solely being driven by higher dust levels. Despite these variables all having a well-established relationship with meningitis outbreaks, our study shows that such climatic associations are still present at the continental level, when accounting for spatiotemporal effects

Background Severe acute respiratory infections (SARI) strain healthcare systems. Sentinel surveillance remains central to SARI monitoring, but routinely collected hospital discharge data offer a scalable, population-wide complement. In Finland, national registers now enable register-based surveillance, yet SARI case definitions remain unevaluated. Aim To evaluate whether routinely collected electronic health records can support register-based SARI surveillance and establish a national case definition. Methods We conducted a retrospective register-based study linking inpatient discharge data from the Finnish Care Register for Health Care (Hilmo) and laboratory-confirmed pathogen notifications from the National Infectious Diseases Register (NIDR). Admissions were aggregated into hospitalisation episodes using generic and pathogen-specific respiratory ICD-10 codes and linked to laboratory-confirmed respiratory pathogens within an admission-centred window. We assessed the impact of diagnostic coding position, laboratory linkage windows and alternative case definitions on age distribution, seasonality and epidemic trend detection. Results We included 145,435 respiratory hospitalisation episodes. Laboratory confirmations clustered around admission, and a -7-to-+3-day window was selected; 51,498 (35.4%) had a linked laboratory confirmation. Specific primary-position diagnoses preserved clear seasonality and age distributions consistent with SARI epidemiology, whereas secondary-position diagnoses showed attenuated seasonality. A combined case definition incorporating specific primary diagnoses and laboratory-supported syndromic episodes produced stable epidemic curves while improving sensitivity over laboratory confirmation alone. Conclusion National discharge and laboratory registers can support robust SARI surveillance in Finland when case definitions are carefully designed. A combined register-based definition balances specificity, sensitivity and feasibility, complementing sentinel surveillance and integrated respiratory monitoring. Keywords Severe acute respiratory infection (SARI); surveillance; electronic health records; ICD-10; case definition; Finland

Background: Seasonal influenza, commonly known as flu, is an acute respiratory, highly contagious illness caused by influenza viruses. A clear understanding of influenza seasonality is crucial for guiding prevention and treatment strategies, including decisions on vaccination timing to prevent outbreaks. While well documented in temperate regions, data on influenza epidemiology in tropical areas, particularly sub-Saharan Africa, remain limited. We described the types, subtypes and positivity rate of seasonal influenza in Uganda during 2019-2023. Methods: We abstracted data from the National Influenza database on positive seasonal influenza cases confirmed by Polymerase Chain Reaction. The cases were disaggregated by age group, sex, region, month and year of reporting. Using Microsoft excel, we calculated the influenza positivity rate and disaggregated it by strain, sex, age, region and time. Test positivity rate was computed as the number of positive cases as a percentage of the total samples tested. Results: Among 17,957 individuals tested, the overall positivity rate for seasonal influenza was 5% (936 cases). Positivity was higher among males compared to females (7% vs. 4%), with children aged 5-9 years having the highest positivity rate (16%), while individuals aged 50-54 years had the lowest (1%). The median positivity rate was 4%, with a range of 1-16%. Regionally, the central region reported a positivity rate of 5%, with rates across all regions ranging from 5% to 8%. Over time, there was a gradual decline in positivity rates, decreasing from 16.5% in 2019 to 5.3% in 2023. Seasonal influenza exhibited bimodal peaks, with the primary peak occurring between March and May and a secondary peak from October to December. Influenza A was the predominant strain, accounting for 70% of seasonal influenza cases (669/936). Among the Influenza A subtypes, H3N2 was most common, representing 63% of cases (425/669). Conclusions: The declining seasonal influenza positivity rates from 2019 to 2023 and the predominance of Influenza A and H3N2 highlight the need for sustained surveillance in Uganda. Given Influenza A's high genetic variability and potential for novel strain emergence, monitoring circulating strains, informing vaccine development, and implementing targeted interventions for high-risk groups and regions are critical to controlling and preventing outbreaks.

Background: Severe malaria remains a major cause of hospitalization in malaria-endemic sub-Saharan Africa, and anemia is among its most frequent severity criteria. Data on the impact of anemia on hospital length of stay (LOS) among adults with severe malaria remain limited in Central Africa. We assessed the impact of anemia on LOS among adults hospitalized for severe malaria in Brazzaville, Republic of Congo. Methods: We conducted a cross-sectional, descriptive, and analytic study of medical records from adult patients ([&ge;]18 years) diagnosed with severe malaria (WHO criteria) and admitted to four hospitals in Brazzaville between January 2020 and December 2024. We dichotomized LOS as short (<5 days) or prolonged ([&ge;]5 days). Multivariable logistic regression, using a backward stepwise procedure, identified factors independently associated with prolonged LOS; isolated hemoglobinuria served as the reference severity category. Results: Among 523 patients hospitalized for severe malaria, 296 met the inclusion criteria. Median age was 25.5 years (IQR 20-40); 51.7% were female, and 82.1% had a low socioeconomic status. Median hemoglobin was 10.55 g/dL, and median LOS was 4 days (IQR 3-5). In multivariable analysis, prolonged LOS was independently associated with delay to consultation (aOR 1.25/day, 95% CI 1.09-1.44), isolated anemia (aOR 7.07, 1.23-40.55), convulsions (aOR 5.86, 1.81-18.97), prostration (aOR 4.42, 1.21-16.2), and impaired consciousness (aOR 4.29, 1.17-15.7). The strongest associations involved combined severity criteria: anemia with prostration (aOR 8.58), anemia with jaundice or hemoglobinuria (aOR 16.21), and impaired consciousness with anemia (aOR 33.31). Conclusions: Anemia is a major, potentially modifiable determinant of prolonged hospitalization in adults with severe malaria, with a markedly amplified effect when combined with neurologic impairment. Early anemia screening, improved access to safe blood transfusion, and reduced delays to care could shorten hospital stays and ease the burden on health systems in this setting.

Background Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.

BackgroundPopulation-based spirometry data from sub-Saharan Africa remain limited. We characterised lung function, chronic obstructive pulmonary disease (COPD), lung restriction and associated factors from two Sub-Saharan African countries. MethodsWe performed spirometry using ndd Easy On-PC spirometers among adults aged [&ge;]40 years from population-based cohorts in four communities in Burkina Faso and South Africa from January 2019-April 2022. We included 1,619 participants (936 women, 683 men) with repeatable forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). COPD was defined as FEV1/FVC<0.70 and lung restriction as FEV1/FVC[&ge;]0.70, with FVC<80% predicted. We used multivariable models to test factors associated with lung function measurements (FEV1, FVC and FEV1/FVC), COPD and lung restriction. ResultsMedian FEV1 and FVC ranged from 1.940-2.273L and 2.521-2.883L, respectively. COPD prevalence was 16.1% (95% CI 14.4-18.0; site range 10.8%-24.5%) and lung restriction prevalence was 21.3% (95% CI 19.4-23.4; site range 11.3%-36.2%). Prior tuberculosis was associated with higher odds of COPD (OR 2.86, 95% CI 1.75-4.59) and lower FEV1, FVC and FEV1/FVC. HIV infection was associated with higher COPD odds (OR 1.67, 95% CI 1.01-2.72) and lower FEV1/FVC. Hypertension was associated with higher lung restriction odds (OR 1.46, 95% CI 1.07-2.00) and lower FEV1 and FVC. Diabetes was associated with lower COPD odds (OR 0.50, 95% CI 0.24-0.94), lower FVC and higher FEV1/FVC. Ever-smoking and older age were associated with higher COPD odds (OR 2.21, 95% CI 1.48-3.32; OR 1.05, 95% CI 1.03-1.07, respectively); older age was associated with higher lung restriction odds (OR 1.02, 95% CI 1.00-1.04). ConclusionThis multisite study highlights substantial heterogeneity in COPD and lung restriction prevalence across African populations and identifies respiratory multimorbidity with infectious and cardiometabolic conditions. These findings provide population-based evidence to inform respiratory surveillance in sub-Saharan Africa.

Background: Influenza and respiratory syncytial virus (RSV) both cause annual peaks in hospitalisation and with considerable overlap. Epidemiological studies suggest an inhibitory relationship, which is supported by laboratory studies. Several biological mechanisms including resource competition and immune activation have been identified, but limited evidence exists to distinguish their effects at the population level. Methods: We developed an influenza-RSV compartmental model to estimate and compare potential interactions using data on virus-associated hospitalisations in Valencia, Spain from 2010 through 2020. We considered five interaction mechanisms: altered susceptibility, transmissibility and severity, a refractory period post-infection, and a residual positivity period. Using Bayesian inference, we fit the model to weekly hospitalisations with influenza, RSV or both, and to national surveillance data for influenza-like illness. Results: We found evidence for inhibition between influenza and RSV, with several interaction mechanisms being supported. In the best-fitting model, active RSV infection reduced the probability of hospitalisation with influenza to 20% of the baseline (with the data supporting values from 0%-60%). Compared to a model without interaction, this mechanism reduced the number of hospital cases with influenza-RSV co-detection by 63%. Conclusions: Our results support the existence of inhibitory mechanisms, with small but substantial effects on disease epidemiology. These results highlight the importance of understanding these interactions under the changing epidemiology of respiratory viruses and vaccinations.

Introduction: Neurocysticercosis (NCC) is an infection of the central nervous system caused by the tapeworm Taenia solium. Despite documented increases of NCC in California, large-scale studies characterizing affected populations remain limited. The spectrum of NCC associated neuropsychiatric comorbidities has not been well defined in U.S. populations. This study aimed to estimate the prevalence of NCC within the University of California (UC) Health System, characterize the population demographic and clinical features, and identify factors associated with epilepsy among individuals with NCC. Methodology/Principal Findings: We conducted a cross-sectional analysis of electronic health records from 2012 through March 2026 using the UC Health Data Warehouse, which integrates data from six UC Health systems. Among individuals aged [&ge;] 1 year, there were 713 individuals with a diagnosis of NCC corresponding to a prevalence of 6.17 per 100,000. A comparison group was randomly selected at a 1:10 ratio. Relative to the comparison group, NCC patients were significantly older, more likely to identify as Hispanic or Latino, more likely to speak Spanish as a primary language, and more likely to have Medicaid insurance. NCC was strongly associated with epilepsy (OR = 19.20, 95% CI: 15.74-23.46), as well as migraines, cognitive impairment, mood disorders, Parkinsons disease, substance use, stroke, and sleep disorders. After adjusting for age, gender, and ethnicity, male NCC patients had 26% higher odds of epilepsy compared to female patients. Conclusion/Significance: In addition to epilepsy, NCC was associated with a broad range of neuropsychiatric comorbidities and occurred disproportionately among patients more likely to face socioeconomic and structural barriers to care, including limited insurance coverage, language barriers, and immigration-related challenges. These findings highlight the importance of recognizing NCC in non-endemic settings, where this often underrecognized disease contributes substantially to neurologic morbidity in a vulnerable population.

Objective: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections present a significant public health challenge in the United States due to multidrug resistance, substantial added inpatient costs, and subsequently high mortality rates. Method: A decision-analytic model was developed to evaluate the cost-effectiveness of sulbactam-durlobactam compared to colistin for treating CRAB infections, using data from the Acinetobacter Treatment Trial Against Colistin (ATTACK) trial, in which patients received either sulbactam-durlobactam or colistin alongside imipenem-cilastatin. The model incorporated survival rates, clinical outcomes (complete or incomplete cure), and the incidence and costs of acute kidney injury, which is more frequent in colistin-treated patients. Deterministic sensitivity analysis and two scenario analyses were performed. Results: The base case analysis estimated an expected per-patient cost of $57,887 for sulbactam-durlobactam compared to $55,157 for colistin. Patients treated with sulbactam-durlobactam had higher survival than those treated with colistin (0.66 versus 0.46), corresponding to 0.19 additional life saved per patient. The incremental cost-effectiveness ratio (ICER) for sulbactam-durlobactam compared with colistin was $14,097 per additional life saved. The ICER was most sensitive to the proportion of survivors with incomplete clinical cure for both treatments, the costs of sulbactam-durlobactam and cefiderocol, and survival outcomes in patients treated with sulbactam-durlobactam. Scenario analyses showed that the cost-effectiveness of sulbactam-durlobactam was sensitive to clinical cure outcomes, with ICERs ranging from $69,758 per additional life saved to dominance favoring sulbactam-durlobactam under different assumptions. Conclusions: Although treatment costs were higher, sulbactam-durlobactam has a favorable cost-effectiveness profile as compared with colistin when accounting for the costs of managing acute kidney injury.

Background: Dengue fever has become an epidemiological concern worldwide, with 531,617 cases reported in Argentina during the 2023-2024 season. The El Nino Southern Oscillation (ENSO) phenomenon has been linked to changes in dengue dynamics. This study assessed the relationships among ENSO, local climatic variables, and dengue outbreaks in Argentina from 2018 to 2024. Methods: A nationwide spatiotemporal analysis was conducted using dengue cases and monthly mean temperature, relative humidity, and rainfall. The Southern Oscillation Index (SOI) was used as the ENSO indicator (El Nino phase=< minus0.5, neutral phase= minus0.5 to 0.5, and La Nina phase= > 0.5). We fitted Hierarchical Bayesian models with Integrated Nested Laplace Approximation (INLA). A Negative Binomial distribution of dengue cases was used to account for overdispersion. Spatial dependence was modeled by using the Besag York Mollie 2 (BYM2) structure, adjusted for population. Results: The final model explained 53.7% of the variation in Argentinas departmental monthly dengue cases during the study period. Exposure response curves of posterior probability and 95% credible intervals suggested that dengue risk increased when monthly mean temperatures were between 20 and 30 degrees Celsius during the El Nino or neutral phase, with less consistent effects during the La Nina phase. Humidity >50% was associated with increased dengue risk during the La Nina phase, with less steep or absent associations during El Nino or neutral phases. Negative SOI scores were associated with an increased risk of dengue after controlling for the covariates. Conclusion: Dengue outbreaks in Argentina were independently associated with temperatures between 20 and 30 degrees celsius during the El Nino and neutral phases, humidity > 50% during the La Nina phase, and the El Nino phase of the ENSO. Incorporating ENSO indices into predictive models could enhance early warning systems and timely public health interventions in Argentina.

Background: The relationship between recent viral infection and subsequent susceptibility to, or protection against, other viruses remains unclear, particularly across ages and symptom status. Methods: A prospective cohort study enrolled participants aged 6 months to 49 years in Washington and Oregon, USA, 2022-2024. Weekly nasal swabs were tested for SARS-CoV-2, respiratory syncytial virus (RSV), and influenza A/B; additional swabs were collected during symptomatic illness and were also tested for parainfluenza (PIV) 1-4, endemic human coronaviruses (hCOV), adenovirus, human metapneumovirus, human rhinovirus (hRV), and enteroviruses. Proportional hazards regression models were used to characterize associations between incident symptomatic infection (illness) and history of recent illness due to other viruses (within 1-7, 8-14, 15-30, 31-60, 61-90, 91-180 days), adjusted for geographic region, age, sex, daycare/school/work attendance, household size, and number of children in the household. For SARS-CoV-2, influenza, and RSV, these analyses were repeated to study incidence of infection (including asymptomatic cases). Findings: Of 3,560 participants, 2,969 (83%) had [&ge;]1 illness over 4,299 person-years. Adjusted hazard ratios (aHRs) in the short term ([&le;]2 weeks) after an illness were predominantly below 1, indicating that recent viral illness was often associated with lower risk of subsequent illness with other viruses. Across age groups, recent hRV illness was associated with lower risk of hCOV, PIV, and RSV illness (aHRs 0.07-0.27). SARS-CoV-2 illness was associated with a higher short-term risk of adenovirus and PIV illness (aHRs 3.20-3.33). In children aged 6 months-4 years, recent influenza illness was associated with higher short-term risk of SARS-CoV-2 illness. Including asymptomatic infections generally attenuated these associations. Interpretation: Some viral illnesses may alter short-term susceptibility to subsequent viral illnesses. Interactions may differ by age and symptom status. Funding: US Centers for Disease Control and Prevention; Washington State Department of Health.

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Climate change is increasingly invoked to explain long-term shifts in vector-borne disease, yet observed incidence reflects both ecological processes and the systems used to detect disease. Distinguishing environmental signals from changes in surveillance is therefore essential for attributing disease trends to global change. We used Lyme borreliosis in Poland as a national case study, analysing 259,003 notifications across 16 administrative regions from 2009 to 2024 (1,024 region-quarters). Multivariable negative binomial models estimated associations with lagged climatic conditions while accounting for temporal trend, a post-2016 structural step, COVID-19 healthcare disruption, seasonality and regional heterogeneity. Hospitalisation proportion provided an independent population-level indicator of changing observed case mix. Reported incidence increased 2.93-fold, whereas hospitalisation proportion declined from 26.4% to 3.5%. Temperature at a three-quarter lag (incidence rate ratio [IRR] 1.069 per 1'C, 95% CI 1.045 - 1.093) and cloud cover at a one-quarter lag (IRR 1.127 per okta, 1.063 - 1.195) were independently associated with reported incidence. However, changes in the observation process were of greater magnitude: the post-2016 structural step was associated with a 57% increase in notifications (IRR 1.571, 1.465 - 1.684), whereas the COVID-19 period was associated with a 48% reduction (IRR 0.524, 0.482 - 0.568). The divergence between increasing notifications and declining hospitalisation indicates substantial expansion in ascertainment of milder disease, such that notification trends cannot be interpreted as proportional changes in transmission. Our findings show that climatic signals can coexist with, and be obscured or amplified by, changes in disease observation. Robust attribution of vector-borne disease responses to global environmental change therefore requires explicit modelling of surveillance processes and integration of epidemiological, healthcare and ecological data.

Background Rising antimicrobial resistance (AMR) in the African region contributes to high morbidity and mortality. Continuous national AMR surveillance is critical in understanding the spread of AMR and informing policies on containment. We present results of national AMR surveillance in Kenya Methods Passive surveillance was prospectively conducted in 20 sites in Kenya between 2021 and 2025. Sites included national and sub-national level tertiary public and private hospital laboratories. Non-duplicate isolates of WHO priority Gram-negative and Gram-positive pathogens were included in this analysis. Bacterial isolates were identified using either conventional identification methods, Analytical Profile Index or automated systems while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method or automated systems and interpreted using the Clinical and Laboratory Standards Institute guidelines. The primary outcomes were the proportions of various priority bacteria isolated and the proportions resistant to commonly used antibiotics. Results Between 2021 and 2025, there were 15,124 priority pathogens isolated with 7,592 (50.2%) from urine, 5,430 (35.9%) from blood (35.9%), and 1,784 (11.8%) from respiratory specimens. Escherichia coli and Klebsiella pneumoniae accounted for 76.3% of the priority pathogens. Resistance to 3rd generation cephalosporins was 63.2% for Escherichia coli and 79.1% for Klebsiella pneumoniae for the period 2021 to 2025 while carbapenem-resistance was 30.4% for Klebsiella pneumoniae and 7.2% for Escherichia coli. Resistance to carbapenems by Klebsiella pneumoniae increased from 17.9% in 2021 to 35.9% in 2025 while Methicillin resistance in Staphylococcus aureus increased from 36.5% in 2021 to 56.4% in 2025. Conclusion Resistance to critical antibiotics is a significant problem in Kenya, with alarming rates of Methicillin Resistant Staphylococcus aureus and carbapenem resistant Klebsiella pneumoniae. Ugent and sustained infection prevention and control measures and appropriate antimicrobial stewardship activities should be instituted across all health facilities in the country. There is need for improved access to antibiotics with activity against these resistant pathogens.

Objective: This study estimated the vaccine effectiveness (VE) of 20-valent pneumococcal conjugate vaccine (PCV20) against culture-confirmed pneumococcal pneumonia hospitalizations among adults using a test-negative case-control design. Methods: We included adults ([&ge;]18 years) hospitalized with pneumonia in the U.S. Veterans Affairs Healthcare System between January 2023 and December 2025 who had respiratory cultures collected. VE was estimated using multivariable logistic regression adjusted for demographic and clinical characteristics. Subgroup analyses were conducted by age, risk group, and U.S. census region. Sensitivity analyses included inverse probability of treatment weighting (IPTW) and evaluation allowing previous PCV13 vaccination. Results: Among 34,009 pneumonia hospitalizations, 837 (2.5%) were Streptococcus pneumoniae culture-positive and 7,428 (21.8%) individuals had received PCV20. PCV20 vaccination was associated with lower odds of culture-confirmed pneumococcal pneumonia hospitalization among adults aged [&ge;]65 years (VE 20.4%; 95% CI: 2.1%, 35.3%), with greater effectiveness observed among those with chronic medical conditions (VE 24.4%; 95% CI: 0.7%, 42.4%). VE was highest in the Western region among adults aged [&ge;]65 years (39.6%; 95% CI: 3.2%, 62.3%), a region with a high burden of serotype 4 disease. Overall, VE among adults aged [&ge;]18 years was 8.8% (95% CI: -8.8%, 23.6%). Findings were consistent across multivariable and IPTW-adjusted analyses. Conclusion: PCV20 provided significant protection against pneumococcal pneumonia hospitalizations among older adults, with greater effectiveness in regions where vaccine-covered serotypes are more prevalent. These findings support the importance of aligning pneumococcal vaccination strategies with regional serotype distribution to maximize vaccine impact.