Pediatric Infectious Disease Journal

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

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

Importance: Maternal vaccination and long-acting monoclonal antibodies are now available in the U.S. to prevent RSV. Long-acting monoclonal antibody administration in the U.S. commonly occurs after hospital discharge in outpatient settings, leaving some infants unprotected early in life when severe RSV risk is highest. Comparative effectiveness between the two interventions and whether delays affect effectiveness estimates have not been quantified. Objective: To evaluate the effectiveness of infant long-acting monoclonal antibody strategies and a maternal vaccination strategy, each compared to no intervention, and the comparative effectiveness of intervention strategies when accounting for real-world delays in monoclonal antibody receipt. Design: Cohort study using target trial emulation to compare four strategies for prevention of RSV-related outcomes. Setting: The U.S. between 2023 and 2025 using a nationwide database of employer-sponsored commercial insurance claims. Participants: 120,586 commercially insured mother-infants, whose infants were born in the U.S. during the 2023-2024 or 2024-2025 RSV season. Infants who could not be paired with their mother's record, did not enroll in commercial insurance within 75 days from birth, received palivizumab, and had an implausible birth date were excluded. Interventions: Comparison of four RSV prevention strategies: (i) maternal RSVpreF; (ii) long-acting monoclonal antibody given within the first week of life (mAb as intended); (iii) long-acting monoclonal antibody given within a six-month grace period from birth (mAb within grace period); and (iv) a control. Main outcomes and measures: Effectiveness against first RSV-associated hospitalization and medically-attended RSV illness was summarized using adjusted hazard ratios (aHR) and estimated using an inverse propensity weighting approach, with weights accounting for maternal age, maternal comorbidities affecting pregnancy, obstetric and newborn complications, season, region, and birth timing relative to October 1. A weighted Kaplan Meier estimator was used to estimate strategy-specific cumulative incidence of RSV outcomes over time. Results: In the first five weeks of life, the mAb within grace period strategy doubled the hazard of RSV hospitalization (aHR: 2.0 [95% CI: 1.0-4.9]) and increased the hazard of medically-attended RSV (aHR: 1.6 [95% CI: 1.0-2.7]) compared to the maternal RSVpreF strategy. The hazard for RSV hospitalization was similar for the mAb as intended strategy compared to the maternal RSVpreF strategy (aHR = 0.9 [95% CI: 0.3-1.9]). Conclusions and relevance: RSVpreF and monoclonal antibodies were similarly effective when monoclonal antibodies were administered close to birth, but when accounting for real-world delays in monoclonal antibody receipt, the maternal RSVpreF strategy was more effective than the mAb within grace period strategy.

Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

BACKGROUND: We used anthropometric data from electronic health records (EHRs) of Swiss childrens hospitals to evaluate growth references and estimate centile curves. METHODS: We received EHRs extracted from seven Swiss childrens hospitals and analysed two samples: all children with a height, weight, body mass index (BMI), or head circumference recording, and a subsample restricted to children without diseases potentially affecting growth, weighted to represent the general population. We calculated mean z-scores based on the World Health Organization growth references adopted for Switzerland in 2011 (CH-WHO 2011) and current Swiss growth references (Swiss 2026). We estimated sex-specific centile curves in the subsample using generalised additive models for location, scale, and shape. RESULTS: We included 213,868 children with height, 448,002 with weight, 209,244 with BMI, and 67,397 with head circumference recordings. Mean z-scores in the all children sample were (CH-WHO 2011; Swiss 2026): height (0.10; -0.19), weight (0.16; -0.09), BMI (0.04; -0.07), head circumference (-0.28, -0.28); and in the subsample: height (0.34; 0.00), weight (0.27; 0.01), BMI (0.18; 0.05), and head circumference (0.04; 0.01). The 50th height, weight, BMI, and head circumference centiles of girls and boys in the subsample closely followed those of Swiss 2026, with slightly wider 3rd and 97th centiles in infancy and adolescence. CONCLUSION: Height, weight, BMI, and head circumference centiles aligned well with the Swiss 2026 growth references in Switzerland, demonstrating that hospital EHRs could contribute to future growth references.

Background. Urine-based testing offers a promising non-sputum approach for diagnosing paediatric tuberculosis. However, the currently available lipoarabinomannan (LAM) assay shows limited sensitivity in children and is primarily indicated for those living with HIV. Co-detection of LAM with Mycobacterium tuberculosis (Mtb) proteins in urine could provide complementary pathogen-derived biomarkers that improve diagnostic performance. Methods. We developed an ultrasensitive multiplex electrochemiluminescence (ECL) immunoassay to measure Ag85B, CFP-10, ESAT-6, MPT32, and MPT64 in urine. We determined the analytical limits of detection and evaluated the diagnostic performance of individual proteins and LAM using urine samples from children with Confirmed, Unconfirmed, and Unlikely pulmonary tuberculosis enrolled across five high-burden countries (The Gambia, India, Peru, South Africa, and Uganda). Performance was assessed overall, by HIV and nutritional status, and across biomarker combinations. Findings. Urine samples from 630 children were analysed (median age was 4 years [IQR 2-8]; 44% female, 15% living with HIV, 19% underweight, 24% with Confirmed tuberculosis). The ECL assay achieved femtomolar limits of detection (1.5 to 4.0 fM). The sensitivity and specificity of individual Mtb proteins were 12-33% and 98-100%, respectively. Ag85B had the highest sensitivity (33%, 95% CI 26-41) for Confirmed tuberculosis and was similar to LAM. A four-antigen signature (Ag85B, MPT64, MPT32, LAM) was 50% sensitive (95% CI 42-58) and 94% specific (95% CI 90-96), and was significantly more sensitive than LAM alone, in particular among those without HIV. An additional sixteen (10%) of children with Unconfirmed TB had at least one Mtb protein or LAM detected. Interpretation. Multiple Mtb proteins are detectable in paediatric urine with high specificity, and multi-antigen signatures can augment sensitivity versus LAM alone. These findings demonstrate the potential of multi-antigen urine detection for childhood TB and define analytical targets for the development of future point-of-care diagnostics. Funding. National Institutes of Health.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

Background Rural-urban disparities in SARS-CoV-2 infection epidemiology remain poorly quantified and understood in Zambia despite differences in healthcare access, services and preventive interventions. This study examined the geographical distribution and associated factors of SARS-CoV-2 cases across selected rural and urban districts of Zambia. Methods A convergent mixed-methods study comprised of quantitative survey and qualitative interviews was conducted in; Ndola (Urban), Kafue (Peri-urban) and Lufwanyama (Rural). The proximate determinant framework guided variable selection and interpretation. Quantitative combined (Hospital-surveillance data with community survey), while qualitative included In-depth interviews. Participants were sampled using multistage sampling technique. Quantitative data were analysed using STATA version 17, while qualitative data were analysed thematically. Findings were integrated through triangulation. Results A total of 528 participants were included, with a median age 31 years (15-71). Overall SARS-CoV-2 positivity was 12.6%, varying across rural (16.5%), peri-urban (14.9%), and urban (9.9%) settings, though residence was not associated with infection (P<0.132). Participants aged [&ge;]49 years had significantly higher odds of infection (aOR=8.78; 95% CI:1.15-66.99), whereas secondary education (aOR=0.37; 95% CI:0.16-0.86) and hospital-based testing (aOR=0.37; 95% CI:0.15-0.92) were associated with lower odds of infection. Vaccine uptake was highest in urban areas but was not independently associated with infection. Qualitative findings revealed marked rural-urban differences in perceived susceptibility, testing access, vaccine decision-making, and adherence to preventive measures, explaining several quantitative observations. Conclusion SARS-CoV-2 infection across rural and urban settings in Zambia was influenced by demographic, behavioral, and health-system factors rather than geographic residence alone. These findings highlight the need for context-specific prevention strategies, equitable access to testing, strengthened community surveillance, and targeted risk communication to improve preparedness and response for future respiratory disease outbreaks.

Background The historic decline in childhood pneumonia mortality was driven substantially by single-pathogen vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Yet the pathogen spectrum underlying child pneumonia deaths is diversifying: the effective number of pathogens rose from 5.57 in 1990 to 9.94 in 2023, and the residual burden is shifting toward opportunistic and hospital-associated pathogens for which no licensed childhood vaccines exist. This paper asks how resources should be sequenced between single-pathogen interventions and platform investments as this transition proceeds. Methods We analyzed Global Burden of Disease Study 2023 deaths from 29 pathogens in ages 0-19 years by super-region, combined with WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) for PCV3 and Hib3. We quantified the spectrum transition under two denominators (26- and 29-pathogen calibers), constructed a share-by-intervenability matrix assigning each pathogen to a dominant intervention channel (vaccine-reachable, mixed, platform-sensitive) under explicit classification rules, compared platform-sensitive deaths with a transparently computed scenario of residual vaccine-preventable deaths, and cross-classified pathogens by age tropism and poverty lock. We anchored platform interventions to verified published evidence. Results The vaccine-preventable group share fell from 54.0% to 40.2% while the opportunistic/hospital group rose from 18.1% to 23.1% (29-pathogen caliber, 1990-2023). Super-region vaccine coverage showed no significant association with pathogen-share change (PCV3 Spearman rho = 0.108, p = 0.818; Hib3 rho = -0.036, p = 0.939), a null result we report as evidence that simple coverage-burden correlations do not hold at the regional level, not as evidence against vaccine value. In 2023, vaccine-reachable pathogens accounted for 441,410 deaths (45.7%, channel including COVID-19), mixed for 126,926 (13.1%), and platform-sensitive pathogens for 396,995 (41.1%). Platform-sensitive deaths were 2.9-5.1 times the scenario estimate of residual vaccine-preventable deaths (52,435-77,512). Nine of 14 classifiable pathogens fell into the poverty-locked, infant-tropic cell (480,922 deaths; Fisher OR = 9.0, p = 0.1758). Conclusions The marginal value of single-pathogen strategies declines as the spectrum diversifies and residual deaths concentrate in platform-sensitive, poverty-locked, infant-tropic pathogens. Vaccine scale-up remains a certain and sizeable opportunity; the next increment of marginal resources should increasingly fund platform capabilities (oxygen systems, antimicrobial access and stewardship, infection prevention and control, referral, and nutrition) delivered as a package to the populations where the residual burden is locked.

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: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

Background Scrub typhus, an acute bacterial infection caused by Orientia tsutsugamushi, is an important, under-recognized etiology of febrile illness in South Asia. Accurate surveillance for scrub typhus in Nepal is challenging due to non-specific symptoms and limited diagnostic tools. Methods We conducted a representative school-based cross-sectional serosurvey in Kavrepalanchok and Dolakha, Nepal between November 2021 and April 2022 using two-stage sampling, we randomly selected 13 public schools and then up to 100 children aged 4-18 years per school. We collected capillary blood samples and tested for IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercially available ELISA kits. We estimated seroincidence rates using previously-published models of antibody decay dynamics from confirmed scrub typhus cases. We compared seroincidence to seroprevalence estimates using cutoffs derived from Gaussian finite mixture models applied to the study population. Results We enrolled a total of 827 children (participation rate: 94.8%). The median age was 10 years (IQR: 8-13), and 53.08% of the participants were female. The overall seroincidence rate was 6.3 new infections per 1000 person-years (95% CI: 4.7- 8.4), and the rate was slightly higher in peri-urban Kavrepalanchok (7.3; 95% CI: 4.9 - 10.3) compared with rural Dolakha (5.3; 95% CI: 3.3 - 8.5). Seroincidence increased with age, from 3.6 new infections per 1000 person-years (95% CI: 1.4- 9.7) among children aged 4- 7 years to 9.4 (95% CI: 6.2-14.3) among children aged 14-18 years. Seroincidence was higher in females (8.3; 95% CI: 5.9 -11.8) than in males (4.1; 95% CI: 2.4 - 6.9) (p=0.02). The overall seroprevalence was 6.5% (95% CI: 4.9-8.4) and followed a similar age and geographic trend to the seroincidence rate. Discussion Our findings reveal a substantial burden of pediatric scrub typhus in the Kavrepalanchok and Dolakha districts of Nepal. Seroincidence increased with age and was higher among females. School-based serosurveys offer an efficient sampling frame to rapidly assess population-level scrub typhus transmission intensity among children and adolescents, though may not represent out-of-school populations.

Background: Case fatality reflects the quality and timeliness of clinical care for leptospirosis, yet no study has examined it at a national level in the Dominican Republic (DR), where leptospirosis is endemic. We describe the case fatality rate (CFR) of leptospirosis in the DR between 2012 and 2026 and identify associations with mortality. Methods: We conducted an analytical cross-sectional study, using national surveillance records merged with a discharge-condition extract via a composite key. We calculated CFR with Wilson 95% confidence intervals among 5,412 valid cases (suspected, probable, or confirmed) reported from January 2012 through June 2026. We compared proportions with Pearson's chi-square test, assessed annual trend with ordinary least squares linear regression, and fitted multivariable logistic regression models to account for confounding. Results: Overall CFR was 8.5% (460/5,412), with no significant annual trend (p=0.372). CFR was higher in men than women (p < 0.001) and increased significantly with age (p < 0.001). Male gender (OR: 1.79; 95%CI: 1.18-2.73) and pre-existing comorbidity (OR: 1.76; 95% CI: 1.21- 2.57) were independent predictors of death. Clinical complications were the strongest predictor in the adjusted model (OR: 3.16; 95%CI: 2.17-4.61), attenuating the gender effect. CFR varied widely by province (2.43-22.22%) and correlated negatively with incidence at the province level (p = 0.066). Conclusions: Leptospirosis case fatality is concentrated among men, people with comorbidity, and those who develop clinical complications. These national, long-term findings can help prioritize clinical and surveillance resources as extreme weather events are expected to intensify across the Caribbean.

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 Childhood respiratory infectious deaths are partitioned across four Global Burden of Disease cause modules-26 etiological attributions within lower respiratory infections, tuberculosis, COVID-19, and whooping cough-never jointly reported. Whether the structure of this combined mortality spectrum has changed over time, and with what implications for intervention design, has not been quantified. We assembled and analyzed the integrated spectrum for children and adolescents aged 0-19 years, 1990-2023. Methods We integrated Global Burden of Disease Study 2023 (release v8352) estimates into a 29-node spectrum-26 lower respiratory infection etiologies plus tuberculosis, COVID-19, and pertussis-globally and across seven super-regions, with uncertainty propagated by summing bounds. We computed Shannon diversity, Herfindahl concentration, and effective cause counts; phenotyped pandemic-window collapse and rebound per cause; linked pathogen shares to WHO/UNICEF vaccine coverage; and mapped geographic concentration in sub-Saharan Africa and South Asia. Reporting follows GATHER. Results In 2023 the 29 causes jointly accounted for 965,330 deaths (95% uncertainty interval [UI] 680,096-1,342,437). Shannon diversity rose from 2.336 to 2.711 (+16.1%) between 1990 and 2023; the effective number of causes nearly doubled (5.57 to 9.94), inversely coupled to total deaths (Spearman rho = -0.997). Whooping cough ranked second (112,954 deaths; 95% UI 64,576-185,708; 11.7%) and showed the spectrum's only rebound above 100% (-57.4% collapse, +111.0% rebound). Tuberculosis ranked third (87,764; 57,779-124,912; 9.1%) with the highest concentration in sub-Saharan Africa and South Asia (87.1%). COVID-19 entered at rank five (52,899; 47,275-59,183; 5.5%). Nineteen of 29 causes exceeded the poverty-lock threshold (>80.59% of deaths in sub-Saharan Africa plus South Asia). Conclusions Childhood respiratory infectious mortality has become more diverse and more concentrated in poverty as it has declined. Single-pathogen interventions now address a shrinking share; the spectrum's structure argues for platform interventions-oxygen, antimicrobial access, referral-tailored jointly by age and geography, implying that pathogen-specific strategies alone cannot finish the remaining mortality agenda.

Background: Tuberculosis (TB) remains a major public health challenge globally, with Pakistan ranking among the highest TB burden countries worldwide. Although several novel TB vaccine candidates for adolescents and adults are advancing through late-stage clinical trials, little is known about how these vaccines may be introduced in high-burden settings such as Pakistan. Understanding stakeholder perspectives is crucial for informing early implementation planning and policy development. Methods: We conducted an exploratory qualitative study using semi-structured in-depth interviews with key stakeholders involved in TB control, immunization, clinical care, and health policy in Pakistan. Participants were purposively selected from national and provincial TB programs, Expanded Programme on Immunization (EPI), clinical settings, and academia. Interviews were conducted in English or Urdu, audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis following the Braun and Clarke framework. A hybrid deductive-inductive coding approach was used. Results: Ten stakeholders participated including one whose interview also served as a pilot test of the interview guide. Participants expressed strong support for the introduction of a new TB vaccine, driven largely by Pakistan's high TB burden and the limitations of current prevention strategies. However, support was based on the availability of strong evidence regarding vaccine safety, effectiveness, and feasibility. Key barriers to vaccine acceptability included low perceived risk of TB, misinformation, stigma, sociocultural influences, and limited public awareness. Stakeholders emphasized community engagement, trusted healthcare providers, and effective communication as critical enablers. Health system challenges included workforce shortages, cold chain limitations, and financing constraints. Household contacts of TB patients were consistently identified as the priority group followed by adolescents and people living with HIV. A phased implementation strategy was broadly preferred followed by gradual integration into existing health services. Conclusion: Stakeholders in Pakistan broadly support new TB vaccines for adolescents and adults. Successful implementation will require addressing sociocultural barriers, strengthening health system capacity, and developing context-specific delivery and prioritization strategies. Early stakeholder engagement and implementation planning are essential for meaningful public health impact in Pakistan.

In primary healthcare centers lacking advanced imaging, community-based active tuberculosis (TB) case finding often relies on basic symptom screening. This approach often misses cases and leads to the inefficient allocation of rapid molecular testing (RMT). We aimed to develop and internally validate a simple clinical triage scorecard to improve TB detection and guide RMT use in resource-constrained settings. We conducted a retrospective cross-sectional study of 15,137 adults ([&ge;]18 years) evaluated within the Zero TB Yogyakarta program (2020-2025). Participants with complete clinical assessments and confirmatory GeneXpert results were included. Using multivariable logistic regression, we identified independent clinical predictors, which were subsequently transformed into an integer-based point scorecard. Model performance was evaluated via discrimination and calibration, utilizing bootstrap resampling (1,000 iterations) for internal validation. Among the 15,137 participants, 251 (1.7%) were GeneXpert-positive. The final multivariable model identified eight independent predictors: age, male sex, body mass index, prolonged cough, hemoptysis, unexplained weight loss, TB contact history, and diabetes mellitus. The model demonstrated strong predictive accuracy, with an optimism-adjusted AUROC of 0.836 and good calibration. When translated to the integer scorecard and compared directly to standard national symptom screening, the scorecard performed (AUROC 0.81 vs. 0.73; p<0.001). At a high sensitivity cut off score of [&ge;] 0, the tool achieved 93.63% sensitivity and 41.33% specificity. This point-of-care clinical scorecard provides higher diagnostic accuracy than standard symptom screening algorithms. By offering flexible operational thresholds, it empowers local health programs to dynamically balance the urgency of case detection with available diagnostic capacity, optimizing GeneXpert allocation where advanced radiological imaging is unavailable.

Background National childhood respiratory pathogen spectra are diversifying nearly everywhere - within-country diversity rose in 203 of 204 countries between 1990 and 2023 - yet whether countries are diversifying toward a common spectrum or along divergent paths is unknown. We quantified between-country compositional distance of national pathogen spectra over the same period. Methods We built national pathogen share vectors from Global Burden of Disease Study 2023 lower respiratory infection etiologic attributions (26 pathogens, 204 countries, ages 0-19 years) at five timepoints spanning 1990-2023. Between-country distance was measured as all pairwise Jensen-Shannon divergences (JSD; primary) and Bray-Curtis dissimilarities, with Baselga and Jaccard decompositions; robustness was assessed across metrics, pathogen panels, low-count thresholds and a balanced panel of 107 countries. Results Mean pairwise JSD rose from 0.0084 in 1990 to 0.0283 in 2023 (+238%; trend p = 0.030), peaking in 2021 (+283%) with a partial 2023 pullback. Bray-Curtis dissimilarity rose +120% and the balanced panel +423%. Divergence was entirely balanced variation (share reallocation), with spectrum richness rising from 18.5 to 21.1 of 26 pathogens. Dispersion rose fastest for influenza (coefficient of variation 0.03 to 0.55) and respiratory syncytial virus (0.08 to 0.48). Within-region distance rose in every computable GBD super-region (five of seven): divergence occurs within regions, not between blocs. Conclusions National spectra are re-sorting along country-specific axes as vaccine-preventable dominance recedes at different speeds. Diversification is universal, but convergence is absent: the transition at the etiologic-spectrum level is asynchronous and path-dependent, with implications for empirical treatment policy and pathogen surveillance.

Public genomic repositories can support antimicrobial resistance (AMR) surveillance, but unequal sampling can bias interpretation. We characterised AMR determinants, multicountry genomic cluster overlap and surveillance gaps across Africa using an NCBI Pathogen Detection snapshot retrieved on 24 August 2026 for 55 African Union member states. Records were validated and deduplicated by BioSample, and complete AMRFinderPlus calls were summarised across five United Nations M49 subregions and eight overlapping regional economic communities (RECs). Country-pair cluster overlap was assessed using the Jaccard index, while project-based and composition-standardised sensitivity analyses evaluated repository bias. The dataset contained 86,829 unique BioSamples from 51 states; South Africa, Malawi and Kenya contributed 55.8%. Complete extended-spectrum {beta}-lactamase calls were detected in 21,513 isolates and carbapenemase calls in 4,642. blaCTX-M-15 dominated the ESBL profile, while NDM and OXA types predominated. Seventy clusters contained carbapenemase-positive isolates from at least two countries. A shared REC covered all participating countries in 38 clusters, while 32 crossed REC boundaries. Normalised country-pair overlap was low, with a maximum Jaccard index of 9.5%. Project balancing reduced the Northern African carbapenemase estimate from 32.3% to 17.9% and the Eastern African ESBL estimate from 36.9% to 12.5%. Public repositories identify determinants and clusters for investigation but do not estimate prevalence or transmission. AMR surveillance should combine national confirmation, regional institution-led investigation where countries share an REC, and continent-wide coordination through Africa CDC for cross-REC signals, supported by representative One Health sampling, standardised metadata and sustained African sequencing capacity.