International Journal of Infectious Diseases

Tuberculosis (TB) remains a major global health challenge, particularly in low- and middle-income countries such as Mozambique. To address this burden, promising new preventive TB vaccines targeting adolescents and adults are currently in phase III efficacy trials. This study aimed to assess stakeholders perspectives on priority high-risk groups, the challenges in reaching them, and potential strategies for delivering a TB vaccine. We conducted a qualitative study using semi-structured interviews with members of the National TB Program, the National Immunization Program, and the National Immunization Technical Advisory Group. Data were collected between March and July 2024. Our findings suggest that a TB vaccine program in Mozambique should prioritize individuals with comorbidities, especially those living with HIV or diabetes, and close contacts of TB patients, followed by healthcare workers, miners, and incarcerated populations. Although uptake is expected to vary across groups, relatively high coverage was anticipated among people living with HIV, TB contacts, and older adults, as well as healthcare workers, incarcerated individuals, formal miners, and in-school adolescents. To improve uptake, campaign-based strategies using mobile brigades were considered promising approaches to expand coverage. Stakeholder perspectives highlight the importance of prioritizing high-risk groups and adopting context-specific delivery strategies to support the effective introduction of a TB vaccine in Mozambique. Clinical trial numbernot applicable.

Use of fungal mycelia, which has antiviral properties, constitutes a novel strategy for addressing existing and newly emerging viral diseases. We evaluated safety and feasibility of fungal mycelia (Fomitopsis officinalis and Trametes versicolor, FoTv) for treatment of COVID-19 and assessed its antiviral effects and potential to reduce symptoms. In a randomized, double-blind, placebo-controlled, dual site (UCSD/UCLA medical centers) clinical trial we examined non-hospitalized patients who contracted mild-to-moderate COVID-19 [≤] 96 hours, and experienced symptom onset [≤] nine days, before enrollment. FoTv was safe, well-tolerated, and feasible for COVID-19 treatment. Minor differences in biochemical markers were observed between groups (26 FoTv, 24 Placebo). FoTv significantly reduced the number and severity of symptoms, particularly sore throat/cough, and in vitro SARS-CoV-2 (pseudovirus) cellular infection. In conclusion, FoTv was safe and reduced COVID-19 symptoms and cellular viral infection. Future studies should investigate therapeutic benefits of fungal mycelia for SARS-CoV-2 and other viruses. Clinicaltrials.gov registration:NCT04667247.

BackgroundTuberculosis (TB) remains a critical public health challenge, with two-thirds of the global TB burden in ten Asian countries. Social vulnerabilities, comorbidities, health inequity, multi-dimensional poverty, malnutrition, and barriers to healthcare access continue to fuel TB epidemic. Inability to detect asymptomatic and sub-clinical TB, combined with passive approach in service delivery and overreliance on smear microscopy, leads to delayed diagnosis, a substantial burden of undetected cases, and continuing TB transmission in the communities. In such a context, the introduction and scale-up of active case-finding approaches - including community-based TB screening using highly sensitive screening tools and novel rapid diagnostics - becomes a strategic priority to interrupt transmission. The growing availability of multiple screening and diagnostic options makes evidence-based decision-making increasingly complex. MethodsTo estimate the potential epidemiological impact and cost implications of scaling up TB diagnostics and community-based screening in ten high-burden Asian countries, we constructed a mathematical model and evaluated multiple intervention scenarios. We then assessed and compared four service delivery models: 1) digital ultraportable chest x-ray (UPCXR) & Xpert/Truenat in community, 2) digital UPCXR in community and Xpert/Truenat at health facilities, 3) digital UPCXR in community and near point of care (nPOC) at health facilities, 4) nPOC in community & Xpert/Truenat at health facilities - for total investment required and projected health benefits for their cost-effectiveness. Results and conclusionsThe modelling study indicated that strengthening health facility capacity (with enhanced TB screening, expanded molecular diagnostics, reduced loss to follow-up, private sector standard of care, leading to increased treatment coverage & quality of active disease treatment and reduced post-treatment relapse, scale-up of TB preventive treatment (TPT), and provision of nutritional support to 80% of TB patients and their household contacts) can significantly reduce TB incidence and mortality; however, community-wide mass screening remains essential to achieving TB elimination targets. Targeted screening of vulnerable populations demonstrated greater cost-effectiveness than untargeted screening approaches. Achieving the End TB goals will ultimately require an effective TB vaccine with high population-level coverage. AI-enabled digital UPCXR-based screening combined with Xpert/Truenat testing at the community level demonstrated maximum epidemiological impact potential, while the most cost-efficient model is Digital UPCXR in the community combined with nPOC testing at health facilities. An investment of USD 12.7 billion over the next five years in community-level implementation of digital UPCXR and molecular diagnostics could avert an additional 9.8 million TB cases and 1.9 million deaths across ten Asian countries over a ten-year horizon

Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population where the majority are or have been on antiretroviral therapy (ART), comparing mortality between those who received empiric TB treatment and those who did not. Materials and Methods: From November 2017 to December 2020, Xpert-negative presumptive TB adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29-45) years, 82.3% on ART, median CD4 206 cells/mm3 (IQR 36-507). Of the 300 participants, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 91.4% among inpatients, 72% within three months post-enrolment. Mortality was higher among those who received empiric TB treatment (51.5 vs. 30.2 per 1,000 person-months; p=0.013) compared to those who did not. TB cultures were positive in 5.0% (15/300), of whom seven (46.7%) were also TB-LAM positive. CrAg was positive in 12.3% and 3.7% had positive blood culture. Conclusion: We found high mortality among Xpert-negative PLHIV, particularly those who received empiric TB treatment, despite high ART coverage. Cryptococcal antigenemia and bacteremia were not uncommon. In presence of negative Xpert results in PLHIV, clinicians should perform extensive laboratory evaluations to identify possible comorbidities or alternative non-TB diagnosis.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460). Conclusions Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) are leading causes of infectious disease deaths, with disproportionate impact in low- and middle-income countries (LMICs). Despite well-established biological relationships between these diseases, there is limited information on how TB prevalence differs between people living with and without HIV. MethodsWe conducted a systematic review and meta-analysis of TB prevalence surveys conducted in LMICs and published during January 1st 1993-October 13th 2025 (PROSPERO CRD42024503853). We extracted bacteriologically-confirmed TB prevalence estimates stratified by participant HIV status. Surveys that offered HIV testing to all, sputum-collection-eligible, or TB-positive participants were included in the primary analysis. We applied Bayesian meta-regression to estimate pooled risk ratios (RR) of bacteriologically-confirmed TB prevalence among participants living with versus without HIV. Additionally, we estimated country-level and overall TB notification-to-prevalence (N:P) ratios by HIV status. FindingsOf 10,211 potentially relevant publications, 12 TB prevalence surveys--representing 264,530 participants within nine countries in Southern and Eastern Africa--were used in the primary analysis. Reported TB prevalence was higher among participants living with versus without HIV in 11/12 surveys, with an overall pooled RR of 3{middle dot}86 (95% credible interval: 2{middle dot}41-5{middle dot}53). N:P ratios were higher among participants living with HIV in all examined countries. The overall pooled N:P ratios were 1{middle dot}74 (0{middle dot}59-4{middle dot}56) and 0{middle dot}48 (0{middle dot}17-1{middle dot}20) among participants living with versus without HIV, respectively. InterpretationIn Southern and Eastern Africa, bacteriologically-confirmed TB prevalence is three- to six-times higher among people living with HIV. Comparison of prevalence and notification data suggest higher rates of TB diagnosis for people living with versus without HIV, but also indicates substantial delays in the detection of untreated TB cases for both populations. FundingWellcome Trust, UK National Institute for Health and Care Research, UK Foreign, Commonwealth and Development Office, NIH. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is limited systematic evidence on how the prevalence of TB disease differs between people living with HIV and without HIV. Multiple observational cohorts have described substantially elevated TB incidence among populations with HIV, but disease prevalence will also be affected by differences in mortality and treatment uptake rates. We searched PubMed from inception through January 21, 2026 using the search string ((HIV AND TB) OR HIV/TB) AND (prevalence AND (systematic review OR meta-analysis)) without any restrictions on language. We also reviewed investigators personal libraries. This search yielded 506 publications; however few of these included prevalence data. An analysis conducted in 2020 synthesized HIV status-stratified data from seven national TB prevalence surveys in Africa and found that HIV prevalence was lower among prevalent TB cases than among notified cases. This study did not include subnational surveys and did not distinguish between survey participants with self-reported or test-confirmed HIV status. Added value of this studyThis study synthesized TB prevalence data, stratified by participant HIV status, from national and subnational surveys conducted in LMICs and published between January 1st 1993 and October 13th, 2025. Collated data represented 681,402 survey participants across ten countries. All but one study were conducted in Southern and Eastern Africa. We limited our primary analysis to surveys that systematically tested participants for HIV and bacteriologically-confirmed TB. The prevalence of bacteriologically-confirmed TB was estimated to be three to six times higher than among people living with versus without HIV. Ratios of TB notifications to TB prevalence were higher for people living with HIV compared to people without HIV, suggesting higher rates of TB case detection (and likely shorter duration of disease) for people living with HIV and untreated TB than those without HIV. Implications of all available evidenceFew estimates of community-representative TB prevalence stratified by participant HIV status exist. These surveys have been concentrated in Southern and Eastern Africa, despite TB-HIV burden being distributed globally. Our findings highlight the elevated burden of TB among people living with HIV in these settings, as well as the limited data on the intersection of TB and HIV epidemiology in other world regions. Furthermore, our comparison of notification and prevalence data demonstrate substantial shortfalls in TB case detection, regardless of an individuals HIV status.

BackgroundDuring Nigerias largest recorded diphtheria outbreak, hospital capacity in Kano State was rapidly overwhelmed. Medecins Sans Frontieres introduced home-based care (HBC) for patients with mild disease to prioritise facility-based care for severe cases. We assessed whether HBC was non-inferior to facility-based treatment in terms of mortality, sequelae, and household transmission. MethodsWe conducted a retrospective matched cohort study. Mild diphtheria cases treated between January 2023 and May 2024 were matched 1:1 by treatment modality (HBC or diphtheria treatment centre [DTC]) on sex, age group, vaccination status, and residence. Conditional logistic regression estimated the association between treatment modality and mortality, with robustness assessed through propensity score weighting, sensitivity analyses, and E-value computation. FindingsOf 990 sampled patients, 678 (367 HBC, 311 DTC) were enrolled (68{middle dot}5%). After adjustment, treatment modality was not independently associated with mortality (HBC vs. DTC: aOR 0{middle dot}40, 95% CI 0{middle dot}13-1{middle dot}30), with similar estimates across sensitivity analyses (E-value 4{middle dot}40). Clinical complications were the strongest predictor of death (aOR 23{middle dot}1, 95% CI 1{middle dot}73-307). Vaccination was protective (aOR 0{middle dot}28, 95% CI 0{middle dot}08- 0{middle dot}94) and treatment delay of four or more days increased mortality (aOR 4{middle dot}15, 95% CI 1{middle dot}23-14{middle dot}0). HBC was not associated with increased household transmission or long-term sequelae. InterpretationVaccination and early treatment, rather than care setting, were the main determinants of survival. When supported by clinical triage and structured follow-up, decentralised care can be used to manage mild cases during diphtheria epidemics in settings with constrained hospital capacity. FundingMedecins Sans Frontieres, West and Central Africa. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Google Scholar for articles published between January 1, 2000, and February 28, 2026, using combinations of the terms "diphtheria", "outbreak", "home-based care", "outpatient", "ambulatory", "community care", and "decentralised care". We found no published studies evaluating any form of decentralised or home-based clinical management for diphtheria. The existing literature on diphtheria case management is confined to facility-based settings: outbreak reports from multiple affected countries describe hospital-based treatment with diphtheria antitoxin (DAT) and antibiotics, and a systematic review pooled epidemiological and clinical data from historical outbreaks. Decentralised care models have been evaluated for other epidemic-prone diseases, including a measles epidemic in the Democratic Republic of the Congo (DRC) where decentralised management reduced mortality among children, and Ebola virus disease outbreaks in DRC where decentralised treatment centres were piloted to improve geographic access, though with limited outcome data. No study has assessed whether patients with diphtheria can be safely managed outside hospital settings. Added value of this studyNo prior evaluation of home-based care for diphtheria has been published. Using a retrospective matched cohort design with 678 patients during the largest diphtheria outbreak in Africa in decades, we found no evidence that home-based care increased mortality, long-term complications, or household transmission compared with facility-based care, and acceptability was high among patients in both groups. The study also provides one of the largest datasets on household transmission of diphtheria in an urban epidemic setting, finding no evidence that home-based care increased secondary transmission, and showing that vaccination status of the index case was the main factor influencing spread within the household. Implications of all the available evidenceProvided that triage is reliable, antibiotics are started promptly, and a functioning referral pathway exists, mild diphtheria can be managed safely at home during large epidemics. This approach preserves limited hospital and DAT resources for patients with moderate or severe disease, shortens treatment delays, and is acceptable to patients. Given ongoing outbreaks across West and Central Africa and persistent DAT supply constraints, decentralised care warrants inclusion in epidemic preparedness.

Background: Community-acquired pneumonia (CAP) remains a major global health burden disproportionately affecting older adults and people with comorbidities, with Streptococcus pneumoniae as one of the leading bacterial causes in Europe. The Hungarian Occurrence and Burden of PnEumonia (Hungarian-HOPE) study examined the incidence, hospitalization rates, and mortality of CAP between 2016 and 2020 in Hungary. Methods: The National Health Insurance Fund database was used to identify adult CAP patients (all-cause) based on ICD-10 codes J10-18. Outcomes included CAP incidence, 0-15-day hospitalization, and 0-30-day mortality after hospitalization, stratified by age, sex, and comorbidities (chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease [CVD], and type 1 and 2 diabetes [T1DM, T2DM]). Risk maps visualized relative risk gradients across population strata. Results: During the pre-pandemic period (2016-2019), over 100,000 CAP cases and more than 50,000 hospitalizations were recorded annually. In 2020, recorded cases fell to approximately 98,000, while hospitalizations increased to 66,200. Hospitalization rates increased from 25.1% in 2016 to 29.1% in 2019, then increased to 43.1% in 2020. The 30-day mortality among hospitalized patients rose from 22.7% in 2016 to 23.6% in 2019. Incidence, hospitalization, and mortality all increased with age. Relative to healthy males aged 30-39 years, CAP risk escalated steeply in the [≥]80 years cohort (incidence 5-15-fold; hospitalization >3-fold; mortality 11-24-fold) and was further amplified by COPD, CVD, or T2DM, with a lesser effect for T1DM. Conclusions: The results highlight the substantial age- and comorbidity-driven CAP burden in Hungary and support prioritization of preventive strategies including pneumococcal vaccination for older adults and high-risk groups.

The A(H1N1)pdm09 virus remains a major global health threat. This study examined the burden of ICU admission, mortality, and associated predictors among patients with A(H1N1)pdm09 pneumonia in a leading center for infectious diseases in Vietnam. Information on demographic, clinical, and laboratory characteristics, and outcomes was retrieved from medical records of adults admitted with influenza A(H1N1)pdm09 during 2009-2019. Among 729 cases, 21.7% (158/729) developed pneumonia. Among 158 pneumonia cases, 36.7% (58/158) developed moderate-to-severe acute respiratory distress syndrome (ARDS), and 15.2% (24/158) received invasive ventilation. ICU admission and mortality rates were 48.7% (77/158, 95%CI 41.1-56.5%) and 8.2% (13/158, 95%CI 4.9-13.6%), respectively. Predictors of ICU admission included being >60 years old (adjusted OR [AOR] 13.864, 95%CI 2.185-87.956, P=0.005), comorbidities (AOR 6.527, 95%CI 1.710-24.915, P=0.006), AST (AOR 1.013, 95%CI 1.001-1.025, P=0.029), and moderate-to-severe ARDS (AOR 14.027, 95%CI 4.220-46.627, P<0.001). Predictors of mortality were invasive ventilation (AOR 55.355, 95%CI 1.486-2062.375, P=0.030) and double-dose oseltamivir or combination therapy (AOR 32.625, 95%CI 1.594-667.661, P=0.024). In conclusion, mortality is not rare in A(H1N1)pdm09 infection. Monitoring of older patients and those with comorbidities, liver enzyme elevation, or moderate-to-severe ARDS is essential for the timely detection of complications requiring intensive care.

New tuberculosis (TB) vaccines for adults and adolescents could transform TB prevention programs, but their impact depends on successful implementation. We investigated willingness to be vaccinated with a new TB vaccine in a high HIV and TB burden setting in southern Mozambique in 2024 using a mixed methods approach involving a cross-sectional survey and concurrent in-depth interviews. In 151 surveys and 23 interviews, we found that willingness to receive a new TB vaccine among adults and adolescents was 77% (148/192) overall. In multivariable analysis, adolescents were more willing to receive a new TB vaccine than adults even when adjusting for other factors which may influence vaccination decisions (adjusted OR: 5.6, 95% CI: 1.7-17.7). Personal experience with TB and greater knowledge of the disease was also linked with willingness to be vaccinated. Qualitative findings reinforced quantitative findings, further clarifying that even among those who expressed hesitancy, a safe and effective TB vaccine endorsed by healthcare workers, government agencies, and community leaders would likely have high uptake. Our findings are specific to southern Mozambique and can shape vaccine introduction efforts after a TB vaccine is licensed and approved for use in this age group.

BackgroundThe World Health Organisation (WHO) recommends digital chest radiography (dCXR) with computer-aided detection (CAD) for tuberculosis (TB) screening of individuals >15 years of age. MethodologyAdults ([&ge;]18 years) were enrolled (March 2021-December 2022) in South Africa into a community-based Screening Cohort (household contacts) and a facility-based Triage Cohort (symptomatic clinic attendees). Microbiologically-confirmed pulmonary TB required positive sputum culture and/or Xpert Ultra. Asymptomatic TB was diagnosed in participants without TB symptoms. dCXR were read by blinded human readers and qXR CAD (0.5 threshold; Qure.AI, India). ResultsdCXR from 1,353 participants (886 Screening Cohort; 467 Triage Cohort) were analysed. Microbiologically-confirmed TB occurred in 48 (5.4%) Screening Cohort [9 symptomatic (19%) and 39 asymptomatic (81%)]; and 116 (24.8%) Triage Cohort (all symptomatic) participants. dCXR sensitivity (human readers) for asymptomatic TB in the Screening Cohort was 56.4%, vs. 72.4% for symptomatic TB in the Triage Cohort (difference -16%; 95%CI -2.9 to -29.1); with specificities 94.1% and 81.2%, respectively. Corresponding qXR CAD sensitivities were 69.2% vs. 83.6% (difference -14.4%; 95%CI -26 to -2.8), with specificities 89.3% and 73.5%, respectively. The difference in dCXR sensitivity and specificity for asymptomatic TB between qXR CAD and human readers was 12.8% (95%CI -0.48 to 26.1) and -4.8% (95%CI -12.4 to 28.2), respectively. ConclusionSensitivity of community-based dCXR screening for microbiologically-confirmed asymptomatic TB among household contacts was lower than for facility-based triage of symptomatic TB, but approached 70% with CAD. Neither human reader nor qXR CAD evaluation met WHO targets for a TB screening test (90% sensitivity; 80% specificity). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe World Health Organisation (WHO) recommends digital chest radiography (dCXR) with computer-aided detection (CAD) for tuberculosis (TB) screening of individuals >15 years of age, based on data from prevalence surveys and facility-based studies. Performance data for community-based screening of asymptomatic TB are lacking. We searched PubMed for literature published in English between January 1, 2000, and November 1, 2025, for community-based, active case-finding studies of adolescents and adults aged 15 years and older that used dCXR CAD for asymptomatic TB screening. We used the following search terms: "Tuberculosis" AND ("asymptomatic" OR "subclinical") AND ("computer aided diagnosis" OR "artificial intelligence") AND "community-based screening" AND "chest radiography" AND ("diagnostic performance" OR "sensitivity"). We identified five studies reporting on microbiologically-confirmed asymptomatic TB and dCXR CAD performance. Three of five studies tested sputum only in those who were symptomatic and/or had abnormal CXR. One study did measure prevalence of asymptomatic TB by universal sputum testing of all participants, but did not report sensitivity and specificity for asymptomatic TB separately. One case-control study of CAD4TB (v7), which pooled data from five active case-finding cohorts, reported sensitivity of 61.4% and specificity of 86.7% for asymptomatic TB. However, the case-control design and inclusion of two cohorts using prevalence survey methodology and three cohorts enrolling high TB risk groups, two of which did not perform CXR on all participants, suggest potential for selection bias. Added value of this studyWe evaluated discriminatory performance of dCXR screening for asymptomatic TB among adult household contacts of TB patients, using human readers and qXR CAD (QURE.AI, India), in three communities in South Africa (Screening Cohort). Performance was benchmarked against that for symptomatic TB among adult clinic attendees (Triage Cohort), to enable comparison with traditional published approaches. All participants underwent universal sputum testing, regardless of symptom status or dCXR results. Sensitivity of human readers for asymptomatic TB in the Screening Cohort was 56.4%, compared to 72.4% for symptomatic TB in the Triage Cohort, with specificity 94.1% and 81.2%, respectively. The corresponding sensitivity of qXR CAD for asymptomatic TB, using the manufacturers 0.5 threshold score, was 69.2%, compared to 83.6% for symptomatic TB, with specificity 89.3% and 73.5%, respectively. The difference in dCXR sensitivity and specificity for asymptomatic TB between qXR CAD and human readers was 12.8% and -4.8%, respectively. The adjusted qXR threshold score (0.007) required to achieve 90% sensitivity for asymptomatic TB reduced specificity to 18.9%; and did not meet the WHO Target Product Profile (TPP) for a high sensitivity (90%), high specificity (80%) TB screening test. Implications of all the available evidenceSensitivity of community-based dCXR screening of household contacts for asymptomatic TB was low, compared to facility-based triage of symptomatic TB. Neither human reader nor qXR CAD evaluation of dCXR met the minimal WHO TPP for a high sensitivity (90%), high specificity (80%) TB screening test. Although dCXR CAD community screening would detect more than two-thirds of all people with previously undiagnosed, microbiologically-confirmed asymptomatic TB, the significant proportion of people with TB that would remain undetected, and untreated, might allow ongoing Mycobacterium tuberculosis transmission and hinder elimination efforts.

ObjectiveLong-term sequelae following viral infections, such as Chikungunya and SARS-CoV-2, are associated with persistent symptoms, with a notably higher prevalence in women. This study investigated the early determinants of progression to chronic chikungunya (CC) and examined the specific role of biological sex on disease outcomes. MethodsWe analysed peripheral blood mononuclear cells (PBMCs) sampled within seven days of disease onset, recruited between 2016 and 2020. The study compared patients who eventually recovered (RC, n = 11) with those who progressed to develop CC (n = 24). We analysed gene signatures through transcriptomics and validated the results using qRT-PCR and flow cytometry ResultsTen genes were differentially expressed between the cohorts. Specifically, the study identified an upregulation of IKZF2 (encoding Helios) in CC patients, which was confirmed by qRT-PCR. Conversely, ACKR3 (encoding a CXCL12 scavenger in the ACKR3/CXCR4/CXCL12 axis) was upregulated in RC patients and validated by flow cytometry. Furthermore, CC cases demonstrated higher viral loads and downregulation of IFN- and IFN-{gamma} pathways. We also found that immune profiles differed between men and women; specifically, interferon /{gamma} and TNF signalling pathways were upregulated in women with CC but downregulated in men with CC relative to recovered individuals. DiscussionImmune profiles differed significantly between men and women within both the CC and RC groups. These findings suggest that progression to chronic disease is influenced by an impaired early antiviral response combined with sex-specific immune regulation. Furthermore, ACKR3 and IKZF2 are identified as potential prognostic biomarkers for chronic chikungunya.

Objectives: A pooled testing algorithm for tuberculosis (TB), in which sputum specimens from multiple individuals are tested in pools with individual testing of positive pools, can optimise diagnostic resources. This study evaluated the diagnostic accuracy and cartridge savings of pooled testing with the Xpert MTB/RIF Ultra assay (Xpert Ultra) relative to individual Xpert Ultra testing. Methods: We conducted a cross sectional study among 2,396 adults (aged above 15 years) with presumptive TB enrolled between July 2024 and February 2025, through facility based case finding (FBCF) and community based case finding (CBCF). Participants submitted two sputum specimens. The first underwent individual Xpert Ultra testing; remnant specimens were combined into four specimen pools and tested again with Xpert-Ultra. The second specimen was used to inoculate liquid culture (BACTEC MGIT). Data were used to simulate an up-front pooled testing strategy; sensitivity and specificity of this approach was estimated against culture, and cartridge use was compared with individual Xpert-Ultra testing. Results: Of 2,396 participants, 395 (16.5%) had a positive Xpert Ultra and/or culture, including 360/912 (39.5%) in FBCF and 35/1484 (2.4%) in CBCF. The pooled testing approach had sensitivity of 82.4% (95% confidence interval [CI], 77.9; 86.3) and specificity of 98.5% (97.8; 99.0) compared to culture, with lower sensitivity than individual Xpert-Ultra testing (86.5%, 82.4; 89.9) but high specificity (98.1%, 97.4; 98.7). Sensitivity of pooled testing was lower in CBCF (59.1%, 36.4; 79.3) than in FBCF (84.0%, 79.5;87%), whereas cartridge savings were greater in CBCF (69.1% vs 9.6%). The pooling strategy reduced Xpert-Ultra cartridge use by 46.5%, saving USD 14,447. Conclusions: Pooled Xpert-Ultra testing among adults appears resource-efficient for TB screening in Vietnam. As sensitivity is lower compared to individual Xpert Ultra testing, particularly for paucibacillary disease, these losses should be carefully weighed against gains in affordability and expand access to molecular testing. Careful, context-specific implementation is essential to maximise programmatic benefit while minimising missed persons with TB.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

Scrub typhus remains a persistent public health concern with strong spatial and temporal variability. This study analyses the spatio-temporal distribution, clustering patterns, and forecasting of scrub typhus across five districts, Chittoor, Ranipet, Tirupattur, Vellore, and Tiruvannamalai, using long-term surveillance data from May 2005 to May 2024. We applied spatio-temporal exploratory analysis to identify trends, seasonal behaviour, and inter-district heterogeneity in disease incidence. Hotspot analysis was conducted using the Getis-Ord Gi* statistics to detect statistically significant hotspots and coldspot clusters and examine their evolution over time. To support decision-making, we developed statistical, machine learning (ML), and deep learning (DL) based forecasting models using monthly scrub typhus and climatic features. Root mean square error (RMSE), and R-square error (R2) evaluation metrics are used to compare the performance of the prediction model. Scrub typhus shows clear and recurring seasonal peaks across all five districts, and incidence increases are associated with precipitation, dew point, relative humidity, and vegetation cover. Temperature shows a strong negative correlation, while relative humidity and normalized difference vegetation index (NDVI) show strong positive correlations in all districts. Hotspot analysis identifies Vellore and Chittoor as persistent core transmission zones, with weaker clustering in surrounding districts. Forecasting results indicate that model performance varies by location. The results reveal persistent hotspots, clear seasonal signals, and short-term forecasts across districts. This integrated spatiotemporal and forecasting framework provides actionable insights for targeted surveillance and timely intervention strategies to control scrub typhus.

BackgroundDolutegravir (DTG)-based regimens are currently the preferred first-line therapy in many HIV programs; however, the influence of baseline advanced HIV disease (AHD) on virologic outcomes in routine national data in the DTG era remains unclear. MethodsWe conducted a retrospective cohort analysis using routinely collected data from Tanzanias National AIDS, STIs, and Hepatitis Control Programme (NASHCoP) database (2017-2021). A simple random sample of 50,000 patients was drawn from the de-duplicated national dataset, yielding 49,863 patients after data processing. The analytic cohort included 4,044 patients with baseline CD4 and endpoint viral load measurements. Viral load suppression was defined as <1000 copies/mL. Associations between baseline AHD, regimen status, and suppression were assessed using risk ratios and multivariable Poisson regression models, including an interaction term between AHD and DTG. ResultsOverall viral load suppression was 89.2% (3,607/4,044). Patients with baseline AHD had lower suppression than those without AHD (81.3% vs. 91.1%; RR 0.48, 95% CI 0.40-0.57). Suppression was higher among patients receiving DTG-based regimens than among those receiving non-DTG regimens (91.5% vs. 77.2%; RR 2.67, 95% CI 2.23-3.20). In the adjusted analysis, baseline AHD remained associated with reduced suppression (aRR 0.89, 95% CI 0.86-0.92), whereas DTG use was associated with improved suppression (aRR 1.15, 95% CI 1.10-1.20). A significant interaction between AHD and DTG was observed (aRR 1.40, 95% CI 1.20-1.63), indicating that the relative benefit of DTG was greater among patients with baseline AHD. ConclusionsAlthough viral load suppression was high in this Tanzanian routine-care cohort, patients with baseline AHD had poorer outcomes. DTG-based regimens were associated with improved overall suppression, with a greater relative benefit among patients with advanced disease. These findings support the continued prioritization of DTG-based therapy and reinforce the importance of early diagnosis and targeted management of patients with AHD.

Introduction: Following a large chikungunya outbreak during 2006 to 2008, Sri Lanka did not report any outbreaks for a 16 year period until end of 2008, possibly due to population immunity. Therefore, understanding baseline immunity prior to outbreaks is crucial to inform implementation of vaccine strategies. Methods: We assessed the age stratified seroprevalence for chikungunya in an urban (n=816) and a semi urban (n=380) community in Colombo, Sri Lanka, from September to November 2024, prior to the commencement of the large chikungunya outbreak, in December 2024. Sociodemographic, socioeconomic and clinical data were collected and chikungunya specific IgG measured in serum samples. Results: Of 1196 participants, 410 (34.3%) were chikungunya IgG seropositive. Seroprevalence was significantly higher in urban populations compared with semi urban populations (39.6% vs 22.9%; p<0.001) and increased significantly with age in urban areas but not in semi-urban areas. Living in an urban area was the strongest independent risk factor of chikungunya seropositivity (aOR 7.48, 95% CI 4.05 to 13.81; p<0.001), consistent with the higher population density, poor housing conditions and overcrowding observed in that setting. The use of mosquito nets was independently associated with reduced risk of seropositivity (aOR 0.50, 95% CI 0.27 to 0.93; p=0.029). Almost no individuals aged <16 years had evidence of prior infection (0.55%), indicating minimal transmission in the preceding 16 years. In the urban cohort, seropositivity was significantly associated with diabetes, central obesity, overweight, and hypertension. Conclusions: There appears to have been minimal chikungunya transmission in the 16 years preceding the 2024 outbreak, with a large population susceptible to chikungunya. Higher seroprevalence in urban populations highlights the role of population density, overcrowding, and housing conditions as key drivers of transmission.

BackgroundSystematic screening for tuberculosis (TB) is recommended in people with diabetes; however, data on the accuracy of screening tools in this population are lacking. We assessed the accuracy of symptom and chest X-ray screening among people with diabetes. MethodsWe consecutively enrolled adults with diabetes attending routine care in South Africa. All participants underwent symptom screening and chest X-ray. A single sputum specimen was collected from all participants and tested by Xpert Ultra. A positive Xpert Ultra result was used as the reference standard. ResultsWe enrolled 673 participants. The median age was 54 years (interquartile range 47-60 years), and 63.8% were female. HIV prevalence was 17.2%. Prevalent TB was diagnosed in nine participants (1.33%). Any cough had a sensitivity of 22.2% (95% confidence interval [CI] 2.1-60.0%) and a specificity of 97.5% (95%CI 96.0-98.6%). Expanding the symptom definition to include any of cough, fever, weight loss, or night sweats did not improve sensitivity (22.2 %, 95 % CI 2.1-60.0) and slightly reduced specificity to 96.0 % (95 % CI 94.2-97.0). Chest X-ray abnormalities suggestive of TB demonstrated a sensitivity of 55.6% (95%CI 21.2-86.3%) and a specificity of 95.4% (95%CI 93.4-97.0%). The specificity of chest X-ray was significantly lower in participants with prior TB (87.6%, 95% CI: 79.8-90.6%), compared to 97.2% (95% CI: 95.2-98.5%) in those without (p < 0.01). ConclusionSymptom-based TB screening has poor sensitivity in people with diabetes. Although chest X-ray improved the sensitivity, it remained suboptimal, with a reduced specificity in people with previous TB.

Background Appendicitis is a readily treatable surgical emergency, yet it remains a cause of preventable death among children in resource-limited settings. While recent studies have documented the global burden of pediatric appendicitis, none have systematically examined its geographic clustering or spatial spillover effects. Understanding whether high-mortality countries cluster geographically, and whether neighboring countries influence each other's outcomes, is essential for designing regional surgical capacity strategies. Methods We conducted a spatial analysis of pediatric appendicitis case fatality rates in children aged 0-14 years across 169 countries from 2000 to 2019. Data were obtained from the Global Burden of Disease Study 2023 and World Bank databases. We calculated global Moran's I to assess spatial autocorrelation, used Getis-Ord Gi* to identify local hotspots, and fitted spatial lag and spatial error regression models to quantify spatial spillovers while adjusting for GDP per capita, physician density, and basic sanitation access. Results Global Moran's I was 0.621 in 2000 (p < 0.001), 0.621 in 2010 (p < 0.001), and 0.592 in 2019 (p < 0.001), indicating strong and persistent spatial clustering. Hotspots at 99% confidence were consistently concentrated in sub-Saharan Africa and parts of South Asia, with little change in geographic distribution over two decades. The spatial error model provided the best fit (AIC = 212.6), with a spatial error coefficient ({lambda}) of 0.663 (p < 0.001), suggesting that approximately 66% of residual variation was explained by unobserved regional factors. In the final model, higher GDP per capita ({beta} = -0.497, p < 0.001) and higher physician density ({beta} = -0.568, p < 0.001) were independently associated with lower case fatality, while basic sanitation access showed no significant association (p = 0.284). Conclusions Pediatric appendicitis case fatality exhibits strong and persistent geographic clustering. The substantial spatial spillover effect suggests that regional coordination of surgical capacity building may be more effective than country-by-country investments. Priority should be given to hotspot countries in sub-Saharan Africa and South Asia, with emphasis on surgical workforce expansion rather than broad economic development alone.

Background: The traditional wealth index, based on principal component analysis (PCA), used in the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), suffers from urban bias, distorting estimates of health inequality. We compared the traditional index (PEAR1) with an alternative two-component polychoric PCA index (POLY2) using annual expenditure from 12 LSMS surveys as the gold standard to determine which provides more accurate SEP measures for equitable policy targeting. Methods: We compared the traditional wealth index (PEAR1) with a two-component polychoric PCA approach (POLY2) using 12 LSMS (Living Standards Measurement Study) surveys (2015-2022) from 12 African countries. Annual household consumption expenditure was the gold standard. We assessed agreement using weighted Cohen's kappa and validated against education (proportion of households with secondary or higher education) using the concentration index (CIX) and slope index of inequality (SII). Results: The POLY2 index showed higher agreement with expenditure quintiles (average national weighted kappa = 43.3%) than the PEAR1 index (35.1%), with notable improvements in urban (43.5% vs. 27.5%) and rural (35.3% vs. 22.4%) areas. POLY2 also attenuated extreme household distributions observed in PEAR1. Education validation showed that POLY2 produced intermediate inequality gradients between the flatter expenditure-based gradient and the steeper PEAR1-based gradient. Conclusion: The POLY2 wealth index is superior to the traditional index, reducing urban-rural bias and providing more accurate socioeconomic classifications. Its adoption in large-scale surveys such as DHS and MICS is recommended to improve equitable monitoring of health inequalities in low- and middle-income countries.