Journal of Infection and Public Health

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.

Background: The Colour Blind Quality of Life Scale (CBQoL) is a questionnaire developed to assess the quality of life of individuals with congenital colour vision deficiency (CVD). This study aimed to translate the English version of the CBQoL into Vietnamese and evaluate the validity and reliability of the Vietnamese version (CBQoL-VN). Methods: A forward-backward translation method was performed to produce the Vietnamese text. Content validity was assessed by six experts in vision care. Reliability testing involved 30 participants with congenital CVD, while discriminant validity was evaluated by comparing this group against 30 participants with normal colour vision. Results: Following expert consensus, two items were removed and one transportation-related item was added. The content validation index (CVI) values of 1.0 for relevance, clarity, and understandability indicated excellent content validity. Internal consistency was high, with a Cronbach's alpha of 0.95 for the full scale. Discriminant validity analysis showed that participants with congenital CVD scored significantly lower across all CBQoL-VN domains compared to those with normal colour vision. Conclusions: The modified CBQoL-VN is a valid and reliable instrument for assessing the quality of life of individuals with congenital CVD in the Vietnamese population.

Introduction: Stroke care is time-sensitive, yet patients in low-resource settings may reach tertiary services only after passing through multiple formal and informal care options. This study examined documented care-seeking pathways and time to presentation among stroke cases recorded at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria. Methods: A retrospective hospital record review was conducted using secondary data from the Stroke Registry, radiology department records, referral notes, and ambulance records at UNIMEDTH. The analysis included 371 stroke cases with documented time from symptom onset to UNIMEDTH presentation and reconstructable care pathways. First-contact routes were classified as hospital/biomedical, self/informal or traditional/faith-based care, and the number of documented steps defined pathway complexity before and including tertiary presentation. Frequencies and percentages described pathway patterns; median presentation times were compared using Mann-Whitney U and Kruskal-Wallis tests. Results: The median time to tertiary presentation was 24 hours (interquartile range [IQR] 9-72), and 317 patients (85.4%) presented after four hours. Only 30 patients (8.1%) presented directly to UNIMEDTH; 44 distinct care-pathway sequences were recorded. Hospital-facility first contact was documented for 81 patients (21.8%). It was associated with a median presentation time of 3 hours (IQR 2-6), compared with 48 hours (IQR 24-72) among patients whose initial contact was outside a hospital facility (U = 699.50, p < 0.001). The median time also differed across grouped first-contact categories and pathway complexity levels (both p < 0.001). Conclusion: Non-hospital or multi-step care-seeking pathways commonly preceded tertiary stroke presentations in this setting. The findings indicate that delayed tertiary arrival is partly embedded in the pathway followed after symptom onset. Interventions should combine public recognition of stroke warning signs with urgent referral linkages involving hospitals, patent medicine vendors, traditional and faith-based providers, and emergency transport systems.

To explore the safety of combined use of lidocaine/prilocaine aerosol and condoms of different materials, this study conducted compatibility tests between them. By observing changes in various physical properties of condom materials after exposure to the aerosol, the compatibility of different polymer materials with the aerosol was analyzed.The results showed that within 15 minutes of exposure to the aerosol, there was no significant difference in all physical properties of natural rubber latex condoms compared with the blank control group (P>0.05), indicating they can be used together. In contrast, obvious changes in physical properties of polyurethane condoms occurred within 5 minutes of exposure (P<0.05), and their performances failed to meet industrial application standards, so combined use is strictly prohibited.This study clarifies the compatibility differences between two mainstream condom materials and lidocaine/prilocaine aerosol, providing experimental evidence and theoretical references for rational matching in clinical and daily use as well as avoiding potential safety risks.

The blood-sucking ectoparasite Rhipicephalus B. microplus represents one of the greatest economic threats to livestock worldwide. The discovery of novel acaricidal molecules based on environmentally sustainable technologies is therefore required, particularly those suitable for use in dairy and meat-producing livestock without generating contaminant residues. This study aimed to identify and validate plant-derived metabolites with dual activity on acetylcholinesterase and mitochondrial targets as sustainable acaricidal agents against R. microplus, integrating computational screening, biochemical assays and field evaluation. Following in silico screening of 1.300 plant metabolites targeting acetylcholinesterase and mitochondrial function, fourteen compounds were selected for in vitro and in vivo mortality assays using immersion and larval vessel methods. Carvacrol was identified as the most promising metabolite and showed an inhibitory mechanism of action on acetylcholinesterase and mitochondrial complexes I, III, and IV. Its acaricidal efficacy was subsequently confirmed under field conditions using ethanolic and oily formulations (spray and pour-on) applied to cattle (Bos taurus). The spray formulation significantly reduced tick infestation, decreasing tick counts by 20% every 10 days (p < 0.001), whereas the pour-on formulation showed no significant reduction (p = 0.093). These results demonstrate that an integrated discovery pipeline from computational screening to field validation provides a robust strategy for identifying plant-derived acaricidal agents targeting key physiological pathways in R. microplus. HighlightsO_LIStructured and sequential workflow (pipeline) from in silico to Bos taurus C_LIO_LIIdentification and validation of phytometabolites against R. microplus C_LIO_LICarvacrol multitarget activity on acetylcholinesterase and bioenergetic in ticks C_LIO_LIThe spray formulation reduces tick infestation by 20% every 10 days C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/727743v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@11c9931org.highwire.dtl.DTLVardef@8d6088org.highwire.dtl.DTLVardef@1bcc09aorg.highwire.dtl.DTLVardef@108d1d1_HPS_FORMAT_FIGEXP M_FIG C_FIG Created in BioRender. Avendano, G. (2026) https://BioRender.com/7pm1ffj

Fucoidans have been widely reported to show SARS-CoV-2 antiviral activity. In this study, we observed a striking difference in the inhibitory potency between two commercially available fucoidans: Fucus vesiculosus crude (Fvc) and pure (Fvp). SEC-MALS analysis revealed two molecular weight populations for Fvc (1098 kDa, 58.58 kDa) and one for Fvp (40.48 kDa). At micromolar concentrations of fucoidans, the binding affinities (KDs) of Fvc_1098 (223 nM) and Fvc_58 (4.27 {micro}M) for the amine-biotinylated SARS-CoV-2 receptor binding domain (RBD) were higher than that of Fvp (76.5 {micro}M). At nanomolar concentrations, binding was observed only to the Avi-tag-, but not amine-biotinylated RBDs, suggesting better accessibility of their binding sites. The association rates (kon) were faster for Fvc than for Fvp. Similarly, affinities of Fvc_1098 (23.4 nM) and Fvc_58 (4.48 M) for ACE2 were greater than that of Fvp (66.8 M), indicating that Fvc can bind directly to both RBD and ACE2. Fvc demonstrated enhanced inhibitory potency (IC50 = 58 g/mL) compared to Fvp (IC50 > 239 g/mL) in the pseudovirus entry assay and did not induce cytotoxicity in HEK293T cells. In conclusion, crude fucoidan with high fucose content and high molecular weight shows promising antiviral activity.

Introduction: Women aged 45-49 occupy a heterogeneous late-reproductive-life stage, but population research often treats them as a uniform group. This study examined correlates of Demographic and Health Survey (DHS)-defined infecund/menopausal status among Nigerian women aged 45-49. Methods: This cross-sectional secondary analysis used the 2024 Nigeria Demographic and Health Survey Women Recode dataset. Weighted descriptive statistics summarised reproductive exposure status among 3,237 women. Out of these, 3,110 women classified as either fecund or infecund/menopausal were subjected to Survey-adjusted Chi-square tests and Binary Logistic regression at p<0.05, where pregnant and postpartum amenorrhoeic women were excluded. Results: More than half of women were classified as infecund/menopausal (54.1%), while 41.5% were fecund; 3.2% were postpartum amenorrhoeic, and 1.3% were pregnant. Findings indicated that currently married/cohabiting women (AOR=4.87; 95% CI: 2.24-10.56) and formerly married women (AOR=8.30; 95% CI: 3.69-18.66) had higher odds of infecund/menopausal classification than women never in a union. Secondary education, higher education, middle-to-richest wealth quintiles, and five or more children ever born were associated with lower odds, while Northern minority ethnicity was associated with higher odds. Adding the current contraceptive method attenuated several education, wealth and parity associations; modern-method and traditional-method users had markedly lower odds than non-users. Conclusion: Late-reproductive-life exposure status among Nigerian women aged 45-49 is socially patterned, with union status showing the most stable association. DHS-defined infecund/menopausal status is a demographic exposure category rather than clinically confirmed menopause. It is therefore concluded that the cross-sectional associations should not be interpreted causally.

Abstract Background: Mean platelet volume (MPV) is a simple, low-cost biomarker that reflects platelet activation. Its prognostic value in septic shock remains controversial. We aimed to determine whether MPV at intensive care unit (ICU) admission is associated with hospital mortality in patients with septic shock. Methods: Retrospective cohort study of consecutive adults with septic shock (Sepsis-3 criteria) admitted to a single ICU. MPV, severity scores (SOFA, APACHE II, SAPS II), procalcitonin, and clinical data were collected. The primary outcome was in-hospital mortality. Spearman correlation, univariate and multivariate logistic regression (with Firth's correction), ROC curves, and subgroup analyses were performed. Results: Fifty-eight patients were included; mortality was 58.6%. MPV did not differ between non-survivors and survivors (13.09 {+/-} 1.37 vs. 12.66 {+/-} 1.45 fL, p = 0.259). MPV showed a weak correlation with procalcitonin ({rho} = 0.394, p = 0.002) but not with severity scores. In multivariate analysis adjusting for age, sex, SOFA and comorbidity count, MPV was not an independent predictor of mortality (OR 1.075, 95% CI 0.682-1.755, p = 0.749). The area under the ROC curve for MPV was 0.598 (95% CI 0.444-0.752), significantly lower than that of SOFA (0.837) and procalcitonin (0.836). Subgroup analyses showed no significant association between MPV and mortality in any stratum. Conclusions: In this cohort of septic shock patients, MPV at ICU admission was not associated with hospital mortality and had poor discriminative ability. Widely used severity scores and procalcitonin remain superior prognostic markers. MPV should not be used as a prognostic tool in septic shock. Keywords: Septic shock, Mean platelet volume, Mortality, SOFA, Procalcitonin, Biomarker

Migraine headaches affect over one billion people internationally and can be defined as episodes of acute severe pain wrapping around the head and are normally accompanied by nausea, blurry vision, and sensitivity to light and sound. While triggers that cause migraines may vary among patients, evidence shows they are involved with the trigeminovascular system (a network of blood vessels in the brain in conjunction with the trigeminal nerve). Activation of the trigeminal neurons triggers the release of vasoactive neuropeptides, such as calcitonin gene-related peptide (CGRP), leading to neurogenic inflammation and vasodilation of cranial blood vessels. The development of 5-HT1B serotonin agonist drugs, commonly known as triptans, have been an effective measure of migraine relief. The drugs created in this research were found to have improved docking scores within the 5-HT1B binding site compared to that of naratriptan. The two drugs proposed in this paper would need to undergo further investigation to determine the feasibility of laboratory synthesis and clinical trials.

BackgroundTuberculous meningitis (TBM) is the most sinister form of extrapulmonary tuberculosis (EPTB), associated with high mortality due to delayed diagnosis and limited sensitivity of conventional and molecular tests. Current study evaluated the diagnostic utility of Lipoarabinomannan antigen (LAM) detection in CSF and urine and explored host inflammatory biomarkers for diagnosis and prognosis of TBM. MethodsThis prospective observational study enrolled 80 patients with presumptive TBM at a tertiary care centre. CSF samples were subjected to AFB microscopy, liquid culture(MGIT-960), GeneXpert MTB/RIF (GX), and LAM lateral flow assay. Urine LAM was performed at baseline. Serum and CSF levels of IL-1{beta}, IL-6, TNF-, IFN-{gamma}, IL-17A, and IP-10 were measured at baseline and after 1 month treatment. ResultsAmong 80 participants, 23 (28.7%) had definite TBM and 46 (57.5%) had probable TBM. CSF LAM sensitivity and specificity against microbiological reference standards was 43.5% and 80.7%, while urine LAM sensitivity (60.9%) and specificity 82.5% was higher. Against composite reference standards, both CSF and urine LAM showed reduced sensitivity but achieved 100% specificity. Serum IL-1{beta} showed the best diagnostic performance (AUC 0.943; sensitivity 88.9%, specificity 90.9%). Elevated serum and CSF IP-10 levels were associated with poor outcomes, whereas declining IL-6 and TNF- levels correlated with treatment response. ConclusionLAM detection in CSF and urine may serve as a highly specific, rapid rule-in test for TBM. Host inflammatory biomarkers, especially IL-1{beta} and IP-10, show additional diagnostic and prognostic value. Combining LAM testing with cytokine biomarkers may improve early diagnosis and efficient clinical management of TBM.

Objective: To identify facility-level characteristics - including care level, ownership type, and funding model - associated with poor HIV treatment outcomes, and quantify their independent contributions after adjustment for patient-level clinical factors. Design: Retrospective cross-sectional analysis using multivariable logistic regression with HC3 cluster-robust standard errors to account for facility-level clustering. Setting: HIV care facilities in the Nigerian national HIV programme, spanning primary health centres, secondary health facilities, and tertiary hospitals. Participants: 27,288 HIV-positive patients enrolled on ART, from a publicly available de-identified Quality of Care dataset. Main outcome measures: Composite poor outcome (poor ART adherence, treatment interruption, or mortality); individual outcomes including poor adherence rate, mortality, ART interruption, and diagnosis-to-ART delay exceeding 90 days. Results: Primary health centres had 15.4% composite poor outcome versus 10.2% at tertiary hospitals. After adjustment for patient age, sex, WHO stage, and CD4 count, primary health centre patients had 95% higher odds of poor outcome (OR=1.95; 95%CI 1.45-2.61; p<0.001). NGO-funded facilities had 24% higher odds (OR=1.24; 95%CI 1.10-1.39; p<0.001) and federally funded facilities 25% higher odds (OR=1.25; 95%CI 1.06-1.48; p=0.008). Female sex was independently protective (OR=0.87; 95%CI 0.79-0.96; p=0.003). Diagnosis-to-ART delays exceeded 90 days in 47.3% of patients, with significant variation by facility level (chi-squared=49.4, p<0.001). Conclusions: Facility level and funding model independently predict HIV treatment outcomes after patient-level adjustment. Primary health centres and NGO/federally funded facilities may require targeted quality improvement support. These findings have direct implications for PEPFAR, the Global Fund, and national HIV programme managers.

Background High-risk subgroups among household contacts of persons with tuberculosis (TB) might benefit from additional interventions. However, the significance of an abnormal baseline chest radiograph (CXR) suggestive of TB, despite negative sputum microbiology, is uncertain. Methods Adults ([&ge;]18 years) with recent household TB exposure were enrolled at three South African sites (April 2021-September 2022). All participants underwent symptom screening, CXR, and sputum Xpert Ultra and MGIT culture. Pulmonary TB diagnosis was microbiologically-confirmed. Participants without prevalent TB were followed for symptomatic incident TB through 12 months. Multivariable logistic regression identified factors associated with abnormal CXR suggestive of TB. Poisson regression estimated adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95%CI). Results Baseline CXR were available for 795/846 (94.0%) participants without prevalent TB and were abnormal in 157/795 (19.7%); associated with older age (adjusted odds ratio, aOR=1.04, 95%CI 1.02-1.05); prior TB (aOR=6.39, 95%CI 4.18-9.78); and current smoking (aOR=1.61, 95%CI 1.00-2.62). Symptomatic incident TB developed in 8/795 (1.0%) participants, including 7/8 (87.5%) who were asymptomatic and 4/8 (50.0%) with abnormal CXR at baseline. TB incidence was higher in those with abnormal versus normal CXR (aIRR=4.11, 95%CI 1.29-13.09), but after median 12.1 (IQR 11.1-13.1) months follow-up, 153/157 (97.5%) had not progressed to incident TB. Conclusions Adult household contacts with CXR abnormalities, but without prevalent TB, had a four-fold higher incidence of TB within one year, compared to those with normal CXR. This additional risk warrants targeted preventive treatment and extended surveillance, but since most remained TB-free, therapeutic TB treatment is not justified.

Japanese encephalitis virus (JEV) causes significant encephalitis across the Asia-Pacific region. Current vaccines target historical genotype III strains, but emerging genotypes,potentially driven by vaccine-mediated selective pressure, threaten vaccine effectiveness through altered envelope protein sequences that may reduce antibody cross-neutralisation. This study employed integrated sequence and structural analyses to identify E protein mutations affecting neutralising antibody binding and protein stability. The study curated JEV polyprotein sequences from NCBI, performed multiple sequence alignment, and used Shannon entropy to pinpoint highly variable positions. Mutations occurring at [&ge;]1% frequency within high-entropy regions were selected for analysis. From 34 initially identified mutations, four candidates were prioritized based on structural stabilization potential. Mutations were evaluated through FoldX stability predictions, molecular docking with antibody 2H4 using HADDOCK3, and molecular dynamics simulations. Binding energies were calculated using MM-GBSA analysis. Results demonstrated that all mutant E-2H4 complexes remained stable during simulations, with root-mean-square deviation plateauing after equilibration and minimal localized changes in root-mean-square fluctuation. These findings suggest that EDIII substitutions represent important candidates for further investigation to understand genotype-specific variations and inform next-generation vaccine development strategies against emerging JEV strains.

Background: Tuberculosis (TB) remains the leading infectious cause of death worldwide, with India accounting for nearly one-fourth of global TB cases. Ni-kshay, the countrys digital case-based TB notification platform is rich in data pertaining to the continuum of care of TB patients. This study aims to develop a standardized analytical approach to programmatic data to identify predictors of unfavourable treatment outcomes and mortality among adult drug-sensitive TB patients at the state level for Maharashtra during 2021 and 2022. Methods: Two separate analyses were undertaken comparing treatment success with: (1) unfavourable outcomes (death, treatment failure, loss to follow-up, regimen change, or not evaluated); and (2) mortality. Multivariate logistic regression was used to compute adjusted odds ratios (aOR) for key risk factors, adjusting for age, gender, and weight. Results: The final cohort included 323,124 cases for unfavourable outcome analysis and 315,579 cases for mortality analysis. Increasing age, male gender, lower body weight, known HIV and diabetes comorbidities, tobacco and alcohol consumption, and "unknown" status for behavioural risks and comorbidity status were significantly associated with increased odds of both unfavourable outcomes and mortality. Conclusions: This study highlights the utility of programmatic data in identifying high-risk TB patients and offers a reproducible analytic framework.

Objectives Tuberculosis (TB) in the United States disproportionately affects non-U.S.-born individuals. While testing this population for TB infection is recommended, little is known about individuals' willingness to take treatment for latent TB infection (LTBI). To address this gap, we conducted a pilot preference survey among individuals from countries with high TB incidence. Design Cross-sectional survey supported by language concordant community health workers. Setting Federally qualified health center, serving a primarily Asian immigrant community, in San Francisco. Participants Adults eligible for risk-based LTBI testing based on place of birth seeking primary care. Outcome measures Perspectives on TB disease, risk of reinfection, and willingness to accept treatment if diagnosed with LTBI conditional on different factors, such as side effects, costs, and other treatment burden. Results Among 60 participants, the median age was 48 years (interquartile range 35-63 years), 52% were women, and 100% spoke Chinese. Infecting others (n=35, 58%), risk of death (n=30, 50%), and potential isolation (n=25, 42%) were the most worrisome consequences of TB disease. Reinfection risk, risk of liver damage, cost, TB progression risk, clinic visits, and blood draws were most often considered moderately or very important when deciding whether to take LTBI treatment (n=53 to 57, 88-95%). While most participants (n=56, 93%) were willing to take treatment if diagnosed with LTBI even at a 10-year TB progression risk below 1% and willing to accept a risk of liver damage (n=41, 68%), less than half would accept LTBI treatment if there were any associated cost (n=28, 47%). Finally, many participants had concerns about their reinfection risk after completing LTBI treatment (n=34, 57%). Conclusions Amongst surveyed participants, TB disease and its consequences such as hospitalization, death and infecting others were worrisome, and participants had a high level of willingness to take treatment if diagnosed with LTBI. Future assessments of how people weigh tradeoffs regarding LTBI diagnosis and treatment could inform interventions to increase LTBI treatment acceptance and completion.

Methicillin-resistant Staphylococcus (MRS) infections are a significant public health concern. Anterior nares serve as a major reservoir and source of spread of MRS ssp. People living with HIV (PLWHIV) tend to be at higher risk of colonisation with MRS organisms due to frequent healthcare exposure. We assessed the prevalence of MRS nasal carriage and associated factors among PLWHIV at the HIV clinic of Kiruddu National Referral Hospital, Kampala, Uganda, from May to July 2024. Nasal swabs from 256 PLWHIV were cultured, and microbiological isolation was performed at MBN Clinical Laboratories. Prevalence was calculated as proportions, and logistic regression identified associations with clinical and socio-demographic factors (p < 0.05). Of 256 participants, 163 (63.7%) carried Staphylococcus, with 82 (32%) identified as MRS carriers (8.9% MRSA, 23% MRCoNS). Frequent hospital visits ([&ge;]3) (adjusted incidence risk ratio [A-IRR] = 1.18 x 107, p < 0.001), second-line antiretroviral therapy (ART) (A-IRR = 3.82, p = 0.041), and unsuppressed viral load (>1000 copies/mL) (adjusted odds ratio [AOR] = 11.3, 95% CI: 2.11-60.58, p = 0.005) were significantly associated with MRS carriage. Mask-wearing was protective against MRCoNS (A-IRR = 1.66, 95% CI: 1.06-2.58, p = 0.026). MRS isolates exhibited high resistance to erythromycin (81.7%) and trimethoprim-sulfamethoxazole (79.3%), but susceptibility to linezolid (93.9%). MRS nasal carriage is prevalent among PLWHIV. Individuals with frequent health care contact and those on second-line ART regimens are more susceptible to MRS colonization, while individuals who wear face masks and those with an undetectable HIV viral load are less susceptible. Antimicrobial Resistance (AMR) surveillance within HIV programs, enhanced infection control, ART adherence, and targeted screening for high-risk groups are critical to mitigate colonization.

Background Microbiological confirmation of paediatric pulmonary tuberculosis is frequently unattainable, rendering chest radiography a critical yet underutilised diagnostic tool. Methods We conducted a retrospective diagnostic accuracy study of the qXR version 4.2.1 (Qure.ai), a paediatric optimized computer-aided detection (CAD) algorithm, for pulmonary tuberculosis. Diagnostic performance was assessed against microbiological (MRS) and clinical reference standards (ClRS). Bayesian latent class analysis (LCA) was applied to address the imperfection of both reference standards in children. Performance was quantified using area under the receiver operating characteristic curve (AUROC) and estimates of sensitivity and specificity. Results We included digital chest radiographs of 932 Gambian children (< 15 years) comprising 80 (9%) children with confirmed tuberculosis, 163 (17%) with unconfirmed tuberculosis, and 689 (74%) classified as unlikely tuberculosis. Against MRS, qXR demonstrated AUROC, sensitivity and specificity of 0.68 (95% CI, 0.61 to 0.75), 54% (95% CI, 43 to 64%), and 82% (95% CI, 79 to 84%), respectively. Against ClRS, the AUROC, sensitivity and specificity were 0.73 (95% CI, 0.69 to 0.77), 41% (95% CI, 34 to 49%), and 87% (95% CI, 84 to 89%), respectively. Bayesian LCA, assuming conditional independence, estimated sensitivity of 79% (95% CrI, 65 to 89%) and specificity of 82% (95% CrI, 79 to 84%). Assuming conditional dependence between qXR and expert radiologist, and between culture and Xpert, estimated sensitivity increased to 89% (95% CrI, 71 to 98%), with specificity remaining at 82% (95% CrI, 79 to 84%). Conclusions Paediatric optimized qXR algorithm provides a valuable complementary tool for diagnosis of paediatric pulmonary tuberculosis. Conventional reference standards likely underestimate the true diagnostic performance of CAD systems in children.

Soil-transmitted helminths (STH) are a plausible but under-characterized comorbidity in tuberculosis. In this prospective South Indian cohort, multiplex stool PCR detected STH in 43% of 137 adults with pulmonary tuberculosis and 34% of 230 household contacts. Food insecurity independently predicted co-infection. Current adult deworming gaps warrant evaluation.

Background Community-wide active case-finding (ACF) is being increasingly implemented as a tuberculosis (TB) elimination intervention. However, conventional site selection strategies may result in low yields from screening. We evaluated whether an artificial intelligence (AI) software guided targeting strategy could improve detection of TB during screening activities (called camps) relative to routine approaches to site selection in the programmatic setting in Pakistan. Methods We conducted a stepped-wedge cluster-randomised trial embedded within Global Fund supported ACF activities implemented by Pakistan s National TB Program and private sector partners. Thirty mobile X-ray van teams operating in 68 districts were randomly assigned to transition from routine site selection approaches (based on field-staff experience and historical data) to an AI-guided targeting strategy, using the software MATCH-AI. We assessed the effect of the intervention on the primary outcome, Camp Positivity Yield, defined as the number of individuals diagnosed with bacteriologically confirmed TB per camp, using generalised linear mixed models. The primary analysis was by intention to treat. Camps conducted within a 5-km radius of the AI selected locations were included in a validated per-protocol analysis. We conducted several district-level subgroup analyses. This trial is registered, number NCT06017843. Findings Between August 2023 and September 2024, 3,936 screening camps were conducted (2,046 control, 1,890 intervention), screening 269,254 individuals. In the intention-to-treat analysis, Camp Positivity Yield was 7% higher in the intervention group relative to the control group, however this difference was not statistically significant (adjusted risk ratio [RR] 1.07, 95% CI: 0.94 -1.22). In the validated per-protocol analysis, Camp Positivity Yield was 32% higher in the intervention group relative to the control group (adjusted RR 1.32, 95% CI: 1.12-1.54). Yields were highest in districts that had moderate baseline yields of 0.5-1% per population screened prior to the trial (adjusted RR: 1.57, 95% CI: 1.13 - 2.18) and in rural districts (adjusted RR 1.43, 95% CI: 1.23 -1.65). Interpretation The use of an AI-guided targeting strategy significantly increased detection of bacteriologically confirmed TB during active case-finding in the validated per-protocol analysis, relative to conventional site-selection approaches employed by field-staff. This software may be considered as a supportive tool to improve the efficiency of community-based TB case-finding interventions in other high burden countries.

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.