Background: Tuberculous meningitis (TBM) in children causes high mortality and frequent disability. Intensified anti-tuberculosis treatment (ATT) and adjunctive aspirin may improve outcomes. Methods: SURE (ISRCTN 40829906) was a factorial, partially blinded, randomised-controlled trial in African (Zimbabwe, Zambia, Uganda) and Asian (India, Vietnam) children (29 days to <18 years) with confirmed or suspected TBM. Participants were randomised to receive intensified-ATT [isoniazid(20mg/kg), rifampicin(30mg/kg), pyrazinamide(40mg/kg), levofloxacin(20mg/kg) daily for 24-weeks] or standard-ATT [isoniazid(10mg/kg), rifampicin(15mg/kg), pyrazinamide(35mg/kg), ethambutol(20mg/kg) daily for 8 weeks, then isoniazid(10mg/kg) and rifampicin(15mg/kg) for 40 weeks] and simultaneously to receive aspirin(20mg/kg) or placebo daily for 8 weeks; all received corticosteroids for 8 weeks. Primary outcomes for ATT and aspirin/placebo randomisations were mortality and modified Rankin Scale (mRS) respectively at 48 weeks, analysed by modified-intention-to-treat. We specified a 10% non-inferiority margin for ATT and 16% minimal clinically significant difference for aspirin. Findings: Between March 2021 and July 2024, 369 children were randomised; five children were lost-to-follow-up before week-48, and 17 had no week-48 mRS. 174(47%) were female; median(IQR) age was 4.8(1.3-10) years, 15(4%) were HIV-infected, and 203(55%) had moderate/severe (MRC grade 2/3) disease. 29/177(16%) randomised to intensified-ATT died versus 21/181(12%) standard-ATT (adjusted risk difference 5.1%; 95% confidence interval -1.7% to +12.0%; p=0.14), not meeting the 10% non-inferiority margin. Severe disability/death (mRS 5/6) occurred in 38/176(22%) children randomised to aspirin versus 25/170(15%) placebo (adjusted odds ratio 1.80; 95%CI 0.95-3.41; p=0.07). Grade 3/4 adverse events were more frequent in intensified-ATT than standard-ATT (86/186(46%) versus 65/183(36%); p=0.03). Drug-liver injury (grade 2 or above) were also more frequent (64/186(34%) versus 32/183(17%); p<0.001). Grade 3/4 adverse events were also more frequent with aspirin than placebo 86/185(46%) versus 65/184(35%); p=0.03); bleeding events were rare and similar between arms. Interpretation: Neither 24-week intensified-ATT nor aspirin improved outcomes in children with TBM. New therapeutic strategies are urgently needed to increase survival and reduce disability from TBM.

Background:Rifampicin-resistant tuberculosis (RR-TB) is a major threat to public health in Viet Nam, with nearly 10,000 incident cases estimated annually. It is uncertain whether these cases are driven by transmission of resistant strains or de novo resistance acquisition during treatment. Methods:We undertook dense, city-wide sampling of adults newly diagnosed with pulmonary RR-TB in Ho Chi Minh City, Viet Nam's largest city, between March 2020 and April 2024. Participants provided sputum for culture and whole-genome sequencing (WGS), and demographic and clinical data were collected at enrolment. Phylogenetic analyses were combined with clinical histories to infer transmitted versus acquired rifampicin resistance. Estimates were corrected for sampling coverage using simulation-extrapolation (SIMEX). Temporal emergence of rifampicin resistance was reconstructed by lineage using Bayesian phylogenetic dating, and the geographic and demographic structure of transmission clades was assessed using geocoded residential data and commute time-based analyses. Findings:Among 2319 RR-TB cases diagnosed during the study period, 1491 (64%) isolates were successfully sequenced. Among these, 1320 (89%) were Lineage 2. After accounting for sampling and phylogenetic uncertainty, we estimated that 72-87% of RR-TB was attributable to transmission of already-resistant strains, with the remainder reflecting de novo acquired resistance. Bayesian dating analyses revealed that resistance emergence events occurred repeatedly from the 1980s to the present, with early events seeding long-lived, city-wide transmission clades. Transmission clades were geographically dispersed across the city, with limited household clustering, and only weakly structured by host demographics, consistent with diffuse, city-wide transmission rather than localised or assortative spread. Interpretation:RR-TB in Ho Chi Minh City is driven predominantly by ongoing transmission, but a substantial minority of cases arise from newly acquired resistance. Alongside promoting early diagnosis and treatment to interrupt transmission, the main drivers of acquired resistance need to be identified to control RR-TB. Funding:The Rhodes Trust, Wellcome.

Novel clade 2.3.2.1e A(H5N1) virus was detected in cerebrospinal fluid but not in respiratory, rectal swab, or blood samples of an 8-year-old boy presenting with meningoencephalitis without respiratory symptoms. Cerebrospinal fluid A(H5N1) hemagglutinin-specific antibody levels were higher than those of sera. Clinicians should be aware of emerging clade 2.3.2.1e A(H5N1)-associated meningoencephalitis.

Background:Pulmonary TB (PTB) patients present with a wide range of pre-treatment Mycobacterium tuberculosis ( Mtb ) burdens, which predict poor treatment outcomes. We sought to identify immune pathways and biomarkers associated with pre-treatment Mtb burden. Methods:We conducted whole-blood RNA sequencing in 295 Vietnamese adults with PTB, quantifying bacterial load using GeneXpert Ct values. Weighted gene co-expression network analysis (WGCNA) identified gene modules, pathways, and hub genes associated with Mtb burden. Deconvolution analysis assessed contributions of immune cell types. Key findings were validated in independent PTB (n=171) and TB meningitis (TBM, n=281) cohorts, and publicly available animal datasets. We used non-linear regression for variable selection to identify gene predictors of Mtb burden and hurdle regression to model Mtb loads below the detection limit. Findings:Higher Mtb burden correlated with prolonged symptom duration, elevated neutrophil and monocyte counts, and severe lung pathology. WGCNA identified a 1,093-gene module associated with Mtb burden, characterized by coordinated innate-adaptive pathway interactions. Within this module, IFN-γ signaling participates in modulating the increase of innate signaling (Toll-like, Nod-like receptors, TNF) and the decrease of adaptive signaling (T- and B-cell receptor) pathways in high-burden patients. These responses were primarily driven by neutrophils and classical monocytes. CNIH4 emerged as the strongest hub-gene and a top predictor of bacterial burden, with consistent validation across independent PTB and TBM cohorts. Interpretation:Our study reveals systemic innate-adaptive immune dynamics underlying bacterial burden in PTB and identifies CNIH4 as a potential biomarker for treatment monitoring as well as a therapeutic target. Funding:National Institute of Health; Wellcome Trust, UK. Research in Context:Evidence before this study: We searched PubMed from Jan 1, 2000, to Dec 10, 2025, without language restrictions, for human studies examining the relationship between Mycobacterium tuberculosis (Mtb) burden and host blood transcriptional responses in pulmonary tuberculosis. Search terms were used in combination as follows: ("Tuberculosis, Pulmonary" OR "pulmonary tuberculosis" OR PTB) AND ("Mycobacterium tuberculosis" OR mycobacter*) AND ("bacterial load" OR "bacterial burden" OR "sputum smear" OR "smear grade" OR xpert OR genexpert OR "cycle threshold" OR ct OR "time to positivity" OR TTP OR CFU OR "molecular bacterial load" OR MBLA)) AND (blood OR "whole blood" OR "peripheral blood") AND (RNA-seq OR "RNA sequencing" OR transcriptom* OR "gene expression" OR microarray). We included studies of active pulmonary tuberculosis that measured quantitative or semi-quantitative bacterial burden and profiled host blood transcriptome-wide responses at baseline, reporting either differential expression by burden strata or associations between bacterial burden and host gene expression. We excluded studies limited to latent tuberculosis, animal or in vitro models, diagnostic or prognostic signature studies without bacterial burden measurement, studies focused on treatment response, and studies using targeted assays without transcriptome-wide profiling.This search identified 12 articles describing blood transcriptional signatures for tuberculosis diagnosis, prognosis, and treatment response. However, only one study directly examined the relationship between pre-treatment bacterial burden and whole-blood transcriptome-wide profiles. That study demonstrated differences in systemic gene expression between patients with higher and lower sputum mycobacterial load and proposed a 20-gene blood signature associated with bacterial burden. However, the analysis was limited by small sample size, lack of pathway-level and cellular interpretation or assessment of correlation between signature with bacterial load.Added value of this study: Our study advances existing evidence by leveraging the wide spectrum of pre-treatment bacterial burden observed in routine clinical populations, quantified using GeneXpert Ct values, and integrating this with whole-blood RNA sequencing in large, well-characterized clinical cohorts. Through network-based transcriptomic analysis, immune cell deconvolution, and non-linear modelling, we identify a bacterial burden-associated gene network characterized by enhanced innate inflammatory signaling and relative suppression of adaptive immune pathways, predominantly driven by neutrophils and classical monocytes and modulated by IFN-γ signaling. Within this network, CNIH4 emerges as a central hub gene and a robust predictor of bacterial burden, with consistent validation across independent pulmonary tuberculosis and tuberculous meningitis cohorts.Implications of all the available evidence: Taken together, the available evidence indicates that host blood transcriptional responses correlate with bacterial burden in pulmonary tuberculosis, but previous studies have provided limited insight into the underlying immune processes. Our findings strengthen the biological link between pre-treatment mycobacterial burden and systemic immune dysregulation, showing that higher bacterial burden is associated with transcriptional state marked by coordinated upregulation of innate immune responses and downregulation of adaptive immune pathways. These results support the use of host transcriptomic profiling as a biologically informative complement to sputum-based measures of bacterial burden and highlight burden-associated immune pathways, particularly CNIH4, as a potential target for treatment monitoring and host-directed therapeutic development.

Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are among the WHO's highest-priority antibiotic-resistant pathogens. Plasmids are the main drivers of ESBL dissemination, yet their reservoirs and transmission dynamics remain poorly understood in low- and middle-income countries such as Vietnam, where infections caused by ESBL-producing bacteria are prevalent. Methods: Here, we characterised the genetic structure of 68 ESBL-encoding conjugative plasmids isolated from the human gut microbiome (HGM) of healthy Vietnamese children. We further examined the extent of ESBL plasmid transfer between the HGM and human disease-causing Enterobacteriaceae pathogens (including Shigella sonnei, non-typhoidal Salmonella, extraintestinal pathogenic Escherichia coli ST131), as well as E. coli isolated from animals. Results: The dominant plasmid Inc groups found in cephalosporin-resistant human gut bacteria were IncF, IncB/O/K/Z and IncI1, carrying mainly blaCTX-M-14, blaCTX-M-15, blaCTX-M-27 and blaCTX-M-55. These plasmids from the HGM, rather than from animal E. coli, share higher genetic similarity to plasmids in human pathogens, suggesting that human gut is the main reservoir for clinically relevant ESBL plasmids. We also found that widespread ESBL plasmid variants exhibited higher conjugation frequencies, facilitating broader geographical and host dissemination. In contrast, less mobile plasmids persisted mainly through clonal expansion of their bacterial hosts. Conclusions: These findings highlight the central role of the human gut as a reservoir for ESBL plasmids and provide insights into the biological factors contributing to their successful spread among pathogenic Enterobacteriaceae. Our work underscores the need for targeted interventions to reduce colonization and transmission of ESBL-producing bacteria within the human gut. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Duy Thanh Pham is funded by Wellcome Trust International Training Fellowship (222983/Z/21/Z). Experimental work done in Christoph M. Tang's lab is funded by Wellcome Trust (221924/Z/20/Z). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Samples used in this study were collected from a longitudinal cohort study monitoring diarrhoeal disease episodes in children in Ho Chi Minh City (HCMC), Vietnam. Ethical approval for the study was granted by Oxford Tropical Research Ethics Committee (OxTREC number: 1058-13)32. Informed consent was obtained from all participants prior to enrolment. All procedures were conducted in accordance with the Declaration of Helsinki and relevant institutional guidelines. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in this work are publicly available in the European Nucleotide Archive (ENA) under project numbers PRJEB96742 (https://www.ebi.ac.uk/ena/browser/view/PRJEB96742)

Distinguishing enteric (typhoid and paratyphoid) fever from other causes of fever is challenging. The diagnostic accuracy of Typhoid Rapid Diagnostic Tests (RDT) are suboptimal but might improve if combined with a clinical score. We aimed to develop a clinical score, incorporating a point of care C-reactive protein (CRP) and Typhoid RDT, that could be used for febrile patients attending a health facility with limited laboratory capability, to identify those suitable for further investigations such as a blood culture, an empirical antimicrobial choice that covers enteric fever, or to rule out enteric fever as a likely diagnosis. Overall, 1168 Bangladeshi, Cambodian and Nepali children and adults attending hospital with fever were randomly split (80:20) into derivation and validation cohorts. There were 208/1168 (18

Tuberculous meningitis causes death or disability in approximately 50% of affected individuals and kills approximately 78 200 adults every year. Antimicrobial treatment is based on regimens used for pulmonary tuberculosis, which overlooks important differences between lung and brain drug distributions. Tuberculous meningitis has a profound inflammatory component, yet only adjunctive corticosteroids have shown clear benefit. There is an active pipeline of new antitubercular drugs, and the advent of biological agents targeted at specific inflammatory pathways promises a new era of improved tuberculous meningitis treatment and outcomes. Yet, to date, tuberculous meningitis trials have been small, underpowered, heterogeneous, poorly generalisable, and have had little effect on policy and practice. Progress is slow, and a new approach is required. In this Personal View, a global consortium of tuberculous meningitis researchers articulate a coordinated, definitive way ahead via globally conducted clinical trials of novel drugs and regimens to advance treatment and improve outcomes for this life-threatening infection.

SUMMARYBackgroundSotrovimab is a neutralising monoclonal antibody that has been proposed as a treatment for patients admitted to hospital with COVID-19.MethodsIn this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 pneumonia. In the sotrovimab comparison, eligible and consenting patients were randomly allocated to either usual care alone or usual care plus a single 1g dose of sotrovimab, using web-based unstratified randomisation. Participants were retrospectively categorised according to their baseline serum SARS-CoV-2 nucleocapsid antigen concentration as ‘high-antigen’ or ‘low-antigen’, using the median concentration as a cut-off. The primary outcome was 28-day mortality assessed by intention to treat. Secondary outcomes were time to discharge alive from hospital, and, among those not on invasive ventilation at baseline, progression to invasive ventilation or death. Recruitment closed on 31 March 2024 when funding ended. ISRCTN (50189673) andclinicaltrials.gov(NCT04381936).FindingsFrom 4 January 2022 to 19 March 2024, 1723 patients were recruited to the sotrovimab comparison. 720 (42%) were classified as high-antigen, 717 (42%) as low-antigen, and 286 (17%) had unknown antigen status. Over 80% of patients were vaccinated, over 80% had anti-spike antibodies at randomisation, and almost all were infected with Omicron variants. In the prespecified primary efficacy population of high-antigen patients, 82/355 (23%) allocated sotrovimab versus 106/365 (29%) allocated usual care died within 28 days (rate ratio 0.75; 95% CI 0.56-0.99; p=0.046). In an analysis of all randomised patients (regardless of antigen status), 177/828 (21%) allocated sotrovimab versus 201/895 (22%) allocated usual care died within 28 days (rate ratio 0.95; 95% CI 0.77-1.16; p=0.60).InterpretationIn patients hospitalised with COVID-19, sotrovimab was associated with reduced mortality in the primary analysis population of patients with a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).

BACKGROUND:Non-sputum-based, point-of-care triage tests for pulmonary tuberculosis could enhance tuberculosis diagnostic programs. We assessed the diagnostic accuracy of 2 finger-stick blood tests: the Cepheid 3 gene host-response cartridge (Xpert-HR), which measures 3 host messenger RNA transcripts, and the 3-host protein multibiomarker test (MBT). METHODS:We performed a prospective diagnostic accuracy study of consecutive participants with symptoms compatible with pulmonary tuberculosis in The Gambia, South Africa, Uganda, and Vietnam. A composite reference standard for active pulmonary tuberculosis incorporated chest radiography, symptom resolution, and sputum microbiological test results. A training-test set approach was used to evaluate test cutoff specificities at 90% sensitivity. RESULTS:Between 1 November 2020 and 1 May 2023, we screened 1262 participants aged 12-70 years with cough lasting >2 weeks and another symptom suggestive of tuberculosis. Of those who were classifiable by reference tests, 1154 participants had evaluable Xpert-HR results and 961 had evaluable MBT results. Xpert-HR had an area under the receiver operating characteristic (AUROC) curve of 0.92 at a cutoff of -1.275 or below, with a sensitivity of 92.8%, specificity of 62.5%, positive predictive value of 47.9%, and negative predictive value of 95.9%. The MBT had an AUROC of 0.91 at a cutoff of ≥0.42, with a sensitivity of 91.4%, specificity of 73.2%, positive predictive value of 52.0%, and negative predictive value of 96.4%. CONCLUSIONS:Our results show that both Xpert-HR and the MBT are promising non-sputum-based point-of-care tests. The MBT met the World Health Organization target product profile for a triage test, which suggests it should be further developed.

Diphtheria has resurged globally, including in Indonesia, despite widespread vaccination since the 1970s. Knowledge gaps persist in understanding contemporary transmission drivers and effective outbreak control, especially in densely populated areas like Jakarta. We analyzed the 2017 Jakarta outbreak data and developed a compartmental model incorporating estimates of population susceptibility and asymptomatic carriers. Key epidemiological parameters were estimated, and various control measures were simulated. Our study found overall diphtheria susceptibility at 12.9 % (95 % CrI: 8.6 %–19.0 %) and 28.0 % (95 % CrI: 20.5 %–36.0 %) in children under 5 under different modeling scenarios, which were below the 'herd immunity threshold'. We estimated asymptomatic carriers to be highly prevalent, substantially contributing to the reproduction number. The model indicated that contact tracing and treating suspected cases and their contacts were more effective in preventing new cases than catch-up vaccination alone. These findings provide valuable insights for future outbreak management strategies in similar settings.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host leukotriene A4 hydrolase (LTA4H) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): ‘Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis’. The primary hypothesis addressed by the trial is that LTA4H genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an LTA4H genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6–8 weeks in addition to standard anti-tuberculosis drugs. LTA4H genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host leukotriene A4 hydrolase (LTA4H) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): ‘Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis’. The primary hypothesis addressed by the trial is that LTA4H genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an LTA4H genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6–8 weeks in addition to standard anti-tuberculosis drugs. LTA4H genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.

Tuberculous meningitis remains the most lethal form of tuberculosis. Despite significant physiological differences adults and children with tuberculous meningitis receive similar treatment and are often grouped together in research. Consequently, differences in tuberculous meningitis characteristics across the lifespan are poorly understood but may be relevant to developing more effective and age-appropriate interventions. In this review we discuss potential age-specific considerations in pathogenesis and pathophysiology, and review literature over the last 5 years to describe clinical characteristics, management, and outcomes across age groups. Children aged <5 years are vulnerable to tuberculosis disease and dissemination due to an immature immune system and the developing brain is highly susceptible to injury associated with neuroinflammation, leading to a greater likelihood of disability that has lifelong impact. Amongst adults, those with human immunodeficiency virus and older people are at greatest risk of death, but more research into the frequency of neurocognitive disability is needed.

Background: Collecting and storing large number of sputum samples with a view to culturing these in the future requires an efficient initial handling method. We devised a modified sputum digestion and decontamination method that maximised storage capacity and Mycobacterium tuberculosis (M.tb) recovery from culture while minimising laboratory workload and risk of contamination. Methods: We collected smear microscopy positive sputum samples from patients with pulmonary tuberculosis (TB). The sputum samples were split and processed using both the standard N-Acetyl-L-cysteine and sodium hydroxide (NALC-NaOH) method and our modified method before freezing and later culturing in BD BACTEC 960 Mycobacterium Growth Indicator Tubes (MGIT) system. We assessed the Time to Positivity (TPP) and Growth Unit (GU) data. Results: We selected 22 sputum samples to compare two digestion and decontamination methods. The samples that underwent the modified method had longer TTP (p < 0.05) but similar GU in comparison to standard method. Overall, 1/22 samples failed to grow in MGIT after being processed by the modified method. We then applied the modified method to 348 sputum samples with Rifampicin resistance detected by GeneXpert MTB/RIF assay, which were frozen for between 1-25 months. The overall MGIT positive, negative, and contamination rate was 90.5%, 7.8%, and 1.7%, respectively. There was no significant difference in MGIT result when samples were grouped by duration of storage or positive smear grade. Conclusions: Our modified method yielded acceptable M.tb recovery rate and low contamination risk while allowing us to collect and store thousands of sputum samples over a long period of time for future tests.

INTRODUCTION:Tuberculous meningitis (TBM) leads to high mortality, especially amongst individuals with HIV. Predicting the incidence of disease-related complications is challenging, for which purpose the value of brain magnetic resonance imaging (MRI) has not been well investigated. We used a convolutional neural network (CNN) to explore the complementary contribution of brain MRI to the conventional prognostic determinants. METHODS:We pooled data from two randomised control trials of HIV-positive and HIV-negative adults with clinical TBM in Vietnam to predict the occurrence of death or new neurological complications in the first two months after the subject's first MRI session. We developed and compared three models: a logistic regression with clinical, demographic and laboratory data as reference, a CNN that utilised only T1-weighted MRI volumes, and a model that fused all available information. All models were fine-tuned using two repetitions of 5-fold cross-validation. The final evaluation was based on a random 70/30 training/test split, stratified by the outcome and HIV status. Based on the selected model, we explored the interpretability maps derived from the models. RESULTS:215 patients were included, with an event prevalence of 22.3%. On the test set our non-imaging model had higher AUC (71.2% [Formula: see text] 1.1%) than the imaging-only model (67.3% [Formula: see text] 2.6%). The fused model was superior to both, with an average AUC = 77.3% [Formula: see text] 4.0% in the test set. The non-imaging variables were more informative in the HIV-positive group, while the imaging features were more predictive in the HIV-negative group. All three models performed better in the HIV-negative cohort. The interpretability maps show the model's focus on the lateral fissures, the corpus callosum, the midbrain, and peri-ventricular tissues. CONCLUSION:Imaging information can provide added value to predict unwanted outcomes of TBM. However, to confirm this finding, a larger dataset is needed.

In 2022, we established a residual sample serosurveillance program in Ho Chi Minh City, Vietnam. During September 2022-April 2024, we found low measles antibody seroprevalence in children in the city's western region, where a measles outbreak began in May 2024. Serosurveillance could be a useful tool for outbreak prediction and prevention.

BACKGROUND:The Burkholderia cepacia complex (Bcc), a group of environmentally ubiquitous bacteria, are inherently resistant to antiseptics and antibiotics. Bcc can proliferate in pharmaceutical products, resulting in nosocomial outbreaks. However, Bcc is often dismissed as blood culture contaminants, and precise identification of Bcc species remains challenging in resource-limited settings, leading to under-treatment and delay in outbreak detection. This paper reports the first identified Bcc bacteraemia outbreak in a Vietnamese intensive care unit (ICU). METHODS:In June 2023, a Bcc bacteraemia outbreak was acknowledged by the hospital authorities after examination of clinical and microbiological evidence. A comprehensive investigation was performed, encompassing epidemiological and clinical review, environmental sampling, whole-genome sequencing (WGS), and implementation of enhanced infection prevention and control (IPC) measures. RESULTS:The bacteraemia outbreak involved 19 ICU patients between May and August 2023. The causative bacteria were identified as B. cenocepacia belonging to a novel sequence type, and did not carry any acquired antimicrobial resistance genes. Although these organisms were susceptible to the commonly used antibiotics, the outbreak was associated with a high case fatality rate. Three B. cenocepacia isolates were also found in used syringes for drug infusion in three cases, exhibiting a genomic link to the outbreak cluster. Enhanced IPC measures targeting aseptic techniques in handling intravenous medications resulted in termination of the outbreak. CONCLUSIONS:WGS plays a crucial role in outbreak control, particularly for under-studied opportunistic pathogens. This work also highlights key gaps in IPC measures, species identification, and treatment of Bcc infections, warranting further research to improve hospital prevention and treatment strategies.

Nontuberculous mycobacteria are environmental mycobacteria that rarely cause human disease, especially in the central nervous system. Central nervous system infection by Mycobacterium avium complex, the most common pathogen among nontuberculous mycobacteria species, is rare and seldom reported, even in those with advanced human immunodeficiency virus infection. We describe a case of Mycobacterium avium complex meningitis with cerebral hemorrhage in an human immunodeficiency virus uninfected man in Vietnam. A 56-year-old Vietnamese man with hypertension was hospitalized with a 5-day history of headache, dizziness, low-grade fever, and unresponsive to 5 days of oral antibiotics. A brain magnetic resonance imaging, performed on day 12, showed hydrocephalus and lacunar infarct. The patient did not improve with 8 days of empirical treatment with ceftriaxone, vancomycin, dexamethasone, and meropenem, and was transferred to a referral hospital for tropical diseases. At the second hospital admission, a cerebrospinal fluid analysis showed a white cell count of 22,518 cells/μL with 81