Our current research objectives are improving TB diagnosis, treatment and prevention by carrying out clinical trials of new diagnostic tests, therapeutic approaches and vaccines. We also aim to understand the mechanisms by which both host and pathogen influence disease severity, treatment responses and outcomes using human macrophage models and omics technologies.
We focus on six research areas:
Clinical team members include study doctors, study nurses, study coordinators and data coordinators. The team’s responsibilities are working at hospitals and district TB units to recruit participants, making clinical assessments, taking samples, and follow-up until the end of the study.
Bacterial lab team members include lab technicians, research assistants and PhD/post-doc scientists.
The team works in our laboratories at OUCRU (clinical lab, BSL2 and BSL3 labs). They are responsible for running all the microbiological lab tests (diagnosis tests, drug-susceptible and tolerance testing) required by all studies and managing many types of samples. Some of these tests are routine TB tests; some are novel tests which are still in the development and research stage.
Similar to the Bacterial Lab team, the Cell-Immunological lab team members work in our labs at OUCRU. The team works mainly on cells, molecular lab experiments and analysis, which include host-pathogen interaction, cytokines, whole genome sequencing (WGS), next-generation sequencing (NGS) and omics.
Data team members include research assistants and PhD/post-doc biostatisticians who are in charge of analysing data collected by the clinical team and lab teams. Their works focus on omics, WGS and NGS.
The Paediatrics TBM team structure is similar to the clinical team. The team is working on clinical trials and observational studies in diagnosing and treating TBM in children.
The epi-Microbiology team structure is similar to the clinical team. The team is conducting many observational-epidemiological studies and genetic data analysis focusing on drug resistance, epi-microbiology, and epi-genomics of TB and TB vaccine.
Associations between cell size and structure and drug resistance have been shown ( & ), whilst the spread of the Beijing lineage and positive selection of the EsxW Beijing variant in Vietnam have also been demonstrated (); Sources of multi-drug resistance (); Risk factors for poor treatment outcomes of multidrug-resistant TB (). 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis ().
We defined the use of GeneXpert MTB/RIF in the diagnosis of TBM () and pediatric TB (). The largest prognostic study to date of mortality in TBM with 1699 cases (, ) identified predictors for increased mortality. Xpert MTB/RIF Ultra for the diagnosis of TBM (). Cepheid 3-gene host response fingerstick blood test for PTB diagnosis ().
Human Leukotriene A4 Hydrolase (LTA4H) genotype was found to determine TBM susceptibility and predict the effectiveness of adjunctive dexamethasone ( and , ). Two large multi-centre clinical trials to personalised TBM treatment are underway (). Effect of bacterial burden on inflammatory response and outcome (, ).
Thuong NTT, Heemskerk D, Tram TTB, et al. Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis. J Infect Dis. 2017;215(7):1020-1028. https://pubmed.ncbi.nlm.nih.gov/28419368/
Mai NT, Dobbs N, Phu NH, et al. A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults. Elife. 2018;7:e33478. https://pubmed.ncbi.nlm.nih.gov/29482717/
Van LH, Phu PT, Vinh DN, et al. Risk factors for poor treatment outcomes of 2266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study. BMC Infect Dis. 2020;20(1):164. https://pubmed.ncbi.nlm.nih.gov/32087682/
Tram TTB, Ha VTN, Thu DDA, et al. Variations in Antimicrobial Activities of Human Monocyte-Derived Macrophage and Their Associations With Tuberculosis Clinical Manifestations. Front Cell Infect Microbiol. 2020;10:586101. https://pubmed.ncbi.nlm.nih.gov/33194825/
Sutherland JS, van der Spuy G, Gindeh A, et al. Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results. Clin Infect Dis. 2022;74(12):2136-2141. https://pubmed.ncbi.nlm.nih.gov/34550342/
Walker TM, Miotto P, Köser CU, et al. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis. Lancet Microbe. 2022;3(4):e265-e273. https://pubmed.ncbi.nlm.nih.gov/35373160/