Mohammad Uddin Poster 2025

Dr Mohammad Uddin

icddr,b, Bangladesh

Innovating Extrapulmonary Tuberculosis Care with RISK6: Diagnosis and Treatment Monitoring

Poster Abstract

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging due to the diverse clinical manifestations of the disease and the requirement for invasive sampling and specialized processing. Moreover, current methods cannot monitor or predict treatment efficacy even though standard EPTB treatment regimens often require extension. In this context, we aimed to evaluate the performance of the RISK6 transcriptomic signature, previously investigated solely in pulmonary TB, for EPTB diagnosis and treatment monitoring.

We enrolled 382 individuals (> 11 years old) presumed to have EPTB because of signs and symptoms, and 30 healthy controls, in Dhaka, Bangladesh, from March 2022 to 2023. Clinical samples from presumed EPTB cases underwent GeneXpert, culture, and microscopy testing to confirm the diagnosis of EPTB. Blood samples were obtained from all participants at enrolment (and post-treatment for confirmed cases) to assess the RISK6 signature score via RT-qPCR. RISK6 signature performance was evaluated using the receiver-operating characteristic curve (ROC AUC) and Student’s t-test.

Among 382 enrolled individuals, 75 were microbiologically confirmed for EPTB and 307 were unconfirmed (not diagnosed with EPTB). Ongoing RISK6 score analysis is available for 38 confirmed cases at baseline (36 with post-treatment scores), 22 unconfirmed cases, and 22 controls. RISK6 effectively discriminated confirmed cases from controls (AUC of 95%) and unconfirmed cases (AUC of 87%). Furthermore, RISK6 scores for confirmed cases decreased significantly (p < 0.001) post-treatment. Our initial findings suggest that the RISK6 signature performance for EPTB meets the biomarker test criteria defined by the target product profile released by WHO. Minimally invasive, this signature can potentially transform EPTB diagnosis by providing an accessible testing option, even for challenging cases lacking sufficient evidence for biopsy. Additionally, the signature’s post-treatment performance indicates a future role in helping clinicians elucidate treatment outcomes.

Biography

Dr Mohammad Khaja Mafij Uddin is an Associate Scientist at icddr,b’s infectious disease division, with 12+ years of experience in Tuberculosis (TB) and Leprosy research. His work focuses on TB diagnostics using molecular, microbiological, and immunological approaches. He has developed in-house diagnostic methods, trained junior staff, and adopted advanced techniques. His research interests include molecular diagnosis, TB pathogenesis, genetic epidemiology, and immunological biomarkers. He supervises projects funded by Fondation Merieux, ICGEB, Stop TB, and USAID’s ACTB, working on DR-TB detection, transmission dynamics, and non-sputum diagnostics. He also coordinates lab activities and collaborates with national and international partners.