Title: Clinical Application of Whole Genome Sequencing in Multidrug-Resistant Tuberculosis Patients in Tanzania

Duration: October 2020 – March 2025
Coordinator: Dr. Bugwesa Z. Katale
Funding: €150,000 from European and Developing Countries Clinical Trials Partnerships (EDCTP)
Acronym: CWGSMDR-TB

Project Summary

This project brought cutting-edge genomic technology to the frontline of the TB fight in Tanzania. It integrated whole genome sequencing (WGS), drug susceptibility testing (DST), patient treatment histories, and geographic mapping (GIS) to investigate how drug-resistant TB develops and spreads.

Primary objective

· To describe the incidence of drug resistance mutations in MDR-TB patients in Tanzania, establish epidemiological associations and evaluate the clinical application of this approach.

Secondary objective

· To describe drug susceptibility against first and second line antituberculosis drugs

· To identify molecular markers associated with drug resistance M. tuberculosis in these population isolates

· To describe associations between drug resistance genotype and clinical outcome

· To determine the genetic relatedness of drug resistance M. tuberculosis isolates

· To determine the genetic relatedness and phylogenetic relationship of drug resistance M. tuberculosis isolates

· Determination of the role of genotypic mutation alone or in combination in clinical outcome.

· To monitor the microevolution events in drug resistance genes during antituberculosis therapy

Key Findings

· Early Detection Power: WGS detected resistance mutations before they showed up in lab tests.

· Mutation Tracking: Identified evolving resistance to bedaquiline and clofazimine, signalling urgent need for careful drug stewardship.

· Beijing Strain Discovery: Found the virulent Lineage 2 (Beijing strain) spreading in Tanzania – a known global challenge.

· Association of drug resistance mutation with clinical outcomes in drug resistance tuberculosis patients

· Importance of integrating molecular epidemiology with spatial analysis to guide targeted surveillance, resource allocation, and localized interventions.

Innovation & Impact

· First of its Kind in Tanzania to integrate WGS with spatial mapping for TB.

· Policy-Informed Recommendations: Tailored interventions for hotspots like Dar es Salaam.

· Advancement of Precision Medicine: Enabled treatment plans based on genetic profiles of TB strains.

· Influence on National Strategy: Advocate for incorporating Whole Genome Sequencing in the diagnostic algorithm.

Geographical Information System & Phylogenetics

The project revealed how TB lineages spread differently across Tanzania.

· Dar es Salaam was the hotspot for drug-resistant TB, followed by Kilimanjaro and Shinyanga.

· TB lineages 3 and 4 dominate, but Lineage 2 (Beijing) poses a growing threat.

· Four major phylogenetic clusters suggest ongoing local transmission.

 Dissemination & Publications

· Published in Annals of Clinical Microbiology and Antimicrobials and submitted to BMC Infectious Diseases and Frontiers in Microbiology. The article published on Annals of Clinical Microbiology and Antimicrobials is available at https://ann clinmicrob.biomedcentral.com/articles/10.1186/s12941-024-00737-9.

· Policy Briefs developed for sharing with TB stakeholders.

· Community Engagement and exploitation of results conducted in Dar es Salaam and Kibing’oto Infectious Diseases Hospital respectively to inform and involve the public and health practioners.

· Featured in MedicoPress article: “Why Genetic Technology Offers New Hope For Resistant TB Fight”

Recommendations for Tanzania

1. Make WGS routine for retreatment and drug-resistant TB cases.

2. Expand genomic surveillance for early outbreak detection.

3. Improve treatment adherence through behavioral and digital interventions.

4. Strengthen regional collaboration for cross-border TB control.

Societal & Economic Impact

· Better diagnostics = fewer deaths and hospitalizations.

· Precision treatment saves costs and improves recovery.

· Early detection prevents outbreaks of deadly drug resistance tuberculosis.

· Increased health equity through localized interventions and awareness.

Final Thoughts

This project demonstrates that modern genomics can transform TB care even in resource limited settings. By combining Whole Genome Sequencing (WGS) and Geographic Information Systems (GIS), Tanzania is building a stronger foundation to detect drug resistance early, tailor treatments to individual patients, and contain the spread of resistant TB strains. It serves as a powerful call to scale up innovation, inform policy, and strengthen collaboration for a TB-free future.