Drug Resistant Tuberculosis in Kampala, Uganda: Complementing Susceptibility Testing With Whole Genome Sequencing

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Thematic Focus:
Life Sciences and Health
Involved Countries:
Switzerland, Uganda

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Proposed activities to be funded by this grant:

a) Workshop at the Makerere University on bioinformatic and phylogenetic tools (2 weeks). We propose a workshop on the usage of next generation sequencing technologies and population genomics to tackle biological problems. Sessions would be comprised of lectures introducing the tools and the conceptual issues underlying them, followed by practical sessions where problems will be presented and participants will be asked for a bioinformatics solution.

b) Visit of a member of Prof. Moses Joloba team (Dr. David Kateete) to the laboratory of Prof. Sebastien Ganeux at the Swiss Tropical and Public Health Institute (2 months).  At the Swiss TPH, Dr. Kateete was trained in analyzing whole-genome sequences of M.tuberculosis isolates in order to characterize its genetic variation. Additionally, he will be trained in the downstream analysis genetic variation (phylogenetic and molecular evolution methods) and in the interpretation of the data.

Upon completion of the activities proposed, the capacity to analyze high throughput data at Makerere University i at hand. After his stay at the Swiss TPH, Dr. Kateete i asble to benefit its own research but he is also able to assist local researchers at Makerere University. Gradually, Bioinformatics courses in graduate curricula could be also be introduced. The activities proposed will furthermore enhance the generation of important scientific outputs; the spectrum of resistance mutations to first-line and second-line TB drugs in Kampala is available, and this will inform on the performance of rapid and conventional DST tests currently in practice, as well as those to be introduced in future. Given that resistance mutations against in M. tuberculosis vary geographically their prevalence and patterns will be described for the first time in Uganda.

The primary objectives of the proposed activities to be funded by this grant are i) and ii).  However, scientific objectives iii) iv), whose activities are not funded by this grant, are of great relevance and depend on the first two to be attained. We propose to initially start by sequencing and analysing data at the Swiss TPH by the team of Prof. Gagneux and gradually,as funds become available and bioinformatic capacity is built, start sequencing and analysing data at Makerere University.

i) The implementation of whole-genome sequencing as a tool to characterize clinical isolates of Mycobacterium tuberculosis in Kampala, Uganda.
ii) The development of bioinformatic capacity in order to deal with whole-genome sequences of M. tuberculosis isolates.
iii) To determine the prevalence and patterns of resistance conferring mutations to anti-Tuberculosis drugs in M. tuberculosis in Kampala
iv) To investigate the relationship between polymorphisms in resistance-encoding genes and its association with drug resistance phenotype.

-Sebastian Gagneux, University of Basel, Swiss Tropical and Public Health Institute, Basel
-David Patrick Kateete, Makerere University College of Health Sciences, Kampala, Uganda