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The emergence of extremely drug-resistant tuberculosis (XDRTB) poses a growing threat to national and international biosecurity and to TB control achievements. Current standard indirect drug susceptibility testing (DST) takes up to 3 months to identify XDR-TB, undermining efforts to control it. The University of California at San Diego, along with collaborators from around the world, aim to reduce the time for DST and identify the genetic basis of drug-resistant strains from distinct geographical areas with a large TB burden.
This study, funded by the National Institutes of Health, will in Year 1, create new probes and assay procedures for the rapid tests (Version-1), which will be based on published information, publicly-available genomic databases and new information from genotypic analysis of existing XDR and drug-susceptible strains from four study sites - South Africa, Moldova, India, the Philippines. These study sites will enroll over 2,000 TB patients in Years 2-4; collect clinical data, sputa, and culture isolates; and perform the three rapid tests and DST onsite.
New mutations discovered through the process of sequencing target genes, neighboring genes, or whole genomes to find new regions or points of difference compared to drug-susceptible strains will inform creation of probes for Version-2 rapid tests, as needed, to be tested at the study sites along with Version-1. This 5-year study will result in novel tests to rapidly detect XDR-TB in a broad range of laboratory settings as well as a repository of diverse well-characterized TB strains for future studies. The longterm implication is the development of technologies and methods that can be adapted to rapidly detect new drug-resistant TB strains and to test for resistance to other anti-TB drugs.
The GCDD gratefully acknowledges the support of the National Institutes of Health