Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania

• Published in: BMC genomics Vol. 21; no. 1; pp. 174 - 15
• Main Authors: Katale, Bugwesa Z., Mbelele, Peter M., Lema, Nsiande A., Campino, Susana, Mshana, Stephen E., Rweyemamu, Mark M., Phelan, Jody E., Keyyu, Julius D., Majigo, Mtebe, Mbugi, Erasto V., Dockrell, Hazel M., Clark, Taane G., Matee, Mecky I., Mpagama, Stellah
• Format: Journal Article
• Language: English
• Published: London BioMed Central 21.02.2020; BioMed Central Ltd; BMC
• Subjects: Adult; Animal Genetics and Genomics; Antitubercular agents; Antitubercular Agents - therapeutic use; Biodiversity; Bioinformatics; Biomedical and Life Sciences; Cohort Studies; Computational biology; Diagnosis; DNA; DNA sequencing; Drug approval; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Extensively drug-resistant tuberculosis; Female; Gene mutation; Gene sequencing; Genes; Genetic aspects; Genetic diversity; Genetic research; Genomes; Genomics; Humans; Life Sciences; Male; Methods; Microarrays; Microbial drug resistance; Microbial Genetics and Genomics; Microorganisms; Multidrug resistance; Multidrug resistant organisms; Multidrug-resistant tuberculosis; Mutants; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - physiology; Patient outcomes; Plant Genetics and Genomics; Prokaryote microbial genomics; Proteomics; Research Article; Setting (Literature); Tanzania; Time; Time-to-culture-conversion; Treatment Outcome; Treatment-outcomes; Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology; Whole genome sequence; Whole Genome Sequencing; Tanzania; United States > US; Africa; Multidrug-resistant tuberculosis; Time-to-culture-conversion; Whole genome sequence; Treatment-outcomes; Mycobacterium tuberculosis
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-020-6577-1

Background Tuberculosis (TB), particularly multi- and or extensive drug resistant TB, is still a global medical emergency. Whole genome sequencing (WGS) is a current alternative to the WHO-approved probe-based methods for TB diagnosis and detection of drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). This study compared WGS and clinical data in participants with TB. Results This cohort study performed WGS on 87 from MTBC DNA isolates, 57 (66%) and 30 (34%) patients with drug resistant and susceptible TB, respectively. Drug resistance was determined by Xpert® MTB/RIF assay and phenotypic culture-based drug-susceptibility-testing (DST). WGS and bioinformatics data that predict phenotypic resistance to anti-TB drugs were compared with participant’s clinical outcomes. They were 47 female participants (54%) and the median age was 35 years (IQR): 29–44). Twenty (23%) and 26 (30%) of participants had TB/HIV co-infection BMI < 18 kg/m 2 respectively. MDR-TB participants had MTBC with multiple mutant genes, compared to those with mono or polyresistant TB, and the majority belonged to lineage 3 Central Asian Strain (CAS). Also, MDR-TB was associated with delayed culture-conversion (median: IQR (83: 60–180 vs. 51:30–66) days). WGS had high concordance with both culture-based DST and Xpert® MTB/RIF assay in detecting drug resistance (kappa = 1.00). Conclusion This study offers comparison of mutations detected by Xpert and WGS with phenotypic DST of M. tuberculosis isolates in Tanzania. The high concordance between the different methods and further insights provided by WGS such as PZA-DST, which is not routinely performed in most resource-limited-settings, provides an avenue for inclusion of WGS into diagnostic matrix of TB including drug-resistant TB.