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

Authors
  • Katale, Bugwesa Z.1, 2
  • Mbelele, Peter M.3, 4
  • Lema, Nsiande A.5
  • Campino, Susana6
  • Mshana, Stephen E.7
  • Rweyemamu, Mark M.8
  • Phelan, Jody E.6
  • Keyyu, Julius D.2
  • Majigo, Mtebe1
  • Mbugi, Erasto V.1
  • Dockrell, Hazel M.6
  • Clark, Taane G.6, 9
  • Matee, Mecky I.1
  • Mpagama, Stellah3
  • 1 Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania , Dar es Salaam (Tanzania)
  • 2 Tanzania Wildlife Research Institute (TAWIRI), Arusha, Tanzania , Arusha (Tanzania)
  • 3 Kibong’oto Infectious Disease Hospital (KIDH), Sanya Juu, Tanzania , Sanya Juu (Tanzania)
  • 4 Nelson Mandela African Institution of Science and Technology (NM-AIST), Arusha, Tanzania , Arusha (Tanzania)
  • 5 Field Epidemiology and Laboratory Training Programme, Dar es Salaam, Tanzania , Dar es Salaam (Tanzania)
  • 6 Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine (LSHTM), Keppel Street, London, WC1E 7HT, UK , London (United Kingdom)
  • 7 Catholic University of Health and Allied Sciences, Mwanza, Tanzania , Mwanza (Tanzania)
  • 8 Sokoine University of Agriculture (SUA), Morogoro, Tanzania , Morogoro (Tanzania)
  • 9 Faculty of Epidemiology and Population Health, London School of Hygiene &Tropical Medicine (LSHTM), Keppel Street, London, WC1E 7HT, UK , London (United Kingdom)
Type
Published Article
Journal
BMC Genomics
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 21, 2020
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s12864-020-6577-1
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundTuberculosis (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.ResultsThis 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/m2 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).ConclusionThis 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.

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