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.
Highlights
Tuberculosis (TB), multi- and or extensive drug resistant TB, is still a global medical emergency
Baseline demographic and clinical characteristics of study participants A total of87study participants with positive Mycobacterium tuberculosis complex (MTBC) culture results were included in the genetic study of whom, 47 (54%) were females
Analysis of mutations associated with phenotypic drug resistance to anti-TB drugs Of the 87 MTBC isolates sequenced, 57 (65.5%) had at least one mutation in a gene that was predictive for 7
Summary
Tuberculosis (TB), multi- and or extensive drug resistant TB, is still a global medical emergency. HIV infection is the most important single predictor of TB incidence across the African continent [3]. This is critical because HIV/AIDS is likely to increase in the risk of progression TB infection by 30 times, due to impairment on the immune system [3]. Sub-Saharan Africa carries a disproportionate burden of HIV, accounting for more than 70% of the global burden of infection [4]. Despite the gaps in documentation of MDRTB cases in several Sub-Saharan African countries (SSA), pooled analysis that involved several studies reported a prevalence of 2.1% of MDR-TB in new cases, signifying a low prevalence of MDR-TB cases in SSA [7]. The relatively low prevalence of MDRTB in SSA might be attributed by the recent introduction of rifampicin in Africa, by the use of rifampicin-free treatment regimens in the continuation phase (during months three to eight), by the growing use of directly observed treatment as recommended under the directly observed treatment, short course (DOTS) strategy, and by the use of fixeddose combination tablets in a few countries [8, 9]
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