Abstract
BackgroundWhole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico.MethodsWGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized.FindingsPrediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively. Lastly, four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition.ConclusionsThe results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis.
Highlights
According to the annual report of the World Health Organization in 2017, 10.5 million new cases and 1.7 million deaths were related to tuberculosis (TB), establishing TB as the infectious disease with the greatest impact on human health. [1]Close to 25% of TB cases recorded worldwide every year show resistance (DR-TB) to at least one of the four antibiotics used in first line treatment against this disease; Rifampicin (R), Isoniazid (H), Ethambutol (E) and Pyrazinamide (Z)
The results illustrate the utility of Whole genome sequencing (WGS) for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region
Of these DR-TB isolates, about 5% evolve into multi-drug resistant tuberculosis; i.e., they present a combined resistance to isoniazid and rifampicin (MDR-TB), which may evolve into an aggravated form known as extreme drug-resistant tuberculosis (XDR-TB), which are MDR-TB isolates that possess simultaneous resistance to a flouroquinolone and at least one of the three second-line injectable drugs
Summary
Close to 25% of TB cases recorded worldwide every year show resistance (DR-TB) to at least one of the four antibiotics used in first line treatment against this disease; Rifampicin (R), Isoniazid (H), Ethambutol (E) and Pyrazinamide (Z). Of these DR-TB isolates, about 5% evolve into multi-drug resistant tuberculosis; i.e., they present a combined resistance to isoniazid and rifampicin (MDR-TB), which may evolve into an aggravated form known as extreme drug-resistant tuberculosis (XDR-TB), which are MDR-TB isolates that possess simultaneous resistance to a flouroquinolone and at least one of the three second-line injectable drugs (amikacin, kanamycin and capreomicin). Whole Genome Sequencing (WGS) provides accurate information about polymorphisms, insertions and deletions (indels) of potential relevance to the rapid prediction of drug susceptibility phenotypes of clinical importance [3,4]. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico.
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