Phenotypic and Genotypic Analysis of Anti-Tuberculosis Drug Resistance inMycobacterium tuberculosisIsolates in Myanmar

Abstract

BackgroundTuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar.MethodsWe determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid).ResultsOf 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01).ConclusionsThe results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar

“…Frequencies of RIF-and INH-resistance associating mutations among the isolates in this study were compered with those among isolates from surrounding countries and Myanmar as presented in Table 4 and 5, respectively, and the results of Fisher's exact test were shown in Table 6 and 7. The frequency of RIF-resistant isolates having mutations in RRDR was significantly lower than those in the studies from India [12], South China ( [14]), Thailand ( [11]), Bangladesh ( [17]) and Myanmar (isolates from Yangon and Mandalay in 2013 [26]) than those in our study. Mutation causing amino acid substitution at the position of codon 531 in rpoB is most frequently observed worldwide.…”

“…The frequency of mutations at this position in this study was significantly lower than that in the studies from Myanmar in 2013 [26]. The frequency of INH-resistant isolates having mutations in katG at codon 315 or in inhA promoter regionn at the position of -15 was significantly lower than those in the studies from Thailand [22], Bangladesh [17] and Myanmar in 2013 [26]. In addition, the frequencies of mutations in katG at codon 315 was significantly lower than those in the studies from Bangladesh ( [17]) and Myanmar in 2013 [26] than that in our study.…”

“…Mutation causing amino acid substitution at the position of codon 531 in rpoB is most frequently observed worldwide. The frequency of mutations at this position in this study was significantly lower than that in the studies from Myanmar in 2013 [26]. The frequency of INH-resistant isolates having mutations in katG at codon 315 or in inhA promoter regionn at the position of -15 was significantly lower than those in the studies from Thailand [22], Bangladesh [17] and Myanmar in 2013 [26].…”

Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

“…However, performance of genotypic/molecular DST has been shown to be comparable with that of phenotypic DST and is unlikely to be a major factor. [16,17,[43][44][45] We did not analyse second-line resistance and some of these isolates might have demonstrated resistance to second-line drugs, which would render them XDR-TB rather than MDR-TB isolates. Further research in this regard is recommended.…”

Avaliação da resistência aos tuberculostáticos de primeira linha em cepas do complexo Mycobacterium Tuberculosis isolados no Distrito Federal

“…A mutação S531L foi observada em 75% dos casos, seguida pela mutação H561Y nos demais casos. A alta frequência da mutação S531L é também a mais relatada por outros estudos realizados em diferentes países (Telenti et al, 1993;Somoskovi et al, 2001;Bai et al, 2007;Asante-Poku et al, 2015;Aung et al, 2015).…”