Prevalence and patterns of rifampicin and isoniazid resistance conferring mutations in Mycobacterium tuberculosis isolates from Uganda

Abstract

BackgroundAccurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of Mycobacterium tuberculosis, and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin- and isoniazid- resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa.ResultsNinety seven M. tuberculosis isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the rpoB rifampicin-resistance determining region (rpoB/RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in rpoB/RRDR. Furthermore, sequence analysis of katG and inhA gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance, occurred in 88% of the isoniazid resistant isolates. However, 20% (10/50) of the isoniazid-resistant isolates lacked mutations both in katG and inhA gene promoter. The sensitivity of sequence analysis of rpoB/RRDR for rifampicin-resistance via detection of high confidence mutations (Ser531Leu, His526Tyr, Asp516Tyr) was 81%, while it was 77% for analysis of katG and inhA gene promoter to detect isoniazid-resistance via detection of high confidence mutations (Ser315Thr, C(-15)T, T(-8)C). Furthermore, considering the circulating TB genotypes in Uganda, the isoniazid-resistance conferring mutations were more frequent in M. tuberculosis lineage 4/sub-lineage Uganda, perhaps explaining why this genotype is weakly associated with MDR-TB.ConclusionSequence analysis of rpoB/RRDR, katG and inhA gene promoter is useful in detecting rifampicin/isoniazid resistant M. tuberculosis isolates in Uganda however, about ≤20% of the resistant isolates lack known resistance-conferring mutations hence rapid molecular assays may not detect them as resistant.

Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study

“…Cigarette smoking was associated with MDR-TB. This is similar to other study findings [ 23 , 25 , 35 ]. Cigarette smoking directly causes ciliary dysfunction; this diminishes the immunity of individuals, which makes them prone to primary MDR-TB [ 56 , 57 ].…”

Rifampicin resistance patterns and dynamics of tuberculosis and drug-resistant tuberculosis in Enugu, South Eastern Nigeria

“…None of the isolates showed complete mutation in more than one region. These results are in contrast to many reports across the globe, including some reports from East Africa, that had reported the most frequent mutations in codons 531 [24,25]. Although it had been Figure 2.…”

“…suggested that variations may exist in different ethnic groups and geographic locations [24], most reports have shown mutations in codon 531 to be the most frequent, leading to the conclusion that codon 531 is the most prevalent region associated with rifampicin resistance [24][25][26][27][28][29][30]. Given the observation in this study, however, there may be need to carry out further investigation into the geographical variations.…”

Pattern of InhA and KatG mutations in isoniazid monoresistant Mycobacterium tuberculosis isolates

“…similarly observed that 80% had kat G mutations and 6% had inh A mutations. [ 18 ] Tavakkoli and Nazemi also reported that in 17.24% and 82.76% of the strains, inh A genes and kat G genes, respectively, were responsible for INH resistance. [ 19 ] Niehaus et al .…”