Abstract
BackgroundAvailability and access to the detection of resistance to anti-tuberculosis drugs remains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi.ObjectivesWe aimed to determine mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis strains which were defined as resistant to rifampicin by the Xpert MTB/RIF assay.MethodsRifampicin-resistant isolates from 43 adult patients (≥ 18 years) from various districts of Malawi were characterised for mutations in the RRDR (codons 507–533) of the rpoB gene by DNA sequencing.ResultsMutations were found in 37/43 (86%) of the resistant isolates in codons 511, 512, 513, 516, 522, 526 and 531. The most common mutations were in codons 526 (38%), 531 (29.7%) and 516 (16.2%). Mutations were not found in 6/43 (14%) of the resistant isolates. No novel rpoB mutations other than those previously described were found among the rifampicin-resistant M. tuberculosis complex strains.ConclusionThis study is the first to characterise rifampicin resistance in Malawi. The chain-termination DNA sequencing employed in this study is a standard method for the determination of nucleotide sequences and can be used to confirm rifampicin resistance obtained using other assays, including the Xpert MTB/RIF. Further molecular cluster analysis, such as spoligotyping and DNA finger printing, is still required to determine transmission dynamics and the epidemiological link of the mutated strains.
Highlights
Tuberculosis remains an important public health problem especially in the developing world
The Xpert MTB/RIF assay detected rifampicin resistance in 64/995 (6.4%) specimens, which were selected for further DNA sequencing of the larger region of the rpoB gene
Most of the rifampicin-resistant cases detected by Xpert MTB/RIF were associated with probe B (23/64) and probe E (23/64)
Summary
Tuberculosis remains an important public health problem especially in the developing world. Rapid detection of drug resistance is crucial in choosing the most effective treatment to avert morbidity and mortality of infected individuals and reduce the risk of MDR tuberculosis transmission.[1]. Rifampicin, if the isolate is susceptible, is a very important component of the current tuberculosis treatment regimen and has proved to be effective to both susceptible strains and strains resistant to streptomycin and isoniazid.[1] there is growing resistance to rifampicin, largely due to particular genomic mutations in the rpoB gene of Mycobacterium tuberculosis.[2] The rpoB gene encodes the β subunit of RNA polymerase, which is involved in chain initiation and elongation. Availability and access to the detection of resistance to anti-tuberculosis drugs remains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/ RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi
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