Abstract
BackgroundMulti-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective.MethodsA total of 2391 specimens, received at Programmatic Management of Drug Resistant TB (PMDT) Unit, Lady Reading Hospital (LRH) Peshawar, Pakistan, between October 2011 and December 2014, were analyzed by Xpert MTB/RIF test. MTB positive with rifampicin resistance were further analyzed to first line anti-mycobacterial drug susceptibility testing (DST) using middle brook 7H10 medium. The data was analyzed using statistical software; SPSS version 18.ResultsOut of 2391 specimens, 1408 (59 %) were found positive for MTB and among them, 408 (29 %) showed rifampicin-resistance with four different rpoB gene mutations within 81 bp RRDR. The frequency of various probes among RIF-resistant isolates was observed as: probe E, in 314 out of 408 isolates; B, 44 out of 408; A, 5 out of 408; D, 34 out of 408; and probe C was observed among 6 out of 408 RIF-resistant isolates. The probe A&B and E&D mutation combination was found in only 1 isolate in each case, while B&D mutation combination was detected among 3 out of 408 RIF-resistant isolates.ConclusionsHence, it is concluded from our study on a selected population, 29 % of patients had MDR-TB. Probe E related mutations (also known as codon 531and 533) were the most common rpoB genetic mutation [314 (77 %)], acknowledged by Xpert MTB/RIF assay. Least mutation was detected within the sequence 511 (1.2 %).
Highlights
Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries
Multi-drug resistant tuberculosis (MDR-TB), is defined as a form of TB infection caused by Mycobaterium tuberculosis that is resistant to treatment with at least two of the most powerful first-line anti-TB drugs, isoniazid and rifampicin [1]
RpoB mutations is found in 95–97 % of RIFresistant Mycobacterium tuberculosis (MTB) strains worldwide and these mutations are typically located in a region at the 507–533 amino acid residuals (81 bp) within the rpoB genetic factor, that is usually referred to as Rifampicin Resistant Determinant Region (RRDR) [6]
Summary
Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective. Data on prevalence of rpoB gene mutations in Pakistan is limited, so this study is aimed to provide reference line data on these mutations using Xpert MTB/RIF assay. The detection of rpoB gene mutations is most important for accurate diagnosis of RIF resistance in MTB strains [10]. The current study was aimed to investigate the frequency of RIF-resistant MTB strains in specimens collected from TB presumptive patients in Khyber Pakhtoonkhwa, Pakistan and mutations at RRDR within the rpoB gene of RIF-resistant MTB using Xpert MTB/RIF assay
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