Abstract
BackgroundTuberculosis (TB) is one of the major public health problems in Congo. However, data concerning Mycobacterium tuberculosis drug resistance are lacking because of the insufficient processing capacity. So, the aim of this study was to investigate for the first time the resistance patterns and the strain lineages of a sample of M. tuberculosis complex (MTBC) isolates collected in the two main cities of Congo.MethodsOver a 9-day period, 114 smear-positive sputa isolated from 114 patients attending centers for the diagnosis and treatment of TB in Brazzaville and Pointe Noire were collected for culture and drug susceptibility testing (DST). Detection of mutations conferring drug resistance was performed by using line probe assays (GenoType MTBDRplus and MTBDRsl) and DNA sequencing. Strain lineages were determined by MIRU-VNTR genotyping.ResultsOf the 114 sputa, 46 were culture positive for MTBC. Twenty-one (46%) were resistant to one or more first-line antiTB drugs. Of these, 15 (71%) were multidrug resistant (MDR). The most prevalent mutations involved in rifampin and isoniazid resistance, D516V (60%) in rpoB and S315T (87%) in katG respectively, were well detected by MTBDRplus assay. All the 15 MDR strains were susceptible to fluoroquinolone and injectable second-line drug. No mutation was detected in the rrs locus involved in resistance to amikacin and capreomycin by both the MTBDRsl assay and DNA sequencing. By contrast, 9 MDR strains belonging to the same cluster related to T-family were identified as being falsely resistant to fluoroquinolone by the MTBDRsl assay due to the presence of a double substitution T80A-A90G in GyrA.ConclusionsTaken together, these data revealed a possible spread of a particular MDR clone in Congo, misidentified as fluoroquinolone resistant by MTBDRsl assay. Thus, this test cannot replace gold-standard culture method and should be interpreted carefully in view of the patient's native land.
Highlights
Tuberculosis (TB) remains an important cause of morbidity and mortality in 2012 with 8.6 million cases and 1.3 million deaths worldwide [1]
This emphasized that detection of gyrA mutations by line probe assay should be interpreted with caution and cannot replace conventional drug susceptibility testing in countries such as Congo
It is worth noting that the neighboring countries such as RD of Congo and Cameroon reported an increase in multidrug resistant (MDR)-TB in recent years suggesting a possible spread of MDR-TB strains in this region of Africa [1,16]
Summary
Tuberculosis (TB) remains an important cause of morbidity and mortality in 2012 with 8.6 million cases and 1.3 million deaths worldwide [1]. This study represents the first phenotypic and molecular study of tuberculosis in Congo with the goal to (i) determine drug susceptibility patterns in samples collected in the two main Congo’s cities (Brazzaville and Pointe-Noire) that account for two third of the population and (ii) characterize mutations prevalent in clinical isolates by using the commercially available GenoType MTBDRplus and GenoType MTBDRsl assays, as well as DNA sequencing [2,3]. We showed that reverse hybridization assay with DNA probes falsely detected fluoroquinolones resistance in a predominant MDR clone harboring a double substitution T80A-A90G known to confer hypersusceptibility to fluoroquinolones [4,5,6] This emphasized that detection of gyrA mutations by line probe assay should be interpreted with caution and cannot replace conventional drug susceptibility testing in countries such as Congo. The aim of this study was to investigate for the first time the resistance patterns and the strain lineages of a sample of M. tuberculosis complex (MTBC) isolates collected in the two main cities of Congo
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