Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in tuberculosis patients from high-burden countries, according to concordance or discordance of results from drug susceptibility testing (DST) done locally and in a reference laboratory. Methods: We collected Mycobacterium tuberculosis isolates from adult patients in Côte d’Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status. Findings: 634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases. Overall, sensitivity and specificity to detect any resistance were 90.8% and 84.3%, respectively. Mortality ranged from 6.0% (20/336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57.1% (8/14) in patients with resistant strains who were under treated. In logistic regression, compared to concordant DST results, the adjusted odds ratio of death was 7.33 (95% CI 2.70–19.95) for patients with discordant results potentially leading to under treatment. Interpretation: Inaccurate DST by comparison to a reference standard led to under treatment of drug resistant tuberculosis and increased mortality. Rapid molecular DST of first- and second-line drugs at diagnosis is required to improve outcomes in patients with MDR-TB and pre-XDR/XDR-TB.
BackgroundIn Côte d’Ivoire, multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem with a prevalence estimated at 2.5% in 2006. Zinc and copper are essential Trace element needed to strengthen the immune system and also useful in the fight against tuberculosis. The Cu / Zn ratio is a good indicator of oxidative stress.The principal aim of this study was to evaluate the serum concentration of some trace element and determine the Cu / Zn ratio in patients with multidrug resistant pulmonary tuberculosis (MDR-TB) before and after second line treatment of TB.MethodsBlood samples were obtained from 100 MDR-TB patients after confirmation of their status through the microscopic and molecular diagnosis of resistance to Isoniazid and Rifampicin by GeneXpert. The concentration level of zinc and copper were determined using flame air / acetylene atomic absorption spectrometer (AAS) Type Varian Spectr AA-20 Victoria, Australlia.ResultsA significant decrease in zinc levels (P < 0.05) and an increased Cu / Zn ratio (P < 0.05) was observed in MDR-TB patients compared to controls TB free. During treatment a significant reduction in Cu / Zn ratio (P < 0.05) was observed compared to the initial result.ConclusionsThe decrease in serum zinc level and the high Cu / Zn ratio could explain the immune system dysfunction and the high level of oxidative stress in patients with MDR-TB. Therefore the evaluation of the zinc and copper status could represent essential parameters in monitoring of TB second line treatment for better treatment management.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2343-7) contains supplementary material, which is available to authorized users.
We conducted an evaluation study on the GenoType MTBDRplus assay's ability to detect mutations conferring resistance to rifampin and isoniazid directly from sputum taken from 120 smear positive pulmonary patients from tuberculosis (TB) centers in Cote d'Ivoire.The sputum was decontaminated by N-acetyl-l-cysteine (NALC) and comparatively analyzed with the MTBDRplus assay version 2.0 and the mycobacterial growth indicator tube (MGIT) 960 automated drug susceptibility testing (MGIT-DST). The GeneXpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay was performed for 21 sputa with absence of hybridization for at least one rpoB wild-type probes. Four and seven, respectively, discordant and concordant results were also analyzed.The mutations in the rpoB gene were 21 (17.5%), 20 (16.7%), 7 (5.8%), and 10 (8.3%), respectively, for D516V, H526Y, H526D, and S531L. S315T mutation in katG gene associated or not with mutation in promoter of inhA was detected in 76 (63.3%) of the sputum. Compared to MGIT-DST, the sensitivity and specificity of the MTBDRplus for rifampin resistance detection were 100% (75-100%) and 73.2% (61.3-84%), respectively. For isoniazid resistance detection, the sensitivity and specificity were, respectively, 95% (90-99) and 95.1% (88.5-100%).Interpretation of 16 sputa without hybridization of rpoB wild-type probe 8 compared to those obtained with MGIT-DST and GeneXpert MTB/RIF was discordant and concordant, respectively, for 11 and 5.
For accurate diagnostic of pulmonary TB, TB-LAMP could be used as a tool of the first intention.
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