Drug-susceptibility Patterns of Mycobacterium tuberculosis in Mpumalanga Province, South Africa: Possible Guiding Design of Retreatment Regimen

AIDS Virus Research Laboratory, Department of Microbiology, University of Venda, South Africa.
Journal of Health Population and Nutrition (Impact Factor: 1.04). 02/2010; 28(1):7-13. DOI: 10.3329/jhpn.v28i1.4518
Source: PubMed


Multidrug-resistant tuberculosis (MDR-TB) has been a cause of concern in both developed and developing countries. The prevalence of drug resistance in Mycobacterium tuberculosis (MTB) isolates (n=692) from Mpumalanga province was assessed. In total, 692 (64%) MTB strains from cases with pulmonary TB were tested for susceptibility against rifampicin, isoniazid, ethambutol, and streptomycin using the MGIT 960 instrument. Two hundred and nine (30.2%) strains were resistant to one or more drugs. Resistance to one drug ranged from 1.4% for ethambutol to 17.7% for rifampicin. The prevalence of MDR-TB ranged from 6.7% for three drugs to 34% for four drugs, with significant predictors being patients' age-groups of 25-54 years (p=0.0012) and >55 years (p=0.007). The result showed a high level (58.4%) of MDR-TB from cases in Mpumalanga province. To achieve a higher cure rate in this province, drug-susceptibility tests must be done for every case.

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Available from: Roland N Ndip, Sep 30, 2015
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    • "Two recent follow-up studies evaluating this regimen observed, even after cure, very high rates of recurrence in TB patients with MDR-TB at base-line [21,22]. Notwithstanding, most TB programmes in low-income countries in sub-Saharan Africa treat, empirically, every year 10-20% of their TB patients using this regimen [2,15,19]. The design of NTP retreatment regimens depends on the epidemiological context, the program's performance, and the means available. "
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    ABSTRACT: The number of pulmonary tuberculosis (PTB) patients reported with resistance to first-line anti-tuberculosis drugs after a standardized retreatment regimen in Cameroon is increasing. Hence, the National Tuberculosis Control Program (NTP) implemented, in one of the ten Regions of the country, a pilot programme aimed at performing routine drug susceptibility testing (DST) for previously treated PTB cases. The objectives of the programme were to evaluate the feasibility of monitoring drug resistance among retreatment cases under programme conditions and to measure the presence and magnitude of anti-TB drug resistance in order to inform NTP policies. This retrospective cohort study was conducted in the Littoral Region of Cameroon in 2009. It included all sputum smear positive (SM+) PTB cases registered for retreatment. TB cases were identified and classified according to World Health Organization (WHO) recommendations for national TB programs. Bacterial susceptibility testing to first-line anti-TB drugs was performed using standard culture methods. In 2009, 5,668 TB cases were reported in the Littoral Region, of which 438 (7.7%) were SM + PTB retreatment cases. DST results were available for 216 (49.4%) patients. Twenty six patients (12%) harbored multi-drug resistant (MDR) strains. Positive treatment outcome rates were particularly low in retreatment patients with MDR-TB (46.2%; 95% CI: 27.1-66.3). Thirteen MDR-TB patients were treated using a standardized MDR treatment regimen. Delivery of laboratory results took on average 17 (12-26) weeks. WHO-recommended routine DST in retreatment patients seems feasible in Cameroon. However, coverage needs to be improved through better management. Moreover, diagnostic delay should be shortened by introducing more rapid diagnostic tools. The high risk of MDR in standard regimen failure cases virtually rules out the standard retreatment regimen for such patients without prior DST.
    BMC Research Notes 03/2012; 5(1):160. DOI:10.1186/1756-0500-5-160
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    • "At present very few drugs are available in the market for treatment of M. tuberculosis infection as evolution of drug-resistant strains have resulted in little efficacy and some of them have shown undesired side-effects in host [1]. Studies suggest that the prevalence of Multi Drug Resistant tuberculosis (MDR-TB) ranged from 6.7% for three drugs to 34% for four drugs and has caused an annual loss of around $4 - $5 billion [2-5]. Keeping in mind the rapidly changing pathogenesis of this lethal micro-organism, identification of novel inhibitors for recently discovered targets has become pressing need of the hour. "
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    ABSTRACT: The emergence of drug resistant tuberculosis poses a serious concern globally and researchers are in rigorous search for new drugs to fight against these dreadful bacteria. Recently, the bacterial GlmU protein, involved in peptidoglycan, lipopolysaccharide and techoic acid synthesis, has been identified as an important drug target. A unique C-terminal disordered tail, essential for survival and the absence of gene in host makes GlmU a suitable target for inhibitor design. This study describes the models developed for predicting inhibitory activity (IC50) of chemical compounds against GlmU protein using QSAR and docking techniques. These models were trained on 84 diverse compounds (GlmU inhibitors) taken from PubChem BioAssay (AID 1376). These inhibitors were docked in the active site of the C-terminal domain of GlmU protein (2OI6) using the AutoDock. A QSAR model was developed using docking energies as descriptors and achieved maximum correlation of 0.35/0.12 (r/r2) between actual and predicted pIC50. Secondly, QSAR models were developed using molecular descriptors calculated using various software packages and achieved maximum correlation of 0.77/0.60 (r/r2). Finally, hybrid models were developed using various types of descriptors and achieved high correlation of 0.83/0.70 (r/r2) between predicted and actual pIC50. It was observed that some molecular descriptors used in this study had high correlation with pIC50. We screened chemical libraries using models developed in this study and predicted 40 potential GlmU inhibitors. These inhibitors could be used to develop drugs against Mycobacterium tuberculosis. These results demonstrate that docking energies can be used as descriptors for developing QSAR models. The current work suggests that docking energies based descriptors could be used along with commonly used molecular descriptors for predicting inhibitory activity (IC50) of molecules against GlmU. Based on this study an open source platform,, has been developed for predicting inhibitors GlmU.
    BMC Pharmacology 07/2011; 11(1):5. DOI:10.1186/1471-2210-11-5 · 1.84 Impact Factor
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    • "The first (H37Ra) is sensitive and the second (a local isolate) is resistant to all five first-line antituberculosis drugs (streptomycin, isoniazide, rifampin, ethambutol, and pyrazinamide). The clinical isolate was isolated, identified, and characterized in the Mycobacteriology Laboratory at the University of Limpopo, MEDUNSA Campus, Pretoria, South Africa from a patient with advanced pulmonary tuberculosis [14]. "
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    ABSTRACT: Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the most notified disease in the world. Development of resistance to first line drugs by MTB is a public health concern. As a result, there is the search for new and novel sources of antimycobacterial drugs for example from medicinal plants. In this study we determined the in vitro antimycobacterial activity of n-Hexane sub-fraction from Bridelia micrantha (Berth) against MTB H37Ra and a clinical isolate resistant to all five first-line antituberculosis drugs. The antimycobacterial activity of the n-Hexane sub-fraction of ethyl acetate fractions from acetone extracts of B. micrantha barks was evaluated using the resazurin microplate assay against two MTB isolates. Bioassay-guided fractionation of the ethyl acetate fraction was performed using 100% n-Hexane and Chloroform/Methanol (99:1) as solvents in order of increasing polarity by column chromatography and Resazurin microtiter plate assay for susceptibility tests. The n-Hexane fraction showed 20% inhibition of MTB H37Ra and almost 35% inhibition of an MTB isolate resistant to all first-line drugs at 10 μg/mL. GC/MS analysis of the fraction resulted in the identification of twenty-four constituents representing 60.5% of the fraction. Some of the 24 compounds detected included Benzene, 1.3-bis (3-phenoxyphenoxy (13.51%), 2-pinen-4-one (10.03%), N(b)-benzyl-14-(carboxymethyl) (6.35%) and the least detected compound was linalool (0.2%). The results show that the n-Hexane fraction of B. micrantha has antimycobacterial activity.
    BMC Complementary and Alternative Medicine 04/2011; 11(1):28. DOI:10.1186/1472-6882-11-28 · 2.02 Impact Factor
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