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Title: DRUG RESISTANCE PATTERNS OF TUBERCULOSIS AMONG RE-TREATMENT CASES IN St PETER’S TB SPECIALIZED HOSPITAL, ADDIS ABABA
Authors: DAWIT, WOLDE MESKEL
Advisors: Dr Getahun Abate
Dr Abraham Aseffa
Dr Mekuria Lakew
Dr Solomon Goshu
Copyright: 2003
Date Added: 27-May-2008
Publisher: Addis Ababa University
Abstract: Tuberculosis (TB) is a major public health problem worldwide. About 3.8 million TB cases were reported to WHO in the year 2001 from the 8.5 million estimated new cases. In Ethiopia the estimated incidence of all cases of tuberculosis has reached 292 per 100000 populations. This figure placed the country to rank 10th among the 22 high burden countries. The resurgence of tuberculosis has been accompanied by high frequency of drug resistant strains from all over the world. In most TB patients drug resistance predominantly arises as a result of multiple interruptions of treatment. To avoid this problem fixed-dose combinations (FDCs) tablets are now recommended by WHO and IUATLD. However, in FDC formulations the bioavailability of the component drugs, and especially of rifampicin, may be reduced. Simple, rapid and inexpensive methods of detecting drug resistant tuberculosis are also essential for effective treatment. This study has the objectives of assessing the prevalence of drug resistance among re-treatment cases after introduction of Three Fixed Dose Combination (3FDC) therapy for tuberculosis; evaluation of MTT assay for direct detection of rifampicin resistance and analysis of the RFLP pattern of the different TB strains. Single sputum samples were collected from 100 smear positive re-treatment TB cases who attended St Peter’s TB specialized Hospital between 21 December 2001 and 15 October 2002. The sputum samples were cultured on Lowenstein- Jensen (LJ) media and 7H9 broth. Drug sensitivity was done on 7H10 agar using the proportion method. Broth media (7H9) supplemented with PANTA and Oleic acid Dextrose Catalase (OADC) were used for MTT assay. Formazan production was quantified by measuring the optical density (OD) at 570nm. Relative optical density unit (RODU) was calculated and resistance was defined as RODU> 0.5 and susceptibility as RODU< 0.2. Among the 89 culture positive isolates, 75 were tested for drug sensitivity pattern. Totally 58.7% of the isolates were resistant to one or more drugs. Isolates resistant and partially resistant to isoniazid were found to be 42.7% and 6.7% respectively. Resistance to rifampicin was 33.3%. Isolates resistant and partially resistant to streptomycin were found to be 21.3% and 12% respectively. The percentage of isolates resistant to ethambutol was 9.3% while 25.3% were partially resistant. Multidrug resistant isolates (MDR) were observed in 29.3% of the patients. Patients who had a history of treatment with 3FDC had a statistically significant higher rate of resistance to isoniazid (P< 0.05) and rifampicin (P< 0.05) compared to those treated with loose drugs. Direct MTT assay identified 30.7% isolates as rifampicin resistant and 69.3% as susceptible within three weeks of time. Comparing MTT assay to the proportion method resulted in 97.3% matching. RFLP analysis of ten isolates showed the presence of eight unique patterns. Two isolates showed the dominant type of RFLP profile existing in Ethiopia. Contrary to our expectation, patients treated with 3FDC regimen had more rifampicin and isoniazid resistant isolates than those treated with loose drugs. This is a good indicator for a more systematic study to evaluate the efficacy of the 3FDC drug formulation. There has been a marked increase in drug resistant tuberculosis. Therefore, nationwide drug resistance surveillance with a larger number of samples is needed to monitor drug resistance tuberculosis in the country.
Description: A THESIS SUBMITTED TO THE SCHOOL OF GRADUATE STUDIES ADDIS ABABA UNIVERSITY IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN BIOLOGY
URI: http://hdl.handle.net/123456789/1250
Appears in:Thesis - Biology

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