Drug Resistance Patterns of Tuberculosis Among Re-Treatment Cases in St Peter’s Tb Specialized Hospital, Addis Ababa
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Date
2003-07
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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
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Biology