Pharmacognosy
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Browsing Pharmacognosy by Author "Aseffa, Abraham(PhD)"
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Item Anti Tuberculosis Drug Induced Hepatotoxicity in Hiv Positive and Negative Patients(Addis Ababa University, 2005-06) Yimer, Getnet; Aseffa, Abraham(PhD)Anti-tuberculosis drug induced hepatotoxicity (DIH) is a common problem in the management of tuberculosis. This study was intended to identify possible risk factors for development of DIH, including degree of immunosuppression. In this prospective 2-month cohort study, 103 HIV positive and 94 HIV negative newly diagnosed tuberculosis patients were followed after initiation of DOTS (direct observed treatment short course). CD4 count was measured for the HIV positive patients. All patients were also evaluated for different risk factors including HBsAg, Anti-HCV, alcohol intake, use of other drugs including traditional medicines, acetylation status and presence of chronic illness. Patients were monitored biochemically (by liver function tests) and clinically for development of DIH weekly in the first month and bi-weekly in the second month after start of therapy. Biochemical hepatotoxicity was seen in 17.3% of the patients. CD4 counts of these patients were 0-50 for 7 (35%), 51-100 for 8 (40%), 101-200 for 4 (20%), and > 200 for 1 (5%). Three patients were positive for HBsAg and none had anti-HCV. Five patients died of non-hepatic causes among the patients who developed DIH. Eight out of the 34 patients with biochemical hepatotoxicity (23.5%) developed clinical hepatotoxicity that necessitated discontinuation of their anti-TB drugs. Seven of the eight were HIV positive, seven were female, and 2 were positive for HBsAg. Biochemical hepatotoxicity was significantly associated with HIV co-infection (p=0.002), concomitant drug intake (p=0.008), decrease in CD4 count (p=0.001), high mortality (p=0.001), and having Wt/Wt allele for acetylation status (p=0.026). Clinical hepatotoxicity is also significantly associated with being female (p=0.027), HIV co-infection (p=0.043), concomitant drug intake (p=0.003), HBsAg (p=0.046), decrease in CD4 count (p=0.025), and high mortality (p=0.0001). No significant association was seen between hepatotoxicity with alcohol intake, age, body mass index, type of TB and anti HCV positivity. The findings would assist in selectively managing patients at risk. It is recommended to have a regular biochemical and clinical follow up for those patients who are at risk of developing DIH .These patients include HIV positive patients, with special emphasis to those with a lower CD4 count, and patients who take drugs other than their anti TB medication. We also recommend that further work should be done to explore the reason for the observed association between DIH and female sex, HBsAg positivity, and acetylation status. Key words: Tuberculosis, HIV, Hepatotoxicity, Acetylation status, NAT2 geneItem Drug Susceptibility Pattern of Mycobacterium Tuberculosis Isolates In Addis Ababa(Addis Ababa University, 2005-07) Asmamaw, Dawit; Aseffa, Abraham(PhD); Makonnen, Eyasu (Professor)Background:-Addis Ababa, the capital city of Ethiopia, has an estimated population of 3.5 - 4 million. Previous reports on anti-TB drug resistance suggested an increasing trend of anti-TB drug resistance despite differences in the methodology. A study in previously treated individuals also suggested an increased incidence of Rifampicin (RMP) and Isoniazid (INH) resistance in individuals treated with fixed dose combination (FDC) anti-TB drugs. Objectives:-To determine the prevalence of resistance to the four first line anti-TB drugs and to see whether there is association between HIV and drug resistance. Methods: - A cross-sectional survey on anti-TB drug resistance was done in 19 health centres (out of 21) and 3 hospitals in Addis Ababa. Sputum and serum was collected from each patient. Sputum was digested and decontaminated using Petroff’s method with 4% NaOH and inoculated on to Lowenstein Jensen media. Proportion method with Middlebrook 7H10 media & 10% OADC enrichment was used for drug sensitivity determination. HIV testing was also done for each patient with rapid assays (Determine®, Capillus® and Unigold®). Species identification was done with a combination of Thiophene-2- Carboxylic acid Hydrazide (TCH) test and species specific PCR amplification (pncA gene) Results & Discussion :-269 (242 new and 27 previously treated) patients were included in the study. Out of these, 75% were culture positive. Sensitivity result was available for 173 isolates from new cases and 19 isolates from previously treated patients. Among the isolates from new patients 78.6% were sensitive to all drugs tested and 21.4% were resistant to any one drug while these figures in previously treated patients were 47.4% and 52.6% respectively. Prevalence of MDR-TB among new cases was 0.6% (1 isolate). Resistance to RMP, INH, Streptomycin (STM) and Ethambutol (EMB) was 1.2%, 13.3%, 16.8 and 3.5% respectively. In previously treated patients RMP, INH, STM and EMB resistance was 5.3%, 36.9%, 52.6% and 11.1% respectively. The prevalence of resistance in a similar survey conducted in 1998 was lower and the increase in the current study was statistically significant for any type of resistance, any EMB resistance, any STM resistance and resistance to multiple drugs. However the prevalence of RMP resistance and multidrug-resistant (MDR) TB was not changed. There was also no association observed between drug resistance among new cases and HIV. Conclusion:- Multidrug-resistance did not show increase in the city particularly in the last six years, compared to the previous reports. However non-MDR type of drug resistance, precursor of MDR, is on the rise.