Genetic diversity and drug susceptibility profiles of Mycobacterium tuberculosis obtained from Saint Peter's TB specialized Hospital, Ethiopia.

BACKGROUND: Tuberculosis (TB) is one of the major public health problems in Ethiopia. Data on genetic diversity and resistance profile of circulating TB strains is critical for informing the national TB control program. METHODS: A cross-sectional study was conducted on 213 smear positive pulmonary TB patients between 2015 and 2016. Sputum samples were cultured on LJ media following the Petroff's method. Region of difference-9 (RD9)-deletion typing and spoligo-typing were performed for molecular analysis of M. tuberculosis at species and strain levels, respectively. Drug sensitivity and mutation patterns of the isolates were assessed by the conventional indirect proportion method and molecular line probe assays (LPAs), respectively. Data were analyzed using statistical package for social sciences (SPSS) software version 20. RESULTS: Spoligo-typing of 150 M. tuberculosis isolates led to 57 different patterns of which 25 were new strains. The majority (71.6%) of the isolates were grouped in to 17 clusters consisting 2 to 24 isolates. The majority of the strains belonged to Euro-American lineage and the predominant spoligotypes were SIT 37 and SIT 149. MDR-TB was detected in 5.2% and 20.3% of new and retreatment cases, respectively. Two MDR-TB isolates exhibited additional resistance to one of the second line anti-TB drugs. Common gene mutations including S531L, S315T1 and M306V were detected in RIF, INH and EMB resistant strains, respectively. CONCLUSIONS: The identification of several new strains, higher proportion of MDR-TB and higher clustering rate in this study, warrants the need for re-enforcement of the national TB control program. The detection of common gene mutations in the majority drug resistant strains might suggest the feasibility of LPAs for rapid screening of drug resistant M. tuberculosis strains in Ethiopia.

Nephrotoxicity and ototoxic symptoms of injectable second-line anti-tubercular drugs among patients treated for MDR-TB in Ethiopia: a retrospective cohort study.

BACKGROUND: Nephrotoxicity and ototoxicity are clinically significant dose-related adverse effects associated with second-line anti-tubercular injectables drugs (aminoglycosides and capreomycin) used during intensive phase of treatment of multi-drug resistant tuberculosis (MDR-TB) patients. Data are scarce on injectable-induced nephrotoxicity and ototoxicity in Ethiopian MDR-TB patients. The aim of this study was to assess the prevalence, management of nephrotoxicity and ototoxic symptoms and treatment outcomes of patients treated for MDR-TB with injectable-based regimens. METHOD: This was retrospective cohort study based on review of medical records of about 900 patients on MDR-TB treatment from January 2010 to December 2015 at two large TB referral hospitals in Addis Ababa, Ethiopia. Nephrotoxicity in study participants was screened using baseline and monthly measurement of serum creatinine and clinical diagnosis and patient reports. RESULTS: Overall, 473 (54.2%) of participants were male. Children accounted for 47 (5.5%) of cases and the mean age of participants was 32 ± 12.6 years with range of 2-75 years. The majority (n = 788, 84.6%) of participants had past history of TB. The most commonly used injectable anti-TB drug was capreomycin (n = 789, 84.7%), while kanamycin and amikacin were also used. There was a statistically significant increment (p<0.05) in the mean serum creatinine values from baseline throughout intensive phase of treatment with a 10-18% prevalence of nephrotoxicity. Based on clinical criteria, nephrotoxicity was detected in 62 (6.7%) and ototoxic symptoms were detected in 42 (4.8%) participants. Nephrotoxicity and ototoxic symptoms were clinically managed by modification of treatment regimens including dose and frequency of drug administration. CONCLUSION: Nephrotoxicity and ototoxic symptoms were significant problems among patients on follow-up for MDR-TB treatment. Based on laboratory criteria (serum creatinine), nephrotoxicity remained significant adverse events throughout intensive phase of treatment, indicating close monitoring of patients for successful outcome is mandatory until countries adopt the recent injectable-free WHO guideline and under specific conditions.

Drug-resistance patterns of Mycobacterium tuberculosis strains and associated risk factors among multi drug-resistant tuberculosis suspected patients from Ethiopia.

BACKGROUND: Multidrug drug-resistant tuberculosis (MDR-TB) is a major health problem and seriously threatens TB control and prevention efforts globally. Ethiopia is among the 30th highest TB burden countries for MDR-TB with 14% prevalence among previously treated cases. The focus of this study was on determining drug resistance patterns of Mycobacterium tuberculosis among MDR-TB suspected cases and associated risk factors. METHODS: A cross-sectional study was conducted in Addis Ababa from June 2015 to December 2016. Sputum samples and socio-demographic data were collected from 358 MDR-TB suspected cases. Samples were analyzed using Ziehl-Neelsen technique, GeneXpert MTB/RIF assay, and culture using Lowenstein-Jensen and Mycobacterial growth indicator tube. Data were analyzed using SPSS version 23. RESULTS: A total of 226 the study participants were culture positive for Mycobacterium tuberculosis, among them, 133 (58.8%) participants were males. Moreover, 162 (71.7%) had been previously treated for tuberculosis, while 128 (56.6%) were TB/HIV co-infected. A majority [122 (54%)] of the isolates were resistant to any first-line anti-TB drugs. Among the resistant isolates, 110 (48.7%) were determined to be resistant to isoniazid, 94 (41.6%) to streptomycin, 89 (39.4%) to rifampicin, 72 (31.9%) to ethambutol, and 70 (30.9%) to pyrazinamide. The prevalence of MDR-TB was 89 (39.4%), of which 52/89 (58.4%) isolates were resistance to all five first-line drugs. Risk factors such as TB/HIV co-infection (AOR = 5.59, p = 0.00), cigarette smoking (AOR = 3.52, p = 0.045), alcohol drinking (AOR = 5.14, p = 0.001) hospital admission (AOR = 3.49, p = 0.005) and visiting (AOR = 3.34, p = 0.044) were significantly associated with MDR-TB. CONCLUSIONS: The prevalence of MDR-TB in the study population was of a significantly high level among previously treated patients and age group of 25-34. TB/HIV coinfection, smoking of cigarette, alcohol drinking, hospital admission and health facility visiting were identified as risk factors for developing MDR-TB. Therefore, effective strategies should be designed considering the identified risk factors for control of MDR-TB.