Resistance to pyrazinamide in Mycobacterium tuberculosis complex isolates from previously treated tuberculosis cases in Southwestern Oromia, Ethiopia.

Objective: Pyrazinamide (PZA) susceptibility testing is important to develop evidence-based algorithms for case management. We aimed to assess the prevalence of PZA-resistance and its impact on treatment outcomes in previously treated tuberculosis (TB) cases in southwestern Oromia, Ethiopia. Methods: A Phenotypic Drug Susceptibility Testing (DST) of PZA with BACTEC MGIT 960 was conducted at the Mycobacteriology Research Center of Jimma University (MRC-JU) from June to November 2021 on sixty-six Mycobacterium tuberculosis complex (MTBC) isolates from previously treated TB cases. SPSS software package version 21 was used. The differences in the proportion of PZA resistance between the groups were compared using the chi squared test. Logistic regression was used to identify the association between PZA resistance and treatment outcomes. Results: Among 66 MTBC isolates (49 rifampicin-resistant and 17 rifampicin-sensitive) included in this study, 31.8 % were resistant to PZA. The proportion of PZA resistance was almost three times higher in previously treated TB cases with rifampicin resistance than in rifampicin-sensitive patients (38.8 % vs. 11.8 %, p = 0.039). An unfavorable treatment outcome was documented for 23 % (15/65) of the participants. Patients with PZA resistance were almost four times more likely to have an unfavorable treatment outcome than patients with PZA sensitive (aOR 4.2, 95 % CI: 1.13-15.3). Conclusions: The prevalence of PZA resistance was high compared to the pooled PZA resistance estimated worldwide. The majority of TB cases with PZA resistance had an unfavorable treatment outcome. PZA susceptibility testing should be included in the multidrug-resistant TB diagnostic algorithm to improve management of these patients.

Discordance between genotypic and phenotypic methods for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis and the correlation with patient treatment outcomes.

Background: Accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis (MTB) is essential for proper patient management. We investigated discordance between genotypic (Xpert MTB/RIF and MTBDRplus) and phenotypic (MGIT 960) methods for the detection of rifampicin (RIF) and isoniazid (INH) resistant MTB and its correlation with patient treatment outcomes in Jimma, Southwest Oromia, Ethiopia. Methods: A retrospective study was conducted on 57 stored MTB isolates with known Xpert RIF resistance status (45 RIF resistant and 12 RIF susceptible) at Jimma University Mycobacteriology Research Center from November 2, 2021, to December 28, 2022. We did MTBDRplus and phenotypic DST (using the Mycobacterial Growth Indicator Tube (MGIT) system). The Xpert and MTBDRplus results were compared using phenotypic DST as a reference standard method. The treatment outcome was determined as per national guideline. The discordance between the genotypic and phenotypic DST was calculated using GraphPad software. Results: Among the 57 MTB isolates, six (10.5 %) had discordant results between the two DST methods. Xpert yielded five discordant results for RIF when compared with phenotypic DST (kappa coefficient (κ) = 0.76, 95 % confidence interval 0.56-0.96). The MTBDRplus compared with phenotypic DST gave three discordant results for RIF (κ = 0.86, 95 % confidence interval 0.71-1.00) and three for INH (κ = 0.86, 95 % confidence interval 0.70-1.00). Compared with Xpert, MTBDRplus yielded lower discordance with phenotypic DST for RIF. Out of six patients with discordant results, three had unfavorable outcomes while the other three were cured. Of the three patients with unfavorable outcomes, only one patient has received an inappropriate treatment regimen. There was no correlation between unfavorable outcomes and incorrect treatment regimens due to discordant results (Χ2 = 0.404; P = 0.525). Conclusions: Discordance between genotypic and phenotypic DST for RIF or INH occurred in 10.5 % of isolates. Only one patient with discordant results has received an inappropriate treatment regimen, resulting in an unfavorable outcome. The impact of parallel use of rapid molecular assay with phenotypic DST on patient treatment outcomes requires further study.

Genomic transmission clusters and circulating lineages of Mycobacterium tuberculosis among refugees residing in refugee camps in Ethiopia.

BACKGROUND: Understanding the transmission dynamics of Mycobacterium tuberculosis (Mtb) could benefit the design of tuberculosis (TB) prevention and control strategies for refugee populations. Whole Genome Sequencing (WGS) has not yet been used to document the Mtb transmission dynamics among refugees in Ethiopia. We applied WGS to accurately identify transmission clusters and Mtb lineages among TB cases in refugee camps in Ethiopia. METHOD AND DESIGN: We conducted a cross-sectional study of 610 refugees in refugee camps in Ethiopia presenting with symptoms of TB. WGS data of 67 isolates was analyzed using the Maximum Accessible Genome for Mtb Analysis (MAGMA) pipeline; iTol and FigTree were used to visualize phylogenetic trees, lineages, and the presence of transmission clusters. RESULTS: Mtb culture-positive refugees originated from South Sudan (52/67, 77.6%), Somalia (9/67, 13.4%). Eritrea (4/67, 6%), and Sudan (2/67, 3%). The majority (52, 77.6%) of the isolates belonged to Mtb lineage (L) 3, and one L9 was identified from a Somalian refugee. The vast majority (82%) of the isolates were pan-susceptible Mtb, and none were multi-drug-resistant (MDR)-TB. Based on the 5-single nucleotide polymorphisms cutoff, we identified eight potential transmission clusters containing 23.9% of the isolates. Contact investigation confirmed epidemiological links with either family or social interaction within the refugee camps or with neighboring refugee camps. CONCLUSION: Four lineages (L1, L3, L4, and L9) were identified, with the majority of strains being L3, reflecting the Mtb L3 dominance in South Sudan, where the majority of refugees originated from. Recent transmission among refugees was relatively low (24%), likely due to the short study period. The improved understanding of the Mtb transmission dynamics using WGS in refugee camps could assist in designing effective TB control programs for refugees.

Treatment outcomes and associated factors in tuberculosis patients at Jimma University Medical Center: A 5-year retrospective study.

BACKGROUND: Monitoring the outcome of tuberculosis (TB) treatment and investigating factors associated with unsuccessful outcome are essential, as unsuccessful treatment fuels resistance to antibiotics. This study aimed to investigate the treatment outcome and associated factors with an unsuccessful outcome at Jimma University Medical Center (JUMC), Southwest Ethiopia. METHODS: A 5-year retrospective analytical study, including all types of TB cases who sought care at JUMC between September 1, 2012, and August 31, 2017, was conducted. Treatment outcomes and TB types were categorized according to the National TB Control guideline. Bivariate analysis was used to analyze the association between treatment outcome and potential variables. RESULTS: Overall data from 1249 patients' records were included in the study. The proportion of male patients was higher (815, 65.3%) than that of females. The mean age (± standard deviation, range) of the cases was 26 (±11. 6, 1-71) years. Of the total, 292 (23.3%) were smear-positive pulmonary TB (PTB), 489 (39.2%) smear-negative PTB, and 468 (37.5%) extra-PTB (EPTB) cases. Available treatment outcomes indicate that 253 (20.2%) were cured, 850 (68.0%) completed therapy, 58 (4.8%) died, 83 (6.6%) defaulted, and 5 (0.4%) failed the therapy. About 76 (5.6%) cases were transferred out and 44 (3.2%) cases were lost to follow-up. In total, 146 (11.7%) patients had an unsuccessful outcome. Unsuccessful treatment outcome was associated with smear-negative PTB (odds ratio [OR] =2.0, 95% confidence intervals [CI] =1.1, 3.7), EPTB (OR = 2.1, 95% CI = 1.2, 3.4), and unknown human immunodeficiency virus (HIV) status (OR = 7.9, 95% CI = 2.5, 25.0). CONCLUSION: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate. Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome.

Factors associated with unsuccessful treatment outcome in tuberculosis patients among refugees and their surrounding communities in Gambella Regional State, Ethiopia.

BACKGROUND: Tuberculosis (TB) is a leading cause of public health challenges among immigrant refugees and their surrounding communities in developing countries. Evaluating the treatment outcome of TB patients is one of the key indicators to understand the performance of TB control program. Hence, this study aims to assess profile, treatment outcome and factors associated with unsuccessful outcome of TB patients treated under the TB control program among refugees and their surrounding communities (SCs) in Gambella Regional State, Ethiopia. METHODOLOGY: Retrospective study was conducted in the health facilities of refugee and their SCs in Gambella Regional State from March 1 to May 30, 2017. Demographic and related data of all TB patients registered in TB Control Program between September, 2008 and October, 2017 in health facilities of refugee and the SCs was extracted using data extraction format. Eight years trend of TB, treatment outcome and factors associated with unsuccessful outcome among refugees and the SCs were computed using SPSS version 20.0 software. RESULT: A total of 886 refugees and 3284 SCs TB patients, registered for anti TB treatment in the last eight years, were evaluated in the study. The trend of all forms of TB is progressively increasing among refugees contrary to the SCs in the course of the study period (X2 trend = 207.7; P<0.0001). Smear positive pulmonary TB (PTB+) was found to be predominant (57.6%) TB form in refugees while smear negative pulmonary TB (PTB-) (44.8%) is in the SCs (X2 = 185.834; P<0.0001). There was also significant difference in the treatment outcome (X2 = 170.915; P<0.0001). Mean treatment success rate was 74.2% and 88.1% for refugees and the SCs, respectively (X2 = 92.887; P<0.0001). The study also revealed that the risk of unsuccessful TB treatment outcome was significantly higher among refugee (AOR = 2.17; 95% CI: 1.69-2.77), retreated cases (AOR = 1.53; 95% CI: 1.07-2.17), patients aged between 35-44 years (AOR = 1.38; 95% CI: 1.0-1.91), and greater than 44 years old (AOR = 1.77; 95% CI: 1.28-2.44), and patients with extra pulmonary TB (EPTB) form (AOR = 1.34; 95% CI: 1.04-1.73) compared to their counterparts. Patient coming from rural area (AOR = 0.77; 95% CI: 0.62-0.97), who are female (AOR = 0.76; 95% CI: 0.63-0.91) and TB/HIV non-infected (AOR = 0.63; 95% CI: 0.51-0.77) were more likely to be successfully treated. CONCLUSION: The study confirmed that there was low treatment success rate among refugees compared to the SCs. Being refugee, retreated case, patient's age ≥35 years old, EPTB form, gender, rural patient address and HIV status were predictor factors for unsuccessful treatment outcome. Hence, the study urges the need for strengthened TB prevention program among refugees with due consideration of identified predictor factors to prevent the potential effect of hosting refugee to the SCs and the nations at large.

Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis and Rifampicin resistance in high Human Immunodeficiency Virus setting in Gambella regional state, southwest Ethiopia.

BACKGROUND: The introduction of a new and rapid molecular diagnostic for tuberculosis (TB) and rifampicin resistance (RIF) in the national TB program has improved the diagnosis of TB by shortening the turnaround time and detecting the presence of RIF resistance in high TB and human immunodeficiency virus (HIV) settings such as Ethiopia. However, the implementation of this new diagnostic tool for the diagnosis of M. tuberculosis (MTB) and rifampicin (RIF) resistance in clinical setting is limited known in the country. Hence, this study intended to describe the program of GeneXpert MTB/RIF in the diagnosis of TB and RIF in high HIV setting in Gambella Regional State, Southwest Ethiopia. METHOD: Institutional based retrospective study was conducted among presumptive TB patients diagnosed with GeneXpert assay in the last three years (2015-2017) in Gambella Hospital from May 1-30, 2017. The data were collected from GeneXpert registration book using standard data extraction sheet. The data were entered and cleared using EPI data 3.1 and then, exported and analyzed using SPSS version 20.0 statistical software package. RESULT: Of the 995 presumptive TB patients who received the GeneXpert test in the last three years, 20.0% (95% CI: 17.4-22.7) of them had proven MTB detection while 4.9% (95% CI: 2.2-8.1) had RIF resistance. The prevalence of RIF resistance was 2.3% and 14.3% among the new and retreated cases respectively. There was also a 35.5% TB/HIV co-infections. The odd of MTB detection was higher among 15-29 [AOR 2.17 (95% CI: 1.25- 3.76)] and 30-44 [AOR 2.35 (95% CI: 1.36-4.07)] year old participants. The figure was however significantly lower among female [AOR 0.64 (95% CI: 0.45-0.91)] and unknown HIV status [AOR 0.38(95% CI: 0.24-0.61)] participants of the study. In addition, the odd of RIF resistance was significantly low among HIV unknown case [AOR 0.14 (95% CI: 0.02-0.96)]. It was also learnt that there was progressively decline of invalid or error Xpert result from 4.7% to 2.0% in the course of the study period (X2, 25.54; P = 0.001). CONCLUSION: The study confirms the high prevalence of TB, RIF resistance and TB/HIV co-infection among the study participants. Age, sex, and HIV status of the study participants were predictor factors for MTB detection while HIV status was associated with RIF resistance. Therefore, the results of the study indicate that there is the need for collaborative and intensified prevention of TB and HIV in the study area. The ongoing supervision and mentoring to improve the performance of Xpert in the institution need to be promoted.