Acquired bedaquiline and fluoroquinolones resistance during treatment follow-up in Oromia Region, North Shewa, Ethiopia.

Background: Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB) treatment. However, resistance to this new drug is emerging. We discussed the characteristics of the first patient in Ethiopia who acquired BDQ and fluoroquinolones (FQs) resistance during treatment follow-up. Case report: In this case report, we present the case of a 28-year-old male pulmonary TB patient diagnosed with MDR-TB who is a resident of the Oromia Region of North Shewa, Mulona Sululta Woreda, Ethiopia. Sputum specimen was collected initially and for treatment monitoring using culture and for phenotypic drug susceptibility testing (DST) to first-line and second-line TB drugs. Initially, the patient was infected with a mycobacterial strain resistant to the first-line anti-TB drugs Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA). Later, during treatment, he acquired additional drug resistance to ethambutol (EMB), ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX), and BDQ. The patient was tested with MTBDRplus and MTBDRsl to confirm the presence of resistance-conferring mutation and mutation was detected in rpoB, katG, and gyrA genes. Finally, the patient was registered as having extensively drug-resistant tuberculosis (XDR-TB) and immediately started an individualized treatment regimen. Conclusion: This case report data has revealed the evolution of BDQ resistance during treatment with a BDQ-containing regimen in Ethiopia. Therefore, there is a need for DST to new second-line drugs to monitor and prevent the spread of DR-TB.

Molecular epidemiology of tuberculosis in the Somali region, eastern Ethiopia.

Background: Tuberculosis (TB) is one of the leading causes of morbidity and mortality in low-income countries like Ethiopia. However, because of the limited laboratory infrastructure there is a shortage of comprehensive data on the genotypes of clinical isolates of Mycobacterium tuberculosis (M. tuberculosis) complex (MTBC) in peripheral regions of Ethiopia. The objective of this study was to characterize MTBC isolates in the Somali region of eastern Ethiopia. Methods: A cross-sectional study was conducted in three health institutions between October 2018 and December 2019 in the capital of Somali region. A total of 323 MTBC isolates (249 from pulmonary TB and 74 from extrapulmonary TB) were analyzed using regions of difference 9 (RD 9)-based polymerase chain reaction (PCR) and spoligotyping. Results: Of the 323 MTBC isolates, 99.7% (95% CI: 99.1-100%) were M. tuberculosis while the remaining one isolate was M. bovis based on RD 9-based PCR. Spoligotyping identified 71 spoligotype patterns; 61 shared types and 10 orphans. A majority of the isolates were grouped in shared types while the remaining grouped in orphans. The M. tuberculosis lineages identified in this study were lineage 1, 2, 3, 4, and 7 with the percentages of 7.4, 2.2, 28.2, 60.4, and 0.6%, respectively. Most (87.9%) of the isolates were classified in clustered spoligotypes while the remaining 12.1% isolates were singletons. The predominant clustered spoligotypes identified were SIT 149, SIT 21, SIT 26, SIT 53, and SIT 52, each consisting of 17.6, 13.3, 8.4, 7.4, and 5%, respectively. Lineage 3 and lineage 4, as well as the age group (15-24), were associated significantly with clustering. Conclusion: The MTBC isolated from TB patients in Somali region were highly diverse, with considerable spoligotype clustering which suggests active TB transmission. In addition, the Beijing spoligotype was isolated in relatively higher frequency than the frequencies of its isolation from the other regions of Ethiopia warranting the attention of the TB Control Program of the Somali region.

Pre-extensively drug-resistant tuberculosis among multidrug-resistant tuberculosis patients in Ethiopia: a laboratory-based surveillance study.

Background: The rise of drug-resistant tuberculosis (DR-TB) has presented a substantial challenge to the national tuberculosis (TB) control program. Understanding the epidemiology of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) could help clinicians to adapt MDR-TB treatment regimens at an earlier stage. This study aimed to assess second-line anti-TB drug resistance among MDR-TB patients in Ethiopia using routine laboratory-based data. Methods: Laboratory-based cross-sectional data were collected from the national TB reference laboratory and seven regional tuberculosis culture laboratories in Ethiopia from July 2019 to March 2022. The required data, such as drug-susceptibility testing (DST) results and sociodemographics, were collected on a structured checklist from laboratory registration books and electronic databases. Data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS version 23. Descriptive statistics were performed to show the distribution and magnitude of drug resistance. Results: Second-line drugs (SLDs) susceptibility testing was performed for 644 MDR isolates, of which 19 (3%) were found to be pre-XDR-TB cases. Of the total MDR-TB isolates, 19 (3%) were resistant to at least one fluoroquinolone drug, while 11 (1.7%) were resistant to at least one injectable second-line drug. Of the 644 MDR-TB isolates, 1.9% (5/261) pre-XDR were from new MDR-TB cases, while 3.7% (14/383) were from previously treated MDR-TB patients. The most frequently identified mutations, based on MTBDRsl results, were in codon A90V of the gyrA gene (77.3%) and A1401G of the rrs gene (45.5%). Conclusion: The overall prevalence of pre-XDR-TB in Ethiopia is considerable. The majority of SLD resistance mutations were in the gyrA gene at position A90V. Modern, rapid DST is necessary to enable identification of pre-XDR-TB and XDR-TB in supporting proper regimen administration for patients.

Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis patients in Addis Ababa, Ethiopia from 2014 to 2021.

Objective: This study aimed to determine the frequencies and trends of Mycobacterium tuberculosis and rifampicin resistance among presumptive tuberculosis patients in Ethiopia, who were tested using the Xpert MTB/RIF assay between 2014 and 2021. Methods: Data were collected retrospectively from patient registries. Laboratory-based data were extracted from the national tuberculosis (TB) referral laboratory database. All patients referred to the National Tuberculosis Reference Laboratory (NTRL) for TB diagnosis from all over the country between March 1, 2014 and September 30, 2021, and tested using the Xpert MTB/RIF assay, were included. The extracted data were entered into a Microsoft Excel sheet and analyzed by Statistical Package for Social Sciences (SPSS) version 23. Results: Among a total of 13 772 individuals tested using the Xpert MTB/RIF assay, the majority (8223; 59.7%) were males, and 48.5% (6678) of the individuals were aged between 15 and 39 years. Mycobacterium tuberculosis (MTB) was detected in 17.0% (2347) of the examined individuals. Of the detected MTB cases, nearly 9.9% (233) were rifampicin resistant (RR-TB), while 24 (1.0%) were RR-intermediate. Among all RR-TB cases, more than half (125; 53.6%) were detected in males, and 105 were new TB cases. Extrapulmonary (EPTB) patients had a greater rate of rifampicin resistance (11.0%) than pulmonary (PTB) patients (9.6%). Conclusion: The frequency of TB and RR-TB remains high in the study setting. RR-TB was found to have a statistically significant association with previous anti-TB medication treatment. As a result, improving treatment adherence in recognized instances could assist in preventing MTB and RR-TB cases.