Search

Background: The genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. Methods: A cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Löwenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first-and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. Results: Of 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%.Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. Conclusions: Diverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.

PurposeThis study examined the patterns and frequency of genetic changes responsible for resistance to first-line (rifampicin and isoniazid), fluoroquinolones, and second-line injectable drugs in drug-resistant Mycobacterium tuberculosis (MTB) isolated from culture-positive pulmonary tuberculosis (PTB) symptomatic attendees of spiritual holy water sites (HWSs) in the Amhara region.Patients and methodsFrom June 2019 to March 2020, a cross-sectional study was carried out. A total of 122 culture-positive MTB isolates from PTB-suspected attendees of HWSs in the Amhara region were evaluated for their drug resistance profiles, and characterized gene mutations conferring resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs), and second-line injectable drugs (SLIDs) using GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0. Drug-resistant MTB isolates were Spoligotyped following the manufacturer’s protocol.ResultsGenetic changes (mutations) responsible for resistance to RIF, INH, and FLQs were identified in 15/122 (12.3%), 20/122 (16.4%), and 5/20 (25%) of MTB isolates, respectively. In RIF-resistant, rpoB/Ser531Lue (n = 12, 80%) was most frequent followed by His526Tyr (6.7%). Amongst INH-resistant isolates, katG/Ser315Thr1 (n = 19, 95%) was the most frequent. Of 15 MDR-TB, the majority (n = 12, 80%) isolates had mutations at both rpoB/Ser531Leu and katG/Ser315Thr1. All 20 INH and/or RIF-resistant isolates were tested with the MTBDRsl VER 2.0, yielding 5 FLQs-resistant isolates with gene mutations at rpoB/Ser531Lue, katG/Ser315Thr1, and gyrA/Asp94Ala genes. Of 20 Spoligotyped drug-resistant MTB isolates, the majority (n = 11, 55%) and 6 (30%) were SIT149/T3-ETH and SIT21/CAS1-Kili sublineages, respectively; and they were any INH-resistant (mono-hetero/multi-). Of 15 RIF-resistant (RR/MDR-TB) isolates, 7 were SIT149/T3-ETH, while 6 were SIT21/CAS1-Kili sublineages. FLQ resistance was detected in four SIT21/CAS1-Kili lineages.ConclusionIn the current study, the most common gene mutations responsible for resistance to INH, RIF, and FLQs were identified. SIT149/T3-ETH and SIT21/CAS1-Kili constitute the majority of drug-resistant TB (DR-TB) isolates. To further understand the complete spectrum of genetic changes/mutations and related genotypes, a sequencing technology is warranted.

BackgroundDespite the decline in tuberculosis (TB) incidence across many regions worldwide, including Ethiopia, the disease remains highly concentrated among vulnerable or socially marginalized populations and in high-risk settings. This systematic review and meta-analysis aims to estimate the pooled prevalence of pulmonary tuberculosis (PTB) among key and vulnerable populations (KVPs) residing in hotspot settings in Ethiopia.MethodsPotential papers were searched systematically in PubMed, Scopus, ScienceDirect databases, Google Scholar search engine, and institutional electronic repositories/registrars. A total of 34 potential articles that provide necessary information on the prevalence of PTB were reviewed and data were analyzed to determine the pooled prevalence of PTB among KVPs. The relevant data were recorded and analyzed using STATA 17.0. Cohen's kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) to evaluate heterogeneity across studies, and Egger's test to identify publication bias. A random effect model was used to determine the pooled prevalence of PTB, subgroup analysis was computed by types of hotspot settings and year of publication.ResultsThis meta-analysis demonstrates that the pooled prevalence of PTB among populations residing in hotspot settings in Ethiopia was 11.7% (95% confidence interval (95CI): 7.97-15.43) with an I2 of 99.91% and a p< 0.001. Furthermore, the subgroup analysis unveiled the pooled prevalence of PTB among KVPs residing in different hotspot settings as follows: Prison inmates 8.8% (95CI: 5.00-12.55%), University students 23.1% (95CI: 15.81-30.37%), Refugees 28.4% (95CI: -1.27-58.15%), Homeless peoples 5.8% (95CI: -0.67-12.35%), Healthcare settings 11.1% (95CI: 0.58-21.63%), Spiritual holy water sites attendees 12.3% (95CI: -6.26-30.80%), and other high-risk settings 4.3% (95CI: 0.47-8.09%). Besides, the subgroup analysis revealed that the pooled prevalence of PTB post-2015 was 10.79% (95CI: 5.94-15.64%), whereas it stood at 14.04% (95CI: 10.27-17.82%) before 2015.ConclusionThe prevalence of PTB among KVPs residing in the hotspot settings in Ethiopia remains significant, with a weighted pooled prevalence of 11.7%. Thus, the national TB control programs should give due attention and appropriate control measures should be instituted that include regular systematic TB screening, compulsory TB testing for presumptive TB cases among KVPs, and tightened infection control at hotspot settings.

Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein–Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4–25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18–33 years of age (28.5% (95 CI 23.4–34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38–5.10), married participants (aOR 2.43; 95 CI 1.28–4.63), family members >5 per household (aOR 1.84; 95 CI 1.04–3.24), and sharing living space (aOR 10.57; 95 CI 3.60–31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4–9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.