Pre-extensively and extensively drug-resistant tuberculosis prevalence among multidrug-resistant tuberculosis cases in Ethiopia: A systematic review and meta-analysis

Background: The burden of pre-extensively drug-resistant tuberculosis (Pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases in Ethiopia has become one of the most challenging problems for monitoring the treatment of patients with multidrug-resistant tuberculosis (MDR-TB). This study aimed to provide a valuable evidence synthesis on the pooled prevalence of Pre-XDR and XDR-TB among MDR-TB patients in Ethiopia. Methodology: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data from relevant articles were analyzed using STATA version 17.0. The pooled estimate of the effect size was computed using a restricted maximum likelihood random-effects model, considering a 95% confidence interval, and a forest plot was used to visualize the proportion of Pre-XDR and XDR-TB. Because the Pre-XDR and XDR-TB cases are rare, the Freeman-Tukey double arcsine transformation was applied to estimate the pooled proportions. The I2 statistic and Galbraith plot confirmed heterogeneity. A univariate meta-regression, sensitivity, and subgroup analyses were conducted to identify the source of heterogeneity. Egger’s test and funnel plot were used to check publication bias. Results: Eight studies comprising 1,518 MDR-TB patients, with 656 new and 862 previously treated cases, were included. Among those, 52 Pre-XDR and 13 XDR-TB cases were identified. According to the Freeman-Tukey transformation, the overall pooled prevalence of Pre-XDR-TB was 3% (95% CI: 2%-5%, I2 = 43.69%) and XDR-TB was 1% (95% CI: 0%-4%, I2 = 54.07%). In the subgroup analysis, the prevalence of Pre-XDR-TB across studies from multiple regions of Ethiopia was 7% (95% CI: 3%-13%), and in Addis Ababa, it was 3% (95% CI: 2%-4%). Single studies in the Amhara, Tigray, and Oromia regions reported Pre-XDR-TB prevalence of 6%, 5%, and 3%, respectively. The pooled prevalence of XDR-TB in Addis Ababa was 1% (95% CI: 0%-2%). A single study conducted in Oromia reported a relatively higher prevalence of XDR-TB; 10% (95% CI: 3%-26%). Regarding the study year, the XDR-TB prevalence was 3% (95% CI: 0%-11%) in 2005–2018 and 1% (95% CI: 0%-2%) in 2019–2024. A statistically significant publication bias was observed in XDR-TB prevalence (p = 0.024). Conclusion: There is a significant prevalence of Pre-XDR and XDR-TB cases among MDR-TB patients in Ethiopia. It highlights the need for strengthened surveillance in all regions and expanded drug susceptibility testing of local strains for better management of MDR-TB patients. Author summary: The emergence of Pre-XDR and XDR-TB poses a severe threat to public health in Ethiopia, complicating patient monitoring and treatment success. This study aimed to synthesize evidence on the pooled prevalence of these highly resistant strains among MDR-TB patients across various Ethiopian regions. We conducted a systematic review and meta-analysis of eight studies involving 1,518 MDR-TB patients using PRISMA guidelines. The pooled prevalence analysis was calculated based on the study’s sample size, which reported 52 Pre-XDR-TB cases from 1,472 MDR-TB patients and 13 XDR-TB cases from 836 MDR-TB patients, separately. Our Freeman-Tukey transformed meta-analysis revealed a pooled prevalence of 3% for Pre-XDR-TB and 1% for XDR-TB among the reported MDR-TB patients. Subgroup analysis showed geographic variation, with a pooled prevalence of XDR-TB ranging from 1% in Addis Ababa to 10% in the Oromia region. Although temporal trends indicated a relatively higher prevalence in earlier study periods (2005–2018) compared to recent years (2019–2024), studies differ in case definitions, drug-susceptibility testing panels, diagnostic methods, populations, and geographic coverage, and are affected by the small number and heterogeneity of the included studies. The COVID-19 pandemic also had an impact on the under-detection of drug-resistant TB cases. Moreover, recent data revealed critical resistance to newer Group A drugs, including emerging dual resistance to fluoroquinolones combined with bedaquiline or linezolid among MDR-TB isolates.The results indicate a significant prevalence of highly drug-resistant TB within Ethiopian MDR-TB treatment centers. These findings highlight an urgent need for the national TB program to strengthen laboratory surveillance, expand drug susceptibility testing, and enhance resource allocation for managing complex cases. Standardizing diagnostic tools across all regions is essential to close existing surveillance gaps and improve treatment outcomes for drug-resistant TB.