The prevalence of vancomycin-resistant Staphylococcus aureus in Ethiopia: a systematic review and meta-analysis
Authors: Belete Melaku Ashagrie , Gedefie Alemu , Alemayehu Ermiyas , Debash Habtu , Mohammed Ousman , Gebretsadik Daniel , Ebrahim Hussen , Tilahun Mihret 
Published: August 2023

Abstract
Introduction
Vancomycin-resistant Staphylococcus aureus, identified as a “high priority antibiotic-resistant pathogen” by the World Health Organization, poses a significant threat to human health. This systematic review and meta-analysis aimed to estimate the pooled prevalence of vancomycin-resistant Staphylococcus aureus in Ethiopia.

Methods
This systematic review and meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that reported VRSA prevalence due to infection or carriage from human clinical specimens were extensively searched in bibliographic databases and grey literatures using entry terms and combination key words. Electronic databases like PubMed, Google Scholar, Wiley Online Library, African Journal Online, Scopus, Science Direct, Embase, and ResearchGate were used to find relevant articles. In addition, the Joanna Briggs Institute quality appraisal tool was used to assess the quality of the included studies. Stata version 14 software was used for statistical analysis. Forest plots using the random-effect model were used to compute the overall pooled prevalence of VRSA and for the subgroup analysis. Heterogeneity was assessed using Cochrane chi-square (I2) statistics. After publication bias was assessed using a funnel plot and Egger’s test, trim & fill analysis was carried out. Furthermore, sensitivity analysis was done to assess the impact of a single study on pooled effect size.

Results
Of the 735 studies identified, 31 studies that fulfilled the eligibility criteria were included for meta-analysis consisted of 14,966 study participants and 2,348 S. aureus isolates. The overall pooled prevalence of VRSA was 14.52% (95% CI: 11.59, 17.44). Significantly high level of heterogeneity was observed among studies (I2 = 93.0%, p < 0.001). The region-based subgroup analysis depicted highest pooled prevalence of 47.74% (95% CI: 17.79, 77.69) in Sidama region, followed by 14.82% (95% CI: 8.68, 19.88) in Amhara region, while Oromia region had the least pooled prevalence 8.07% (95% CI: 4.09, 12.06). The subgroup analysis based on AST methods depicted a significant variation in pooled prevalence of VRSA (6.3% (95% CI: 3.14, 9.43) for MIC-based methods, and 18.4% (95% CI: 14.03, 22.79) for disk diffusion AST method) which clearly showed that disk diffusion AST method overestimates the pooled VRSA prevalence. The total number of S. aureus isolates was found to be the responsible variable for the existence of heterogeneity among studies (p = 0.033).

Conclusion
This study showed an alarmingly high pooled prevalence of VRSA necessitating routine screening, appropriate antibiotic usage, and robust infection prevention measures to manage MRSA infections and control the emergence of drug resistance. Furthermore, mainly attributable to the overestimation of VRSA burden while using disk diffusion method, there is an urgent need to improve the methods to determine vancomycin resistance in Ethiopia and incorporate MIC-based VRSA detection methods in routine clinical laboratory tests, and efforts should be directed at improving it nationally.

Trial Registration
PROSPERO registration identification number: CRD42023422043.