Buruli Ulcer Diagnosis: Current Status, Diagnostic Gaps, and Future Prospects for Point-of-care Testing

Abstract

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans, remains an under-recognised neglected tropical disease whose control is constrained by limited access to accurate, timely diagnosis in the remote, resource-poor settings where it is most prevalent. Methods: A narrative review of primary diagnostic-accuracy and diagnostic-development literature indexed in PubMed, PLOS Neglected Tropical Diseases, the Journal of Clinical Microbiology, Clinical Infectious Diseases, medRxiv, and World Health Organization (WHO) surveillance publications was conducted to synthesise performance data for established laboratory methods and emerging point-of-care platforms. Results: Polymerase chain reaction (PCR) targeting IS2404 remains the diagnostic gold standard (sensitivity 90–100%, specificity 94–100%) but is confined to centralised reference laboratories. Microscopy, culture, and histopathology retain limited standalone clinical utility. Experienced clinical diagnosis achieved 92% sensitivity in one large cohort, rivalling laboratory testing. Portable and isothermal amplification platforms, including battery-operated mobile quantitative PCR (sensitivity 97–100%, specificity 94–100%), electricity-independent loop-mediated isothermal amplification (approximately 84% sensitivity, 100% specificity), and recombinase polymerase amplification (88% sensitivity, 100% specificity), substantially reduce infrastructure requirements while approaching reference-standard accuracy. Mycolactone biomarker assays, including fluorescent thin-layer chromatography (66–73% sensitivity, 86–89% specificity) and a prototype lateral flow immunoassay, offer conceptually attractive alternatives but remain less accurate or have not yet been clinically validated. Conclusion: No single available test fully satisfies the World Health Organization's target product profile for a Buruli ulcer point-of-care test. Closing the diagnostic gap will require a strategic combination of validated clinical algorithms with the best-evidenced decentralised molecular platforms, sustained clinical training, and rigorous, standardised multi-site validation of emerging biomarker-based assays.