Diagnosis of Ebola Virus Disease: Past, Present, and Future

Abstract

Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward.

FIG 1

Detection of Ebola virus infection in nonfatal versus fatal cases. Solid lines indicate that the analyte of interest is detected in the majority of cases at the corresponding time point (days post-symptom onset); dashed lines indicate that the analyte of interest is detected in the minority of cases at that time point. Data for IgG and IgM detection were compiled from references , , and to . Data for antigen detection were compiled from references , , , and . Data for RNA detection were compiled from references , , , , , and . RT-PCR, reverse transcription-PCR; ELISA, enzyme-linked immunosorbent assay.

FIG 2

Diagnostic testing in Ebola virus outbreaks. The information provided for each outbreak includes the affected country (or countries), the agencies primarily responsible for clinical diagnostic testing during the outbreak, where testing took place (the location is shown in parentheses; field laboratories are also highlighted in red), and the primary testing methods used for clinical diagnosis. The size of the box denotes the relative size of the outbreak, categorized in the following groups: <100 cases, 100 to 200 cases, 200 to 300 cases, 300 to 400 cases, and 400 to 500 cases; the West Africa epidemic exceeded 28,600 cases (132). The color of the box denotes the outbreak's Ebola virus species (EBOV, Zaire/Ebola; SUDV, Sudan; BDBV, Bundibugyo). Abbreviations: DRC, Democratic Republic of Congo; RC, Republic of Congo; MRE, Microbiological Research Establishment; ITMA, Institute of Tropical Medicine, Antwerp; CIRMF, Centre International de Recherches Medicales de Franceville; PHAC, Public Health Agency of Canada; KEMRI, Kenya Medical Research Institute; NICD, National Institute of Communicable Diseases; UVRI, Uganda Virus Research Institute; INRB, Institut National de Recherche Biomedicale.