Recent advances in the development and evaluation of molecular diagnostics for Ebola virus disease

The 2014-16 outbreak of ebola virus disease (EVD) in West Africa resulted in 11,308 deaths. During the outbreak only 60% of patients were laboratory confirmed and global health authorities have identified the need for accurate and readily deployable molecular diagnostics as an important component of the ideal response to future outbreaks, to quickly identify and isolate patients. Areas covered: Currently PCR-based techniques and rapid diagnostic tests (RDTs) that detect antigens specific to EVD infections dominate the diagnostic landscape, but recent advances in biosensor technologies have led to novel approaches for the development of EVD diagnostics. This review summarises the literature and available performance data of currently available molecular diagnostics for ebolavirus, identifies knowledge gaps and maps out future priorities for research in this field. Expert opinion: While there are now a plethora of diagnostic tests for EVD at various stages of development, there is an acute need for studies to compare their clinical performance, but the sporadic nature of EVD outbreaks makes this extremely challenging, demanding pragmatic new modalities of research funding and ethical/institutional approval, to enable responsive research in outbreak settings. Retrospective head-to-head diagnostic comparisons could also be implemented using biobanked specimens, providing this can be done safely

Use of the FilmArray System for Detection of Zaire ebolavirus in a Small Hospital in Bo, Sierra Leone: TABLE 1

Laboratories associated with small hospitals often have limited expertise, personnel, and equipment to rapidly identify rare and emerging infectious diseases. We describe the successful use of the FilmArray system for rapid detection of Ebola virus directly from clinical samples in 6 out of 83 tested subjects in a small health care center in Sierra Leone

Comparison of FilmArray and Quantitative Real-Time Reverse Transcriptase PCR for Detection of Zaire Ebolavirus from Contrived and Clinical Specimens

Rapid, reliable, and easy-to-use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the agreement among emergency use authorization (EUA) tests for the detection of ZEBOV nucleic acids, including the BioFire FilmArray BioThreat (BT) panel, the FilmArray BT-E panel, and the NP2 and VP40 quantitative real-time reverse transcriptase (qRT) PCR assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole-blood, plasma, and urine clinical specimens collected from persons diagnosed with Ebola virus disease (EVD). The agreement for FilmArray and qRT-PCR results using contrived whole-blood specimens was 100% (6/6 specimens) for each ZEBOV dilution from 4 × 10(7) to 4 × 10(2) 50% tissue culture infective dose (TCID(50))/ml, as well as the no-virus negative-control sample. The limit of detection for FilmArray and qRT-PCR assays with inactivated ZEBOV, based on duplicate positive results, was determined to be 4 × 10(2) TCID(50)/ml. Rates of agreement between FilmArray and qRT-PCR results for clinical specimens from patients with EVD were 85% (23/27 specimens) for whole-blood specimens, 90% (18/20 specimens) for whole-blood specimens tested by FilmArray testing and matched plasma specimens tested by qRT-PCR testing, and 85% (11/13 specimens) for urine specimens. Among 60 specimens, eight discordant results were noted, with ZEBOV nucleic acids being detected only by FilmArray testing in four specimens and only by qRT-PCR testing in the remaining four specimens. These findings demonstrate that the rapid and easy-to-use FilmArray panels are effective tests for evaluating patients with EVD