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

Abstract

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. Clinical diagnostic laboratories associated with small health care facilities often lack the personnel, resources, and expertise for rapid identification of rare or emerging infectious diseases, relying instead on reference diagnostic laboratories for specialized tests. In developing countries, especially in outbreak situations, this strategy can cause significant delays in isolation and treatment of infected (and potentially highly infectious) individuals. The ability for a small clinical lab to identify persons infected with a sporadic or epidemic pathogen, while maintaining a low logistical burden, would be of great advantage in remote or resource-limited regions, where patients with high-impact pathogens are encountered infrequently. This study describes the deployment and use of the FilmArray multiplex PCR instrument for detection of Zaire ebolavirus in patients and health care workers (HCWs) suspected to have Ebola virus disease (EVD) in Mercy Hospital in Bo, Sierra Leone.Study. Mercy Hospital is a small private hospital in Bo, Sierra Leone, that refers about 2,000 patients per year to its own clinical laboratory for testing (1). Prior to the 2014 EVD outbreak, Mercy Hospital Research Laboratory (MHRL) initiated a communitybased research study that included use of BioFire's FilmArray instrument and the associated BioThreat (BT) Panel in a "researchonly" (rather than diagnostic) capacity. The research protocol was approved by the Sierra Leone Ethics and Scientific Review Committee (SLESRC) and by the institutional review boards of Njala University, George Mason University, and the U.S. Naval Research Laboratory. Infectious agent detection using the BT Panel is based on nested PCR (coupled with reverse transcription for RNA viruses) and melting curve analysis for amplicon discrimination (2). The BT Panel simultaneously tests for 16 pathogens, including Zaire ebolavirus; analysis is complete within 60 min, and the system yields a dichotomous detected/not detected result for each of the 16 targets tested. Given that this test requires only simple handling steps-dilution of whole blood and loading of the specimen into the test pouch-and an identical assay (the BioThreat-E test, limited to reporting results for Zaire ebolavirus) has recently received emergency use authorization (EUA) for use in the current outbreak in West Africa (3), we sought to detect the occurrence of Zaire ebolavirus among persons referred to the MHRL facilities for diagnostic testing and to assess the system's utility under conditions of sporadic use. No medical decisions were based on the BT Panel testing results.

Performance of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in Sierra Leone: A Field Evaluation Study

“…The Corgenix lateral flow immunoassay for detection of EBOV VP40 matrix protein performed very well for fingerstick testing in a recent field study [ 4 ] and satisfies additional critical goals of low cost and POC use, but its sensitivity and specificity were lower than that of benchmark RT-PCR assays performed in parallel (including the Trombley assay used in this study), leading to controversy around optimal deployment [ 15 ]. The BioFire FilmArray sample-to-answer molecular assays (BioFire FilmArray BioThreat panel and FilmArray BT E-panel) have the advantage of requiring no refrigeration and performed well in three recent studies [ 6 , 16 , 17 ] compared to the EBOV RT-PCR assays developed by the US Centers for Disease Control and Prevention [ 6 , 16 ] or the Trombley assay used by PHE [ 17 ]. However, the analytical sensitivity compared to the Xpert Ebola test was inferior [ 2 ].…”

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

“…Our studies did not evaluate the specificity of the assays, but the EUA documentation includes results of extensive studies that were performed with the help of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the U.S. Department of Defense, which confirmed the high analytical specificities of all three tests (9)(10)(11). Further, clinical specificity was documented in a study in Sierra Leone in which the FilmArray assay was used for research purposes to test patients and health care workers who had been referred for diagnostic testing (12). In that study, 83 individuals were tested.…”

Point-of-Care Diagnostics: Recent Developments in a Connected Age

“…Field use requires uninterrupted electricity, temperature control, and moderately trained personnel to conduct sample preparation 168 . In addition, without subsidies, cost of instruments and cartridges are also prohibitive for lower-resource settings (for example, the manufacturer list price for Filmarray reader is $39,500, with $129 per test kit) 173 .…”