A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases

Science Translational Medicine
12 December 2018  Vol 10, Issue 471
http://stm.sciencemag.org/

Research Article   Diagnostics
A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases
By David Sebba, Alexander G. Lastovich, Melody Kuroda, Eric Fallows, Joshua Johnson, Ambroise Ahouidi, Anna N. Honko, Henry Fu, Rex Nielson, Erin Carruthers, Cyrille Diédhiou, Doré Ahmadou, Barré Soropogui, John Ruedas, Kristen Peters, Miroslaw Bartkowiak, N’Faly Magassouba, Souleymane Mboup, Yanis Ben Amor, John H. Connor, Kristin Weidemaier
Science Translational Medicine12 Dec 2018 Restricted Access
A multiplexed point-of-care diagnostic using surface-enhanced Raman scattering detects Ebola, Lassa, and malaria in blood and serum samples.
Discerning febrile diseases
Many infectious diseases present with common clinical symptoms, such as fever, which complicates diagnosis at the point of need. Sebba and colleagues developed an assay using surface-enhanced Raman scattering (SERS) nanotags to distinguish Ebola virus infections from Lassa and malaria. The no-wash triplex assay workflow adds a small volume of blood and buffer to dried SERS reagents and delivers a readout within 30 min. The assay detected parasite- and virus-specific antigens spiked into the blood, Ebola infections in nonhuman primates, and Ebola and malaria infections in human blood samples collected from endemic regions during field testing. Although further testing is required, this assay could be useful during febrile disease outbreaks.
Abstract
Hemorrhagic fever outbreaks such as Ebola are difficult to detect and control because of the lack of low-cost, easily deployable diagnostics and because initial clinical symptoms mimic other endemic diseases such as malaria. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need. Although rapid tests such as lateral flow can be broadly deployed, they are typically not well-suited for differentiating among multiple diseases presenting with similar symptoms. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect and differentiate infection with Ebola virus from other more common febrile diseases. Here, we developed and tested an immunoassay technology that uses surface-enhanced Raman scattering (SERS) tags to simultaneously detect antigens from Ebola, Lassa, and malaria within a single blood sample. Results are provided in <30 min for individual or batched samples. Using 190 clinical samples collected from the 2014 West African Ebola outbreak, along with 163 malaria positives and 233 negative controls, we demonstrated Ebola detection with 90.0% sensitivity and 97.9% specificity and malaria detection with 100.0% sensitivity and 99.6% specificity. These results, along with corresponding live virus and nonhuman primate testing of an Ebola, Lassa, and malaria 3-plex assay, indicate the potential of the SERS technology as an important tool for outbreak detection and clinical triage in low-resource settings.