A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors

Abstract

Ebola virus disease causes widespread and highly fatal epidemics in human populations. Today, there is still great need for point-of-care tests for diagnosis, patient management and surveillance, both during and post outbreaks. We present a point-of-care test comprising an immunochromatographic strip and a smartphone reader, which detects and semiquantifies Ebola-specific antibodies in human survivors. We developed a Sudan virus glycoprotein monoplex platform and validated it using sera from 90 human survivors and 31 local noninfected controls. The performance of the glycoprotein monoplex was 100% sensitivity and 98% specificity compared to standard whole antigen enzyme-linked immunosorbent assay (ELISA), and it was validated with freshly collected patient samples in Uganda. Moreover, we constructed a multiplex test for simultaneous detection of antibodies against three recombinant Sudan virus proteins. A pilot study comprising 15 survivors and 5 noninfected controls demonstrated sensitivity and specificity of 100% compared to standard ELISA. Finally, we developed a second multiplex subtype assay for the identification of exposure to three related EVD species: Sudan virus, Bundibugyo virus and Ebola virus (formerly Zaire) using recombinant viral glycoprotein. This multiplex test could distinguish between the host's immunity to specific viral species and identify cross-reactive immunity. These developed serological platforms consisted of capture ligands with high specificity and sensitivity, in-house developed strips and a compatible smartphone application. These platforms enabled rapid and portable testing, data storage and sharing as well as geographical tagging of the tested individuals in Uganda. This platform holds great potential as a field tool for diagnosis, vaccine development, and therapeutic evaluation.

Microfluidic Point-of-Care Devices: New Trends and Future Prospects for eHealth Diagnostics

“…The merge of information and communication technologies (ICTs) with PoC devices for continuous real-time health monitoring, for storage and processing of medical records (eHealth), has become a trend in biosensing technology [77][78][79][80][81][82][83][84][85][86][87][88][89][90]. Although it all started as a cost-effective alternative to deliver diagnostic strategies in the developing world, especially in rural, remote, and underserved communities, it has rapidly proliferated as a revolutionary tool that may enable virtual appointments between patients and doctors [17][18][19][20].…”

“…The transmission of detection results to remote sites or health databases, via Internet or mobile networks, as depicted in Figure 8C, can be used for telemedicine or patient's health-data storage and analysis. This technology has been tested for geotagging and patient management of ebola virus survivors from the 2000-2001 Gulu outbreak in Uganda [90]. A test strip was designed for detecting EVD (ebola virus disease) IgG (immunoglobulin G) antibodies in the human serum.…”

“…A box plot analysis of 30 blind serum samples from 25 survivors and 5 noninfected subjects (controls), obtained across Uganda, is shown in Figure 10A. These results were used as part of the assay validation in conjunction with other samples/measurements [90]. Insets in this figure correspond to readout results using GP 1−649 monoplex strips for three survivors (S1-S3) and two noninfected controls (C1-C2).…”

Rapid detection of severe fever with thrombocytopenia syndrome virus (SFTSV) total antibodies by up‐converting phosphor technology‐based lateral‐flow assay

“…In the early days this technology was mainly used to conduct pregnancy testing and drugs‐abuse testing . However, recently, LF has also been widely applied in infectious disease diagnostics . Up‐converting phosphor technology‐based lateral‐flow (UPT‐LF) assay is a new type of LF assay, which utilizes the up‐converting phosphor (UCP) particle, a rare element‐containing nanoparticle, as the reporter in the immunoreactions .…”

Ultrasensitive Ebola Virus Antigen Sensing via 3D Nanoantenna Arrays

“…There are also a few alternative EBOV antigens and antibodies assays, which are currently in research phase. These include an antibody gold‐nanoparticle‐based lateral flow colorimetric immunoassay (LoD of 200 ng mL −1 EBOV antigen) and an antigen field‐effect transistor (LoD of 1 ng mL −1 EBOV antigen), but these tests also show lower sensitivity compared to RT‐PCR. Therefore, there is an urgent need to advance highly sensitive EBOV immunoassay for early antigen quantification and disease diagnosis.…”