ApoH: A novel tool to support the response to the current Ebola outbreak?
ApoH enhances 100-fold the sensitivity of existing assays to detect Ebola virus particles
Contact between the biological fluids of Ebola virus (EBOV)-positive victims and healthy individuals continues the transmission chain of the current West African Ebola outbreak. Past Ebola outbreaks may have involved viruses exhibiting higher mortality rates; however, the outbreaks were limited to the rural areas of their origins, persisted for very limited periods, and therefore had a limited number of victims.
The current Ebola outbreak has been extremely difficult to control on multiple fronts. Contributing factors have been cultural healthcare habits and burial customs, uncontrolled high mobility of the regions inhabitants, including travel to densely populated and very impoverished cities of other West African countries. The lack of coordinated healthcare structures and policies, a result of recent regional civil instability, has greatly exasperated these problems.
The greatest reasons for the unchecked expansion of the epidemic are the near-absence in the region of clinical lab capacity, healthcare structures and trained healthcare workers. There has also been a lack of affordable fieldable ultrasensitive diagnostic tools, therapeutic drugs and vaccines used to detect, treat and prevent further spread. Combined, these shortfalls have given EBOV the increased space and time it needed for wider dissemination.
It is pivotal to point out that, because of the increases in case numbers, there is the growing potential for pre-symptomatic EBOV-positive individuals to infect healthy contacts. Today, Ebola involves more than 2300 deaths and more than 4000 reported EBOV-positive patients. There are probably far more because the current diagnostic techniques generate false negatives, and because the vast majority of cases and deaths in the rural areas are never tested or reported. Ebola is progressing from an outbreak to an epidemic, and is teetering on the verge of becoming a pandemic; it threatens 10s of millions of people in West Africa, and, because of air and boat travel, all other regions of the World as well.
Thus, in addition to symptomatic patients that are easily diagnosed and isolated in most cases, as yet undiagnosed cases may be seriously contributing to the present Ebola outbreak, including:
- a/pre-symptomatic and /or early phase Ebola-infected patients
- symptomatic patients with EBOV-negative diagnostics
- natural (self-cured) convalescents
- potential for convalescents to donate their blood or sera for therapeutic antisera treatments of
Ebola patients, which should be clear of infectious viral particles (following the fast-track procedures recommended by WHO).
Current diagnostic procedures have difficulty detecting most of these critical cases, potentially generating false-negative EBOV diagnostic results. This could lead to wrong and dramatic decisions from health authorities. For example, it might let carriers go out of isolation areas and potentially spread the virus.
Together, ApoH-Technologies (ApoH-T) and the Comparative Molecular Immuno-Physiopathology lab (LIPMC) from the French Institute of Research for Development (IRD) in Montpellier, aim to reduce drastically the Ebola outbreak. They will address the problem by using their technology to permit isolating, at the very earliest stages of the infection, those Ebola contacts who are presenting what would otherwise be undetected (false-negative diagnosis with the current applied tests) and/or subclinical or pre-clinical infections. Such promising advances would help healthcare authorities make appropriate decisions and countermeasures.
Our original technology, based upon the high-affinity capture of pathogens by the acute phase serum protein Apolipoprotein-H (Beta2-glycoprotein1), is a unique reagent allowing non-specific concentration of blood and body fluid pathogens for ultra-sensitive, and thus very early, pathogen detection and diagnostics in people exhibiting otherwise difficult to detect viral loads.
We have a diverse and long-standing expertise in drastically reducing false negative diagnoses observed in different clinical cases of infectious pathologies, including the cardiopulmonary Hantavirus infection, Dengue, HCV, HBV, Norovirus, etc., as well as bacterial infections, such as sepsis (Staphylococcus aureus).
A consortium of the European USDEP project, promoted by ApoH-T and the LIMPC, have collaborated with S. Becker’s BSL4 Lab at the Phillips University in Marburg, Germany to show a 100-fold enhanced sensitivity to detect infectious Ebola virus like-particles (iEBOV-VLPs), when they were spiked in either human plasma or serum. They achieved similar results for Marburg VLPs. This study was presented at the 19th German Congress of Virology (see the poster).
