Saturday, December 20, 2014

Ebola 2014: December updates


Fig 1: Ebola deaths in key areas.
Once again it is time for some updated news on Ebola 2014. As of he official reports, the total number of Ebola cases is 18,000, a figure more than all the cases combined, ever reported in past Ebola outbreaks. Also a recent outbreak discovered in Kono by the WHO, has brought in fresh concerns. The news report is that 87 bodies have been buried by 2 teams in past 11 days. The concern is Ebola outbreak hasn't completely leveled off. As Olushayo, an official in WHO's response Ebola team puts it, "Our team met heroic doctors and nurses at their wits end, exhausted burial teams and lab techs, all doing the best they could, but they simply ran out of resources and were overrun with gravely ill people". This underlines an important point. The total number of Ebola is probably under reported, as WHO agrees in their reports.

Other than the deaths of civilians, doctors killed in outbreak is also part of the headlines. Victor Willoughby, senior doctor involved in combating the outbreak, has died just when the experimental drug ZMab (Different from Zmapp) arrived from Canada on request. ZMab is also a monoclonal antibody preparation, targetting different epitopes- 1H3, 2G4, and 4G7. These monoclonal antibodies, raised in mice immunized with a VSV-based EBOV vaccine (VSVΔG-EBOVGP), recognizing the Ebola glycoprotein. The cocktail was tested recently in a Cuban doctor Felix Baez, who successfully recovered.

With favorable results from ChAd3 Ebola vaccine, in Phase I, plans to begin a Phase II trial has been initiated and currently under review by WHO. The trials are expected to begin by February 2015. In West Africa, trial has begun to check the efficiency of plasma exchange from a Ebola recovered donor (Link). A clinical trial is also underway, using a attenuated replication competent Ebola strain. The trial in Geneva has been halted a week after inception, based on four patients complaining of joint pain. 59 people have been vaccinated so far. Though it is expected that there would be side effects of mild nature, the replication competence of virus is to be considered. Hence the careful observation. The experts suggest it would be better to try and understand the reason behind side effects.

Fig 2: Action of FX-06. Source
A team from Frankfurt University Hospital, has published the use of a experimental drug on a A 38-year-old male doctor who had contracted Ebola. One of the major problems in EBOV is the vascular hemorrhage. The patient received a 3 day treatment course with FX06. The safety and efficacy of FX06 (The fibrin Bbeta chain-derived peptide) in the treatment of vascular leak syndrome has previously been explored in animal models of lipopolysaccharide induced and dengue haemorrhagic shock. FX-06 competitively binds to vascular endothelial (VE)-cadherin, thereby inhibiting leukocyte transmigration and initiating VE-cadherin-mediated signaling, which tightens the endothelial barrier and reduces capillary leakage. The sequence of FX-06 resembles that of a physiological peptide, and the compound has been well tolerated in clinical trials. On treatment, improvement was seen from an almost fatal case to improved respiratory and vascular function, reduction in viral load in blood. The virus was not detectable after 30 days.

With currently more than 53 different treatment regimens under R&D testing, the chances of developing a good vaccine and drug to combat Ebola Outbreak, the prospects appear good.
Audet J, Wong G, Wang H, Lu G, Gao GF, Kobinger G, & Qiu X (2014). Molecular Characterization of the Monoclonal Antibodies Composing ZMAb: A Protective Cocktail Against Ebola Virus. Scientific reports, 4 PMID: 25375093

Callaway, E. (2014). How do you test an Ebola vaccine? Nature DOI: 10.1038/nature.2014.16579

Timo Wolf, Gerrit Kann, Stephan Becker, Christoph Stephan, Hans-Reinhardt Brodt, Philipp de Leuw, Thomas Grünewald, Thomas Vogl, Volkhard A J Kempf, Oliver T Keppler, Kai Zacharowski. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. The Lancet; Published online December 19, 2014