Jan 2, 2015

Ebola caught us by surprise, or may be not…?

The current outbreak in West Africa (first cases documented in March 2014) is the largest and most complex Ebola outbreak since the Ebola virus was first discovered in 1976. On August 28, 2014, the World Health Organization (WHO) warned the public that the number of people affected by Ebola virus could rise to 20,000 within the coming 9 months.[1]

The disease usually has an abrupt onset after an incubation period of 2-21 days (average 4-10 days). Humans are not infectious until they develop symptoms (fever, fatigue, muscle pain, followed by vomiting, diarrhea, or symptoms of impaired kidney and liver function, among others). The outcome of the disease, in terms of death or recovery, usually can be observed within 6-11 days of symptoms. The outbreak of Ebola Virus Disease (EVD), associated with case fatality rates of 50% to 90%, is generated by infected bats or non-human primates and is spread by human-to-human transmission, either through direct contact with patient's blood or various body fluids, or indirect contact with environment contaminated with such fluids. No evidence suggests the role of insects in disease transmission.[2]

Monoclonal antibody based therapy gained the attention of the entire world during the current outbreak after two American health workers with Ebola recovered from the disease after being treated with ZMapp TM, three "humanized" monoclonal antibodies manufactured in tobacco plant.[3]

Although a wide range of potential treatments are currently being evaluated, just two potential vaccines are undergoing human safety testing.[4]

At the beginning of 2014, Stephan Günther et al. evaluated the efficacy of the pyrazinecarboxamide derivative T-705 (Favipiravir) against Zaire Ebola virus (EBOV) in vitro and in vivo. Favipiravir, belonging to the order of Mononegavirales, works by blocking the enzyme called ‘viral RNA polymerase’, a enzyme responsible of copying the pieces of RNA that form the new viruses. By blocking this process, favipiravir prevents the multiplication of the virus inside the cells. The therapeutic efficacy was probed in small animals and as expected, EBOV infection of untreated mice resulted in 100% lethality within 10 days of infection. Rapid loss of weight, strong elevation of serum aspartate and alanine aminotransferase (AST and ALT) levels and substantial decreases of body temperature were observed in the untreated mice. Mice in the T-705 group showed the same symptoms the first day of treatment (day 6 p.i.) but within four days of T-705 treatment (day 10 p.i.), all the animals had cleared the virus from their blood and were recovered at the end of the 3-week observation period, each developing EBOV-specific antibodies. These results provide some hope that a successful Ebola cure may be on the way.[5]

The other drug that has just been given FDA approval for the treatments of Ebola is TKM-Ebola, a systemically delivered RNAi that binds to specific parts of the Ebola virus, interfering with virus replication.[6]

The U.S. Food & Drug Administration (FDA) has recently announced the modification of the full clinical hold placed on the TKM-Ebola Investigational New Drug Application (IND) to a partial clinical hold, something that enables the potential use of TKM-Ebola in individuals infected with Ebola virus, underscoring the critical need for effective therapeutic agents to treat the current outbreak.

Until now, the threat of the virus for the world outside Africa was mainly for its potential as a biological weapon, but now it seems that Ebola is closer than we all thought, and currently no specific anti-Ebola drug (neither a vaccine nor an effective antiviral treatment) is available for use in humans. Maybe because this is typically a disease of poor people in poor countries?

Compared with malaria or HIV, “Ebola is just not that much of a public-health problem worldwide,” said Heinz Feldmann, a virologist at the US National Institute of Allergy and Infectious Disease (NIAID) in Hamilton.[6]

[1], [2]
[3] Goodman JL. Studing "Secret Serums"- Toward Safe, Effective Ebola Treatments. N Engl J Med 2014.
[4], [5], [6], [7]

Written by Dr. David Alcantara and Dra. Belén Suárez Jiménez for The All Results Journals

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