Ebola: from Bats to Gorillas

The Ebola virus (EBOV), together with Marburg virus, belongs to the Filoviridae family, a group of linear RNA viruses. Four different genetic subtypes have been described in Africa (Sudan ebolavirus, Zaïre ebolavirus, Ivory Coast ebolavirus) and in Asia (Reston ebolavirus). Ebola remains one of the most mysterious emerging diseases, although very important advances towards elucidating its origins and its mode of transmission have been made in recent years.

Outbreaks in Great Apes
Ebola causes severe hemorrhagic fever in humans and apes. After an incubation period of 4-7 days, the infected person rapidly develops high fever, diarrhoea, vomiting, respiratory disorders and haemorrhaging. Death can occur within a few days. The case-fatality rate is about 80% for the Zaïre ebolavirus subtype, which is the most pathogenic strain in Gabon, Republic of the Congo (RC), and Democratic Republic of the Congo (DRC).
In Africa, there have been 15 outbreaks of Ebola with 1,300 deaths from 1,850 infected persons. Accidental transmission of the disease to humans occurs by direct contact with infected dead animals, mainly great apes. Chimpanzees and gorillas are very vulnerable to Ebola virus infection. During Ebola outbreaks in 2001 and 2003 in the Gabon/RC region, a considerable number of ape carcasses were recovered, and it is now well established that the Ebola virus was responsible for the rapid and dramatic decline of great apes in areas where Ebola outbreaks occurred. Wild populations of gorillas decreased by 50%, and those of chimpanzees by 80%, as a result of these outbreaks. Similarly, in the Minkebe forest block in northeastern Gabon near the border with Cameroon, gorilla and chimpanzee densities fell dramatically between 1994 and 1998.
Two hypotheses have been proposed to explain the transmission of EBOV in wild great ape populations. The first is that the virus spread between gorillas from the same or from neighbouring groups, creating a single wave outbreak spreading outward in the forest. The second hypothesis is that large-scale, independent viral transmission occurred from a reservoir species to individual gorillas, creating numerous but limited spot outbreaks. Viruses isolated from great ape carcasses showed genetic differences that supported the second hypothesis, although horizontal transmission from one animal to another remains possible.

Bats as Reservoirs
Since the first report of Ebola outbreaks in DRC and Sudan in 1976, extensive surveys have tried to identify the reservoir which is the original source of the virus. Thousands of animals were collected in many countries and tested for the presence of the virus. Despite these efforts, no conclusive result was obtained until recently.
During the outbreaks in Gabon in 2001 and RC in 2003, bats, birds and small terrestrial vertebrates (mainly rodents) were captured. We have shown for the first time that fruit bat specimens were asymptomatically infected with EBOV, suggesting that they may be the reservoir. There was evidence for Ebola virus (antibodies and viral RNA) in three frugivorous bat species, Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata. If bats are a reservoir for EBOV, it is very important to understand how the virus can be transmitted to other species.
EBOV outbreaks mainly occur during the end of the dry season, which is the birthing season for bats. At this time, fruit is scarce in the forest and numerous bats and gorillas may forage in the same trees for food, and EBOV transmission to great apes may occur directly through infected fluids such as saliva, blood or foetal envelopes. In Asia, bats are the reservoir for the Nipah and Hendra viruses, both of which belong to Paramyxoviridae, a virus family that shares strong genetic similarities with the Filoviridae. Viral transmission from bats to vulnerable species (pigs and horses) can occur either by saliva (Nipah) or by placenta (Hendra).
A better understanding of viral transmission from bats may help to develop strategies to prevent Ebola outbreaks in great apes and humans.

Therapies and Vaccines
During the last ten years, intensive research has been done to develop effective medical therapies and vaccines against Ebola infection. Recombinant nematode anticoagulant protein c2 (rNAPC2) and Phosphorodiamidate morpholino oligomers (PMOs) both gave good results when used to treat experimentally infected macaque monkeys. Interesting results were also obtained with recombinant vaccines using adenovirus and vesicular stomatitis virus (VSV) vectors, which gave good protection against EBOV infection in macaques.
Although vaccines against Ebola are promising, their use in wild animals may be unfeasible, because great apes live in large, remote areas where access is difficult, if not impossible.

Xavier Pourrut, Eric Leroy and Jean-Paul Gonzalez

References
Leroy, E. M. et al. (2004) Multiple Ebola virus transmission events and rapid decline of central African wildlife. Science 303: 387-390
Leroy, E. M. et al. (2005) Fruit bats as reservoirs of Ebola virus. Nature 438: 575-576
Pourrut, X. et al. (2005) The natural history of Ebola virus in Africa. Microbes and Infection 7: 1005-1014

Dr. Xavier Pourrut (DVM) is an epidemiologist who works in the research program "Ebola reservoir" in the Centre International de Recherches Médicales de Franceville.
Dr. Eric Leroy is a virologist and the chief of the "Emerging Viruses Unit" in the Centre International de Recherches Médicales de Franceville.
Prof. Dr. Dr. Jean-Paul Gonzalez is the Director of UR178 "Conditions et territoires d'émergence des maladies" at the Institut de Recherche pour le Développemen, Mahidol University at Salaya, Thailand.

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