Unravelling the Ebola virus’s biological cycle

Ebola virus infection in humans provokes a violent haemorrhagic fever. It usually flares up as intense epidemics. These kill 80 % of the people infected. Seven such outbreaks have hit Gabon and the Republic of Congo since 1994, leading to 445 cases resulting in 361 deaths.

Ebola virus thus constitutes a grave public health problem in these countries. No medicine or vaccine is currently available, only prevention and rapid control of epidemics by isolation of disease victims can limit its spreading.

Since 2001, IRD research scientists and their partners have been working to unravel the virus’s biological cycle, in other words the whole range of ways in which the virus circulates in its natural environment, from its natural host (or reservoir) right up to humans. They showed that strong epidemics of Ebola have decimated populations of large primates over the past several years in the border regions between Gabon and the Republic of Congo. Human infection appears to occur only in a secondary way, through contact with carcasses of dead animals. However, the virus’s natural cycle is not restricted just to transmission from the reservoir to the non-human primate and then to humans. It is quite possible that several reservoir species co-existent and that many other animal species can become infected, thus contributing to propagation of the virus in nature.

A serological investigation conducted from 1980 to 2000 on 790 nonhuman primates from Cameroon, Gabon and the Republic of Congo, belonging to 20 different species, hence revealed that 12.9 % of wild chimpanzees carry Ebola virus antibodies, several of the positive samples dating from before the first epidemics in these countries. These results therefore indicate that chimpanzees are regularly in contact with the animal virus reservoir and that some of them develop non-fatal infections. The presence of specific antibodies in the animals taken before the epidemics means that the Ebola virus has probably been circulating for a long time in Central African forests. The detection of such antibodies in other primate species (including 5 drills, 1 baboon and 1 mandrill) suggests that circulation of the virus involved many contamination events between distinct animal species. Thus, the multiplicity of infected species, their different susceptibilities to the virus and the great differences in their ways of life, are indicators of the complexity of Ebola virus’s circulation in its natural environment. These observations also show that an epidemic or sporadic cases can appear at any moment in the sub-region of Central Africa as a whole.

Moreover, during the latest epidemics in Gabon and the Republic of Congo, there were many cases where dogs had eaten remains of dead animals infected with the virus, nonetheless without showing visible clinical signs. In order to confirm that these dogs had indeed come into contact with the virus, the scientists looked for the presence of specific Ebola virus antibodies in their blood. The percentage of dogs carrying such antibodies increases linearly and significantly the closer they are found to foci of the outbreaks. From 9 % in the two large cities of Gabon, antibody prevalence goes up to 25 % in the untouched villages of the epidemic area, reaching 32 % in the villages where human cases have been attributed to an infected-animal source. These domestic animals could therefore become infected and excrete virus over a given period, thus becoming a potential source of infection for humans. This could explain certain as yet un-elucidated human infections. It now appears necessary to assess the role of dogs in Ebola fever outbreaks and take this risk into account in epidemic-control measures. These animals could furthermore be used as indicators of the presence of the virus in the regions where, besides the appearance of cases of both animal and human deaths, there is no external sign as to whether or not Ebola virus is present.

This research work as a whole indicates the progress that has been made over the past years in the understanding the ways in which the virus circulates in its natural environment. Although the reservoir has not yet been identified, investigations are under way to identify the stages which, starting from this reservoir, lead to the emergence of human epidemics. Knowledge of the reservoir animal and of the virus’s natural cycle should assist in devising suitable prevention strategies against Ebola epidemics.