By Dean Haycock

Special to BioWorld Today

Somewhere along the northeast coast of Africa, where the continent juts into the ocean, the North Atlantic turns into the South Atlantic. Under this eastward projecting shelf, south of Cameroon and tiny equatorial Guinea, the country of Gabon straddles the equator. Rainfall there is heavy, reaching 150 inches per year in some regions.

Approximately 75 percent of the country is covered by equatorial rain forest, containing thousands of species of plants and animals, including monkeys and chimpanzees.

In 1996, a dead chimpanzee was found by several inhabitants of the isolated village of Mayibout on the Ivindo river, deep in the rain forest of northeast Gabon. The chimpanzee was dismembered, cooked and eaten by 18 villagers. The meat was contaminated with the Ebola virus, the hemorrhagic virus that became the macabre subject of popular books and a big-budget film in the West. A total of 31 persons were eventually infected with Ebola in Mayibout. Sixty-six percent of them died. There was another Ebola outbreak in Gabon six months later, in the town of Booui. Seventy percent of those infected during that outbreak died.

Survivors Show Prolonged T-Cell Response

Blood samples taken during these two separate outbreaks are now yielding a detailed picture of the immune system¿s response to the virus early in the course of infection. In the April issue of Nature Medicine, a team of French researchers describe the first detailed look at the way the body responds to Ebola in their article, ¿Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.¿

Gary Nabel, of the Howard Hughes Medical Institute at the University of Michigan Medical Center, in Ann Arbor, describes the results in a ¿News & Views¿ article in the same issue as being ¿among the most comprehensive analyses of the immune response to Ebola virus infection in humans.¿ The work shows that the initial response of the human immune system to infection by the emerging virus is a prime factor in determining whether a victim will live or die. The lucky 30 percent or so who survived Ebola were found to have had a more prolonged T-cell response to infection, and to have developed an early, more effective antibody response to the proteins on the surface of the Ebola virus.

The researchers found that Ebola survivors respond to infection with ¿orderly and well-regulated humoral and cellular immune responses, characterized by the early appearance of specific IgM and IgG followed by activation of cytotoxic cells at the time of antigen clearance from blood.¿ No IgG antibodies were observed in the blood samples taken from those who later died.

The approximately 70 percent who died showed evidence of extensive programmed cell death, or apoptosis, in their peripheral blood cells. They also manifested something that might be used as a marker or predictor of the expected outcome of the infection. Compared to survivors, those who succumbed produced more interferon-gamma soon after they became infected.

From Gabon, Ph.D. students Sylvain Baize and Eric Leroy, along with Joseph Lansoud-Soukate, chief of the unit of emerging disease and delegate general director of the Centre International de Recherches Midicales de Franceville (CIRMF) in Gabon, discussed their work with BioWorld Today via e-mail.

¿The results we obtained are very preliminary and further investigations will be necessary to understand what is really implicated in the control of the infection (antibodies, cytotoxic cells, inflammatory responses),¿ the authors wrote. The same cautions, they said, apply to their finding that Ebola fatalities are associated with programmed cell death in peripheral blood cells. If, however, the massive apoptosis they observed in fatalities is a major contributing factor in the virus¿s high mortality rate, then ¿it may be beneficial to counteract the immune activation observed in fatalities (early cytotoxic cell activation),¿ they said.

¿Nevertheless,¿ they continued, ¿these data suggest that the immune system is able to control the viral replication in 30 percent of patients, which leaves open the hope for a vaccine.¿ Their findings thus support work currently being conducted to develop a vaccine, using a guinea pig model of the disease.

¿Furthermore, if the antibody responses observed in survivors are really implicated in the resolution of infection, passive immunization with specific IgG could be effective,¿ the authors told BioWorld Today. They add parenthetically that these ¿experiments have been realized during the Kikwit outbreak,¿ in which the virus killed approximately 250 persons in 1995, in the town of Kikwit, in southwestern Zaire.

Upcoming Paper Describes Diagnostic Tool

The results described in the Nature Medicine report represent just a portion of the efforts by the French scientists to understand Ebola and its effects. They now have several other papers submitted or in preparation, which further describe immune responses to the virus. In vitro experiments are in progress to provide a better understanding of the mechanisms leading to the immune responses observed in vivo and, they tell BioWorld Today, they have recently submitted for publication a paper describing a new diagnostic tool for Ebola disease. ¿Moreover, we will work soon with the survivors of the 1996 outbreaks to study the memory immune responses to the Ebola virus,¿ Sylvain and co-authors reported.

The researchers report they now have a biosafety level 4 glove box that increases their own level of precaution in the field.

¿To have a BSL-4 in an Ebola endemic zone permits the CIRMF to quickly react in case of epidemic, and to perform sophisticated research (all the experiments have been done at CIRMF) in a developing country,¿ the authors said.

¿In fact,¿ they added, ¿it will be much more difficult to perform this study without a lab in an endemic zone, because Ebola infections often occur in villages located deep in the rain forest which are difficult to access.¿