Death Called a River

By Jason Socrates Bardi


"And the priest shall look upon the plague, and shut up those who hath the plague seven days."

—Exodus 13:50


Ebola hemorrhagic fever is one of the most virulent diseases known to humankind. Very few pathogens are more dangerous than Ebola virus once a person is infected. There is no cure, and with a case-fatality rate of between 50 and 90 percent, depending on which strain in involved, it is one of the deadliest viruses on the planet.

But Ebola virus is also one of the rarest viral infections in humans. Despite the tremendous attention it has received in recent years, of all the pathogens that have plagued mankind throughout history, Ebola virus is little more than a bit player. It has sustained but nine major outbreaks since it was first recognized some 25 years ago, claiming at most a few hundred lives each time. By comparison, five times as many people die in workplace accidents in the United States each year than all those who have ever died of Ebola hemorrhagic fever.

"People say to me, 'Why do you work on Ebola virus when it has still killed less than 1,000 people that we know of?'" says Immunology Professor Dennis Burton.

"My answer," he says, "is that we don't know where the virus is headed—whether sooner or later [it] could become more dangerous to a wider population."

The scariest thing about Ebola virus is not what it has done but what it might do.

A Virus Emerges

In the summer of 1976, Ngoy Mushola, a doctor from Bumba, Zaire, traveled to Yambuku, a town on the shores of the Ebola river.

There, at a local hospital, Mushola recorded the first clinical description of a new disease that was killing almost all of the patients who contracted it. "The illness is characterized with a high temperature of about 39°C, hematemesis [the vomiting of blood], diarrhea with blood, retrosternal abdominal pain, prostration with "heavy" articulations, and rapid evolution death after a mean of three days," he wrote in his daily log.

The illness, which was later named Ebola hemorrhagic fever after the nearby river, was successfully contained in Zaire over the course of a few months, but not before 318 people contracted the virus. Nearly 90 percent of the victims died within a few days of becoming infected.

Hundreds of miles away, in Maridi and Nzara, two cities in the southern tip of Sudan, doctors were witnessing an outbreak, describing patients with high fevers, aches, nausea, bleeding, delirium, and what they termed a "mask-like" or "ghost-like" face. Two hundred and eighty-four were infected and over half died.

One of the main risk-factors associated with Ebola virus in the Sudan outbreak was caring for the sick. The disease was spread within hospitals, and many medical care personnel were infected. In several of the Ebola hemorrhagic fever outbreaks that have followed, health care workers have been at risk, and there have been many documented cases of doctors and nurses contracting Ebola virus from the patients they were tending.

Scientists and laboratory personnel working with the live virus are also at risk, and a few months after the Sudan outbreak, a scientist working with the virus in England became infected after he accidentally stuck himself with an infected needle.

Virulent and Rare

Burton, who does not work with live virus, began to study Ebola virus in the mid-1990s, expanding his successful studies on the interplay of viruses and antibodies in humans. In particular, he had been looking at several "slow" viruses—including human immunodeficiency virus and herpes simplex virus—and wanted to raise antibodies against a virus that was very different. He chose Ebola.

"The virus is intriguing because it acts so quickly," says Burton. "It kills people in two weeks or less."

As deadly as Ebola virus is, it has never sustained a large outbreak, probably due to its speed of action and how powerfully sick it makes people. Even as case-fatality can approach 90 percent, infected patients become bed-ridden while they are most infectious, and infection is spread only through direct contact with bodily fluids. Thus, patients are easily quarantined and outbreaks contained.

"Humans are the unlikely target," says Neuropharmacology Professor Michael Buchmeier, who has studied Ebola virus and related viruses for a number of years. Humans are not the natural reservoir for Ebola virus, but merely incidental or accidental hosts.

Until recently, Buchmeier and Burton were co-investigators on a National Institutes of Health project to research immune therapies against Lassa virus and Ebola virus. Now Buchmeier is concentrating his research on the virus that causes Lassa Fever, which is believed to infect over 100,000 people a year, cause 3,000 to 5,000 deaths, and be the leading cause of fetal death in some West African countries.

Ebola and Lassa are both non-human viruses. They are persistent in animal populations in the wild, and remain in this animal "reservoir" population because they are not deadly enough to kill the infected animals—an evolutionary advantage for a virus to remain endemic in its host species population.

In the case of Lassa fever virus, the animal host is the multimammate rat, a rodent common to many parts of Africa. Humans become infected when they come into direct contact with virus particles in rat waste. Scientists suspect a similar host for the Ebola virus.

"There has to be something out there that harbors Ebola virus," says Buchmeier.

Though much work has gone into identifying the source of this virus, none has yet been found. Ebola virus and the closely related Marburg virus have both been found to infect humans and monkeys—some strains infect one or the other, and some strains infect both—but neither human nor monkey populations harbor the virus in between outbreaks.

Some believe that the natural source of the Ebola and Marburg viruses might be bats, because of the association of some outbreaks with people who had visited caves and mines containing many bats. Given the source of Lassa virus, rodents are another good candidate. However, despite repeated attempts to culture Ebola virus from animals in the wild, the source of the virus has never been found.

Burton thinks an antibody he has made might provide a technology that would help.


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Immunology Professor Dennis Burton studies a number of viruses, including the Ebola virus.