HEMORRHAGIC FEVERS: the name says it all, and it conjures up many of our darkest fears. These diseases all, it seems, come out of the rain forests of Africa. They are described as “terrorizing” or “stalking” the human race. The agents are always “deadly,” and they are “killers.” They are reason enough for firebombing African villages and threatening to do the same to American cities, as in the movie Outbreak. They have names such as Lassa, Ebola, and Marburg. Marburg? Germany? Yes, and the strange thing is that if you are a virologist, used to looking at electron micrographs, you would say that Lassa was the one that doesn’t belong. It’s an arenavirus, you would say. The others are filoviruses; they look kind of stringy.
For non-virologists, what is more important is this: they all, more or less, start with malaise and aching muscles and then move on to high fever, coughing, diarrhea, pain everywhere, and, in the worst cases, bleeding all over, brain problems, shock, and death.
In 1969, a nurse in Lassa, North-Eastern State, Nigeria, came down with fever, aches, and pains—the unremarkable symptoms of serious tropical diseases such as malaria, or diseases of poverty such as typhoid fever. When she didn’t get better after being treated locally, she was flown to a hospital in the Nigerian city of Jos. She died. One of the nurses who had taken care of her there also died. A third nurse, who had helped with the post-mortem of the first, became ill and was flown home to the United States in a commercial airliner. The Yale Arbovirus Unit isolated a virus from her blood and called it Lassa virus. A laboratory worker at the Yale laboratory fell ill, was treated with a transfusion of serum from the nurse, who was recovering and presumably had antibodies. The lab worker recovered. Five months later, another laboratory technician at the lab died of Lassa fever. No one knows how it happened.
The natural home of the Lassa fever virus is an African soft-furred rat, also called a multimammate rodent, Mastomys natalensis. Mastomys are at home in savanna woodlands common throughout parts of sub-Saharan western Africa. The rodents are sometimes described as pests and sometimes as food. I guess that depends on where they are found and how hungry you are.
Lassa fever virus belongs to a larger family of rodent lovers. Members of this family include Machupo virus (causing Bolivian hemorrhagic fever), Junin virus (Argentinian hemorrhagic fever), Guanarito virus (Venezuelan hemorrhagic fever), and lymphocytic choriomeningitis virus (found in Europe and North America and causing “flu-like” lymphocytic choriomeningitis disease, or LCM, and only rarely meningitis in people).
In the early 1970s, Lassa was considered a rare disease, which killed about half the people it infected, mostly in hospitals. But then, many diseases are considered serious when first discovered, simply because the most serious cases are the ones first reported. For a few years, small outbreaks with high death rates were reported from hospitals in Nigeria and Liberia. Then, investigators of a hospital outbreak in Sierra Leone reported that less than 10 percent of the people infected there picked it up in the hospital. The case-fatality rate was less than 5 percent.
Using this news as a starting point, an intrepid group of investigators from the Centers for Disease Control and Prevention in Atlanta, led by Karl Johnson and, later, Joseph McCormick, set out to describe the epidemiology and ecology of the disease in its natural setting. They found that the disease was endemic in much of western Africa. A few hundred thousand people a year may get infected, and 15 percent of them die with “multisystem” failure— which basically means that all their body organs shut down.
Occasionally, people still pick up Lassa fever virus in Africa and carry it home to other parts of the world. In 2004, a businessman returned to New Jersey after a five-month stay in Liberia. Toward the end of his visit to Africa, he developed fever, chills, sore throat, diarrhea, and back pain. Doctors in the hospital in Trenton, New Jersey, treated him with antimalarial drugs and antibiotics (for typhoid fever). He got worse and had trouble breathing. The doctors went down their list of possibilities and came up with yellow fever and Lassa fever as candidates. Both of these require expensive antiviral treatments. He died before they could start treatment. Since getting sick, he and/or his bodily fluids (blood) had come into contact with fellow airplane passengers, train passengers, family members, and laboratory workers. Nobody else, fortunately, got sick. But they could have.
In 1967, twenty-five laboratory personnel in Frankfurt and Marburg, Germany, and in Belgrade, Yugoslavia, fell acutely ill with high fevers, muscle and joint pain, vomiting, diarrhea, rashes, and bleeding, both internally and from the nose. Some of the people who took care of them also got sick. One spouse was infected through her husband’s semen. Seven of the infected people died.
All of those originally infected were working with tissues and blood from African green monkeys (Cercopithecus aethiops) imported from Uganda. Cell lines derived from African green monkeys are used for vaccine research and various kinds of testing. For instance, the disease associated with the infamous E. coli O157:H7, sometimes called hamburger disease, is also called verotoxin-producing E. coli. The actual disease is caused by a so-called verotoxin, which means that it kills African green monkey kidney cells in the laboratory. The original monkeys had not appeared to be ill, but there had been daily deaths among the monkeys in transit from Uganda, and experimentally inoculated monkeys of various sorts did become ill and die. Still, some of the African green monkeys experimentally infected did not get sick.
Almost a decade later, in 1976, dramatic epidemics of a hemorrhagic disease struck southern Sudan and northern Zaire. In the Sudan, about three hundred people got sick and more than half of them died; in Zaire (now the Democratic Republic of the Congo), about three hundred people got sick, and about 80 percent of them died. The virus that was isolated from the victims looked exactly like the Marburg virus, but it turned out to be something different. Doctors called it Ebola virus, after the Ebola River, one of the headwaters of the Congo (Zaire) River.
In the twenty years after that, only half a dozen incidents of Marburg virus disease were recorded, in Kenya, South Africa, and Zimbabwe, involving altogether a few dozen people, about a quarter of whom died. This changed abruptly in 1998, when an outbreak of Marburg disease started among “unofficial” gold mine workers in the Democratic Republic of the Congo; 149 people were struck with the disease and 123 of them died. Then, in 2004 and 2005, an outbreak of fever, vomiting, coughing, hemorrhaging, and diarrhea was reported from northern Angola. One hundred and twenty-four people got sick; three-quarters of them were children under five years. Of those who were sick, 117 died.
The disease seems to come out of nowhere but spreads among people who have very close contact with each other, either in hospitals or through burial practices. Then the disease disappears. Where does it come from? Where does it go back to? No one knows.
Initial suspicions fell on the monkeys as a reservoir. The monkeys in Marburg had been imported from an island in Lake Kyoga, that shallow, swampy lake near Mount Elgon, on the Kenya-Uganda border—the same (pleasant) area where our sleeping sickness work was done (see chapter 5). There were rumors that there had been a large number of monkey deaths in the wild colonies there, but these rumors were not corroborated.
A little more is known about the ecology and epidemiology of Ebola virus fever. Since the 1976 epidemics, scientists have determined that there are at least four different strains of the virus. The Maridi strain, which has struck in southern Sudan and northwest Uganda, kills from a third to two-thirds of its victims. The Zaire subtype, involved in attacks in Zaire, Gabon, the Democratic Republic of the Congo and the Republic of Congo, kills from 60 to 90 percent of its victims. The third African strain, from the Ivory Coast, is known to kill chimpanzees but not people. Another strain of Ebola, the Reston virus, was isolated from monkeys at a quarantine station in Reston, Virginia; the cynomolgus monkeys (and the virus) came from the Philippines, and, although it has been capable of killing the monkeys and instilling panic in the general public, this strain does not appear to cause serious disease in people.
The frequency of serious outbreaks of Ebola virus seems to be increasing in Africa, and there has been a concerted effort to find the natural reservoir for the disease. Scientists investigating five recent outbreaks of the Zaire strain in Gabon and the Republic of Congo found that the index cases (the sick people who start the epidemic) were people who handled dead gorillas, chimpanzees, and duikers. These animals are important sources of what is called bush meat, that is, wild-caught meat. The primates are particularly dangerous, because for a microbe, the jump from a monkey to a human being is more of a small step than a great leap.
People eat wild primates and other bush meat because they (the people) are poor and hungry and the animals are freely available to anyone with a gun. As people probe or are pushed deeper into new ecosystems in search of food, the bush meat trade has become a continuing potential source of new diseases, including, probably, several strains of the viruses that cause AIDS. The human epidemics of Ebola virus fever appear to have been preceded by, or associated with, deadly epidemics in animals, and biologists are afraid that Ebola may be devastating some wildlife populations in central Africa.
In all the Ebola outbreaks studied so far, once a person is infected, the epidemic is spread by close contact between the sick individual and his or her caregivers and through burial rites and the preparation of bodies for those burials. Controlling the spread of the disease thus requires culturally sensitive engagement with local people; caring for loved ones, and burial rites, are profoundly rooted in history and culture and are not changed through lecturing from medical experts. Often the very techniques that are so effective for treating disease (chain of command, control, reliance on technical expertise) are the least effective for promoting prevention and long-term health. To their credit, many medical organizations, including the World Health Organization, are discovering the value of anthropologists and of building local trust.
The reservoirs of both Ebola and Marburg viruses have remained elusive. If the wild primates are dying from the disease, they make a lousy natural home. Investigators have tried to narrow down the possibilities by studying the ecological situation and the geographic scope of the disease. Of the thousands of animals tested, the most promising candidates for reservoirs, as of late 2005, were several species of African fruit bats, which seem to be infected without becoming sick.
The good news is that these bats don’t migrate beyond Africa and that if we can work together to establish sustainable communities in that troubled continent, to educate women and children and men, to build effective farming practices and create meaningful employment, the disease can be contained.
The bad news is that people move themselves and a wide range of species, legally and illegally, out of Africa every day. The animals are transported to become pets, to be used in research, or for food, or just because that’s what humans do. In 2003, monkeypox (fortunately not a fatal disease in people) got into the United States when an animal distributor imported a variety of rodents from Ghana. These included species such as rope squirrels (Funiscuirus sp.), tree squirrels (Heliosciurus sp.), Gambian giant rats (Cricetomys sp.), brushtail porcupines (Atherurus sp.), dormice (Graphiurus sp.), and striped mice (Hybomys sp.). The animals were then shipped to pet stores across the country and housed in the same stores that sold prairie dogs, those pesky things that farmers like to shoot. Apparently, there is a market for these little beasties as pets; apparently, the market does not know that these animals act as vessels for microbes out to see and colonize the wide world.
It may be time to re-examine some of the things we “just do.”