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The Mystery of Ebola, A natural born killer

THE BALTIMORE SUN

Since the April outbreak of Ebola virus infection in Africa, I have been asked by a concerned public to allay concerns about the risk of Ebola for Americans. I also have been asked why this and other terrifying viruses seem to emerge from places like Africa on a regular basis to threaten us with illness and destruction. I hope to answer these questions in this article.

For those of you who have not followed the African outbreak of Ebola virus in the news media, I can tell you that the illness caused by Ebola virus is riveting. Since the current outbreak started late in April, 121 of 160 patients have died, and the epidemic is not yet over.

[However, the World Health Organization announced Thursday that the virus' spread appeared to have stopped. It gave the death toll as 164 of 211 known victims.]

The virus and the illness it causes are worthy of some description. Ebola is a member of the family of viruses called filovirus. These are thin molecular tubes seen as long looped or bent threads under the powerful electron microscope. If they enter cells of the body, they multiply exuberantly, destroying these cells and packing them with crystals of Ebola virus.

A person infected with Ebola usually first complains of an abrupt, splitting headache followed by high fever and by pain in muscles and joints. Knife-like chest and abdominal pains may occur early, and the patient rapidly becomes so sick and exhausted that he or she cannot climb out of bed. As a result of the fever and severe watery diarrhea that develops, the patient becomes depleted of salt and water, causing even more weakness. A raised or splotchy red rash develops about a week after the onset of the illness, growing for three to four days. After this, the flesh may peel off in places like a snake shedding its skin.

After one week, the blood of most patients fails to clot, and they begin to bleed. This is why the illness is called Ebola hemorrhagic fever. Patients bleed into their lungs and cough up blood clots. They bleed into their intestines and vomit blood and pass black bloody stools. They bleed from the nose, gums and vagina. They bleed into their skin, developing bruises, and the whites of their eyes turn blood red. They ooze blood from needle puncture sites and from ordinary cuts. The majority of such patients, about one in four or up to nine of 10 depending on the virus subtype, die in one to two weeks after massive blood loss, death of internal organs and shock. It is easy to understand why emerging viruses of such virulence are attention-getters.

But one must remember that not all infected persons die, and many may not even get sick. Like most viral infections, some individuals with Ebola undoubtedly resist even the most virulent varieties of the virus. But we don't know how many people can resist, nor how they do this. Resistance could be a matter of low doses of infecting virus, a change in the virus itself which weakens it, or immunity of the infected individual to the virus. Surprisingly, antibody surveys in Africa reveal that many people have been infected with Ebola in the past, up to 21 percent of some populations in Central Africa, for example. So obviously, most people infected do not die, but we do not know how many will remain well or how many will become sick.

We know that humans can be infected by innocuous Ebola viruses. For example, six years ago some animal handlers in Virginia were infected by Ebola virus spread from infected monkeys imported from the Philippines, but the handlers had not become sick, whereas the monkeys died. (How monkeys from the Philippines got Ebola is a mystery.) One wonders if such "weakened" viruses account for some of the anti-Ebola antibodies found in perfectly healthy Africans.

What triggered the current outbreak of Ebola virus in Zaire? The virus was first identified 19 years ago, when the disease broke out simultaneously in southern Sudan and northern Zaire. The virus in fact is named after a Zairian river.

No clinical case was confirmed for 15 years in Africa. Where had the virus been lurking all these years? Small or large mammals, biting insects or even plants are all possible incubators of the virus, allowing it to go into hibernation. We simply do not know the environmental reservoir, but there must be one because viruses cannot live and replicate by themselves outside of living cells.

I'm hopeful that we will eventually discover the haunts of Ebola virus, because until we do, it will be nearly impossible to prevent or control it. Teams of African, European and American investigators are actively searching out the origins of the current Zairian epidemic.

We do know that once Ebola virus emerges from its natural environment and takes hold in a human population, the virus can be transmitted person-to-person. Fortunately, close and prolonged contact seems to be necessary for successful transmission. This implies that you will not catch the virus simply by riding in an airplane with an infected person, or by chatting with him or her, unless you have physical contact with their virus-infected blood, secretions or semen. The virus did not infect an individual who shared a bottle of soda pop with a nurse in Zaire who fell sick and died three days later. Please be assured the virus is difficult to catch.

In three previous African outbreaks as in the current one, Ebola was spread among hospital care workers or family members who were caring for an ill person infected with the virus. Transmission has also occurred as a result of reusing hypodermic needles contaminated with traces of Ebola-infected blood. It is customary to reuse needles and syringes in impoverished countries where health care budgets cannot afford to replace even such simple equipment. These unsterile practices are responsible in part for the spread of the AIDS virus in Africa and elsewhere. Rest assured that sterile needles and syringes are required in the United States. Ebola virus has been spread through sexual contact with patients while the patients were sick or recovering from their illness.

[A team of international scientists reported Thursday that the epidemic began when a laboratory worker was transferred between hospitals in Kwikwit, Zaire.]

What about airborne transmission? This is a scenario I dread, because if it exists, the possibility of widespread viral dispersion and infection becomes plausible. An experiment conducted 12 years ago by the U.S. Army at Fort Detrick revealed that Ebola could indeed pass airborne from monkey to monkey. The virus contaminates lung fluid of sick and dying animals, so the Army results are not surprising.

Unproven anecdotes suggest that respiratory spread may have occurred during the 1976 outbreak in a Zairian hospital. In my opinion, we cannot exclude the possibility of airborne spread in those few infected individuals who had no prolonged contact with Ebola patients. Given all these considerations, it is unclear why respiratory spread has not been definitely implicated among humans in Africa. Perhaps the virus is fragile and easily destroyed in respiratory secretions outside the body. In any event, we are lucky the virus acts as tamely as it does when it comes to respiratory spread.

We have no vaccine to prevent Ebola and no medicine to cure it. We can only hope to contain it until it burns itself out. We don't know why Ebola burns itself out any more than we know what

triggers it.

Quarantine required

Previous outbreaks of Ebola hemorrhagic fever have been limited in time and place by isolating sick persons in a quarantine facility. Such facilities require that masks, gowns, and gloves be worn by care-givers to prevent contact with contaminated blood and secretions; that needles and syringes be sterilized; and that wastes be properly disposed of and the dead be buried quickly. If the virus contaminates floors, walls, furniture and equipment, it can be destroyed by wiping surfaces with disinfectants. Research on Ebola virus must be done in special high-tech laboratories at the Centers for Disease Control in Atlanta and at the U.S. Army Institute of Infectious Diseases at Fort Detrick. Workers wear space suits connected to air hoses for breathing and work through airtight hoods to protect themselves and the environment from infected blood and tissue.

Are people in the United States at risk? Clearly not. People are at risk only if they have close personal contact with infected patients in Zaire. Travelers proposing to leave Zaire are currently being surveyed and sick patients are put under quarantine. Moreover, unlike the AIDS virus, which kills slowly over many years, Ebola sickens and kills within one to two weeks, lessening the chance the victim will expose and infect others.

The Ebola outbreak is but the latest example of mysterious microbes that emerge suddenly to sicken and kill. It is also unclear why so many hemorrhagic fever viruses in addition to Ebola, such as Marburg and Lassa viruses, seem to have originated in Central Africa.

It can be argued that the emergence of virulent new pathogens is connected to the increasing movement of native peoples into wild areas, such as rain forests, and subsequent contact with exotic animals. For example, three times more pygmy hunters living in the forests had anti-Ebola antibodies than did subsistence farmers living at the edge of the forest. Africa's primate population may have provided the nidus for transmission of these hemorrhagic viruses to humans.

Microbes transmitted from animals to man are called zoonoses. Many zoonotic infections are benign, but some, like Ebola virus, can kill. I will cite three examples of recent zoonotic infections in addition to Ebola which illustrate that ecological features are of critical importance.

First, the AIDS virus, called human immunodeficiency virus or HIV, may be the most infamous zoonotic. It is theorized that in Africa, the HIV virus, or a monkey virus similar to HIV, jumped from monkey to man. We are unsure if HIV was transmitted to man in the 1970s or many decades earlier and only recently spread person-to-person, aided by the breakdown of the traditional socio-economic order in Africa.

Lyme disease, caused by a bacteria related to syphilis but spread by tick bite, is the second example. The Lyme bacteria infects about 10,000 Americans every year and affects the skin, joints, nerves and heart.

Although prevalent in Europe for almost a century, Lyme disease did not emerge in the United States until the 1970s. Interestingly, the Lyme disease bacteria quietly lurked in American field mice and ticks for 40 years or more, but the recent sharp increase in vTC the deer population of the Middle West and Northeastern states may have provided the critical mass of infected deer ticks needed to infect humans and spread disease. Suburbs built in forested or semiforested areas increase the chance that householders can be infected by ticks in their own back yards.

Hantavirus

The third example, hantavirus, was known to cause kidney failure in Asia for 40 years. In the United States, hantavirus infects the lung and fills it with fluid, causing a breakdown in the ability of the lung to oxygenate the blood. If this happens, patients can suffocate and die within hours. The hantavirus is transmitted by infected urine deposited by a species of field mice living in the rural Southwest and elsewhere. After the urine dries, the virus is aerosolized and inadvertently inhaled to infect the lungs. The dramatic increase in the mouse population in the Southwest is thought to lie at the root of the hantavirus problem there. This increase was promoted by an abundant food supply produced by return of the rains to the Southwest after an extended drought. Fortunately, hantavirus infections are uncommon; less than a hundred individuals are known to have developed hantavirus lung disease. Vaccines against AIDS, Lyme disease and hantavirus are being developed.

What are the forces driving the emergence of new zoonotic infections like Ebola and HIV, or the appearance of old infections in new places like Lyme disease and Hantavirus? Factors modulating the emergence of zoonotic diseases are complex. They include changes in the virulence of pathogens, the immune status of humans and animals, social and economic conditions and population growth and movement. But changes in the environment may be the most important.

Anything that upsets the natural balance of things, such as climatic changes, deforestation and road building, can expose humans to unusual microbes. For such reasons, we will almost assuredly encounter more outbreaks of exotic disease as we move into the 21st century.

Dr. Robert Edelman is a professor in the Department of Medicine and the Center for Vaccine Development at the University of Maryland School of Medicine.

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