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AIDS Connection : Third World Diseases: No Borders

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Times Medical Writer

For 20 years ending in the mid-1960s, British surgeon Denis Burkitt roamed the lavishly green highlands of Uganda seeking the cause of a rare form of cancer that primarily afflicted children in that African nation.

His work was to lead to the first well-accepted association between a virus and a human form of cancer--in this case a disease of the lymph gland now known as Burkitt’s lymphoma.

Late last year, however, Dr. Robert Gallo, a researcher for the National Cancer Institute, began looking at the work started by Burkitt with a new goal in mind. Gallo was looking for clues to the origins of AIDS, the immunity suppressing disease that has killed more than 3,800 Americans since its discovery in this country in 1981.

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Exposure to Virus

When Gallo looked at the blood samples collected from Ugandan children and adults, he came to a startling observation: almost two-thirds of the children had evidence of exposure to the virus now believed to be the cause of AIDS.

Scientists have long suspected that AIDS, or acquired immune deficiency syndrome, had its origins in Central Africa. But the blood--collected in the early 1970s by a French scientist following up Burkitt’s research--provided the strongest evidence to date that indeed, the AIDS virus was present in Africa almost a decade before the first AIDS case was detected in the United States.

This African connection most likely will do nothing to help treat victims of AIDS, scientists point out.

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But the connection does serve notice to the developed world that lethal diseases respect no boundaries, neither racial nor geographic. Put simply, it means that medical problems that plague the developing nations can no longer be ignored, if for no other reason than that they occasionally can become worldwide problems.

Classic Example

AIDS, many researchers believe, may be a classic example of what can emerge from the caldron of disease-causing organisms--some known, some unknown to science--that infect hundreds of millions of people in the Third World.

But because of the association in the United States between AIDS and homosexuality--an association not seen in African AIDS cases--researchers must be aware of the extreme sensitivity of the subject, especially when a host nation is not particularly enamored with the thought of being identified as a potential source of the ailment.

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There are cities in Africa where the incidence of AIDS is as high as in major American cities. One study by an international team estimates the annual rate of AIDS in Kinshasa, Zaire, to be about 17 cases per 100,000 people.

“This is a minimal estimate, and it is comparable with or higher than the rate in San Francisco or New York,” the researchers said in a report published in the British journal Lancet last summer.

Another recent study of blood drawn from 100 healthy mothers in 1980 in Kinshasa revealed that 5% had been previously exposed to the virus. In the United States, less than 1% of blood donors test positive.

In the rural eastern part of Zaire, Belgian and American scientists have found that 12% of several hundred hospitalized patients had antibodies to the AIDS virus.

But in countries where medical systems are undeveloped, malnutrition is common, infectious diseases rampant and sophisticated diagnostic services nonexistent, even AIDS could have passed unnoticed for an indefinite period, researchers say.

Researchers in the United States feel certain that the virus responsible for the disease did not appear here before 1978, an estimate that allows for a two- or three-year incubation period before the report of the first case in June, 1981.

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Extremely Unlikely

It is extremely unlikely, they say, that a disease with the unique characteristics of AIDS could long avoid detection in the United States.

But, as the new African research is showing, the AIDS virus or one very similar to it could have been present on that continent for years, perhaps even for centuries.

“I believe the virus was present in Central Africa for a long period of time,” said Gallo, who along with Dr. Luc Montagnier of France is credited with identifying the virus responsible for AIDS. He believes that originally the virus was present in animals, and that it became transmitted to man at an unknown time in the past.

“I don’t know when it got into man in Africa, but clearly it was not widespread there until recently. Suddenly, for reasons we don’t understand, this virus began spreading (beyond Africa) in the mid- or late-1970s.”

Gallo came to his discovery--that 65% of the Ugandan children studied in 1972 had been exposed to the virus believed to cause AIDS by applying the newly developed AIDS test to search their blood samples for antibodies against the virus. The presence of antibodies means that the individual has come in contact with the virus at some time during his or her life.

Blood Collection

The National Cancer Institute scientist obtained the blood recently from Dr. Guy de The, formerly of the International Agency for Research in Cancer based in Lyon, France. During the early 1970s, De The collected blood from 42,000 Ugandans ranging in age from 5 to 50 as part of a study of Burkitt’s lymphoma.

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In a telephone interview, De The said that Gallo also found that 48% of the adults had also showed evidence of the exposure to AIDS virus.

Still, De The noted, there was no epidemic of AIDS in Uganda in 1972--further proof that the virus may have been around for some time before it turned fatal.

“This was an extraordinary situation,” De The said. “(Almost) 50% of the adults tested positive but had no disease. It means possible that the virus at that time was not as deadly as today.”

De The said that one possible explanation is that the AIDS virus they found in the 1972 blood samples underwent a transformation that changed its capacity to cause disease. Such a change is known to happen with other types of viruses.

Another theory is that there may be several AIDS viruses.

10 of the Type

“There may be 10 other (viruses of the AIDS type) in Africa that we know nothing about,” said Dr. Robert Biggar, a National Cancer Institute epidemiologist who has done AIDS studies in Zaire.

Gallo said that he doubts that today’s virus is a variant of the one, for example, that he detected in Ugandan blood. However, he has recently done comparisons of the AIDS virus taken from patients in New York and Haiti and they do show some differences.

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This was accomplished by looking at the sequence of the units, called nucleotides, which make up the genetic material of the virus. It is known that the AIDS virus is composed of 9,700 nucleotides.

Gallo found that when compared to the virus isolated from patients in New York City, the Haitian samples showed differences in 900 of the 9,700 nucleotides. Gallo said that he was surprised to learn that such a large difference exists.

The meaning of the difference, if any, is not yet clear, he said. Conceivably it could represent a difference in the type of T-cell that is infected. (T-cells are a key element in the body’s defense system against infectious diseases and cancer; the AIDS virus zeroes in on T-cells--and destroys them--when it invades the body.) Or, perhaps the difference could be attributed to the virulence of the different viruses.

The AIDS virus is known as HTLV-III, which stands for human T-cell leukemia-lymphoma virus type three. Although HTLV-III does not cause leukemia, it is so-called because it belongs to the retrovirus family that causes an unusual kind of adult leukemia. That leukemia most commonly is found in southwestern Japan, but also in Jamaica, Trinidad, parts of Africa and South America and, to a lesser extent, the southeastern United States. The virus responsible for the leukemia is called HTLV-I.

Historical Connection?

But is there a historical connection with HTLV-I and the AIDS virus? Gallo, who in 1980 isolated and identified HTLV-I, thinks so. And again, the track leads back to Africa.

Beginning in 1543, and for nearly 100 years thereafter, ships flying the Portuguese flag sailed into the harbors of southwestern Japan carrying trade goods and Christian missionaries.

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Gallo believes that the Portuguese sailors brought the virus there from African ports, where the ships stopped for supplies on the long voyage to the Japanese islands.

A recent study by three Nagasaki University researchers appears to give Gallo’s speculation some credence. The researchers catalogued the incidence of human-T-cell leukemia in various parts of Japan and compared them to the number of Catholics living in each region.

The final tabulation showed that the incidence of leukemia was considerably higher in the Catholic areas, which are those parts of Japan where the Portuguese did their trade and the missionaries were most active.

Portuguese, Africans

This finding caused the researchers to conclude that “the HTLV of southwest Japan was probably directly brought by the Portuguese or their associated black Africans.” Researchers believe it still exists today because their evidence points to its transmission in semen from generation to generation--another similarity with the AIDS virus.

Until the HTLV-I virus was identified in 1980, retroviruses were unknown in man. There were, however, a number of retroviruses that cause leukemia or other kinds of cancer in animals. These include cancers in mice, chickens, cats, cows, monkeys and apes.

New studies reported only last month by a group of scientists from the National Cancer Institute, Harvard University and several private companies concluded that while the AIDS virus is similar to the leukemia virus, it has structural characteristics that are unique among all known retroviruses.

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It is believed that this unique genetic structure is what gives the AIDS virus the capacity to kill T-cells, whereas the leukemia virus merely makes them reproduce themselves endlessly, as in cancer.

Other researchers have reported that the AIDS virus has striking similarities with another family of organisms, called visna virus, that causes slowly progressive neurological disease in sheep. A similar degeneration of the brain afflicts many AIDS patients in the later stages of the disease.

Original Reservoir

Gallo and some other scientists have speculated that the original reservoir for the virus in Africa before it infected humans was either monkeys or hoofed animals such as sheep and cattle.

How the virus may have gotten from animal to human is unknown. But several theories have been offered. Among them are transmittal through insect bites, or by exposure to virus-infected animal blood during sacrificial rituals.

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