AIDS relative endemic in Japan

By William Wetherall

A version of this article appeared in
The Japan Times, 10 May 1987, page 10

French and American scientists discovered the AIDS virus as quickly as they did in 1983 and 1984 because, like Newton, they were "standing upon the shoulders of Giants" -- the Japanese and American researchers who, in the late 1970s and early 1980s, had found the causes of an infectious cancer called ATL, or adult T-cell leukemia.

The incidence of ATL is high in parts of Japan where the virus causing the disease may have been endemic since antiquity. And ATL may hasten AIDS when the related viruses coexist.

ATL begins when a virus called HTLV-1 (human T-cell lymphotropic virus) attacks white blood cells, known as T lymphocytes, and causes them to proliferate malignantly.

Just the opposite occurs in AIDS. The most common AIDS virus -- called LAV (lymphadenopathy-associated virus) by the French, HTLV-3 by the Americans, and HIV-1 (human immunodeficiency virus) by the International Committee on the Taxonomy of Viruses -- kills T4 white blood cells, which are crucial to the immune system. As the immune system is disabled, the body becomes vulnerable to other infections.

ATL is endemic to several parts of Japan, in Haiti and Jamaica in the Caribbean, and possibly in New Guinea. It is common in the north of South America, which faces the Caribbean, and in parts of Africa. And some cases are known in most other areas where data is available.

Statistics on ATL incidence are confusing. Most reports claim that about one million people in Japan are carrying the virus. One says that carriers are increasing at the rate of 40,000 each year. A second states that each year 200 or 300 people develop symptoms, and a third observes that one in 2,000 carriers are stricken every year.

Once the malignancy begins, death comes quickly. The course of the disease can run from one month to over six years. One report puts the median survival from time of diagnosis to death at 4.4 months. This means that 50 percent of all patients die within five months. Practically all of the rest die within two years.

Like the AIDS viruses, the ATL virus is spread primarily through blood, intimate contact, and congenital infection -- in other words, contaminated blood transfusions, needle sharing by drug addicts, homosexual or heterosexual contact, infection in the womb of mothers who harbor the virus, and milk from an infected mother's breast.

There are also reports that the ATL virus can be carried by mosquitoes, though infection by mosquitoes must be extremely rare. An article in a recent issue of the American journal Futurist forecast that, by December 1989 it will be discovered that AIDS, too, can be spread by mosquitoes.

In Japan, the main route of ATL infection may be from mother to child during breast feeding, but also from husband to wife over the years of their sexual relationship. The latency period is long -- 40 or more years - and most patients are between the ages of 40 and 60.

In order to prevent the spread of this infectious blood cancer, Japan began to screen all blood for the presence of HTLV-1 antibodies in November 1986, along with screening for AIDS antibodies. And female ATL carriers are being counseled not to breast feed.

Earliest reports described ATL as endemic mainly in Kyushu and Okinawa. On the basis of these, Robert Gall, at the National Cancer Institute in the United States, suggested that 16th-century Portuguese traders may have brought the ATL virus to Japan in their African slaves or monkeys. (Scientific American, December 1986; Eizu e no chosen, Bessatsu Saiensu 81, march 1987).

Kyoto University virologist Yorio Hinuma thinks differently. Hinuma reports that about 8 percent of the populations of Kyushu and Okinawa are carriers of the ATL virus, compared with from 0.3 percent to 1.2 percent for the rest of Japan. From Hokkaido to Okinawa, the rates are highest for isolated coastal areas and remote islands, not cities.

Relatively high rates of ATL are found in the region west of the Hidaka range in Hokkaido (apparently among Ainu Japanese); the Sanriku coast of Iwate; Tobishima off the coast of Yamagata; the Oki islands off Shimane; the tip of Kii Peninsula in Wakayama; Muroto and Ashizuri points in Kochi; Uwajima in Ehime; Iki and Tsushima islands in the Korean straits; the Goto islands near Nagasaki; and Okinawa.

Neighboring Korea and China seem to have very few ATL carriers.

Hinuma speculates that Japan was first occupied by "native old mongoloid carriers," whose gene pools became diluted about two millennia ago by the continental ,Yamato new mongoloid noncarriers" who came to Japan via Korea and settled primarily in the interior of Honshu, centering on Nara and Kyoto. (Chuo koron, March 1986)

Studies comparing the immunological traits of dogs, field mice, and people in Japan and the rest of Asia, seem to support the theory that Central Asians recently settled in the heart of Japan, and that even today, genetic mixture is less complete to the south and north.

In 1985, Hinuma shared a major cancer award with Gallo and compatriot researchers Isao Miyoshi and Kiyoshi Takatsuki. Takatsuki was the first to describe ATL, then known as Takatsuki disease, later called new leukemia. Miyoshi was the first to culture ATL cells, and Hinuma further described the first human retrovirus which Gallo had isolated in 1978 and named HTLV-1 by 1979. (Bungei shunju, special issue, April 1987)

Luc Montagnier of the Pasteur Institute was the first to isolate the main AIDS virus from a patient in 1983. A year later, Gallo more definitively described what turned out to be the same virus, resulting in conflicting claims of discovery which have since been resolved.

Double infections of ATL and AIDS are increasing in the United States. At a medical conference held in Tokyo this April, Gallo reported that 50 percent of all black AIDS victims in New York, most of whom had become infected through intravenous drug injections, were also ATL carriers. This was twice the double infection rate of 27 percent in 1982.

In Japan, also, doubly infected patients are said to be developing AIDS symptoms faster. Japanese researchers have also reported that the AIDS virus reproduces more rapidly in a lymphocyte already infected with the ATL virus. Other Japanese investigators have found some ATL patients who test negative for HTLV-1 antibodies and show no trace of the virus, which suggests that the blood cancer may also be caused by nonviral agents.

Whatever the relationship between AIDS and ATL, both are spreading in Japan through essentially the same kinds of infection routes. And both are fatal. One consolation is that AIDS has been entering mainly urban populations, while most ATL carriers are found in rural areas.

But unless preventive measures are adopted by all people who risk exposure to either disease, it is only a matter of time before the two converge and the double infection rate increases. And if true that the ATL virus reserves a commensal seat for AIDS and reduces its incubation period, then AIDS mortality in Japan will be higher than it would be without ATL.