A Vaccine That Comes Up Short : Drugs: Safe products were available abroad, but Japan wanted to develop its own. Deaths and illness have resulted.

Four years ago, Kyoko Kawabe took her 17-month-old son to the doctor for what was supposed to be a routine vaccination. A few weeks later, he had high fevers and convulsions diagnosed as meningitis. After three weeks in the hospital, the meningitis seemed cured, but the weakened toddler died of pneumonia.

“They took a healthy boy and gave him a shot of poison,” said Kawabe.

The same “poison” changed Hideo Ueno’s life when his daughter Hana received the vaccination three years ago before her second birthday. She also contracted encephalitis--a brain infection that can be fatal or cause serious paralysis. The child survived, but she is partially paralyzed and cannot speak.

The family has moved to be close to the hospital and Ueno’s wife has quit her job to devote herself full time to taking care of Hana.

The two families are among many who have become victims of a disastrous government effort to support Japan’s pharmaceuticals industry. Although safe products were already available in the United States and Europe, the government, industry and academic elite banded together to develop a Japanese vaccine and promote its use based in large part on safety studies of a similar, but not identical, vaccine made by Rahway, N.J.-based Merck & Co. and other drug companies.

In fact, the Japanese called their vaccine MMR, a Merck trademark. Studies showed that the Merck product has been used to inoculate more than 100 million children, with no confirmed cases of serious side effects.

Last week, following reports of abnormally high levels of disease among children who were given the Japanese vaccine to prevent measles, mumps and rubella, Japan’s Ministry of Health and Welfare halted its use.

The issue has drawn attention in Japan because of charges that the government continued to promote the vaccine long after its dangers had become clear. What has yet to be reported is that the government promoted the development and use of the risky vaccine even though it knew a better alternative had been available overseas since 1975.

As part of a broader, nationalistic effort to promote its still- weak pharmaceuticals companies, Japan wanted its own domestically produced version of MMR.

“Rather than use foreign products, we wanted Japanese products because they are of better quality,” said a woman who answered the phone at the Assn. of Biologicals Manufacturers and declined to be identified.

It is not the first time Japanese policy aimed at supporting domestic drug companies has had dreadful public health consequences. Antibiotics, for example, are one of the few areas in which Japanese pharmaceutical companies are strong. Critics say the companies have made huge sums of money by making it profitable for doctors to overprescribe antibiotics.

The vaccine story began in 1988, when the Ministry of Health and Welfare called together Japan’s three largest vaccine manufacturers. In an effort to speed development and avoid unnecessary competition, the government told the three companies to take the one best strain produced by each company and combine them to produce a single unified MMR vaccine to be used in a nationwide compulsory immunization program. Takeda Chemical Industries, Japan’s largest drug company, provided its vaccine for rubella (German measles), for example, while Tanabe Seiyaku offered its mumps vaccine.

“We wanted to produce the safest possible vaccine,” said Hiroshi Maruyama of the Ministry of Health and Welfare’s Office of Infectious Disease Control. Maruyama said no foreign vaccine was considered because there was no vaccine that had been approved for use in Japan at the time.

Within a year, the vaccine had been tested on 313 people. Based on these clinical tests and the experience of similar vaccines used overseas, the Ministry of Health and Welfare said it expected no more than one in 100,000 inoculated children to show side effects. By referring to the safety of MMR vaccines used overseas in its studies, the Japanese companies implied that their products were virtually the same as the foreign products.

Shigeyoshi Nakata, a pediatrician at Hannan Central Hospital, recalls being very excited. “We had been waiting for a long time for it to be available; we knew the vaccine had a good record in America,” he said.

Nakata said he heavily promoted the use of the vaccine in the city’s immunization program.

But within a few months, Nakata was having second thoughts. Over the course of a few weeks, he had three patients come to him with meningitis, a serious infection of the membranes that envelop the brain and spinal cord.

“It got to the point where if a child came to me with meningitis, I knew they had recently been vaccinated,” Nakata recalled. Both meningitis and encephalitis are related to the mumps virus.

In October, 1989, six months after the start of the mandatory immunization program, the Japanese government admitted that the incidence of side effects was 100 times higher than initially expected. A warning was sent out to physicians mentioning the danger of side effects. The vaccine was made voluntary rather than mandatory.

Nakata wrote an article in January, 1990, that quoted studies showing that in some towns there were as many as 31 cases of meningitis from a population of 12,500 children vaccinated--one in 400. He called on the government to stop the use of the vaccine completely. Nakata said his calls and others were ignored because drug companies were afraid of losing the estimated $45 million in annual sales from the vaccine.

Although at least one American drug company contacted the Ministry of Health and Welfare offering its own, far safer, vaccine for use in Japan if the ministry would speed up the approval process, talks made little progress. Foreign companies have long complained of the overly cumbersome process for approving drugs already in widespread use elsewhere in the world.

Instead, the medical community sought to reassure doctors that the Japanese vaccine was still preferable to none at all.

“It was a question of balancing risks,” said Maruyama of the Office of Infectious Disease Control. “Where do you draw the line?”

As the problems associated with the Japanese vaccine continued to mount, the Japanese Ministry of Health and Welfare made an odd decision.

In October, 1991, it decided to allow the various drug companies to market their own versions of the vaccine.

Not surprisingly, the vaccines produced separately by the Japanese companies were no better.

“We didn’t have much experience with combining different vaccines,” said Shoji Kinoshita, a spokesman for Takeda Pharmaceuticals. “We have learned how difficult this is to do.”

It was a lesson learned at the expense of families like the Uenos and the Kawabes and at the expense of public health.

“If they had stopped a little earlier this wouldn’t have happened to Hana,” Ueno said of her lifeless daughter.

The government recognized that the vaccine caused the brain damage in the Ueno child and agreed to pay medical costs and a monthly stipend to help support the child. But the Kawabe family received only the cost of medical care after the government concluded that the illness was related to the vaccine but the death was caused by something else.

The government has recognized two other child deaths as resulting from the vaccine and awarded the families roughly $160,000 each.