Successful hepatitis A vaccine debuts.

Each year, some 30,000 cases of hepatitis A surface in the United States. Though this viral infection tends to be fairly benign, the liver inflammation it causes cannot be taken lightly: It claims roughly 100 lives annually.

The virus typically spreads by contaminated food and water. Public health officials combat it with water chlorination, sewage treatment, educational campaigns for good hygiene (such as hand washing), and the administration of immune globulin (antibodies harvested from survivors of the disease). Researchers now announce the development of a far more potent weapon: a safe and highly effective vaccine.

Though hepatitis A tends to crop up in sporadic outbreaks, one community of Hasidic Jews in Brooklyn has been plagued for years with a small, seemingly intractable annual recurrence of infection, especially among families with toddlers. So when David Nalin and his co-workers at Merck Sharp & Dohme Research Laboratories in West Point, Pa., were ready to test the efficacy of their new hepatitis A vaccine, they decided to focus on children in Kiryas Joel, a Hasidic community in Monroe, N.Y. Many residents of the hepatitis-plagued Brooklyn community regularly spend their summers at this resort in the lower Catskill Mountains.

"It was virtually certain that the start of summer vacation in late June would bring the virus up [to Monroe] with children from that community in Brooklyn," explains Nalin. Working with Kiryas Joel pediatrician Alan Werzberger, Nalin's team identified 1,037 Hasidic children who were full-time residents of the Monroe community and who had no previous exposure to hepatitis A. Beginning in June 1991, Werzberger's staff gave each child an intramuscular injection; half the children received the new vaccine, while half received a placebo.

Because the disease has a latency period of two to three months, the researchers could judge vaccine efficacy only by cases of clinical disease that appeared 50 or more days after the inoculations. In "one of the shortest vaccine efficacy trials in history," Nailin says, the investigators broke the codes identifying the vaccine and placebo groups after a little more than five months. The data showed that all 25 cases of hepatitis A occurring 50 or more days after treatment occurred in children who received the placebo, the team reports in the Aug. 13 NEW ENGLAND JOURNAL OF MEDICINE.

Seven cases of hepatitis did appear among vaccinated children, but only within 18 days after inoculation. Nalin interprets the trial to mean that "at least as early as day 21 - and probably before that-the vaccine was 100 percent protective."

The data also suggest that this or related chemically inactivated (killed-virus) vaccines now under development may reduce or eliminate clinical symptoms in many persons who receive their inoculations shortly after becoming infected with the hepatitis A virus, says Leslye D. Johnson, chief of the enteric diseases branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Moreover, she notes, "because you don't have [asymptomatic] carriers of this disease as you do with hepatitis B and C, the only real reservoir [of the virus] is going to be people in the acute phase of infection." The result? Johnson says it is now possible to envision eradication hepatitis A - as smallpox was once eliminated - through a program of worldwide immunization.

Data from this trial and unpublished results from an ongoing study conducted by SmithKline Beecham with children in Thailand suggest "it is likely that the levels of antibody developing after a complete series of three immunizations will lead to protection for at least five to 10 years," asserts Stanley M. Lemon of the University of North Carolina School of Medicine in Chapel Hill, in an editorial in the June HEPATOLOGY. That's much longer than the four to six months of protection afforded by immune globulin, Johnson notes.

Nalin adds that controlled studies performed for Merck in Israel "showed that [injections of] immune globulin caused more pain and local irritation than did the vaccine." Moreover, unlike immune globulin, the vaccine is not derived from blood, so the new immunizations pose no risk of transmitting pathogenic viruses that may have contaminated a donor's blood.

Indeed, Johnson concludes, the new vaccine represents "the first major advance" in hepatitis A prevention in more than 50 years.

Merck plans to submit its vaccine data to the Food and Drug Administration this year. Nalin predicts the vaccine will become commercially available "certainly by 1994."