Friday, December 20, 2002

BY KITTA MacPHERSON
Star-Ledger Staff

As he walked the corridors of one of the world's most famous cancer hospitals earlier this year, Kent Sepkowitz thought about smallpox vaccines and squirmed.

A physician who heads up infection control at the Memorial Sloan-Kettering Hospital in New York, Sepkowitz said he couldn't figure out how doctors and nurses could be vaccinated and then re-enter a world where nearly every patient lacked the requisite immune defenses to ward off infection.

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As federal health officials, prompted by bioterror concerns, gear up for next month's first mass smallpox vaccination campaign in 55 years, researchers like Sepkowitz are examining whether the current patient population can handle the coming public health campaign.

And they are urging caution.

Writing in a special edition of the New England Journal of Medicine released electronically yesterday a month before its scheduled publication date, Sepkowitz noted that much discussion has gone into debating the safety of the smallpox vaccine. However, the risk of getting infected by a person who has been vaccinated has been relatively ignored.

That's bad, he said, because much has changed since the last time.

"Everything good we have done in medicine in the past few decades has necessarily spawned a generation of independent, productive citizens who have chronic diseases," he said. It also means, he said, that from a public health standpoint, the biological landscape has been dramatically redrawn.

"Vaccination can be avoided," Sepkowitz said. "But contact with a recent vaccinee probably cannot."

Sepkowitz's work is part of a package of studies on the smallpox vaccine released by the New England Journal as the country is prepared to go to war against Iraq, known for using bioweapons, and just weeks before vaccination programs are to start nationwide. Among the papers are a Harvard School of Public Health survey showing that Americans are ill-informed about the disease and a Rand Corp. mathematical analysis detailing death rates from vaccines and smallpox that concludes that mass vaccination should only occur if people are sure a bioterror attack is imminent.

"Vaccination in the past was relatively easy as opposed to addressing all of the ramifications of being vaccinated today," said Clifton R. Lacy, New Jersey's commissioner for health and senior services. The state is planning to start vaccinating health workers in late January.

The smallpox vaccine does not contain the smallpox virus, known as variola, and cannot infect anyone with smallpox. Instead, the vaccine is made from a cousin of variola called "vaccinia," a live virus that stimulates the body's disease-fighting system, creating antibodies that protect the body from future viral invasions.

Smallpox is far more deadly than vaccinia.

There are other factors further complicating the picture, according to Lacy. Half the country has never been inoculated for smallpox and there is evidence that a person receiving a vaccination for the first time sheds more viral particles, increasing the possibility of infecting others.

Routine smallpox vaccination among the American public stopped in 1972 after the disease was wiped out in the United States.

Modern American society is filled with people susceptible to infection because of compromised immune systems, from AIDS, cancer, organ transplant and burn patients to those suffering from immune disorders like asthma and rheumatoid arthritis.

The effects of a vaccination program on such a population would not have been considered in 1947 during the last mass inoculations, because many people afflicted with such disorders would not have been alive to be vaccinated.

Information regarding secondary transmission -- the movement of the disease from someone who has been vaccinated -- is particularly important for hospitals, which will need to vaccinate workers while ensuring patients' safety. The composition of hospitalized patients in the 21st century, Sepkowitz said, is different from that of the mid-20th century.

Patients treated before the 1950s were very unlikely to be immuno-suppressed -- cancer chemotherapy was just beginning, transplantation had not yet been performed, HIV was unheard of and corticosteroid therapy had only recently been introduced.

Now, about 506,154 Americans are known to be living with HIV, 1.2 million new non-skin cancers are diagnosed annually, 2.1 million people have rheumatoid arthritis and receive immune-suppressing agents, and more than 14 million people have asthma, many of whom require intermittent steroid use.

The vaccine, drawn from old stockpiles, will be mandatory for about 500,000 military personnel and will be recommended for another half-million who work in emergency rooms and on special response teams. Government officials will make the vaccine available by late spring or summer to anyone else who would want it.

"The medical community is so unfamiliar with every aspect of this," Sepkowitz said. "Mistakes could happen because we're in a hurry. My view is that this is probably very safe, but we can't know. The only way is to proceed quite slowly."

In his own research, he scoured 50-year-old medical reports of children, packed eight to a room, who died of secondary transmission of vaccinia in hospital wards in Germany, Scotland, New York and Philadelphia. They were all being treated for skin problems, from eczema to burns.

It is still not clear to researchers whether the skin problems make people more susceptible to vaccinia or whether it means they are adept at transmitting the sickness to others.

Government health officials as well as hospital planners are designing ways, Sepkowitz said, to monitor vaccinated health care workers so that the disease cannot be spread. Physicians and nurses may have to stay away from patients with depressed immune systems or skin rashes for weeks until they are no longer infectious. Vaccination lesions may have to be monitored daily by experts stationed at the entrance to hospitals.

"We need to tip-toe our way toward this, watching our every step," Sepkowitz said.