By SUSAN ASCHOFF, Times Staff Writer
Unexpected side effects of the vaccine have weakened enthusiasm for mass inoculations as protection against bioterrorism.
DELAND - Called to serve during the Iraq war, Florida National Guardsman Lloyd Clements Jr. had been on active duty only days when he slumped over the steering wheel of a truck.
Clements had suffered a fatal heart attack.
His death, and that of a nurse's aide in St. Petersburg and a nurse in Maryland, all within one week in March, occurred after they had received smallpox vaccinations. The three had cardiovascular disease, medical investigators found. The smallpox vaccine was not to blame.
But the deaths dealt a blow to the U.S. government's $600-million plan to defend against a bioterror threat by vaccinating a million soldiers and health care workers. President Bush announced the program in December 2002. By March, 350,000 military personnel and 25,000 health care workers had been vaccinated.
When three people died, federal health officials changed who should get the vaccination. Next month, they will meet to talk about what will happen with smallpox vaccinations in 2004.
"We think this program is over," says Dr. William Schaffner of Vanderbilt University, a participant in the discussions.
The vaccination campaign has struggled from the beginning. A hundred hospitals opted out, many for practical reasons: Managers feared that vaccinated employees would become sick and leave them short-staffed. Health care unions advised their members to wait until Congress passed provisions for compensation in case something went wrong.
This summer, the Institute of Medicine, an independent, nonprofit organization that reviews health and science issues, said the vaccine should not be given to the public.
"It does not make sense to give a vaccine with substantial risks against a disease that does not exist," advisory committee chairman Dr. Brian Strom of the University of Pennsylvania School of Medicine had cautioned earlier.
"In fact, that could be considered unethical."
New motto: Be prepared
Soon after the nation marked the one-year anniversary of the Sept. 11 terrorist attacks, the medical community received a preparedness plan of its own from the Centers for Disease Control and Prevention. Called a "logistical blueprint on how to conduct mass vaccination," it described how the entire U.S. population could be immunized against smallpox in 10 days. Thousands of grocery stores, post offices, shopping malls and schools would be sites for inoculation against a disease not seen in the United States in 50 years.
A single case of smallpox, the experts said, would herald a bioterror attack.
Intelligence reports said Saddam Hussein had the lethal virus and could unleash it on U.S. troops in the Iraqi desert. A terrorist purposely infected could move through a crowded subway station and spread it in the United States.
Up to a third of those who get smallpox die. There is no cure.
The smallpox vaccine carries risks of its own: Death, albeit rare, is one of its potential complications. It contains a live virus, vaccinia. The virus is introduced through a two-pronged needle and multiple pricks through the skin of the upper arm. The recipient's body responds by producing antibodies and T-cells to fight the virus. These defenders then stand ready, if needed, to fight off smallpox.
But the inoculation can make people sick. Severe reactions, from encephalitis to blindness, occur in one of every 20,000 to 70,000 people vaccinated. One or two in a million die.
In June 2002, the Advisory Committee on Immunization Practices, 15 experts selected to make recommendations at CDC on all immunizations, initially advised vaccinating only medical teams at select sites, or about 15,000 people. An alternative plan, reportedly backed by Vice President Dick Cheney, called for vaccinating more than 10-million health care workers, emergency medical technicians and law enforcement officers in addition to the military. Neither plan called for vaccinating the public.
President Bush opted for the second approach with far greater numbers, citing national security concerns. He announced the program Dec. 13 and was one of the first to be vaccinated.
"President Bush was quite courageous in making this decision despite people telling him to wait," said Dr. David McKalip, a St. Petersburg neurosurgeon who lobbied for the plan and serves on the St. Petersburg Metropolitan Medical Response System.
The vaccination blueprint had three phases. In Phase 1, almost a half-million military personnel and a half-million volunteer health care workers would be vaccinated. Phase 2 would include as many as 10-million so-called first-responders: EMTs, police officers, sheriff's deputies and firefighters. Phase 3 would be vaccination of the public.
Health and Human Services Secretary Tommy Thompson ordered 300-million doses of vaccine, so all Americans "could know they have their name on a vaccine shot in our inventory."
Unleash the antibodies
As recently as 1967, 10-million to 15-million people in 43 countries got smallpox, and up to 3-million died. The disease's virulence led to the practice of trying to immunize whole populations.
In the United States, all toddlers received a smallpox vaccination.
"This was considered to be a very safe procedure," says Dr. Herbert Pomerance, a professor of pediatrics at the University of South Florida. No one was bandaged, no warnings on side effects were distributed, no consent forms were signed. In 1947, when a man died of smallpox in New York after visiting Mexico, Pomerance, now 85, helped vaccinate more than 5-million people in two weeks.
In 1966, the United Nations' World Health Organization announced a campaign to eradicate smallpox.
The challenge was to protect more people than there were vaccine and workers to administer it. The breakthrough came in a technique called "ring" vaccination: If workers could encircle an area where there was an outbreak, prevent movement in and out, and vaccinate everyone within, the disease's spread could be stopped.
By 1980, smallpox was declared extinct. The virus lived only in laboratories in the United States and the Soviet Union. Intelligence experts believe it has since been acquired by others.
The uncertainty of who has it and who may use it makes mass vaccination in advance prudent, the Bush administration says.
There will be enough time after an outbreak, others say. The speedy containment of smallpox in New York City in the '40s and the WHO's success with ring vaccination prove that the best strategy is not vaccinations for everyone now but for the exposed when.
"Smallpox does not spread nearly as effectively as chicken pox and measles," says Dr. Parker Small, an emeritus professor of pathology and pediatrics at the University of Florida College of Medicine. Prolonged face-to-face contact is usually required. After exposure, an individual has four to seven days to be vaccinated, he says.
"The real value of mass vaccination," Small says, "is to decrease the clamor."
Ready to serve
When Cindy Clements' husband was activated on the eve of the war in Iraq, she knew he might be sent overseas and shot.
A week after his departure, as she shopped for groceries at a Publix in DeLand, she got a call telling her he had suffered a heart attack.
Sgt. 1st Class Lloyd Clements, a 55-year-old mechanic, had been deployed to El Paso, Texas, with a 265th Air Defense Artillery unit out of Palatka. He had been called to active duty stateside during the 1991 Persian Gulf War and after the Sept. 11 attacks.
"I think he was so proud to serve the country," his wife says.
"I know what you need," she told her comatose husband, "and I'm going to take care of it."
His breathing tube was removed.
The Clements family did not know that his March 26 death was the third from a heart attack in less than a week among people recently vaccinated against smallpox.
In Maryland, Andrea Deerheart Cornitcher died March 23.
Cornitcher, a nurse, told her husband she wanted to get the smallpox vaccination to help people, the Baltimore Sun reported. She said she liked the irony that she might save others from the fate of her American Indian ancestors, who died in the 1700s of smallpox contracted from germ-laden blankets given to them by white men seeking to wipe out their tribes.
Several days after Cornitcher, 55, received the vaccination, she began vomiting. She thought it was food poisoning. Her friends found her dead in bed the next day.
In St. Petersburg, a nurse's aide at Northside Hospital & Heart Institute collapsed while helping her husband deliver the St. Petersburg Times. Virginia Jorgensen, 57, had a heart attack two weeks after receiving the vaccine. She was in a coma for 10 days, then died the same day as Clements, after her family also removed life support.
"She'd been a nurse most of her life. She thought she could help people if she got the vaccine," says her husband, Robert Jorgensen.
His wife was "so stubborn," he says. "I told her only fools volunteer."
"I have her death certificate in front of me," says Jorgensen's son, Everett Vance of Kenneth City. "To me, it should have been put in there: Due to vaccination. They're just trying to run circles around it."
Autopsies revealed that the three who died had pre-existing cardiovascular disease. Definitive answers will require more research, but investigators say the deaths were coincidental to the vaccination.
"We've reached the conclusion that your risk of a heart attack is the same whether you're vaccinated or not," says Col. John D. Grabenstein, deputy director for military vaccines for the Army's surgeon general.
Heart as unintended target
After Clements died, Florida, New York and several other states suspended all smallpox vaccinations, citing the possible link between the vaccine and heart attacks. Members of the Advisory Committee on Immunization Practices talked by phone March 28 in an emergency session.
Suspension of the program or overly broad exclusions - one proposal would have barred anyone age 50 or older from getting the vaccine - would all but doom the vaccination effort, committee members decided. Instead, they recommended, and the CDC agreed, to exclude people with heart conditions and people who had three or more known cardiac risk factors, including high blood pressure or cholesterol, diabetes, use of tobacco or an immediate family member who had heart problems before age 50.
The CDC added another caution: Several dozen cases of heart inflammation had been reported after vaccination. Inflammation of the heart membrane (pericarditis), muscle (myocarditis) or both appeared particularly prevalent in those being vaccinated for the first time, typically men and women in their 20s and 30s. Some were too ill to return to work. In about half of all cases of myocarditis, the heart is permanently damaged, says Dr. Vibhuti Singh, director of cardiology at Bayfront Medical Center in St. Petersburg.
Heart attacks and heart inflammation are different diseases. But a possible link between the vaccine and heart problems took experts by surprise.
"The deaths did cause everyone to say, "Wait, what's going on,' " says Dr. John Sinnott, director of infectious and tropical diseases at Tampa General Hospital.
He says there is an "evidentiary chain" that cannot be ignored: A person who has cardiovascular issues could suffer a heart attack after receiving the vaccine because his weakened cardiovascular system cannot deal with vaccine-induced inflammation.
"Did it cause a heart attack? No. Did it contribute to the cause of death? Yes."
Rethinking the bioterror drill
On Aug. 12, the Institute of Medicine recommended that smallpox vaccinations not be given to the public - Phase 3 of the now-foundering blueprint - because of concerns about side effects.
Officials had anticipated one or two deaths from known side effects: encephalitis, pox or other complications.
What officials did not expect were heart problems. More than 60 cases of heart inflammation and more than a dozen cases of angina and heart attack had been reported by summer's end.
The Department of Defense and the CDC continue to report that the association between the vaccine and heart problems is unclear. Soldiers, health care workers and some law enforcement officers and firefighters continue to get vaccinations. Vaccination suspensions in Florida and other states lasted only a day or two. Candidates are screened for risk factors that, since March, include cardiovascular health.
More than 480,000 military personnel and 38,000 civilians have received the vaccination. In Florida, where plans called for 35,000 health care workers to be vaccinated by spring, 3,930 had been vaccinated as of early October.
The pace was significantly slower than planned. The vaccination blueprint has proved to be a tough sell.
With the lower numbers, the advisory committee suggested that "SWAT" teams of the vaccinated be readied to inoculate their colleagues and the public if smallpox resurfaces. "At this time, the (Advisory Committee on Immunization Practices) feels it is unwise to expand beyond (vaccinating medical teams) because of the new and unanticipated safety concerns, such as myopericarditis, whose extent and severity . . . are not yet known."
Next month, the CDC is expected to make its recommendation on what to do next year in light of reduced numbers of vaccinees.
"The general public should be able to go to their primary care doctor for the vaccine. Even better, I'd like to see public service announcements" encouraging them to do so, says Dr. McKalip of St. Petersburg. He was vaccinated and says he wants his wife and children protected as well.
"If it's safe enough for the government to require it" for everyone through the 1960s, "then it's safe enough now."
No fatalities in connection with the program have been reported since the deaths of Clements, Jorgensen and Cornitcher.
No one knows if smallpox as a weapon of terror exists.
"How do you decide what risks and benefits are?" says Dr. Kathy Edwards of Vanderbilt Medical Center. "If you lived next door to the World Trade Center, your perception would be a lot different. Risks are personal.
"It's not one in a million.
"It's yes. Or no."* * *
May 14, 1796 - Edward Jenner administers first smallpox vaccination, to 8-year-old boy in Gloucester, England.
1947 - Smallpox outbreak in New York City sparks mass vaccination of nearly eight in 10 residents.
1949 - Last smallpox case in the United States reported in Elsa, Texas.
1966 - United Nations' World Health Organization announces its goal to eradicate smallpox worldwide.
1977 - Last naturally occurring case of smallpox reported, in a hospital cook in Somalia.
1980 - Health officials declare smallpox eradicated.
2000 - Centers for Disease Control and Prevention contracts with Acambis of Cambridge, Mass., for 40-million doses of smallpox vaccine to supplement estimated 15.4-million doses on hand.
Sept. 11, 2001 - Terrorists hijack four planes and crash into World Trade Center, Pentagon and Pennsylvania field.
June 20, 2002 - Advisory Committee on Immunization Practices recommends vaccination of a limited number of health care workers and workers who respond first to emergencies.
July 2002 - About 100-million, or 160-million diluted, doses of smallpox vaccine are available.
Dec. 13, 2002 - President Bush announces vaccination plan, saying "regimes hostile to the United States" may possess the smallpox virus; Department of Defense begins vaccinating military personnel.
Jan. 24, 2003 - State vaccinations of health care workers begin.
February 2003 - Department of Defense reports first case of heart inflammation (myo- or pericarditis) after smallpox vaccination.
March 23, 2003 - Andrea Deerheart Cornitcher, a nurse in Maryland, dies of a heart attack suffered after vaccination.
March 26, 2003 - National Guardsman Lloyd Clements Jr. of DeLand and nurse's aide Virginia Jorgensen of St. Petersburg die of heart attacks suffered after vaccinations.
March 28, 2003 - The CDC revises guidelines for vaccination to exclude anyone with heart disease and anyone with multiple cardiovascular risk factors; study shows diluted vaccine retains potency, so supply can be stretched.
Aug. 12, 2003 - Institute of Medicine recommends public not be vaccinated, citing continuing questions about health risks.
Sept. 18, 2003 - Associated Press and other media report that American scientists assigned to weapons hunt in Iraq found no evidence of smallpox virus.
- SOURCES: Centers for Disease Control and Prevention, Department of Health and Human Services, New York Times, Washington Post, Baltimore Sun, St. Petersburg Times files.