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Like most 14-year-old girls, Natalie Morton probably didn't spend too much time worrying about cervical cancer. But along with all of her female classmates at the Blue Coat Church of England School in Coventry, she received a vaccine on Sept. 28 designed to protect her from the disease. Within a few hours, she was dead.

Amid the ensuing media bonanza, local health officials immediately announced a "full and urgent" investigation into Morton's death and ordered a batch of the vaccine to be withheld as a precaution. Less than a day later, a preliminary postmortem examination found that the vaccine was unlikely to have killed Morton and blamed instead a "serious underlying medical condition." Still, as many Western nations are about to begin massive inoculation programs against the H1N1 influenza, Morton's death underlines the cruel reality behind any vaccination campaign: there's always the risk that a small number of vaccine recipients will suffer an adverse reaction — and that it sometimes can be deadly.

"You can never ensure a vaccine is completely safe," says Hugh Pennington, an emeritus professor of virology at the University of Aberdeen in Scotland. "Clinical trials are on the magnitude of thousands and can screen out common and mild reactions for the vaccine — fever and sore arms mostly. But if a vaccine causes a severe reaction in one in a million people, there's no way to test for that."

Morton died after receiving GlaxoSmithKline's Cervarix, one of two vaccines designed to protect women from the human papillomavirus (HPV), a sexually transmitted infection linked to most cervical cancers. (American women receive Gardasil, an HPV vaccine manufactured by Merck.) Introduced last year, Cervarix is expected to cut deaths from cervical cancer in Britain by about 75% — or 650 deaths a year. So far, the vaccine has been given to 1.4 million women in Britain, and Morton's death is the first to be possibly linked to the shot. But there have also been less serious side effects in recipients. Britain's Medicines and Healthcare Products Regulatory Agency has recorded more than 2,000 suspected reactions to the vaccine since April 2008, although the most commonly reported reactions of soreness, fainting and nausea may be a result of the act of injection rather than the vaccine itself.

Given the risks of mass vaccination, the decision to launch a program can be fraught. According to Jacob Weisberg's book The Bush Tragedy, President George W. Bush and Vice President Dick Cheney were split in 2002 over whether to administer a nationwide smallpox vaccination program in the U.S. Cheney said that doing so would be a prudent counterterrorism step. Bush overruled him because the program could have resulted in dozens of deaths. (Statistical analysis has shown that the smallpox vaccine kills between one and two people per million inoculated.) Health officials don't always get the decision right. In March 1976, the U.S. government ordered a mass vaccination program against a swine flu virus they feared would cause a pandemic. Within weeks, reports surfaced of people developing Guillain-Barré syndrome, a paralyzing nerve disease that can be caused by the vaccine. More than 30 people eventually died of the condition. Facing protests, federal officials abruptly canceled the program in December.

But conclusively linking deaths to a vaccine can be difficult, Pennington says, pointing out that there is still debate among experts as to how many of the 1976 Guillain-Barré deaths were actually caused by the vaccine. For this reason, health officials fear that adverse reactions in vaccine recipients can make the already difficult job of convincing healthy people to receive inoculations even more challenging. For whatever reason, people tend to fear vaccines more than other medicines. This has been the case since the first vaccinations were given to prevent a spread of smallpox in England in the late 18th century. That vaccine used bovine ingredients (the word vaccine comes from the Latin word for cow, vacca) and people feared the injections would turn them into cows.

"The oft-cited example is concern over an autism link with the [measles, mumps and rubella] vaccine," Pennington says. "In America, high uptake of the vaccine led to the eradication of measles. But in Europe, enough parents refused to let their children have the vaccine that it gave the virus a home to circulate and continue to infect people."

As there is currently not enough H1N1 vaccine to inoculate all Americans, officials are worried that frontline health workers, who should be among the first in line for the injections, might refuse over safety concerns. That could compromise health workers' ability to treat patients who are hospitalized with the disease. A study of 11 focus groups conducted in Canada prior to the H1N1 outbreak found that health-care workers might refuse to immunize their children and themselves if they believed the risks of a new vaccine outweighed the benefits, according to a report in the Emergency Health Threats Journal in August. Another study published last month in the online edition of the British Medical Journal found that less than half of Hong Kong's health-care workers said they intended to receive a H1N1 influenza vaccine.

• Eben Harrell / London
• The recent death of a 14-year-old British girl who received a cervical-cancer vaccine has renewed concern over the risks associated with inoculations. But is fear of the injections warranted, or is it just paranoia?