Dr. Joan Chesney listened in stunned disbelief last Dec. 5 as a young doctor at Madison General Hospital in Wisconsin described his patient's puzzling symptoms -- a high fever, a sunburn-like rash, and blood pressure so low that it had caused kidney failure.
The 23-year-old woman's illness sounded identical to that of a teen-ager whom Chesney's husband, also a doctor, had been treating for several days. And on Dec. 4, Joan Chesney herself had seen a third, desperately ill patient with the same symptoms.
Within a few days of each other, all three -- healthy young women in their teens or 20s -- had been stricken with a disease that had started with vomiting and diarrhea and had rapidly brought them close to death. It could not be coincidence.
Then Chesney remembered an article she had read in a medical journal a year earlier, describing a strange new disease.
"Things clicked," Chesney recalled. " wrote a note to the (young doctor) saying, 'Do you think this could be toxic-shock syndrome?'"
The moment may have marked the medical community's first awareness of what has since become a national disease outbreak. Toxic-shock syndrome, a disease born in the mid-1970s, is a gripping medical mystery: an illness that in the past year has claimed increasing numbers of victims, virtually all of them female.
With the announcement last month that the disease had been linked to Rely tampons, and the removal of Rely from the market, many people were led to believe that the mystery was solved, the danger removed. They are wrong.
The search for the solution to toxic-shock syndrome continues. The risk remains, affecting all women who use tampons. The federal Center for Disease Control in Atlanta has now tallied 344 cases of the disease, 330 of them in women. Twenty-nine women died. So far, the center's total includes one case from the District of Columbia, eight from Maryland, and nine from Virginia.
The morning after her brainstorm, a Friday, Chesney called Dr. Jeffry Davis of the Wisconsin state health department to alert him to a possible outbreak of the formerly rare syndrome.
In the next few weeks, Davis tracked down four more Wisconsin cases. At the end of January, he contacted the federal center in Atlanta, the government agency that monitors and investigates health hazards and epidemics. So did a colleague in the Minnesota health department, where doctors had reported five similar cases.
In both states, most of the sick women had one thing in common: they were having their menstrual periods when they fell ill.
Thus began the nationwide medical search for the cause of toxic-shock syndrome. The disease's victims ranged in age from 12 to 52, but half of them were under 25. Their illness started with a high fever, vomiting, diarrhea and often headache and muscle pain. Within two days they developed shock and a sunburn-like rash that later peeled. Many had kidney failure, bleeding, and damage to other organs severe enough to require treatment in hospital intensive-care units.
The trail led disease detectives -- in Atlanta and in state health departments -- first to the discovery that tampon use somehow promoted the illness, then to the surprising finding that one brand of tampon, Procter and Gamble's Rely, was more dangerous than others. Their results prompted Procter and Gamble to withdraw the tampon from the market, and moved the U.S. Food and Drug Administration to make the Rely recall mandatory, propose warning labels for all tampon boxes, and order Rely's manufacturer to finance an unprecedented media campaign, scheduled to start today.
But the withdrawal of Rely tampons does not abolish the risk. The strain of bacteria responsible for the disease -- believed to be a new variety of staphylococcus germ, caused by a mutation -- has not yet been isolated.
Cases of toxic-shock syndrome has occurred in users of every brand of tampon. In some states, the majority of toxic-shock victims used brands other than Rely.
The Atlanta center's Toxic-Shock Task Force -- three dedicated young disease investigators, aided by about 25 statisticians, infection specialists and lab workers -- say they are seeking answers to a number of questions about the disease. For instance:
It is caused by as new strain of germ? Rare reports of an illness very similar to toxic-shock syndrome have appeared in medical journals since 1927. However, all the cases prior to about 1975 occurred in patients who had a definite infection of the skin, bone, or other organs caused by staphylococci (or "staph"). not until the mid-1970s did cases begin to appear in healthy young women during their menstrual periods.
This -- and the finding of staph as the predominant bacteria in the vaginas of most victims of the disease -- leads researchers to speculate that during the mid-1970s, the staph germs mutated in some way that made it possible for them to grow better in the vagina and produce the illness.
What is the role of tampons? Speculation has centered on the marketing of so-called "super-absorbent" tampons, starting with Rely in 1974 and followed over the next three years by other manufacturers' competitive products. These tampons contained a variety of new ingredients -- for instance, carboxymethylcellulose, rayon polyacrylate, and polyester fibers. Because the change in tampons coincides with the appearance of the illness in menstrating women, many have suggested that the new products were at fault, either because of the chemicals they contained or because women used them in a different way.
But the Atlanta researchers say that, apart from Rely, there is no proof that super-absorbent tampons are more risky than ordinary ones. Thus far, there is also no evidence that using smaller tampons or changing them more frequently offers any protection.
All tampons increase a woman's risk -- whether from promoting growth of the bacteria, abrading the skin of the vagina, weakening the woman's defenses against infection, or in some other way, no one knows.
Does the bacteria produce a chemical toxin that causes the shock and other symptoms? Most experts believe so, including Dr. James Todd, the University of Colorado pediatrician who discovered toxic-shock syndrome in 1978. One microbiologist, Patrick Schlievert at the University of California at Los Angeles, said he has isolated the toxin from the bacteria found in toxic-shock patients, and can reproduce the illness in animals injected with it. He has also found the toxin in staph cultured from toxic-shock patients, and says he can detect antibodies against it in the blood of patients who have recovered from the illness.
If Schlievert's toxin is responsible for the disease, researchers may be able to use it to produce a curative antiserum, or a vaccine to prevent the illness. But the CDC team is skeptical, pointing out that Schlievert's theory of how the toxin works is complex, and that the toxin is also found in most staph cultured from women who did not develop the illness.
"He may have found the toxin," said Dr. Kathryn Shand, head of the task force. "We just don't think he's proved that it's the toxin yet."
Why do only certain women get the disease? Shands said there are 70 million women of menstrual age in the United States, and more than 70 percent of them use tampons. Yet, she extimates that toxic-shock syndrome strikes only 10 to 15 out of every 100,000 women.
The researchers do not know why or how, in some women, the dangerous strain of staph is able to invade the vagina and become the predominant bacteria. They also believe it is possible that not all women fall ill when exposed to the germ.
"Who is the real population at risk here? It's not all women.It's not all women who wear tampons. It may be random -- but most things in nature are not random," said Dr. Bruce B. Dan, one of Shands' co-workers.
Other toxic-shock investigators are convinced that the stricken women have some other risk factor in addition to use of tampons. Michael Osterholm, a Minnesota epidemiologist, has designed a study with colleagues in Wisconsin and Iowa to compare the lifestyles of the victims to other women who stayed healthy. Besides tampons, their questionnaire includes such topics as sexual practices, bluejean styles, birth control methods and whirlpool baths.
The calls from Minnesota and Wisconsin last January were not the first news federal disease investigators had of toxic-shock syndrome, according to Shands. For several years, the center had received occasional reports of a strange illness whose victims developed vomiting, diarrhea, high fever, a rash, and a fall in blood pressure sometimes severe enough to cause shock and damage kidneys or other organs.One such patient was Stephanie Haley, the wife of a center epidemiologist, who became seriously ill on a Thanksgiving visit to Washington in 1977. But experts at the center speculated that her illness, and the others, had been caused by a virus.
Then in 1978, Todd published an article in a medical journel, describing seven cases of a new disease he called toxic-shock syndrome and suggesting that staph bacteria might be the cause. His patients were between 8 and 17 years old. Three were boys, and four were girls of menstrual age.
Researchers now believe that boys or men can get the disease only when they have an infection of the skin or other organs with staph. However, Todd did not investigate whether the girls' illnesses was connected with menstruation.
In retrospect, Haley's case and others have been identified as toxic-shock syndrome. Infection specialists at hospitals around the country are now convinced that they have been seeing women with the illness for several years without knowing what it was.
Dr. Mary Wilson, chief of the infectious disease division at Mt. Auburn Hospital in Cambridge, Mass., recalled looking up the records of two women she had treated in 1976, who received abdominal X-rays because they were having fever, vomiting, diarrhea and stomach pain.
In both cases, she said, "the radiologist's report just happened to comment that there was a tampon present."
When Shands, a pediatrician spending two years in the center's special pathogens branch, was assigned to toxic-shock, one of her first moves was to call Todd and ask whether he thought she was dealing with an epidemic. Todd thought not. He believed the case reports last January simply meant that more doctors were recognizing a disease that had been around for a while.
So the tall, bespectacled investigator, working with other experts, developed a written description of the disease and circulated it to several state health departments. By May, she had received reports of 55 cases from 13 states.
The center's weekly bulletin carried an article on the outbreak, and it prompted widespread publicity and a Congressional hearing. More case reports poured into the federal center in Atlanta.
In June, Wisconsin's Davis completed a study that proved the illness was linked to tampon use, and a CDC study reached the same conclusion. More publicity, more new cases. The center assigned two other doctors, Bruce Dan and George P. Schmid, to work with Shands. Dan nicknamed the trio "the tampon kings."
By mid-summer, the three investigators' findings had begun to suggest that the brand of tampon used might be important. But they weren't certain. So with the help of statistician Wally Schlech, they decided to question all 52 women who had fallen ill during July and August, and compare their pattern of tampon use with 150 women who had stayed well. They spent September 11, 12 and 13 on the telephone, calling the women. On Sunday, September 14, Dan stayed at the center, surrounded by data charts and computer printouts, tabulating the answers.
That evening, he called Shands and Schlech at home and said, "Why don't you come down here and look at this?"
They had found the Rely connection.
The next morning, Shands and the center's director, Dr. William H. Foege, flew to Washington to meet with Health and Human Services Secretary Patricia Harris, surgeon general Julius Richmond, and Food and Drug Administration commissioner Jere Goyan. On Tuesday they presented their results to tampon manufacturers -- first Procter and Gamble executives, then a large roomful of directors of other companies.
Procter and Gamble at first questioned the center's finding. But studies done by the Minnesota and Utah health departments also pointed to Rely. On Sept. 22, company executives called the center to say they would withdraw the product.
Despite the spotlight on Rely, the disease detectives have no idea why that particular tampon should be more risky than the others. Although its design is different -- it contains pieces of foam rather than fibers -- its chemical ingredients occurred in other tampons. As new toxic-shock cases continue to pour into the CDC, much about the disease remains a mystery.
Meanwhile, the three federal disease detectives have become media wizards. "The only thing that will get me excited now is to be in People magazine," Dan proclaimed last week. From 8 a.m. to 5 p.m., he said, the tampon kings and their assistants field hundreds of phone calls daily -- from doctors, tampon manufacturers, lawyers suing tampon manufacturers, worried tampon users, and people who have found The Answer.
At 5 p.m., according to Dan, they close the doors, ignore the phones, and get on with the work of tracking the disease. They are trying such tactics as feeding tampon ingredients to growing staph bacteria and seeing whether the chemicals promote illness in rabbits. They work until midnight or later, often seven days a week.
Only the most severe cases are accepted for study by the center. Shands says that there may be thousands of other women suffering milder episodes of toxic-shock -- fever, diarrhea, dizziness and a rash occurring during one or more menstrual periods.
Dan's favorite solution to the mystery so far came from a woman who called the center one day. "I know why all this happened," she said. "They finally found a tampon that worked."