Finally the Culprit: Cheese : A Doctor’s Hunch Breaks Open the Listeriosis Case

Strawberries were an early suspect. For medical experts investigating the deadly outbreak of Listeria monocytogenes, the strawberry-as-villain theory made some sense: they were often eaten raw; they could be contaminated from manure used as fertilizer. Moreover, strawberries had been responsible for a previous epidemic in Connecticut.

There were other theories. One suggested that water might be the culprit. Another speculated that the disease might be limited to certain neighborhoods, a conjecture that set off a hasty search for the ZIP codes of all known victims.

In the end, a brainstorming session at County-USC Medical Center produced the theory containing the answer to the epidemic that has killed at least 28 people in California. Dr. Peter Heseltine, an epidemiologist at the hospital, suggested to investigators from the U.S. Centers for Disease Control in Atlanta that they might look into fresh Mexican cheese.

Heseltine is now out of the country, but a colleague at the hospital, Dr. John Leedom, described the meeting:

“Peter grew up in Latin America and he loves Latin food himself. He also knew two things: that there had been a milk-borne epidemic of Listeria just recently in Massachusetts, and that we were seeing a lot of Latino victims.

“Peter said, ‘Well, one of the things Latinos really like is the fresh cheese. You might take a look at that.’ ”

At the time, fresh cheese was just another theory, another check-mark on a long list of possibilities in an investigation that ultimately would require all the resources available to the modern medical sleuth. Solving the mystery would require computers, a little luck and, most important, an enormous amount of what one official would later call “shoe leather epidemiology.”

Over the course of two months, the painstaking process would put enormous pressure on the participants. They worked with the knowledge that people were dying almost daily from the Listeria outbreak and that any delay would result in additional deaths. And throughout, they could never be certain they were asking the right questions, never sure they would find the answer.

There were, in fact, two investigations. First, it was necessary to determine if there actually was an epidemic and not just a freak of statistics. Second, there came the all-out hunt for the cause.

The first hint that something was amiss emerged at the L.A. County-USC Medical Center, the vast sprawl of four hospitals in East Los Angeles that, with 17,000 births a year, delivers more babies than any other institution in the nation. And it was at this point that a fortunate collision of interest and talents occurred, a piece of luck that county officials would later credit for what they consider a quick solution to the deadly mystery.

Because of its enormous volume, doctors and nurses at the facilities are accustomed to encountering rare diseases, and many make them matters of special research interest.

For instance Dr. M. Lynn Yonekura, the medical director of the labor and delivery service, has been keenly interested for a decade in a certain organism which is particularly dangerous to pregnant mothers and their newborns. The organism is Listeria monocytogenes.

In her top desk drawer, Yonekura keeps a blue-green log book in which she records every case of the disease that appears at Women’s Hospital at the medical center. She uses the cases for research, and last year alone helped produce three papers on Listeria.

Her curiosity was born of the kind of experience that often dictates a path of research for young doctors. Early in her training at the facility, Yonekura treated a mother and her infant who showed what the doctor now recognizes as “all the classic signs and symptoms of listeriosis.”

Yonekura had never dealt with the disease before, and although the proper antibiotics were administered, it was only later that she learned the affliction was the result of the Listeria organism.

In the meantime, the baby had died.

“Any time you have a bad outcome you want to learn from that so that you can prevent that from happening to anyone in the future,” Yonekura said in an interview last week. “And especially when you get the result and you had not necessarily ever heard of the organism before. You say, ‘Wait a minute. There is something I need to know more about.’ ”

And so, over the years, Yonekura made herself an expert on Listeria, carefully keeping her log. This spring, she found herself making entries at an alarming rate. Where Women’s Hospital might see three to five cases of Listeria a year, a span of four weeks from mid-March to mid-April alone produced five.

“It became obvious to me that this was very unusual, knowing the general trend,” Yonekura said. “For one paper we did, to get 20 mother-baby pairs to look at, I had to look back over 10 years.”

Yonekura was not alone in her suspicion something was wrong. A major threat to all hospitals are organisms that can’t be seen, and so they employ in-house epidemiologists to keep tabs on infections. Their job is to ensure that infections do not spread to other patients and are not the result of some flaw in the way the hospital does business.

Carol Salminen has been the nurse epidemiologist at Women’s Hospital since 1978, although she does prefers a less weighty title: “I don’t go by ‘nurse epidemiologist.’ That is the official title. But I call myself the bug lady.”

Much of her job involves watching how the hospital staff functions--surveillance, she calls it--looking for windows of vulnerability in the battle with unseen organisms. She also keeps a close track on charts, looking out for trends that might merit closer attention.

The five Listeria cases in late March and early April did not escape her attention, and she began to consult with Yonekura and other doctors. A first question to be resolved was whether the hospital might be culpable for the upswing. Salminen checked the charts and concluded that the patients had not contracted the disease after they were admitted.

She also studied previous years, wondering if it was possible that the hospital normally gets its annual cases in a bunch in the spring, a time when raw fruit, a possible carrier, is in abundance.

“I found what the incident rate was for Listeria, “ she said, “and definitely there was no cluster over the spring. It was spread throughout the year.”

In mid-April, Salminen recalled, she consulted with Yonekura and other doctors and then called the county Health Department. “I’m seeing an increase in Listeria, “ Salminen said she informed workers there, “and definitely it is coming from the community.”

She asked if other hospitals had reported a similar increase, and was told they had not. She advised the health workers to start checking around, and said she would get back to them if more cases occurred.

Several days passed without any new cases being diagnosed at the facility. In late April, however, a second cluster began, and it became even clearer that an epidemic was at hand.

“We got trouble,” Salminen recalled telling a county Health Department worker.

A staff meeting was held at Women’s Hospital and steps were outlined to deal with the situation and reduce the risk of additional deaths.

Salminen and others began to conduct their own search for clues to solve the riddle, but to no avail. It appeared the outbreak was restricted to Latinos. Other than that, they were stumped.

In early May, a formal report of the possible epidemic was made by the medical center staff to the county Health Department. Other hospitals were surveyed and the Listeria caseload roughly doubled to 33. State officials were notified and it was determined the outbreak extended into other counties, including Orange County where doctors at the UC Irvine Medical Center also had begun to suspect an epidemic.

A decision was made to summon experts from the federal Centers for Disease Control in Atlanta. The second investigation was about to begin.

There are dozens, and perhaps hundreds, of ways to contract Listeria. The problem confronting the investigators was separating the false leads from the true source.

In epidemiology, all such detective work begins with a questionnaire known as a “food history.” The questionnaire, given to each victim and completed with the help of a case worker, must include every possible source of infection. Data from the food histories become the basic source of information for all later work.

“The whole trick is the get the right things on the questionnaire and to ask the questions properly,” said Leedom, director of infectious diseases at County-USC. “If you don’t do it right you can miss the solution or get sent off in wrong directions.”

Dr. Shirley Fannin, associate director of communicable disease control for Los Angeles County, said the majority of such medical hunts, in fact, do fail.

“Sometimes the investigators just don’t come up with anything. Other times, the disease disappears before an answer is found. There are many outbreaks where the cause has been discovered long after the disease has passed.”

With Fannin’s staff and the CDC investigators working together, about 70 questions were put on the food history for Listeria victims. It included questions about strawberries, water, milk, fresh fruits and vegetables. And cheese.

Working out of the Department of Health Services offices on Figueroa Street, the case workers were faced not only with the task of finding 60 victims of the disease but about 120 other people who had not contracted listeriosis. Those interviews, known in epidemiology as “controls,” provided information about people who matched the victims in age, ethnicity and sex but had not fallen ill.

It was not easy. Some of the victims were reluctant to cooperate; others were hard to find. But by early June about 60 of the 180 interviews, with thousands of answers, had been fed into the Health Department’s computers.

Dr. Laurene Mascola of the CDC said the first computer sweep of the raw data revealed a crucial piece of information: virtually all the victims had all reported eating “specialty cheeses.” The controls reported a far smaller rate of consumption.

By design, the first questionnaire had not contained inquiries about brand names. With the new information, the investigators fashioned a second questionnaire that asked specifically about brands of cheese eaten by the victims. The field workers returned to the victims to round up a second set of answers.

“All of a sudden one brand fell out: Jalisco,” Fannin said. “It showed a clear association with those who were sick. The other brands did not.”

Still, the Health Department had no proof that anything was wrong with the Jalisco brand; the investigators needed one final piece of evidence. They picked a grocery store at random and pulled from the shelves two packages of Jalisco Mexican Products Inc. cheese and several packages of cheese from other manufacturers. All were put on an airplane for the CDC’s laboratory in Atlanta.

That was Saturday, June 8. On Thursday Fannin received a call from the CDC laboratory. Both packages of Jalisco cheese had grown cultures of Listeria monocytogenes. The other boxes were clean.

By most accounts, the search for the cause of the Listeria outbreak had been a model of efficiency and speed. Still, almost two months had passed since the first signs appeared at County-USC, and at lease 28 people had died.

In the wake of the recall there have been questions. Could the county have responded more swiftly to the first signs of a crisis? And should they have notified the public sooner, perhaps before the search was narrowed to one brand of cheese?

Fannin acknowledges that the first phone calls suggesting something amiss at County-USC occurred in mid-April and that three weeks passed before the Health Department began its survey of other hospitals. But those first calls from County-USC, Fannin insists, did not suggest that an epidemic was in progress.

“Their staff talks to my staff all the time about problems and possible problems,” she says. “In mid-April they (hospital staff) was saying, ‘We’ve got a cluster of Listeria cases over here.’ Well, a cluster of cases can happen anytime at a hospital like County-USC. It does not mean an epidemic.”

Indeed, County-USC had not completed its own survey of past Listeria cases to compare with the 1985 illnesses until late April, Fannin says. It was only then, and after a second cluster of cases appeared, that the pattern of an epidemic began to emerge.

“You don’t fly on the first case,” Fannin says.

As for issuing an earlier warning, Health Department officials say such a warning probably would have prevented investigators from finding the ultimate solution. And, they note, the department bears liability for damages to innocent businesses that would have been hurt by an announcement that all speciality cheeses were suspect.

County-USC officials support the Health Department’s contentions. “I was really pleased with the speed this was done,” says Dr. Yonekura. “The American public sometimes is impatient, they want answers quickly and don’t understand why.

“There is still a lot of art in medicine . . . If it was that easy, there would be no sickness.”

Times staff writers Marcida Dodson and Harry Nelson contributed to this story.