The Medical Detectives Volume I
Page 42
"I wasn't exactly alarmed," Dr. McMillin told me, with a shrug and a tight little smile. "But it was a disturbing piece of news. If the outbreak was spreading into Sioux Falls, we could be in for big trouble. Our investigation so far showed that in the area Jan had mapped the disease was occurring at a rate of at least one in every hundred persons. If it spread to Sioux Falls at that rate, we could be seeing patients in the thousands. So I had some serious questions for Mrs. Peskey. I asked if she and her family spent much time in Valley Springs. No—not really. Did they ever eat or drink the water there? Or stay overnight? Well, they never stayed overnight. They hardly ever ate anything there. Her parents had a little coffee shop attached to the main store, and she and her husband sometimes had a cup of coffee. She thought she knew most of the Valley Springs patients, but not as friends, and hardly ever saw them. She did sometimes bring some groceries home from the family store. I advised her to see her doctor—her and her husband and the little boy—and have the standard thyroid studies done, and to ask the doctor to report the results to me as soon as possible. I said I thought she could stay on her job. But I thought she should be very careful in handling food, and be careful about washing her hands. I hung up and did some thinking. The Longs, as far as I knew, were not among our Valley Springs cases. We knew there was little, if any, evidence of person- to-person transmission of this disease. Dan and Jan and I had talked that over and over. It was beginning to look less and less likely that we were dealing with an ordinary viral disease. Or any kind of viral disease. In that case, the possibility of some common source of infection was strongly indicated. There were several possible vectors. But the most likely—the most common—would be some food or drink that was shared by all."
"We're now well into July. We had made a point of keeping as quiet as possible about the outbreak. We didn't want a lot of community excitement until we knew a lot more than we did. That could only muddy the waters. But the news leaked out, as it always does, to the media. And nothing much happened. It was only a one-day story. We had been in touch with the Minnesota Health Department all along, of course, but now all hands decided it was time to meet. We set up a conference for July 8 in Worthington, which is between here and Minneapolis. Hedberg and Oster- holm were there, along with various other health workers in the community. Hedberg presided. We brought each other up to date. We heard reports that a lot of the patients were worried that the water supply might somehow be to blame. Or insecticides. There was even a group that thought the trouble might have been brought on by some recent tornadoes. We discussed the question of genetic susceptibility. As it turned out, many people in the outbreak area had evidence of thyroid hormone in their blood but were not clinically ill. Even fairly high levels of hormone can be tolerated by some young people and adults in good health. We decided to send a letter to physicians in a wide area of the two states soliciting information about cases of painless hyperthyroidism. The South Dakota letter went out over the signatures of Kenneth A. Senger, director of the Division of Public Health, and myself. The results, I might as well say now, were positive in a negative sense. The response left the geography of the outbreak much as it had been earlier defined. The number of cases rose from week to week, but there were none really outside the area.
"I received a phone call from Rhonda Peskey's doctor. He had confirmed that she and her son were both thyrotoxic. I decided it was time to treat myself to a little shoe-leather epidemiology. The next morning, I drove over to Valley Springs. The Clover Farm store wasn't hard to find. It's practically the only store in town. With Sioux Falls only ten miles away, a convenience store is about all a little place like Valley Springs can support. I went in and introduced myself to Larry Long. We had a cup of coffee together and talked about where he bought his stock. We talked about bread and eggs and meat and milk and soft drinks and staples. Practically everything came from distributors in Sioux Falls or one of several other Large distributors in the region. There was nothing surprising in that. And, of course, the same distributors supplied the various stores in Sioux Falls. Practically all the Clover Farm meats came from Sioux Falls. Some came from a plant in Luverne. That was a special kind of beef that Larry Long ground himself, for customers who liked their hamburger lean. He called it his lean cuisine. It was extra lean, almost no fat at all. We talked for about an hour, and Margaret Long joined us for another cup of coffee. We talked about the outbreak. Some of their customers were sick. Some weren't. They themselves were well. I drove back to Sioux Falls, thinking about what I had learned. There was only one thing that stood out. That was that extra-lean hamburger. Was that a clue? But how? When I got back to my office, I found a message from Dan. The number of confirmed cases was climbing. There were more than fifty now in Luverne alone.
"We were all more or less convinced that we were dealing with a food-borne agent centering on Luverne. What was needed now was a case-and-control study and a review of food sources. As it turned out, we did two such studies. Fifty confirmed cases were matched with fifty well individuals for age, sex, neighborhood, and so on. The first study narrowed the suspected food sources to commercially processed chicken and lean ground beef. The second eliminated the chicken and identified the ground beef as coming from the plant in Luverne that Larry Long had told me about. The store in Valley Springs and similar stores in Beaver Creek, Hills, and Luverne all sold that lean-cuisine beef. We had these findings by the end of July or early August. Our case total by then included two families in Sioux Falls. One of these was the Peskey family, and that presented no epidemiological problem. We knew where Mrs. Peskey got her ground lean beef. The other family could have been alarming—or, at least, confusing. Dan went to see them. He asked if they ate ground beef. They said yes. And where did they buy it? They said there was a little store over in Valley Springs that carried the best hamburger meat they'd ever had. It was so lean. We laid another worry to rest. At about the same time, we got an even more interesting report on a family living some little distance east of Luverne, outside the charted outbreak area. It was an extended family—three generations, numbering about fifteen people. All ages. There was no question about their illness. They were all confirmed cases of thyrotoxicosis—all but one, a boy of twelve. They got their ground beef from the plant in Luverne. One of the family worked there, and he brought the meat home. What about the boy? Oh, he was a vegetarian. Well, that was the 'My God— that's got to be it!'
"We had the vehicle, we were sure of it. There was no doubt in my mind or in the minds of Dan and Jan that the source of the outbreak was something in the extra-lean beef from the Luverne plant. Some of the others thought otherwise. Very well. But just what was that something? We didn't see how it could be a viral or bacterial contamination. The control studies showed us that practically all the cases liked their hamburgers well done. This isn't steak-tartare country. And, of course, cooking would have destroyed any microorganisms. That left the possibility of some chemical agent. But that couldn't be. I mean, there was no chemical agent known to us that could cause thyrotoxicosis. We came to a halt. The next move would be an investigation at the plant. The public-health officials in Minnesota were quietly making the necessary arrangements. That sort of thing is a delicate business. If the plant was deliberately doing something wrong, an impetuous move could alert it. But once the Luverne lean beef was clearly indicated I decided to take a look at the meat myself. I made another visit to the Clover Farm store in Valley Springs. Larry Long showed me into the walk-in cooler and pointed out the extra-lean beef. It was in chunks—dark-red meat. There was nothing visibly wrong with it. It's been a long time since I studied anatomy, but I could remember enough to recognize that what I was looking at was neck muscle. Well, the thyroid gland and the neck-strap muscle are very close neighbors. I had to think there was a good possibility that some of that meat was thyroid. In fact, there were traces of white tissue along the edges of some of the chunks. I bought a pound of that. Then, as I was leaving, I asked Larry Long somet
hing I probably should have asked long before. He and his wife were not on our list of cases, and he said they had never been sick. I asked him if he often ate that extra-lean beef. Often? He gave a little laugh. He said he and his wife owned the store. They didn't have to eat hamburger. They ate sirloin.
"I took my hamburger over to Jerry Simmons. Dr. Simmons is the pathologist at the medical school and the Laboratory of Clinical Medicine in Sioux Falls. I showed him my meat and told him what I had in mind. I pointed out those areas of white. Jerry gave me a look. He said, 'I could put this under the microscope, but it would be a waste of time. That white isn't thyroid. Thyroid gland is red—very dark red. That white is salivary gland.' I suggested we go back to Valley Springs together, and he would pick out some better samples. So we did, and he got some likely chunks, and we went back to the lab, and he prepared some samples for freezing. When the meat was frozen, he would slice off some razor-thin sections and stain them and put them under the microscope. He'd let me know the result. Which he did, about an hour later. He said, 'Mike, I think I can help you with your problem.' "
A Public-Health inspection of the Luverne plant was undertaken in the third week of August, under the general direction of Dr. Robert B. Janssen, from the Centers for Disease Control. A few days earlier, the plant had agreed to halt production of neck trim and to recall all known supplies from the stores. The findings of the investigating team were definitive. The plant was not a packinghouse. It was primarily a slaughterhouse. Dressed carcasses were shipped to another plant for processing. Only the heads were retained at Luverne. Neck muscle was trimmed from these heads and distributed to local retailers for sale as ninety-per-cent-lean beef. As was usual in the trade, every effort was made to recover as much trim as possible. The strap muscles were trimmed from their attachment to the trachea. It was apparent to the investigators that thyroid tissue was often inadvertently included in the beef trim. The plant produced an average of nine hundred pounds of trim each day. Certain changes had recently occurred at the plant. Until April of 1983, the plant had selectively removed the thyroid glands and sold the tissue to manufacturers of thyroid extract. That market vanished with the development of a synthetic thyroid extract. It was also learned that the plant had operated for many years as a kosher killing plant. That ended in November of 1984. Kosher killing made the thyroid gland readily recognizable. The neck meat remained red after the blood was drained off, but the thyroid turned pale. It was presumed that the end of this practice made it difficult for the trimmer to avoid including thyroid-gland tissue in the trim. Samples of trim were taken for extensive examination by three investigators in Massachusetts— Drs. Sidney Ingbar and Lewis Braverman (of "The Thyroid" fame) and Dr. Bruce Meyers. Their findings confirmed that the suspected beef trim produced and sold by the plant contained high concentrations of thyroid hormones. This confirmation was further confirmed by a test involving human volunteers. That test was performed, with the approval of the Human Subjects Institutional Review Committee, at the University of Massachusetts Medical School. Four volunteers ate samples of the implicated beef trim that had been ground and cooked into hamburgers. The samples had previously been cultured to exclude such disease organisms as salmonella; shigella, and Campylobacter. Blood samples for thyroid-related hormone analyses were obtained before and after eating. All the volunteers remained asymptomatic, but the serum tests showed the presence of thyroid hormone. The recall of the meat from the Minnesota and South Dakota stores brought an end to the outbreak. The known cases of thyrotoxicosis totaled a hundred and twenty-one, but it is probable that there were many cases in the affected area that were unknown to the investigators. There were no deaths, but a number of sufferers, mostly elderly people, were hospitalized. The investigation also led to the resolution of the uncertainties of the York County, Nebraska, outbreak of the year before. A significant majority of its victims were found to have eaten ground lean beef purchased from a single supermarket.
The 1985 thyrotoxicosis outbreak and its successful investigation had consequences of more than local interest. One of these was that on August 29 the United States Department of Agriculture issued an advisory to all U.S.D.A.-inspected plants which temporarily prohibited trimming near the gullet in beef (and pork) used for human consumption. That prohibition was later made permanent.
[1988]
CHAPTER 25
The Foulest and Nastiest Creatures That Be
I saw my first tick in the back yard of a rented house in East Hampton, on the oceanic East End of Long Island, one afternoon in July of 1949. It was on my wife's back. We had just come home from the beach, and the tick was conspicuously poised on the bare skin between the top and the bottom of her two-piece bathing suit. We had only recently moved east from Missouri, where the insect pest of summer is not the tick but the chigger. Still, I knew what a tick looked like, and I knew—or had heard—that there was an approved way of removing one from the flesh of its victim: apply the lighted end of a cigarette. I had a cigarette in my hand (as I often did in those innocent days), and I carefully applied the lighted end to my wife's nicely tanned back. She gave a scream. The tick did not, as the approved method promised, drop to the ground. It merely crawled a millimeter or two to the right. Instinct guided me next. I reached out and plucked it off with my thumb and forefinger. Before I killed it, before I crushed it with a pebble, I took a closer look. It was almost the size of a ladybug, only flat, with a shiny brown carapace and a yellowish capelike collar. It had eight spindly legs and a tiny snout of a head. It was ugly, but it looked—though I knew it wasn't—harmless. That, as I say, was my first tick, but hardly my last. I have since seen hundreds, perhaps thousands, in the wild and—crawling, sitting, or embedded—on me, on my wife, on my son, and on several generations of dogs.
The tick is not, to be puristic, an insect. It belongs, in the nomenclature of science, to the phylum Arthropoda and is a member (along with spiders, scorpions, mites, and the horseshoe crab) of the class Arachnida. Ticks are found in incomprehensible numbers throughout the world, and man has probably been unpleasantly aware of them since his beginnings. Human detestation of the tick easily surpasses that aroused by snakes and spiders. "Ill- favored ticks," Pliny the Elder (23-79 a.d.) cried out in his "Natural History." "The foulest and nastiest creatures that be." I know of no better confirmation of the theory of evolution than the tick. That is to say, it is hard to think of the tick, which lives on the blood of other creatures but is itself food for none, as a deliberate creation, as one of the creatures in Genesis "that creepeth upon the earth," and to believe that it had a Creator who "saw that it was good." My first tick—and, with one considerable exception, all of the many ticks I have seen—was of the species Dermacentor variabilis, the dog tick. It is, like all ticks, parasitic, but is itself often host to the bacterium Rickettsia rickettsii, the agent of Rocky Mountain spotted fever. Rocky Mountain spotted fever takes its name from the region (the mountains of Idaho and Montana) in which, in the eighteen-nineties, it was first identified, but it is no longer seen as merely a provincial menace. Its geography is now known to embrace most of the Western Hemisphere. It has, however, its favored haunts. These include, along with the mountain West, much of the states of Georgia, North Carolina, Virginia, and Maryland, coastal Connecticut and Massachusetts, and eastern Long Island.
Rocky Mountain spotted fever is a dangerous disease. The average incubation period—the interval between the bite and leisurely blood meal of an infected tick and the appearance of illness—is about seven days. The onset is often abrupt, with high fever, chills, headache, prostration, and other more or less equivocal manifestations. The characteristic spotted rash seldom appears before about the fourth day. Immediate diagnosis is consequently difficult unless the disease is suspected—unless the diagnostician is morbidly alert to its possible presence or unless the victim can inform him of a recent tick bite. This last is only sometimes feasible. Ticks seem to seek out secluded feeding sites—the armpit, the scal
p, the navel. An effective treatment for Rocky Mountain spotted fever, involving a tetracycline antibiotic, has been available since the middle nineteen-fifties. Untreated or improperly treated cases have a high mortality—around twenty per cent. I was aware of Rocky Mountain spotted fever at the time of my introduction to D. variabilis, and I made it my business to learn more. I learned from local lore that the vector tick is ubiquitous in range, finding a comfortable habitat in fields and pastures, in brush and woods, in the grassy dunes that border the most pleasant beaches, and even in the best-kept lawns, and that its preferred hosts are rabbits, mice, squirrels, and dogs. Man is merely faute de mieux. I learned from a local doctor that there was no effective treatment for Rocky Mountain spotted fever (the tetracyclines were yet to come), but that there was a vaccine. My wife and son and I presented ourselves at the local clinic and were immunized. I have a vivid recollection of that vaccination: a moment after the injection, my arm received what felt like a blow from a baseball bat, and an ache that persisted for some hours. But it seemed well worth that little discomfort. I lived the next thirty-odd years—sunning myself on beachy dunes, strolling in brushy pastures, cutting firewood—in the carefree knowledge that my wife and son and I were immune to Rocky Mountain fever, and I removed any ticks I attracted as nothing more than nuisances. It was only recently that I learned that all R. rickettsii vaccines had long since been found to be unreliable and had been withdrawn from the market.