The Medical Detectives Volume I

by Berton Roueche

  "The other phase of the investigation was hardly more productive. We talked to all the Vineyard doctors, and we burned the midnight oil at the hospital checking out their records. The records in the emergency room showed that four thousand three hundred and ninety-four persons were seen there during July and August of 1977. In the same period of 1978, the number was four thousand three hundred and seventy-three. No leads there. Then we checked admissions. We came up with three patients in 1977 who had been admitted and subsequently discharged with a diagnosis of pneumonia. The total for the period in 1978 was six, of which one was Patsy Lord Hooper. We ran down the five other patients and arranged for blood samples. One of the few positive findings was that there seemed to be no possible connection between the activities of the Lord group and the five other pneumonia patients. And those five were also unconnected. So the indications were reasonably clear that we were dealing with an outbreak concentrated at the Lord cottage. The only really encouraging news came from Colorado. Dan Stafford was off the critical list. He was still very sick, still in intensive care, but they had taken him off the respirator. We couldn't take much credit for that."

  Dr. Teutsch's arrival on Martha's Vineyard had been noted in a front-page story in the biweekly Vineyard Gazette on Tuesday, August 29. The story, written by an industrious reporter named Mary Breslauer, was headed:

  epidemiologists will probe chilmark family's illness Three days later, on September 1, on the eve of Dr. Teutsch's departure, the results of the investigation were also given front page prominence. The story, also the work of Mary Breslauer, was headed:

  epidemiologists still baffled by chilmark family's illness It began: "To the investigating federal epidemiologists, the attending Island physician, and the affected family, the respiratory illness which blighted a Chilmark summer vacation is a medical mystery. . . ."

  And ended: " 'We don't know what is going on here,' Dr. Teutsch added. 'It's not a classical presentation of anything at this point, including Legionnaire's disease. We don't know much about Legionnaire's, and it probably has a very broad spectrum, like most diseases. What's happened here is consistent with Legionnaire's, but it's not something that jumps out at us. Nothing is obvious to us yet.' "

  "Oh, yes," Dr. Teutsch says. "That's the way it was. We were very definitely thinking of Legionnaire's disease. It had always been Alex's first choice, and Ed and I were quite willing to go along. So was everybody in Atlanta. It was at the top of everybody's list. An attack rate of one hundred per cent is most unusual—seven people, seven illnesses. It means a highly infectious organism, and Legionella pneumophila is that kind of organism. But then the first serologic results came through from our laboratory. We had ordered the tests in order of probability, and the first results were for Legionnaire's. And they were negative. Well! The next best possibility on our list was mycoplasmal pneumonia. Those results were also negative. Well, that was interesting, too. I think the next results were on psittacosis. Negative. So were the tests for influenza A and B. And adenovirus infection. And respiratory syncytial virus disease. And parainfluenzas 1, 2, and 3. And the fungus infections. That left only tularemia. And tularemia seemed to be it. The first four convalercent blood samples—from the three Hoopers and from Anne Lord Stafford—had very significant tula-remia-agglutinating antibodies. The levels ranged from 1:40 up to 1:640, and three of the patients had readings in the upper range. When the results of the tests on the other three came through— on Lord and Betty Smith and Dan Stafford—it was very much the same. They all had significantly high readings on the tularemia organism. I have to say that those reports left us all a little bit astonished. Tularemia was the very last thing we expected. But that was it. Our epidemic was an epidemic of tularemia."

  Tularemia is one of an unpleasant handful of infectious diseases that made their first scientifically recorded appearance in the United States. Its companions in this morbid union include rickettsialpox, babesiosis, Lyme arthritis, St. Louis encephalitis, murine typhus, the several Coxsackie-virus infections, and, of course, Rocky Mountain spotted fever and Legionnaire's disease. Like many of these, its name declares its place of origin. The Coxsackie viruses are native to Coxsackie, New York; Lyme arthritis is a native of Lyme, Connecticut; St. Louis encephalitis was first identified in St. Louis and environs; Rocky Mountain spotted fever is the now widely travelled native of the Continental Divide; and Legionnaire's disease made its disastrous debut at the American Legion's 1972 convention in Philadelphia. Tularemia was first recognized as a specific disease in Tulare County, in south-central California, in 1911. ("Tulare" derives from the Spanish tule, a kind of reed that grows abundantly in California—so abundantly that "out in the tulies" has the same meaning in California that "out in the boondocks" does elsewhere.) The discoverer of tularemia was a United States Public Health Service investigator named George W. McCoy. "During the routine examination of ground squirrels," McCoy noted in a report to the Public Health Bulletin in April, 1911, "we have encountered an infection the lesions of which are readily mistaken for those of plague." This slippery new infection, he further noted, had been transferred to healthy squirrels, guinea pigs, domestic rabbits, rats, mice, and a monkey, and "attempts to grow the causative organism are still being made." His conclusion was a muted warning: "We do not know whether the organism causing this disease is pathogenic for man, but judging from the large number of species that are susceptible, we are inclined to suspect that man might contract the infection." The following year, his attempts to grow the organism were finally successful, and he and an associate, C. W. Chapin, announced its laboratory generation under the name of Bacterium tularense, from which (at the suggestion of Edward Francis, a celebrated bacteriologist and 1928 Nobel Prize nominee, who largely completed the elucidation of the disease) tularemia in turn derived its name. A year later, in 1913, Bacterium tularense confirmed McCoy's natural suspicions and felled its first recorded human victim—a meat-cutter in a Cincinnati restaurant specializing in wild-rabbit dishes; he is known to medical history only as "E. E." The historic diagnosis of E. E.'s illness (fever, prostration, a plaguelike lesion), and its subsequent substantiation by a perspicacious professor of bacteriology at the University of Cincinnati named William H. Wherry, was somewhat more than the mere premiere of human tularemia. It led to the identification, as tularemia, of a long-puzzling occupational complaint called variously "market-men's disease" and "meat-cutter's disease" and, most commonly, "rabbit fever," and it also established the wild cottontail rabbit as the chief source of the infection in human beings. It was, in fact, the threat of tularemia that eventually led most American municipalities to restrict the sale of wild rabbits as food.

  Bacterium tularense—or Francisella tularensis, as the organism is now called for keener definition and to honor the illuminations of Edward Francis—stands well apart from most other pathogens in two rapacious respects. It has, for one thing, an extraordinary pathological vigor, a seething virulence, an almost matchless capacity to communicate disease. Most infectious diseases require an assault force of thousands, even millions, of organisms to successfully (depending upon a complex of physiological variables) invade the human body. Tularemia is one of a ferocious few (influenza, measles, Lassa fever) that can overwhelm their victims with a force of no more than a dozen. There are four general portals through which a disease organism may stage an invasion. Many infections (typhoid fever, cholera, trichinosis) are transmitted by the ingestion of contaminated food or water. Many (pneumonia, whooping cough, the common cold) are transmitted by way of the respiratory system, by inhalation. Others (malaria, yellow fever, Rocky Mountain spotted fever) are transmitted by injection—by the bite of an insect carrier or (as in serum hepatitis) the thrust of a contaminated hypodermic syringe. A few (boils and other staphyloccus infections, tetanus, conjunctivitis) are transmitted by contact—by entry into the body through a fortuitous cut or scratch. Numerous pathogens are capable of entering the body by more than one of these routes, som
e by as many as three. F. tularensis can avail itself of any available route.

  The route by which F. tularensis enters the body largely determines the clinical nature of the disease, the organs most particularly affected, and, to a considerable extent, its severity. Tularemia is most commonly acquired (as in the classic case of E. E.) by contact—by handling the carcass of an infected animal, most commonly a wild rabbit. This can be, and often is, wholly inadvertent. In New Orleans, in 1949, a woman became infected (an investigation finally determined) by merely resting her wrist on a marble counter where a butcher had recently cut up a wild cottontail rabbit; entry was made through a little abrasion, the pinprick of a rose thorn. Contact with an infected carcass, the bite of a carrier tick or deer fly, and (though much less commonly) the ingestion of water contaminated by the carcass of an infected animal or of undercooked infected meat account for practically all of the some two hundred cases of tularemia that occur in this country each year. The tiny remainder—less than one per cent— are cases of pulmonary, or inhalation, tularemia. Practically all these are isolated cases, and practically all of them involve laboratory technicians working with cultures of F. tularensis. Epidemics of pulmonary tularemia—a cluster of related cases—are very rare, almost unheard of. Indeed, as it happens, an epidemic involving as many as seven cases had never been heard of until the outbreak on Martha's Vineyard in the summer of 1978.

  The second phase of the C.D.C. investigation of the ill-fated Lord family reunion was undertaken by a differently constituted, more sharply focused team. Its members all were epidemiologists with specific training and experience in the natural history of tularemia. The team was headed by Arnold F. Kaufmann, a veterinarian and the chief of the Bacterial Zoonoses Branch of the Bacterial Diseases Division (the zoonoses are diseases of animals that may be transmitted to man), and included Morris Potter, a veterinarian on Dr. Kaufmann's staff, and William J. Martone, an E.I.S. physician assigned to the Bacterial Zoonoses Branch. Dr. Kaufmann and Dr. Martone are co-authors of an authoritative monograph entitled "Tularemia."

  "I guess you could say that we were picking up on Steve Teutsch and Ed Brink and the others," Dr. Kaufmann says. "They laid the groundwork for our study. But in a sense we were still at the beginning. In a lot of epidemiological investigations, maybe in most, the basic problem—the cause of the outbreak, the disease responsible—is known at the outset. The purpose of the investigation is to identify its source and control any possible wider spread. So, in a way, we were only just starting. We were investigating an outbreak of pneumonic tularemia. The seven clustered cases were, of course, the center of our study. But that wasn't our only interest. We wanted to know if the case cluster was an isolated event. Or did it represent a larger problem. Was tularemia —animal tularemia—endemic on Martha's Vineyard? We got under way on September 19. We couldn't have moved much faster. It didn't much matter, though. There was no great pressure. The clinical problem had been taken care of. As soon as we knew we were dealing with tularemia, we discussed the outbreak and appropriate treatment with Dan Stafford's doctor in Denver. Streptomycin is a specific for tularemia, and it makes a big difference in the pneumonic form of the disease. Pneumonic tularemia can be fatal. But a proper treatment is desirable in any variety. Untreated or improperly treated tularemia can drag on for weeks, even months. Tetracycline is effective, at least in treating the first rush of symptoms, but relapses often occur.

  "Bill Martone led the way to the Vineyard. He left Atlanta on the nineteenth, and Morris Potter followed him up on the following day. Potter's particular job was to get source samples for testing for the tularemia organism—animal material, insects, soil, rotted wood, water, house dust from the cottage. That had been done before, of course, but now we knew what we were looking for. The sample material would be injected into laboratory mice, and a positive reaction would give us a pretty good idea of where the Lord exposure came from. And it might lead to other cases —sporadic, unrelated cases. That was Martone's job. He was working at the hospital, with the local doctors, rechecking the pneumonia-like admissions. But he was also interested in any suspicious skin diseases, anything that might resemble the classic lesion of what we call ulceroglandular tularemia—the mark of handling an infected carcass or suffering an infected bite. Anybody who seemed to qualify would be tested for antibody evidence of tularemia infection. Potter finished up on September 23, and he and I had a conference here in Atlanta. Then I went up to the Vineyard, on the twenty-sixth. Martone was still there. I can't say it was a very exciting visit. There are few things duller than checking hospital records. But Martone hadn't wasted his time. He had learned something, and when I joined him we learned a little more. We found a total of twenty cases of pneumonia-like illness and ten cases involving suspicious skin lesions. They were run down, one by one; some were locals on the Vineyard, some were summer visitors. We ended up with serologic evidence of tularemia in eight of the twenty, six of them local residents. Two of these were gardeners. One of the visitors, an itinerant sheep-shearer, was still sick, up in New Hampshire, with pleuropulmonary disease. We talked to his doctor and learned that he was being treated for tuberculosis. His doctor then put him on streptomycin, with the usual good results. The way he had been going, he might never have got out of bed. Well, all those findings told us a couple of things. One was that there is tularemia on the Vineyard, as there is in most places. And now the doctors there are well aware of it. They have it in mind as a possibility. I don't think many future cases of tularemia on Martha's Vineyard will be misdiagnosed. The other thing we learned was that the Lord outbreak was self-contained. The other cases had no relation to the cottage or to each other.

  "I don't know what to say about the central problem—the outbreak at the cottage. It is officially still unsolved. We established certain things. There was, of course, no question about its nature. It was a case of airborne transmission. The intensity of the epidemic—an attack rate of one hundred per cent—suggested very strongly that the exposure occurred inside the cottage when the family was all together. We were able to eliminate certain possibilities—bare possibilities, I would say. An analysis of house dust was negative. So was an analysis of dust and what could have been mouse material found in the Heat-o-Lator system. In any event, the Heat-o-Lator didn't have much propulsion: it couldn't throw out much of an aerosol. On the positive side, we established the infection in several rabbit carcasses. We also learned that the Hooper dogs chased rabbits, and caught them more than once. Dogs seem to have some resistance to tularemia. At least, they don't usually seem to show any clinical evidence of disease. But we can detect exposure, and both of the Hooper dogs showed serologic evidence of tularemia infection.

  "Well, those are the facts. I have my own ideas, and they are generally supported by the facts. I think what happened was this, and I think it must have happened on August 2: August 2 was a rainy day, and the houseparty stayed indoors. The dogs were out, as usual—in and out. It seems quite likely to me that one or both of them killed a rabbit that day. Killed and ate or mangled it. Then they came into the house. You know how a wet dog shakes itself. It doesn't just shake its body. It also shakes its head, its muzzle, its jowls. And there is always a certain spray of saliva."

  [1980]

  CHAPTER 22

  Live and Let Live

  I talked with Carol Terry one October afternoon in 1978 in her office at the Department of Energy, in Washington, D.C., where she had been employed for almost a year as an auditor. She said she felt well, and she looked it. Mrs. Terry—Mrs. Michael Terry—is an attractive young woman, small and slim, with thick brown hair and large hazel eyes and a somewhat lopsided smile. That—her crooked smile—and an occasional catch or hesitation in her speech seemed to be the only remaining signs of her dismaying experience. Later, when she stood up from her desk to see me to the door, I saw that she also had a slight limp, a favoring of her right leg. But that was all.

  It is hard to say precisely when Mrs.
Terry's trouble began. In one sense, and a very real one, it began at the moment of her birth. That was on June 23, 1946, in Los Angeles. Its first manifestations, however, came later, much later—in the summer of 1971, when she had just turned twenty-four. "It was strange," she told me. "Looking back, I would call it insidious. But at the time I didn't know anything was even happening. I thought I was well and happy. I was an Army brat. I grew up all over the country. But now I thought I was finally settled down. I'd been married for two years to a young Italian from Italy named Pasquale Francone, and we had a nice apartment near L.A., in Brentwood. Pat and I were both working, and I was taking fertility pills because we wanted a baby. The beginning of it all must have been around the middle of July. I seemed to be getting kind of shaky, and sometimes my mouth felt a little tight. Then one day at work, right out of the blue, I fainted. My job was handling claims for an insurance company, and I suppose you could say it was a pressure job. But even so! They were very nice. They sent me home and told me to take a week off. I went to the neighborhood family doctor we knew. He looked me over and said it was overfatigue, and gave me a prescription for Valium. My parents were living in Salt Lake City then. I knew and liked Salt Lake City—I went to high school there—so it seemed like a good idea to spend my week off with them. No, I'm not a Mormon; I was raised a Catholic. Pat got some time off, and we drove up. I really felt very funny—shaky and very nervous. When I told my mother, she just laughed. She said I was simply growing up. She said she had been nervous all her life.