Rabid (26 page)

At 4:30 p.m. on Giese’s second day of hospitalization in Milwaukee, her test results came back from the CDC laboratory. She was positive for rabies, based on the presence of rabies antibodies in her blood and cerebrospinal fluid. None of the rabies virus itself could be recovered from her tissues, but based on her history and clinical signs, and in the absence of another likely cause for her symptoms, the positive antibody test was clinically adequate proof of rabies infection. An hour later, at 5:30, her physicians met at the hospital to discuss her treatment.

Willoughby brought to the meeting his idea for a new rabies treatment. He had developed it on the basis of two published assertions about the disease. The first was that rabies seemed—though this is somewhat controversial—to kill patients without causing any significant damage to their neuronal cells. The second was that the immune system does mount a response to rabies that could, in principle, fight off the infection. Willoughby had come to subscribe to the theory that rabies was a disease primarily affecting neurotransmission, or the
electrochemical communication that takes place between the cells in the central nervous system. By disrupting signal transmission through the brain, so the theory went, rabies interrupted its ability to orchestrate such essential functions as breathing, blood pressure, and cardiac rhythm. These key roles are performed by what is called the autonomic nervous system—the unconscious, primitive seat of the brain. It is by disrupting the autonomic nervous system that rabies kills the patient, often through circulatory collapse or simple suffocation.

On Willoughby’s theory, the battle against rabies was primarily a battle for time. Rabies wasn’t killing the brain directly, but it was directing the brain to kill the body before the body had time to fight it off. Willoughby put a question to his colleagues at the Children’s Hospital of Wisconsin: What if they induced a coma in Giese? By suppressing her brain activity, and by controlling her respiration and circulation—the functions of that autonomic nervous system—they would try to give her immune system the time it needed to mount its own response.

He gave his colleagues an opportunity to raise objections. “I set it up so that any of them could blackball it,” Willoughby recalls. “If we had one blackball, then we wouldn’t do it—because it was such a simple idea it had to be wrong. It was just too obvious. Someone had to have tried it before. So if anybody could see a reason why it would clearly cause harm, they could object and we would drop the plan. Instead, thirty minutes later, we didn’t have an objection to it.”

Later that evening, Willoughby met with Giese’s shaken parents, Ann and John, to inform them of the test results and to discuss their daughter’s grim prognosis. “We brought the parents in and gave them the bad news,” recalls Willoughby. “The Giese parents, I think, especially John, still really didn’t fully understand that this was irrevocable.” He gave them three treatment options for their daughter: hospice care, which would allow their daughter a comfortable death at home; the standard critical care regimen, which so far had never been successful in saving an unvaccinated victim of rabies; or the experimental
plan that Willoughby and his colleagues had laid out. The Gieses chose the third option without hesitation. They pointed out to Willoughby that even if their daughter didn’t survive her infection, the knowledge gained might help some future child with rabies. But even as they said this, their hopes were fastening themselves securely to the idea of a miracle. (John Giese would later tell a reporter from the
Milwaukee Journal Sentinel
about the desperate optimism that helped him through this terrible moment. “Somebody has to be the first person to walk away from this,” he recalls thinking. “Jeanna’s going to be it.”)

In the tense days that followed, the girl lay motionless in a hospital room, animated only by monitors and by the rhythmic whoosh of the mechanical ventilator. An infusion of ketamine, a dissociative anesthetic, maintained her state of unconsciousness. Willoughby chose ketamine for a particular reason: not only would it keep the patient in a state of coma, but it had been shown in a 1992 study on rats to have an antiviral effect against rabies. The effect of the ketamine was broadened by the addition of amantadine, an antiviral with a similar molecular mechanism of action but with an affinity for a different part of the brain. Midazolam, a sedative similar to Valium, was administered to smooth out the effects of the ketamine and to help maintain unconsciousness; this was supplemented occasionally with barbiturates, to keep the girl perfectly calm. On the second day, under counsel from the CDC, Willoughby added ribavirin, a broad-spectrum antiviral agent often used in treating hepatitis C. Nothing remotely resembling this regime, with its high-stakes induction of coma, had ever been administered to a rabies patient before. Tension pervaded the ward of the Children’s Hospital of Wisconsin where Jeanna Giese slept unperturbed, busy nurses hovering above her.

Onto the wall above Giese in the pediatric ICU, Willoughby had tacked up a blurry black-and-white photograph. It showed the bright gaze of a six-year-old boy in another hospital bed, far from Milwaukee in both space and time. The boy’s name was Matthew Winkler, and the
photograph had been published with the report, in 1972, announcing his own recovery from rabies—the first scientifically supported case of survivorship ever published.

At 10:00 p.m. on the evening of October 10, 1970, six-year-old Matthew Winkler’s sleep had been interrupted by a terrible pain in his left thumb. The boy awoke to find a brown bat fiercely clinging to his digit with its tiny jaws. The resulting clamor startled awake the entire Willshire, Ohio, farmhouse, bringing Winkler’s father quickly to his bedside. The bat was wrenched free from Winkler’s thumb, leaving two bleeding puncture wounds that the family cleaned thoroughly. The next day, the Winklers sent the bat off to the Ohio Department of Health, which identified rabies lesions in a cut section of its brain. The test results were reported back on October 14, and that same day Winkler’s family physician initiated a fourteen-day course of duck-embryo vaccine. He did not, however, use immunoglobulin therapy—which by then was a common supplement to vaccination, providing a local immune response against the virus before the effects of the vaccine kick in. On October 30, two days after completing his inoculations, the boy began to complain to his parents of neck pain. Fever, loss of appetite, vomiting, and dizziness followed over the next few days, despite several doses of oral tetracycline initiated by the family doctor. Winkler was referred to pediatricians in Lima, Ohio, who admitted him to St. Rita’s Hospital on November 4.

Over the next few days, Winkler’s condition deteriorated precipitously. The normally studious and well-behaved first grader became uncoordinated, obstinate, unable to walk or write, then altogether mute. The left side of his body was markedly weak, and his bitten thumb tightened into a stiff flexion across his palm. Increased pressure in his skull necessitated the placement of a drainage catheter in the lateral ventricle of his brain. He developed frightening cardiac irregularities, as well as respiratory distress that could be relieved only with a tracheotomy and oxygen supplementation. Small seizures afflicted the left side of his body, and a rash appeared on his arms and torso. Winkler had
slipped into a coma, however, and so was now mercifully unaware of the violent ordeal his body was undergoing.

Although no virus was isolated from Winkler’s skin or saliva, or even on his brain biopsy, abundant rabies antibody was present in his blood serum—much more than would be expected in response to vaccination alone. Antibodies were also present in his cerebrospinal fluid, which is expected to contain antibody only in the presence of natural infection. Tests for alternative diagnoses, infectious and noninfectious, were all negative. A diagnosis of rabies was thus established, and hope for the boy’s survival seemed bleak.

After days spent motionless in a coma, Winkler gradually began to show signs of improvement. First, he became able to sit up with assistance. By November 30 he was sitting up on his own and making squeaking sounds in an effort to speak. More improvements followed rapidly. On December 1, he said his first recognizable word, and by December 7 he could take a few steps on his own, although his left side was still notably impaired. After weeks of physical and speech therapy, Winkler’s doctors declared him normal in both voice and intellect. He was discharged from the hospital on January 21, 1971—his seventh birthday. At a recheck in May, he was found to have no lingering neurological abnormalities.

In their 1972 report in the
Annals of Internal Medicine,
Winkler’s clinicians—led by Dr. Michael A. Hattwick—tentatively attributed the boy’s survival to one of three possible factors. The first was the vaccinations received prior to onset of clinical infection, though the authors noted that no prior victims of vaccine failure were known to have survived. The second was the possibility that Winkler had been infected with a relatively low-virulence strain of bat rabies—though the authors also acknowledged that a test performed at the Ohio Department of Health indicated a high degree of virulence in the infecting strain. The third was the advanced critical care measures employed at St. Rita’s Hospital, including the intraventricular catheter, tracheostomy tube, antiseizure medications, and intensive nursing
care. “Since no specific antiviral agent is known to be effective once symptoms have developed,” the report concluded, “the treatment of clinical rabies must rely on aggressive supportive care. We now know that such care can cure.”

Another, similar case of purported survivorship took place two years after Winkler’s. On August 8, 1972, a forty-five-year-old Argentinean woman was bitten by her suddenly furious dog; within a few days, the dog succumbed to its illness. At first, her doctor treated the deep wounds in her arm with cleaning, suturing, and a dose of tetanus antitoxin. She did eventually begin postexposure vaccine treatment for rabies, ten days after the attack. But less than two weeks later, before she had even completed the fourteen-day course, she began to feel tingling in her left arm. On September 8, she was admitted to the hospital with headaches and depression. She was found to be feverish and weak, with neuromuscular spasms, particularly on her left side. A clinical diagnosis of rabies was made, confirmed by positive antibody titers in her blood and cerebrospinal fluid. But over the next few months, despite setbacks, her condition generally improved under intensive care. By September 1973, her doctors described her recovery as “nearly complete.”

Since then, three additional “partial” recoveries from rabies in vaccinated patients have been described in medical case reports. One was a New York laboratory worker who inhaled rabies virus in the course of vaccine research. The second, a nine-year-old boy in Mexico, was bitten on the forehead and face by a dog that had already attacked twenty-five other dogs in the neighborhood. The third case, in India, resembled the second: a six-year-old girl bitten by a street dog. But in these three cases, the patients wound up with permanent handicaps after their infections, ranging from blindness and quadriplegia to severe brain damage.

All five survivors documented between 1972 and 2002 shared one important characteristic at the moment of developing their first symptoms: they had all received at least part of a course of vaccine against
rabies. For each case like these, though, many more would perish despite having received some treatment before developing signs of illness. And for those who had never received vaccine when their illness set in, there was still no precedent of survival.

After Jeanna Giese had spent seven days in a coma, samples were taken of her blood and cerebrospinal fluid, which demonstrated a marked increase in the number of rabies virus antibodies compared with samples obtained on the first day of hospitalization. Her body was on the attack, striking back at the viral invasion. Giese’s immune system had mounted a robust defense against the rabies virus and delivered it to the embattled central nervous system. With this welcome piece of news, her doctors began gradually to withdraw the anesthetics. The girl’s return to consciousness was observed anxiously by Willoughby, who could not be sure what to expect. The medical literature had described survivorship among unvaccinated animals, he wryly notes—but in animal studies, “every time you get a survivor, you euthanize it.”

Although the electroencephalographic findings improved after the withdrawal of ketamine, the only immediate change on Giese’s physical exam was that her pupils became responsive to light. No other reflexes were apparent. Her limbs lay flaccid on the bed. Willoughby worried silently to himself. “Oh God, I created a lock-in,” he thought—meaning someone who is conscious but unable to communicate or respond in any physical way. “It’s, like, the worst thing you can do.”

The idea that Giese might survive rabies only to be left severely disabled was a constant source of worry during the days and weeks that followed. But her steady, slow improvements kept Willoughby’s worst-case scenarios at bay. Three days after the anesthesia was withdrawn, Giese’s lower leg resumed kicking in response to the reflex hammer. Two days later, she regained eye movement. In two more days, she was raising her eyebrows in response to speech; then, a few days after that, she began to wiggle her toes, and to squeeze people’s hands in response
to commands. “Every day was something new, and it was just miraculous,” recalls Willoughby with a slow shake of his head.

Giese was clearly responding to her environment, but doctor and family both craved more definitive evidence of her return. At that point, to test the girl’s ability to recognize a familiar face, Dr. Willoughby and Ann Giese removed their protective face shields and stood side by side next to Jeanna’s bed. Her eyes, held open by Willoughby, flickered between them briefly and then fixed on her mother. Clearly she was in there, after all.

From there, Giese’s recovery took weeks of incremental improvement. She had to regain her alertness and her attention span, as well as her ability to communicate her thoughts and feelings. Only very gradually did she regain governance of her five-foot-ten frame: gesture, movement, expression, swallowing, and speech all had to be relearned. After a total of one month in medical isolation, Giese was transferred for intensive inpatient rehabilitation that lasted several more weeks.