Health Sciences

The almost fairy tale-like story of 15-year old Jeanna Giese, who became a medical first in 2004, by surviving rabies without any post-exposure prophylaxis, has sparked renewed interest and enthusiasm in the treatment of this fatal disease. The completely novel medical protocol that was used to treat Giese was crafted by Dr Rodney Willoughby and his team at the Children’s Hospital in Wisconsin, Milwaukee. Befittingly, this treatment protocol has been dubbed the ‘Milwaukee protocol’ and has since been deployed in several other hospitals to successfully treat five additional cases of clinical rabies till date.

Before we turn to some of the salient features of the Milwaukee protocol, it is worth perusing the history of medicine in order to fully appreciate the importance of this achievement. Rabies or hydrophobia enjoys a singularly dubious honor of having the highest case fatality ratio of any communicable disease. The first landmark in the treatment of rabies was made by the great Louis Pasteur in 1885, when he used a vaccine developed jointly by him and his colleague, Emile Roux, to save a 9-year old boy, Joseph Meister, who had been mauled by a rabid dog. Thereafter, barring a few isolated instances in recorded medical literature, the treatment of rabies has remained literally unchanged- the crucial “message” being that without timely administration of post-exposure vaccine, rabies is invariably fatal once symptoms begin to manifest. The Milwaukee protocol, which is given to patients presenting with symptoms of clinical rabies and who have not had a course of the prophylactic vaccine or rabies antibodies, indeed does deserve historic if not histrionic attention.

The essence of the Milwaukee protocol is best brought out by briefly recounting the case report of Jeanna Giese. Giese had sustained a small wound in her left index finger during her attempts to rescue and free a bat that had found its way indoors. Approximately a month later, she developed a progression of ominous symptoms that included a tingling in her left hand, generalized fatigue, double vision, and an unsteady gait, gradually followed by blurred vision, nausea and slurred speech. At the Children’s hospital in Milwaukee, the 15-year old was diagnosed with clinical rabies on the second hospital day. Taking into account the grim prognosis of the disease, the physicians who treated her, laid down two alternative courses of action before Giese’s parents: a palliative approach aimed at toning down the morbidity while accepting the inevitable fatality of the disease and an intrepid, never-before-tested aggressive protocol that promised a slim ray of hope for Giese’s survival. The latter proposal seemed more worthy to the parents and was implemented.

The aggressive protocol involved the use of two sets of drugs: (a) ketamine and midazolam, that exert anti-excitotoxic effects on the central nervous system, and (b) ribavirin and amantidine, two antivirals. A combination of these agents was used to achieve a medically induced coma while the patient was placed on life- support by intensive care. Continuous monitoring of the patient’s vital signs along with measurement of serum levels of rabies antibodies served as endpoints for evaluating therapy benefit. Although a multitude of medical complications did set in, including hemolysis, pancreatitis and partial liver failure, these toxicities were kept under check via administration of apropos and timely medical interventions. Increasing levels of rabies antibody were noted from the eight day, with concomitant resolution of many of the central nervous system symptoms. The triumph of Giese’s removal from isolation after a month and her subsequent discharge from the hospital, cured of the fatal disease, has found its way into countless articles and news clippings worldwide.

The Milwaukee protocol has since undergone minor modifications, but its key tenets remain the same. Specifically, later versions of the protocol have done away with the antiviral drug, ribavirin, since clearance of the virus from the brain seemed to depend solely on the maturation of a native immune response.