Four years ago, Jeanna Giese, now 19, became the first person to survive rabies without a preventive vaccine. Now, the medical procedure developed for treating Giese may have saved the lives of two children in South America.
Last month, ScientificAmerican.com chronicled Giese's remarkable recovery after she had been infected with the deadly virus. In the absence of the vaccine regime or rabies antibodies, the virus kills by interfering with the brain's ability to regulate crucial body functions, including respiration and heart rate. With little hope for Giese's survival, Rodney Willoughby, an infectious disease specialist at the Children's Hospital of Wisconsin in Milwaukee, induced a coma to protect her brain from viral attack, giving Giese's immune system time to rev up to combat the virus.
The unorthodox treatment—known as the Milwaukee protocol—is now also credited with saving the life of eight year-old Nelsy Gomez, only the second person known to recover from rabies without prophylaxis. Exhibiting symptoms a month after being bitten by a rabid cat, Gomez was transferred from her rural village to the Hospital Universitario del Valle in Cali, Colombia, where infectious disease specialist Yolanda Caicedo initiated the protocol.
Caicedo reports that Gomez appeared to be recovering quickly following two weeks in a medically induced coma. But her immune response was 10 times greater than that of Giese, Caicedo says, causing her brain to swell. Fearing that she may have lasting neurological complications, doctors carefully monitored Gomez; she eventually regained movement in her head, legs and fingers. Unfortunately, doctors were never able to communicate with the young girl, who succumbed to pneumonia (unrelated to the rabies infection) on October 24. Despite the setback, Caicedo has no doubt that the protocol worked to arrest the initial rabies infection.
And last week, another victory for the protocol emerged in Brazil where physicians successfully treated 15-year-old Marciano Menezes da Silva. The teen was bitten by a rabid vampire bat on September 7, and a month later developed symptoms, including tremors, anxiety, agitation and salivation. Infectious disease specialist Gustavo Trindade Henriques Filho administered the Milwaukee protocol to him on October 13 at the Federal University of Pernambuco Oswaldo Cruz Hospital in Recife.
According to an e-mail from Henriques, the coma persisted for two weeks under medical supervision. Although the teen's eyes are open and he moves spontaneously, Henriques writes that Menezes still is on a respirator to help him breathe. Willoughby notes that this is not unusual for a rabies survivor, as the virus fully paralyzes patients requiring extensive rehab to restore use of their muscles.
Although the Menezes's case provides further support for the protocol, Willoughby emphasizes that the teen received prophylactic treatment prior to developing symptoms. Menezes was vaccinated as soon as he was bitten, Henriques says, but notes that he only received four of the five recommended doses before symptoms appeared and was not given rabies antibodies. An injection of synthesized rabies antibodies—or immunoglobulin—is administered to help patients combat the virus while their immune system creates antibodies in response to the vaccine.
"The patient is typical of historical cases of vaccine failures," says Charles Rupprecht, chief of the Rabies Program at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta. Incomplete prophylaxis is believed to induce some immunity in these patients, Rupprecht says, but survivors may develop encephalitis resulting in severe neurological complications. To date, only six patients (including Menezes) for whom the vaccination strategy failed have survived, the first was 6 year-old Matthew Winkler from Ohio, who was bitten by a rabid bat in 1970 and developed symptoms after receiving a full course of the vaccine (prior versions of the rabies vaccine were not as effective as current formulations). Menezes is the first to recover with the help of the Milwaukee Protocol.
Henriques is optimistic about Menezes's future. Doctors are currently weaning the teen off the ventilator, he says, and they are working to control his convulsions. Willoughby warns, however, that Menezes may fare worse than Giese because he received a partial course of the vaccine. The rabies virus itself does not lead to much inflammation, Willoughby says, but the vaccine is engineered to radically increase the inflammatory responses of the body, which can wreak havoc on the brain.
For now, Giese remains the gold standard for recovery from rabies. Although she required a year of extensive rehabilitation to regain her skills and cognitive functions, Giese now drives and studies biology at the Marian University in Fond du Lac, Wisc. She does recognize, however, that effects of her battle linger with her speech a bit slower than before her rabies bout.
Despite the recent successes of the Milwaukee protocol, Rupprecht cautions that "we need to focus more on prevention." The protocol provides hope for patients already infected, he says, but "the odds of coming out without neurological deficits are remote, even with the best care."