Rabies in Humans: Symptoms and Treatment
What is Rabies?
Rabies is a disease caused by a rhabdovirus that infects the nervous system. This virus consists of a single strand of RNA in a protein core, surrounded by a lipid sheath. The virus is in the genus lyssavirus, named for the Greek goddess of madness and frenzy. There are different species of lyssavirus, dependent on the host animal.
Once an animal (mammal) is infected, the virus migrates centrally throughout the nervous system, then spreads outward to other tissues. The salivary glands become infected, and the animal will demonstrate no fear of humans.
This is often when a bite occurs: an aggressive and apparently "tame" animal will bite a human. The rabies virus has an incubation time of one to three months, but can vary from 1 week to a year in length. If an individual obtains a rabies vaccination (in addition to human Rabies Immune Globulin, or HRIG) promptly after exposure to the virus, the infection is usually prevented.
Unfortunately, infected humans who do not receive prompt vaccination and develop symptoms are likely to die. While this disease used to claim 100% of the lives of those infected, new treatment options have shown that rabies can be survivable if the infected person is placed into a coma until the body can produce enough antibodies to fight off the virus. This protocol protects the body from the effects of an infected brain: the first person to survive a rabies infection was a 15-year-old girl named Jeanna Giese in 2004 (more about her below).
Rabies Virus Infection
Symptoms of a Human Rabies Infection
The early symptoms of rabies can mimic other maladies that affect the brain. If a person has no recollection of being bitten by a rabid animal the diagnosis might be confused with other neurologic disorders. Guillain-Barre Syndrome demonstrates many of the same symptoms as a rabies infection, and may be given as an (incorrect) diagnosis in a patient who does not have a stated history of exposure to an infected animal.
The symptoms of rabies in humans include:
- Flu-like symptoms
- Itching or a "pins and needles" sensation at the site of the bite wound
- Difficulty swallowing
Once the disease advances, it can take two different forms. "Furious" rabies causes aggressive and uncontrollable behavior - this accounts for approximately 80% of rabies cases in humans. "Paralytic" rabies may be confused with Guillain-Barre and occurs in approximately 20% of cases.
Furious rabies causes hallucinations and aggressive behavior. The infected individual will have delusions. Other physical symptoms include the hair standing on end, excessive sweating, and excessive salivation. Spasms in the throat muscles prevent the victim from drinking water, and will cause foaming at the mouth when the thirsty patient attempts to drink. The spasms will eventually cause the victim to avoid water altogether - this is the reason for the use of the name "hydrophobia" (literally, "fear of water") for rabies.
Paralytic rabies causes a gradual loss of sensation, starting in the hands and feet and spreading inward. These victims to not experience hallucinations and do not develop the classic signs of "hydrophobia."
The end result of furious and paralytic rabies is the same: the patient slips into a coma and heart or lung failure causes death.
Group V (single stranded RNA)
Is Rabies Always Caused by a Bite?
While rare, it is possible for rabies to spread in the absence of a bite from an infected mammal. Rare cases of mucous membrane exposure, licks from an infected animal over an open wound, and airborne infection have been reported. This is exceedingly rare: only 5 cases of non-bite rabies were reported in the United States between 1950 and 1980. Four of the five cases were caused by the inhalation of rabies virus: two of these cases were contracted by researchers who were exposed to heavy virus loads in a laboratory. The other two were contracted by cave explorers who were exposed after they entered caves filled with the feces of infected bats.The fifth case of rabies infection in this time period was due to a cornea transplant from an infected individual.
In 2004, three people were killed by rabies after organ transplantation. The organ donor had died of a brain hemorrhage of unknown origin: while he passed the screening questions for becoming an organ donor, a later investigation revealed that he had been bitten by a bat. The three organ recipients received his liver and kidneys, and went on to develop the disease. Laboratory tests confirmed that all three organ recipients died of rabies, due to the transmission of the disease from the infected donor.
In 2013, another organ recipient died from rabies acquired through transplantation. The donor died in 2011, and donated his kidneys, heart, and liver. A male patient who received a kidney died on February 27, 2013 at a VA hospital in Maryland. The donor died of encephalitis and had an altered mental status prior to death: testing for rabies is not performed on organ donors, so the organs were donated despite the suspicious cause of death. The remaining three organ recipients have been treated with immunoglobulin and five doses of the rabies vaccine to prevent the disease.
Wild Animals and Rabies
The following wild animals are the most likely to be infected with rabies:
Rabies Prevention and Avoidance
People who are at high risk for rabies exposure should get a preventive vaccine. These individuals include:
- Rabies laboratory workers.
- Spelunkers (cave explorers).
- Animal handlers.
People who are not in high-risk jobs can avoid rabies by recognizing the signs in infected wildlife. Animals with rabies will be unafraid of humans, aggressive, and will demonstrate bizarre behavior. Avoid any wild animal that is exhibiting strange behavior or that approaches a human without any signs of fear.
Vaccinating domesticated cats and dogs is vital: while 90% of rabies occurs in wild animals, the majority of infected humans obtain bites from their pet cat or dog. Cases of rabies in cats have been on the rise, and nearly 36% of cats do not receive regular care from a veterinarian in the United States. Regular vaccination of pets in the household will prevent exposure to the most common route of rabies transmission.
Oral Rabies Vaccine for Wildlife
The Rabies Vaccine
The first rabies vaccine was developed by Louis Pasteur and Emile Roux: the two scientists took brain tissue from infected and killed rabbits, allowed the tissue to dry, and prepared injections from this material. In 1885, a nine year old boy named Joseph Meister was repeatedly bitten by a rabid dog. On July 6, the first successful rabies vaccination was given to Meister, who never developed any signs or symptoms of a rabies infection.
The development of a Duck Embryo Vaccine (DEV) made the vaccination easier to obtain. This vaccine was injected into the patient's abdominal fat for a period of 14 days (or more). This vaccine is no longer used, and the feared "shots in the stomach" are no longer used. The DEV vaccinehad many side effects, including anaphylactic (allergic) reactions.
The modern rabies vaccine is a recombinant vaccine: the rabies virus glycoprotein is added to vaccinia virus: this induces an immune response against rabies. This vaccine is called V-RG and is sold under the brand name Raboral™. This vaccine has the advantage of oral administration to wildlife, which helps curb the spread of rabies in nature.
Humans now receive 4 injections of the rabies vaccine after exposure to the virus. The first dose is given immediately after exposure, and additional doses are given on the 3rd, 7th, and 14th days after exposure. When the first injection of rabies vaccine is given, Rabies Immune Globulin should be given at the same time.
The Milwaukee Protocol: A Cure for Rabies
Until recently, those who developed the neurological symptoms of a rabies infection had a 100% rate of fatality. A doctor at the Children’s Hospital of Wisconsin changed that statistic with the successful cure of a 15-year-old girl.
Jeanna Giese was attending mass at her local Catholic church when she noticed a small bat flying in the church building. The bat was bothering the congregation, and Jeanna was an animal lover. When the bat landed, she picked up the animal by its wings and took it outside. The bat bit her and wouldn’t release her finger: she was able to pry the animal off her hand and threw it toward a tree. A month later, Jeanna felt sick. She was unable to play at her volleyball game and missed the homecoming parade because she could hardly move. The next thing she remembered was being in the hospital, where the neurologist was told about the bat bite and an MRI was ordered. Astonishingly, the neurologist told her it was nothing to worry about and sent the sick child home.
Jeanna returned the next day, even sicker than she had been the day before. Tests for Lyme Disease, meningitis, and a host of other conditions turned up negative. When the girl’s pediatrician visited and viewed her deteriorating state, Jeanna’s mother informed him of the bat bite. The pediatrician immediately suspected rabies and had Giese transferred to the Children’s Hospital of Wisconsin.
There, Dr. Rodney Willoughby proposed a radical experimental treatment. He knew that the brains of rabies patients often survived the assault of the virus: the patients typically died of organ failure before the immune system could attack the virus. He wanted to put Jeanna into an induced coma to shut down her brain functions. She would be placed on anti-virals and life support until her immune system could mount a response to the virus. Her parents agreed.
Six days later, Giese was brought out of the induced coma and was able to keep her eyes open. She was in the hospital for 11 weeks, and had to re-learn how to walk, talk, and eat. This was a trying time for Jeanna, as she missed her family and friends greatly while in the hospital. Jeanna was released from the hospital on January 1, 2005: the first human survivor of the rabies virus. Jeanna Giese has since graduated with a degree in Biology from Lakeland College.
This treatment for rabies has been dubbed the Milwaukee Protocol, and has saved more than one life.
Nelsy Gomez was bitten by a rabid cat in her village in Columbia. She was transferred to the Hospital Universitario del Valle in Cali, Colombia, where the infectious disease specialist instituted the protocol. Gomez’s immune system response was very strong to the virus, and her brain swelled as she was fighting the infection. While she did regain motor control of her arms and legs, she developed pneumonia and died. While the child did not survive, the rabies infection was halted and the protocol was considered a success.
A 15 year old child in Brazil developed rabies after a bite from a bat. Despite receiving 4 doses of the rabies vaccine, symptoms still developed and Marciano Menezes de Silva was placed in a coma according to the Milwaukee Protocol. The protocol did halt the rabies infection, but Marciano was ventilator dependent after emerging from his medically-induced coma. This case highlights the importance of receiving all five rabies vaccinations after exposure in addition to the immunoglobulin. Most rabies vaccination failures are due to a failure to comply with the vaccination protocol.
In 2011, an 8 year old girl named Precious Reynolds was scratched on the arm by a feral cat during recess. She contracted rabies and was placed under the Milwaukee Protocol at UC Davis Children’s Hospital. After two weeks in intensive care, Precious was released to the general ward to complete her recovery.