Rabies Virus

Type of micro-organism:
Infectious disease

Image or diagram:

Transmission of the disease:
Bited by dogs

Signs and symptoms:

A patient with rabies, 1959.
The period between infection and the first flu-like symptoms is normally two to twelve weeks, but can be as long as two years. Soon after, the symptoms expand to slight or partial paralysis, cerebral dysfunction, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, hallucinations, progressing to delirium.[5] The production of large quantities of saliva and tears coupled with an inability to speak or swallow are typical during the later stages of the disease; this can result in “hydrophobia”, where the patient has difficulty swallowing because the throat and jaw become slowly paralyzed, shows panic when presented with liquids to drink, and cannot quench his or her thirst. The disease itself was also once commonly known as hydrophobia, from this characteristic symptom.
Death almost invariably results two to ten days after the first symptoms; the few humans who are known to have survived the disease[citation needed] were all left with severe brain damage, with the exception of Jeanna Giese (see below). It is neurotropic in nature.

Prevention and/or treatment:

Main article: Rabies vaccine
Almost every infected case with rabies resulted in death until a vaccine was developed by Louis Pasteur and Emile Roux in 1885. Their original vaccine was harvested from infected rabbits, from which the nerve-tissue was weakened by allowing to dry for five to ten days.[10] Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.[11] The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967, however a new and less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available.[citation needed] A recombinant vaccine called V-RG has been successfully used in the field of Belgium, France, Germany and the United States to prevent outbreaks of rabies in wildlife.[12] Currently pre-exposure immunization has been used in both human and non-human populations, whereas in many jurisdictions domesticated animals are required to be vaccinated.[citation needed]
In the U.S., since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths from rabies has dropped from one hundred or more annually in the early twentieth century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.[13]
Post-exposure prophylaxis
Treatment after exposure, known as post-exposure prophylaxis or “P.E.P.”, is highly successful in preventing the disease if administered promptly, generally within ten days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is very effective at reducing the number of viral particles. “If available, a virucidal antiseptic such as povidone-iodine, iodine tincture, aqueous iodine solution or alcohol (ethanol) should be applied after washing…Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water.”[14] In the United States, patients receive one dose of human rabies immunoglobulin (HRIG) and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of the immunoglobulin is injected in the region of the bite, if possible, with the remainder injected intramuscularly away from the bite. This is much less painful compared with administering the immunoglobulin through the abdominal wall with a large needle, as was done in the past. The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days three, seven, fourteen, and twenty-eight after the first. Patients that have previously received pre-exposure vaccination do not receive the immunoglobulin, only the post-exposure vaccinations on day 0 and 3.
In instances when post-exposure prophylaxis is administered as a precaution (e.g. a person wakes up and finds a bat in the room they were sleeping in), it is now mainly given in the gluteal region and deltoid (upper arm). The number of shots delivered to the gluteal area on the first day is determined by weight, and it is not uncommon to require three of these shots. Subsequent shots of the vaccine (to build longer term immunity to rabies) are given to the arm. Recipients of the vaccine have reported that these shots are no more painful than normal shots (such as tetanus boosters).[citation needed] The recommendation for the precautionary use of post-exposure prophylaxis in occult bat encounters where there is no recognized contact has been questioned in the medical literature based on a cost-benefit analysis.[15]
Most official documentation on rabies on the internet and otherwise warn that treatment becomes futile with the onset of prodrome (when symptoms begin to appear). These texts are written to convince the layman not to delay seeking treatment (and rightly so).[citation needed] However, this may also lead them to falsely conclude that their situation is not an urgency and that treatment is possible up until the very end of the incubation period, as it may last 1 to 3 months on average; or it may at least convince them that it is safe to delay treatment by a few days. While the virus is treatable only during the incubation period, it is important to note that it is not treatable during its entirety. Rabies is fully treatable while the virus is present in tissues composed of cells other than neurons, such as skin and muscle. However, once the infection spreads to a neuron, the virus is sequestered from the immune system and will eventually make its way to the spinal cord and then to the brain. Treatment at this point may not be effective, even though symptoms may begin to appear weeks or even months later. Therefore, it is highly recommended that P.E.P. be administered as soon as possible. Begun without delay, or very little delay, P.E.P. is 100% effective against rabies.[16] In the case where there has been a significant delay in administering P.E.P., the treatment should be administered regardless of that delay, as it may still be effective if it is not too late.[citation needed] If there has been a delay between exposure and attempts at treatment, such that the possibility exists that the virus has already penetrated the nervous system, the possibility exists that amputation of the affected limb might thwart rabies, if the bite or exposure was on an arm or leg. This treatment should be combined with an intensive PEP regimen.[citation needed]
Blood-brain barrier
Some recent works have shown that during lethal rabies infection, the blood-brain barrier (BBB) does not allow anti-viral immune cells to enter the brain, the primary site of rabies virus replication.[17] This aspect contributes to the pathogenicity of the virus and artificially increasing BBB permeability promotes viral clearance.[18] Opening the BBB during rabies infection has been suggested as a possible novel approach to treat the disease, even though no attempts have yet been made to determine whether or not this treatment could be successful.[citation needed]
Induced coma
See also: Milwaukee protocol
In 2005, American teenager Jeanna Giese survived an infection of rabies unvaccinated. She was placed into an induced coma upon onset of symptoms. Her doctors administered treatment based on the hypothesis that detrimental effects of rabies were caused by temporary dysfunctions in the brain and could be avoided by inducing a temporary partial halt in brain function that would protect the brain from damage while giving the immune system time to defeat the virus. After thirty-one days of isolation and seventy-six days of hospitalization, Giese was released from the hospital.[19]
Giese's treatment regimen became known as the "Milwaukee protocol". To date only one other patient has survived under the protocol, despite numerous attempts at the treatment. Rodney Willoughby Jr., Giese's primary care physician, has asserted that subsequent failures occurred because patients were not given the same combination of drugs used in the initial incident.[citation needed]
The anesthetic drug ketamine has shown the potential for rabies virus inhibition in rats.[20]

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