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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Syed Hassan A. Kazmi BSc, MD [2] Mahshid Mir, M.D. [3]

## Overview[edit | edit source]

Rabies is a disease that has been classically associated with infected animals, mainly dogs.The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC - written prior to the Code of Hammurabi), which demonstrates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. Although dogs are viewed as the main culprit of rabies, rabies is also associated with animals such as possums, skunks, and more importantly, bats. In 1885, 9-year-old boy named Joseph Meister was the first person to have received an effective shot for rabies after being bitten by a rabid dog. Louis Pasteur treated the first case of rabies by a weak form of virus (which later became the basis of active immunization for rabies). In the 1950s, people who had been bitten by a rabid animal got 23 shots along the abdomen. Today, the shots are more effective and less painful. They consist of a series of 6 shots given in the arm over a 1 month period. One shot is given around the bite and the rest are given in the arm.

## Historical Perspective[edit | edit source]

* The history of rabies dates back to before the invention of microscopic techniques, although the virus itself was not seen under the electron microscope until the 1960s.
* Rabies in animals was reported in early Babylonian, Greek, and Roman records.
* Rabies was likely brought to the Americas when settlers first came from Europe, bringing rabid animals with them.
* In 1885, 9-year-old boy named Joseph Meister was the first person to have received an effective shot for rabies after being bitten by a rabid dog. Louis Pasteur treated the first case of rabies by a weak form of virus (which later became the basis of active immunization for rabies).
* In the 1950s, people who had been bitten by a rabid animal got 23 shots along the abdomen. Today, the shots are more effective and less painful. They consist of a series of 6 shots given in the arm over a 1 month period. One shot is given around the bite and the rest are given in the arm.

### Rabies and animal quarantine[edit | edit source]

* Although rabies has been known to be endemic in many countries, international transport of animals from one region to the other has been discouraged in order to prevent spread of the disease as a quarantine measure.
* Most developed countries, pioneered by Sweden, now allow restriction-free travel between their territories for pet animals that have demonstrated an adequate immune response to rabies vaccination. Such countries may limit movement to animals from countries where rabies is considered to be under control in pet animals. There are various lists of such countries. The United Kingdom has developed a list, and France has a rather different list, said to be based on a list of the Office International des Epizooties (OIE).

### Rabies and dogs[edit | edit source]

* The association of rabies with dogs is as old as the disease itself.
* The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC - written prior to the Code of Hammurabi), which demonstrates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If a person is bitten by a rabid dog and later died, the owner was fined heavily.[1]

### Rabies and possums[edit | edit source]

* The Virginia possum has been known to be a reservoir of rabies, as a result of transfer from other wildlife species such as bats, skunks and the raccoon.
* Cases have been reported all across the United States.[2][3][4]
* In New York state, the Wadsworth Center lists laboratory confirmed cases in possums 5 years out of 10 from 1989 to 1998.

### Rabies and bats[edit | edit source]

* In early 1931, Dr. H. Metivier, a veterinary surgeon, identified bats as the cause of paralytic rabies.
* In September 1931, Dr. J. L. Pawan, a government bacteriologist discovered Negri bodies within the brains of bats.
* In 1934, the Trinidad and Tobago governments began a program of vampire bat control, shooting, netting, trapping and poisoning and vaccination for exposed livestock.
* In 1953, basic research on bats and rabies progressed rapidly under the able direction of Arthur Greenhall, who demonstrated that at least 8 species of bats in Trinidad had been infected with rabies - particularly the Common Vampire Bat, Desmodus rotundus, the rare White-winged Vampire Bat, Diaemus youngi, as well as two abundant species of Fruit Bats: the Seba's Short-tailed Bat or Short-tailed Fruit Bat, Carollia perspicillata, which commonly roosts with Vampires, and the Jamaican Fruit Bat, Artibeus jamaicensis.[5]
* In 1960, Constantine in Frio Cave, Texas, demonstrated non-bite transmission of rabies.[6][7][8]
* In 1996, a single Daubenton's bat was found to be infected with a rabies-like virus usually found only in bats - European Bat Lyssavirus 2 (EBL2) in the United Kingdom, which was thought to be entirely rabies-free before this occurrence. A similar occurrence was reported in September 2002.
* In November 2002 David McRae, a Scottish bat conservationist from Guthrie, became the first human to contract rabies in the United Kingdom since 1902. He died from the disease on November 24 2002.
* In November 2004, Jeanna Giese, a fifteen-year old girl from Fond du Lac, Wisconsin, became the first survivor of rabies, without any vaccine administration.
* On May 12, 2006 Harris County Texas. U.S.A. Health Department officials reported that a teenage boy, Zachary Jones of Humble, Texas, had died of rabies at Texas Children's Hospital in Houston, Texas.
* On November 2, 2006 a 10 year old girl who had been bitten by a bat in Bourbon, Indiana, U.S.A. died of rabies.
* In August of 2006, a 73 year old rural resident located east of Edmonton, Alberta, Canada was bitten by a bat while he slept.
* On August 6, 2006, 950 Girl Scouts were urged to receive rabies shots by the Girl Scouts of America. The nine hundred and fifty girls had attended a camp in Virginia, U.S.A. in July, and had reported seeing bats in their cabins. Even though infections were relatively unlikely, the G.S.A. offered to pay for the shots, at a cost of nearly two million dollars. The Centers for Disease Control reports 27 cases of human rabies caused by the bat variant rabies virus in the United States from 1990 to 2002.[9]

### Rabies and Organ Transplantion[edit | edit source]

* In June 2004, 3 organ transplant recipients were reported dead after transplantion of kidneys and liver from an infected donor from Texarkana.[10] Marijuana and cocaine were found in the donor's urine at the time of his death, according to a report in The New England Journal of Medicine.[11]

> "[The surgeons] thought he had suffered a fatal crack-cocaine overdose, which can produce symptoms similar to those of rabies. 'We had an explanation for his condition,' says Dr. Goran Klintmalm, a surgeon who oversees transplantation at Baylor University Medical Center, where the transplants occurred. 'He'd recently smoked crack cocaine. He'd hemorrhaged around the brain. He'd died. That was all we needed to know'. Because of doctor-patient confidentiality rules, doctors involved with this case would not talk about it on the record, but a few did say that if no cocaine was found in the donor's blood, the E.R. doctors might have investigated his symptoms more aggressively instead of assuming he had overdosed. (Because no autopsy was done, doctors have not been able to establish whether the rabies or the drugs actually killed him)".[12]

* In February 2005, three German patients in Mainz and Heidelberg were diagnosed with rabies after receiving various organs and cornea transplants from a female donor.

### Rabies Vaccine[edit | edit source]

* In 1885, Louis Pasteur and Emile Roux developed the first rabies vaccination .This vaccine was first used on a human on July 6, 1885 - nine-year old boy Joseph Meister (1876–1940) had been bitten by a rabid dog.[4] [5]
* The vaccine consisted of attenuated virus harvested from infected (and necessarily dead) rabbits.
* Similar nerve tissue-derived vaccines are still used now in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective and carry a certain risk of neurological complications.
* In 1967, the human diploid cell rabies vaccine (H.D.C.V.) was started. The purified Vero cell rabies vaccine uses the attenuated Wistar strain of the rabies virus, and uses the Vero cell line as its host.

## Famous Cases[edit | edit source]

The most famous case of rabies disease that lead to survival for the first time in the history was the case of a girl called Jeanna Giese. The treatment that saved Jeanna Giese, a Wisconsin resident, was an innovated and experimental technique. The basics behind the treatment, which would later be called the Milwaukee protocol, were determined by Dr. Rodney Willoughby, an infectious disease specialist. The theory behind the treatment was to basically shut down her brain by medically inducing a coma. This would serve the purpose of giving her own immune system time to build up antibodies against the virus.[13] In other words, doctors thought it would be possible for Jeanna Giese to survive if they suppressed her brain activity, while allowing enough time for her immune system to attack the rabies.[13]

Although radical, the Milwaukee protocol was most likely the only way for Giese to have a chance for survival. It was also the first time that this method had been used.[13]

Inducing a coma was not the only task doctors performed. They also gave her many antiviral drugs such as ribavarin and amantadine. After approximately a week, tests showed that Giese's immune system was fighting the disease, so they began to cut back on the anesthetics. Doctors also gave Giese supplements for about 6 months after initial treatment. They gave her tetrahyrdobiopterin, which is similar to folic acid. This may have been involved in improving Giese's speech, motor, and other bodily functions.[13]

In June 2011, another child survived rabies infection without receiving the vaccine before appearance of symptoms. Precious Reynolds, an eight-year-old girl from Willow Creek, California, contracted the disease in April 2011 but did not receive medical care until mid-May, after her grandmother took her to the doctor because of influenza-like symptoms that grew so serious, her grandmother said they resembled polio. The hospital said doctors followed the protocol established for Giese. Reynolds was placed in a drug-induced coma and received antiviral medications. She survived after spending two weeks in intensive care undergoing the treatments.[14][15]

## References[edit | edit source]

1. ↑ Dunlop, Robert H. (1996). Veterinary Medicine:An Illustrated History. Mosby. ISBN 0-8016-3209-9. Unknown parameter `|coauthors=` ignored (help)
2. ↑ Krebs JW, Smith JS, Rupprecht CE, Childs JE.Rabies surveillance in the United States during 1996. J Am Vet Med Assoc. (1997) 211(12):1525-39. Review. Erratum in: J Am Vet Med Assoc. (1998) 212(8):1280. PMID: 9412679
3. ↑ Krebs JW, Smith JS, Rupprecht CE, Childs JE.(1999) Rabies surveillance in the United States during 1998. J Am Vet Med Assoc. (1999) 215(12):1786-98. Erratum in: J Am Vet Med Assoc 2000 216(8):1223
4. ↑ Krebs JW, Smith JS, Rupprecht CE, Childs JE.Rabies surveillance in the United States during 1996. J Am Vet Med Assoc. (1997) 211(12):1525-39. Review. Erratum in: J Am Vet Med Assoc. (1998) 212(8):1280. PMID: 9412679
5. ↑ Greenhall, Arthur M. 1961. Bats in Agriculture. Ministry of Agriculture, Trinidad and Tobago.
6. ↑ Constantine, D. G. 1962. "Rabies transmission by nonbite route." Public Health Reports 77, pp. 287–289.
7. ↑ Winkler, W. G. 1968. "Airborne Rabies Virus Isolation." Bull. Wildlife Disease Assoc. Vol. 4, April, 1968, pp. 37-40. Available online at: http://www.jwildlifedis.org/cgi/reprint/4/2/37
8. ↑ Messenger, Sharon L., Jean S. Smith, and Charles E. Rupprecht. 2002. "Emerging Epidemiology of Bat-Associated Cryptic Cases of Rabies in Humans in the United States." Clinical Infectious Diseases. 2002; 35, pp. 738–747. Available on line at: journals.uchicago.edu
9. ↑ "Rabies Surveillance". Centers for Disease Control. 2003. Retrieved 2006-11-10.
10. ↑ "Investigation of rabies infections in organ donor and transplant recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004". MMWR Morb Mortal Wkly Rep. 53 (26): 586–9. 2004. PMID 15241303.
11. ↑ Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, Paddock CD, Guarner J, Shieh WJ, Goldsmith C, Hanlon CA, Zoretic J, Fischbach B, Niezgoda M, El-Feky WH, Orciari L, Sanchez EQ, Likos A, Klintmalm GB, Cardo D, LeDuc J, Chamberland ME, Jernigan DB, Zaki SR (2005). "Transmission of rabies virus from an organ donor to four transplant recipients". N Engl J Med. 352 (11): 1103–11. PMID 15784663.CS1 maint: Multiple names: authors list (link)
12. ↑ Reynolds G (2005). "Will Any Organ Do?". The New York Times Magazine (10 July): &ndash, .
13. ↑ 13.0 13.1 13.2 13.3 "Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How?: Scientific American". Retrieved 2012-02-10.
14. ↑ "UC Davis Children's Hospital patient becomes third person in U.S. to survive rabies". UC Davis Medical Center. Retrieved 3 May 2012.
15. ↑ "Human Rabies 
 Indiana and California, 2006".

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