The virus isolated from an infected animal is named street virus : it has a very long incubation period and replicates also in extranervous tissues. After multiple passages on rabbit brain ("fixation") it becomes a fixed virus / virus fixé (remain fixed during further transmission; used for inoculating animals from which rabies vaccine is prepared), with a 4-7 days incubation period and replicating only in nervous tissues.

Table of contents :

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Epidemiology Proteomics Transmission Pathogenesis Symptoms & signs Laboratory examinations Prevention Therapy Prognosis Web resources

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Epidemiology : mortality worldwide is estimated to be 40,000-70,000 people annually, half of which are in children^ref

• USA : of the 47 cases of human rabies reported in the USA since 1990, 4 occurred in organ transplant recipients and were associated with an undetected case of rabies in a single organ donor^ref; the remainder apparently were acquired from contact with animals with rabies virus infections. 38 (81%) of the infections were acquired in the USA. Among the 9 infections acquired elsewhere, 2 were acquired in Haiti (1994 and 2004), 2 in Mexico (1993 and 1994), and 1 each in India (1992), Southeast Asia (1996), Ghana (2000), the Philippines (2001), and El Salvador (2004). The greatest risk for naturally acquired rabies in the USA is from encounters with and bites from insectivorous bats^ref. In particular, a rabies-virus variant associated with 2 small-bodied bats, the eastern pipistrelle bat (Pipistrellus subflavus) and silver-haired bat (Lasionycteris noctivagans) was identified in 20 (69%) of 29 persons with samples tested^ref. The continued availability of rabies vaccine currently relies upon only one licensed manufacturer in the USA; a 2nd manufacturer suspended and has not resumed production after a voluntary recall of its rabies vaccine in March 2004 (CDC. Manufacturer's recall of human rabies vaccine--April 2, 2004. MMWR 2004;53:287-9). In the USA, mandatory vaccination and stray-dog control programs have virtually eliminated circulation of any canine rabies virus variant among dogs^ref. In comparison, occurrence of rabies in dogs remains a problem in Haiti and other developing countries^ref. The patient bitten in Haiti in 2004 by a dog in Haiti 8 months before clinical signs of rabies became evident. This was the longest incubation period among 12 U.S. rabies cases with exposure history reported since 1997 (median: 39 days; range: 21 to 240 days); however, longer incubation periods of 11 months to 6 years were suggested by findings in 3 cases previously described^ref. Although human rabies is rare in the USA, it should be considered in the postmortem differential diagnosis of fatal viral encephalitis cases with short morbidity periods if no cause of disease has been established. Hospitalized patients with encephalitis of unknown etiology should be on contact precautions, and rabies should be part of antemortem differential diagnosis in these patients. Both antemortem and postmortem testing for rabies are available at CDC and can be arranged through state health departments. Retrospective detection of 4 transplant-associated rabies cases^ref and retrospective identification of an additional case in California in an immigrant from El Salvador, brought the total number of 2004 cases in the USA to 8, the highest number of human rabies cases reported since 1956, when 10 cases were reported.
• Europe :
• Austria reported one single rabies case -- in an equine -- during 2003; oral vaccination in wildlife is applied
• Germany : on April 2005 tropus moved in 4 German states and neighbouring parts of France, trying to vaccinate enough foxes to stop the disease spreading, as national and regional authorities trade accusations. The reason for the flare-up appears to be patchy vaccination of wild foxes in the German state of Hesse. Officials at Germany's national rabies laboratory in Wusterhausen say they will stamp out this nest of infection this year, by vaccinating foxes every 6 weeks if they have to. But their counterparts in France, Switzerland and Belgium are expressing "serious concern" that unless recommendations about fox vaccination made by a panel of European Union scientists in 2002 are strictly applied, large areas of Europe where rabies had been eradicated could be reinfected. Rabies eradication was one of Europe's success stories. Switzerland became rabies-free in 1998, thanks to a huge campaign in which biscuits doped with vaccine were distributed in fox habitats. France was next to eliminate the disease, in 2000, followed by Belgium and Luxembourg in 2001. In 2000, this helped convince the rabies-free UK to end compulsory quarantine for mammals brought in from some European countries. But in Germany, stubborn nests of infection persisted. Part of the problem was ensuring even vaccination in urban areas, where placing baits can be difficult, says Thomas Muller, head of the Wusterhausen lab. Another big problem was human error. States managed their vaccination campaigns themselves, with varying effectiveness. Muller's team is trying to get better cooperation. Several former problem states, including Bavaria, have not found any cases for several years. But there has been no let-up in Hesse, which found 24 rabid foxes in 2004. In December, one turned up in Baden-Wurttemberg, which had been rabies-free since 1996 and stopped vaccinating in 2002. And in January 2005, Rhineland-Palatinate, rabies-free since 1998, found rabid foxes near the Hesse border. Late in 2004 all 3 states plus Bavaria carried out emergency vaccination in threatened areas, and this week they are air-dropping vaccine-laced bait across thousands of square kilometres. France stopped vaccinating in 2003, but Florence Cliquet, head of the French national rabies lab in Nancy, says her team will bait fox dens along the German border this week, and will vaccinate a 60-kilometre-wide border strip in May 2005. The virus could really spread fast if it got loose now. The persistence of rabies in Germany is blamed on the ineffectiveness of the German vaccine, and points to figures suggesting that it takes twice as many German as French baits to clear an area of rabies. The virus in German vaccine sometimes reverts to the disease-causing form. This is known to have happened once in Austria,  but there have been only 3 suspected cases in Germany in the past 5 years. He insists the main problem is the way the vaccination campaigns have been run. The EU must hope he is right. New member states such as Poland still have rabies problems, and most vaccination campaigns rely on the German vaccine.  Despite the progress observed and the absence of substantive adverse environmental or health effects, oral vaccination is not a panacea, and should be viewed as an important adjunct to traditional prevention and control techniques in human and veterinary medicine. Local outbreak suppression of rabies among free-ranging wildlife is documented, and regional elimination of particular virus variants among specific, targeted carnivore hosts is demonstrable, but true disease eradication is not achievable at the present time by current techniques. Oral vaccination of wildlife against rabies has been one of the most remarkable achievements in wildlife disease management. As a result of this novel approach, large areas of Europe and North America have been freed of terrestrial rabies. The fox population has indeed increased in certain areas of Europe (up to 8-fold), but it has also decreased in other areas. Significant increase in fox densities, even when restricted to limited areas, might be of epidemiological significance. Several commercial oral rabies vaccines for wildlife are available which use the following rabies virus strains; SAD Berne, SAD B19, SAD P5/88, Vnukovo, ERA, SAD VA1, SAG1, and SAG2. The latter 3 are so-called "escape mutants" with 1 (SAG1, SAD VA1) or 2 (SAG2) substitutions at site 333 of the viral glycoprotein. All these attenuated rabies vaccine viruses are direct or indirect derivates from the original Street Alabama Dufferin (SAD)-strain that was isolated from a rabid dog in Alabama in 1935. Furthermore, a recombinant vaccinia virus expressing the rabies glycoprotein (V-RG) is also available as an oral rabies vaccine. In other words, all commercial available oral rabies vaccines are live virus vaccines and can therefore revert to virulence under field conditions, as has been documented for the SAD Berne and ERA-strain (Wandeler AI (1988) Control of Wildlife rabies. In: Campbell JB, Charlton KM (eds.) Rabies. Boston; Kluwer Academic Publishers, pg. 365-380; Wanddeler AI (1994) ERA induced rabies in Ontario wildlife. In: 5th Annual International Meeting Rabies in the Americas, Ontario, Canada, pg. 43-44). There are documented differences in the residual pathogenicity and immunogenicity between the different SAD-strains. Although the recombinant V-RG cannot induce rabies, other safety issues are involved with this vaccine, as has been demonstrated in the only known serious human incidence associated with an oral rabies vaccine^ref. The information about reversion to virulence of the German vaccine as mentioned in the New Scientist article is misleading and actually incorrect. A short description of this case can be found in the Rabies Bulletin Europe^ref.  On 31 May 2004, a young fox showing apathy and wasting was shot near the village of Gallizien in the district of Volkermarkt, Carinthia.  --- The animal was handed in for routine rabies diagnosis at the Institute for Veterinary Disease Control in Moedling, Austria. Initially the fluorescent antibody test (FAT) of the brain sample showed a positive result. Therefore additional diagnostic tests were carried out. Rabies tissue culture infection test (RTCIT) was performed on mouse neuroblastoma cells according to the OIE Manual of Standards for Diagnostic Tests and Vaccines with positive result. Also the mouse inoculation test (MIT) confirmed this finding. --- While a young fox (approximately 3 months old) was involved,  it was deemed highly unlikely that this animal had reached Gallizien from a rabies-infected area on its own, especially because the nearest rabies foci is over 75 km away (Croatia). The fox brain sample together with the oral vaccine strain used during the vaccination campaign in 2003/2004 were also analysed by means of RT-PCR of the rabies virus nucleoprotein gene yielding positive results. Subsequent sequencing of the 900 bp long PCR products showed that the virus strain from the rabid fox was related very closely to the oral vaccine strain. For confirmation complementary studies were initiated in close collaboration with the WHO Collaborating Centres in Weybridge, Great Britain and Wusterhausen, Germany. The present case showed that infection of a young fox with a live rabies vaccine-like virus is possible. Nevertheless, in the light of the intensive vaccination in this area during the last years the present case may be considered as a rare event". The said description does not refer to the relationship between the causative rabies virus and SAD P5/88. Final results of the complementary studies in the rabies reference labs in Weybridge and Wusterhausen will be helpful^ref. Other attenuated rabies vaccines besides the Vaccinia/antigen vector vaccine are still being used. First of all, there is no such thing as "the" German vaccine; there are actually 3 licensed German vaccines (SAD B19, SAD P5/88 and SAD VA1) from 2 different manufacturers. Although the Austrian case is still under investigation, it was shown by different laboratories that the virus strain isolated from the brain of the fox was a SAD-related virus (as all live-modified oral rabies vaccines) but not identical with the oral rabies vaccine virus distributed in the area (SAD P5/88). The 3 suspected cases in Germany are nothing more than that; suspected cases. The standard rabies diagnostic techniques to identify differentiate field virus from vaccine virus (monoclonal antibodies vs. PCR) have given contradictory results, and hopefully these cases will be clarified in the near future. The claim by Michel Aubert that the German vaccine is ineffective is incorrect, considering that this vaccine virus (SAD B19) still is the most widely used oral rabies vaccine in the world in terms of number of countries and baits used (> 100 million vaccine baits since 1983). Several whole countries and huge areas in other countries that have used this vaccine virus exclusively have already been free of terrestrial rabies for many years (e.g. Finland, the Netherlands, Italy, eastern part of Germany). Other countries will hopefully achieve this goal in the near future (e.g. Austria, limited area in western part of Germany, Poland). The vaccine virus used is just one of the many parameters influencing the success of oral vaccination. The actual rabies situation, density of settlements, and the fox population, together with the selected baiting strategy, are some of the other major factors determining the outcome of the vaccination campaigns.
• Asia accounts for > 90% of all rabies fatalities
• China : from 1984 to 1989, the annual reported cases were between 4000 and 6000 but decreased after 1990. In 1996, the reported cases decreased to the lowest level from 3520 in 1990 to 159. However, number of reported cases has been continuously increasing since 1998, reaching 1122 in 2002, a 7.06-fold increase as compared to the number in 1996. The epidemic areas were mainly located in the southeast and southwest parts of the country, such as Sichuan, Hunan, Guangxi, Guangdong, Anhui, Fujian, etc, where dogs were raised for meat and there was no requirement for such dogs to be vaccinated. In contrast, Beijing was considered to be rabies-free as a consequence of a policy of compulsory vaccination of pet dogs, which was rigidly enforced in urban areas. It seems that Beijing may have lost its rabies-free status, possibly due to population movements. Visitors to China should be made aware of this situation. Furthermore, there was not the significant seasonal distribution it showed before. Numbers of human rabies cases are continuing to rise over the last 5 years in China, with an increase of 44.65%, 1.74%, and 45.93% in 1997, 1998, 1999. Human rabies incidence was also seen an increase from 0.0134 per 100,000 in 1996 to 0.02708 per 100,000 in 1999. The provinces showing increases in rabies were mainly located in south China : among them, Jiangsu province reported 40 human cases in 1999, which increased 207.69% over the corresponding period in 1998. The cases in these high epidemic provinces accounted for 75% of the whole nation's cases. The number of reported rabies case is also rising. In 2003 : > 1000 cases
• important factors responsible for the recurrence of rabies
• increasing numbers of dogs being bred
• low inoculation rate of dogs
• poor control on the quality of (animal ?) rabies vaccine
• mistreatment  of wounds (failure to administer antirabies serum timely or for

the full course after exposure)
• lack of cooperation between different official departments regarding rabies control
The rabies-free status of Beijing in recent years can probably be attributed to the compulsory vaccination of pet dogs, which seems to be rigidly enforced in urban areas. In contrast, there is no requirement for dogs raised and sold for meat to be vaccinated. The majority of dogs which have been killed as a result of rabies outbreaks have been in dog meat production areas, where there are few if any pet dogs. The elevation of the dog from culinary item to household companion in Chinese society is being accompanied by an unexpected increase in the burden of cases of human rabies. Previous reports from China have described the containment of canine rabies in the capital by the licensing and compulsory vaccination of domestic pets. A similar policy will need to be implemented in rural areas throughout the country and in the booming southern province of Guangdong to reduce
both the number of cases of human rabies and the very high number of people seeking protection by vaccination. Guangdong province reported 306 deaths in 2005^ref
• India : a fatal case of imported human rabies has been reported in England in 2005. The patient was bitten by a dog while on holiday in Goa, India. The diagnosis of rabies was confirmed by the United Kingdom National Reference Laboratory for Rabies in Weybridge, Surrey^ref. In February 2005, a German woman died of rabies after spending four weeks in India in late 2004^ref, and in May 2004, a man in Bavaria, Germany died from a rabies infection that he acquired during his 5-month stay in India^ref. India reports at least 30 000 human deaths from rabies per year, i.e. an annual incidence of approximately 3 deaths per 100 000 population^ref
• South America : annual incidences of 0.01-0.2 deaths per 100 000 are reported from Latin America.
• Brazil : between 1986 and 2004, the Ministry of Health was notified of 743 human rabies cases in Brazil, most of which occurred in the north and northeast of the country. Numbers of cases had been falling steadily from 1980 (over 170 cases) to 2003 (under 20 cases), mainly due to control of rabies in dog populations. Up to 2003, most human rabies infections notified in Brazil were transmitted in an urban setting by cats or dogs, but most infections since 2004 have been transmitted by bats in rural parts of the states of Para and Maranhao. From May 2003 to May 2004 600 people were attacked by the thumb-sized vampire bats in municipality of Portel, next to the world's biggest estuarine archipelago of Marajo Island, state of Para, Brazil. During the course of March 2004, there were 17 human cases (13 confirmed and 4 suspected), including 15 deaths (13 confirmed and 2 suspected, almost all in the north (Amazonian Region) and northeast. On May 20 : 22 deaths (10 laboratory confirmed and 16 clinically and epidemiologically compatible). The bat attacks occurred mainly during the months of September and October 2003. In the meantime, these episodes have been frequent in the rural area of the Acuti Pereira River, where the affected persons reside. Initial evaluations indicate the existence of more than one colony of bats in the affected localities. In October 2005 12 rabies deaths were reported in Turiacu, in the state of Maranhao. Rabies deaths have also been reported in 2005 in Godofredo Viana (3), Candido Mendes (2) and Carutapera (2), and the local media reports that several hundred may have been bitten by bats. These areas are in the north of Maranhao, next to the focus of a bat-transmitted human rabies outbreak in the state of Para in 2004. Rabies transmitted by dogs is rare in other areas of the country, whereas rabies associated with vampire bat attacks on humans is not infrequent in the Amazonian region of Brazil and Peru. Outbreaks of bat-related rabies have been linked to the continued deforestation of the Amazon region, which has displaced vampire bats across northern Brazil and increased contact with humans. The Ministry of Health also notes that abandoned gold mines in Maranhao have provided favourable habitats for bat populations^ref
• Venezuela : vampire bat attacks on humans in been documented^ref. About 1130 people in Viseu and 140 inhabitants of Fermiana e Curupati, 2 1/2 hours from Viseu township [Para state, some 280 miles (450 km) to the east of Portel] had been bitten by the thumb-sized bats from May 2003 to May 2004. None of them had been to the health post to get antirabies serum or vaccine. So far, one death due to rabies has been recorded, along with 4 suspect deaths and 16 people admitted to hospital with symptoms. But now all the inhabitants of the 2 localities are being vaccinated, with a series of 5 doses. Dogs and cats are also being vaccinated there. > 130 bats have been captured and 5% of those will be tested for rabies. 1 patient arrived at the hospital on 13 May 2004 with paralyzed legs and is now in a coma and on a ventilator. 7 other patients ranging in age from 11 to 49 years are in stable condition and will be discharged in the next few hours. Only one of them had been bitten by a bat; agricultural pesticide poisoning was suspected to be the cause of the symptoms. They could not have had rabies, because nobody recovers after symptoms appear. Genetic characterization and antigenic analyses of isolates from human cases of rabies in Venezuela^ref have revealed considerable diversity and identified several antigenic variants
• Africa : 0.001-13 deaths per 100 000 are reported, but rabies is grossly under-reported in many countries.
• Morocco : officially reported rabies cases were: 2002: 23 humans, 192 dogs, 25 cats; 2003: 17 humans, 173 dogs, 14 cats. Obviously, the actual incidence in animals was much higher. In addition, there were numerous cases in domestic farm animals etc.

In a 1995 PAHO document vampire bat rabies (derriengue) is identified as an important public health and economic concern in Latin America, French Guinea, Guyana, Suriname and Trinidad and Tobago^ref. From 1989 to 1995, 73 human deaths were attributed to rabies transmitted by vampire bats. It is likely that both vampire and insectivorous bats play a role in the maintenance of rabies infection in Venezuela and in other Latin American countries. The increased number of human attacks may be linked to a change in the bats' migration pattern due to deforestation : such attacks usually occur when bats are deprived of their usual source of food, such as domestic pigs and cattle. Elsewhere (Australia, Chile, Europe, and North America), insectivorous bats are usually associated with transmission of rabies virus to humans. Vampire bats pose a significant problem also in the remote Mosquitia area of Honduras and Nicaragua, especially in the middle and upper ranges of the Coco River. Children represent 60-70% of the cases; most common sites affected were the great toe, the foot, the scalp and the tip of the nose. This empirical observation seems to contradict some studies that have shown increased vampire bite prevalence in adult (mostly male) humans. The discrepancy could be due to a number of reasons, including the demographics of the population studied (some of these surveys have done in mining areas of the Brazilian and Venezuelan Amazon region, where the population at risk would be expected to be predominantly adult and male); the food-seeking behavior pattern of the animals, which locate and recognize their hosts by detection of radiating body heat by means of special receptors in their noseleaf, as well as by the sense of smell and by echolocation: perhaps young children, having higher metabolic rates than adults, present an easier-to-find source for a bloodmeal. Children also have a thinner corneal layer in their epidermis and more superficial and larger number of capillary vessels in their skin, all of which would make the bite more "productive" from the bat's perspective. Lastly, there could be differences in bloodmeal-seeking behavior between northern (e.g. Central American) and southern (South American) bats, even belonging to the same species (probably the common vampire, Desmodus rotundus). Finally, it is important to remember that most people (adults or children) do not realize they have been bitten until they wake up then next morning, usually with a moderate amount of blood surrounding the lesion, due to the anticoagulant effect of the bat's saliva. Vampire bats bites are typically painless, and one wonders if, in addition to the known anticoagulants, the animal's saliva also contains some compound which acts as a form of topical anesthetic^{ref1, ref2, ref3}
Proteomics :

• nucleocapsid (NC) protein acts as a SAg for human Vb8- and murine Vb6-containing TcRs, triggering T_h2 polarization.
• rabies virus G glycoprotein (RVG) is a trimeric ligand for the N-terminal Cys-rich domain of TNFRSF16 / p75^NTR

Transmission :

• bites of infected (rabid) vertebrates^{ref1, ref2} :
• urban rabies : Carnivora (Canis familiaris (canine rabies is prevalent in Africa, Asia, and Latin America. Worldwide estimates of human rabies deaths exceed 50,000 cases each year, and >95% of reported cases occur in regions where canine rabies is endemic. Dogs account for 99% of human cases worldwide, and for 95% of post-exposure vaccinations), Felis catus (stray cats)), Microchiroptera (chiropterans (frugivorous, hematophagous and insectivorous bats); most human cases in the USA : in several South American countries, vampire bat rabies is a problem for both livestock and the human population. There are 3 species of vampire bats, the most important disease-transmitter being Desmodus rotundus. Protection of livestock has depended on the use of bovine vaccines and/or use of anticoagulants, such as diphenadione or warfarin, which can be administered to bovines as slow-release boluses, or mixed with grease and applied to the skin. Vampire bats suffer fatal hemorrhages in their wing capillaries as a result of ingesting bovine blood containing anticoagulant, or during grooming to remove adherent grease. Humans can be protected by vaccination with standard human rabies vaccine, or less effectively by protective netting at night. The vulnerability of children may be a consequence of greater depth of sleep and reduced awareness of attack by vampire bats), Rodentia (including squirrels, Mus musculus, Rattus spp.), Martes foina, or Meles meles). There is vaccine approved for horses and for cattle. In areas where rabies is known to be a concern, vaccinating horses and cattle is a cheap insurance policy against the devastating effects of this disease.
• sylvan rabies : Vulpes spp., Meles meles, weasels, Mustela putorius furo, marmots and Mustela eversmannii.
Properly cooked vertebrate meat do not constitute a source of rabies infection.
During the period 1980 to 2000, a total of 26 (74%) of rabies virus variants obtained from patients in the USA was associated with insectivorous bats (24 (74%) of the 32 cases since 1990), most commonly silver-haired and eastern pipistrelle bats^{ref1, ref2}, including a variant from a fatal case of rabies reported in Wisconsin in 2000^ref, although a history of a bite was established in only 2 cases. In this case, only 5 health-care workers received PEP. Contact with bats occurred in approximately half of the other cases. These cases represent various bat-contact histories: a bat bite, direct contact with bats with multiple opportunities to be bitten, and possible direct contact with a bat. Although rabies is usually transmitted by a bite, persons may minimize the medical implications of a bat bite. Unlike bites from larger animals, the trauma of a bat bite is unlikely to warrant seeking medical care. Unless the potential for rabies exposure is known to the patient, rabies post-exposure prophylaxis (PEP) will not be received. Although bat rabies virus variants can be transmitted secondarily from terrestrial mammals, the lack of other animal-bite histories and the rarity of bat rabies virus variants found in terrestrial mammals suggest that this means of transmission is rare. Persons who are bitten or scratched by any animal should wash wounds thoroughly and seek immediate medical attention to evaluate the need for PEP. In all cases where bat-human contact has occurred or is suspected, the bat should be collected and tested for rabies. If the bat is unavailable, the need for PEP should be assessed by public health officials. PEP should be considered after direct contact between a human and a bat, unless the exposed person can be certain a bite, scratch, or mucous membrane exposure did not occur. PEP may be considered for persons who were in the same room as a bat and who might be unaware that a bite or direct contact had occurred (e.g., when a sleeping person wakes to find a bat in the room or an adult witnesses a bat in the room with an unattended child, mentally disabled person, or intoxicated person). PEP is not warranted when direct contact between a human and a bat did not occur. Seeing a bat or being in the vicinity of bats does not constitute an exposure
• rarely, if ever, do non-bite exposures, including scratches, contamination of an open wound, or direct mucus membrane contact with infectious material (such as saliva or neuronal tissue) cause rabies. Rabies, a Lyssavirus, normally affects the neurological tissue. However, the virus is most often transmitted through saliva or contact with oral or gastric mucosa^ref. Additionally, rabies virus also has been detected in the kidney, prostate, pancreas, and other tissues and body fluids (Debbie JG, Trimarchi CV. Pantropism of rabies virus in free-ranging rabid red fox Vulpes fulva. J Wildl Dis 1970;6:500-6). In naturally occurring cases, the proven vehicle for transmission is saliva and neural tissue. Anecdotal reports exist of rabies transmission by ingestion of milk by a nursing lamb from its mother^ref. However, in all of these reports, a bite or mucous membrane exposure could not be ruled out.
• unpasteurized milk : there are no published studies that have demonstrated the presence of rabies virus in cows' milk. Although transmission of rabies virus from consuming unpasteurized milk from an infected animal is theoretically possible, no human has ever been reported to develop rabies via this route -- apart from the cases described in Oklahoma in December 2005^ref. Most persons who consume raw milk or cream prepared from rabies virus-infected cows are at minimal risk for rabies exposure. Infants and persons with certain medical conditions may be at higher risk. Medical conditions that would place a person at higher risk are those that suppress the immune system, cause abnormalities of the palate, or cause open sores, erosions, or ulcerations in the mouth, throat, or esophagus. The risk of contracting rabies through milk could be better defined if samples of milk and mammary tissue were collected from rabid livestock and assayed for the presence, viability, and infectivity of rabies virus. Regardless of the amount of viable rabies virus that may be shed in cow's milk, the theoretical risk for transmission of rabies from this route can be eliminated if all dairy products are pasteurized before consumption. An outbreak of rabies as a result of consumption of dairy products from rabies virus-infected cattle occurred in Bhutan since January 2006^ref
• laboratory aerosols
• healthcare-associated transmission : the risk is extremely low; transmission of rabies virus from infected patients to health-care providers has not been documented^ref. The use of Standard Precautions^ref for contact with blood and body fluids (for example, gloves, gown, mask, goggles, or face shield as indicated for the type of patient contact) prevents exposure to the rabies virus.
• human-to-human transmission of rabies among household contacts : no laboratory-confirmed cases of have been reported^ref.
• fomites or environmental surfaces : no cases of rabies have been reported
Routes of possible exposure include percutaneous and mucocutaneous entry of the rabies virus through a wound, non-intact skin, or mucous membrane contact. Intact skin contact with infectious materials is not considered an exposure to the rabies virus. Types of exposures in domestic settings for which administration of PEP would be appropriate include bites, sexual activity, exchanging kisses on the mouth or other direct mucous membrane contact with saliva, and sharing eating or drinking utensils or cigarettes. In health-care settings, additional opportunities that can lead to contamination of mucous membranes or non-intact skin with oral secretions include procedures such as intubation or suctioning of respiratory secretions or injuries with sharp instruments (needlesticks or scalpel cuts). Percutaneous injuries (as from needlesticks) are considered exposures because of potential contact with nervous tissue. Contact with patient fluids (such as blood, urine, or feces) does not pose a risk for rabies exposure^ref.
• transplantation from infected donor : rabies testing is not part of the routine screening process^ref. To decrease the risk of this happening again, one of the questions that should be asked before organs are harvested for transplant is whether the potential donor has traveled in a rabies endemic country within the last 3 to 6 months
• solid organ transplantation
• lungs, kidneys, liver and a segment of iliac artery were recovered from an Arkansas resident who had reported being bitten by a bat and died from SAH  in June 2004 after visiting 2 hospitals in Texas and were later transplanted on 4 May 2004 into 5 recipients (the liver, kidneys, and segment of iliac artery at the Baylor University Medical Center (BUMC) in Dallas, Texas to a man with ESLD, a female with ESRD caused by DM and HTX, a male with ESRD caused by FSGS and a man with ESLD receiving liver from an uninfected donor (the circumstances suggest that rabies virus may have passed from the infected artery tissue to the brain of the organ recipient by a non-neural route); the lungs in an Alabama hospital), one of whom (the lung transplant patient) died during transplant surgery, while the remaining 4 developed encephalitis and died. No other organs or tissues were recovered from the donor, and the donor did not receive any blood products before death)
• in Neu-Isenburg the Deutsche Stiftung Organ-transplantation (DSO, German Organ Transplantation Foundation; Federal Organ Procurement Agency) announces that 3 patients suspected of having rabies may have been infected through organ transplants (lungs, combined kidney/pancreas, and kidney) performed in 3 German transplant centers (Hanover, Marburg, Hannovers Muenden) at the end of 2004-Jan 2005. These 3 recipients have been hospitalized with suspected rabies encephalitis within 6 weeks and are in extremely critical condition. 3 other patients who received the liver and the corneas from the same donor and who were transplanted in Heidelberg and Mainz are well. The donor was a 26-years old woman who was hospitalized in December 2004 without symptoms of rabies : the patient contacted at least 3 hospitals because of her "mysterious" illness in the last weeks before her death. This included neurology (because of severe headache) and psychiatry (because of aggressive/bizarre behavior) and a recent examination of her brain showed typical signs of the disease. How the woman may have contracted rabies was unclear, but she had been in India in October 2004. For several reasons, predominantly travel to a malaria-endemic country, the organ donor would have been disqualified as a blood donor according to German legislation. She suffered a cardiac arrest that led to cerebral ischemia despite resuscitation measures that transiently stabilized her circulation. The last 2 deaths from rabies in Germany occurred in 1996 and 2004, and both patients caught the disease abroad^ref. In 2 of the patients who received organs from this donor, the rabies virus was isolated by means of molecular biological tests. It is thus obvious that these recipients have been infected. In another recipient, the neutralization test identified rabies-specific antibodies. This result may also be due to an earlier exposure to the virus and thus does not provide clear-cut evidence of an acute rabies infection. All health professionals who were involved in the transplants or caring for the patients have been identified and inoculated^ref. In March 2005, the 70-year-old man who received the donor's kidney died, along with the patient who received a lung from the woman : on April 7 the 45-yo man who received the other kidney and the pancreas died, too.
• corneal allograft (8 recipients of transplanted corneas in 5 countries^ref) : success has been achieved in detecting virus in implants and initiating PEP within 24 hours of transplantation

Pathogenesis : replication in skeletal muscle cells (Negri bodies) => peripheral nerves => salivary glands, pancreas and adrenal glands^ref. Rabies did not permanently damage any brain structure. Instead, death comes because the virus seems to cause temporary dysfunction of brain centers that control critical functions like breathing and swallowing.
=> rabies (a.k.a. lissa in Italy) after 10 days-some years : the development of rabies generally takes 10 to 90 days when the virus is transmitted through a bite^ref.

• excitation or furious stage : aerophoby and hydrophoby (spasm of deglutition muscles at sight of water), convulsions due to encephalitis, alterations of heart and breath rates, urinary retention and constipation. Respiratory failuire may lead to death within 4-5 days
• (paralytic stage : apathy, exitus due to heart failure)
• relaxed stage : coma

Laboratory examinations : antemortem diagnostic samples consist of a full-thickness skin biopsy (4 to 6 mm in diameter) from the nape of the neck, fresh saliva, serum, and CSF. Although postmortem rabies diagnosis can be performed on formalin-fixed brain material, fresh brain material provides the optimal sample for maximum sensitivity, specificity, and time efficiency. Rabies virus antigen is detected by a modification of the direct fluorescent antibody test^ref
Prevention^ref :

• travelers to endemic countries are advised to avoid contact with dogs and other animals, and rabies pre-exposure prophylaxis (consisting of 3 intramuscular doses of killed rabies vaccine on days 0, 7, and 21 or 28) is recommended for persons planning to stay longer than 30 days in remote areas without access to medical facilities^ref. 2 kinds of oral vaccine bait are used for raccoons : an extrusion of fish meal with a hole in the centre containing a vaccine-filled sachet and sachets simply coated with fish meal. Surrent vaccines (all derived from canine rabies) do provide protection against bat rabies viruses
• rabies postexposure prophylaxis (RPEP)^ref : human rabies is preventable if the exposure is recognized and the patient receives appropriate wound care and postexposure prophylaxis before clinical signs of rabies are evident. RPEP consists of rabies immune globulin (homologous immune antiserum) infiltrated at the site of the exposure (bite) and 1 dose of killed rabies vaccine administered in the deltoid (or anterolateral thigh of infants and small children) on days 0, 3, 7, 14, and 28^ref. When applied appropriately, this combination has been effective in preventing death after an exposure. PEP is recommended for all persons with a bite, scratch, or mucous-membrane exposure to a bat, unless the bat tests negative for rabies. When direct contact between a human and a bat has occurred and the animal is not available for testing, PEP should be administered when a strong probability of exposure exists. However, if a bat bite is unrecognized or if the significance of exposure is underestimated, medical intervention might not be sought and appropriate treatment not administered. Persons bitten by a potentially rabid animal should immediately :
• wash the wound thoroughly with soap and water
• capture the animal (if this can be done safely by avoiding direct contact) and submit it for testing or quarantine
• contact local or state public health officials
• visit a physician for treatment and evaluation regarding the need for PEP.
Persons should not handle or keep bats as pets and should keep bats away from living quarters and public places.Previous reports of rabies cases have noted large numbers of contacts being treated^ref; however, delivery of health care to a patient with rabies is not an indication for PEP unless the mucuous membranes or open wound of a health-care worker are contaminated by infectious material (e.g., saliva, tears, CSF, or neurologic tissue). Adherence to standard precautions for infection control will minimize the risk for exposure^ref. Several aspects of post-exposure prophylaxis also need mentioning :
• immediate and extensive washing of all bite wounds and scratches with soap and water and a virucidal agent such as povidine-iodine irrigation are important in preventing rabies. Indeed, in animals, this alone reduces the likelihood of rabies markedly^{ref1, ref2}.
• small rodents (such as squirrels, hamsters, guinea pigs, chipmunks, rats, and mice) as well as lagomorphs (rabbits and hares) are almost never found to be infected with rabies and have not been known to transmit rabies to humans. The woodchuck, quite a large rodent, accounts for most rodent rabies in endemic areas of rabies.
• much of the rabies prophylaxis is given related to dog and cat bites. This can be minimized by immunizing one's pets against this infection.
• HRIG has always been located in town even if it is not in stock at the institution that requires it

Therapy : behavioural or histopathological examination of the vector for > 10 days, cleaning wound with water & soap, ethanol 40-70%, benzalchonium chloride 0.1%, therapeutical killed vaccine. The approach to management of the rabies normally should be palliative. In unusual circumstances, a decision may be made to use an aggressive approach to therapy for patients who present at an early stage of clinical disease. No specific course of treatment for rabies in humans has been demonstrated to be effective, but a combination of treatments, which might include killed rabies vaccine, homologous immune antiserum, monoclonal antibodies, ribavirin, IFN-a, or ketamine, has been proposed. Corticosteroids should not be used^ref.
Prognosis : historically, the mortality rate among previously unvaccinated rabies patients has been 100% once symptoms develop^ref. Only 6 cases of human recovery after rabies infection and onset of symptoms have been described :

• 5 people were either previously vaccinated or received some form of PEP before the onset of symptoms. Viral antigen was not detected nor was virus isolated from those patients; increased antibody titers detected in serum and CSF (inconsistent with vaccination alone) confirmed the diagnosis of clinical rabies
• 1966^ref
• 1972 : the only one of the 5 patients recovered without neurologic sequelae^ref
• 1978 : a 45-year-old woman from Mendoza, Argentina, was severely bitten by a dog that died 4 days later. Before death, the dog was nervous, aggressive, and had occasional seizures. Ten days after the woman had been bitten, rabies vaccine treatment was begun: 14 daily doses of suckling mouse brain vaccine followed by 2 booster doses. Twenty-one days after the biting episode, she developed a cerebellar striatal syndrome, which persisted throughout several months, and severe encephalitic symptoms, which persisted for 75 days. After 13 months, recovery was nearly complete. The patient's serum and CSF contained rabies-neutralizing antibodies reaching maximum titers of 1:640 000 and 1:160 000, respectively. Titers of this magnitude have never been previusly recorded after suckling mouse brain vaccine treatment^ref.
• 1994 : a 9-year-old boy from Mexico^ref
• 2002 : a partial recovery in a 6-year-old girl^ref
• in a unique case the patient received no rabies prophylaxis either before or after illness onset. 15-year-old Jeanna Giese from Fond du Lac, Wisconsin, USA, was infected when she was bitten by a bat while at a church service on 12 Sep 2004. She did not visit a doctor and so didn't received RPEP, as is standard medical practice for such an exposure. The bite was quick and small, so the girl thought she had just been scratched. Her fellow churchgoers assumed that only healthy bats could fly, so they picked it up after it flew into a window and threw it out the door. She began showing rabies symptoms on 13 Oct and on 18 Oct, she was admitted to the hospital with fluctuating consciousness, slurred speech and other symptoms typical of full-blown rabies. The original description of the bat attack suggested that the rabid bat was not preserved. This is unfortunate, because isolation of rabies virus from this animal might establish whether the genome of the virus carried any attenuating mutations that might have played a role in the survival of the patient. The treatment includes 2 anesthetics and 2 antiviral medications. The history of a bat bite one month before this patient's illness suggests an etiology of bat-associated rabies virus variant. This is consistent with the epidemiologic pattern of rabies in humans in the USA during the preceding 2 decades. Treatment included induction of coma while a native immune response matured; rabies vaccine was not administered. Clinical management of the patient consisted of supportive care and neuroprotective measures, including a drug-induced coma and ventilator support. The patient was treated with ketamine, midazolam, ribavirin, and amantadine. Probable drug-related toxic effects included hemolysis, pancreatitis, acidosis, and hepatotoxicity. Lumbar puncture after 8 days showed an increased level of rabies antibody, and sedation was tapered. Paresis and sensory denervation then resolved. Intravenous ribavirin was used under an investigational protocol. Given the lack of therapeutic utility observed to date, and because the patient had rabies virus-neutralizing antibodies on diagnosis, a decision was made to avoid use of immune-modulators (e.g., rabies vaccine, rabies immune globulin, or interferon). The patient was kept comatose for 7 days; during that period, results from lumbar puncture indicated an increase in antirabies IgG by immunofluorescent assay from 1:32 to 1:2048. Her coma medications were tapered, and the patient became increasingly alert. On the 33rd day of illness, she was extubated; 3 days later she was transferred to a rehabilitation unit. At the time of transfer, she was unable to speak after prolonged intubation. She was able to walk with assistance, ride a stationary cycle for 8 minutes, and feed herself a soft, solid diet. She solved math puzzles, used sign language, and was regaining the ability to speak. The prognosis for her full recovery is unknown. Her parents said she stood up for the first time on Nov 23 and recognizes people when they came in the room. The patient was removed from isolation after 31 days and discharged to her home after 76 days. At nearly 5 months after her initial hospitalization, she was alert and communicative, but with choreoathetosis, dysarthria, and an unsteady gait^ref. Even if the girl's treatment proves successful in a 2nd patient, it is not clear how widely it could be used in poorer parts of the world, since it requires an intensive care unit, with all its high technology. Clinicians and the public should recognize the risk for contracting rabies from any direct contact with bats and not regard it as a curable disease on the basis of the outcome of this case^ref. Artificial hibernation, was introduced in 1952 by a French Navy Surgeon, Henri Laborit, who demonstrated, for the 1st time, the use of chlorpromazine to tranquilize patients without sedation. Subsequently, Laborit devoted himself to research and became the leader in therapy of psychotropic syndromes. He received the Albert Lasker prize in 1957. In 1958, Laborit opened the Laboratory of Eutonologie, at the Boucicaut Hospital in Paris. He directed this laboratory until his death in 1995. Artificial hibernation was also used in Viet Nam to treat patients recovering from surgery, or undergoing severe post-traumatic shock, or suffering from massive septicemia. The usual lytic cocktail consisted of a mixture of Largactil-Phenergan-Dolosal, and it was believed that the induced hypothermia would depress the defense mechanisms of the patient and inhibit, at least for a while, the active participation of organs, thus minimizing large expenditures of energy. Having lost a very close friend to rabies, who was not given the possible benefit of artificial hibernation, I find it marvelous that the procedure was resurrected successfully to treat this recent rabies patient, and Dr. Willoughby should be praised for his courageous initiative^ref

Web resources : RABNET at WHO