(Hydrophobia, Lyssa)
Infectious viral disease caused by neurotropic virus characterised by nervous symptoms and lesions followed by ascending paralysis and always terminates in death. Other than Australia, England, Singapore, Bahrain and Japan it is reported from all other parts of the globe. Japan is the first Asian country that eradicates Rabies.

Etiology: Bullet shaped RNA virus which belongs to Rhabdo viridae and genus Lyssa. This is a neurotropic virus and occurs in CNS. Nucleocapsid core is formed of RNA and three other proteins viz. Nucleoprotein, glycoprotein and non-structural protein. G protein possesses the biological and immunological functions. Lyssa virus genus contain 25 viruses of which Lagos bat (serotype II), Mokala (serotype III), Duvenhage (serotype IV), European bat lyssa virus I and European bat lyssa virus II are closely related to Rabies virus. Virus can be grown in embryonated eggs (5-6 days old) and suckling mice are used as experimental animals.
	It can be cultured in chicken embryo, cell cultures of hamster, mice, and pigs, human and bovine cells. 50% glycerine can preserve the virus. Most common reservoir hosts are fox, dogs, wolf, jackal, skunk, bats etc. Occasional hosts are man, cat, cattle and horse. Bats are the only species where the virus is not pathogenic. A pH below 4 or above 10 will destroy the virus. Virus is sensitive to UV light and heat (>56˚C). It will be inactivated by most of the disinfectants but partially resistant to phenol.

Virus is grouped into street virus and fixed virus.
No.PropertiesStreet virusFixed virus
1OccurrenceNatural infectionPassaged by serial intracranial root in rabbit
2Incubation periodVariable, 11-47 daysShort, 6-7 days
3Negri body productionYesNo
4Presence in salivaYesNo
5Self limiting or notNoYes
6Use in vaccineNoYes
Transmission: Mainly through bite of the infected ones. Virus can be introduced by inhalation and through mucus membranes of eyes and mouth. Virus may be found in saliva 3-7 days before appearance of clinical signs. Infected cattle also excretes virus in saliva. Rarely virus found in milk, blood, urine and other secretions. All warm blooded are susceptible and fowl can be infected experimentally. 

Pathogenesis: Minimum incubation period required is 10 days and it can go up to 12 months. Primary replication occurs in muscle fibres and aggregates around nerve endings and centripetal migration happens. When it enters spinal cord, migration towards brain will be faster and ultimate target of virus is CNS. Virus also infects salivary gland by centrifugal movement. Presence of virus in nerve and brain causes severe irritation and this leads to development of aggressiveness, excitement, madness and convulsion.

Symptoms: Disease is manifested in two main forms. a. Dump or paralytic b. Furious

a.	Dumb or paralytic: Initially there is change in voice which is howling or bellowing. Short period of excitement followed by incoordination, paralysis, dropped jaw, dehydration, loss of condition and death. In cattle there is ruminal tympany, tenesmus and sometimes diarrhoea occurs. Progressive paralysis follows leading to coma and death. Animal will not be able to close eyes and staring of eyes can be noted.

b.	Furious: Most common form. This form can be divided in to two stages. 
1. Stage of melancholy: Change in behaviour. There will be a tendency to bite animate or inanimate objects, does not obey master and chewing iron chain. This period lasts for 1-3 days. 
2. Stage of excitement: Dog become more aggressive; try to hide in dark places due to photophobia. Animal attack without provocation. There will be change in sound due to paralysis of vocal cord, incoordination, convulsion, fly catching, aimless wandering, causing self injury, hanging of lower jaw (due to paralysis), copious drooling of saliva, ascending paralysis, coma and death follow within 3-10 days of showing signs. Animal will die due to paralysis of respiratory muscle. The female dog may show the signs of heat and accept the male. In many cases animal become docile and become aggressive later. Dog may attack the owners. This period lasts for 1-7 days. 

Cats: Furious form is the most common. Scratching is main symptom. Usually cats don’t like the handling by others. So this can be misinterpreted.

Cattle: 
1. Dumb: Paralytic signs like swaying of hindquarters, knuckling of fetlock, frequent attempt for defaecation, ballooning of rectum, unable to drink water and a sound will be produced after dipping the head in water. 
2. Furious: Attack any moving object, jumping, recumbency, hypersensitivity reaction if they hear sound.

Horses & Pigs: Furious form is common.

Classification of exposure
Class I: Slight or negligible exposure. All cases of lick except on fresh cut drawing blood.
Class II: Moderate exposure. Includes licks on fresh cut and all bites except on head, neck, face, palm and finger.
Class III: Severe exposure. All bites on neck or above, palm and finger, lacerated wounds, multiple wounds (5 or above), bite from wild animals viz. wolf, jackal and others. 

Diagnosis
1.	Clinical signs: not always confirmatory. Throughout the course of the disease, the animal may not secrete the virus. Even if the bite is from an infected animal only 30% of bitten are getting infected.
 
2.	Laboratory tests: Brain of the dead animal preserved in glycerine saline should be sent to laboratory. In this search for Negri bodies can be done in sections of brain after staining with Seller’s stain or Giemsa stain. Only 50-60 % of the cases show Negri body. 6-10 Negri bodies will be present in a cell. Oval or circular shape, smaller than 1µ (0.25 – 30 µ), red or magenta colour when stained with Seller’s stain. Preferred site for taking impressions are:
a.	Dog: Hippocampus Cattle: Purkinje cells, cerebellum, Pons, medulla.
		FAT is the preferred test in which results can be declared with 100% accuracy. In decayed material, FAT is more sensitive. Smears from hippocampus, medulla and cerebellum can be used.

3.	Corneal test or saliva test: Based on demonstration of Rabies virus antigen in corneal epithelium and saliva of patient (by FAT). This is the only one test that can be done prior to death.

4.	Animal inoculation studies: Mice and rabbit can be used. Prepare 5% suspension of material (hippocampus, salivary gland, and saliva), centrifuge, and take the supernatant, 0.03 mL is introduced into brain of mice (6 numbers). It takes 5-20 days for development of symptoms and death. Confirmation with mice is absolute. If rabbits are used then introduce 0.3 mLl into brain after making a drill. Inoculate two rabbits to avoid error. After 10 days nodding of the head can be seen. By 14 days symptoms of paralysis can be seen and within 3-4 days animal will die. Prepare impression smear and demonstrate.

Treatment: No recovery is possible in natural infection. But there are some reported cases of recovery in experimental cases. Wound should be cleaned with water and soap. Alkali prevents multiplication of virus. If suture is necessary do it after 48 hours of exposure only. Wound can be infiltrated with hyper immune serum. 

Control
1.	Vaccination. Two types. a. Prophylactic and b. Post exposure
a.	Prophylactic: Primary vaccination – 3 months of age, then revaccination annually. If primary vaccination is given below 3 months of age, then booster should be given at 3 months of age.
b.	Post exposure: 0, 3, 7, 14, 28, 90 days. 0 day means the day of dog bite or within 24 hours of dog bite.
	Dose and route: 1 mL SC/IM. Generally proved vaccines that can produce 2.5 IU 	antibodies can be used.
2.	Strict quarantine measures for imported canine.
3.	Enhancement of people’s awareness.
4.	Control of street dogs and practice of ABC measures and vaccination of street dogs.
5.	Practice of prophylactic vaccination programme.
6.	Proper fencing to avoid wild animal population.