BASIC INFORMATION ABOUT RABIES

DR.MOHAMMAD KHALID MBBS,FCPS(Medicine)

History of Rabies
Rabies is known to be one of the oldest and most dreaded disease reported since ancient times Rabies has been reported in early Babylonian, Greek, Roman Record The virus was not seen under the E/M until 1960s People/settlers from Europe Brought rabies to America through their animals who were carriers of the virus Louis Pasteur experimented his rabies vaccine on a 6 years old boy Joseph Meister in 1885
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What is Rabies
Rabies comes from a Latin word meaning To Rage It is a deadly but preventable viral disease It is transmitted through bite of Rabid animals It affects mammals (warm blooded animals)
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What is Rabies (Contd)

Wild:
Dog, Fox, Jackal, Raccoon, Wolf, Cat, Bat etc.

Domestic/pets
Dog, cat, livestock Rabies in Rodents not found PEP usually not required, treatment can be given on individual assessment.
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Classification and structure

Most rabies viruses belong to genus Lyssavirus and family Rhabdoviridae: - Bullet shaped RNA viruses - Approx 180 nm long 75 nm wide - The negative stranded RNA genome contain five genes - The genes encodes five proteins
Nucleoprotein, phosphoprotein, Matrix protein, glycoprotein, polymerase
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Transmission
Rabies passes from
animal to animal animal to human.

Most common route is bite from infected animal Non bite exposures Infectious material from rabid animal i.e. virus laden saliva, infected brain tissue accidentally coming in contact with mucous membrane, or wound
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Transmission (Contd)
Aerosol Lab workers working with virus Few documented cases of rabies being contracted in caves where vampire bat reside Human to human transmission usually does not occur (risk if patient bites) eight documented cases - recipients of corneal transplants where donors had symptoms resembling rabies Thailand (2), India (2), Iran (2), USA (1), France (1)
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Incubation period
(time from exposure to the onset of clinical sign of disease) Typically 1-3 months (20 90 days) but varies from few days to several years

Viral entry and spread

Following primary infection, there is eclipse phase i.e. virus is not detected in the host tissue - varies from days to several months Presence of viral antigen in host tissue stimulates Cell Mediated Immune response and it can stop viral entry in nerve
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Viral entry and spread (contd)

Once virus enters the nerve, the process is progressive infection Entry may be direct or indirect Myocytes unmyelinated fibers motor/sensory neurons Move at rate 8-20 mm/day Retrograde axoplasmic flow
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Stages of entry and spread

Attachment to nerve cell Penetration in nerve cell (adsorption) Replication in nerve cell Budding attack new cells Centrifugal spread from CNS to nerves of skin, intestine, salivary gland
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Dissemination
Once inside the CNS the process become rapid Active CNS infection is followed by passive centrifugal spread Invasion of highly innervated sites i.e. salivary gland, skin and intestine Period of cerebral infection is followed by behavioral changes
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Symptoms/signs
Clinical history History of bite, suspicion of rabies No history of bite problematic especially prodromal stage Rabies progression takes 7-14 days Mean time between initial presentation and death is about 16 days
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Symptoms/signs (contd)
Prodromal stage (2 10 days) Flu-like symptoms nonspecific pharyngitis fever, malaise, headache, anorexia and vomiting Paresthesias at site of bite or scratch begins during prodromal stage
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Symptoms/signs (contd)
Neurologic Stage (2 7 Days) Patient present with: Aphasia, incoordination, paresis, paralysis, behavioral changes, unusual anxiety, agitation, hyperactivity, hyper salivation, hyperlacrimation, myoclonus Difficulty in swallowing (foaming at mouth, inability to swallow), hydrophobia &aerophobia
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Symptoms/signs (contd)
Neurologic Stage (2 7 Days) Complications
Hypotension, Cardiac arrhythmias, Cardiac arrest, Coma, DIC and respiratory failure

Differential Diagnosis
Bacterial Meningitis Viral Encephalitis herpes simplex encephalitis Gullien barrie syndrome Cerebral Malaria
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Pathology
Encephalitis/Myelitis Brain tissue infiltrated by lymphocytes, neutrophils and plasma cells Eosinophilic inclusions (Negri-bodies) in neuronal cells
Pyramidal cells of hippocampus Purkinjee cells of cerebellum cortex Spinal ganglia.

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Thank you
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Situation Analysis (Contd)

The majority of Rabies cases reported to CDC occur in wild animals. Domestic animal account for less than 10%. In Pakistan data about Rabies is an adequate. Data at HMIS is about animal bite cases. During 1994-1997 47,059 animal bite cases and 1998-2000 1,70,508 cases were registered A 5% mortality rate would lead to the death of approximately 1800-2000 rabies cases every year.
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Situation Analysis
More than 60,000 deaths occur per annum globally. Human Rabies cases have been documented on all continents except Australia and Antarctic. In USA Rabies is reported in wild animals In 1997 4 people died of human Rabies in USA. Hawaii has been declared free of Rabies.

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Post Exposure Prophylaxis

All unprovoked animal attacks are considered high risk for rabies If bite or m.m contact is inflicted by domestic animal already vaccinated and owner quarantine it for 10 days PEP can be with held If animal shows signs of rabies, euthenize and send for lab testing Treatment is started and if result is negative then treatment is with held
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Post Exposure Prophylaxis (contd)

Immediate treatment for bites scratches from high risk animal. Although no human to human transmission documented but exposure to CSF, saliva or m.m of a person suspected of having rabies. The handler should receive complete prophylaxis. Human/Equine Immune globulin and vaccine recommended for treatment.
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Post Exposure Prophylaxis (contd)

Five shots of vaccine given on day 0, 3, 7, 14, 28 on deltoid region Vaccine take 7-30 days to induce active response lasting 2 year. For children dose same as for adults anterolateral thigh.

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Post Exposure Prophylaxis (contd)

Gluteral area not preferred - poor absorption. Passive Immunization HRIG/ERIG. Immediate protection with serum half life 21 days. I.G. half infiltrated in and around the wound locally and rest injected in gluteal area. In Immune-compromised person measures serum antibodies to detect adequate Immune response.
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Post Exposure Prophylaxis (contd)

I.G. safe during pregnancy I.G may cause hypersensitivity. Do not administer IG in repeated doses once treatment started with vaccine. Administer live vaccines 14 30 days before or 6-12 weeks after I.G.

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Post Exposure Prophylaxis (contd)

Ab response to vaccine may be delayed if I.G. administered simultaneously with rabies I.G Hypersensitivity reaction may occur with vaccine also. Corticosteroids, anti malarial radiations therapy and Immune suppressive drugs may reduce protective efficacy of vaccine. Persons receiving Immune suppressive therapy should receive RIG.
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Treatment schedule
Wash wound with soap water copiously Administer T.T Do not stitch the wound. If need be then stitch after infiltrating it with I.G If wound is cat-I reassurance

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Treatment schedule (contd)

If wound is cat-II 5 shots Rabies vaccine. If wound is cat-III, HRIG/ERIG+Rabies vaccine. Blood test done after 1month of the last shot. If titer 0.5 IU/ml and above it is safe. If less than 0.5 IU/ml inject boosters.
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Prophylaxis Before Exposure

Pet handlers, vet, lab workers. Traveling to area where medical care difficult to find/or rabies endemic area. Inject 3 shots 0, 7, 21 or 28 doses. Pre-exposure prophylaxis obviates the need for post exposure RI but not R.V.

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Prophylaxis Before Exposure (Contd)

Rabies Fatality 100% fatal Only 6 documented cases of Rabies who survived, H/O pre or post exposure treatment was present in those cases Rabies in animal: If an an animal get rabies it act differently from the healthy animal. Wild move slowly or act as if they are tame. A pet that is friendly snap or bite
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Signs
Changes in animal behaviour General sickness, fever, loss of appetite. Problem in swallowing Excessive irritability Increase drooling Unusual vocalization. Aggression Restlessness Paralysis and death
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Prevention
Get your pet registered and vaccinated. Leashed wear vaccination tag. Stray dog elimination campaign launched. Community should also participate.

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