RabiesRhabdovirus : RabiesRhabdovirus Dr.T.V.Rao MD Early Rabies : Early Rabies Rabies has been recognized in India since the Vedic period (1500–500 BC) and is described in the ancient Indian scripture Atharvaveda,
Rabies is endemic in India, a vast country with a population exceeding 1.02 billion and a land area of 3.2 million km. Rabies widely spread in Asia and Africa : Rabies widely spread in Asia and Africa Rabies is widely distributed across the globe. More than 55 000 people die of rabies each year. About 95% of human deaths occur in Asia and Africa.
Most human deaths follow a bite from an infected dog. Between 30% to 60% of the victims of dog bites are children under the age of 15. What is Rabies : What is Rabies Rabies is a zoonotic disease (a disease that is transmitted to humans from animals) that is caused by a virus. Rabies infects domestic and wild animals, and is spread to people through close contact with infected saliva (via bites or scratches). The disease is present on nearly every continent of the world but most human deaths occur in Asia and Africa (more than 95%). Once symptoms of the disease develop, rabies is fatal. Rabies - Common facts : Rabies - Common facts Mad Dog biting Humans lead to Rabies.
Latin Rabhas means Frenzy.
Hydrophobia Fear of Water, Saliva of Rabid dogs
Pasture’s success – Vaccination
Fixed virus from Rabbit injected into Joseph Meister
Injected 13 injection of the cord vaccine. Rabies- A Zoonotic Disease : 7 Rabies- A Zoonotic Disease Rhabdovirus family; genus Lyssavirus
Enveloped, bullet-shaped virions
Slow, progressive zoonotic disease
Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals by bites, scratches, and inhalation of droplets. Rabies – A fatal Zoonotic Disease : Rabies – A fatal Zoonotic Disease Rabies in USA : Rabies in USA Most of the recent human rabies cases in the United States have been caused by rabies virus from bats. Awareness of the facts about bats and rabies can help people protect themselves, their families, and their pets. Rhabdoviruses : Rhabdoviruses A Bullet shaped virus/ Enveloped
Contains ss RNA virus
Rhabdoviridae – infects mammals.
Lyssa virus- Rabies virus
Lyssa means Rage. Rabies virus : Rabies virus Bullet shaped virus
Size is 180 x 75 nm
Has Lipoprotein envelop
Knob like spikes /Glycoprotein S
Genome un segmented
Linear negative sense RNA What is a Fixed Virus : What is a Fixed Virus One whose virulence and incubation period have been stabilized by serial passage and remained fixed during further transmission.
Rabies virus that has undergone serial passage through rabbits, thus stabilizing its virulence and incubation period and called as fixed virus What is a Street Virus : What is a Street Virus Virus from a naturally infected animal, as opposed to a laboratory-adapted strain of the virus.
The virulent rabies virus from a rabid domestic animal that has contracted the disease from a bite or scratch of another animal, and called as street virus. Any mammal can get rabies. : Any mammal can get rabies. Raccoons, skunks, foxes and bats
Dogs, cats, cattle and ferrets
Humans too What kind of animals get Rabies? : What kind of animals get Rabies? The rabies virus can infect all mammals.
Mammals are warm-blooded animals that have hair and mammary glands to produce milk for their babies.
Animals like frogs, birds, and snakes do not get rabies. Man’s best friendbut can spread Rabies if not vaccinated : Man’s best friendbut can spread Rabies if not vaccinated Rabies viruses are sensitive to common Chemicals : Rabies viruses are sensitive to common Chemicals The virus is sensitive to
Soap / Detergents
Ether, Chloroform, Acetone
Destroyed at 500 c in 1 hour
at 600 c in 5 minutes. Antigenic properties : Antigenic properties Surface spikes composed of Glycoprotein G
Produces Pathogenicity by binding to Acetyl choline receptors in the neural tissue
Stimulate T lymphocytes Cytotoxic effect. Transmission : Transmission Abrasions or scratches on skin.
Mucous membrane exposed to saliva.
Most frequently via deep penetrating bite wounds.
Inhalation in bat infected caves.
Ingestion of dead /infected animal meat
Corneal transplantation Pathogenesis of Rabies : Pathogenesis of Rabies Bite by Rabid dog or other animals
Virus are carried in saliva virus deposited on the wound site.
If untreated 50% will Develop rabies.
Rabies can be produced by licks and corneal transplantation.
Virus multiply in the muscle ,connective tissue, nerves after 48 – 72 hours.
Penetrated nerve endings. Slide 22: PATHOGENESIS Live virus Epidermis, Mucus membrane
CNS ( gray matter )
Other tissue (salivary glands,…) centripetally centrifugally Spread of Virus : Spread of Virus From Brain virus spread to
Conjunctival cell released into tears
Lactating glands and Milk after pregnancy Pathogenesis : Pathogenesis Virus travels through axoplasam toward the spinal cord, at the rate of 3 mm/hour,
Towards the brain
Spread from brain centrifugally to various parts of the body.
Multiplies in the salivary glands and shed in the saliva.
Cornea, facial tissues skin. Pathogenesis : Pathogenesis Incubation 1 – 3 months.
May be average from 7 days to 3 years.
Stages of the disease.
Coma / Death. Broad category - Presentations : Broad category - Presentations Furious Rabies
Dumb ( Rage tranquille )
(Landry/Guillain-Barre Syndrome Category - WHO : Category - WHO Category I: touching or feeding suspect animals, but skin is intact
Category II: minor scratches without bleeding from contact, or licks on broken skin
Category III: one or more bites, scratches, licks on broken skin, or other contact that breaks the skin; or exposure to bats Clinical Findings : Clinical Findings Bizarre behavior.
Difficulty in drinking.
Patients will be able to eat solids
Afraid of water - Hydrophobia.
Even sight or sound of water disturbs the patient.
But suffer with intense thirst.
Spasms of Pharynx produces choking
Death in 1 -6 days.
Respiratory arrest / Death / Some may survive. Symptoms : Headache, fever, sore throat
Pain or tingling at the site of the bite
Seeing things that are not really there
“Fear of water" due to spasms in the throat
Unable to move parts of the body
Coma and death Symptoms Slide 34: CLINICAL MANIFESTATIONS 1 – Non specific prodrome
2 – Acute neurologic encephalitis
Profound dysfunction of brainstem
3 – Coma
4 - Death ( Rare cases recovery ) Slide 35: CLINICAL MANIFESTATIONS Non specific prodrome
1 - 2 days 1 week
Fever, headache, sore throat
Anorexia, nausea, vomiting,
Parenthesis or fasciculation's at or Around the site of inoculation of virus. Acute Neurologic Encephalitis : Acute Neurologic Encephalitis 1 – 2 days to < 1 week
Excessive motor activity, Excitation, Agitation
Confusion, Hallucinations, Delirium,
Bizarre aberrations of thought, Seizures,
Muscle spasms, Meningismus,
Mental aberration ( Lucid period coma )
Hypersalivation, Aphasia, Pharyngeal spasms
Incordination, Hyperactivity Acute Neurologic Encephalitis Phase - Presentations : Acute Neurologic Encephalitis Phase - Presentations Fever T > 40.6
Dilated irregular pupils
Lacrimation, Salivation & Perspiration
Upper motor neuron paralysis
Deep tendon reflexes
Extensor plantar responses ( as a rule )
Hydrophobia or Aerophobia (50 -70% ) Rabies can present as Grave condition : Rabies can present as Grave condition Majority will succumb to Disease : Majority will succumb to Disease Clinical presentation – Leads the clues in Diagnosis : Clinical presentation – Leads the clues in Diagnosis In most cases, human rabies is diagnosed primarily on the basis of clinical symptoms and signs, and a corroborative history of or evidence of an animal bite, death of an animal, and incomplete or no vaccination following exposure. The facility for laboratory diagnosis and confirmation of rabies, be it in humans or in animals, is available premortem in only a few institutions in India. T Common confirmatory test - Rabies : Common confirmatory test - Rabies The standard premortem test is a fluorescent antibody test to demonstrate the presence of viral antigen. The standard postmortem test is biopsy of the patient's brain and examination for Negri bodies. Autopsies are rarely performed. Slide 42: DIAGNOSIS Laboratory finding: ( CBC, CSF )
Exclusion of other etiologies
Formation of cytoplasmic inclusions:
( Negri bodies )
( Ammon’s horn, Cerebral cortex,
The Purkinje cells of cerebellum,
Dorsal spinal ganglia ) Laboratory Diagnosis : Laboratory Diagnosis Survival possible. May need Laboratory Diagnosis
Clinical differentiation other cases of Encephalitis.
Post mortem Diagnosis by
By demonstration of Negri bodies.
Isolation of virus fro Mice brain
tissue culture on culture lines
W 138, BHK,
PCR emerging method.
IF methods corneal impression method. Diagnostic methods : Diagnostic methods Antigen detection by specific Immuno fluorescence.
Ante-mortem - Conjunctival,skin biopsy from nape of neck.
Postmortem impression from surfaces of salivary glands Hippocampus,
ELISA specific antibody detection.
PCR Negri bodies – A gold standard in Diagnosis : Negri bodies – A gold standard in Diagnosis Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but found only in 20% of cases Negri bodiesin Brain Tissue : Negri bodiesin Brain Tissue Negri bodies round or oval inclusion bodies seen in the cytoplasm and sometimes in the processes of neurons of rabid animals after death.
Negri bodies are Eosinophilic, sharply outlined, pathognomonic inclusion bodies (2-10 µm in diameter) found in the cytoplasm of certain nerve .. Emerging Methods in Diagnosis : Emerging Methods in Diagnosis The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death. The diagnosis can also be reliably made from skin samples taken before death. It is also possible to make the diagnosis from saliva, urine and cerebrospinal fluid samples, but this is not as sensitive. Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but found only in 20% of cases. Slide 48: DIFFERENTIAL DIAGNOSIS Other viral encephalitis
Hysteria reaction to animal bite
Allergic encephalomyelitis ( rabies vaccine ) Slide 49: PREVENTION Preexposure Prophylaxis
Postexposure Prophylaxis Ist Vaccine for Rabies : Ist Vaccine for Rabies Prepared by Pasteur by drying various periods pieces of spinal cord of Rabbits infected with fixed virus
1885 Joseph Meister 9 year boy vaccinated 13 injections were given
Patient saved Preexposure vaccination : Preexposure vaccination Indicated in
Veterinarians and technical staff.
Bat handlers. Supporting care in Animal/Dog Bites : Supporting care in Animal/Dog Bites Basic care in Animal bites : Basic care in Animal bites Before exposure to infection
In Veterinary surgeons animal handlers.
After exposure to Dog bite.
Scrub with Soap and clean.
Use cetavalon, tincture of Iodine
Antirabic serum don't suture If you are bitten or scratched : Tell an health care worker immediately
Wash the wound out with soap and water
Inform the doctor right away If you are bitten or scratched Slide 55: POSTEXPOSURE PROPHYLAXIS 1 – Wound cleaning & treatment Post exposure vaccination : Post exposure vaccination Anti Rabis vaccines are given when person is
By Rabid animal
animal to be kept for 10 days ? Vaccines : Vaccines Semple vaccine
Contain 5 % suspension. Of infected Sheep brain, ( Infected with fixed virus )
Inactivated with Phenol at 370c
Vaccines available after inactivation with Beta propiolactone Used in India
Vaccine contains Nucleic capsid antigen,
Small quantities of Glycoprotein G
Used in Developed countries Neural complications. Neural Vaccines* : Neural Vaccines* Class I slight risk
Class II Moderate risk
Class III Great risk
Nerual vaccines may cause Neuroparlytic complications, Laundry’s type ascending paralysis
Dose is regulated according to grade/class of bites
Many countries do not use in view of neurological complications Slide 61: HUMAN RABIES Cell culture Vaccines Vaccine:
Human diploid cell vaccine (HDCV)
Developed by Koprowsky,Wiktor,and Plotkin
Purified chick embryo cell vaccine (PCEC)
Purified Vero cell vaccine (PVRV)
Purified duck embryo vaccine (PDEV) Post exposure Prophylaxis : Post exposure Prophylaxis The vaccination is given on
0, 3, 7, 14, 30, and 90th day
Immunity lasts for 5 years
Injected on deltoid region IM/SC
Not to be given in the gluteal region Slide 63: POSTEXPOSURE PROPHYLAXIS 3 – Active immunization Cell culture Vaccines in – commonly prescribed : Cell culture Vaccines in – commonly prescribed 1 Human diploid cell vaccine.
2 Purified chick embryo cell vaccine
3.Purified Vero cell vaccine Human Diploid CellVaccine : Human Diploid CellVaccine Koprowsky, Viktor, Plokin discovered
Inactivated in Betaproprionate.
No serious side effects.
Human Diploid cell vaccines purified .
Sub Unit vaccines in progress/developed. Human Diploid Cell Vaccines : Human Diploid Cell Vaccines Dosage
0 – 7 – 21 – or 28 – 56 days
A booster after 1 year,
Repeat once in 5 days,
Post exposure Prophylaxis
0 -3 -7-14 – 30 - 90 days
Given IM or SC in the Deltoid region
Don't inject inGluteal region. Preexposure prophylasixis doses : Preexposure prophylasixis doses Given on the following days
0, 7, 21,or 28 and 56th day
Generally given to Vet nary personal Passive Immunization : Passive Immunization Human Rabies Immunoglobulin HRIG
High Risk bitten on face and neck
Given a dose of 20 IU /Kg wt
Half at the site of bite and rest IM route.
Active immunization should be initiated with passive immunization. Future of Rabies Vaccines : Future of Rabies Vaccines A number of experimental vaccines are under development that may provide alternative safe and potent but less expensive vaccine options. These include DNA vaccines, recombinant viral vaccines, and recombinant protein vaccines. Further testing is needed to determine if and which one of these novel vaccines will make their way into mass production and application in the future. Subunit or Genetically Engineered vaccines for Rabies : Subunit or Genetically Engineered vaccines for Rabies A viral immunizing agent that has been treated to remove traces of viral nucleic acid so that only protein subunits remain. The subunits have less risk of causing adverse reactions.
Several trails in progress Epidemiology : Epidemiology No Danger of Nursing Rabies patients but do take precautions
Any animal bite can cause Rabies except Mice
BATS in caves in spread he disease by respiratory disease.
India around 30,000 die with Rabies.
Vaccination of the Dogs and Licensing of the Dogs In spite of Health Education several die due to Rabies infection in Developing world : In spite of Health Education several die due to Rabies infection in Developing world World's Rabies Day (on September 28) : World's Rabies Day (on September 28) World Rabies Day is a cooperative global event planned to reduce the suffering from rabies. This day celebrates Dr. Louis Pasteur’s vision of a rabies free world. Created by Dr.T.V.Rao MD for ‘e’ learning Programme in developing world : Created by Dr.T.V.Rao MD for ‘e’ learning Programme in developing world Email