rabies, world rabies day

Rabies Rhabdovirus basics : 

Rabies Rhabdovirus basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1

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 1.2 billion and a land area of 3.2 million km. Dr.T.V.Rao MD 2

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Dr.T.V.Rao MD 3

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. Dr.T.V.Rao MD 4

What is Rabies: 

What is Rabies Rabies is a Zoonotic viral disease 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. Dr.T.V.Rao MD 5

Rabies - Common facts: 

Rabies - Common facts Mad Dog biting Humans lead to Rabies. Latin word 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. Dr.T.V.Rao MD 6

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. Dr.T.V.Rao MD 7

Rabies – A fatal Zoonotic Disease: 

Rabies – A fatal Zoonotic Disease Dr.T.V.Rao MD 8

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. Dr.T.V.Rao MD 9

Rhabdovirus: 

Rhabdovirus A Bullet shaped virus/ Enveloped Contains ss RNA virus Rhabdoviridae – infects mammals. Important virus Lyssa virus- Rabies virus Lyssa means Rage. Dr.T.V.Rao MD 10

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 Dr.T.V.Rao MD 11

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 Dr.T.V.Rao MD 12

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 . Dr.T.V.Rao MD 13

Any mammal can get rabies.: 

Any mammal can get rabies . Raccoons, skunks, foxes and bats Dogs, cats, cattle and ferrets Humans too Dr.T.V.Rao MD 14

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 . Dr.T.V.Rao MD 15

Man’s best friend but can spread Rabies if not vaccinated: 

Man’s best friend but can spread Rabies if not vaccinated Dr.T.V.Rao MD 16

Rabies viruses are sensitive to common Chemicals: 

Rabies viruses are sensitive to common Chemicals The virus is sensitive to Ethanol Iodine Soap / Detergents Ether, Chloroform, Acetone Destroyed at 50 0 c in 1 hour at 60 0 c in 5 minutes. Dr.T.V.Rao MD 17

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. Dr.T.V.Rao MD 18

Transmission: 

Transmission Abrasions or scratches on skin. Mucous membrane exposed to saliva. Most frequently via deep penetrating bite wounds. Other routes . Inhalation in bat infected caves. Ingestion of dead /infected animal meat Corneal transplantation Dr.T.V.Rao MD 19

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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. Dr.T.V.Rao MD 21

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PATHOGENESIS Live virus  Epidermis, Mucus membrane Peripheral nerve CNS ( gray matter ) Other tissue (salivary glands,…) centripetally centrifugally Dr.T.V.Rao MD 22

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Spread of Virus: 

Spread of Virus From Brain virus spread to Salivary glands, Conjunctival cell released into tears Kidney Lactating glands and Milk after pregnancy Dr.T.V.Rao MD 26

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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. Dr.T.V.Rao MD 28

Pathogenesis: 

Pathogenesis Incubation 1 – 3 months. May be average from 7 days to 3 years. Stages of the disease. Prodrome Acute encephalitis. Coma / Death. Dr.T.V.Rao MD 29

Broad category - Presentations: 

Broad category - Presentations Furious Rabies Dumb ( Rage tranquille ) (Landry/Guillain-Barre Syndrome Dr.T.V.Rao MD 30

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 Dr.T.V.Rao MD 31

Clinical Findings: 

Clinical Findings Bizarre behavior. Agitation Seizures. 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 . Dr.T.V.Rao MD 32

Symptoms: 

Headache, fever, sore throat Nervousness, confusion Pain or tingling at the site of the bite Hallucinations Seeing things that are not really there Hydrophobia “Fear of water" due to spasms in the throat Paralysis Unable to move parts of the body Coma and death Symptoms Dr.T.V.Rao MD 33

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CLINICAL MANIFESTATIONS 1 – Non specific prodrome 2 – Acute neurologic encephalitis Acute encephalitis Profound dysfunction of brainstem 3 – Coma 4 - Death ( Rare cases  recovery ) Dr.T.V.Rao MD 34

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CLINICAL MANIFESTATIONS Non specific prodrome 1 - 2 days  1 week Fever, headache, sore throat Anorexia, nausea, vomiting, Agitation, depression Parenthesis or fasciculation's at or Around the site of inoculation of virus . Dr.T.V.Rao MD 35

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, Opisthotonic posturing Mental aberration ( Lucid period  coma ) Hypersalivation, Aphasia, Pharyngeal spasms Incoordination, Hyperactivity Dr.T.V.Rao MD 36

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% ) Dr.T.V.Rao MD 37

Rabies can present as Grave condition: 

Rabies can present as Grave condition Dr.T.V.Rao MD 38

Majority will succumb to Disease: 

Majority will succumb to Disease Dr.T.V.Rao MD 39

Clinical presentation –clues in Diagnosis Leads : 

Clinical presentation – clues in Diagnosis Leads 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 can diagnose. Dr.T.V.Rao MD 40

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 inoculation. tissue culture on culture lines W 138, BHK , PCR emerging method. IF methods corneal impression method. Dr.T.V.Rao MD 41

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 post-mortem test is biopsy of the patient's brain and examination for Negri bodies . Autopsies are rarely performed . Dr.T.V.Rao MD 42

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DIAGNOSIS Laboratory finding: ( CBC, CSF ) Exclusion of other etiologies Pathology: Formation of cytoplasmic inclusions: ( Negri bodies ) ( Ammon’s horn, Cerebral cortex, Brainstem, Hypothalamus, The Purkinje cells of cerebellum, Dorsal spinal ganglia ) Dr.T.V.Rao MD 43

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, Histological examination ELISA specific antibody detection. PCR Dr.T.V.Rao MD 44

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 Dr.T.V.Rao MD 45

Negri bodies in Brain Tissue: 

Negri bodies in 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 .. Dr.T.V.Rao MD 46

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 . Dr.T.V.Rao MD 47

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DIFFERENTIAL DIAGNOSIS Other viral encephalitis Hysteria reaction to animal bite Landry/Guillan-barre syndrome Poliomyelitis Allergic encephalomyelitis ( rabies vaccine ) Dr.T.V.Rao MD 48

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P REVENTIO N Preexposure Prophylaxis Post exposure Prophylaxis Dr.T.V.Rao MD 49

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 Dr.T.V.Rao MD 50

Preexposure vaccination: 

Preexposure vaccination Indicated in Laboratory workers Veterinarians and technical staff. Bat handlers. Dr.T.V.Rao MD 51

Supporting care in Animal/Dog Bites: 

Supporting care in Animal/Dog Bites Dr.T.V.Rao MD 52

Basic care in Animal bites: 

Basic care in Animal bites Before exposure to infection In Veterinary surgeons animal handlers. Specific Prophylaxis After exposure to Dog bite. Local treatment Cauterization Scrub with Soap and clean. Use cetavalon, tincture of Iodine Antirabic serum don't suture wound unless highly essential. Dr.T.V.Rao MD 53

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 Dr.T.V.Rao MD 54

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POSTEXPOSURE PROPHYLAXIS 1 – Wound cleaning & treatment Dr.T.V.Rao MD 55

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Post exposure vaccination: 

Post exposure vaccination Anti Rabies vaccines are given when person is 1 Bitten 2 Scratched 3 Licked By Rabid animal animal to be kept for 10 days ? Dr.T.V.Rao MD 58

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 Dr.T.V.Rao MD 59

Vaccines: 

Vaccines Semple vaccine Contain 5 % suspension. Of infected Sheep brain, ( Infected with fixed virus ) Inactivated with Phenol at 37 0 c 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. Dr.T.V.Rao MD 60

*Dose Semple Vaccine: 

*Dose Semple Vaccine Semple vaccine BPL vaccine Class I 2ml x 7 days 2mlx7 days Class II 5ml x 14 days 5mlx10days Class III 10ml x 14 days 5 ml x 10 days * Many health institues abandoded its use Dr.T.V.Rao MD 61

Neural Vaccines*: 

Neural Vaccines* Class I slight risk Class II Moderate risk Class III Great risk Neural 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 Dr.T.V.Rao MD 62

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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) Dr.T.V.Rao MD 63

Post exposure Prophylaxis WHO: 

Post exposure Prophylaxis WHO Category Type of exposure prophylaxis 1 Touching and feeding No 2 licking on intact skin Minor scratches, licks Start vaccine on broken skin 3 Transdermal bites contaminated Rabies Immunoglobin + Vaccine Dr.T.V.Rao MD 64

Post exposure Prophylaxis: 

Post exposure Prophylaxis The vaccination is given on 0, 3, 7, 14, 30, and 90 th day Immunity lasts for 5 years Injected on deltoid region IM/SC Not to be given in the gluteal region Dr.T.V.Rao MD 65

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POSTEXPOSURE PROPHYLAXIS 3 – Active immunization Dr.T.V.Rao MD 66

Cell culture Vaccines Commonly prescribed: 

Cell culture Vaccines Commonly prescribed 1 Human diploid cell vaccine . 2 Purified chick embryo cell vaccine 3.Purified Vero cell vaccine Dr.T.V.Rao MD 67

Human Diploid Cell Vaccine: 

Human Diploid Cell Vaccine Koprowsky, Viktor, Plokin discovered Inactivated in Betaproprionate. No serious side effects. Human Diploid cell vaccines purified . Sub Unit vaccines in progress/developed. Dr.T.V.Rao MD 68

Human Diploid Cell Vaccines: 

Human Diploid Cell Vaccines Dosage Preexposure prophylaxis 0 – 7 – 21 – or 28 – 56 days A booster after 1 year, Repeat once in 5 days, Post exposure Prophylaxis Six doses 0 -3 -7-14 – 30 - 90 days Given IM or SC in the Deltoid region Don't inject inGluteal region. Dr.T.V.Rao MD 69

Preexposure prophylaxis doses: 

Preexposure prophylaxis doses Given on the following days 0, 7, 21,or 28 and 56 th day Generally given to Vetnary personal Dr.T.V.Rao MD 70

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. Dr.T.V.Rao MD 71

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. Dr.T.V.Rao MD 72

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 Dr.T.V.Rao MD 73

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 Dr.T.V.Rao MD 74

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 Dr.T.V.Rao MD 75

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 . Dr.T.V.Rao MD 76

Never touch an unfamiliar or wild animal. Always ask permission to touch someone else’s pet.: 

Never touch an unfamiliar or wild animal. Always ask permission to touch someone else’s pet. Dr.T.V.Rao MD 77

Follow me for More Articles of Interest on Infectious Diseases on : 

Follow me for More Articles of Interest on Infectious Diseases on Dr.T.V.Rao MD 78

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Created by Dr.T.V.Rao MD for for Medical and Health care workers in Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 79