Mononuclear inflammatory inflammation in leptomeninges,perivascular regions and parenchyma
Wound healed by this point
fever, confusion, hallucinations, combativeness,muscle spasms, hyperactivity, and seizures. Autonomicdysfunction is common and may result in hypersalivation,excessive perspiration, gooseflesh, pupillary dilation,and/or priapism. In encephalitic rabies, episodes ofhyperexcitability are typically followed by periods ofcomplete lucidity that become shorter as the diseaseprogresses. Rabies encephalitis is most distinguished byearly brainstem involvement, which results in the classicsymptoms of hydrophobia and aerophobia: involuntary,painful contraction of the diaphragm and accessory respiratory,laryngeal, and pharyngeal muscles in responseto swallowing liquids (hydrophobia) or a draft of air(aerophobia). These symptoms are probably due to dysfunctionof infected brainstem neurons that normallyinhibit inspiratory neurons near the nucleus ambiguus,resulting in exaggerated defense reflexes that protect therespiratory tract.The combination of hypersalivation andpharyngeal dysfunction is also responsible for the classicappearance of “foaming at the mouth”
Disturbance in water balance (syndrome of inappropriate antidiuretichormone secretion or diabetes insipidus), noncardiogenicpulmonary edema, and cardiac arrhythmias due tobrainstem dysfunction and/or myocarditis
For unknown reasons,muscle weakness predominates andcardinal features of encephalitic rabies (hydrophobia, aerophobia,fluctuating consciousness) are lacking in ∼20% ofrabies cases. Paralytic rabies is characterized by early andprominent muscle weakness, often beginning in the bittenextremity and spreading to produce quadriparesis andfacial weakness. Sphincter involvement is common, butsensory involvement is usually mild. Guillain-Barré syndromeis a common misdiagnosis. Transplantation ofcorneal tissue from donors in whom paralytic rabies wasmisdiagnosed as Guillain-Barré syndrome has resulted inclinical rabies and death in recipients. Patients with paralyticrabies generally survive a few days longer than istypical in encephalitic rabies, but multiple-organ failureensues even with aggressive supportive care.
There is no established treatment for rabies. There havebeen several recent treatment failures of antiviral therapy,ketamine, and therapeutic coma—measures thatwere used in a healthy survivor who had rabies virusantibodies present at the time of presentation. Expertopinion should be sought before any course of experimentaltherapy is embarked upon. A palliative approachmay be appropriate for some patients.
MULTISITE INTRADERMAL PROTOCOLS
Algorithm for rabies post exposure prophylaxis
After 1 months if viral antibodytitre less again administrd till antibody demonstrabl
This year, World Rabies Day is focussing on 'notifiability'. In many rabies endemic nations, it is not compulsory to report rabies deaths. In many others, the requirement is not carried out. Without proper records, the scale of the problem continues to be underestimated and people and animals continue to die from this preventable disease.
DEFINITION• A/c,highly fatal disease of CNS• Caused by Lyssavirus type 1• Zoonotic disease of warm blooded animals• Transmitted by bites of rabid animal• Long and variable IP with short period of illness• no treatment,only prevention
Problem statement• Enzootic as well as epizootic disease• Occurs in more than 100 countries and territories• Potential threat to more than 3 billion people• Incidence --35,000-50,000deaths/Year (WHO) 20,000deaths/yr in India 24,000deaths/yr in Africa• Age- most common in children below 15years• Sex- 15 million people receive rabies prophylaxis annually with majority males
Rabies free areas• Australia• New zealand• Taiwan• Cyprus• Iceland• Ireland• Japan• U.K.• Islands of western pacific• Liberian peninsula• Finland• Norway• Sweden• Andaman nicobar• Lakshadweep
AGENT-RABIES VIRUS• Rhabdovirus• Lyssavirus-type 1• Bullet shaped virus• Size is 180 x 75 nm• Has Lipoprotein envelop• Knob like spikes /Glycoprotein G• M protein layer• Genome- unsegmented,Linear, neg ative sense RNA
• Surface spikes composed of Glycoprotein G• Produces Pathogenicity by binding to Acetyl choline receptors in the neural tissue• Stimulate T lymphocytes Cytotoxic effect.• Also has hemagglutinating activity
Rabies viruses are sensitive to common Chemicals• The virus is sensitive to Ethanol Iodine Soap / Detergents Ether, Chloroform, Acetone Destroyed at 500 c in 1 hour at 600 c in 5 minutes.
Types of Rabies virus STREET VIRUS FIXED VIRUS Definition: the virus Definition: the virus recovered from which has a short, fixed naturally occurring and reproducible cases of rabies is called incubation period is “street virus” called “fixed virus Sources: it is naturally Sources: it is prepared occurring virus. It is by repeated culture in found in saliva of brain of rabbit such that infected animal. its I.P. is reduced &(continue) fixed
Features Features1. It produces Negri 1. It does not form Negri bodies bodies2. Incubation period is 2. Incubation period is long i.e. 20 to 60 constant between 4-6 days days3. It is pathogenic for all 3. It can pathogenic for mammals humans under certain conditions4. Cannot be used for 4. Is used for preparation of preparation of antirabies vaccine vaccine
RESERVOIR OF INFECTION1) URBAN RABIES:• From Dogs and cats.• 99% cases in india• A single infected dog capable of transmitting over an area of 40km
2)WILDLIFE RABIES• SYLVATIC RABIES• Unidentified reservoir of infection• Foxes,jackals,hynas,skunks etc• Enzootic in south america by mongoose• Transmit infection among themselves and to dogs and man
3)BAT RABIES• Latin american countries,USA• Vampire bats-feed on blood of man and animals• Found from mexico to northern argentina• Cause havoc to cattle population• Not repotrted in india• Constant source of infection to man and animals• Transmission by bites and aerosols
Source of Infection• Saliva of Rabid animal• Dogs and cats-virus in saliva 3-4 days before clinical symptoms• Variable in quantity
Carrier state• Serological survey-anti rabies antibody in a proportion of unvaccinated animals• Dogs living for years with virus isolated from saliva,yet no record of transmission• Asymtomatic animals-unlikely to infect man
Host Factors• All warm blooded animals including man.• Rabies in man is a dead-end infection.• People at risk-lab workers, veteinerians, dog handlers, hunters, etc
Mode of Transmission1. Animal bites2. Licks3. Aerosol4. Person to person
INCUBATION PERIOD:• Normally 3 - 8 wks• May be short that is 4 days or may be prolonged for years.• Depends on-site of bite Severity of bite Number of wounds Amount of virus injected Species of biting animal Protection provided by clothing Treatment taken
• NEGRI BODIES• EOSINOPHILIC CYTOPLASMIC INCLUSIONS in brain neurons• Randomly oriented rabies virus nucleocapsids embedded in the matrix• Seen mainly in purkinje cells of cerebellum pyramidal cells of hippocampus• Absence of negri bodies-not an exclusion to rabies
Symptoms• Headache, fever, sore throat• Nervousness, confusion• Pain or tingling at the site of the bite• Hallucinations• Hydrophobia• Paralysis• Coma and death
Clinical Findings• Bizarre behavior.• Agitation• Seizures.• Difficulty in drinking.• Patients will be able to eat solids• Afraid of water - Hydrophobia.• Spasms of Pharynx produces choking• Death in 1 -6 days.• Respiratory arrest / Death / Some may survive.
STAGES OF RABIES INFECTION1 – Non specific prodrome2 – Acute neurologic encephalitis3 – Coma4 - Death
DIFFERENT STAGES OF RABIES INFECTION D B O A G T S S VIRUS IN SALIVA INHALED AEROSOLS VIRUS IN SALIVA INVASION PHASE INVASION PHASE EXCITEMENT PARALY SIS PARALYDEATH SIS DEATH
1. Non specific prodrome 1 - 2 days 1 weekFever, headache, sore throatAnorexia, nausea, vomitingAgitation, depressionPain/tingling sensation at bitten siteDue to infection of dorsal root or cranial sensory ganglia.
Encephalitic rabies• Fever, confusion, hallucinations, combativeness,• Muscle spasms, hyperactivity, seizures.• Autonomic dysfunction hypersalivation, Excessive perspiration, gooseflesh, pupillary dilation, Priapism.• Hyperexcitability followed by periods of complete lucidity• Hydrophobia and aerophobia• “Foaming at the mouth”• Due to dysfunction of infected brainstem neurons• Severe brainstem damage coma death
COMPLICATIONS OF ENCEPHALITIS• Disturbance in water balance• Noncardiogenic pulmonary edema• cardiac arrhythmias• myocarditis.
Paralytic rabies• Early and prominent muscle weakness,• Quadriparesis and facial weakness.• Sphincter involvement is common,• Sensory involvement is usually mild.• Guillain-barré syndrome is a common misdiagnosis.• Patients survive a few days longer• Multiple-organ failure even with aggressive supportive care.
DIAGNOSIS1. History2. Signs and symptoms3. Clinical examination4. Detection of antigen by taking skin biopsy using immunofluorescence5. virus isolation from saliva & other secretions.6. CSF analysis and CT scan7. ELISA8. RT-PCR9. DFA testing10. Negri bodies
TREATMENT• No established treatment for rabies.• Recent treatment failures of antiviral therapy,ketamine, and therapeutic coma-milwaukee protocol• Expert opinion to be sought before any experimental therapy• A palliative approach may be appropriate for some patients.
Case management• Isolation of the patient• Post-exposure prophylaxis• Antianxiety drugs and sedatives• Muscle relaxants with curare like action• Ensure hydration and diuresis• Cardiac and respiratory support
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
1.POST-EXPOSURE PROPHYLAXIS• To reduce viral load by elimination from the wound• To neutrilise the virus at site of entry• To prevent nerve infection• To induce systemic immunity• Includes -1.wound treatment 2.observation of the animal 3.immunization 4.advice to patient
Category of bites (WHO)Category • Licks on unbroken skin • Touching/ feeding animals ICategory • Nibble, cuts, scratches without oozing of blood IICategory • Licks on mucous membrane or broken skin III • Bites with breach of skin, bleeding
Recommended TreatmentCategory • None ICategory • Local Rx of wounds II • Anti rabies vaccine • Local Rx of woundsCategory • Anti rabies vaccine III • Rabies immunoglobulin
WOUND MANAGEMENTCleansing-with soap and water (minimum 10min) punctured wound irrigated with cathetersChemical treatment-virucidal agents- 70%alcohol, povidine iodine, tincture iodine, etcLocal adminisration of rabies antiserumSuturing -done after 24-48hrs with antiserum locallyAntibioticsImmunization against tetanusWound not to be dressed or bandaged
OBSERVATION OF ANIMAL• To determine the risk of infection• For 10 days• Look for any abnormal behavior of animal• If animal died, look for negri bodies• If possible do FRA test• If animal healthy and alive after 10 days-no treatment• If animal cannot be observed-suspected to be rabid
IMMUNIZATIONINDICATIONS1. Immediately started when a person bitten,scratched or licked by animal2. If animal not available for observation3. Bites4. If animal is suspected to be rabid5. If the animal is confirmed rabid6. Person drinking raw milk of rabid animal7. If patient comes late
ACTIVE IMMUNIZATION• Antirabies vaccination• For both category 2 and 3PASSIVE IMMUNIZATION• Rabies immunoglobilins• For category 3
ADVICE TO PATIENT• Treatment-correctly and completely• Avoid steroids,spicy food,spirit,smoking,strain during treatment period
Vaccines for immunization It is fluid or dried preparation of Rabies “Fixed” virus grown in the Neural tissue of Rabbits, Sheep, Goats, Mice or RatsOR in embryonated duck eggsOR in cell culture
1.Nerve tissue vaccinea) BPL-vaccine• Prepared by inoculating fixed virus into nervous system of sheep,goat,rabbit,mice• Killed on 7th or 8th day, brain removed• 5% emulsion prepared with saline• Virus killed by BPL• If sheep is employed-semple vaccine• Dosage schedule-1ml to 5ml,s/c around the umbilicus,7-10 days• Demerits-killed vaccine only 50%effective slow immunity, which lasts for only 6 months neuroparalytic reactions• Not recommended by WHO
b) Suckling mouse vaccine• Prepared by inoculating fixed virus into brain of young suckling mice less than 9 days old• Safer than semple vaccine• No neuroparalysis• Extensive use in latin america• Not recommended by WHOGovt of india stopped nerve tissue vaccine productionby 2004
2.Duck embryo vaccine• Flury’s vaccine• Vaccine free of neuroparalytic disorder• Causes allergic reactions in egg protein sensitive individual• Not used in india
3.Cell culture vaccine• Great advance in rabies prophylaxis• More potent,safer,stable,effective• Less reactogenic• Less dose required, painless injection, irrespective of age and sex• Freeze dried vaccines supplied with diluent and syringe• Includes HDCV PCEC-V second generation vaccines PVRV
HUMAN DIPLOID CELL VACCINE• By propogating fixed rabies virus in human diploid fibroblast cells• Generally safe and highly potent• Available as liquid vaccine• Gold standard anti rabies vaccine• Costly
SECOND GENERATION VACCINES• Purified chick embryo cell vaccine-from chick embryo fibroblast with diluent-sterile distilled water• Purified vero-cell rabies vaccine-from vero cells with sterile normal saline as diluent• Less cost,highly potent• WHO reference vaccine
Anti-rabies serum• Equine Anti Rabies serum: 40 IU/kg• Human rabies immunoglobin : 20 IU/kg• Recommended dose around the wound and rest in IM on 0 day• Booster doses are essential whenever anti rabies serum is given with the vaccine• ARG-local viricidal/neutrilising effect
2.PRE-EXPOSURE PROPHYLAXIS• Done in persons who have high risk of repeated exposures. Animal Handlers Wildlife officers Veterinarians Lab: staff working with rabies virus• Cell-culture vaccine 1ml I/M OR 0.1ml I/D ( 0,7& 28day)• Booster dose every 2 years
3.PEP FOR PREVIOUSLY VACCINATED PEOPLE• If antibody titre unknown or bite severe-1ml HDC vaccine 0,3,7 days• If antibody titre>0.5IU/ml and bite not severe-0,3 days• Rabies immunoglobulin not to be administerd• if re-exposure within 1 yr of PEP-no treatment• If re-exposure after 3 yrs-full schedule PEP
• INCUBATION PERIOD:• 3-8 wks.• Range from 10 days to 1year• CLINICAL FEATURES:• Rabies in dogs may manifest itself in two forms.• Furious rabies• Dumb rabies
a. Furious rabies- Typical mad-dog syndromei. Change in behavior.ii. Running amuck.iii. Change in voice due to paralysis of laryngeal muscles.iv. Excessive salivation & foaming at the angle of the mouth.v. Paralytic stage
b. Dumb rabies.i. No excitative or irritative stageii. Predominantly paralytic.iii.Dog withdraws itself from being seen or disturbed.iv. Elapses into a stage of sleepiness and dies in about 3 days.
IMMUNIZATION OF DOGS• Most important weapon in rabies control• 80-90% dog popoulation-accesible for vaccination• Mass vaccination-effective tool• Primary immunization-age-3 to 4 months• Booster dose-regular interval based on type of vaccine
VACCINES FOR DOGS1. BPL inactivated nervous tissue vaccine• 20% suspension of infected sheep brain• Dose-5 ml• Revaccination-after 6 months followed by every year• Low efficacy-not recommended
2. Modified live virus vaccine• 33% chick embryo suspension infected with modified virus• Dose-3ml by single injection• Booster-every 3 years• Raksharab,Nobivac-R,Robigen,Rabisin
URBAN RABIES CONTROL• Elimination of stray and ownerless dogs• Swift mass immunization of dogs• Registration and licensing of all domestic dogs• Restraint of dogs in public places• Immediate destruction of dogs and cats bitten by rabid animals• Quarantine for about 6 months of imported dogs• Health education of people• Oral vacine baits-succesful control of wildlife rabies,particularly fox
RABIES CONTROL UNITS IN INDIA• Launched by agriculture ministry of india in 6th five year plan aiming 100%rabies free india by 13th 5 year plan• 30 rabies control units where set up• Overall charge-senior officer of animal husbandry dept• Each unit-veterinary surgeon,supervisor,10 dog catchers• Each unit provided with a diesel van, cold storage system for vaccines, equipments for catching dogs• Immunization and sterilization of dogs• No merciless killing after prevention of cruelty against animals act was implemented• Only rabid and seriously ill dogs are killed
Worlds 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.