Man’s best friend but not vaccinatedMan’s best friend but not vaccinated

Rabies

(Rhabdovirus)Rabhas means Frenzy

World Rabies Day

• … … to reduce to reduce the suffering the suffering from rabiesfrom rabies

At the end of session you will learnAt the end of session you will learn

• Rabies: an invariably fatal Rabies: an invariably fatal encephalitisencephalitis• Only mammals affectedOnly mammals affected• Always endemic in the wildAlways endemic in the wild• Virus Virus descends descends from brain to salivary glandsfrom brain to salivary glands• 90% are from rabid dog90% are from rabid dog• Bats spread it by Bats spread it by aerosolaerosol• It can be prevented (100%)It can be prevented (100%)• Bangladesh stands 2Bangladesh stands 2ndnd in mortality in mortality

Key factsKey facts

• Globally >Globally >60k deaths/60k deaths/yy in >in >150150 countries countries• 1111thth biggest c/of death biggest c/of death• 95% in Asia Africa95% in Asia Africa• 50% children50% children• India: (~30k)India: (~30k)• Wound cleansing & immunization can prevent itWound cleansing & immunization can prevent it• Bangladesh: mBangladesh: most people are unprotectedost people are unprotected• Rabies costs the Rabies costs the world $124 billion/yworld $124 billion/y

What is Rabies?What is Rabies?

• .. a zoonosis c/by .. a zoonosis c/by rabiesrabies virusvirus• Infects both domestic & wild animalsInfects both domestic & wild animals• Causes ac. EncephalitisCauses ac. Encephalitis

Symptomatic rabies: Symptomatic rabies: 100% fatal100% fatal

Rhabdo/lyssa viruses

• Bullet shaped. Bullet shaped. RNARNA• EnvelopedEnveloped• Killed by Killed by ethanol ether, iodine, ethanol ether, iodine,

soap/detergents,soap/detergents, chloroform, acetone, heat chloroform, acetone, heat (60(6000c x5 min)c x5 min)

Lyssa means rageLyssa means rage

EpidemiologyEpidemiology

• Fixed virus Fixed virus (lab virus)(lab virus): : R. virus after serial passage through R. virus after serial passage through rabbits to stabilize its virulence & IPrabbits to stabilize its virulence & IP

• Street virus:Street virus: wild viruswild virus• Primary reservoirs: Primary reservoirs: wild mammalswild mammals• Only Only mammals mammals affected; except affected; except mice !mice !• ManMan, dogs, raccoons, skunks, foxes, bats, cats, cattle , dogs, raccoons, skunks, foxes, bats, cats, cattle

commonlycommonly affected affected• It is endemic in many countries It is endemic in many countries except Australia, Malaysia, except Australia, Malaysia,

Japan, Bhutan, NepalJapan, Bhutan, NepalIP: incubation periodIP: incubation period

Distribution of rabies reservoirs Distribution of rabies reservoirs

RaccoonsRaccoons

Skunks; a major reservoir of rabies in USASkunks; a major reservoir of rabies in USA

• Bites, abrasionsBites, abrasions• Scratches, Scratches, aerosol (bats)aerosol (bats)• Mucosal exposureMucosal exposure

• RarelyRarely• eating infected meateating infected meat• corneal transplantationcorneal transplantation

TransmissionTransmission

PathogenesisPathogenesis

• IP: IP: 9-90d 9-90d (several years): (several years): depends on:depends on:• InoculumInoculum• SiteSite• Wound severityWound severity• InnervationInnervation

• Untreated:Untreated: 50% rabid bites will develop R:50% rabid bites will develop R:• virulence, dosevirulence, dose• route, site, age, host defenseroute, site, age, host defense

Pathogenesis ..Pathogenesis ..

• RV replicates in muscles: enters nerves & ascends to RV replicates in muscles: enters nerves & ascends to CNS (CNS (3 mm/h)3 mm/h)

• Spread within CNS is rapidSpread within CNS is rapid• Then spreads centrifugally by nerves to salivary g., eyes, Then spreads centrifugally by nerves to salivary g., eyes,

kidneys, breastskidneys, breasts• This time the classic CF developThis time the classic CF develop

RV: rabies virusRV: rabies virus

Pathogenesis ..Pathogenesis ..

Live virus Live virus skin: mucosa: muscle skin: mucosa: muscle

Peripheral nervePeripheral nerve

CNS (gray matter)CNS (gray matter)

Salivary, eyes, breast, kidneysSalivary, eyes, breast, kidneys

moves centripetally

moves centrifugally

HistopathologyHistopathology

• EncephalomyelitisEncephalomyelitis• Perivascular inflammatory cellsPerivascular inflammatory cells• Neuronal cytoplasmic inclusion (Negri bodies)Neuronal cytoplasmic inclusion (Negri bodies)

esp. in pyramidal cellsesp. in pyramidal cells

• Inclusion bodies Inclusion bodies (elementary bodies):(elementary bodies): are nuclear/cytoplasmic aggregates; usually are nuclear/cytoplasmic aggregates; usually proteins: typically represent sites of viral replication & consist of viral capsidproteins: typically represent sites of viral replication & consist of viral capsid

• Pyramidal neurons (pyramidal cells): Pyramidal neurons (pyramidal cells): found in found in c. cortex, hippocampus, & amygdalac. cortex, hippocampus, & amygdala. . They are primary excitation units of mammalian prefrontal cortex & They are primary excitation units of mammalian prefrontal cortex &

corticospinal tractcorticospinal tract

Early CF: (often vague)Early CF: (often vague)

• Flu-like: Flu-like: malaise, F: malaise, F: 38C or above38C or above, chills, HA, f, chills, HA, fatigue, atigue, problems sleeping, anorexiaproblems sleeping, anorexia

• Anxiety, irritability, sore throatAnxiety, irritability, sore throat• Discomfort/ paresthesia Discomfort/ paresthesia at bite site (50%)at bite site (50%)• BBizarre behavior, fear of death!izarre behavior, fear of death!

On progression: On progression: neuro-symptoms:neuro-symptoms:

Neuro-symptoms: Neuro-symptoms: bbroad categoryroad category

• Furious rabies (80%)Furious rabies (80%)• Dumb or paralytic rabies Dumb or paralytic rabies

(GBS) 20%(GBS) 20%

Furious rabiesFurious rabies• anxiety, confusion, insomnia, nervousness, seizure, anxiety, confusion, insomnia, nervousness, seizure,

aggressivenessaggressiveness, , hallucinations, delirium, fear of deathhallucinations, delirium, fear of death• biting, biting, delusions, HGF, hyperhydrosis, goose skin, priopism, delusions, HGF, hyperhydrosis, goose skin, priopism,

hypersalivation, dysphagia, hypersalivation, dysphagia, hydro-phobiahydro-phobia (50%), (50%), aero-, photo-: a aero-, photo-: a few days later coma & deathfew days later coma & death

Dumb/paralytic rabiesDumb/paralytic rabies• S/of partial/full paralysisS/of partial/full paralysis usually begins in limbs & spreads usually begins in limbs & spreads

all overall over• Hydrophobia is Hydrophobia is unusualunusual• Progress to coma & death (heart or lung failure)Progress to coma & death (heart or lung failure)

A rabid dog displaying A rabid dog displaying the classic form of the classic form of paralytic R, cranial-paralytic R, cranial-

nerve deficits & nerve deficits & hypersalivationhypersalivation

Routine rabies tests:Routine rabies tests:• Direct fluorescent Ab. test (dFA:) (only post mortem)Direct fluorescent Ab. test (dFA:) (only post mortem)• Biopsy: Biopsy: Negri Negri bodies. Immunohistochemistry (IHC). EMbodies. Immunohistochemistry (IHC). EM

Importance:Importance:• For timely post-exposure prophylaxis (PEP) orFor timely post-exposure prophylaxis (PEP) or• avoid unnecessary physical & psychological traumaavoid unnecessary physical & psychological trauma

Diagnosis in AnimalsDiagnosis in Animals

dFAdFA detects RVdetects RV

• Ideal tissue is nerve (brain)Ideal tissue is nerve (brain)• Fl. anti-rabies Ab incubated with brain tissue fixes RV; seen Fl. anti-rabies Ab incubated with brain tissue fixes RV; seen

by Fl. MC. Unbound Ab can be washed awayby Fl. MC. Unbound Ab can be washed away

IHCIHC• Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues. Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues.

More sensitive than histopathologyMore sensitive than histopathologyFl: fluorescence. MC: microscopeFl: fluorescence. MC: microscope

DFA negativeDFA negative

DFA positiveDFA positive

• Negri bodiesNegri bodies are pathognomonic incl. bodies in cytoplasm are pathognomonic incl. bodies in cytoplasm of certain nerves (of certain nerves (only in 20%)only in 20%)

Rabies Dx in Humans Rabies Dx in Humans

• No test available before cl. diseaseNo test available before cl. disease• Confirmed pre- & post mortem by detecting RV, viral Ag in Confirmed pre- & post mortem by detecting RV, viral Ag in

brain, skin, urine, salivabrain, skin, urine, saliva• Saliva is tested by reverse transcription followed by PCR (RT-Saliva is tested by reverse transcription followed by PCR (RT-

PCR)PCR)• Antibody: serum, CSFAntibody: serum, CSF

Ag: antigenAg: antigen

Prevention Prevention

• Vaccinating pet & killing stray dogsVaccinating pet & killing stray dogs• Vaccine for at risk personsVaccine for at risk persons• Care of biteCare of bite• No contact with stray/wild animals. Don’t capture or No contact with stray/wild animals. Don’t capture or

provoke stray animalsprovoke stray animals• Not touching animal carcassesNot touching animal carcasses• Secure garbageSecure garbage• Cover chimneys & other entrancesCover chimneys & other entrances

• If bitten by bats, skunks, foxes, other carnivoresIf bitten by bats, skunks, foxes, other carnivores• regard as rabid unless the area is R free or until animal regard as rabid unless the area is R free or until animal

is negative by lab testingis negative by lab testing• immediate immunization & HRIGimmediate immunization & HRIG

• Bites by squirrel, gerbil, hamster, G. pig, rat, mice, other Bites by squirrel, gerbil, hamster, G. pig, rat, mice, other rodents, rabbits, hare almost never require anti-R Rxrodents, rabbits, hare almost never require anti-R Rx

HRIG: human rabies immunoglobulinHRIG: human rabies immunoglobulin

Prevention … Prevention …

VaccinationVaccination

Killed R virus vaccine PreexposurePreexposure PostexposurePostexposure Animal vaccinationAnimal vaccination

15million vaccines are 15million vaccines are pushed worldwidepushed worldwide

Who should get the Vaccine?Who should get the Vaccine? Pre-exposurePre-exposure

• High-risk people: High-risk people: vets., animal handlers, R. lab. workers, vets., animal handlers, R. lab. workers, cave/wild explorers, forestry workers, cave/wild explorers, forestry workers, travelers in travelers in endemic endemic areas, areas, people having frequent contact with R. people having frequent contact with R. virusvirus

• 3 doses: 0-7-21/283 doses: 0-7-21/28thth d d

BenefitsBenefits• No need of HRIG, less post-expo. vax. dosesNo need of HRIG, less post-expo. vax. doses• Post exposure Rx might be delayedPost exposure Rx might be delayed• Protects from inapparent exposures to R.Protects from inapparent exposures to R.• For repeated exposure screen for boosterFor repeated exposure screen for booster

Post-exposurePost-exposure

• Bitten by an animal, or contactBitten by an animal, or contact• 4 doses: 0-3-7-144 doses: 0-3-7-14thth days days• They should also get HRIG with first dose vax.They should also get HRIG with first dose vax.• Pre-vaccinated person get 2 doses: 0-3Pre-vaccinated person get 2 doses: 0-3rdrd d; no HRIG d; no HRIG• Should the animal be kept for 10 d?Should the animal be kept for 10 d?

Cell culture VaccinesCell culture Vaccines

Human diploid cell vaccine (HDCV)Human diploid cell vaccine (HDCV) Purified chick embryo cell vaccine (PCEC)Purified chick embryo cell vaccine (PCEC) Purified Vero cell vaccine (PVRV)Purified Vero cell vaccine (PVRV) Purified duck embryo vaccine (PDEV)Purified duck embryo vaccine (PDEV)

Vaccines in BD: Vaccines in BD: Rabipur (PCEC)Rabipur (PCEC)Verorab (PVRB)Verorab (PVRB)Rabix Rabix ,, ,,

Future Rabies VaccinesFuture Rabies Vaccines

• Vax. under dev. may be safe, potent & cheaperVax. under dev. may be safe, potent & cheaper• DNA vaccinesDNA vaccines, recombinant vaccines, recombinant vaccines• Plant biotechnology for making AgPlant biotechnology for making Ag• Neutralizing monoclonal antibodyNeutralizing monoclonal antibody

Adverse ReactionsAdverse Reactions

Less in childrenLess in children• Adults: local reactions (25%), systemic- (20%)Adults: local reactions (25%), systemic- (20%)

• HA, nausea, AP, aches & dizziness (5-40%)HA, nausea, AP, aches & dizziness (5-40%)• Very rare: Very rare: illness like GBSillness like GBS• Immune-complex with boosters: hives, arthralgia, F (6%)Immune-complex with boosters: hives, arthralgia, F (6%)

• Different brands differDifferent brands differ• Anaphylaxis, Anaphylaxis, if any, occurs within a min- to an hr. with if any, occurs within a min- to an hr. with

dyspnoea, hoarseness, wheeze, throat swelling, hives, dyspnoea, hoarseness, wheeze, throat swelling, hives, pallor, weakness, tachycardia, or dizzinesspallor, weakness, tachycardia, or dizziness

Human Rabies IG (HRIG)Human Rabies IG (HRIG)

• Category iii bite: Category iii bite: 20iu/kg 20iu/kg with vax. but different siteswith vax. but different sites

• ½ at the site (infiltrate the ½ at the site (infiltrate the wound); ½ IMwound); ½ IM

Basic Care in Animal BitesBasic Care in Animal Bites

• Immediate thorough toileting x15min with soap Immediate thorough toileting x15min with soap water, detergent, povidone iodinewater, detergent, povidone iodine

• Don't suture!Don't suture!

• Categorize the bite:Categorize the bite:• Post- exposure prophylaxisPost- exposure prophylaxis

Bite CategoryBite Category ( (WHO)WHO)

• Category I: 1. Category I: 1. touching/feeding suspect animalstouching/feeding suspect animals

2.2. licks on intact skinlicks on intact skin• Category II: 1. Category II: 1. nibbling of skinnibbling of skin

2. 2. scratches/abrasionsscratches/abrasions, but no hge., but no hge.

3.3. licks on broken skin licks on broken skin• Category III: Category III: 1 or more 1 or more bites/scratches, licks with hge.; bites/scratches, licks with hge.;

mucosal contamination with saliva, contacts with batsmucosal contamination with saliva, contacts with bats

Category ICategory Ino treatmentno treatment

Category IICategory IIwound disinfectionwound disinfectionvaccine onlyvaccine only

Category III bite: Category III bite: bites with bites with bleedingbleeding

Category IIICategory III

wound cleansing, HRIG & vaccinewound cleansing, HRIG & vaccine

• Animal observation in our country is not practical: Animal observation in our country is not practical: frequent frequent bitesbites

• Delay Rx only ifDelay Rx only if• Species unlikely to be infectedSpecies unlikely to be infected• Lab Dx in 48hrLab Dx in 48hr• Dog >1yr old with current vaccination (observe for 10d)Dog >1yr old with current vaccination (observe for 10d)

To date only 6 cases survivedTo date only 6 cases survived• Once clinical, rabies is always fatalOnce clinical, rabies is always fatal• Rx is only supportiveRx is only supportive• Typically life ends after 2-10 d (6d)Typically life ends after 2-10 d (6d)

No danger of nursing R pts with precautionsNo danger of nursing R pts with precautions

PrognosisPrognosis

DDDD

Other encephalitis Other encephalitis Hysteria reaction to animal biteHysteria reaction to animal bite GBS GBS PoliomyelitisPoliomyelitis Allergic encephalomyelitis ( rabies vaccine )Allergic encephalomyelitis ( rabies vaccine )

Shots for Dogs Would Save PeopleShots for Dogs Would Save People

• Mass vaccination for dogs could eliminate it in humanMass vaccination for dogs could eliminate it in human• R. is rare in HICsR. is rare in HICs• Lack of international commitment is among the reasons Lack of international commitment is among the reasons

why rabies in people persistswhy rabies in people persists

MCQMCQ• Most rabies are from bite by rabid dogsMost rabies are from bite by rabid dogs• Most of rabid-dog bites develop into rabiesMost of rabid-dog bites develop into rabies• HDCV is at present the best ARVHDCV is at present the best ARV• Rabies is not transmitted by contaminated corneal graftRabies is not transmitted by contaminated corneal graft• Rabies is always endemic in the forestRabies is always endemic in the forest• India has the greatest rabies deathsIndia has the greatest rabies deaths• Bangladesh stands second in mortalityBangladesh stands second in mortality

MCQMCQ• Vaccinating pet dogs is essential to control rabiesVaccinating pet dogs is essential to control rabies• Everyone should be vaccinated against rabiesEveryone should be vaccinated against rabies• Rabies virus spread to CNS via bloodRabies virus spread to CNS via blood• It can be transmitted by foodIt can be transmitted by food• Saliva contains R virus after brain involvementSaliva contains R virus after brain involvement• Rabies can be eradicatedRabies can be eradicated

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