CLASSIFICATION PATHOGENESIS CLINICAL FEATURES PROPHYLAXIS RABIES RELATED VIRUSES

1. RhabdovirusesRhabdoviruses
DR.RAJESH KUMAR R SDR.RAJESH KUMAR R S

2. RhabdovirusesRhabdoviruses
 A Bullet shaped virus/A Bullet shaped virus/
EnvelopedEnveloped
 ContainsContains ss RNAss RNA
 Rhabdoviridae – infectsRhabdoviridae – infects
mammals, reptiles, birds,mammals, reptiles, birds,
fish, insects & plantsfish, insects & plants
 Important generaImportant genera
VesiculovirusVesiculovirus
Lyssa virusLyssa virus

3. Rabies virusRabies virus
 Bullet shaped virusBullet shaped virus
 Size is 180 x 75 nmSize is 180 x 75 nm
 Has LipoproteinHas Lipoprotein
envelopeenvelope
 Knob like spikesKnob like spikes
/Glycoprotein G/Glycoprotein G
 Genome unsegmentedGenome unsegmented
 Linear negative senseLinear negative sense
RNARNA
 RNA dependent RNARNA dependent RNA
polymerasepolymerase

4. RESISTANCERESISTANCE
 Lipid solventsLipid solvents
 Sensitive to ethanol, iodine, quaternarySensitive to ethanol, iodine, quaternary
ammonium compounds, soap, detergentsammonium compounds, soap, detergents
 Inactivated by phenol, formalin, BPL, COInactivated by phenol, formalin, BPL, CO22,,
UV & sunlightUV & sunlight
 Thermal inactivation (50˚C for 1h & 60˚CThermal inactivation (50˚C for 1h & 60˚C
for 5 min)for 5 min)
 Dies at room temperature but can surviveDies at room temperature but can survive
for weeks when stabilised with 50%for weeks when stabilised with 50%
glycerolglycerol

5. ANTIGENIC PROPERTIESANTIGENIC PROPERTIES
 Glycoprotein GGlycoprotein G
 NucleoproteinNucleoprotein
 GlycolipidGlycolipid
 RNA dependent RNA polymeraseRNA dependent RNA polymerase

6. GLYCOPROTEIN GGLYCOPROTEIN G
 Pathogenesis, virulence and immunityPathogenesis, virulence and immunity
 Mediates binding to acetylcholineMediates binding to acetylcholine
receptorsreceptors
 Heamagglutination inhibition antibodiesHeamagglutination inhibition antibodies
 Neutralising antibodiesNeutralising antibodies
 Stimulates cytotoxic T cell immunityStimulates cytotoxic T cell immunity
 Serotype specific antigenSerotype specific antigen
 Safe and effective subunit vaccineSafe and effective subunit vaccine

7. NUCLEOPROTEINNUCLEOPROTEIN
 Induces complement fixing antibodiesInduces complement fixing antibodies
 The antibodies are not protectiveThe antibodies are not protective
 Group specificGroup specific
 Cross reactionsCross reactions
 Antiserum used in diagnosticAntiserum used in diagnostic
immunofluorescence testsimmunofluorescence tests

8. HOST RANGE ANDHOST RANGE AND
CULTIVATIONCULTIVATION
 Cattles, cat & fox – highly susceptibleCattles, cat & fox – highly susceptible
 Skunks, Opposums & fowl – resistantSkunks, Opposums & fowl – resistant
 Humans, dogs – intermediate positionHumans, dogs – intermediate position
 Laboratory animal - miceLaboratory animal - mice

9. SKUNKSSKUNKS

10. OPPOSUMSOPPOSUMS

11. STREET VIRUSSTREET VIRUS
 Isolated from natural human or animalIsolated from natural human or animal
infectioninfection
 Fatal encephalitis in laboratory animalsFatal encephalitis in laboratory animals
after a long and variable incubation periodafter a long and variable incubation period
of about 1- 12 weeks.of about 1- 12 weeks.
 Negri bodies (cerebellum & hippocampus)Negri bodies (cerebellum & hippocampus)

12. FIXED VIRUSFIXED VIRUS
 Serial intracerebral passages in rabbitsSerial intracerebral passages in rabbits
 More neurotropicMore neurotropic
 Less infectiousLess infectious
 Fatal encephalitis after a short and fixedFatal encephalitis after a short and fixed
incubation period (6 – 7 days)incubation period (6 – 7 days)
 No negri bodiesNo negri bodies
 Vaccine productionVaccine production

13. Pathogenesis of RabiesPathogenesis of Rabies
 Bite by Rabid dog or other animalsBite by Rabid dog or other animals
 Virus present in the saliva is deposited in theVirus present in the saliva is deposited in the
woundwound
 If untreated 50% will develop rabies.If untreated 50% will develop rabies.
 Rabies can be produced by licks and cornealRabies can be produced by licks and corneal
transplantation.transplantation.
 Virus multiply in the muscle ,connectiveVirus multiply in the muscle ,connective
tissue & nerves for 48 – 72 hours.tissue & nerves for 48 – 72 hours.
 Penetrates nerve endings and travels in thePenetrates nerve endings and travels in the
axoplasm towards the spinal cord & brainaxoplasm towards the spinal cord & brain
(3mm per hour)(3mm per hour)

14.  CentripetalCentripetal spread from axons to thespread from axons to the
neuronal bodiesneuronal bodies
 Multiplies in the brainMultiplies in the brain
 CentrifugalCentrifugal spread along the nerve trunksspread along the nerve trunks
to various parts of the body including theto various parts of the body including the
salivary glandssalivary glands

15. INCUBATION PERIODINCUBATION PERIOD::
Normally 1 - 3 monthsNormally 1 - 3 months
May be short as 7 days or as long as 3 years.May be short as 7 days or as long as 3 years.
Depends on- Site of biteDepends on- Site of bite
Severity of biteSeverity of bite
Number of woundsNumber of wounds
Amount of virus injectedAmount of virus injected
Species of biting animalSpecies of biting animal
Protection provided by clothingProtection provided by clothing
Treatment takenTreatment taken

16. CLINICAL STAGESCLINICAL STAGES
1 – Prodromerodrome
2 – Acute Encephalitic phase2 – Acute Encephalitic phase
3 – Coma3 – Coma
4 - Death4 - Death

17. PRODROMEPRODROME
 Non specific symptompsNon specific symptomps
 An early symptom is often a neuritic typeAn early symptom is often a neuritic type
of pain or paresthesia or fasciculation atof pain or paresthesia or fasciculation at
the site of virus entrythe site of virus entry
 Apprehension, anxiety, agitation,Apprehension, anxiety, agitation,
irritability, nervousness, insomnia &irritability, nervousness, insomnia &
depression (2 – 4 days)depression (2 – 4 days)
 Excessive libido, Priapism & spontaneousExcessive libido, Priapism & spontaneous
ejaculationejaculation
 2 – 10 days2 – 10 days

18. ACUTE ENCEPHALITISACUTE ENCEPHALITIS
PHASEPHASE
 Hyperactivity (intermittent) with bouts ofHyperactivity (intermittent) with bouts of
bizarre behaviour, agitation or seizuresbizarre behaviour, agitation or seizures
 Spontaneous or precipitated by externalSpontaneous or precipitated by external
stimulistimuli
 HydrophobiaHydrophobia
 Generalised convulsions followGeneralised convulsions follow
 2 – 10 days2 – 10 days

19. Rabies can present as GraveRabies can present as Grave
conditioncondition

20. Majority will succumb toMajority will succumb to
DiseaseDisease

21. RABIES IN DOGSRABIES IN DOGS
 Incubation period is 3 – 6 weeksIncubation period is 3 – 6 weeks
 Signs - Alert, troubled air and a change inSigns - Alert, troubled air and a change in
disposition with restlessness, snapping atdisposition with restlessness, snapping at
imaginary objects, licking or gnawing atimaginary objects, licking or gnawing at
the site of bitethe site of bite
 2 types – furious & dumb2 types – furious & dumb

22. FURIOUS RABIESFURIOUS RABIES

23. DUMB RABIESDUMB RABIES

24. LABORATORY DIAGNOSISLABORATORY DIAGNOSIS
 Animal inoculationAnimal inoculation
 Tissue culture – WI 38, BHK 21, CERTissue culture – WI 38, BHK 21, CER
 Antibody demonstration – CSFAntibody demonstration – CSF
 RT PCRRT PCR

25. Common confirmatory test -Common confirmatory test -
RabiesRabies
The standard antemortemThe standard antemortem
test istest is DirectDirect
ImmunofluorescenceImmunofluorescence
test to demonstrate thetest to demonstrate the
presence of viral antigen.presence of viral antigen.
The standard postmortemThe standard postmortem
test is biopsy of the patient'stest is biopsy of the patient's
brain and examination forbrain and examination for
Negri bodies.Negri bodies.

26. LABORATORY DIAGNOSIS INLABORATORY DIAGNOSIS IN
DOGSDOGS
 Whole carcassWhole carcass
 severed head of the animalsevered head of the animal
 The brain – 50 % GLYCEROL SALINEThe brain – 50 % GLYCEROL SALINE
- ZENKER’S fixative- ZENKER’S fixative

27. DEMONSTRATION OF NEGRIDEMONSTRATION OF NEGRI
BODIESBODIES
 Impression smears of the brainImpression smears of the brain
 Seller’s techniqueSeller’s technique
 Basic fuchsin + methylene blue inBasic fuchsin + methylene blue in
methanolmethanol
 Tissue sections with Giemsa or Mann’sTissue sections with Giemsa or Mann’s
methodmethod

28. NEGRI BODIESNEGRI BODIES

29. PROPHYLAXISPROPHYLAXIS
 Pre exposurePre exposure
 Post exposurePost exposure
Local treatmentLocal treatment
Antirabic vaccineAntirabic vaccine
Antirabies serumAntirabies serum

30. Preexposure ProphylaxisPreexposure Prophylaxis
 Indicated inIndicated in
LaboratoryLaboratory
workers.workers.
VeterinariansVeterinarians
and technical staff.and technical staff.
Bat handlers.Bat handlers.

31. LOCALLOCAL
TREATMENTTREATMENT
Prompt cauterisation of the woundPrompt cauterisation of the wound
Soap and waterSoap and water
Quaternary ammonium compound & iodine orQuaternary ammonium compound & iodine or
alcohol (40 – 70%)alcohol (40 – 70%)
Antirabic serumAntirabic serum
Postpone suturing of the woundPostpone suturing of the wound
Anti – tetanus measures & antibioticsAnti – tetanus measures & antibiotics

33. Ist Vaccine for RabiesIst Vaccine for Rabies
 Prepared by PasteurPrepared by Pasteur
by drying pieces ofby drying pieces of
spinal cord of Rabbitsspinal cord of Rabbits
infected with fixedinfected with fixed
virusvirus
 18851885 JosephJoseph
MeisterMeister 9 year boy9 year boy
vaccinated with 13vaccinated with 13
injectionsinjections
 Boy survivedBoy survived

34. ANTIRABIC VACCINEANTIRABIC VACCINE
 Neural vaccineNeural vaccine
Semple vaccineSemple vaccine
BPL vaccineBPL vaccine
Suckling mouseSuckling mouse
brain vaccinebrain vaccine
Non neural vaccineNon neural vaccine
Egg vaccineEgg vaccine
Duck egg vaccineDuck egg vaccine
Live attenuated chickLive attenuated chick
embryo vaccines –embryo vaccines –
LEP, HEP (flury strain)LEP, HEP (flury strain)
Tissue culture vaccineTissue culture vaccine
Subunit vaccineSubunit vaccine

35. TISSUE CULTURE VACCINETISSUE CULTURE VACCINE
 Human diploid cell vaccine(WI38 orHuman diploid cell vaccine(WI38 or
MRC5)MRC5)
Pitman – Moore strainPitman – Moore strain
Inactivated with BPL or Tri- n- butylInactivated with BPL or Tri- n- butyl
phosphatephosphate
 Primary cell culture vaccinesPrimary cell culture vaccines
 Continuous cell culture vaccinesContinuous cell culture vaccines

36. vaccination schedulesvaccination schedules
 Anti Rabies vaccines are given whenAnti Rabies vaccines are given when
person isperson is
1 Bitten1 Bitten
2 Scratched2 Scratched
3 Licked3 Licked
By Rabid animalBy Rabid animal
animal to be kept for 10 days ?animal to be kept for 10 days ?

37. WHO guidelines on PostWHO guidelines on Post
exposure prophylaxisexposure prophylaxis
 Category I – Touch or feeding of animalCategory I – Touch or feeding of animal
- Lick on intact skin- Lick on intact skin
 Category II – Nibbling of uncovered skinCategory II – Nibbling of uncovered skin
- Minor scratches or abrasions- Minor scratches or abrasions
without bleedingwithout bleeding
 Category III – Single or multiple bitesCategory III – Single or multiple bites
- licks on broken skin- licks on broken skin
- contamination of mucous- contamination of mucous
membrane with salivamembrane with saliva
- Exposure to bats- Exposure to bats

38. Post exposure ProphylaxisPost exposure Prophylaxis
 The vaccination isThe vaccination is
given ongiven on
0, 3, 7, 14, 30,0, 3, 7, 14, 30,
and 90and 90thth
dayday
Immunity lasts for 5Immunity lasts for 5
yearsyears
Injected on deltoidInjected on deltoid
region IM/SCregion IM/SC
Not to be given in theNot to be given in the
gluteal regiongluteal region

39. Cell culture Vaccines in –Cell culture Vaccines in –
commonly prescribedcommonly prescribed
11 Human diploid cellHuman diploid cell
vaccine (HDC)vaccine (HDC)
22 Purified chickPurified chick
embryo cellembryo cell
vaccine (PCEC)vaccine (PCEC)
3.Purified Vero Cell3.Purified Vero Cell
vaccine (PVC)vaccine (PVC)

40. Pre exposure prophylaixisPre exposure prophylaixis
dosesdoses
 Given on the followingGiven on the following
daysdays
0, 7, 210, 7, 21
oror
0, 28 and 560, 28 and 56thth
dayday
Booster – 1 yearBooster – 1 year

41. Passive ImmunizationPassive Immunization
 Equine Rabies IgEquine Rabies Ig
 Human RabiesHuman Rabies
ImmunoglobulinImmunoglobulin
 High Risk bitten onHigh Risk bitten on
face and neckface and neck
 Given a dose of 20 IUGiven a dose of 20 IU
/Kg wt/Kg wt
 Half at the site of biteHalf at the site of bite
and rest IM route.and rest IM route.

42. VACCINE FOR ANIMALSVACCINE FOR ANIMALS
 Neural vaccines are not satisfactoryNeural vaccines are not satisfactory
 Concentrated cell culture vaccinesConcentrated cell culture vaccines
12 weeks of age12 weeks of age
Repeated at 1 – 3 years intervalRepeated at 1 – 3 years interval
Vaccine baits in EuropeVaccine baits in Europe

43. TREATMENTTREATMENT
 Intensive supportive careIntensive supportive care
 Management of complicationsManagement of complications
 No antirabies agent is availableNo antirabies agent is available

44. EpidemiologyEpidemiology
 No Danger of Nursing RabiesNo Danger of Nursing Rabies
patients but do take precautionspatients but do take precautions
 Corneal transplantCorneal transplant
 2 epidemiological types – Urban & Sylvatic2 epidemiological types – Urban & Sylvatic
 RESERVOIR – Mustelids, Viverids &RESERVOIR – Mustelids, Viverids &
frugivorous batsfrugivorous bats

45. MUSTELIDSMUSTELIDS

46. VIVERIDSVIVERIDS

47. FRUGIVOROUS BATSFRUGIVOROUS BATS

48.  Rabies is endemic in indiaRabies is endemic in india
 30,000 deaths per year30,000 deaths per year
 7,00,000 people receive antirabies vaccine7,00,000 people receive antirabies vaccine
 Registration, licensing, vaccination of pets &Registration, licensing, vaccination of pets &
destruction of stray animalsdestruction of stray animals
 Elimination is possible only if the wild vectorsElimination is possible only if the wild vectors
(eg. Foxes, jackals) and the reservoirs are(eg. Foxes, jackals) and the reservoirs are
controlledcontrolled
 No Rabies in AustraliaNo Rabies in Australia

49. In spite of Health Education several die dueIn spite of Health Education several die due
to Rabies infection in Developing worldto Rabies infection in Developing world

50. World's Rabies Day (on SeptemberWorld's Rabies Day (on September
28)28)
 World Rabies Day isWorld Rabies Day is
a cooperative globala cooperative global
event planned toevent planned to
reduce the sufferingreduce the suffering
from rabies. This dayfrom rabies. This day
celebrates Dr. Louiscelebrates Dr. Louis
Pasteur’s vision of aPasteur’s vision of a
rabies free worldrabies free world..

52. RABIES RELATED VIRUSRABIES RELATED VIRUS
 Lagos bat virus – pooled brains ofLagos bat virus – pooled brains of
frugivorous batsfrugivorous bats
 Mokola virus – shrewsMokola virus – shrews
 Duvenhage virusDuvenhage virus
 European bat Lyssavirus types 1 & 2European bat Lyssavirus types 1 & 2
 Australian bat LyssavirusAustralian bat Lyssavirus

53. SHREWSSHREWS