Rabies is a fatal viral disease spread to humans through animal bites, especially from rabid dogs. It causes acute encephalitis and is almost always fatal once symptoms start. Mass dog vaccination programs can eliminate rabies transmission by vaccinating at least 70% of dogs. In Bangladesh, efforts are underway to reduce rabies deaths by 90% by 2015 and eliminate the disease by 2020 through dog vaccination campaigns and ensuring bite victims receive post-exposure prophylaxis.

6. Man’s bestMan’s best unvaccinatedunvaccinated friendfriend

8. Rabies
(Rhabdovirus)Rabhas means Frenzy

9. World Rabies Day (Sept. 28)World Rabies Day (Sept. 28)
…… to reduce theto reduce the
suffering fromsuffering from
rabiesrabies

11. At the end of session you will learnAt the end of session you will learn
• Rabies:Rabies: an invariably fatalan invariably fatal encephalitisencephalitis
• Only mammals affected. Always endemic in the wildOnly mammals affected. Always endemic in the wild
• 1111thth
killer IDkiller ID
• Wound Rx and ARV ± ARIg are main Px measureWound Rx and ARV ± ARIg are main Px measure
• VirusVirus descendsdescends from brain tofrom brain to salivary glandssalivary glands
• 90% from rabid domestic dog bite.90% from rabid domestic dog bite. Bats spread by aerosolBats spread by aerosol
• Elimination is feasibleElimination is feasible by vaccinating dogsby vaccinating dogs
• BangladeshBangladesh 22ndnd
in mortalityin mortality
100% preventable100% preventable
ARVL: anti-rabies vx. ARIg: AR ImmunoglobulinARVL: anti-rabies vx. ARIg: AR Immunoglobulin

13. KEY FACTS: RABIESKEY FACTS: RABIES
• Globally >60k deaths/yGlobally >60k deaths/y (150 countries)(150 countries)
• Almost always fatal once symptomaticAlmost always fatal once symptomatic
• 95% deaths in Asia Africa.95% deaths in Asia Africa. India: (~30,000)India: (~30,000)
• 40% children <15y40% children <15y
• >15million worldwide get a post-bite vax./y>15million worldwide get a post-bite vax./y
• Bangladesh: mBangladesh: most people are unprotectedost people are unprotected
• Rabies costs the world $124 billion/yRabies costs the world $124 billion/y
• Mass dog vaccination breaks the transmissionMass dog vaccination breaks the transmission

15. Bangladesh Scenario

16. • R. is an imp. PH problem and is the top zoonotic d.R. is an imp. PH problem and is the top zoonotic d.
• >2k deaths in2010; now <1k in 2013>2k deaths in2010; now <1k in 2013
• Control centre, at IDH: Rx 400 dog bites/d. Still, many bitesControl centre, at IDH: Rx 400 dog bites/d. Still, many bites
remains untreated.remains untreated. 2 targets:2 targets:
reducing deaths by 90%/2015 and eliminating R./2020reducing deaths by 90%/2015 and eliminating R./2020
• Dog is the main transmitter (95%); others: cats and jackalsDog is the main transmitter (95%); others: cats and jackals
Mass canine vax. program is running to stop transmission.Mass canine vax. program is running to stop transmission.
This can be achieved with 3 rounds vax. of 70% dogsThis can be achieved with 3 rounds vax. of 70% dogs
Bangladesh ScenarioBangladesh Scenario

17. Good News for BangladeshGood News for Bangladesh
• WHOWHO pilot project in Cox's Bazaarpilot project in Cox's Bazaar is a success. GoB is nowis a success. GoB is now
vaccinating dogs in all 64 districtsvaccinating dogs in all 64 districts
• Dog killers are now friendly dog catchers! >1k dogDog killers are now friendly dog catchers! >1k dog
catchers now focus on vax.catchers now focus on vax.
• Despite progress in this, fund remains a major challengeDespite progress in this, fund remains a major challenge
• Dog-bite victims can get free ARV, in all 64 districtsDog-bite victims can get free ARV, in all 64 districts
• Dog vax. costs, US $3/dog (total 1.2 million)Dog vax. costs, US $3/dog (total 1.2 million)
GoB: govt. of Bangladesh. ARV: anti-rabies vax. Vax.: vaccineGoB: govt. of Bangladesh. ARV: anti-rabies vax. Vax.: vaccine

18. What is Rabies?What is Rabies?
.. a zoonosis c/by.. a zoonosis c/by rabiesrabies virusvirus
• Infects both domestic and wild animalsInfects both domestic and wild animals
• Causes ac. encephalitisCauses ac. encephalitis
Symptomatic rabies:Symptomatic rabies: 100% fatal100% fatal

19. Rhabdo/lyssa virusesRhabdo/lyssa viruses
• Bullet shaped.Bullet shaped. RNARNA
• EnvelopedEnveloped
• Killed by ethanol ether,Killed by ethanol ether,
iodine, soap/detergents,iodine, soap/detergents,
chloroform, acetone,chloroform, acetone,
heat (60heat (6000
c x5 min)c x5 min)
Lyssa means rageLyssa means rage

20. Fixed and Street VirusFixed and Street Virus
• Fixed virusFixed virus (lab virus)(lab virus):: Rabies virus after serial passageRabies virus after serial passage
through rabbits to stabilize its virulence and IPthrough rabbits to stabilize its virulence and IP
• Street virus:Street virus: wild viruswild virus
IP: incubation periodIP: incubation period

21. EpidemiologyEpidemiology
• R. is present on all continents except AntarcticaR. is present on all continents except Antarctica
• Endemic in countries except Australia, Malaysia, Japan,Endemic in countries except Australia, Malaysia, Japan,
Bhutan, NepalBhutan, Nepal
• Primary reservoirs: wild mammalsPrimary reservoirs: wild mammals
• Only mammals affected;Only mammals affected; except mice !except mice !
• A neglected d. of poor remote rural people; deaths rarelyA neglected d. of poor remote rural people; deaths rarely
reported; vax and Ig are NA/affordable or accessiblereported; vax and Ig are NA/affordable or accessible
• Common:Common: man, dogs, raccoons, skunks, foxes, bats, cattleman, dogs, raccoons, skunks, foxes, bats, cattle
Ig: immunoglobulin. NA: not availableIg: immunoglobulin. NA: not available

23. Distribution of rabies reservoirsDistribution of rabies reservoirs

24. RaccoonsRaccoons

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

27. WHOWHO

28. • Bites, abrasionsBites, abrasions
• ScratchesScratches
• AAerosol (bats)erosol (bats)
• Mucosal exposureMucosal exposure
RarelyRarely
• eating infected meateating infected meat
• corneal transplantationcorneal transplantation
TransmissionTransmission

29. PathogenesisPathogenesis
• IP: 9-90dIP: 9-90d (several years):(several years):
depends on:depends on:
• inoculum, siteinoculum, site
• wound severity, innervationwound severity, innervation
• 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

30. Pathogenesis ..Pathogenesis ..
• Commonly RV replicates in muscles: enters nerves andCommonly RV replicates in muscles: enters nerves and
ascends to CNS (ascends to 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

31. Pathogenesis ..Pathogenesis ..
Live virusLive virus  skin: mucosa: muscleskin: mucosa: muscle
Peripheral nervePeripheral nerve
CNS (gray matter)CNS (gray matter)
Salivary, eyes, breast, kidneysSalivary, eyes, breast, kidneys
moves centripetally
moves centrifugally

32. HistopathologyHistopathology
• EncephalomyelitisEncephalomyelitis
• Perivascular inflammatory cellsPerivascular inflammatory cells
• NeuronalNeuronal cytoplasmic inclusioncytoplasmic inclusion (Negri bodies) esp. in(Negri bodies) esp. in
pyramidal cellspyramidal cells

34. Early CF: (often vague)Early CF: (often vague)
• Flu-like:Flu-like: malaise, LGF, chills, HA, fmalaise, LGF, chills, HA, fatigue, poor sleepatigue, poor sleep
• Anorexia, anxiety, irritability, sore throatAnorexia, anxiety, irritability, sore throat
• Discomfort/ paresthesiaDiscomfort/ paresthesia at bite site (50%)at bite site (50%)
• BBizarre behaviorizarre behavior
On progression:On progression: neuro-symptoms:neuro-symptoms:

35. Neuro-symptomsNeuro-symptoms
BBroadlyroadly
• Furious rabies (80%)Furious rabies (80%)
• Dumb/paralytic R (GBS)Dumb/paralytic R (GBS)

36. Furious rabiesFurious rabies
• Anxiety, delirium, insomnia, nervousness, seizure,Anxiety, delirium, insomnia, nervousness, seizure,
aggressivenessaggressiveness, hallucinations,, hallucinations, fear of deathfear of death
• BitingBiting, delusions, HGF, hyperhydrosis, goose skin, priopism,, delusions, HGF, hyperhydrosis, goose skin, priopism,
hypersalivationhypersalivation, dysphagia, hydrophobia (50%), aero-, photo-, dysphagia, hydrophobia (50%), aero-, photo-
• Coma and death in a few daysComa and death in a few days

38. Dumb/paralytic rabiesDumb/paralytic rabies
• S/of partial/full paralysisS/of partial/full paralysis usually begins in the limbs andusually begins in the limbs and
spreads all overspreads all over
• Hydrophobia isHydrophobia is unusualunusual
• Progress to coma and death (heart or lung failure)Progress to coma and death (heart or lung failure)

39. 3 dogs with classic dumb/3 dogs with classic dumb/
paralytic R: depression, self-paralytic R: depression, self-
imposed isolation; cranial-nerveimposed isolation; cranial-nerve
deficits and hypersalivationdeficits and hypersalivation

40. Routine rabies tests:Routine rabies tests:
• Direct fluorescent antibody test (dFA): only post mortem.Direct fluorescent antibody test (dFA): only post mortem.
Ideal tissue is nerve (brain). Fl. anti-R Ab incubated withIdeal tissue is nerve (brain). Fl. anti-R Ab incubated with
brain fixes RV; seen by Fl. MC. Unbound Ab washed awaybrain fixes RV; seen by Fl. MC. Unbound Ab washed away
• Histopathology:Histopathology: NegriNegri b. Immunohistochemistry. EMb. Immunohistochemistry. EM
Importance:Importance:
• For timely PEPFor timely PEP
• Save a pt. from unnecessary physical and psycho. traumaSave a pt. from unnecessary physical and psycho. trauma
if the animal is not rabidif the animal is not rabid
Diagnosis in AnimalsDiagnosis in Animals

41. 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 histopathology
Fl: fluorescence. MC: microscopeFl: fluorescence. MC: microscope

42. DFA negativeDFA negative
DFA positiveDFA positive

43. • Negri bodiesNegri bodies are pathognomonic:are pathognomonic: only in 20%only in 20%

44. Rabies Dx in HumansRabies Dx in Humans
• No test available before cl. diseaseNo test available before cl. disease
• Confirmed pre- and post mortem by detecting RV, viral Ag inConfirmed pre- and 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

45. PreventionPrevention
• Vaccinating dogsVaccinating dogs
• Vax. for at risk personsVax. for at risk persons
• Cost of PEP can be catastrophic for poor: income is $ 2/dCost of PEP can be catastrophic for poor: income is $ 2/d
• No contact with stray/wild animalsNo contact with stray/wild animals
• Not touching animal carcassesNot touching animal carcasses
• Don’t capture or provoke stray animalsDon’t capture or provoke stray animals
• Secure garbageSecure garbage
• Cover chimneys and other entrancesCover chimneys and other entrances

46. Treat the biteTreat the bite
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 animalregard as rabid unless the area is R free or until animal
is negative by lab testingis negative by lab testing
• immediate immunization and HRIGimmediate immunization and HRIG
•Bites by squirrels, gerbils, hamsters, G. pigs, rats, mice,Bites by squirrels, gerbils, hamsters, G. pigs, rats, mice,
other rodents, almost never require anti-R Rxother rodents, almost never require anti-R Rx
HRIG: human rabies immunoglobulinHRIG: human rabies immunoglobulin
PreventionPrevention

48. VaccinationVaccination
Killed R virus vaccine
 PreexposurePreexposure
 PostexposurePostexposure
 Animal vaccinationAnimal vaccination
15million vaccines are pushed worldwide15million vaccines are pushed worldwide

49. Who should get the vaccine?Who should get the vaccine?
Pre-exposure (PrEP)Pre-exposure (PrEP)
• High-risk people:High-risk people: vets., animal handlers, R lab. workers,vets., animal handlers, R lab. workers,
spelunkers (cave explorer), forestry workers, wildspelunkers (cave explorer), forestry workers, wild
explorers,explorers, travelers in endemic areastravelers in endemic areas
• Also for:Also for: people having frequent contact with RV, travelerspeople having frequent contact with RV, travelers
to endemic areasto endemic areas
• 3 doses: 0-7-21/283 doses: 0-7-21/28thth
dd

50. Benefits of pre-exposure VaxBenefits of pre-exposure Vax
• No need of HRIGNo need of HRIG
• Less post-expo. vax. dosesLess post-expo. vax. doses
• Post exposure Rx might be delayedPost exposure Rx might be delayed
• Protects from inapparent exposures to RProtects from inapparent exposures to R
• For repeated exposure screen for boosterFor repeated exposure screen for booster

51. 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
daysdays
• 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 HRIGd; no HRIG
• Should the animal be kept for 10 d?Should the animal be kept for 10 d?

53. 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)

54. Future Rabies VaccinesFuture Rabies Vaccines
• Vaccines under development may be safe, potent andVaccines under development may be safe, potent and
cheapercheaper
• DNA vaccinesDNA vaccines, recombinant vaccines, recombinant vaccines
• Plant biotechnology for making AgPlant biotechnology for making Ag
• Neutralizing monoclonal antibodyNeutralizing monoclonal antibody

55. Adverse ReactionsAdverse Reactions
• Less in childrenLess in children
• Adults: local reactions (25%), systemic- (20%)Adults: local reactions (25%), systemic- (20%)
• HA, nausea, AP, aches and dizziness (5-40%)HA, nausea, AP, aches and 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, if any, occurs within a min- to an hr. withAnaphylaxis, 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

56. Human Rabies IG (HRIG)Human Rabies IG (HRIG)
• Category iii bite: 20iu/kgCategory iii bite: 20iu/kg
with vax. but different siteswith vax. but different sites
• ½ at the site (infiltrate the½ at the site (infiltrate the
wound); ½ IMwound); ½ IM

57. Basic Care in Animal BitesBasic Care in Animal Bites
• Immediate thorough toileting x15min with soapImmediate thorough toileting x15min with soap
water, detergent, povidone iodine.water, detergent, povidone iodine. Don't suture!Don't suture!
• Categorize the bite:Categorize the bite:
• Post- exposure prophylaxisPost- exposure prophylaxis

59. CategoryCategory -- WHOWHO
• 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 skinlicks on broken skin
• Category III:Category III: 1 or more1 or more bites/scratches, licks with hge.;bites/scratches, licks with hge.;
contamination of m. membrane with saliva, contactscontamination of m. membrane with saliva, contacts
with batswith bats

60. Category ICategory I
no treatmentno treatment
Category IICategory II
wound disinfection, vaccine onlywound disinfection, vaccine only

61. Category IIICategory III
wound cleansing, HRIG and vaccinewound cleansing, HRIG and vaccine
• Animal observation in our country is not practical: frequentAnimal observation in our country is not practical: 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 forDog >1yr old with current vaccination (observe for
10d)10d)

62. Category III bite:Category III bite: bites withbites with
bleedingbleeding

65. • To date only 6 cases survivedTo date only 6 cases survived
• Once clinical, rabies is always fatal, Rx is only supportiveOnce clinical, rabies is always fatal, Rx is only supportive
• Rabies typically ends after 2-10 d (6d)Rabies typically ends after 2-10 d (6d)
No danger of nursing R pts with precautionsNo danger of nursing R pts with precautions
PrognosisPrognosis

66. DDDD
 Other encephalitisOther encephalitis
 Hysteria reaction to animal biteHysteria reaction to animal bite
 GBSGBS
 PoliomyelitisPoliomyelitis
 Allergic encephalomyelitis ( rabies vaccine )Allergic encephalomyelitis ( rabies vaccine )

67. 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

68. 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

70. Next LecNext Lec
Snake BiteSnake Bite

71. THANK YOU