Rabies. Rabies is the most lethal of all infectious diseases. Even the most extreme modern medical interventions are usually not successful. The.

RabiesRabies

Rabies is the most lethal of all infectious diseases.Rabies is the most lethal of all infectious diseases. Even the most extreme modern medical interventions are Even the most extreme modern medical interventions are

usually not successful. usually not successful.

The disease was recognized in Egypt before 2300 B.C. and The disease was recognized in Egypt before 2300 B.C. and in ancient Greece, where it was described by Aristotle.in ancient Greece, where it was described by Aristotle.

The method of transmission of rabies was not recognized The method of transmission of rabies was not recognized until 1804.until 1804.

Rabies is thought to be responsible for the origin of vampire Rabies is thought to be responsible for the origin of vampire legends (bats, biting, hypersexuality are associated with legends (bats, biting, hypersexuality are associated with rabies).rabies).

Rhabdoviridae: A large number of member viruses Rhabdoviridae: A large number of member viruses that are serologically unrelated.that are serologically unrelated.

Rabies belongs to the genus lyssa virus (rabies in Rabies belongs to the genus lyssa virus (rabies in Greek means mad or frenzy).Greek means mad or frenzy).

It is bullet shaped, enveloped and has a diameter of It is bullet shaped, enveloped and has a diameter of

75X180 nm. 75X180 nm.

Rabies VirusRabies Virus

G, M, L, N, and NS Proteins

transmissiontransmission Rabies is transmitted by rabid animals that have the Rabies is transmitted by rabid animals that have the

virus in their saliva. virus in their saliva.

Bites or licks of a rabid animal transmit rabies.Bites or licks of a rabid animal transmit rabies.

Rabies can be transmitted by moisture droplets in Rabies can be transmitted by moisture droplets in the air. the air.

Unusual modes of transmission (inhalation, Unusual modes of transmission (inhalation, aerosoles, ingestion, and corneal and other aerosoles, ingestion, and corneal and other transplants).transplants).

Ulceroglandular disease

PathogenesisPathogenesis Exact pathogenic mechanisms are not fully Exact pathogenic mechanisms are not fully

understood.understood.

Following the bite or a lick of a rabid animal, local Following the bite or a lick of a rabid animal, local multiplication takes place in striated muscles.multiplication takes place in striated muscles.

Virus attaches at neuromuscular junctions via the Virus attaches at neuromuscular junctions via the acetylcholine receptor.acetylcholine receptor.

Retrograde axoplasmic transport to the spinal cord.Retrograde axoplasmic transport to the spinal cord.

The virus reaches the brain and a wide disseminated The virus reaches the brain and a wide disseminated encephalitis develops.encephalitis develops.

Little discernable damage and very little Little discernable damage and very little histopathologic changes.histopathologic changes.

Cytoplasmic inclusions (Negri bodies) are Cytoplasmic inclusions (Negri bodies) are detectable in infected cells.detectable in infected cells.

Centrifugal dissemination of virus via afferent Centrifugal dissemination of virus via afferent

neurons to highly innervated sites.neurons to highly innervated sites.

CDC

Rabies Virus Rabies Virus (Rhabdovirus)(Rhabdovirus)

Figure 22.12

Clinical FeaturesClinical Features Incubation- mean 30-90 d; range 5days-7yearsIncubation- mean 30-90 d; range 5days-7years

Stages: incubation, prodrome, acute neurologic period, Stages: incubation, prodrome, acute neurologic period, coma and death or very rarely recovery. coma and death or very rarely recovery.

The prodromal phase is characterized by flu-like The prodromal phase is characterized by flu-like manifestations, malaise, headache, fever and a profound manifestations, malaise, headache, fever and a profound sense of apprehension and feeling of irritation with sense of apprehension and feeling of irritation with paraesthesia at the wound site.paraesthesia at the wound site.

There are complaints of dry throat, cough and thirst but There are complaints of dry throat, cough and thirst but patients will not drink.patients will not drink.

Difficulty in swallowing and revulsion of water Difficulty in swallowing and revulsion of water (hydrophobia).(hydrophobia).

Other manifestations include; photophobia, priapism, Other manifestations include; photophobia, priapism, increased lipido, insomnia, nightmares and depression.increased lipido, insomnia, nightmares and depression.

Frank manifestations of encephalitis including; bizarre Frank manifestations of encephalitis including; bizarre behavior, excitement, agitation, hallucinatory seizures, behavior, excitement, agitation, hallucinatory seizures, laryngeal spasm, chocking and gagging intermingled with laryngeal spasm, chocking and gagging intermingled with lucid intervals. lucid intervals.

This state gradually subsides into delirium, convulsions, This state gradually subsides into delirium, convulsions, coma and death.coma and death.

Signs of rabies in animalsSigns of rabies in animals Two clinical forms; furious rabies and dumb or paralytic Two clinical forms; furious rabies and dumb or paralytic

rabies. rabies.

Unusual behavior Unusual behavior Wild animals that appear friendlyWild animals that appear friendly Nocturnal animals active during the dayNocturnal animals active during the day

An increase in drool or saliva An increase in drool or saliva

Animals that act very sick or meanAnimals that act very sick or mean

Animals that have difficulty moving or are deadAnimals that have difficulty moving or are dead

Laboratory DiagnosisLaboratory Diagnosis LP, imaging: nonspecific, antibodies: appear lateLP, imaging: nonspecific, antibodies: appear late

Identification of rabies antigen by DFA (Salivary, Identification of rabies antigen by DFA (Salivary, corneal or conjunctival smears or biopsy of neck corneal or conjunctival smears or biopsy of neck nape >5 days, 2/3 +). nape >5 days, 2/3 +).

PCR saliva for rabies- > 5daysPCR saliva for rabies- > 5days

Virus Isolation: from saliva or CSFVirus Isolation: from saliva or CSF

Serology: Serology: ELISAELISA

Negri Body in neuron cell (source: CDC) Positive DFA test (Source: CDC)

Diagnosis of Rabies

Prognosis and Treatment Prognosis and Treatment Death from asphyxia, exhaustion, or general paralysis Death from asphyxia, exhaustion, or general paralysis

usually occurs within 3 to 10 days after onset of usually occurs within 3 to 10 days after onset of symptoms.symptoms.

However, recovery of one patient has occurred after However, recovery of one patient has occurred after

aggressive, vigorous, supportive treatment to control aggressive, vigorous, supportive treatment to control respiratory, circulatory, and CNS symptoms.respiratory, circulatory, and CNS symptoms.

If rabies develops, treatment is symptomatic.If rabies develops, treatment is symptomatic.

The case fatality ratio approaches unity. Consultation The case fatality ratio approaches unity. Consultation should be sought to assist in management.should be sought to assist in management.

Treatments: old myths to cure rabiesTreatments: old myths to cure rabies

Eating liver of a rabid dog.Eating liver of a rabid dog.

Eating a paste made from the eyes of a crayfish.Eating a paste made from the eyes of a crayfish.

Drenching wound with acid or burning area with a Drenching wound with acid or burning area with a red hot iron.red hot iron.

Sprinkling wound with gun powder and lighting it.Sprinkling wound with gun powder and lighting it.

ManagementManagement Proper care of woundsProper care of wounds

Immunoprophylaxis (Rabies human immunoglobulin)Immunoprophylaxis (Rabies human immunoglobulin)

Vaccination as soon you the patient is bitten (HDCV at 0, 3, Vaccination as soon you the patient is bitten (HDCV at 0, 3, 7, 14, 28 and 90 days after exposure).7, 14, 28 and 90 days after exposure).

Putting patient on respirator and maintaining support of Putting patient on respirator and maintaining support of vital functions.vital functions.

RealityReality: Once the virus attacks the brain, family should : Once the virus attacks the brain, family should organize the funeral because the patient is going to DIE.organize the funeral because the patient is going to DIE.

Rabies Vaccines for HumansRabies Vaccines for Humans

Inactivated whole virus vaccines are available for Inactivated whole virus vaccines are available for humans. humans.

Nervous Tissue Preparations are associated with Nervous Tissue Preparations are associated with the rare complication of demyelinating allergic the rare complication of demyelinating allergic encephalitis.encephalitis.

Duck Embryo Vaccine is grown in embryonated Duck Embryo Vaccine is grown in embryonated duck eggs. The vaccine has a lower risk of duck eggs. The vaccine has a lower risk of allergic encephalitis but is considerably less allergic encephalitis but is considerably less immunogenicimmunogenic

Human Diploid Cell Vaccine (HDCV) - this is Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine available with an currently the best vaccine available with an efficacy rate of nearly 100% and rarely any efficacy rate of nearly 100% and rarely any severe reactions. However it is very expensive. severe reactions. However it is very expensive.

Other Cell culture Vaccines - because of the Other Cell culture Vaccines - because of the expense of HDCV, other cell culture vaccines are expense of HDCV, other cell culture vaccines are being developed for the developing countries. being developed for the developing countries.

However recent data suggests that a much However recent data suggests that a much reduced dose of HDCV given intradermally may reduced dose of HDCV given intradermally may be just be effective. be just be effective.

EpidemiologyEpidemiology 35.000-50.000 cases are reported annually worldwide with the highest 35.000-50.000 cases are reported annually worldwide with the highest

numbers in Asia, particularly in India. In Asia 90% of cases result numbers in Asia, particularly in India. In Asia 90% of cases result from dog bites. from dog bites.

UK, Japan, Cyprus, Iceland, Australia, Taiwan and Hawaii are rabies-UK, Japan, Cyprus, Iceland, Australia, Taiwan and Hawaii are rabies-freefree

Among animals the disease may spread via two pathways, urban and Among animals the disease may spread via two pathways, urban and sylvatic.sylvatic.

Urban modeUrban mode: among domestic dogs and cats, a situation prevailing in : among domestic dogs and cats, a situation prevailing in the third world.the third world.

Sylvatic modeSylvatic mode: Foxes ( Europe, Canada and Northern USA), : Foxes ( Europe, Canada and Northern USA), Raccoons Raccoons ( Eastern seaboard, USA), Skunks (Southern USA), ( Eastern seaboard, USA), Skunks (Southern USA), Mongoose (West Indies)Mongoose (West Indies)

Animal Rabies in the USA is Common Animal Rabies in the USA is Common (n=7560*)(n=7560*)

RaccoonSkunkBatFoxCatCattleDogEquidsMongooseWoodchuckBobcatOther WildlifeSheep/GoatsOther Domestic* Current 5 year mean value

Usually 1-3 human cases per year

Dogs - especially stray & unvaccinated

Cats - especially stray and unvaccinated

Red Fox Silver tailed Bat

Striped SkunkRaccoon

Raccoons, Skunks, Foxes and Bats Are Major Rabies Reservoirs

Mammals that are less likely to carry rabies

Animals that don’t carry rabies

ControlControl Rabies has been controlled among dogs in the developed Rabies has been controlled among dogs in the developed

countries by vaccination.countries by vaccination.

Control of stray dogs and cats and dissemination of vaccine Control of stray dogs and cats and dissemination of vaccine virus among animals is very important.virus among animals is very important.

Vaccination of groups at risk; Lab. workers, those who Vaccination of groups at risk; Lab. workers, those who handle animals (Zoo workers, vets, quarantine workers, handle animals (Zoo workers, vets, quarantine workers, hunters), and those traveling to endemic areas.hunters), and those traveling to endemic areas.

Wildlife - Rabies in wild animals is much more difficult to control than canine rabies. However, on-going trials in the USA and Europe using bait containing rabies vaccine given to foxes and raccoons reduces rabies levels.