Hassanein Rabies

8/6/2019 Hassanein Rabies

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RABIES


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What are Rabies?What are Rabies?

Rabies virus causes an acute encephalitisRabies virus causes an acute encephalitis(inflammation of the brain) in all warm(inflammation of the brain) in all warm--bloodedbloodedhosts.hosts.

Rabies is not, in the natural sense, a disease ofRabies is not, in the natural sense, a disease ofhumans.humans.

Raccoons, skunks, foxes, coyotes, and severalRaccoons, skunks, foxes, coyotes, and several

species of insectivorous bats have been identifiedspecies of insectivorous bats have been identifiedas reservoirs for the disease.as reservoirs for the disease.


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EpidemiologyEpidemiology

In the Third World: An estimated 40In the Third World: An estimated 40--70,000 people die from the disease70,000 people die from the diseaseeach yeareach year

Rare in U.S.Rare in U.S.

40 cases/year prior to vaccination of40 cases/year prior to vaccination of

domestic animals that began in 1947domestic animals that began in 1947 3 cases/year now reported3 cases/year now reported


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World wide: Dogs most commonlyWorld wide: Dogs most commonlyinfected and cause more transmissioninfected and cause more transmissionto humansto humans

Bats: An important source in North &Bats: An important source in North &

South America and Mexico.South America and Mexico.


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In U.S.In U.S.-- >>9090%% ofofrabies occurs in wildrabies occurs in wild

animals: Principalanimals: Principalreservoirs arereservoirs areracoonsracoons,, skunks,skunks,foxes and batsfoxes and bats


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MorphologyMorphology

Member of theMember of the RhabdovirusRhabdovirusfamilyfamily

OrderOrder-- MononegaviralesMononegavirales

NeurotropicNeurotropic RNA virusRNA virus NonsegmentedNonsegmented

Negative stranded RNA genomeNegative stranded RNA genome

Bullet shapedBullet shaped-- RhabdovirusRhabdovirus180180nm xnm x7575nmnm

400400 trimerictrimeric spikes on surface ofspikes on surface ofvirusvirus

22 major structural componentsmajor structural components

Helical RNP coreHelical RNP core

Surrounding envelopeSurrounding envelope


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PhysiologyPhysiology

Genome encodesGenome encodes 55 proteins:proteins: NucleoproteinNucleoprotein-- encases RNAencases RNA

PhosphoproteinPhosphoprotein-- associated with ribonuceoprotein coreassociated with ribonuceoprotein core

Matrix proteinMatrix protein-- central protein of rhabdovirus assemblycentral protein of rhabdovirus assembly

GlycoproteinGlycoprotein-- formsforms 400400 trimeric spikestrimeric spikes

PolymerasePolymerase-- transcribes genomic strand of rabies RNAtranscribes genomic strand of rabies RNA


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VirulenceVirulence

Depends on severity of biteDepends on severity of bite

If treatment is given and whenIf treatment is given and when

Once the disease manifests in CNS:Once the disease manifests in CNS:ultimate deathultimate death


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PathogenicityPathogenicity

Defined by encephalitis andDefined by encephalitis and myelitismyelitis

Uses N receptors.Uses N receptors.

PerivascularPerivascular infiltration throughout entire centralinfiltration throughout entire central

nervous systemnervous system CausesCauses cytoplasmiccytoplasmic eosinophiliceosinophilic inclusion bodiesinclusion bodies

((NegriNegri bodies) in neuronal cellsbodies) in neuronal cells

Several factors may affect outcome of rabiesSeveral factors may affect outcome of rabiesexposure.exposure.

Rabies variantRabies variant DoseDose

RouteRoute

Location of exposureLocation of exposure

Individual host factorsIndividual host factors


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TransmissionTransmission

Begins when infected saliva of host isBegins when infected saliva of host is

passed to uninfected animal.passed to uninfected animal. ScratchesScratches

BitesBites


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Almost allAlmost alltransmission is by bitetransmission is by bite

50 times greater risk50 times greater risk

than a scratchthan a scratch

One human case mayOne human case mayhave been acquired inhave been acquired in

a laboratorya laboratory(transmitted by(transmitted byaerosol)aerosol)


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In wild animals: Rabies can beIn wild animals: Rabies can betransmitted transplacentallytransmitted transplacentally

Transplants in humanTransplants in human-- possiblepossible

HumanHuman--toto--human: Never has beenhuman: Never has beenconfirmedconfirmed

Rabies virus never isolated from bloodRabies virus never isolated from blood


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Vehicles of TransmissionVehicles of Transmission

SalivaSaliva

Mucous membranesMucous membranes

Aerosol transmissionAerosol transmission

Corneal transplantationsCorneal transplantations


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Virus lifestyleVirus lifestyle

Virus replicated in muscle cells nearVirus replicated in muscle cells nearsite of bite for most of incubationsite of bite for most of incubation

time.time. Incubation timeIncubation time 3030--9090 days. Latency updays. Latency uptoto 77 yearsyears

Then ascends along motor andThen ascends along motor and

sensory axons at rate ofsensory axons at rate of 1212--100100mm/day and has predilection formm/day and has predilection forbrainstem and medullabrainstem and medulla

Enters salivary glands after replicationEnters salivary glands after replication

in CNS.in CNS.


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Rabies virusRabies virus

Risk of developing rabies after a bite:Risk of developing rabies after a bite:55--8080%.%.

Depends upon.Depends upon. Severity of exposureSeverity of exposure

Location of the biteLocation of the bite

The biting animalThe biting animal

**Bites on head and neck have shorter**Bites on head and neck have shorterincubation time (as short asincubation time (as short as 1515 days) becausedays) becauseof rich peripheral nerve supplyof rich peripheral nerve supply


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Clinical FeaturesClinical Features

ProdromeProdrome: HA, fever,: HA, fever, rhinorrhearhinorrhea, sore, sorethroat,throat, myalgiasmyalgias, GI upset. Back pain and, GI upset. Back pain and

muscle spasms.muscle spasms. Agitation and anxiety, agitation whichAgitation and anxiety, agitation which

eventually progress to delirium, abnormaleventually progress to delirium, abnormalbehavior, hallucinations, and insomnia maybehavior, hallucinations, and insomnia may

result in diagnosis of psychosis orresult in diagnosis of psychosis orintoxicationintoxication

ParesthesiasParesthesias, pain or severe itching at site, pain or severe itching at sitemay be the first neurological symptom.may be the first neurological symptom.


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Clinical FeaturesClinical Features

Over several days symptoms progressOver several days symptoms progress

Rabies takes two forms:Rabies takes two forms:

Furious/Encephalitic formFurious/Encephalitic form::agitation, hydrophobia, extremeagitation, hydrophobia, extremeirritability, hyperexcitability periodsirritability, hyperexcitability periods

fluctuate with lucidity.fluctuate with lucidity. Vitals abnormal: tachycardia, tachypnea,Vitals abnormal: tachycardia, tachypnea,

feverfever


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Encephalitic FormEncephalitic Form

Hydrophobia: Patient cant swallowHydrophobia: Patient cant swallowbecause violent jerky contraction ofbecause violent jerky contraction of

diaphragm and accessory muscles ofdiaphragm and accessory muscles ofinspiration when pt attempts toinspiration when pt attempts toswallow liquidsswallow liquids

-- Patients will be terrified duringPatients will be terrified duringthis reaction and may even experiencethis reaction and may even experiencethis at the sight of water or if waterthis at the sight of water or if watertouches their face.touches their face.


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Encephalitic FormEncephalitic Form

Aerophobia: an extreme fear of air inAerophobia: an extreme fear of air inmotion can be elicited from somemotion can be elicited from some

patients. This can also cause violentpatients. This can also cause violentmuscle spasms in the neck andmuscle spasms in the neck andpharynx.pharynx.

Hallucinations, seizures, ataxia, focalHallucinations, seizures, ataxia, focalweakness and arrhythmias can occur.weakness and arrhythmias can occur.


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Paralytic RabiesParalytic Rabies

Other form is dumb or paralyticOther form is dumb or paralyticrabies. Similar to Guillainrabies. Similar to Guillain--Barre.Barre.

Prominent limb weakness. ConsciousnessProminent limb weakness. Consciousnessinitially sparedinitially spared

Two forms can overlap or progressTwo forms can overlap or progress

from one to the otherfrom one to the other Coma after one week of neuroComa after one week of neuro

symptoms with death a few days after.symptoms with death a few days after.


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Rabies Diagnosis inRabies Diagnosis in

animalsanimals The direct fluorescentThe direct fluorescent

antibody test (dFA) is theantibody test (dFA) is thetest most frequently used totest most frequently used todiagnose rabies. This testdiagnose rabies. This testrequires brain tissue fromrequires brain tissue fromanimals suspected of beinganimals suspected of beingrabid.rabid.

The dFA test is based onThe dFA test is based onthe fact that infectedthe fact that infected

animals have rabies virusanimals have rabies virusproteins (antigen) presentproteins (antigen) presentin their tissues.in their tissues.

Positive dFA

Negative dFA


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Rabies Diagnosis inRabies Diagnosis in

humanshumans Saliva can be tested by virus isolationSaliva can be tested by virus isolation

or reverse transcription by polymeraseor reverse transcription by polymerase

chain reaction (RTchain reaction (RT--PCR).PCR). Serum and spinal fluid are tested forSerum and spinal fluid are tested for

antibodies to rabies virus.antibodies to rabies virus.

Skin biopsy specimens are examinedSkin biopsy specimens are examinedfor rabies antigen in the cutaneousfor rabies antigen in the cutaneousnerves at the base of hair follicles.nerves at the base of hair follicles.


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ManagementManagement

Once symptoms occur: fatal inOnce symptoms occur: fatal in 33--1010daysdays

ICU support: can prolongICU support: can prolong 44 months.months.

Six patients have survived clinicalSix patients have survived clinicalrabies:rabies: 55 had pre or postexposurehad pre or postexposureprophylaxis before onset of symptomsprophylaxis before onset of symptoms


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ManagementManagement

No effective treatment exists.No effective treatment exists.

Postexposure Prophylaxis/PEP:Postexposure Prophylaxis/PEP: 33

stepssteps 11.. Wound careWound care: immediate thorough: immediate thorough

washing with soap and water and awashing with soap and water and avirucidal agent such as povidinevirucidal agent such as povidine--iodine oriodine or

11--22% benzalkonium chloride.% benzalkonium chloride. Shown to be protective if performed withinShown to be protective if performed within 33

hours of exposurehours of exposure

If puncture, swab deeply in wound andIf puncture, swab deeply in wound and

around edgesaround edges


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PEPPEP

2.2. Passive ImmunizationPassive Immunization: Human rabies: Human rabiesimmunoglobulin (HRIG) 20 IU/kg ASAP, butimmunoglobulin (HRIG) 20 IU/kg ASAP, but

not longer than 7 days after vaccine given.not longer than 7 days after vaccine given.Infiltrate entire dose around wound, anyInfiltrate entire dose around wound, anyremaining IG injectIM at a site distant fromremaining IG injectIM at a site distant fromthe vaccine.the vaccine.

3.3. Human diploid cell vaccineHuman diploid cell vaccine (HDCV):(HDCV):Rabies Vaccine: A killed virus vaccine grownRabies Vaccine: A killed virus vaccine grownin human fibroblasts is available for safe usein human fibroblasts is available for safe usein humans.in humans.

1 ml (deltoid) on days 0,3,7,14,28.1 ml (deltoid) on days 0,3,7,14,28.


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PEPPEP

Vaccine: do not give in gluteal. IfVaccine: do not give in gluteal. Ifinjected into fat, no antibodies formed.injected into fat, no antibodies formed.

HRIG and HDCV: give in differentHRIG and HDCV: give in differentanatomical sites and never in theanatomical sites and never in the

same syringe.same syringe.


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Control and PreventionControl and Prevention

PrePre--exposure prophylaxis vaccinationexposure prophylaxis vaccination

PostPost--exposure prophylaxisexposure prophylaxis

If you are exposed to a possible rabidIf you are exposed to a possible rabidanimal:animal:

Wash wound with soap and waterWash wound with soap and water

Seek medical attention immediatelySeek medical attention immediately


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Control and PreventionControl and Prevention

Be a responsible pet ownerBe a responsible pet owner

Keep vaccinations up to dateKeep vaccinations up to date

Keep pets under direct supervisionKeep pets under direct supervision

Spay and neuter petsSpay and neuter pets

Enjoy wild animals from far awayEnjoy wild animals from far away

Dont adopt wild animalsDont adopt wild animals

Love your own, leave others aloneLove your own, leave others alonepolicypolicy

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Hassanein Rabies