Medical Microbiology

468 8 VirusesasHumanPathogen

Pathogen.Therhabdovirusesofsignificanceinhumanmedicineareclassi-

fiedinsevengenotypes.Type 1 istheclassic,worldwidetypethatoccursin

twoforms:the“streetvirus”isolatedfromhumansandanimalsandthe

“virusfixe”accordingtoPasteur.In 1 882,Pasteurhadtransmittedthevirus

intracerebrallytorabbits.Followingrepeatedpassagesofthevirusintherab-

bits,hehaddevelopedadeadvaccinetype.Duetothebrain-to-brainpas-

sagesinthelaboratoryanimals,the“virusfixe”becamesohighlyadapted

tobraintissuethatitwasunabletoreplicateinextraneuraltissues.Types

2 – 4 wereisolatedfromAfricanbats,types 5 and 6 fromEuropeanbats,

andtype 7 fromAustralianbats.

Rhabdovirusesarerodlike, 60! 180 nminsize,withoneendflatandone

endrounded(“bulletshaped”)andaspikedenvelopesurroundinganucleo-

capsidsimilartothatofthemyxoviruses.Thegenomeconsistsofantisense-

strandRNA.

Pathogenesisandclinicalpicture.Rabiesvirusesarealmostalwaystrans-

mittedbythebite,sometimesalsothescratch,ofarabidanimal(exceptions,

seebelow).Thevirusatfirstreplicatesattheportalofentryinmuscleand

connectivetissue,thenwandersalongthenervecellsintotheCNS,where

moreviralreplicationtakesplace.Usingthesameroute,thevirusthendis-

seminatesfromtheCNSintoperipheralorgans,aboveallthesalivaryglands,

cornea,andkidneys.Theprimaryclinicalpictureisanencephalitiswithlethal

outcomeforhumansandanimalsonceithasbrokenout.

ClinicalCourseofRabies

Thediseasegoesthroughthreestages.Theinitial,orprodromal,stageinvolves

itchingandburningattheportalofentry(bitewound),nausea,vomiting,andpos-

siblyamelancholymood.Inthesecondorexcitativestage,crampsandspasmsof

thepharynxandlarynxarethemainsymptoms,renderingswallowingverypainful.

Thespasmscanbeinducedbythemeresightofwater(“hydrophobia”).Othermild

acousticandvisualstimulimayelicitexaggeratedreactionsincludingattacksof

crampsandviolentanger,hitting,biting,andscreaming.Deathoccurswithinthree

tofourdaysattheearliest.Thethird,paralytic,stagemaydevelopinsteadofearly

death,withascendingparalysisandasphyxia,leadingtoexitus.Therapyisexclu-

sivelysymptomatic.Sincethepatientexperiencesthediseaseinafullyconscious

state,mostofthemedicationservestoalleviatethepainandanxietystates.The

diseaserunsessentiallythesamecourseinhumansandanimals,wherebythebe-

haviorofanimalsisoftenradicallyaltered:wildanimalslosetheirfearofhumans

andtamepetsbecomeaggressive.Rabieswiththeexcitativestageisknownas

“furiousrabies,”withoutitas“dumbrabies.”

Diagnosis.Anintra-vitamlaboratorydiagnosisisestablishedbyexamining

animpressionpreparationfromthecorneaorskinbiopsieswithimmuno-

fluorescence.Postmortem,rabiesvirusescanbefoundinthebraintissue

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Kayser, Medical Microbiology © 2005 Thieme