2 What is RabiesRabies is a zoonotic disease cause by a rhabdovirus which infects the central nervous tissue and salivary gland often resulting in aggressive altered behaviour
3 History One of the oldest infectious diseases recorded 2300 BC Babylonian dog owners fined for deaths resulting from their dogs biting people (possibly rabies?)References are made to “raging dogs” as early as 800BC400BC Aristotle writes that “dogs suffer from the madness” and that their bite confers disease
4 How did Rabies get its name Rabies comes from the Latin word rabere which means to rage or raveLatin work has its roots in the sanskrit word rabhas which means to do violence.The greeks called rabies lyssa, which means frenzy or madness.
5 EpidemiologyRabies is currently distributed worldwide except for Antarctica, Australia and a few island nations.In developing areas where canine rabies remains common and there are a large number of wild dogs, most human cases results from dog bites.In developed nations like Canada where dogs are immunized, most human cases follow exposure to rabid wild animals
6 EpidemiologyTypical route of infections is via bites from infected animalsIn many cases the infected animal exhibitsExceptional aggressionUnprovoked attach behaviourGeneral uncharacteristic behaviourTransmission between humans is rare
8 EpidemiologyThe World Health Organization (WHO) estimates that people die of rabies annually. It is likely that this number is an underestimate and annual fatalities may be as high as About 95% of human deaths occur in Asia and Africa.Most human deaths follow a bite from an infected dog. Between 30% to 60% of the victims of dog bites are children under the age of 15Any warm blooded animal can be infected and as such any warm blooded animal can serve as a reservoir hostOnce symptoms of the disease develop, rabies is fatal
9 Viral Pathogen Rhabdovirus family; genus Lyssavirus Viral envelope bullet shapedContains ss RNALipoprotein envelopeKnob like spikes
10 Mechanism of infection Viral particles enter through:Breaks in the skin (bites, scratches)Through mucosal surfacesThrough the respiratory tractVirus replicates in muscle cellsVirus then docks with specific neural receptors and enters the host neuronsTravels within infected neurons directionally towards the CNSOnce in CNS travels to the brain and the rest of the body via peripheral nerves
11 Mechanism of Infection Salivary glands – virus migrates through peripheral nervous tissue to oral mucosal nerve endingsMigrating viral pathogens shed into the oral mucusReplication also occurs in the salivary glands and is released with salivation.
13 Time Line of InfectionIncubation period varies between 20 and 90 days but can be as long as two years.Incubation period depend on location of infection and severity of viral transferIn humans once incubation period ends flu-like symptoms appearOnce the first symptoms appear the infection is effectively untreatable and usually fatal within days.
14 Immune ResponseThere is a measurable antibody response but this occurs late in the course of infection and is insufficient.Altered cytokine releaseSome studies suggest the virus may persist in macrophages and emerge later to produce disease
15 Types of Rabies Furious rabies: Encephalitis form Hydrophobia AerophobiaCranial nerve lesionsSpasticityInvoluntary movementsFluctuation body tempSweatingtachycardia
16 Types of Rabies Paralytic Rabies: No hydrophobia or aerophobia Flaccid paralysisParalysis begins in limb associated with infection and expands to the rest of the bodyDeath usually due to paralysis of the respiratory tract
17 Altered behaviourMajor characteristic of rabies infection is major host behavioural changes mediated by the virus.Virus alters neuronal transmission of both infected neurons and uninfected neuronsNeural damage is minimal during migrationThis suggests the virus can target specific neurons and alter behaviour with out killing
18 Altered behaviour Problems Not all infections result in aggression some result in paralysis which would appear to reduce transmissionThe virus does not target the areas of the brain associated with aggression!!!Furthermore the distribution of the virus in the brain in both the paralytic and encephalitic forms of rabies is the same!!!So how does the virus produce enhanced aggression?
19 Altered behaviourSuggested that the immunological reactions provoked by the virus play a roleAltered cytokine release can effect the limbic system resulting in aggressionThis has been observed in other auto immune disordersIf host immune response determines aggression then that would explain the varying behavioural alterations observed
20 Identifying Infected hosts Can you pick the rabid animals??
21 Human Symptoms – Early Stage Starts as flu-like symptoms and expands to:Slight or partial paralysisCerebral dysfunctionAnxietyInsomniaConfusionAgitationAbnormal behaviourParanoiaTerrorHallucinationsProgression to delirium
22 Symptoms – Late stageProduction of large quantities of saliva and tearsInability to speak or swallowThroat and jaw become paralyzedHydrophobia and panic when presented with waterIn animals extreme aggression and risky behaviour appear
23 DiagnosisBiopsies of brain tissue. Can anyone see the problem with this??Analysis of saliva, tracheal aspirates or throat swabs for viral particlesViral antibody screenIf a human is bitten by suspected rabid mammal, the usual course of action is to euthanize the animal and perform a brain biopsy
24 TreatmentCritical that treatment is administered as soon as possible and prior to the onset of severe symptomsTwo general methods of treatment existWound CarePost Exposure prophylaxis (PEP) drugs
25 TreatmentWound CareProbably one of the most basic and important steps in prevention of rabiesEstimated proper wound care alone can reduce risk by up to 90%Virus sensitive to: Ethanol, Iodine, Detergents, general exposure to temperatures above 50 degrees Celsius > 1hourWash wound with any of the above solutionsIrrigation of wound with any virucidal agent
26 Treatment Post Exposure Prophylaxis The following treatment needs to be administered within 10 day following exposureThe Center for Disease Control (CDC) recommends:One dose of human rabies immunoglobulin (HRIG)Followed by four doses of rabies vaccine over 14 daysHRIG should be administered in the transfer site followed by deep intramuscular injection at site far from the entry point.Inevitably the best treatment is prevention via immunization (both human and pet) and not associating with wild animals or domestic stalk that is acting strange
27 Ethical ProblemsHRIG is extremely expensive costing several thousand dollars per injectionFor this reason there is a debate regarding when the drug should be administeredGenerally it was suggested that any individual that awakes to find a bat in the room, or has been exposed to any wild animal while intoxicated or sleeping should receive PEPRecently the use of precautionary PEP for individuals where no contact can be confirmed has been questioned based on a cost benefit analysis
28 Case studyIn September 2000 a young boy in Quebec was found to have been in the presence of a bat while sleepingThe child was observed and no visible contact (ie bite marks) with the bat could be identifiedPEP was not administered based on the lack of any marks on the child's skin3 weeks later the child died from advanced rabiesThe child's doctors criticised the policy that PEP should only be administered when a visible bite or overt break in the skin has occurred
29 ConclusionsFurther research is needed to determine the exact mechanism of altered host behaviourWhere possible vaccination of both humans and dominant wild host should be preformedPEP treatment should be administered as soon as possible after exposure