Rabies

What is Rabies Rabies is a zoonotic disease cause by a rhabdovirus which infects the central nervous tissue and salivary gland often resulting in aggressive altered behaviour

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 800BC 400BC Aristotle writes that “dogs suffer from the madness” and that their bite confers disease

How did Rabies get its name Rabies comes from the Latin word rabere which means to rage or rave Latin work has its roots in the sanskrit word rabhas which means to do violence. The greeks called rabies lyssa, which means frenzy or madness.

Epidemiology Rabies 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

Epidemiology Typical route of infections is via bites from infected animals In many cases the infected animal exhibits Exceptional aggression Unprovoked attach behaviour General uncharacteristic behaviour Transmission between humans is rare

World Distribution

Epidemiology The World Health Organization (WHO) estimates that 55 000 people die of rabies annually. It is likely that this number is an underestimate and annual fatalities may be as high as 100 000. 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 15 Any warm blooded animal can be infected and as such any warm blooded animal can serve as a reservoir host Once symptoms of the disease develop, rabies is fatal

Viral Pathogen Rhabdovirus family; genus Lyssavirus Viral envelope bullet shaped Contains ss RNA Lipoprotein envelope Knob like spikes

Mechanism of infection Viral particles enter through: Breaks in the skin (bites, scratches) Through mucosal surfaces Through the respiratory tract Virus replicates in muscle cells Virus then docks with specific neural receptors and enters the host neurons Travels within infected neurons directionally towards the CNS Once in CNS travels to the brain and the rest of the body via peripheral nerves

Mechanism of Infection Salivary glands – virus migrates through peripheral nervous tissue to oral mucosal nerve endings Migrating viral pathogens shed into the oral mucus Replication also occurs in the salivary glands and is released with salivation.

Time Line of Infection Incubation 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 transfer In humans once incubation period ends flu-like symptoms appear Once the first symptoms appear the infection is effectively untreatable and usually fatal within days.

Immune Response There is a measurable antibody response but this occurs late in the course of infection and is insufficient. Altered cytokine release Some studies suggest the virus may persist in macrophages and emerge later to produce disease

Types of Rabies Furious rabies: Encephalitis form Hydrophobia Aerophobia Cranial nerve lesions Spasticity Involuntary movements Fluctuation body temp Sweating tachycardia

Types of Rabies Paralytic Rabies: No hydrophobia or aerophobia Flaccid paralysis Paralysis begins in limb associated with infection and expands to the rest of the body Death usually due to paralysis of the respiratory tract

Altered behaviour Major characteristic of rabies infection is major host behavioural changes mediated by the virus. Virus alters neuronal transmission of both infected neurons and uninfected neurons Neural damage is minimal during migration This suggests the virus can target specific neurons and alter behaviour with out killing

Altered behaviour Problems Not all infections result in aggression some result in paralysis which would appear to reduce transmission The 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?

Altered behaviour Suggested that the immunological reactions provoked by the virus play a role Altered cytokine release can effect the limbic system resulting in aggression This has been observed in other auto immune disorders If host immune response determines aggression then that would explain the varying behavioural alterations observed

Identifying Infected hosts Can you pick the rabid animals??

Human Symptoms – Early Stage Starts as flu-like symptoms and expands to: Slight or partial paralysis Cerebral dysfunction Anxiety Insomnia Confusion Agitation Abnormal behaviour Paranoia Terror Hallucinations Progression to delirium

Symptoms – Late stage Production of large quantities of saliva and tears Inability to speak or swallow Throat and jaw become paralyzed Hydrophobia and panic when presented with water In animals extreme aggression and risky behaviour appear

Diagnosis Biopsies of brain tissue. Can anyone see the problem with this?? Analysis of saliva, tracheal aspirates or throat swabs for viral particles Viral antibody screen If a human is bitten by suspected rabid mammal, the usual course of action is to euthanize the animal and perform a brain biopsy

Treatment Critical that treatment is administered as soon as possible and prior to the onset of severe symptoms Two general methods of treatment exist Wound Care Post Exposure prophylaxis (PEP) drugs

Treatment Wound Care Probably one of the most basic and important steps in prevention of rabies Estimated 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 > 1hour Wash wound with any of the above solutions Irrigation of wound with any virucidal agent

Treatment Post Exposure Prophylaxis The following treatment needs to be administered within 10 day following exposure The Center for Disease Control (CDC) recommends: One dose of human rabies immunoglobulin (HRIG) Followed by four doses of rabies vaccine over 14 days HRIG 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

Ethical Problems HRIG is extremely expensive costing several thousand dollars per injection For this reason there is a debate regarding when the drug should be administered Generally 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 PEP Recently the use of precautionary PEP for individuals where no contact can be confirmed has been questioned based on a cost benefit analysis

Case study In September 2000 a young boy in Quebec was found to have been in the presence of a bat while sleeping The child was observed and no visible contact (ie bite marks) with the bat could be identified PEP was not administered based on the lack of any marks on the child's skin 3 weeks later the child died from advanced rabies The child's doctors criticised the policy that PEP should only be administered when a visible bite or overt break in the skin has occurred

Conclusions Further research is needed to determine the exact mechanism of altered host behaviour Where possible vaccination of both humans and dominant wild host should be preformed PEP treatment should be administered as soon as possible after exposure

Questions?