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The irreversible progress to death

When rabies virus penetrates the nervous system and travels through the neurons to the brain its progress is unstoppable.
In this activity, we are going to see where the virus replicates what the consequences are, and the diagnosis of the infection. When a rabid animal bites a person or another animal, it inoculates the virus with the saliva. The virus replicates in the muscular and connective cells of the entry tissue and when it has reached a high concentration, it enters the neurons. It progresses through the axons to the neuronal body, where it replicates, budding through the dendrites, crossing the neuronal synapsis to the next axon. This way it continues its centripetal course to the brain. When it reaches the central nervous system, clinical signs develop.
Subsequently, it goes to the salivary glands where it reaches very high concentrations, and can be transmitted to other animals through bites. When clinical signs are observed, the outcome is unfailingly death. The progress of the infection, through the nerve synapses, means that antibodies are only effective when the virus is replicating at the entry site. Once it has entered the neurons, it becomes absolutely unreachable to the immunoglobulins. The incubation period for rabies is typically 1 to 3 months, but may vary from less than 1 week to over 1 year. The initial signs of rabies are fever and often pain or an unusual tingling, pricking or numbness (which is known as paraesthesia) at the wound site, headache and lethargy.
When the virus reaches the central nervous system, progressive, fatal brain inflammation or encephalitis develops.
Two forms of the disease can follow: furious and paralytic. Animals with furious rabies exhibit signs of hyperactivity, hyperesthesia, are irritated by stimuli such as light, sounds and temperature. The animal is aggressive and bites everything around it, even to the point of self-mutilation, has seizures, difficulty in breathing and swallowing and hyper-salivation. After a few days, death occurs by cardio-respiratory arrest. Paralytic rabies runs a less dramatic and usually longer course than the furious form. The muscles gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly develops, and eventually the animal dies. This form of rabies is often difficult to diagnose and is often misdiagnosed.
As we have just seen, clinical rabies is almost always fatal so action must be taken before this happens. It is recommended that the rabies vaccine be given if there is the slightest suspicion that the animal that bit or scratched might be rabid. Although protective antibodies will take a week to develop, they will still be in time to neutralize viruses at the entry site, before they invade the nervous system. However, it is essential to make a correct diagnosis. Suspected animals often remain in observation or quarantine for at least 10 days.
Samples of saliva, serum, cerebrospinal fluid or skin biopsies can be used, and if it has been necessary to put the animal to sleep, samples of two locations of the central nervous system, preferably the brain stem and the cerebellum, should be analysed. Direct viral presence can be demonstrated by culturing saliva, or using the polymerase chain reaction technique or PCR, after having transcribed the viral RNA into DNA. Antibodies may be detected in the cerebrospinal fluid or in the serum. Their presence only proves that the animal or the person were in contact with rabies virus, but does not confirm that it occurred recently, and they could have been produced following vaccination.
Viral antigen may be demonstrated with a direct immunofluorescence test in the nerve endings of the skin or in the brain, recognized by antibodies labelled with a fluorescent substance. In this activity, we would like you to always remember that once the virus enters the nervous system, the progress toward death is unstoppable, so it is advisable to be vaccinated if there is the slightest chance of exposure to the virus.

In this video, we discover that after a short replication in the bite site, the rabies virus penetrates the nervous system.

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Animal Viruses: Their Transmission and the Diseases They Produce

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