Rabies

Infectious diseases

Clinicals - History

Fact Explanation
Neuropathic pain, itching and paresthesia at the site of wound or injection. Due to viral replication in non neural tissue following inoculation and local inflammation Neuropathic pain, itching and paresthesia at the site of wound or injection.
Due to viral replication in non neural tissue following inoculation and local inflammation
Irritability and agitation Due to encephalitis Irritability and agitation
Due to encephalitis
Vomiting, diarrhoea During the initial prodromal period Vomiting, diarrhoea
During the initial prodromal period
Cranial nerve involvement - facial asymmetry, trismus, drooping lower jaw etc Due to neuritis/ encephalitis involving cranial nerve nucleus Cranial nerve involvement - facial asymmetry, trismus, drooping lower jaw etc
Due to neuritis/ encephalitis involving cranial nerve nucleus
Diaphoresis Due to autonomic system excitation Diaphoresis
Due to autonomic system excitation
Excessive salivation Autonomic neuritis, with anterograde flow of the virus it enters the no neural tissues such as the salivary gland, adrenal etc. Excessive salivation
Autonomic neuritis, with anterograde flow of the virus it enters the no neural tissues such as the salivary gland, adrenal etc.
Fear of swallowing/ hydrophobia (laryngeal muscle spasm and inspiratory muscle spasm pathognomonic but can also have spasm of all mucle which can progress to a convulsion or cardio respiratory arrest. Hyper excitability of nerve endings is the key feature seen in furious rabies. stimuli such as water excites the nerve endings of laryngeal muscles and other muscles causing sudden spasm of these muscles. Because of the association with the stimuli they get phobia for swallowing. Fear of swallowing/ hydrophobia (laryngeal muscle spasm and inspiratory muscle spasm pathognomonic but can also have spasm of all mucle which can progress to a convulsion or cardio respiratory arrest.
Hyper excitability of nerve endings is the key feature seen in furious rabies. stimuli such as water excites the nerve endings of laryngeal muscles and other muscles causing sudden spasm of these muscles. Because of the association with the stimuli they get phobia for swallowing.
Aerophobia Hydrophobia can progress to occur for subtle stimuli leading to aerophobia. They progress to death within days to weeks. Aerophobia
Hydrophobia can progress to occur for subtle stimuli leading to aerophobia. They progress to death within days to weeks.
flaccid paralysis usually starting from the bitten limb and ascends This is the other type of presentation - paralytic/dumb rabies. 20 -30% present this way . Due to prominent myelitis.
Usually seen after bat bites or following post exposure prophylaxis.
flaccid paralysis usually starting from the bitten limb and ascends
This is the other type of presentation - paralytic/dumb rabies. 20 -30% present this way . Due to prominent myelitis.
Usually seen after bat bites or following post exposure prophylaxis.
Sphincter disturbance Flaccid paralysis progress to involve the sphincter muscles Sphincter disturbance
Flaccid paralysis progress to involve the sphincter muscles
Difficulty breathing and swallowing Flaccid paralysis progress to involve respiratory muscles and deglutition muscles. Death follows Difficulty breathing and swallowing
Flaccid paralysis progress to involve respiratory muscles and deglutition muscles. Death follows
Cardiac arrhythmias, hypotension. Most likely due to the neuritis of the autonomic nerves which gets involved in anterograde transmission of the virus after multiplying in the CNS Cardiac arrhythmias, hypotension.
Most likely due to the neuritis of the autonomic nerves which gets involved in anterograde transmission of the virus after multiplying in the CNS
Death Established disease is invariably fatal. Only few (4) case reports of survival. But they were left with neurological deficits Death
Established disease is invariably fatal. Only few (4) case reports of survival. But they were left with neurological deficits

Clinicals - Examination

Fact Explanation
Hyperaesthesia of the site wound Stimulation of the sensory ganglia of the bite site. Hyperaesthesia of the site wound
Stimulation of the sensory ganglia of the bite site.
Hyperthermia Initial inflammation Hyperthermia
Initial inflammation
Upper motor neuron lesions(spasticity, hyper reflexia, reduced muscle power) Occurs due to encephalitis, there is hyper excitability of the nerves causing spasms. In between the spasms tone remains normal. Upper motor neuron lesions(spasticity, hyper reflexia, reduced muscle power)
Occurs due to encephalitis, there is hyper excitability of the nerves causing spasms. In between the spasms tone remains normal.
Fluctuating Blood pressure Due to encephalitis and autonomic neuritis. Fluctuating Blood pressure
Due to encephalitis and autonomic neuritis.
flaccid paralysis (fasciculation, flaccid tone, absent reflexes, reduced muscle power) Seen in paralytic/dumb rabies. flaccid paralysis (fasciculation, flaccid tone, absent reflexes, reduced muscle power)
Seen in paralytic/dumb rabies.
Cranial nerve lesions Due to neuritis/ encephalitis involving cranial nerve nucleus. Cranial nerve lesions
Due to neuritis/ encephalitis involving cranial nerve nucleus.

Investigations - Diagnosis

Fact Explanation
WBC/DC- Peripheral neutrophil leukocytosis It is seen in early stage of the disease. But non specific. WBC/DC- Peripheral neutrophil leukocytosis
It is seen in early stage of the disease. But non specific.
Brain biopsy from the offending animal Antigen detection by direct immunofluorescence or RNA by polymerase chain reaction(PCR).
histopathology findings of the biopsy will show Negri bodies which are cytoplasmic inclusion bodies seen in infected nerve cells, Babes nodules consisting of glial cells and features of inflammation such as mononuclear infiltration, polymorph nuclear cells and lymphocytes surrounding perivascular space.
Brain biopsy from the offending animal
Antigen detection by direct immunofluorescence or RNA by polymerase chain reaction(PCR).
histopathology findings of the biopsy will show Negri bodies which are cytoplasmic inclusion bodies seen in infected nerve cells, Babes nodules consisting of glial cells and features of inflammation such as mononuclear infiltration, polymorph nuclear cells and lymphocytes surrounding perivascular space.
Neck skin biopsy from patient - antigen detection by direct immunofluorescence or RNA by RT-PCR More sensitive than corneal biopsy. skin biopsy immunofluorescence sensitivity 0.86 Neck skin biopsy from patient - antigen detection by direct immunofluorescence or RNA by RT-PCR
More sensitive than corneal biopsy. skin biopsy immunofluorescence sensitivity 0.86
Corneal scrapings Antigen/ RNA detection Corneal scrapings
Antigen/ RNA detection
Antibody detection in Serum/ CSF Not evident until late (usually seen after 8 days from the onset of symptoms - patient might die before that) Antibody detection in Serum/ CSF
Not evident until late (usually seen after 8 days from the onset of symptoms - patient might die before that)
Salivary RT-PCR Sensitivity is less than skin biopsy (0.30) Salivary RT-PCR
Sensitivity is less than skin biopsy (0.30)

Management - Supportive

Fact Explanation
Supportive care This is the mainstay of management after established disease. Usually patients will require ICU care. The WHO recommends that medical and nursing staff must wear mask, gloves, and goggles.Since it is theoretically possible for human-to-human transmission to occur. Supportive care
This is the mainstay of management after established disease. Usually patients will require ICU care. The WHO recommends that medical and nursing staff must wear mask, gloves, and goggles.Since it is theoretically possible for human-to-human transmission to occur.
Sedation To control pain and spasms. Ketamine is appropriate for this purpose.( see specific management for details) Sedation
To control pain and spasms. Ketamine is appropriate for this purpose.( see specific management for details)
ventilation Needed when the respiratory muscles are paralyzed. ventilation
Needed when the respiratory muscles are paralyzed.
Nutritional support Spasm of muscles of deglutition and hydrophobia can cause difficulty in swallowing. So they will need nutrition by other means nasogastric feeding/ total parenteral nutrition. Nutritional support
Spasm of muscles of deglutition and hydrophobia can cause difficulty in swallowing. So they will need nutrition by other means nasogastric feeding/ total parenteral nutrition.

Management - Specific

Fact Explanation
Post exposure prophylaxis Post exposure prophylaxis has been shown to be the only effective way to prevent the disease once there is a bite. once disease is established it is almost always fatal. Only few survived the acute illness but mostly with neurological sequelae Post exposure prophylaxis
Post exposure prophylaxis has been shown to be the only effective way to prevent the disease once there is a bite. once disease is established it is almost always fatal. Only few survived the acute illness but mostly with neurological sequelae
Cleaning the wound. Primary closure of a bite wound is controversial. In some experimental animals when proper wound care was given within 3 hours of exposure rabies transmission was prevented .
Though it had been practiced not to close a bite wound primarily due to the risk of infection, a recent study have shown no significant difference in the rate of infection among those who had and not had primary closure
Cleaning the wound. Primary closure of a bite wound is controversial.
In some experimental animals when proper wound care was given within 3 hours of exposure rabies transmission was prevented .
Though it had been practiced not to close a bite wound primarily due to the risk of infection, a recent study have shown no significant difference in the rate of infection among those who had and not had primary closure
Risk assessment of the exposure depends on- circumstance of the bite (provoked or unprovoked), biting animals behavior, type of contact, extent of contact. Risk determines the treatment which varies according to the countries/ institution's protocol. Risk assessment of the exposure
depends on- circumstance of the bite (provoked or unprovoked), biting animals behavior, type of contact, extent of contact. Risk determines the treatment which varies according to the countries/ institution's protocol.
Anti rabies vaccination 2 types of vaccines are available. Purified chick embryo cell vaccine and Vero cell tissue culture vaccine. Can be given via 2 routes, either intramuscular or intradermal. Intradermal in multiple sites is better than intramuscular because intramuscular takes at least one week to produce the immune response .
Survival from rabies encephalitis in animal is associated with immune response. So its also given in combination therapy after established disease
Anti rabies vaccination
2 types of vaccines are available. Purified chick embryo cell vaccine and Vero cell tissue culture vaccine. Can be given via 2 routes, either intramuscular or intradermal. Intradermal in multiple sites is better than intramuscular because intramuscular takes at least one week to produce the immune response .
Survival from rabies encephalitis in animal is associated with immune response. So its also given in combination therapy after established disease
Human rabies immunoglobulin (HRIG) HRIG neutralizes the virus by binding to it before it enters into the nervous system. since the immunoglobulins doesn't enter through the blood brain barrier it has little impact when it is given once the disease is established.
Most of the dose should be infiltrated in to the wound and the rest given intradermally.
Human rabies immunoglobulin (HRIG)
HRIG neutralizes the virus by binding to it before it enters into the nervous system. since the immunoglobulins doesn't enter through the blood brain barrier it has little impact when it is given once the disease is established.
Most of the dose should be infiltrated in to the wound and the rest given intradermally.
In established disease combination therapy is used - Anti rabies vaccine, HRIG, ribavirin, IFN-alpha, Ketamine Combination of multiple specific therapies is better than single therapy. In established disease combination therapy is used - Anti rabies vaccine, HRIG, ribavirin, IFN-alpha, Ketamine
Combination of multiple specific therapies is better than single therapy.
Ribavirin It has anti viral and immune modulatory effects. Though anti viral activity is shown in vitro it has not proven in vivo in animal models. Ribavirin
It has anti viral and immune modulatory effects. Though anti viral activity is shown in vitro it has not proven in vivo in animal models.
Interferon alpha Immune regulatory protein. generates an intra cellular environment which is not suitable for viral replication. High dose treatment IV and intrathecally at the early stage of disease showed no benefit Interferon alpha
Immune regulatory protein. generates an intra cellular environment which is not suitable for viral replication. High dose treatment IV and intrathecally at the early stage of disease showed no benefit
Ketamine It is a noncompetitive antagonist of the N-methyl-aspartate (NMDA) receptor. It ha sedative and analgesic properties. . It is considered a therapeutic agent as well because in rats it has shown to reduce infection in multiple brain regions.. Ketamine
It is a noncompetitive antagonist of the N-methyl-aspartate (NMDA) receptor. It ha sedative and analgesic properties. . It is considered a therapeutic agent as well because in rats it has shown to reduce infection in multiple brain regions..
Corticosteroids Not considered an option to reduce edema in encephalitis because has proven to increase mortality in mouse models. Corticosteroids
Not considered an option to reduce edema in encephalitis because has proven to increase mortality in mouse models.
Prevention - pre exposure anti rabies vaccination It does not give full protection against rabies but since the immunity is developed it gives the patient time to seek medical care. It is given to those at risk due to their occupation (veterinarians, rabies laboratory staff) and to those who travel to rabies endemic areas for long periods. Prevention - pre exposure anti rabies vaccination
It does not give full protection against rabies but since the immunity is developed it gives the patient time to seek medical care. It is given to those at risk due to their occupation (veterinarians, rabies laboratory staff) and to those who travel to rabies endemic areas for long periods.

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