Rabies

Etiology -

 Lyssavirus type 1 , Rhabdoviridae family , Mononegavirales order , Nonsegmented , Negative stranded Bullet shaped neurotropic RNA virus .

 (Refer image) 170nm long , 80nm wide , encodes 5 protiens Nucleoprotein (N) , Phosphoprotein (P) , Matrix protein (M) , Glycoprotein (G) , Polymerase (L). Has 2 Major components :- RNP(Ribonucleoprotein) core and surrounding Envelope. 2 viral proteins are associated with RNP [Phosphoprotein , Large protein(L-protein)] .  Matrix protein(M-protein) is Central protein of rhabdovirus assembly

Mode of transmission  - 

Infected Animal bites (small rodents like Rats , squirrels , Mice , guineapigs , Lagomorphs like Rabbits are almost never infected with rabies)

Aerosols (Rabies infected bats) 

Licks (abraded skin ; abraded/non abraded mucosa)

Person to person rare but possible

Corneal and organ transplantation 

Rabies is a dead end infection in man

Hydrophobia and aerophobia , Negri bodies (Intracytoplasmic eosinophilic inclusion bodies with basophilic granules in neurons) - Pathognomonic of Rabies

Pathogenesis - 

Virus enters nerve endings following bite  followed by centripetal retrograde axonal transport to brain leading to CNS infection followed by Transsynaptic spread , Viral replication , Negri body formation , Dysfunctional but intact neurons . Now clinical signs of encephalomyelitis begin , our body immune response is initiated leading to centrifugal neuronal transport to salivary glands (Viral excretion) . Virus carried to skin , heart , muscle , tongue but No Viraemia

Clinical course -

Stage 1 - Incubation period - Days to years (usually 20-90 days)

Stage 2 - Prodromal phase - non specific symptoms (Flu like illness , GI symptoms , Myalgia , Fever) ; Pain , Paresthesia , Pruritus at bite site

Stage 3 -Acute neurological illness Phase - 

• Encephalitic (furious) form of rabies (Most common) - Hydrophobia and aerophobia , Involuntary painful pharyngeal muscle spasms to stimuli like drinking water , Agitation , Autonomic dysfunction , increased deep tendon reflexes , Neck stiffness , Babinski sign +ve , Confusion , Tachypnea , Tachycardia , Fever , Hallucination , Photophobia 

• Paralytic form of rabies (less common) - Weakness is hallmark feature . Flaccid paralysis , Paraplegia , Loss of sphincter tone (Bladder dysfunction) , Respiratory failure due to Respiratory muscle paralysis and Death

• Non-classic (rare) - Seizures , Profound motor and sensory symptoms

Stage 4 - Coma stage (Begins within 10 days of stage 3) - Flaccid paralysis , Apnea

Stage 5 - Death

Diagnosis - 

Specimens collected - Saliva , Tears , CSF , Serum , Tissue biopsies (Neck , Immunofluorescent stain)

Lab tests - RTPCR , Cell culture , Antibody titer

Postmortem findings - 

Negri bodies (Intracytoplasmic eosinophilic inclusion bodies with basophilic granules in neurons) - Pathognomonic of Rabies

Treatment- 

Flush and wash wound area with plenty of soap and running water minimum 5 to 10 minutes

Debridement

Suturing not recommended  , Do 24-48 hrs later

Tetanus shot , antibiotics can be given 

Anti Rabies serum 

Observe Animal for 10days

Vaccines approved for Intradermal usage in India- 

Purified Chick embryo cell vaccine (PCECV) - Rabipur,  Vaxirab N

Purified Vero cell Rabies vaccine (PVRV) - Verorab,  Abhayrab,  Indirab

Vaccines approved for IM  use - 

Cell culture Vaccines- 

• Human diploid cell vaccine (HDCV) , 1ml IM

• Purified Chick embryo cell vaccine (PCECV) , 1ml IM

• Purified Vero cell Rabies vaccine (PVRV) , 1ml IM

Embryonated egg based vaccine -

•  Purified duck embryo vaccine (PDEV) - Dose 1ml IM

Rabies Categories :-

Category 1 - Touching or feeding animals , licks on intact skin (No Exposure) (No PEP required - Wound washing only for both Previously immunised and  Previously non immunised)

Category 2 - Nibbling of uncovered skin , Minor scratches or abrasions without bleeding (Exposure)

 ( Previously non immunised - Wound washing + PEP  ;

Previously immunised (Including PrEP) - Wound washing + Booster on day 0 & 3 , ID/IM )

Category 3 - Single or Multiple transdermal bites or scratches , Contamination of mucous membrane with saliva from licks , Exposure to Bats (Severe exposure) 

( Previously non immunised - Wound washing + PEP + RIG  ;

Previously immunised (Including PrEP) - Wound washing + Booster on day 0 & 3 , ID/IM )

Post exposure prophylaxis :-

5- dose (ESSEN) Regimen - (1-1-1-1-1) days 0,3,7,14,28 IM (entire vial) single site

Updated Thai Red Cross Regimen (2-2-2-0-2) days 0,3,7,28 ID (0.1ml) two sites

if a vaccine dose is delayed , Resume PEP schedule don't Restart it

Vaccines should never be withheld regardless of availability of RIG

RIG (Rabies immunoglobulin) :- hRIG - 20IU/Kg ; eRIG - 40IU/Kg administered into / around wound site /sites if RIG is still remaining IM at a site distant from site of vaccine administration

Priority of RIG allocation - Multiple bites > Deep wounds > Bites to highly innervated parts of body like  head , neck , hands , Genitals > severe immunodeficiency > confirmed / probable rabies in bitting animal > when Bites , scratches , exposure of mucous membrane caused by bat can be ascertained

Alternative for RIG - Cocktail Monoclonal antibodies with atleast 2 antibiotics against rabies virus

 Rabies free area - no case of Rabies in man or animals for past 2 years (Australia  , Lakshadweep   , Andaman and Nicobar island)

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