Rabies

Family: Rhabdoviridae Genus : Lyssavirus

Bullet shaped virion 75X 180 nmEnvelop contains 10-nm spike-like  gp G (=400 spike)Protein matrixHelical nucleocapsidNonsegmented ssRNA of –ve sense

•Rabies is a viral infection of the central and peripheral NS ,that causes encephalitis with or without paralysis.

•Zoonosis

The rabies virus genome is RNA of approximately 12 kb. There is a leader-sequence (LDR) of approximately 50 nucleotides, followed by N, P, M, G, and L genes.

The viruses are not viable outside of hosts and are inactivated by sunlight, heat, and desiccation. Within the host, the rabies viruses are highly neurotropichighly neurotropic and replicate slowly within muscle cellsmuscle cells

Transmission Transmission

•ZoonosisZoonosis•Dogs, followed by cats and other wild animals Dogs, followed by cats and other wild animals e.g. foxese.g. foxes• Bats always considered rabid.Bats always considered rabid.

Mode of transmission:Mode of transmission:1.1.Inoculation of infected saliva through a rabid Inoculation of infected saliva through a rabid animal biteanimal bite2.2.Licking of animal on non intact skinLicking of animal on non intact skin3.3.Transplantation : rare Transplantation : rare

No gross abnormalities

Perivascular cuffing & cell degradation.

Negri’s bodies : pathognomic , eosinophilic intracytoplasmic inclusions (viral nucleocapsid aggregates)

Pathology

4 clinical stages:Incubation period:Incubation period:

Asymptomatic.Asymptomatic.1 – 3 m. (5 days -7 years; In rare cases, 1 – 3 m. (5 days -7 years; In rare cases, human rabies with an extended IP (2-7 y) human rabies with an extended IP (2-7 y) has been reported).has been reported).Duration depends on:Duration depends on:

Size of saliva inoculationSize of saliva inoculationSize and depth of bite Size and depth of bite Proximity of the brain. (age)Proximity of the brain. (age)

Prodromal period:Prodromal period:Nonspecific symptoms.Nonspecific symptoms.Pathognomic spesific symptomsPathognomic spesific symptoms

Neurologic stage :Encephalitis or meningo-encephalitisTwo forms:Furious form (encephalitic):

Hyperexcitability, Hyperactivity, and convulsions.Hallucinations Excessive salivationHydrophobia(abnormal contraction of diaphragm, respiratory, laryngeal, pharyngeal)Aerophobia sometimes.

Dumb form (paralytic):Dumb form (paralytic):Generalized flaccid paralysis

Combined form

Coma, Coma, and is associated with MOF regardless and is associated with MOF regardless of the form of presentation. of the form of presentation. HematemesisHematemesis occurs in approximately 30– occurs in approximately 30–60% of patients during the last few hours of life.60% of patients during the last few hours of life.Cardiac arrhythmias Cardiac arrhythmias occur in almost all occur in almost all cases, with the cause of death related to cardiac cases, with the cause of death related to cardiac and circulatory insufficiency.and circulatory insufficiency.It takes 4-16 days from the beginnig of the It takes 4-16 days from the beginnig of the illness up to death.illness up to death.Very few cases are reported to recover(Very few cases are reported to recover(~3~3))

Postexposure prohylaxis:1.Wound care:

• Wash with water, soap. Don’t scrub . Or

• detergent (70% alcohol or ticture of aq. iodine).

• Don’t suture unless excessive.2. Anti-tetanus

3. Prophylactic antibiotics if indicated4. Immunoprophylaxis: both active & passive.

Management:

•Passive immunization:•RIG, 20 IU/ml•Around the wound + I.M

•Active immunization:•The following are safe and immunogenic:

1.Human cell diploid vaccine (HCDV) IM , on 0, 3,7,14,21, ±28 day2.Rabies vaccine adsorbed (RVA)3.Purified Chick embryo cell vaccine (PCEC)4.Vero cell vaccine

•Neural tissue vaccines are used in some developing countries: Neural tissue vaccines are used in some developing countries: A.A.simple vaccine: brain tissue vaccine, (infected brain simple vaccine: brain tissue vaccine, (infected brain

++ββ propol) . 2cc IM for 10 days. propol) . 2cc IM for 10 days. in the past : 5 ml around umblicus( SE: allergic in the past : 5 ml around umblicus( SE: allergic

encephalomyelitis 1:2000- 4000)encephalomyelitis 1:2000- 4000)B. Suckling mice brain tissue.B. Suckling mice brain tissue.

Pre-exposure prophylaxis:

•For persons at risk: vet, lab workers, health officers•Travellers to endemic area.•3 doses•Vaccination is effective for 2 years.

Antemortem diagnosis:Ag detection:•Could be detected early•Skin biopsy: nape of the neck•Corneal impression: IF or ELISA

Virus isolation:• saliva or CSF•Cell culture or IT inoculation of mice.•RT-PCR

Ab detection:•Appears after 8 days•In serum : diagnostic in un vaccinated pts•In CSF is diagnostic ALWAYS. They appear after serum.

Postmortem diagnosis:Brain biopsy:Sections from hippocampus, cerebellum…..Histopathology /IHC

Histopathologic evidence of rabies encephalomyelitis includes the following:•Mononuclear infiltration•Perivascular cuffing•Lymphocytic foci•Babes nodules consisting of glial cells•Negri bodies

Perivascular cuffing

Babes Nodules

Negri

Enlargement of a Negri body in Sellers stained brain tissue. Note the basophilic (dark blue granules in the inclusion).

Rabies-infected neuronal cell with intracytoplasmic inclusions. The red stain indicates areas of rabies viral antigen by using IHC.

Rabies/Differential Diagnosis

Meningitis/Encephalitis: Japanese, eastern equine, West Nile V., enterovirus 71,

Epilepsy Drug toxicity Acute hepatic porphyria,

neuropsychiatric disturbances Substance abuse, acute serotonin

syndrome Pseudohydrophobia (hysterical

reaction to animal bites)