Rabies Virus

•        RABIES VIRUS

•        INTRODUCTION

•        Family:Rhabdoviridae

•        Two genera:

    1.Vesiculovirus

    2.Lyssavirus –Rabies virus

•        The name lyssavirus-derived from lyssa,meaning rage,a synonym for rabies.

•        MORPHOLOGY

•        Bullet shaped

•        Size:180-75nm,with one end rounded or conical and other planer or concave

•        Enveloped (Lipoprotein) with  spikes made of Glycoprotein G which contributes to pathogenesis, virulence and immunity.

•        Spikes do not cover planner end of virion

•        Envelope mediates binding of acetyl choline receptors in neural tissues

•        Used in the production of subunit vaccine

•        Beneath the envelope,the protein membrane layer which may be invaginate d at planner end.

•        The membrane may project outwards from planner end of some virions forms a bleb.

•        Helical symmetry of capsid

•        single stranded RNA

•        RNA dependent RNA transcriptase and proteins.

CLINICAL DISEASE

•        Causes rabies

•        Rabies= Rhabidus (Latin) = Mad

•        Rabies= Rabhas (Sanskrit)= Frenzy

•        Incubation period 1-3months (as short as 7 days, and as long as 3 years)

•        In dogs incubation period is usually 3-6wks ( may range from 10 days to a year)

•        ROUTE OF TRANSMISSION

•        Rabid dog or other animals bite human.

•        Rarely through transplantation of cornea contain virus, licks, aerosols

•        PATHOGENESIS

 

•        Virus present in the saliva of the animal is deposited in the wound.

•        Wound if left untreated can give rise to rabies.

•        Virus multiply in the muscles, connective tissue or nerves at the site of deposition for 48-72 hours.

•        Penetrates nerve endings and travel (3mm/hour) towards spinal cord and brain.

•        Infection spreads centripetally from axon to neuronal bodies and via synapse to the spinal cord and up.

•        Virus ascend to brain, multiplies and travels centrifugally to various parts of the body including salivary glands, facial skin, cornea.

•        Virus is shed in saliva. It may also be shed in milk and urine.

•        COURSE OF DISEASE

•        Prodrome

–     Fever, headache, malaise, anxiety, agitation, irritability, nervousness, insomnia, depression

–     Lasts 2-4 days

•        Acute neurological phase

–     Intermittent hyperactivity, bizzare behaviour, agitation, appearing between normal periods

–     Difficulty in drinking(hydrophobia)

•        Coma

•        Death

–     With in 1-6 days due to respiratory arrest during convulsions

•        LABORATORY DIAGNOSIS

•        SPECIMENS:

–     Corneal smears, skin biopsy (from face or neck), saliva antemortem, and brain postmortem.

•        Direct Immunofluorescence test

–     Using antirabies serum (monoclonal antibody) tagged with fluorescein isothiocyanate.

•        Demonstration of Negri bodies in the brain (post mortem)

–     (absent in about 20% cases)

•        Negri bodies(intracytoplasmic inclusion bodies)

•        ISOLATION:

–     Intracerebral inoculation in mice .

–     Isolation in tissue culture cell lines,

•        Detection of antibodies

–     High titres of antibodies are present after infection but not after immunization.

•        Detection of rabies virus RNA by  PCR

•        PROPHYLAXIS

•        Pre-exposure prophylaxis

•        Post-exposure prophylaxis

•        Pre-exposure prophylaxis

•        Specific prophylaxis is ideally given before exposure to infection

•        Preexposure immunization is given to persons at high risk e.g.veterinarians,dog handlers.

•        Post-exposure prophylaxis

•        Local treatment:

-Wash the wounds immediately with soap

  and water

-Treat the wound with tincture or alcohol

-In severe wounds,antirabic serum may be

 applied topically and infiltrated around the

 wound

-Do not suture the wound.

-Antitetanus measures & antibiotics to

 prevent sepsis(necessary)

•        Antirabic vaccines:

1.Neural vaccines:

•        Semple vaccine

•        Beta propiolactone

•        Infant brain vaccines

2.Non neural vaccines:

•         Egg vaccines:

-Duck egg vaccine

•        Tissue culture vaccines:

-Human diploid cell(HDC) vaccine:

       -first cell culture vaccine

       -Highly antigenic

       -free from side effects

•        Others are:

1.Primary cell culture vaccines:

-Purified chick embryo cell(PCEC)rabies vaccine

-Hamster kidney cell rabies vaccine(HKCV)

-Dog kidney cell rabies vaccine(DKCV)

2.Continuous cell culture vaccine:

-Purified Vero cell(PVC)rabies vaccine

3.Subunit vaccine

•        Vaccination schedules

•        Pre-exposure prophylaxis:

-Requires three doses of vaccine injected on day 0,7,21.

-A booster dose is recommended after one year and then one  every five yrs.

•        Post-exposure prophylaxis;

-Requires five doses on day 0,3,7,14,30.

-This course is expected to give protection for at least five yrs.

-If any further exposure during this period,may need  one or two booster doses(on days 0,3)depends on degree of risk.

-It is advisable to give full doses after five yrs,if exposed to infection.

•        Guide for postexposure prophylaxis

•        POSSIBLE QUESTIONS

1.Write the morphology of rabies virus with

   the help of a diagram

2.Explain the pathogenesis of rabies virus

3.Explain the pre-exposure and post-

   exposure prophylaxis of rabies

4.Discuss the laboratory diagnosis of rabies.

5.Write short notes on:

       a.Rabies virus

       b.Rabies vaccine