World Veterinarian Quiz 36

Rabies

• Rabies is a neurological, invariably fatal, viral disease of mammals characterized by nervous signs, salivation, paralysis , non suppurative encephalitis  and intracytoplasmic inclusion bodies (Negri bodies)  
• Many islands countries are free from rabies like United Kingdom, Ireland, Sweden, Norway, Iceland, Japan, Australia, New Zealand, Singapore, most of Malaysia, Papua New Guinea, the Pacific Islands etc…
• Synonym :
• Hydrophobia ( Animal which fear by water in case of rabies )
• Lyssa ( Due to caused by Lyssa virus )

 Etiology

•       Rabies virus (Genotype 1) – Neurotropic

•       Genus:  Lyssavirus

•       Family: Rhabdoviridae

•       Total 11 distinct species can be distinguished within the genus in lyssavirus

Two biotypes

❶ Fixed virus:                                                                       ❷ Street virus:

•       Laboratory  vaccine virus                                         Produced natural occurring diseases

•       Tropism to CNS                                                        Tropism to CNS and salivary glands

•       Not secreted in saliva                                               Secreted in saliva

•       No Negri bodies                                                         Negri bodies in 70 % cases

•                           Marked neuronal denegation

•       Adapted to CNS by passage               

                     

Host

•       All warm blooded animals /mammals (wild and domestic)

•       Jackals in India are reservoir vectors

•       Bats, foxes, skunks, raccoon, mongoose are reservoir vectors in other part of world 

Transmission

•       Direct contact 

Saliva of infected animals

 

•       Rarely reported other route of transmission of rabies like….

•       Aerosol route of  transmission in laboratories and bat caves

•       Sometimes Organ transplantation like cornea, pancreas, kidneys and liver

•       Also seen Transmission in a human infant and milk to a lamb

•       Ingestion of  infected animals so Not recommended to consume tissues from rabid animals.

(CFSPH,2009)

Pathogenesis

Virus enter in to body via bite of infected animals

•       Initial multiplication in muscles (Which can enter peripheral nerves directly – Short incubation period ) à And enters into peripheral nerves à Ascends (retrograde axonal transport the peripheral nerve (12 to 100 mm/day) à Enter to the dorsal root ganglion à Enters the spinal cord à Ascends to the brain via ascending and descending nerve fiber tractsà reach to Infects brain cellsà Spreads to salivary glands and the eye, replication and is excreted in saliva à

•       Viral envelop G protein  → bind to muscles → virus replication muscles → virus bud out from muscles → bind to acetylcholine receptors at the neuromuscular junction → pinocytosis (it is a process by which liquid droplets are ingested by living cells and it is one type of endocytosis and engulf external substances, gathering them into special membrane-bound vesicles contained within the cell.) → virus in vesicle enter in to nerve and Virus induced neuronal apoptosis and degeneration.

Incubation Period

•       It is depends on

•       Amount of virus transmitted

•       Virus strain

•       Site of inoculation (bites closer to the head have a shorter incubation period)

•       Host immunity

•       Nature of the wound

•       In Dogs and cats - 10 days to 6 months

•       Most cases - 2 weeks and 3 months

•       In Cattle - 25 days to more than 5 months

•       In Humans - few days to several years

•       Most cases become apparent after 1 to 3 months

Clinical Signs

•       Signs in domestic animals are similar with some differences between species

•       Prodromal phases

•       Excitatory phase (furious form)

•       Paralytic phase (dumb form)

        ❶Prodromal phases:

•       Animal can have a subtle change in temperament ( Change the behavior )

•       Restlessness, anorexia or an increased appetite, vomiting, a slight fever.

•       Dilation of the pupils

•       Hyper reactivity to stimuli and excessive salivation

❷Excitatory phase (furious form):

•       Infection of limbic system of brain mainly Hippocampus and other

•       In furious form - Excitatory phase predominant

•       Cattle, Carnivores, Sheep, Pig, Cat seen the furious form

•       Wandering, crying, polypnea, drooling and attacks on animals, people or inanimate objects

•       Often swallow foreign objects such as sticks, stones, straw or feces

•       Cattle with rabies have unique bellowing, general straining, tenesmus( Rectal straining ) and signs of sexual excitement

❸Paralytic phase (Dumb form):

•       It is associated with infection to cerebellum

•       Excitatory phase is extremely short or absent and the disease progresses quickly to the paralytic phase

•       Throat and masseter muscles become paralyzed so unable to swallow

•       Facial paralysis / lower jaw may drop due to paralysis

•       Ascending spinal paralysis (starting from tail)

•       Death usually occurs within 2 to 6 days, as the result of respiratory failure

•       In human seen the Hydrophobia 

Macroscopic Pathology  

•       There are  no gross lesions

•       Cattle and horses may see hemorrhage in the spinal cord

•       Evidence of injury or self-mutilation

•       Presence of unusually material or foreign bodies in stomach/alimentary tract.

Normal Anatomy of Brain

Microscopic Pathology

•       Nonsuppurative encephalomyelitis, with ganglioneuritis and parotid adenitis

•       Perivascular cuffing, Babe’s nodules and Negri bodies are pathognomonic for rabies  

•       Lesions most severe from the pons to the hypothalamus, and the cervical spinal cord; medulla generally not affected

•       Perivascular lymphocytic cuffing; perivascular hemorrhage; leptomeningitis

•       Babe’s (Glial) nodules – composed of Microglial cells

•       Neuronal degeneration and inflammation is most severe in carnivores and mild in pigs and herbivores

•       Negri bodies are round to oval, 2-8 um, eosinophilic intracytoplasmic inclusions

•       Aggregations of strands of viral nucleocapsid; transforms into a granular matrix

•       Negri bodies - hallmark of rabies infection

•       Carnivores – hippocampal neuron

•        Herbivores - Purkinje neuron of cerebellum

•       Negri bodies are rarely found in the ganglion cells of the adrenal medulla, salivary gland and retina.

•       Early infections and up to 30% of rabies infections Negri bodies not found

•       A spongiform lesion with vacuolation of gray matter neuropil, similar to scrapie, was originally described in foxes and skunks with rare reports in the horse, cow, cat and sheep.

•       Parotid adenitis

•       Epithelial cell degeneration

•       Lymphoplasmacytic inflammation

Diagnosis

•       Base on Clinical signs.

•        Laboratory tests like…

•       Fluorescent antibody test (FAT)- recommended by both WHO and OIE -  ‘Gold-standard’ test

•       Immunoperoxidase methods

•       Enzyme-linked immunosorbent assay (ELISA)

•       Mouse inoculation test

•       RT – PCR

Virus neutralisation test in cell culture

How to collect the sample

Brain sampling : 

Treatment

•       There is no treatment of Rabies

•       We prevent the Rabies by Rabies vaccine.

•       Sometime Rabies vaccine is also failure due to not maintain cold chain and faulty vaccination.

•       Post bite rabies schedule is…

1^st vaccine dose 0 day (At time of bite )

2^nd vaccine dose 3 day

3^rd vaccine dose 7 day

4^th vaccine dose 14 day

5^th vaccine dose 28 day and

Some veterinarian given on 90 day also.

But in field condition we given up to 28 day.

Rabies Virus Ag Test

·         Rabies Virus Ag Test is a sandwich lateral flow immunochromatographic assay for the qualitative detection of rabies virus (Rabies Ag) in animal’s saliva or brain tissue.

Time: 5-10 min

Sample for test: Saliva and Brain sample

 

PRINCIPLE: Quicking Rabies Virus Ag Test is based on sandwich lateral flow immunochromatographic assay. The test device has a testing window. The testing window has an invisible T (test) zone and C (control) zone. When sample is applied into the sample hole on the device, the liquid will laterally flow on the surface of the test strip. If there is enough Rabies virus antigen in the sample, a visible T band will appear. The C band should always appear after a sample is applied, indicating a valid result. By this means, the device can accurately indicate the presence of Rabies virus antigen in the sample.

 

PROCEDURE

 

1.       Collect animal’s saliva or 10% brain tissue fluid homogenates with the swab stick.

2.       To collect an animal’s saliva, gently rub the cotton swab inside the mouth, along the gums and cheeks, making sure the swab is sufficiently wet.

3.       Unscrew the cap from the provided assay buffer tube and insert the wet swab.

4.       Agitate it to ensure good sample extraction.

5.       Take out the cassette from the foil pouch and place it horizontally.

6.       Use the pipette to extract solution from the assay tube and transfer 3 drops of sample extraction into the elliptical sample hole on the test cassette.

7.       Interpret the result in 5 - 10 minutes. Result after 10 minutes may be considered invalid.

 

RESULTS

Positive: The presence of both C band and T band, no matter how faint the T band appears.

 

Negative: Only clear C band appears

.

Invalid: No colored band appears in C zone, no matter whether T band appears.

References:

Pathologic Basis of Veterinary Disease Expert Consult

6th edition

By: James Zachary, M. McGavin

 http://www.cdc.gov/rabies/pdf/rabiesdfaspv2.pdf 

https://homehealth-uk.com/