Bullet-shaped RNA viruse

Rhabdoviridae encompasses more than 175 viruses of vertebrates, invertebrates, and plants.

RhabdoviridaeRhabdoviridae

Most famous member is rabies virus. It causes one of the oldest and most feared disease

Medium size 70 nm in diameter and 170 nm long

Enveloped with large peplomers

Helical cylindrical nucleocapsid-giving the virus the

bullet (conical) shape

Non segmented single-stranded negative-sense RNA

Genome is encoding 5 genes.

Rhabdoviridae

Structure and genomic organization of Rhabdovirus (VSV)

[Principles of Virology, 2000-ASM Press, Washington DC]

Four genera

Lyssavirus is the most important genus.

Rabdovirus has different serotypes

Rhabdoviridae ClassificationRhabdoviridae Classification

Each of these viruses is considered capable of causing rabies-like disease in animals and humans

WHAT IS A FIXED VIRUSWHAT IS A FIXED VIRUS

• One whose virulence and incubation period have

been stabilized by serial passage and remained fixed

during further transmission.

• Rabies virus that has undergone serial passage

through rabbits, thus stabilizing its virulence and

incubation period and called as fixed virus

Batvirus - negri bodies brain VSV- ocassional elongated form of virion

Bovine ephemeral fever virus Sawgrass virus –isolated from tick-unassigned

RABIES VIRUS (RV)RABIES VIRUS (RV)

EPIDEMIOLOGYEPIDEMIOLOGY

Rabies can infect all warm-blooded animals, and in nearly all animals, the infection is fatal.

Dogs are the most important source of human rabies infection.

Disease is worldwide, except Japan, United Kingdom, Antarctica, Hawaii and some Caribbean islands.

Bat Rabies in USA

Worldwide, 40,000 to 50,000 people die of rabies/year

approx 10 million receive post-exposure treatment.

Bats in USA and Europe is the source of most human

rabies casesrabies cases. In many cases there is no history of bite.

EpidemiologyEpidemiology

Transmitted by bite or scratch from a rabid animal.

However, in bat caves the infectious virus concentration

may be high resulting in aerosol transmission.

Incubation period: 14 to 90 days (in humans can be more

than 2 years after exposure).

RV PathogenesisRV Pathogenesis

RABIES RABIES AS A CNS DISEASEAS A CNS DISEASE

Development of overt rabies depends on:

(a) Location of the bite – virus must enter the

peripheral nerves to travel to brain

(b) Severity of bite

(c) Species of animal involved (E.g. foxes carry up to

106 infectious particles of rabies virus/ml of saliva)

RV enters peripheral nerves peripheral nerves through sensory and motor sensory and motor

nerve endings nerve endings – primarily through neurotransmitter

acetylcholineacetylcholine as receptor. Also uses gangliosides and

phospholipids.

RV PathogenesisRV Pathogenesis

Sequential event following Rabies Sequential event following Rabies virus infection in a dogvirus infection in a dog

RV PATHOGENESISRV PATHOGENESIS

• Virus enters the brain through the limbic system where it

replicates extensively – affecting the cortical control of

behavior and leading to the furious form of disease.

• As the virus continues to spread within the CNS, it

reaches the neocortex – resulting in change in clinical

disease from fury to dumb or paralytic form.

Virus moves centrifugally from the CNS through the peripheral nerves to:

Adrenal cortex Pancreas Salivary glands

Virus releaseVirus releaseIn CNS, virus is released from cells by budding into intracytoplasmic membrane. However, in the salivary glands, the virus buds at the apical surface of mucous cells resulting in release of large amounts of virus in saliva. By the time when furious form of disease is evident and animals bite indiscriminately, the saliva is highly infectious.

RV PathogenesisRV Pathogenesis

There is a prodromal (warning) phase before clinical

disease that is characterized by change in temperament.

Clinical diseaseClinical disease

NOTE: Higher proportion of dogs, cats, and horses exhibit

the furious form than ruminants and lab animals.

RABIES CLINICAL FORMS: RABIES CLINICAL FORMS: FURIOUS AND DUMB (PARALYTIC)FURIOUS AND DUMB (PARALYTIC)

• Furious form – Animal is restless, nervous, aggressive, and dangerous (fearless). Inability to swallow water (hydrophobia), excessive salivation, exaggerated response to light and sound, hyperesthesia (animals commonly bite or scratch themselves).

• Dumb or paralytic form - As encephalitis progresses, fury gives way to paralysis. Convulsive seizures, depression, coma, and respiratory arrest resulting in death 2 to 14 days after onset of clinical signs.

MAJORITY WILL SUCCUMB TO DISEASEMAJORITY WILL SUCCUMB TO DISEASE

Rabid dog 4 days after

developing clinical signs.

Rough hair coat,

exudates in the eyes,

contracted pupils.

Dog paralysed for 4 hr

and died 8 hr later

Rabid dog - marked mandibular paralysisRabid dog - marked mandibular paralysis

Rabid African ox (furiousform)

Excessive salivation andloss of body condition (top)

Excessive salivationcontinued until death (below)

Developed countries Stray dog and cat removal and control of movement of pets

Immunization of dogs and cats

Routine laboratory diagnosis to obtain accurate incidence

data

Surveillance to assess the effectiveness of all control

measures

Public education to ensure cooperation

Control and preventionControl and prevention

VaccinesInactivated and attenuated RV vaccines are efficacious and safe in animals.

Tell an health care worker immediately

Wash the wound out with soap and water

Inform the doctor right away

IF YOU ARE BITTEN OR SCRATCHEDIF YOU ARE BITTEN OR SCRATCHED

POSTEXPOSURE PROPHYLAXISPOSTEXPOSURE PROPHYLAXIS

Wound cleaning & treatmentWound cleaning & treatment

PREVENTIONPREVENTION

• No effective treatment exists.

• Postexposure Prophylaxis/PEP: 3 steps• 1. Wound care: immediate thorough washing with

soap and water and a virucidal agent such as povidine-iodine or 1-2% benzalkonium chloride.

• Shown to be protective if performed within 3 hours of exposure• If puncture, swab deeply in wound and around edges

PREVENTION PREVENTION

• 2. Passive Immunization: Human rabies immunoglobulin (HRIG) 20 IU/kg ASAP, but not longer than 7 days after vaccine given. Infiltrate entire dose around wound, any remaining IG inject IM at a site distant from the vaccine.

• 3. Human diploid cell vaccine (HDCV): 1 ml (deltoid) on days 0,3,7,14,28. do not give in gluteal. If injected into fat, no antibodies formed.

PREVENTION PREVENTION

(HRIG and HDCV: give in different anatomical sites and never in the same syringe.

If previously vaccinated - no rabies Ig + vaccine at 0, 3 days only)

Dog, cats Healthy and available for observation None -

Rabid or suspected Rabies Ig + vaccine Unknown Consult PH official

Bat Regard as rabid and consider that exposure Rabies Ig + vaccine occurred even if a bite wound is not evident. Unless lab results negative

Skunk, fox, coyote Regard as rabid unless proven Rabies Ig + vaccineBobcat, woodchuck, negativeother carnivores

Livestock, rodents, Case by case-judgment call rabbits, hares

Guides to Human Post-exposure ProphylaxisGuides to Human Post-exposure Prophylaxis

Pre-exposure vaccination

Veterinarians

Lab workers working with RV

wildlife workers in endemic areas

Pre-exposure vaccination regime – 0, 7, 28 days

PREVENTION PREVENTION

كشتن حيوان مشكوك به هاري و ارسال سر حيوان به انستيتو پاستور) بريدن سر حيوان بايد بوسيله

مامورين دامپزشكي يا بهداشت با استفاد هاز وسائل كامل خفاظتي انجام مي گيرد و در يك كيسه نايلوني

ضخيم غير قابل نفوذقرار داده و آن را در يك يخدان پر از يخ قرار مي دهند (.

نمونه برداري از بافت مغز با استفاد ه از كيت هاي مخصوص نمونه برداري.

Lab DiagnosisLab Diagnosis

1. The standard premortem test is a fluorescent antibody test to demonstrate the presence of viral antigen. The standard postmortem test is biopsy of the patient's brain and examination for Negri bodies. Autopsies are rarely performed.

1. Immunofluorescence - Suspected animals must be killed and brain tissues collected for testing. Diagnosed by direct immunofluorescence showing RV antigens in medulla, cerebellum, or hippocampus.- observe Negri bodies in neurons. 2. RT-PCR – test for RV-RNA in brain3. Antemortem diagnosis – only done in suspect human cases. Skin biopsy, corneal impressions, or saliva specimens are used. Only positive results are significant in this method because negative results could be due to the fact that these negative results could be due to the fact that these samples are not optimal.

Lab DiagnosisLab Diagnosis

NEGRI BODIES – A GOLD NEGRI BODIES – A GOLD STANDARD IN DIAGNOSISSTANDARD IN DIAGNOSIS

Inclusion bodies called

Negri bodies are 100%

diagnostic for rabies

infection, but found

only in 20% of cases

NEGRI BODIESNEGRI BODIESIN BRAIN TISSUEIN BRAIN TISSUE

• Negri bodies  round or oval inclusion bodies seen in the cytoplasm and sometimes in the processes of neurons of rabid animals after death. • Negri bodies are

Eosinophilic, sharply outlined, pathognomonic inclusion bodies (2-10 µm in diameter) found in the cytoplasm of certain nerve ..

Light microscopic photograph of multiple intracytoplasmic rabies virus inclusions in a neuron

from the brain of a naturally infected bison

Negri bodies – collection of RV nuclocapsids in neurons