Rabies
Dr. Abhishek Jaiswal
Scientist-B
Dept. of Microbiology
Midnapore Medical College
Rabies Distribution
Disease Transmission
´Almost always a bite
´Virus cannot enter intact skin
´Virus can cross mucus membranes
´Less efficient
´Breaks in skin are a risk only if wet saliva gets
in wound
Characteristics(I)
Characteristics(II)
´ Rabies virus belongs to Rhabdoviridae family, which has a unique
morphology.
´ Bullet-shaped
´ Enveloped: They have a lipid envelope in which 10 nm long peplomers or
spikes (glycoprotein-G) are embedded.
´ Nucleocapsid has a helical symmetry and comprises a single-stranded,
negative-sense RNA, nucleoprotein and polymerase proteins.
´ Antigens: Glycoprotein-G and nucleocapsid are the major antigens of
rabies.
´ Incubation period is prolonged and variable, average being 20–90 days
(ranges from 1 week to 19 years).
Pathogenesis(I)
´ Bite: Following a deep bite or scratch from an infected animal with rabies .
´ Rabid dogs account for 99% of cases
´ Bats are now the major source in America
´ Other animal bites such as foxes, raccoons, skunks, jackals, mongooses and
other wild carnivore host.
´ Non-bite exposures: Direct contact with saliva of infected animals with mucosa or
fresh skin wounds
´ Inhalation of virus-containing aerosols (important for laboratory workers)
´ Cornea or other organ transplantation.
´ Virus enters NM junctions
´ Travels via peripheral nerves to spinal cord
´ Then to brain stem and forebrain
Pathogenesis(II)
Clinical Manifestations
1. Prodromal Phase It lasts for 2–10 days, characterized by non-specific symptoms
such as fever, malaise, anorexia, nausea, vomiting, photophobia, sore throat,
abnormal sensation around the wound site.
2. Acute Neurologic Phase This may be either encephalitic type (80%).
3. Paralytic or dumb rabies:
Paralytic type (20%), characterized by flaccid paralysis, often begins in the bitten limb
and progressing to quadriparesis with facial paralysis.
4. Coma and Death Following acute neurological phase, patient develops coma that
eventually leads to death within 14 days. Patients with paralytic rabies may survive
longer up to 30 days. However, death is almost certain. Recovery and survival are
extremely rare.
Disease in Animals
´ Two major clinical types in dogs and cats
´ Furious
´ Restless, irritable, disoriented, seizures
´ More common in cats
´ Paralytic
´ Extremity paralysis, altered bark, salivating
´ More common in dogs
The Disease in Man
´ Initial clinical symptoms include anxiety, headache,
mild fever, irritation at bite site
´ Progresses to muscle spasms, difficulty swallowing,
hydrophobia
´ Clinical course is typically short
Laboratory Diagnosis
´ Rabies Antigen Detection Direct immunofluorescence test (direct-IF); also called as direct fluorescent
antibody (DFA) test can be performed to detect rabies nucleoprotein antigens in specimens by using
specific monoclonal antibodies tagged with fluorescent dye. Because of its high sensitivity and specificity,
DFA test is considered as the “gold standard” method for rabies diagnosis.
´ The best specimen is hair follicle of the nape of the neck (most sensitive)
Viral Isolation
Mouse inoculation: Intracerebral inoculation into suckling mice can cause encephalitis and death. The brain
biopsies of the inoculated animal are examined for the presence of Negri bodies and rabies antigen
Cell lines: Mouse neuroblastoma cell lines and baby hamster kidney (BHK) cell lines are the preferred cell lines
for rabies virus isolation.
Antibody Detection Detection of CSF antibodies is more significant than serum antibodies.
Serum antibodies appear late and can also be present after vaccination
CSF antibodies appear early and they are produced only in rabies-infected individuals but not in response to
vaccination.
Viral RNA Detection Reverse transcription-polymerase chain reaction (RT-PCR)
Negri Body Detection It is useful to confirm postmortem diagnosis of rabies. It is an intracytoplasmic
eosinophilic inclusion with characteristic basophilic inner granules, composed of rabies virus proteins and viral
RNA Location: Negri bodies are commonly observed in Purkinje cells of the cerebellum and in pyramidal
neurons of the hippocampus, and are less frequently seen in cortical and brainstem neurons
Principles of DFA
Fluorochrome-labeled Rabies Virus Labeled Antibody-
Antibody to Rabies Virus infected Cell Rabies Virus
DFA Results
< Positive Brain
Negative Brain >
Prognosis
Mortality in rabies is almost 100%; however, it is preventable by
administration of post-exposure therapy during the early
incubation period. There are seven well-documented cases
who survived from rabies—mostly because of taking rabies
vaccine in the early incubation period.
Prevention of Human Rabies (WHO Guideline 2018) Rabies is
prevented by providing prophylactic measures such as post-
exposure prophylaxis (PEP) and pre-exposure prophylaxis
(PrEP).
Post-exposure Prophylaxis (PEP) (For Individuals Not
Received PEP/PrEP Previously)
PEP consists of three components—local wound care, rabies vaccine and rabies
immunoglobulin (RIG).
For category I exposures: Require only wound care. Vaccine or RIG are not required
For category II exposures: Require local wound care and rabies vaccine. RIG is not
required except for immunodeficient individuals who need RIG in addition
For category III exposures: All three components of PEP are required such as local
wound care, rabies vaccine and RIG.
Local Wound Care It consists of the following measures. Physical cleansing: All bite
wounds and scratches should be washed thoroughly with soap and water for 15
minutes Chemical inactivation: Antiseptics such as povidone iodine or alcohol
can be used to inactivate the residual viruses Suturing: Suturing causes local
tissue damage, which may help in spreading of the virus. Therefore, suturing should
be avoided.
Deeper wounds that definitely require suturing should be sutured loosely and only
after RIG is infiltrated into the wound Other general measures include: (i)
debridement of devitalized tissues, (ii) tetanus prophylaxis, (iii) antibiotic treatment
to prevent secondary bacterial infection Do not touch the wound(s) with bare
hand
Public Health Response
Rabies Vaccine
Type of vaccines: Cell line derived non-neural vaccines are recommended.
Three vaccines are available
1. Purified chick embryo cell (PCEC) vaccine: It is prepared from chicken fibroblast
cell line
2. Purified Vero cell (PVC) vaccine: It is prepared from Vero cell line
3. Human diploid cell (HDC) vaccine: It is derived from WI-38 (human embryonic
lung fibroblast cell line).
The neural vaccines derived from brain of infected animals such as Semple
vaccine (sheep brain), betapropriolactone (BPL) vaccine and infant mouse brain
vaccines are encephalitogenic and therefore no longer in use. Similarly, the
egg-derived non-neural vaccines (e.g. purified duck embryo vaccine) and
recombinant non-neural vaccines (containing surface glycoproteins) are also
not in use for humans
Public Health Response
´ Human exposed to dog, cat or ferret
´ Observe animal for 10 days
´ Test if illness or death w/in observation period
´ Should be discussed with health director
´ IS NOT DEPENDENT ON VACCINATION STATUS
Public Health Response
´ Expired vaccination
´ Euthanize or 6 month isolation
´ Vaccinate immediately and one month prior to release
´ Depending on the circumstances, some of these animals
can be considered as currently vaccinated
Public Health Response
´ Livestock exposed
´ Vaccinated
´ Boost and 3 months observation
´ Unvaccinated
´ Immediate slaughter or
´ 6 months observation
Public Health Response
´ Wildlife exposures
´ No observation time
´ High risk species
´ Low risk species
´ Test when possible or situation warrants
Public Health Response
´ Control/Education
´ Vaccinate dogs and cats
´ Wildlife vaccination initiatives
´ Animal control
´ Avoid direct contact with wildlife
´ Pre-exp. vaccination for high risk professions
Public Health Response
´ Control/Education
´ Prompt attention to bites
´ Good communication with all parties involved in follow
up
´ Prompt PEP when necessary
Questions?