pathogenesis ,diagnosis, treatment, types

1. LUBNA S SUBAIR
1ST SEMESTER
M.Sc.BIOTECHNOLOGY
CUSAT

3.  Importance to know rabies
 Causative agent
 Transmission
 Pathogenesis
 Types of rabies
 Diagnosis
 Management
 Prevention

4.  Acute fatal disease that causes fatal
encephalomyelitis in all the warm blooded
animals including man.
 It is a zoonotic disease.
 The disease is invariabble fatal and is the
most painful and dreadful of all
communicable diseases in which the sick
person is tormented at the same time with
thirst and fear of water(hydrophobia)
 Till date there is no accurate cure ,once
developed the death is inevitable.

5.  However the development of the disese can
be prevented to a large extent when the
animal bites are treated in time and
appropriately.

7.  Mainly in rural areas and in children
 India: 20,000 deaths per year
 India accounts for 36% of the global human
rabies death.
 Execpt Lakshadeep and Andaman and nicobar
all states have reported rabies.

8.  Family- Rhabdoviridae
 Genus -Lyssavirus
 Serotype 1
 Shape-Bulletshaped
 Neurotropic
 Single stranded RNA
 Non segmented structure
 Consists of 11,932 nucleotides and encodes 5
proteins.

9. All the rhabdovirus has 2 structural
components
Ribonucleoproteincore RNP
Surrounding envelope
The rabies genome encodes 5 proteins
 Nucleoprotein, N
 Phosphoprotein, P
 Matrix protein,M
 Glycoprotein ,G
 Polymerase ,L

10.  The virus is found in wild animals and some
domestic animals
 Through their saliva-bites,scratches,licks on
wounded skin, mucous membrane.
 In India dogs are responsible for about 97% of
human rabies followed by 2%cats,jackals,and
others 1%
 Rabies is mainly caused by the bite of a rabid
dog.

12.  Street virus
 Fixed virus

13.  Naturally found in saliva of infected animals
 Incubation period is long- 20 to 90 days
 Cannot be used for vaccine preparation
 Produce negri bodies

14.  An important pathological CNS finding of
rabies.
 An eosinophilic cytoplasmic inclusion
 Composed of
- rabies virus proteins
- viral RNA
- Purkinje cells of cerebellum
- Pyramidal neuron of hippocampus

16.  Prepared by repeated culture in rabbit brain
such that its IP is reduced and fixed
 Do not produce negri bodies
 Incubation period is short- 4 to 6 days
 Can be used for vaccine preparation.

18.  Period before the virus enter the PNS-
incubation period
 Usually 20-90 days
 During this period, the rabies virus is present
at or close to the site of bite.

19.  The virus now bind to post synaptic nicotinic
acetylcholine receptors (AChR-N)
 Then it spreads along the PNS towards the
CNS .

20.  Inflammation in the CNS region occurs
 Symptoms-
fever,confusion,hallucinations,combativeness
,seizures
 Autonomic dysfunction- hypersalivation,
gooseflesh,cardiac arrhythmia.

22. - virus attack the emotional control centre of
brain.

23.  Swallowing of food or exposure to air-results
in involuntary,painful contraction of
diaphragm and respiratory muscles

24.  Due to autonomic dysfunction
 Produce characteristic foaming at the mouth

25. 1. Encephalitic/Furious rabies - 80%
2. Paralytic rabies - 20%

26.  Muscle weakness or flaccid paralysis
predominates
 Early and prominent muscle weakness in
bitten area & spreading ,resulting in
quadriparesis and facial weakness.
 Spinchter involvment and sensory
disturbances
 Lacks cardial features like
hyperphobia,aerophobia,hyperexcitability
etc.

27. One or more of the following
1. Detection of rabies viral antigens by direct
fluorescent antibody test (FAT) or by ELISA
,preferably brain tissue (collected post mortem).
2. Detection by FAT on skin biopsy (ante mortem)
FAT positive after inoculation of brain tissue, saliva or
CSF in cell culture, or after intracerebral inoculation
in mice or in suckling mice.
3. Detectable rabies-neutralizing antibody titre in the
serum or the CSF of an unvaccinated person.
4. Detection of viral nucleic acids by PCR on tissue
collected (brain tissue or skin, cornea, urine or
saliva).

28.  Broadly classified as
-antemortem tests
-postmortem tests

30.  Ante-mortem specimens for rabies testing include saliva,
nuchal skin biopsy and cerebrospinal fluid (CSF).
Saliva specimens
Collect at least 500μl of saliva into a universal specimen
container – often easiest using a syringe or suction device
It is recommended to collect a saliva specimen as soon
as rabies is considered as part of the differential diagnosis
of a patient.
CSF specimens
Collect at least 500μl of CSF.
CSF is typically collected in untreated sterile plastic tubes

31. Nuchal skin biopsy
-Section of skin, 5-6 mm in diameter and ≈5-
7 mm depth, must be taken from the nape of
the neck .
- It is important that specimen contained hair
follicles and should be of sufficient depth to
include the cutaneous nerves at the base of
hair follicles.

34.  It is important to conduct laboratory
investigations on persons who died from a
suspected rabies virus infections.
 A brain specimen is the preferred specimen
Brain specimens
 Small sections of the both the cerebellum
and the cerebrum should be submitted.

35. RT PCR amplification
 Highly sensitive &specific in rabies virus
detection.
 In fresh saliva,skin,csf,brain tissues

36. Other methods
-MRI of brain-variable and non specific
- EEG -non specific results

37.  No established treatment
 Isolating in a quiet roomwith no bright
light,noise,convulsions etc.
 Sedatives can be given to reduce the anxiety
 Provide intensive cardiac and repiratory
support.
 99.99% cases are preventable if managed in
TIME.

38. 1.Categorization of the wound
2.Wound treatment
3.Vaccination PEP
4.Immunoglobin
5.Counselling the patients

39. Category1 : touching or feeding suspect
animals,but skin is intact.
Category2 : minor scratches without bleedind
or licks on broken area.
Category3 : 1 or more bite,scratches,licks on
broken areaor exposure to bats.

40.  The people who are considered as high risk
group need pre-exposure prophylaxis.
 These groups include a veterinarian, animal
handlers and laboratory workers are people
whose activities bring them in contact with
rabies virus or rabid animals
 c-international travelers likely to come in
contact of the animals in the rabies threaten
areas.
 All these groups should be treated with rabies
vaccines to avoid the chances of sudden
infection.

41. If a person is bitten by an animal, the wound and
scratches should be washed thoroughly with soap
and water to decrease the chances of infection.
 Post-exposure prophylaxis involved one dose of
rabies immune globulin and five doses of rabies
vaccine within the 28 days period.
 Rabies immune globulin contains antibodies from
blood donors who were given rabies vaccine.
 The rabies vaccine works by stimulating a
person’s immune system to produce antibodies
that neutralize the virus.

42.  Human rabies immune globulin is injected at the bite area
immediately because it attacks the virus and slow down or stop
viral progression through the nerves .
 Timing and the ability of the patient to respond by making a
good immune response is a key to patient survival.
 Case management of bitten patients
Immediate and thorough cleaning of the wound with soap,
followed by ethanol or aqueous iodine.
- Postexposure prophylaxis (PEP) : administration of rabies
immunoglobulin in case of severe exposure (WHO category 3).
- PEP to be applied as soon as possible – vaccines with a potency
at least 2.5 IU per single immunizing intramuscular dose
according to one of the following schedules
- Intramuscular schedules ƒ- 1 dose on days 0, 3, 7, 14 and 28. All
intramuscular injections to be given into deltoid region .Never
inject the vaccine in the gluteal region.

43.  This regimen is particularly recommended when no
immunoglobulin is required, i.e. when contact consists in nibbling
of uncovered skin, minor scratches or abrasions without bleeding,
or licks on broken skin.
 Intradermal schedules. The following intradermal regimens have
been shown to be immunogenic
 ƒ
2-site intradermal method (2-2-2-0-1-1 and 2-2-2-0-2) for use with
purified vero cell vaccine (PVRV), purified primary chick embryo
cell vaccine (PCECV) and human diploid cell (HCDV) at 0.1 ml per
intradermal injection site – days 0, 3 and 7
 Intradermal injections must be given by staff trained in this
technique. Vaccine vials to be stored between 2 ºC and 8 ºC after
reconstitution and total content to be used as soon as possible, at
least within 8 hours.
 Rabies vaccines formulated with an adjuvant should not be
administered intradermally.
 The standard dose per id injection site is 0.1 ml.

44. vaccine
 A 1-ml syringe and a needle for each intramuscular
injection (intradermal needles and syringes for intradermal
vaccination).
 Vaccine amounts: between 2 and 5 vials, depending on the
method used.
 Only the following vaccines meet WHO safety, potency
and efficacy requirements when used for post exposure
intradermal treatment of rabies
- ƒhuman diploid cell vaccine (HDCV)
eg:Rabivac™
- ƒpurified vero cell vaccine (PVRV)
eg; Verorab, Imovax, Rabies vero, TRC Verorab™
- purified chicken embryo cell vaccine (PCECV)
eg; Rabipur™.

45.  There is no specific treatment for rabies, which is a
fatal disease.
WHO promotes human rabies prevention through
 well-targeted postexposure treatment using modern
vaccine types and, when appropriate, antirabies
immunoglobulin
 pre-exposure prophylaxis using modern vaccine types
for certain professional groups at higher risk and
 also if vaccines are easily accessible, of children aged
under 15 in areas where rabies is hyperendemic
 increased access of safe and effective rabies vaccines.
 dog rabies elimination through mass vaccination of dogs
and dog-population management.