rabies

1. Neuropsychiatric manifestations of Rabies
A progress report submitted in partial
fulfillment of the requirements for
the award of the degree of
B. Pharm
In
Department of Pharmacology
Govt. College of Pharmacy, Rohru
By
Shruti Choudhary
Under the supervision of
DR. VIVEK SHARMA
April,2018

2.  First of all, I would like to express my profound thanks and deep sense of
gratitude to my respected teacher and guide Dr. Vivek Sharma, I am greatly
indebted to his valuable guidance throughtout the work that has enabled me
to complete this project work.
 I wish to express my sincere thanks to Dr. Rajender Guleria for his
exceptional guidance and support. I would also like to thanks Mr. Athar
Javed, Mr. Pankaj Sharma and Mr. Harish Verma for their teaching and
imparting me the knowledge during my graduation studies. I want to extent
my thanks to Mr. VInod Sharma, librarian of GCP for providing me the
literature for project work.
 It would not have been possible to stand the thick and thin during my bad
times without the help of my friends who not only provided the lighter
moments but also helped in all ways they could, I would like to thanks
Priya, Rishav, Shilpa, Tamanna, Manisha, Pallvi, Samriti, Shobhana and
Sudhanshu for their invaluable help and cheerful companionship.
 My deep sense of gratitude and love always remain for my parents for their
blessings, affection, moral support and encouragement which are the main
source of inspiration in my career.

3.  Introduction
 Causative agent
 Signs and symptoms
 Clinical phases
 Transmission of lyssa
 Mechanism of infection
• Formation of negri bodies
• Other factors causing degenerative changes
• Degenerative changes in neurons
I. Aerophobia
II. Hydrophobia in rabies
a. Central mechanism of rabies
b. Peripheral mechanism of rabies
 Diagnosis
 Management of rabies
 Conclusion

4.  Rabies is an avertable viral disease caused by Lyssavirus of family
Rhabdoviridae transmitted zoonotically to the warm blooded animals,
especially humans.
 The name ‘Rabies’ comes from the Latin word ‘rabere’ which means
raging, furious, savage, or madeness. The word ‘Lyssa’ stands for Greek
goddness of madness, rage and frenzy.
 ‘Lyssa’ is the 10th biggest cause of death due to infectious diseases
worldwide. WHO reports around 50,000 rabies deaths every year, out of
which 20,000 are estimated to occur in India alone.

9. INOCULATION
RECEPTORS AT
NM JUNCTION
 Nicotinic Ach
receptors
 Neural cell
adhesion molecule
 Nerve growth
factor receptors
The virus
enters PNS at
neuromuscular
junction
Virus travels
within motor and
sensory axons by
retrograde fast
axonal transport
Virus enters CNS
(basal ganglia , mid
brain and medulla
oblongata in brain
stem) &
predominantly
infecting neurons.
Formation of
negri bodies
Degenerative
changes in
neurons

10.  Infected neurons may contain eosinophilic inclusions in the cytoplasm,
called Negri bodies which are most prominent in large neurons (eg,
Purkinje cells) and ultrastructurally are composed of large aggregates of
granulofilamentous matrix material and variable numbers of viral particles.
 Negri bodies are also called viral factories since they contain all the viral
RNAs (genome , antigenome , mRNAs) and viral N and P proteins
required for the replication and transcription of virus in human body. Negri
bodies, in fact , appear to be vital functional structures involved in the viral
life cycle.
 Presence or absence of negri bodies is used for the diagnosis of rabies.

11. Cytoskeletal integrity
interrupted
Disappearance
microtubule associated
protein and
neurofilament reactivity
Degenerative changes in
neurons of hippocampi
Decrease Na+ channel &
inward rectifier K+ channel
Decrease firing action
potential
Decrease release of
neurotransmitters from
synaptic end in hippocampi
Dementia & behavioural
changes
(Hydrophobia &
Aerophobia)

12. Decrease
antiviral
response
Downregulation of
cytokine receptor
signaling
accumulation
of INOS
Decrease
binding of
neuro-
transmitters

13.  Aerophobia is a pathological aversion or sensitivity to air or the movement
of air especially as a symptom of rabies. When air blown in the face
produces severe laryngeal or diaphragmatic spasm and a sensation of
choking. This may be related to a violent response of the airway irritant
mechanism.
Pre-Boetzinger
complex
(preBotC)
Brain stem
respiratory
neurons
Hypoglossal
nucleus
Dorsal
respiratory
group
Dorsal medullary
reticular column
(DMRC)
Rabies virus
infects
Responsible for
rhithmicity in
respiration

14.  Hydrophobia is an older term for the disease rabies and the term stands for
fear of water (hydro-water; phobia-fear). Rabies actually doesn’t instil a
fear of water in the infected person but instead causes dysphagia -
difficulty with swallowing.
 Hydrophobia is commonly associated with furious rabies which affects
80% of rabies infected patient.
 Saliva production is greatly increased, and attempts to drink, or even the
intention or suggestion of drinking may cause excruciatiangly painful
spasm of the muscles in the throat, diaphragm, accessory respiratory and
laryngeal muscles.

15. Central Pattern
Generators (CPGs)
of medulla oblangata
Dorsal Swallowing
Group
Present in Nucleus
Tractus Solitari
sends
signals to
Muscles
coordination
for
swallowing
signals
controls
Rabies Virus inhibits
affects

16. When food is
eaten
Ach is
released
Cranial nerves signals NTs release
Inc. salivation &
moistening of
pharynx
Coordination of smooth
muscles of oesophagus
& closing of larynx
Facilitates smooth
swallowing process
Lysaa virus

17. Diagnosis can only be confirmed by laboratory tests preferably conducted
post mortem on central nervous system tissue removed from cranium . Tests
are also performed on the samples of saliva, serum, and skin biopsies of hair
follicles at the nape of the neck.
Diagnosis techniques for rabies
 Direct Fluorescent Antibody Technique (DFA)
 Mouse Inoculation Technique (MIT)
 Tissue Culture Infection technique (TCIT)
 Polymerase Chain Reaction (PCR)

19.  Rabies can be prevented before the latent symptoms can develop, consists
of giving a person an injection of rabies immune globulin and another
injection of rabies vaccine as soon as possible after the bite or exposure to
saliva from an infected animal.
 Two rabies vaccines are now licensed for use in the UK – human diploid
cell vaccine (HDCV) and purified chick embryo cell (PCEC) vaccine .
Both are in 1 mL dose vials. PCEC is cheaper to produce. Elsewhere,
purified vero cell vaccine (PVRV) is widely available, but the dose is a
vial containing 0.5 mL. Experimental DNA based vaccines have not yet
been developed for use in man.

21. Types of vaccination Route Regimen
Primary Intramuscular HDVC or
PCECV ; 1.0 mL
(deltoid area) ,
one each on days
0, 7 and 21 or 28
Booster Intramuscular HDVC or
PCECV ; 1.0 mL
(deltoid area) ,
day 0 only

22. Thank you