Rabies

Dr. Amany Ahmed Ibrahim

Assistant Prof.of Tropical Medicine Department
 Geographical distribution
It is a true zoonosis
It cannot be maintained in human
population without help from other animals
Rabies free areas include UK,
Scandinavia(except Denmark), west
Malaysia, Taiwan, Japan, Australia and the
pacific islands
 Aetiology
Rabies is an RNA virus of Rhabdovirus group
It is readily inactivated by sunlight ultraviolet radiation,
drying and heating especially at PH outside the range 5-
10, by lipid solvents
Virus isolated from naturally infected animals is known
as “Street virus”
Repeated intracerebral passage in rabbits produced
“Fixed virus” which has a relatively constant incubation
period, shortened from 9-15 to 5-6 days, and with
reduced pathogenecity from many non human species.
Rabies is an RNA virus of Rhabdovirus group
 Aetiology
Six rabies related viruses have been
isolated in Africa, all serologically related
to but distinguishable from classical rabies
virus, only two of which have been
associated to human infection.
 Transmission
 Rabies virus can penetrate broken skin and intact
mucosa
 Routes of transmission may be saliva inoculated by:
1. A bite
2. The contact of saliva with preexisting wound or
scratch
3. Inhalation of aerosol
4. Inoculation of conjunctiva
5. Via tissue transplantation from infected cadaver as in
corneal transplantation
 Pathology
 Virus multiplies locally at the site of inoculation
 After a period of days or weeks enters the peripheral nerves
and travels up with the axons to the dorsal root ganglion
where further multiplication takes place, from here it spreads
into the CNS
 In the CNS virus multiplies in neurons and glial cells and is
transmitted from cell to cell then the virus spreads outwards
via the axons of the peripheral nerves to many tissues
including skeletal and cardiac muscle, adrenal medulla,
kidney, cornea and nerves in hair follicles and the most
important transmission is the spread of the virus to the
salivary glands
 Changes on microscopy
• Changes are most marked in midbrain and medulla in
“furious rabies” and in the spinal cord in “paralytic rabies”
• Negri bodies are intracytoplasmic inclusion bodies 24-27 µm
in diameter composed of an acidophilic matrix within which
are smaller basophilic inner bodies 0.2-0.5 µm in size
arranged in rosette fashion. They are found mainly in
Ammon’s horn and in cerebellar purkinje cells. Negri
bodies contained altered virus particles.
• Neuronolysis is seen in foci of degenerative neurons
associated with leucocytic infiltration and gliosis forming
distinctive patterns known as “Babes nodes”
Negri bodies
 Changes on microscopy
• Other organs are infected and there is focal
degeneration in the salivary gland,
pancreas, medulla and lymph nodes. An
interstitial myocarditis with round cell
infiltration is found in about ¼ of the cases
 Immunity
No immune response can be detected until
after symptoms develop
Neutralizing and fluorescent antibodies can
be detected in the blood after 7 days of
illness and a little later in CSF
Interferon has been detected
 Clinical picture
 I.P: varies from 4 days to 2 years but in over
90% of cases lies between 20-90 days
 Prodromal symptoms of fever and headache are
in most cases followed by signs of encephalitis
or paralysis which progress inexorably to fatal
conclusion
 There are two main types of clinical picture:
1. Furious symptoms are those of overactive of
the central nervous system
2. Dumb inhibition or paralysis is the outstanding
feature
 Clinical picture
(symptoms and signs)
 The first symptoms are fever, anxiety, malaise,
headache, photophobia and myalgia
The mood changes towards irritability and
depression and there is often marked anxiety
A characteristic symptom is paraesthesia or pain at
the site of original bite
Rabies is usually of the furious type in man
The most characteristic symptoms is spasm of the
muscle of deglutition often precipitated by an
attempt to swallow (hydrophobia)
Hydrophobia
 Clinical picture
(symptoms and signs)
Spasmodic contractions of the muscle may spread
to respiratory and other muscles leading to attack
of apnea
Symptoms of autonomic dysfunction include
excessive lacrimation, excessive sweating,
derangement of temperature control and the
development of diabetes insipidus
Cranial nerves III,VI, VII, IX, X, XI and XII may
be involved
Symptoms of autonomic dysfunction include
excessive lacrimation, excessive sweating
 Clinical picture
(symptoms and signs)
Paralytic rabies
It is the usual form in bat rabies occurs in
only 20% of cases
After the usual prodromal symptoms, the
patient develop an acute progressive
ascending myelitis symmetrical or
asymmetrical with flaccid paralysis, root
pain and fasciculation in the affected
muscles with mild sensory disturbance
 Diagnosis
• Is clinical
• Specific diagnosis cannot be made before death but in
20% of cases can be made before death by the
identification of virus in corneal impression smears
using fluorescent antibody technique
• D.D:
1. Furious rabies: include tetanus and hysterical reaction
2. Paralytic rabies: viral encephalitis of various sort,
poliomyelitis, Guillian Barre syndrome
• Post mortem diagnosis is made by the finding of Negri
bodies and the typical encephalomyelitis
Fluorescent antibody technique
 Treatment
• Symptomatic treatment: alone is to be carried out. The
aim should be relief of spasms and suffering by
continuous narcosis.A combination of chloropromazine,
diamorphine and barbiturate is effective in producing
narcosis and analgesia
• Post-exposure treatment:
 Should be given as soon as possible after exposure
 The objective of this form of treatment is firstly to
inactivate virus at the site of inoculation by proper
wound toilet and secondly to produce effective antirabies
antibody level as quickly as possible
 Treatment
• Suspect animal:
A. If it is alive 10 days after attack No
excretion of rabies virus
B. Suspect animal should not be killed but if
natural death occurs during the 10 days of
observation, the animal brain should be
examined for rabies by using the
fluorescent antibody test
 Treatment
• Local treatment:
1. The wound should be thoroughly washed with
soap and water or quaternary ammonium
compounds such as Benzakonium
2. After cleaning , the wound can be treated with
tinch I 2 or I 2 solution
3. Delay suturing if the wound in need
4. Hyperimmune serum: given if there is delay
between exposure to rabies and vaccination. The
dose is 40 units/kg for immune serum of animal
origin or 20 units/kg if human immune rabies
serum used. If there is gross wound, it is usual to
infiltrate the wound with half the dose and give
the remainder by deep I.M.I
 :Rabies vaccine
• Human diploid cell vaccine HDCV:
1. The most effective vaccine is Free of CNS complications
2. Dose 1 ml reconstituted freeze dried vaccine s.c or I.M on
day 0,3,7,14,30 and 90
3. Doses of 0.1 ml intradermally produce equally satisfactory
protection
4. If intradermal route is used increased effectiveness, vaccine
depends on its delivery to the local L.N via lymphatics
• Semple vaccine : is still used in the third world. The dose 2
ml daily for 14 days with 2 booster doses after a further 10
and 20 days
• Prexposure vaccination:
1. Needed only by those at high risk such as
veterinaries, animal handlers, cave
explorers and forest ringers
2. Human diploid cell strain vaccine is the
preferred vaccine.Its intradermal route 0.1
ml on days 0,7 and 28 or 2 doses s.c 1ml
(4 weeks apart) followed by yearly
boosters
 Venomous bites and stings
1- Snake venom
 Contains at least two proteases that activate the
mammalian blood clotting cascade. The polypeptide
toxins are mostly responsible for neurological
disorders, while biogenic amines as histamine and 5-
hydroxytryptamine cause local pain and permeability
changes at site of bite.
 In the bitten limb, increased vascular permeability
changes at site of bite leads to swelling and
bruising.Profound hypotension caused by release of
vasodilating agents and splanchnic vasodilatation
 Snake venom - 1
 Venom coagulants produce consumption coagulopathy
leading to incoagulable blood. Thrombocytopenia is common
combination of definition, thrombocytopenia and vessel wall
damage result in massive bleeding
 Acute tubular necrosis 2ry to prolonged hypotension, DIC,
haemoglobiuria, myoglobinuria and hyperkalemia may occur
 Corneal erosions and anterior uveitis occur from spitting of
cobra venom.Blistering, necrosis and local numbness or
paraesthesia in areas of cutaneous nerve distribution.
 Ptosis, blurring vision, headache and vertigo with
hypersalivation and later paralysis of palate, jaw, tongue, vocal
cords and muscles of deglutition
 Snake venom -1
 Treatment is by reassuring the victim, immobilize the bitten
limb by a splint binded with crepe bandage. Oral paracetamol
or pethidine for pain
 Victim should lie on his side with head down to avoid
aspiration of vomitus and give chloropromazine 25-50 mg IV
 Anaphylaxis as vasovagal attack, sweating, colic, diarrhea or
angioneurtic oedema treated by antihistamine as IV or IM
chlophniramine maleate
 Adrenaline 1/1000, 0.5 ml SC for hypotension or
bronchoconstriction
 Oxygen, artificial respiration or mouth to mouth breathing can
help to clear airways
 Snake venom -1
 If patient is shocked, foot of bed should be
raised with IV infusion of plasma
expanders. Monospecific or polyspecific
antivenom given IV or by drip in isotonic
fluid. A second dose is given if severe
cardiorespiratory symptoms persists more
than ½ hour or incoagulable blood persist
more than 6 hours
 Insect stings -2
• I- Hymenoptera stings: Pain, redness, swelling, whealing
and hotness develop rapidly. Massive stings resemble
histamine overdose in form of hypotension, vasodilatation,
vomiting, diarrhea, throbbing headache and may be coma.
• Allergic manifestations as tingling, scalp, flushing,
dizziness, syncope, tachycardia, urticaria and angioneurtic
oedema may occur
• Treatment is by removal of embedded bee sting without
squeezing. Aspirin, local antiseptics and systemic
antihistamine. Adrenaline 0.1% 0.5 ml sc for allergic
effects. Hydrocortisone for angioneurtic oedema
 Insect stings -2
• Scorpion stings: Intense local pain with swelling,
redness, heat and regional lymph node
involvement. Features of autonomic nervous
system excitation as dilated pupils, sweating,
salivation, vomiting, diarrhea, loss of sphincter
control. Release of catecholamines causes
hypertension, toxic myocarditis and arrythmias.
Neurotic effects in form of fasciculations, spasms
and respiratory paralysis. Hyperglycemia and
glycosuria occur and ECG abnormalities.
 Insect stings -2
• Spider bite: Local erythema and blistering up to
extensive tissue necrosis. There may be haemoglobiuria,
jaundice, fever, respiratory distress and collapse.
Numbness around the mouth and spasm of the tongue
may develop rapidely followed by nausea, vomiting,
colic, profuse sweating, salivation and lacrimation.
Dyspnea up to pulmonary oedema and death may occur.
• Treatment by firm crepe bandage and splinting of
affected limb. Antivenom IV & oral dapson 100 mg/
twice daily reduce the extent of necrotic lesions.
Calcium gluconate relieves pain of muscle spasm.