rabies lecture 2

RABIES AND ITS PREVENTIVE MANAGEMENT

Dr M Amir Sohail MBBS DCH

Rabies - A killer disease widespread

throughout the world

It is estimated every 15 minutes one person dies

of rabies, & 15,00,000 bites occur per year

Rabies is endemic in most parts of the world & severe in

developing countries of Africa, Asia & South America, where 99% of world’s human rabies

death occur

Rabies free countries

• Antartica• Australia• British Isles• Cyprus• Japan

• New Zealand• Malaysia• Singapore• Taiwan• Lashwadeep,

Andaman & Nicobar Islands

BANGLADESHAlmost 80000 people seek post-exposure vaccination and 2000

people die of rabies

Hospital records indicate about 2000 cases per yearHospital records indicate about 2000 cases per year

Prevalence of Human Rabiesin Bangladesh

Prevalence of Human Rabiesin Bangladesh

(Z. Ahmed, 4th Int. Symp.On Rabies in Asia, Vietnam, March 2001)

(Z. Ahmed, 4th Int. Symp.On Rabies in Asia, Vietnam, March 2001)

Statistics from I.D.H, Dhaka aloneStatistics from I.D.H, Dhaka alone

173173

101101

151151

140140

171171162162

132132120120116116

145145

00

5050

100100

150150

200200

19911991 19921992 19931993 19941994 19951995 19961996 19971997 19981998 19991999 20002000

nn

Statistics from IDHYear1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

Rabies cases116

120

132

162

171

140

145

151

101

173Z. Ahmed, 4th Int. Symp. On Rabies Vietnam 2001

Children often suffer the major burnt of the trauma due to

animal bites and in several studies account for 60% of

animal bite casesTK Ghosh, Journal of APCRI, 1999; pp21-25

Rabies virus• RNA virus; family - Rhabdoviridae, genus -

Lyssavirus• Bullet shaped• Resistant to cold, dryness, decay & is known to

remain infectious for weeks in cadavers• Readily inactivated by soap, common disinfectants

(Dettol, Savlon, tincture iodine, povidone iodine), acid & alkali, UV light, pasteurization, 40% alcohol

ANIMAL RESERVOIR OF VIRUS

• All mammals are capable of being infected with rabies

• Dogs major vector of transmission of rabies (99% of human rabies transmitted by dog, 90% people seek PET line areas where canine rabies is endemic)

• Other predominant reservoir - cats, jackals, wolves, foxes, mongoose, skunks, raccoons, coyotes, bats

RABIES RESERVOIR IN DIFFERENT COUNTRIES

• Dogs• Foxes• Jackals• Raccoons• Mongooses• Skunks• Bats

Major vector of rabies throughout the world, especially Asia, Latin America & Africa

Eastern Europe, Subartic & eastern parts of N. America, Suartic Asia

Asia & Africa

Eastern United States

Yellow mongoose in Asia & Africa, Indian mongoose in the Caribbean Islands

Midwestern United States, Western Canada

Vampire bats from Northern Mexico to Argentina, insectivorous bats in N. America & Europe

TRANMISSION OF VIRUS

• Broken skin

• Intact mucous membrane

• Aerosol

• Organ transplant

INCUBATION PERIOD

• Average - 30 to 90 days, but varies from days to years

• Depends on degree & site of bite, amount of virus inoculated & host factor (age/ immunodeficiency)

Lower extremity is the commonest site of exposure in 65% of cases followed by the

upper extremity in 28.8%, head, neck & face in 5.8%, abdomen in

5.8% and chest in 0.6%AK Dutta, Journal of APCRI, 1999; pp26 30

PATHOGENESIS IN HUMANS

• Inoculation of the virus mainly through a bite from infected animal

• Multiplication, penetration in the local nerve ending & spread by the axonal route towards CNS

• Virus spread within brain

• Migration through peripheral nerves in the secretory & excretory glands

CLINICAL MANIFESTATION

Prodromal symptoms

Headache, restlessness, fever

Itching at the site of bite, even if it is healed

Classical Manifestation

Occurs in 80- 90% of patients

• Hyperexitability

• Hydrophobia

• Aerophobia

• Photophobia

• Respiratory paralysis, cardiac arrest, death in 1-5 days

Paralytic Rabies

Less common

• Gradual ascending paralysis

• Stupor, coma & death in 1-2 weeks

• Hydrophobia usually absent

LABORATORY DIAGNOSIS

Antemortem

• Skin biopsy from nuchal region

• Corneal impression & saliva smear

Postmortem

• Brain - Negri bodies

• Biological test

MANAGEMENT OF RABIES PATIENT

• Isolation• iv rehydration,

prednisolone, mannitol• Sedatives,

antipyretics, analgesics, antihistamines & anticonvulsants

• Medical attendants - self protection

• Avoid contact with saliva, other body fluids

• Pre-exposure vaccinationWash clothes & other objects

• Room to be washed

RABIES IS A 100% FATAL DISEASE

PREVENTION OF RABIES IN MAN

• Post-exposure treatment

• Pre-exposure immunization

POST-EXPOSURE TREATMENT

• Wound treatment

• Anti-rabies immunization

a. Anti-rabies vaccine

b. Anti-rabies sera/immunoglobulin

WOUND TREATMENT

• Clean & flush wound with profuse water & soap

• Application of viricidal agents

• Thorough exploration of wound, debriment & removal of dirt, dead tissue, foreign bodies

• No dressing/bandaging & avoid suturing

• Proper tetanus prophylaxis

• Systemic antibiotics

RABIES VACCINATION

On July 6, 1885, Louis Pasteur saved a young boy - Joseph Meister bitten by a rabid dog by vaccinating him

with an attenuated virus strain obtained by repeated passage from a

rabbit spinal cord

THE PROGRESS OF RABIES VACCINE IN 100 YEARS

Brain of adult animals

Brain of suckling animals

Embryonated eggs

CELL CUTURE

Human diploid cell

Purified Chick Embryo Cell

Purified Vero Cell Vaccine

NERVE TISSUE VACCINE

Prepared from sheep brain

Virus inactivated with phenol

Composition - 5% infected sheep brain suspension

NERVE TISSUE VACCINE

• High drop out rate- large volume

- daily administration over 7-14 days

- sc tissue of anterior abdominal wall

• Poorly immunogenic

• High incidence of local & systemic reactions

• High risk of neurological complication (1:5000 - 1:1100)

TISSUE CULTURE VACCINE

• Human diploid cell

• Purified Chick Embryo Cell

• Purified Vero Cell Vaccine

TISSUE CULTURE VACCINE

• Relatively painless

• Highly immunogenic

• Very well tolerated

• 5 spaced-out injections in the arm instead of daily injection in abdomen

• Small volume

• Hardly any neurological complaint

• Pre-exposure prophylaxis for high risk person

• Can be given at any stage of pregnancy

Since 1983, the WHO has indicated its support for the trend to limit or abandon completely,

where economically and technically possible, the production of encephalogenetic brain tissue

vaccine, and strongly advocates discontinuation of the nerve tissue vaccines in favour of these cell

culture vaccines in both developed and developing countries

WHO Expert Committee on Rabies, 7th Report, WHO Technical Series 709

(“Essen” Scheme)

Post exposure prophylaxis(Essen schedule)

One injection each on day

0, 3, 7, 14, 30 & 90(optional)Day 0 is the day of first injection & Days

3, 7, etc are to be counted from Day 0

Rabies immunization with tissue culture vaccine

• Preferred site - deltoid region

• In infants & children - lateral aspect of thigh

• Avoid gluteal region

• Same dose for age group

• Use reconstituted vaccine in 6-8 hours

Preferred site : Deltoid

In infants and small children:antero-lateral aspect of thethigh

Avoid gluteal region.- inadvertant deposition of vaccine in thick S.C. adipose tissue instead of muscle, retards immune response

Same dose for all age groups

Use reconstituted vaccine in6-8 hours

Preferred site : Deltoid

In infants and small children:antero-lateral aspect of thethigh

Avoid gluteal region.- inadvertant deposition of vaccine in thick S.C. adipose tissue instead of muscle, retards immune response

Same dose for all age groups

Use reconstituted vaccine in6-8 hours

INDICATIONS FOR ANTI_RABIES IMMUNIZATION

• Stray animal & not available for observation

• Animal shows clinical signs of rabies

• Animal is proved positive for rabies by laboratory examination

SITUATIONS WHERE ANTI-RABIES IMMUNIZATION IS NOT REQUIRED

• Drinking of boiled milk of rabid animal

• Biting animal has remained healthy & alive for 10 days (??)

• Mere touching of a rabid animal

• Bite or scratch over clothing without tearing or piercing it & no sign of injury on skin at all

• Unprovoked & accidental bites by rodents, rats, mice, hares, rabbits, birds, bats & insects

With the advent of modern tissue culture vaccines, and in view of the fact that literature

records several instances where the animal has outlived the man it has bitten, there is no

longer a rationale in observing the animal while withholding treatment

AK Dutta, SK Kanwal, Journal of APCRI, 1999; pp5-13

The post exposure vaccination allows for the rapid induction of

antibodies against rabies virus and to be successful, a full course

should be administered as early as possible at an appropriate

site, and without any delay

Unfavourable host factors like alcoholism, malnutrition,

immunosuppressive treatment, certain chronic disease

- two initial intramuscular injection of the vaccination into both deltoid muscle

followed by the classical regimen

The post exposure vaccination allows for rapid induction of

antibodies against rabies virus and to be successful, a full course

should be administered as early as possible at an appropriate

site, and without any delay

Management of patients, who are previously vaccinated within last

5 years and have re-exposure, involves as always, local

treatment of the wound and repeat vaccination with 2 booster

doses on days 0 and 3

RABIES IMMUNOGLOBULIN

• Single or multiple transdermal bites or scratches (especially near the CNS)

• Contamination of mucous membrane with saliva

Post-exposure Prophylaxis of Rabiestogether with RIG (“Essen” Scheme)

Post-exposure Prophylaxis of Rabiestogether with RIG (“Essen” Scheme)

RABIES IMMUNOGLOBULIN

• Equine RIG - 40IU/kg

• Human RIG - 20IU/kg

• Single dose at the same time as the first dose of vaccine• RIG should be infiltrated around & into the wound.

Any remaining RIG should be injected intramuscularly at a distance from the site of vaccine innoculation

Pre-exposure prophylaxis for high risk persons

• Veterinary doctors

• Doctors treating rabies patients

• Laboratory personnel

• Hunters

• Animal attendants

• Postman

One injection each on days :

0 28 56

0 7 21 or 28

or

Pre-exposure prophylaxis

Day 0, 7, 21 or 28

Day 0, 28 & 56

Booster after 1 year & subsequently 1 injection every 3-5 years

Factors adversely influencing response

• Inappropriate local wound treatment• Delayed initiation of PET• Vaccination not in deltoid region• No rabies immunoglobulin• Failure to infiltrate RIG locally• Treatment with RIG 24 hours before vaccination• Host factors• Vaccination not completed

POINTS TO REMEMBER• Rabies is 100% fatal disease• Immediate & early wound treatment to remove traces of saliva is

very important• Suturing of wounds to be avoided• Correct PET, including the use of serum in high risk exposure, is life

saving• There is no contraindication for post-exposure immunization

including pregnancy, lactation, AIDS and other infectious condition• TCV are superior & safe, & is always preferred & injected

intramuscularly into deltoid (thigh in children) & never in gluteal region

In an endemic & enzootic country where every animal bite is considered a risk, immediate

starting of vaccine in low risk exposures and serum and vaccine

in higher risk exposure is strongly recommended

THANK YOU