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Presented by: Dr. Prabhat Moktan

Moderator: Dr. v.k.mehta

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Content • INTRODUCTION• BURDEN OF DISEASE• EPIDEMIOLOGY• CLINICAL FEATURES• DISEASE MECHANISM• DIAGNOSIS• Prevention• CONTROL• RABIES CONTROL IN INDIA

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Introduction:Key facts

Rabies is a vaccine-preventable viral disease which occurs in more than 150 countries and territories.

Dogs are the source of the vast majority of human rabies deaths.

Rabies elimination is feasible by vaccinating dogs.

Infection causes many deaths every year, mostly in Asia and Africa.

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40% of people who are bitten by suspect rabid animals are children under 15 years of age.

Immediate wound cleansing with soap and water after contact with a suspect rabid animal can be life-saving.

Every year, more than 15 million people worldwide receive a post-bite vaccination to prevent the disease; this is estimated to prevent many deaths annually.

(WHO Fact Sheet Updated September, 2015).

Contd..

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HISTORY• Rabies has been derived from the sanskrit word

“Rabhas” which means “to do violence”.• Latin origin-”Rebere”which means “to rave”.• “Jalasanthra”- agony caused by water.

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Contd..• Sir Louis Pasteur,french chemist was the first person who

prepared the anti rabies vaccine from the spinal cord of an infected rabbit.

• On 6th July 1885,Sir Louis Pasteur successfully treated a 9 year old shepherd boy by the name Joseph Meister who was severely bitten by a rabid dog.

• Consequently, every year July 6th is celebrated as “World Zoonoses Day “or “World Rabies Free Day”.

• In 1903,Negri,an Italian scientist demonstrated the viral particles ,as inclusion bodies in the neurons of the rabid animal,which are named after him as Negri bodies.

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Contd..• In 1911,in India, David Semple, developed a vaccine

from the brain of an infected sheep, popularly known as “Semple vaccine "or BPL vaccine.

• Later, Flury prepared a vaccine from chick embryo and duck embryo.

• In 1964, Witkor and Kaprowski, were successful in preparing a Tissue Culture Vaccine by culturing the virus in human diploid cells.

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• Human rabies is present in 150 countries and territories and on all continents, except for Antarctica and Australia.

• 95% of human deaths occur in Asia and Africa.

BURDEN OF DISEASE

WORLD:

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Contd…

Africa

• Estimates of the burden of rabies in Africa have always been uncertain because of the lack of good data.

• In 2010 the estimated burden of rabies in Africa was approximately 23800 deaths.

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Contd.Latin America and the Caribbean

• Official reports of cases of human rabies transmitted by dogs decreased from about 250 in 1990 to fewer than 10 in 2010,with concomitant declines in dog rabies.

• The Pan American Health Organization has set a target to eliminate dog-mediated rabies from America by 2015.

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Contd..

Asia

• More human deaths from rabies occur in Asia due to endemic canine rabies exceeding 30000 per annum.

• In 2010 the incidence of human deaths from rabies per 100000 population was estimated to be as given below :1.Bangladesh-1–1.8. 2.Bhutan- 2.5–7.5 .3.Cambodia- 2.8–11.5.

• Little information is available on rabies in the Middle East or Central Asia.

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Contd..INDIA

• India is reported to have the highest incidence of rabies globally.

• India accounts for 30,000 deaths due to rabies every year.

• Cases have been reported from all parts of India except for Andaman Nicobar and Lashadeep islands.

• 3 million people take antirabies treatment every year.

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Contd…

Global summary• About 50,000 deaths occur due to rabies annually.• Rabies is present in all continents except in Antarctica and

Australia.• The estimated annual cost of rabies is US$ 6 billion, with almost

US$ 2 billion due to lost productivity after premature deaths and a further US$ 1.6 billion spent directly on post-exposure prophylaxis.

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EPIDEMIOLOGY

AGENT FACTORS• The causative agent is a RNA virus,a lyssa virus type

1 belonging to the family Rhabdoviridae.• It is a bullet shaped virus, single stranded and non

segmented.• A sheath of lipid covers the body surface.• The lipid has spikes containing glycoprotein

projecting all over the body surface of the virus.

SEROTYPE 1 is the causative agent of rabies.

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Contd..

Rabies virus contains two antigens:

• A glycoprotein antigen(G protein).• An internal nucleoprotein antigen.

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RESERVIOR OF INFECTIONThe common reserviors country wise are asfollows:• DOGS-in most parts of the world mostly in Asia,Latin

America and Africa• FOXES- Europe ,Arctic and North America,• RACCOONS-Eastern United States.• SKUNKS- Western Canada.• COYOTES- Asia, Africa and North America.• BATS-Vampire bats in SouthAmerica, Insectivorous bats

in North America and Europe.

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Raccoon

fox

Bats

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SOURCE OF INFECTION • The saliva of rabid animals.• Inhalation of virus containing aerosols.• Less infectious materials are other body fluids like

serum,urine and milk.• In humans-saliva,sweat,semen and tears contain the

virus.• Cornea of human cases constitutes an infective

material.(rabies antigen detected in corneal cells).

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Incubation period• It varies from 3 weeks to 3 months(15 days to 1 year).Factors influencing the incubation period:

1. Site Of The Bite.2. Severity Of The Bite.3. Species Of The Biting Animal.4. Richness Of The Nerve Supply.5. Amount Of Saliva Deposited.6. Protection Through Clothes.7. Partial Treatment Taken .

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Period of infectivity

• The rabid animal is infectious during the last 3 to 5 days of incubation period and also during the entire peiod of illness,which is about 8 to 10 days.

• Thus the total period of infectivity is about 12 to 15 days.

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Host factors

• All warm blooded animals including man.• Rabies in man is a dead end infection and has no

survival value.

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AT RISK• Veterinarians and animal handlers.• Hunters and field naturalist.• Laboratory staff working with rabies vaccine.• Doctors and Nurses handling rabies patients.

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Modes of transmission

• The disease is transmitted from animal to animal and from animal to humans.

• From wild animals(Sylvatic Cycle) it is transmitted to domestic animals (Urban Cycle) and accidentally to humans.

• It is mainly transmitted by bite of rabid animals.

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Contd..

• It is also transmitted by bites of insectivorous bats and by aerosols route by vampire bats.

• Transplacental transmission seen in animals but not in humans.

• Oral transmission through drinking raw milk of rabid cattle is less likely.

• Sexual transmission has also not been reported.

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pathogenesis

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CLINICAL FEATURESProdromal Symptoms: fever, rhinorrhea, sore throat, myalgias, GI upset. Back

pain and muscle spasms. Agitation and anxiety. Paresthesias, pain or severe itching at site may be the first

neurological symptom. The prodromal stage is followed by Widespread excitation and stimulation of nervous system.

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Stage of excitementIn orderI. Sensory system:

irritable,anxious and nervous. sensitive to sensory stimuli like touch,pain and temperature. (convulsions on strong stimuli)

II. Motor system: increased tone and spasticity of muscles. exaggeration of deep reflexes,jerks..Tremors or tic like movements.

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Contd..

III. Sympathetic system: excessive perspiration,lacrimation,salivation and increased libido. meanwhile he develops aerophobia and photophobia.

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Stage of paralysis• Paralysis of muscles of deglutition,resulting in

difficulty swallowing.• An attempt to swallow results in choking sensation .• As the condition progresses an attempt to swallow

food and water,reflexly results in painful spasm of muscles of deglutition.

• Finally even the sight or sound of water causes painful spasms(hydrophobia).

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DUMB RABIES(PARALYTIC RABIES)• This occurs to about 10-20 per cent humans.• Seen mostly among partially immunized persons.• Clinical features:

gradual ascending paralysis. constipation and urinary retention. stupor,coma death within 1- 2 weeks. hydrophobia is usually abscent.

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RABIES IN DOGS

1. “FURIOUS” OR “FRANK” RABIES.2. DUMB RABIES.

Incubation period varies from 2 weeks to 2 months.

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1. “FURIOUS” OR “FRANK” RABIES:(MAD DOG SYNDROME).

• It is observed in 80 to 90 per cent of cases.• In early prodromal stage the dog starts to behave

differently and abnormally.• It goes to dark corners,becomes restless,unusual

agitation and develops fever.

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Contd..• Later it becomes aggressive and more ferocious.• Red eyes,runs here and there.• Develops perversion of taste.• Bites its own chain,stone, paper, wood,iron etc… in

this procees it can bite humans and other animals without provocation.

• Later in the clinical stage it develops paralysis of the lower jaw giving rise to protrusion of tongue, drooling of saliva, foaming at the angle of mouth and paralysis of vocal cords leads to change of tone of bark.

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DUMB RABIES(PARALYTIC RABIES)• It occurs in 10 to 20 per cent of animals.• The dog becomes silent and withdraws itself from

being disturbed.• Paralysis of muscles starts from the headand neck

region.• Difficulty in swallowing.

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Laboratory diagnosis.

1. Antemortem.2. Postmortem.

3. Antemortem :– Skin biopsy(nuchal region)from along the hairline of neck

and Fluorescent Antibody Test.– Corneal impressions and saliva smear for FAT.

2. Postmortem:– Biopsy of brain and seller’s stain for Negri bodies.– Fluorescent Antibody Test.

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Management of hydrophobia.• There is no cure or treatment , prevention is the only

intervention.• Symptomatic with supportive treatment and sedation.• Admission in a quiet room of the hospital.• Sedatives,antipyretics,analgesics,antihistaminics and

anticonvulsants.• IV rehydration,steriods and osmotic diuresis like

mannitol.• Expert nursing care.• Mechanical ventilation if required.• Pre-exposure prophylaxis and PPE.

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Prevention of Rabies in Man.

• Two approaches:1. Post-exposure prophylaxis.2. Pre-exposure prophylaxis.

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Contd..1. Post –exposure prophylaxis:

Wound treament

• Gentle washing of wound with soap preferably under

running tap water for at least 10-15 minutes.• Application of viricidal agents like povidone iodine.• In deep wounds-thorough exploration with removal

of dirt ,dead tissues and foreign bodies

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• Infiltration of rabies immunoglobulin locally into the wound.

• The animal bite wound is not sutured immediately,however ,if unavoidable it should be loose and not occlusive.

• Immunization against tetanus is given .• Prophylactic antibiotics.

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Observation of the animal• Applicable to dogs and cats.• The bitten animal should be observed for 10 days.• Change in behaviour.• Running here and there.• Biting without provocation.• Excessive salivation.• Change in tone of the bark.• Eating unusual objects.• Death of the animal.

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Antirabies immunization

Immunization against rabies is not included inthe Universal Immunization Programme,because• Incubation period is long• The immunity with antirabies tissue culture vaccines is

hardly 3 years.• The vaccines are costly.

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History of rabies vaccineVaccines prepared from animal tissues1. 1885- Louis Pasteur developed the first rabies vaccine

from the spinal cord of a rabbit.2. 1911- Semple Vaccine(from sheep and goat brains).3. 1955- Fuenzalida Vaccine (from suckling mouse brain).4. 1955- Powell prepared Duck embryo cell vaccine.(from

embryonated eggs)(Flury’s vaccine).

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Vaccines prepared from Primary Animal Cells (modern tissue or cell culture vaccines).

1960-1965- purified chick embryo cell vaccine• Primary Hamster Kidney Cells Vaccine.(Kissling).• Primary Dog Kidney Cell Vaccine.

Vaccines prepared from Standardised Cell Lines(Cell Bank).• 1964- Human Diploid Cell Vaccine (HDCV) by Witkor.• 1972- HDCV was also prepared by Wistar and Merieux

institute.• 1985- Purified Vero Cell Rabies Vaccine (PVRV) by Merieux

institute.

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Type of vaccines1. Nerve tissue vaccines.

a) BPL vaccine(Semple vaccine).b) suckling mouse brain vaccine (Fuenzalida vaccine).

2. Duck Embryo Vaccine (Flury’s Vaccine).3. Cell Culture Vaccines

a) Human Diploid Cell Vaccine (HDCV).Rabivaxb) Purified Chick Embryo Cell Vaccine(PCEC-V). Vaxirab, Rabipurc) Purified Vero Cell Rabies Vaccine(PVCR).

Verorab,indirab

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WHO guideline for PEPCATEGORY TYPE OF CONTACT WITH A SUSPECT

OR CONFIRMED RABID ANIMALRECOMMENDED TREATMENT

Category I touching or feeding of animals, licks on intact skin, contact of intact skin with secretions or excretions of a rabid animal or human

no exposure therefore no prophylaxis if history reliable

Category II minor scratches or abrasions without bleeding and/or nibbling of uncovered skin

use vaccine alone

Category III single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva (i.e. licks) and suspect contacts with bats

use immunoglobulin plus vaccine

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Intramuscular regimens for rabies PEP

1. Essen’s schedule: • The 5 dose regimen.• 0-3-7-14-28.• 1-1-1-1-1.

2. Zagreb schedule:• the 3 dose regimen.• 0---7---21.• 2-0-1-0-1.

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Intradermal regimen for rabies PEP

• 2 site intradermal schedule.(Thai Red Cross ID Schedule).

• One dose of vaccine, in a volume of 0.1 ml is given intradermally at two different sites .

• usually in the deltoid muscle on the left and right upper arm and suprascapular area

• Given on days 0, 3, 7 and 28. • 2-2-2-0-2.

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Contd..

• 8 site oxford intradermal schedule.• One dose of 0.1 ml is administered intradermally at

eight different sites :(upper arms, lateral thighs, suprascapular region, and lower quadrant of abdomen) on day 0.

• On day 7, four 0.1 ml injections are administered intradermally into each upper arm (deltoid region) and each lateral thigh.

• Following these injections, one additional 0.1 ml dose is administered on days 28 and 90.

• 8-0-4-0-1-1.

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Passive immunization• Adminstration of readymade antirabies

antibodies,Antirabies Sera o(ARS) or Human Rabies Immunoglobulin in all CAT III cases.

• Given at day 0 along with Active Immunization.• Two types of Rabies Immunoglobulin:

1. Equine Rabies Immunoglobulin (ERIG/ARS).Ionorabdose-40 IU/Kg body weight.

2. Human Rabies Immunoglobulin (HRIG).Rabivaxdose- 20 IU/Kg body weight.

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Advice to patient

1. Importance of taking the treatment correctly and completely.

2. To avoid steriods,spicy foods,spirit(alcohol),smoking and strain(physical and mental ).

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Re-exposure to rabies• History of previous immunization against rabies.• Has received post exposure or pre-exposure

prophylaxis either IM/ID.• 2 doses of vaccine on day 0 and 3 by IM.• If previous immunization is incomplete ,it is treated

as a fresh case.

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Contd..2. Pre-exposure prophylaxis:• It is given to those people who are at risk for e.g.

Veterinarians,animal handlers,laboratory personnel working with rabies vaccine..etc..

• WHO recommended 3 doses to be given intramuscularly on days 0,7 and 28.

Intradermal • One intradermal injection of 0.1 ml is given on each of

days 0, 7, and 21 or 28. (WHO)

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Rabies PEP in immunosuppressed individuals

1. Thorough wound treatment should be further stressed for immunosuppressed individuals.

2. RIG should be administered deeply into the wound for both category 2 and 3 exposures.

3. Vaccine should always be administered and no modification of the recommended number of doses is advisable.

4. An infectious disease specialist with expert knowledge of rabies prevention should be consulted.

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Control of rabies in dogs• Elimination of all stray,sick,dead and ownerless dogs.• Enforcing registration and licensing of pet

dogs(collar for identification).• Pre-exposure immunization of all pet dogs.

first dose at 2 months of age followed by second dose after one month.thereafter, booster dose regularly at once in a year.

• Post exposure prophylaxis. 0-3-7-14-28/30.• Health education of people about rabies.• Veterinary vaccines.

NTV,TCV. Nobivac-r

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PERSONAL PROTECTION AGAINST RABIES

1. Do not touch animal bitten wounds with bare hands.

2. Do not touch the chain,food plate of animals suspected or proven of having rabies.

3. Do not provoke any animal.4. Avoid contact with saliva,urine,tears,semen

or vaginal secretion of a rabies patient.5. Take pre exposure immunization if u fall

under “At Risk” group.6. Veterinians should wear

gloves,glasses,masks and long sleeved aprons while examining rabid animals.

7. Protect yourself from dog bites.

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National Rabies Control Programme • Agriculture ministry of india had launched a canine

control program during 6th five year plan.• Pilot project was launched during the 11th Plan :

Ahmedabad, Bangalore, Pune, Madurai and Delhi.• The government made it a priority disease for control

under the 12th Five Year Plan.• All 35 States/UTs will be covered.• The programme will include :1. Training health professionals to deal with animal

bites.2. Awareness creation.3. Minimizing animal bites.

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National Rabies Control Programme • India’s pilot project under the National Rabies Control

Programme was launched on 13 March 2015 in Haryana.• Humane Society International/India in collaboration with the

Animal Welfare Board of India and the state Government of Haryana. undertook the joint initiative.

• It addresses the management of street dog issues through mass awareness, community engagement, humane catching of street dogs, effective rabies diagnosis and improving dog bite management.

• Program entails dog census, mass sterilization and mass immunization of street and pet dogs to cover at least 70 percent of their population.

• The launch also saw the inauguration of ‘INDIA ONE’; a convoy developed as a part of the Anti-Rabies Task Force to conduct sterilization and rabies vaccinations for dogs in rural locations across India.

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World Rabies Day

• September 28 is observed as World Rabies Day, a global health observance that seeks to raise awareness about rabies and enhance prevention and control efforts.

• First co-sponsored by CDC and the Alliance for Rabies Control (ARC) in 2007, World Rabies Day has been celebrated in countries throughout the world.

• It is an excellent time to take steps that can help prevent and control rabies, such as vaccinating pets including dogs and cats and providing education on how to avoid the animals that typically transmit rabies: raccoons, bats, skunks, and foxes.

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Newer vaccines:• The new : anti-rabies human monoclonal antibody

(RMAb).•  The final phase of human trials are being conducted in

200 patients at different centres across India.• Field Trials of New Oral Rabies Vaccine for Use in

Raccoons, Other Wildlife.• RT-PCR.

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References• WHO Technical Report Series No. 982, 2013.• WHO Expert Consultation on Rabies Second report.• Communicable Disease Control Chapter I – Management of Specific Diseases Rabies May 2015.• www.apcri.org • Institute of Development Studies, University of Sussex, Brighton, England.Public Health Foundation of India,

ISID Campus, 4 Vasant Kunj Institutional Area, New Delhi, 110070, India.

• Role of reverse transcriptase polymerase chain reaction for the diagnosis of human rabiesManisha Biswal, Radha Kanta Ratho & Baijayantimala MishraDepartment of Virology, Postgraduate Institute of Medical Education & Research,Chandigarh, India Received February 8, 2010

• WHO Guide for Rabies Pre and Post Exposure Prophylaxis in Humans Updated 2013• Suryakantha AH.Community medicine with recent advances.epidemioloy of communicable

diseases.rabies,2014,3:489-501.• Briggs DJ et al. Antibody response of patients after postexposure rabies vaccination with small intradermal

doses of purified chick embryo cell vaccine or purified Vero cell rabies vaccine. Bulletin of the World Health Organization, 2000, 78:693–698.

• CDC : http://www.cdc.gov/ncidod/dvrd/rabieshttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5350a1.htm• Harverson G, Post-exposure intradermal antirabies vaccine: a cheaper alternative for developing countries,

Trop Doct. 1984 Apr;14(2):67-70. • Human and dog rabies prevention and control: report of the WHO/Bill & Melinda Gates Foundation

consultation, Annecy, France, 7–9 October 2009. Geneva, World Health Organization. (WHO/HTM/NTD/NZD/2010.1); http://whqlibdoc.who.int/ hq/2010/WHO_HTM_NTD_NZD_2010.1_eng.pdf.)

• WHO: http://www.who.int/mediacentre/factsheet/fs099/en

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Thank you