Rabies is entirely preventable, and vaccines,
medicines, tools, and technologies have long
been available to prevent people from dying of
dog-mediated rabies. Nevertheless, rabies still
kills about 60 000 people a year, of whom over
40% are children under 15, mainly in rural areas
of economically disadvantaged countries in Africa
and Asia. Of all human cases, up to 99% are
acquired from the bite of an infected dog.
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Rabies: a fatal zoonotic threat
1. Hydrophobia, Lyssa
PREPARED BY: Dr. SHUBHAM SAINI
I.d. no. – 43586
DEPTT. OF Veterinary public health & epidemiology
C.v.a.sc., G.b.p.u.a.t. pantnagar
2. a viral disease affecting the CNS of warm-
blooded animals, including humans.
has a long incubation period (~six
months) and symptoms may take several
weeks to appear after infection.
one of the most deadly zoonoses. (WHO)
always fatal in animals once symptoms
appear.
Each year, it kills nearly 60,000 people
worldwide, mostly children in developing
countries. (OIE)
has been recognized for centuries. It
wasn’t until the 1880’s when work done
by Louis Pasteur identified a virus as the
cause of the disease.
listed in the World Organization for
Animal Health (OIE) Terrestrial Animal
Health Code (Multiple species
diseases, infections and infestations
list) and must be reported to the OIE.
3. The rabies virus is a neurotropic RNA
lyssavirus (lyssa=rage), a group of
viruses responsible for causing
encephalitis
Family - Rhabdoviridae, Order -
Mononegavirales
currently 7 known genotypes of
Lyssavirus. Lyssavirus type 1 is the
classic rabies virus.
Rhabdo in Greek identifies the
characteristic bullet or rod-shape of
the viruses.
The RNA of RABV encodes 5 proteins,
including the G glycoprotein that
carries the main antigenic sites.
Source: MSD Veterinary Manual
4. Rabies is a viral zoonosis that occurs in >100
countries and territories except in Japan, UK,
New Zealand, Antarctica, Australia, Hawaii
islands and Switzerland.
number of carnivores and bat species serve as
natural reservoirs, rabies in dogs is the source
of 99% of human infections and poses a
potential threat to >3.3 billion people.
In humans, rabies is almost invariably fatal
once clinical symptoms have developed.
In a number of countries, human deaths from
rabies are likely to be grossly underreported,
particularly in the youngest age groups.
The vast majority of the estimated 55 000
deaths caused by rabies each year occur in
rural areas of Africa and Asia (WHO).
In India alone, 20 000 deaths are estimated to
occur annually; in Africa, the corresponding
figure is 24 000 (WHO).
Although all age groups are susceptible,
rabies is most common in children aged <15
years.
6. World Animal Health Information Database (WAHIS
Interface) – Version 1 (Jan-Jun 2019) for Rabies
OIE WAHIS Interface
7. Endemic in India except in Andaman Nicobar &
Lakshadweep
Occur throughout the year
About 18 000 to 20 000 cases a year and about
36% of the world’s deaths from the disease
(WHO)
76% of all rabies cases in India are reported from
rural populations
Still not a notifiable disease
Constraints - Lack of awareness of preventive
measures, insufficient dog vaccination, an
uncontrolled canine population, poor knowledge
of proper post-exposure prophylaxis on the part
of many medical professionals, and an irregular
supply of anti-rabies vaccine and
immunoglobulin, particularly in primary-health-
care facilities
According to one study, only 70% of the people
in India have ever heard of rabies, only 30% know
to wash the wounds after animal bites and, of
those who get bitten, only 60% receive a modern
cell-culture-derived vaccine
8. Strategic Framework for Elimination of Human Rabies Transmitted
by Dogs in the South-East Asia Region, WHO, 2012
9. Source: Press Information Bureau
Government of India
Ministry of Health and Family Welfare
Updated on: 04-August-2017
10. Dogs - principle reservoirs in
most of the developing countries
including India.
About 96% of the mortality and
morbidity associated with dog
bites.
Bats - major source of human
rabies deaths in the Americas.
Bat rabies - an emerging public
health threat in Australia and
Western Europe.
Other important reservoirs - Cats,
wolves, jackals, skunks, raccoons,
mongooses and monkeys.
Man is dead end of the infection -
no role in spread to new hosts.
11. 1) Bite transmission
Human infection by rabies virus usually occurs as a result of a
transdermal bite from an infected wild or domestic animal
more than 95% of human cases are due to bites by infected dogs
2) Non-bite transmission
Scratches from a rabid animal
Saliva from a rabid animal comes into contact with a victim’s
mucous membranes or fresh skin lesions
3) Rare cases have been reported via:
Inhalation of virus-containing aerosols
Human-to-human transmission through transplantation
Contracting rabies through consumption of milk, raw meat or
animal-derived tissue has never been confirmed in humans.
12. Ranges between 2 weeks and 6 years. Average -
between 30-90 days.
length influenced by:
i. site of bite,
ii. depth of bite,
iii. the amount of virus in saliva of the biting
animal, and
iv. the age and immune status of the victim.
15. INCUBATION PERIOD: Range
from 10 days to 1year (avg. is 3-8
weeks)
CLINICAL FEATURES: manifest
in two forms:
1) Furious rabies - the classic
“mad-dog syndrome’’,
restlessness, wandering,
howling, polypnea, drooling,
attacks on other animals,
people or inanimate objects &
swallow foreign objects.
2) Dumb or Paralytic rabies -
manifest by ataxia and paralysis
of the throat and masseter
muscles. Dropping of the lower
jaw is common. Laryngeal
paralysis - ‘hoarse howling’.
16. Cattle
• Most commonly affected among
farm animals.
• In the paralytic form, knuckling
of the hind fetlocks, sagging and
swaying of the hindquarters while
walking, often deviation or
flaccidity of the tail to one side,
are common signs.
• Decreased sensation over the
hindquarters is one of the best
criterions for the detection of
rabies.
• There is drooling of saliva,
tenesmus, pumping of anus and
followed by recumbency seen in
later stages.
• In furious rabies, the animal
alert, hypersensitive, violently
attack, loud and coarse
bellowing, sexual excitement and
collapses suddenly.
• Cattle are very restless, excited
and aggressive with salivation,
abdominal pain, diarrhoea and
rectal straining. Paralysis of hind
quarters occurs followed by death
in 3-6 days after the first signs of
illness.
Sheep & Goat
• Clinically the picture is similar to
cattle.
• Sexual excitement, violent attack,
vigorous wool pulling, sudden
falling and salivation are
characteristic.
• Goats are commonly aggressive,
and continuous bleating is
common.
Horse
• Muzzle tremors and pharyngeal
paresis are common.
• In addition to these abnormal
postures, frequent whinnying,
kicking, biting, colic, sudden
onset of lameness in one limb
followed by recumbency, high
stepping gait, blindness,
recumbency, paddling,
convulsions and terminally
paralysis.
Pig
• Tendency to attack, twitching of
the nose, rapid chewing
movements, excessive salivation,
walk backward and terminally
paralysis.
17. Enzyme-linked
immunosorbent assay
(ELISA) - referred as rapid
rabies enzyme immuno
diagnosis test (RREID)
Detection of rabies virus
after inoculation:-
a) Cell culture test (also
referred to as rabies
tissue culture infection
test – RTCIT) - preferred
b) Mouse inoculation test
direct rapid immuno
histochemical test (dRIT) -
use of light microscopy -
can detect rabies antigen in
fresh brain impressions
within 1 hour
19. Once acquired virtually
100% fatal
No established treatment
A palliative approach may
be appropriate for some
patients
Management is focused on
confirming the diagnosis,
preventing transmission to
in-hospital staff and
relatives and supportive
treatment and comfort and
care to the patient
20. A three-pronged approach -
All carry equal importance and
should be done simultaneously
as per the category of
exposure:
1. Management of animal bite
wound(s)
2. Passive immunization with
Rabies Immunoglobulin
(RIG)
3. Active immunization with
Anti-Rabies Vaccines (ARV)
22. Cleansing with soap and
water (minimum 10min)
Chemical treatment-
virucidal agents - 70%
alcohol, povidine iodine,
tincture iodine, etc
Local infiltration of rabies
antiserum
Antibiotics
Tetanus toxoid
Wound not to be dressed or
bandaged
Suturing – if inevitable -
done with antiserum
infiltration locally
23. For Category III bites, combined with vaccine.
provides passive immunity in the form of ready-made anti-
rabies antibodies.
Two types of RIGs are available:
Equine Rabies Immunoglobulin (ERIG): dose is 40 IU
per kg of body weight.
Human Rabies Immunoglobulin (HRIG): dose of 20 IU
per kg of body weight.
RIG should be infiltrated into the depth of the wound and
around the wound as much as anatomically feasible.
Remainder should be injected at an intramuscular site
distant from that of vaccine inoculation.
24. For all Category II and III exposures irrespective of age
and body weight.
Provides active immunization.
25. The post-exposure schedule prescribes intra-
muscular doses of vaccine given as 0.5 or 1ml
depending on the vaccine type as four or five doses
over four weeks.
The “ESSEN” regimen administers five
intramuscular doses of rabies vaccine on days
0,3,7,14,28. The four dose regimen prescribes 2 doses
(one on each deltoid/thigh) on day 0 followed by one
dose each on days 7 and 21.
However, recent WHO guideline suggest that in
healthy, fully immunocompetent persons who have
received wound care, RIGs and WHO pre-qualified
rabies vaccine, an alternative PEP vaccine regimen
consisting of four doses administered IM on days 0,
3, 7 and 14 can be used as an alternative to the five
dose regimen.
In other cases, including WHO category II exposure,
the use of the five-dose Essen regimen on days 0, 3,
7, 14 and 28 should continue.
Abbreviated multi-site intramuscular regimen
(2-1-1, Zagreb regimen) : In this regimen, one dose
administered in the right and second dose in the left
deltoid on day 0 followed by one dose in the upper
arm on days 7 and 21. This saves two clinic visits and
one dose of vaccine.
26. The updated Thai Red Cross
Intradermal (ID) Regimen
(2-2-2-0-2) consists of one dose of
vaccine (0.1ml) given
intradermally at two different
sites usually right and left arm on
days 0,3,7 and 28.
Another is the Oxford or eight
site ID regimen (8-0-4-0-1-1).
One dose of 0.1 ml is
administered intradermally at
eight different sites (upper arms,
lateral thighs, suprascapular
region, lower quadrant of
abdomen) on day 0. Four ID
injections on both upper arms
and lateral thighs on day 7
followed by one injection on days
28 and 90.
27. For persons who are at a high risk (veterinarians, those
working in rabies research or diagnostic laboratories,
animal handlers, wildlife officers, people travelling to
high risk areas, children below 15 years ) - one full
dose of vaccine intramuscularly or 0.1ml intradermally
on days 0, 7 and 21 or 28 days.
Serological testing should be done every six months in
above said.
A booster is recommended if the titre falls below 0.5
IU/ml .
28. Purified Chick Embryo Cell
Vaccine (PCECV) by the
name Rabipur, is a highly
purified, potent and
efficacious vaccine
recommended by the WHO
for both pre- and post-
exposure prophylaxis
against rabies.
Purified Vero Cell Rabies
Vaccine (PVRV).
Human Diploid Cell Rabies
Vaccine (HDCV).
29. The Journal of communicable
diseases (June, 2012) - Rabies
epidemiology and control in India : A
review - Acharya Anita S et al
30. In countries where the disease is endemic,
measures include: (OIE)
public awareness and education campaigns (for
the general public, for dog owners and children);
surveillance and reporting of suspected cases in
susceptible animals;
vaccination programmes for domestic dogs;
vaccination programmes for wild animals (usually by
distributing oral vaccine baits in the natural
environment);
stray dog population control programmes, and
vaccination programmes where feasible.
research into disease dynamics, suitable vaccines and
vaccine delivery mechanisms for target populations;
Preventive measures by occupational groups regularly
in contact with animals (such as veterinarians and
animal control and wildlife officers) inc. pre-exposure
vaccination.
31. Human health component
• NCDC - nodal centre for its
implementation.
• Focus - providing timely and
appropriate management to all
animal bite victims.
• This can be attained by:
• Creating awareness in general
community to seek PEP
• Train doctors in appropriate
animal bite management
• Implement ID route of CCVs
inoculation for wider coverage in
available quantity of vaccines.
Animal health component
• AWBI - nodal centre for its
implementation.
• Focus - population survey of dogs.
• Dog population management.
• Mass immunization of pet as well
as stray dogs.
• Being pilot tested in Haryana and
Chennai.
• Approved under the 12th five year plan by MoHFW, Government of India.
• Has both human and animal health components.
32. Roadmap to Combat Zoonoses in India (RCZI) Initiative : Recent Developments in Rabies Epidemiology & Sources of Information
in India – Public Health Foundation of India, 2015
33.
34. The plan –‘Zero by
30: The Strategic
Plan’ – centres on
a One Health
approach and
addresses the
disease in a
holistic and cross-
sectoral manner
while highlighting
the important role
veterinary, health
and educational
services play in
rabies prevention
and control.
The rabies virus is present on all continents except Antarctica. Some countries have implemented vigilant control measures and succeeded in eradicating the disease to meet the OIE requirements for rabies free status.
1) URBAN RABIES:
• From Dogs and cats. • 99% cases in India • A single infected dog capable of transmitting over an area of 40km
2) WILDLIFE RABIES/SYLVATIC RABIES:
• Unidentified reservoir of infection • Foxes, jackals, hyenas, skunks etc. • Enzootic in south America by mongoose • Transmit infection among themselves and to dogs and man
3) BAT RABIES:
• Latin American countries, USA • Vampire bats-feed on blood of man and animals • Found from Mexico to northern Argentina • Cause havoc to cattle population • Not reported in India • Constant source of infection to man and animals • Transmission by bites and aerosols
Infection through inhalation of the virus has been documented, for example, in the environment of a densely populated bat cave.
Human-to-human transmission through bites is theoretically possible but has never been confirmed.
In the Americas, bats are now the major source of human rabies deaths as dog-mediated transmission has mostly been broken in this region. Bat rabies is also an emerging public health threat in Australia and Western Europe.
The proximity of the site of virus entry to the CNS increases the likelihood of a short incubation period.
The disease can be transmitted via the saliva of an infected animal to other animals and humans before the onset of clinical signs of the disease in the infected animal.
-After inoculation the virus replicates in the striated muscle or connective tissue at the point of inoculation and enters the peripheral nerves through the neuromuscular junction.
-The estimated speed of virus migration is 15–100 mm per day. There is a wide spread CNS involvement but few neurons infected with the virus show structural abnormality.
-The virus then moves from the CNS via anterograde axoplasmic flow within peripheral nerves, leading to infection of some of the adjacent non-nervous tissues: for example, secretory tissues of salivary glands, thus allowing further transmission. The virus is widely disseminated throughout the body at the time of clinical onset of the disease.
Initial symptoms include a fever with pain and unusual or unexplained tingling, pricking, or burning sensation (paraesthesia) at the wound site. As the virus spreads to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops.
There are two forms of the disease:
1- People with furious rabies (mostly encephalitic) exhibit signs of hyperactivity, excitable behaviour, increased salivation, hydrophobia (fear of water) and sometimes aerophobia (fear of drafts or of fresh air). Death occurs after a few days due to cardio-respiratory arrest.
2- Dumb or Paralytic rabies accounts for about 30% of the total number of human cases. Runs a less dramatic and usually longer course than the furious form. Four patterns are noted—
flaccid paralysis, quadriplegia, transverse myelitis and an ascending form simulating the Guillain-barre syndrome
Muscles gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the under-reporting of the disease.
Confirmed by virus isolation, detection of anti-rabies antibody, viral protein or RNA. Serum and spinal fluid are tested for antibodies to rabies virus.
Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles (nuchal skin biopsy).
Rabies virus nucleic acid can also be detected in various biological fluids and samples (eg, saliva, cerebrospinal fluid and skin biopsies) by RT-PCR.
more than one test should be used to confirm rabies.
dRIT development will enable transfer of this diagnostic capability to endemic regions where cost precludes laboratory confirmation.
Neuroblastoma cell lines, e.g. CCL-131 is commonly used for isolation of rabies virus.
Serological testing is rarely useful for ante-mortem diagnosis because of late or failing seroconversion and the high mortality rate of host species, but is very useful for assessing seroconversion following vaccination and for epidemiological studies.
Historical reliance on the detection of accumulations of Negri bodies is no longer regarded as suitable for diagnostic assessment because of low sensitivity, and alternative laboratory-based tests have been developed to conclusively confirm infection. Demonstration of Negri bodies by Sellers method (for unfixed sections) or Mann’s method (for fixed sections).
Palliative Rx inc. • Antianxiety drugs and sedatives • Muscle relaxants with curare like action • Ensure hydration and diuresis • Cardiac and respiratory support
In India, tests for rabies diagnosis are available at very few selected centres - NCDC, New Delhi & NIMHANS Bangalore.
NCDC, New Delhi is also a WHO Collaborative Centre for Rabies Epidemiology in South East Asia.
NIMHANS, Bangalore is the WHO Collaborating Centre for Reference and Research in Rabies.
- Bite by all wild animals should be treated as category III exposure.
- A number of experimental therapies (e.g., vaccines, antiviral agents, antibodies to rabies virus, ketamine and/or the induction of a therapeutic coma) have been tried in the past, but were usually ineffective. Some treatments, such as therapeutic coma, are controversial. One young patient who recovered well was treated with ribavirin, amantadine and supportive care including therapeutic coma (the “Milwaukee protocol”); however, the same treatment protocol has been unsuccessful in a number of other patients. Two young patients recently recovered with only supportive therapy. Currently, the CDC does not advocate either supportive therapy or aggressive treatment, and instead states that either may be offered. If treatment is successful in sustaining life, the patient may be left with permanent, and possibly severe, neurological deficits.
Wound cleansing is especially important in rabies prevention since, in animal studies, thorough wound cleansing alone without other post exposure prophylaxis has been shown to markedly reduce the likelihood of rabies.
- Rabies immunoglobulin for passive immunization is administered only once, preferably within 24 hours after the exposure (on day 0 along with the first dose of anti-rabies vaccine).
- If HRIG was not administered when vaccination was begun, it can be administered up to seven days after the administration of the first dose of vaccine. Beyond the seventh day, HRIG is not recommended since an antibody response to the vaccine is presumed to have occurred.
- It is absolutely essential that every batch of CCVs have minimum potency of 2.5 IU per IM dose, irrespective of whether the vaccine is administered by IM or ID route.
- Humoral antibodies play an important role in protection against rabies. Anti-rabies neutralizing antibody titre of 0.5 IU/ml or more in serum is considered as protective. This level is achieved in most healthy individuals by day 14 of a post-exposure regimen, with or without simultaneous administration of rabies immunoglobulin.
For adults, the vaccination should always be administered intramuscularly in the deltoid area (arm). For children, the anterolateral aspect of the thigh is also acceptable. The gluteal area should never be used for rabies vaccine injections because the fat present in this region retards the absorption of antigen and hence impairs the generation of optimal immune response.
- The Drug Controller General of India (DCGI) has approved the following vaccines for intradermal use:
Verorab (Aventis Pasteur (Sanofi Pasteur) India Pvt ltd, Rabipur (Chiron Behring vaccines Pvt ltd ), Abhayrab (Human Biologicals Institute), PVRV vaccine by Pasteur Institute of India, Coonoor.
- Use of vaccine by intradermal route provides two advantages. First, the requirement of the vaccine is less, almost one fifth of the IM dose, which reduces the number of visits by the patient. Secondly, as the requirement of vaccine reduces, the cost also decreases.
- Only two vaccines are considered safe and efficacious for eight site regimen. They are:
Human Diploid Cell Vaccine by Aventis Pasteur and Purified Chick Embryo cell vaccine by Chiron Vaccines.
Humoral antibodies play an important role in protection against rabies. Anti-rabies neutralizing antibody titre of 0.5 IU/ml or more in serum is considered as protective. This level is achieved in most healthy individuals by day 14 of a post-exposure regimen, with or without simultaneous administration of rabies immunoglobulin.
- All the rabies vaccines can be used for IM regimen, but only PVRV and PCECV are approved for ID.
- Production of Nervous Tissue vaccine has been stopped since 2004.
- Government of India on recommendation of WHO has introduced the Intradermal Rabies vaccination (IDRV) since February 2006.
All successful rabies eradication campaigns have included measures combining control and vaccination of stray dog populations and vaccination of all owned dogs.
Vaccination campaigns are set up with the aim of achieving coverage of around 70% of the canine population in a zone where rabies is endemic.
In countries where the disease is endemic, measures are implemented to address and reduce the risk of infection in animal populations susceptible to the disease (wildlife, stray animals, and domestic animals under their owner’s control) and create a buffer between the animal source of the disease and humans.
Rabies control programmes are a major challenge for many countries. Nevertheless, the cost of vaccinating dogs remains minimal compared to the actual cost of emergency post-exposure treatments for people who have been bitten. Indeed, 10% of the overall cost of these treatments would be sufficient to considerably reduce or even eliminate canine rabies.
WHO, the World Organisation for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO) and the Global Alliance for Rabies Control (GARC) have established a global “United Against Rabies” collaboration to provide a common strategy to achieve "Zero human rabies deaths by 2030".
Rabies virus is predominantly neurotropic and kills the host in short period after it has entered the neurons. Before death, virus reaches salivary glands and is excreted in saliva. The saliva gains entry into another host through a pre-existing breach in skin when mere licking or contamination is adequate or the bite of the rabid animal creates a mechanical breach of skin through which the rabies virus gains entry.
