From the site of bite the virus enters a nerve and via axoplasm reaches the central
nervous system (CNS). Thus, there is no viremia and the virus is not accessible to the
normal immune mechanism of the body. Only after travelling efferently from CNS via mostly
autonomic nerves to different (target) organs the antibody production starts. But by that
time the patient’s brain stem neuronal cells are destroyed and he dies in a day or
two either due to respiratory paralysis or due to cardiac arrest.
Theoretically the saliva of a hydrophobia patient is infectious and occasionally such
transmission is reported. But the well documented transmission is through corneal
transplantation. Hence, confirmation of cause of death, particularly in neurological cases
is very important before corneal transplantation. Besides it is also important to avoid
contact with saliva and secretions of a rabies patient.
There are 3 recorded survivors of rabies, 2 from USA (1970and1977) and 1 from Argentina
(1972). All had received some immunoprophylaxis and they recovered following intensive
care. No specific drug/therapy is responsible for their recovery (Kaplan, et. Al.). In
India, 2 Survivors are reported from AIIMS, Delhi (1988) but they are not well acclaimed
due to lack of laboratory evidence in diagnosis.
The saliva of a hydrophobia patient contains the rabies virus and is infective. If there
is suspicion about contact with saliva of hydrophobia patient during kissing the contact
person requires 5 doses of TCV or class II schedule of NTV. If there are ulcers in the
mouth of the contact then even serum or HRIG must be given.
Rabies virus is present in the semen and to some extent in vaginal secretions. In some
patients, priapism, increased sexual libido and indulgence is seen (both in men and women
patients). Hence, in the contact (exposed) person 5 doses of TCV as PET (or class II of
NTV schedule) should be given. If there is doubt of class III exposure viz. Abrasion on
penis or in vagina then even serum or HRIG must be given.
In humans, rabies virus is not known to cross the placental barrier and consequently the
foetus is safe. Hence, the hydrophobia pregnant woman should be clinically managed
and if induction of pregnancy / caesarian section is possible the obstetrician shall do it
with due “personal precautions” and immunoprophylaxis (3doses of TCV usually or
if any accidental negligible exposure/doubt 5 doses of any TCV).
The newborn has to be given 5 doses of any TCV as PET or if the hydrophobia mother (who
will invariably die) is poor then class I PET schedule of NTV should be given.
Rabies is 100% fatal and hence there is no contraindication to PET at all.
All rabies vaccines including Nerve Tissue vaccines are known to be safe during
pregnancy. Besides pregnant woman with h / o animal bite are susceptible to rabies and
should be given PET. Under no circumstances MTP should be done following ARV
Modern TCVs are considered generally safe during pregnancy (as of
reports available till now) and no teratogenicity or other adverse effects are reported
during pregnancy. However, pregnant woman wherever possible may avoid exposure and
pre-exposure vaccination. As Rabies is a 100% fatal disease, there are no absolute
contraindications for prophylaxis and post exposure prophylaxis must be started even in
pregnant and lactating women.
All anti-rabic vaccines are inactivated vaccines and can safely be
given to lactating mothers and it has no effect on the breast fed baby.
Rabies Neutralizing Antibody titre of > 0.5 IU / ml of serum in the vaccine is
considered protective. The facilities for this test are available at select centres like
CRI, Kasauli, Himachal pradesh; Pasteur Institute, Coonoor, Tamilnadu; NICD, Delhi NIV,
Pune; NIMHANS, Bangalore and few other centres.
Antibody tests viz., Rapid Fluorescent Focus Inhibition Test (RFFIT), Mouse Neutralization
Test (MNT), etc., are some sophisticated tests and are done only at select few reference
centres in the country. Besides ARVs, whether NTV or TCVs with proper cold chain
maintenance if given according to the approved schedule, no testing of antibody is
required on a routine basis.
No where in the world is there a single shot ARV [including the often mistaken notion
about expensive HDCV] nor is there a ARV which gives lifelong immunity.
NERVE TISSUE VACCINE
If a person has started NTV then if he shifts to TCV full course of TCV (5 or 6 doses)
should be given irrespective of doses of NTV received earlier. If a person who started TCV
has received minimum 3 doses (day 0, 3 and 7) then the remaining injections of NTV as per
schedule should be given. If he has received 1 or 2 doses of TCV then full course of NTV
as per schedule should be given.
It is generally advisable to abstain from alcohol during the ARV administration as it may
affect the immune response.
In case of TCVs (HDCV/PVRV/PCEC) the dosage is same for all age groups. However, in case
of NTVs it is lesser quantity for younger age groups (lower body weight) according to
The efficacy (ability to protect against rabies) of NTV is known to produce neuroparalytic
accident after 5-7 injections in 1 in 4000 to 11,000 persons. Besides the local and other
systemic side effects of NTV is about 50-70% and often lead to defaults, mostly local
pain, itching, redness, occasionally fever and in about 2-8% persons. Hence, TCVs are
The myelin residue (of sheep brain) in the NTV is known to produce
neuroparalytic accident after 5-7 injections in 1 in 4000 to 11,000 persons. Besides the
local and other systemic side effects of NTV is about 50-70% and often lead to defaults,
wheras in TCVs adverse events are mild, transient, mostly local pain, itching, redness,
ocasionally fever and in about 2-8% persons. Hence, TCVs are safer.
ARV can be given with other EPI vaccines. However, TCV should be given at the recommended
site (deltoid or thigh, IM) and at a site different from EPI vaccine.
It can be given.
TCVs are preferred to NTV and the Day 0 dose (1st injection) should preferably be doubled
and given at two sites (deltoids or thighMI) in young children. However, if facilities for
antibody titres estimation are available it should be done. Rabies immunoglobulins are
life saving in AIDS patients when the CD4 counts are low and sero conversion is
TCVs are preferred to NTVs and the Day 0 dose (1st injection) should preferably be doubled
and given at two sites (deltoids thigh IM in young children). However, if facilities for
antibody titres estimation are available it should be done.
The “potency” is the capacity or antigenic value of the vaccine to
induce immune response. NTVs it is a minimum of 0.3 antigenic value and for TCVs it is
>2.5 IU / dose.
Yes. Hence, their dosage and schedules viz., number of injection, boosters, etc.,
If PET vaccination is required TCVs are to be preferred. If facilities permit antibody
titre estimation is recommended. Serum or RIG (Equine or Human) if required (class III)
should be used.
No. BPL loses its carcinogenicity because of its hydrolysis during the process of
inactivation of rabies virus where it is used in final concentration of 1:4000.
NTV should be immediately replaced with TCV. Patients should be put on absolute
bed rest. Corticosteroids in highest tolerable doses are given parentally. Supportive
therapy with vitamin B complex, Vitamin C and calcium may be given. After recovery,
steroids are tapered off. The dose of TCV should be doubled during this period and if
possible antibody titre estimation must be done.
TISSUE CULTURE VACCINES
The verocell lines are thoroughly tested for their capability of inducing malignancy in
most susceptible animals even in that passage (subculture) which is beyond the passage
used for production of vaccine. Verocell lines have been shown not to produce any
malignancy in both in vivo and in vitro systems, The verocell line used for production of
PVRV has been approved by WHO and is part of American type culture collection (ATCC) which
is accepted worldwide. The same cell line is now used for production of even polio
Vero line used for PVRV (Verorab and verovax-R) is free of any SV40 virus
One dose of 0.1 ml of PVRV (Verorab or Verovax-R) should be given at each of two
sites, either the forearm or the upperarm, on the days 0, 3, 7, and one dose at one site
ondays 30 and 90. It is to be administered in specialised centres and by trained personnel
only with adequate laboratory facilities (for antibody titre estimation facility in the
In the abbreviated multisite schedule, (also known as Zagreb schedule), the 2-1-1
regimen, one dose (of HDCV or PVRV or PCEC) is given in the right arm and one dose in the
left arm (IM) on day 0 and one dose applied intramuscularly in the deltoid region on day 7
and 21. Though this is WHO approved it is not approved by drug controller of India and
hence should not be used by medical practitioners in India.
Since mixing of biological products can lead to physical or chemical interaction and in
the absence of specific studies the TCVs which are costly should not be diluted with any
other diluent (other than provided with the vaccine.)
As freezing and thawing (liquifying frozen substances) is known to affect the potency of
the vaccine, it should not be used.
Antibody tests viz., Rapid fluorescent focus inhibition test (RFFIT), Mouse neutralisation
test (MNT), etc. are some of the sophisticated tests and are done only at select few
reference centres in the country. Besides ARVs, whether NTV or TCVs with proper cold chain
maintenance if given according to the approved schedule, no testing of antibody is
required on a routine basis .
All TCVs viz HDCV, PVRV, AND PCEC are freely interchangeble. This is done in
practice either for cost reason, or due to sudden non availability of one brand or due to
allergy to one of the TCVs.
36. A dog/cat became unavailable or disappeared for observation
from day 4 and the patient was given TCV on day 7 (3rd dose). Subsequently from day 8 it
became reavailable (reappeared). What should be done?
The dog or cat should be observed till day 10 or wherever possible upto day 15
and if healthy and alive then the 4th injection due on day 14 is not required. But the
earlier 3 injections (on day 0,3,&7) may provide protective antibody titres for the
“pre-exposure schedule duration” of 1 year only.
If rabies in the dog cannot be confirmed by postmortem then it is presumed to be
rabid and the remaining (not to restart fresh) 3 doses of day 7, 14 and 28 (or 30) shall
be given as close to the original dates of schedule and all the 5 injections completed by
For all practical purposes from safety and sero-efficacy point of view all are
equally good and approved by WHO. But each vaccine has its own merit which the doctor
should consider while using it in a given situation/case
a) HDCV : This is of homologous (human) origin, considered by many as the
“purest” antigen; the popular vaccine in the developed world and often used as
“Gold standard” in TCVs. But it is the most expensive TCV (about 930/-) per dose
and is imported from France to India.
b) Rabipur (PCEC vaccine) : It is a thermo stable vaccine, it is
indigenously produced in India by Aventis Pharma at Gujarat. It is also
approved by the Food and Drugs administration (FDA) of USA. Besides it is exported from
India to Nepal, Bangladesh, and Srilanka, thus signifying its quality.
c) Verorab (PVRV) : It is a thermo stable vaccine, has a dose of 0.5 ml
and is the WHO reference vaccine for intra-dermal regimen. It is imported from
d) Verovax-R (PVRV) :It is a thermo stable vaccine, has a dose of 0.5 ml
and is the WHO reference vaccine for intra-dermal regimen. It is imported from
France . The diluent is in prefilled syringe and is convenient to use for an otherwise
e) Abhayrab(PVRV) :It is a thermo stable vaccine,
produced in India by Human Biologicals Ltd., a Government undertaking.
Vaccinating the pet dog is primarily to protect it against contracting rabies following
bites by stray rabid dogs/animals. No veterinary vaccine offers 100% protection against
rabies. Rabies is enzootic in our stray animal/dog population. The facility of protective
antibody titre test (in vaccinated dog) is available only at a few centres in the country.
The facility to quarantine the bitten vaccinated pet is limited and difficult. In veiw of
the above facts and practical realities, rabies being 100% fatal, we take no chances and
start PET (immunisation) in the bitten person and presume the vaccinated dog to be
incubating rabies ( and infective) and simultaneously observe the dog.
However, in extremely rare situations exception to the above thumb rule can be made at the
professional discretion of the treating physician.
Genarally the currently available ARS (equine) are purified (enzyme refined and pepsin
digested) and safe and the reported anaphylaxis is 1:40,000 patients. However , in 1-6% of
the patients, even after a negative skin test there may be adverse reactions ranging from
serum sickness like reaction to anaphylaxis. Hence, it is always safer to keep emergency
drugs (like Wysolone, antihistaminics, oxygen etc.) on hand and ARS preferably be given in
an institutional set up.
The immediate reaction are anaphylactiod type viz. Hypotension, dyspnoea, syncope,
urticaria. Serious type of quinckies edema or anaphlactic shock is rare (<1%). This is
treated with adrenaline, oxygen, artificial respiration, hydrocortisone and
antihistamines. Serum sickness like reactions (1% subjects) may occur after 6 days. They
consist of an inflammatory reaction due to compliment activation and formation of immune
complexes (type III hypersensitivity reaction). Clinical symptoms are fever, pruritis,
rash, urticaria, adenopathy, and arthralgia. This is treated with non steroidal anti
inflammatory agents and anti-histamines. If steroids are used an extra dose of TCV should
be used for each remaining schedule of vaccination. Ideally in these situations antibody
titre estimation is required and if possible this must got done at the nearest centre.
Ideally the patient should be persuaded to buy HRIG which is
practically safe and no skin test is required. If the patient cannot afford HRIG, as the
situation is life threatning under signed informed consent a heroic measure of
desensitisation for horse serum may be considered in a institution set up. Alternatively
administration of ARS under cover of antihistamines can also be attempted in a institution
As a last resort if HRIG is not affordable and desensitisation for
ARS (or under cover of antihistamines) is not possible the wounds must atleast be
thoroughly flushed with povidone iodine or surgical spirit or tincture iodine (to
neutralise the virus) and the patient should preferably be given atleast TCVs with two
doses on day 0 (in both deltoids).
Dilute it with normal saline (upto equal volume) and use it both for
local infiltration (as much as possible) and any balance given in gluteal IM
Dilute it with normal immunoglobulin (unto rqual volume) and use as
described above for ARS.
CRI, kasauli, HP : 5 MI vial, 1500 IU (300 IU per ML)
1/300 x 40 IU x body wt (kgs)= Dose in ML.
PM,ARS, France : 5ml vial, 1000 IU (200 IU per ML)
1/200 x 40 IU x Body wt (kgs)= Dose in ML
RIG [Berirab, Berirab-p, Imogamrab] = 2 ML (300 IU) ampoul 5ML (750
1/150 x 20 IU x Body wt (KGS) = Dose in ML
If a wound has healed or healing (scab is formed) if should not be
disturbed and the total dose should be given IM gluteal only.
The combined use of ARS/HRIG (passive immunity) and vaccine (active
immunity) must be carefully adjusted if the effects of one are not to cancel out the
effects of the other. Hence ideally the serum must be given within 72 hours of starting of
vaccine. Hewever, where serum is inevitably to be given beyond 72 hours of starting
vaccine an additional extra dose of vaccine (TCV) is recommended for IM deltiod/thigh
Human normal immunoglobulin (polyvalent) cannot substitute HRIG.
The local infiltration of wounds with ARS/HRIG is of paramount
importance as it neutralises any residual virus still present in wound [after wound
treatment] and thus prevents entry of virus into a nerve ending at bite site.
Besides ARS / HRIG also provides readymade rabies antibody before an
active response to vaccine takes place. The earliest protective level of antibody [>
0.5 IU / ML] response to modern TCVs is by day 14. However, in severe bites/bites close to
brain the incubation may be as short as 4-10 days. In these cases HRIG /ARS is lifesaving.
After ARS HRIG administration the rabies antibody can be detected within 24 hours, with
HRIG it reaches a level of 0.1 IU / ML at 3 days and declines with half – life of about 21
days, whereas in ARS (Equine) this is still of a shorter duration. Hence, ARS /HRIG
provides immediate passive protection before active protection to vaccine is induced by
RABIES IN ANIMALS
No. Hence bat bites do not require post-exposure Immunisation.
No. Rabid dogs can drink water and even swim in water.
If they have heated/boiled the milk the virus is killed at 60’C
in 30 seconds. They do not require any vaccination.
However, if they are still very apprehensive and unconvinced or
unsure about raw milk consumption, they may be advised PET with tissue culture vaccine
viz. 3 doses in doubtful exposure or 5 doses in possible exposure, at the discretion of
physician viz. Day 0,7, and 21(or 28) or day 0,3,7,14 and 28 (or 30). However, if they
have consumed raw milk, full course of PET (5 dose IM, gluteal).
Carrier state in dogs is very rare and are considered freaks of
nature. Besides these dogs (mostly studied in experimental Laboratories) excrete the virus
intermittently and sometimes in low titer. Consequently the observation of dog for 10 days
and appropriate simultaneous immunisation of bitten person is considered valid even by WHO
It is valid. However, in Europe (rabies free areas) it is 15 days
and in india too wherever permissable / feasible this may be considered, only in
individual cases and on merit.
Thoroughly wash the wound with a detergent soap. Apply a household
antiseptic viz. Tr. Iodine, etc. and consult a veterinarian immediately.
Occasional such reports are seen which base their diagnosis of
rabies in man on clinico-epidemiological basis (no laboratory diagnosis) and the most
important thing is the laboratory confirmation of rabies virus secretion in the saliva of
the biting animal (still alive) is not available. Hence, the so called carrier state of
rabies (otherwise healthy) is yet to be conclusively established; and till such time the
current practice of simultaneous starting of vaccination and observation of animal shall
He should receive full course of NTV or 5 doses of TCV. In extremely
rare cases if a person has eaten raw meat of a provenly (laboratory Diagnosis) rabid
animal and if he has oral lesions or ulcers or is apprehensive, he may even be given
ARS/HRIG [full dose in gluteal IM on day o along with first dose of vaccine].
Modern veterinary vaccines (tissue culture) are efficacious. If in
the last 2 years a dog has received 2 doses it is generally considered protected. Ideally
its blood should be tested for protective antibody titre level but this is rarely
practicable/feasible due to scare facilities in our country. Consequently a bite by even a
vaccinated dog is presumed to be rabid and the bitten person is given post exposure
immunisation [day 0, 3,. Injections] and after 5 days [day 7 in case of TCVs] if the dog
is healthy no further vaccination is required. But the dog must be further observed till
10 days from day of bite (wherever possible up to 15 days) and if it is healthy and alive
no further vaccination is required. However, 2 doses of TCV [day 0 and 3] received are not
immunogenically protective and will go waste. Hence, in those who are in constant touch
with animals, the person may be advised to take the 3rd injection on day 21 or
28 (3rd dose) which will offer the same benefit of pre-exposure prophylaxis
with slight modified schedule in this case (day 0,3 and 21 or 28).
If facilities are available post-mortem of the dog for confirmation
of rabies is required. If not possible, (or if the post mortem proves rabies) all those
who came in contact with the saliva of the animal (directly or through its fomites) should
be given PET.
Provocation is subjective and relative and specific to each dog/cat.
However, obvious gross prococation viz., stamping, hitting, chasing, etc. Possibly suggest
that the animal may not be rabid. However, the wound treatment of animal bites is the
Though human ARVs may not be harmful to animal, there is no
dose-weight correlation of immune response nor their efficacy known in animals. Besides
the incubation period of rabies in animals is long. Hence, it is advisable to reserve
human vaccines for human use only.
The wound should be immediately washed with a detergent soap and
Cold water, any household antiseptic like dettol/savlon, Tr.Iodine should be applied. If
the stray dog is suspected to be rabid then the petdog should ideally be put to sleep. But
if the owner is not ready or the rabid status of stray dog is not known then postexposure
vaccination of the pet with tissue culture vaccine and simultaneous for upto 2 months
(upto 6 months desirable) for possible signs of rabies in it. During this period for any
sickness in dog, the owner should take the dog to the veterinarian to get rabies ruled out
at the first instance.
As rabies is enzootic (prevalent in stray dogs) if pet unvaccinated
dog is bitten by a stray rabid dog it will develop rabies and later pose threat at home to
all family members.
Vaccination of the dog is to protect it against rabies following
bite by a (stray) rabid dog. If potent TCV (veterinary) vaccine is given correctly as per
schedule (preexposure) it will mostly prevent rabies in the vaccinated dog. But in
enzootic (rabies prevalence in animals) India, where protection status of vaccinated dog
by antibody estimation (RFFIT/MNT Test) is not possible due to scarce facilities and such
time rabies is eliminated from the stray dog population in our country, the need for PET
in exposed persons continues.
Ideally such dog should be humanely killed (put to sleep ) by a
veterinarian since postexposure prophlaxis is not
very successful. Such dogs pose risk (source of infection) to others and if the owner
[much against professional advice] goes for postexposure immunisation of the dog, he
should be informed of this risk.