Rabies continues to be a major problem in India even as
we enter the 21st century without clear national policies for
its control, in contrast to the progress made by most other
countries in Asia. It is believed that more than 50 per cent of
all rabies cases worldwide occur in India. Our neglect of rabies
may be a matter of lack of political will or of professional
competence and dedication of the public health leadership; it is
also a matter of great concern from the point of view of
violation of ethics and human rights. This latter issue is the
subject of this essay.
Elements of rabies prevention
The main elements of rabies prevention are control of rabies in
dogs and cats, control of stray dogs in human habitats, post-
exposure vaccination of persons after animal bites and pre-
exposure vaccination of persons at risk. Most owners of indoor
(dog and cat) pets get them vaccinated against rabies. Domestic
outdoor dogs and cats are owned usually by less affluent
families and their vaccination is often neglected. These animals
are more likely to come in contact with stray animals and are at
greater risk of rabies than are indoor pets. Stray dogs and cats
are the main vectors maintaining rabies virus circulation within
human communities. Infection among them is replenished from the
sylvatic cycle of rabies virus, about which no serious studies
have been conducted in recent decades (1).
Controlling stray dogs
The problem of stray dogs has been accentuated by a government
directive t o exercise restraint in catching and destroying
them. Many places report an increase in the stray dog menace and
civic authorities are not taking action. The government is
responsible for both animals’ humane treatment and people’s
protection. If the two conflict, the government must sort things
out; perhaps only judicial involvement might clarify this
conundrum. Animal bite victims can and must take this matter to
the courts.
Stray animals need not be destroyed to control rabies; they
could be caught and sterilised or vaccinated, preferably both.
Only after the responsibilities of the different arms of the
government are clarified can we expect action from civic
authorities.
Rabies vaccines for post exposure vaccination
All civilised countries except India use safe rabies vaccines,
but India continues to use the unsafe and obsolete adult animal
brain rabies vaccine. The Semple vaccine is named after the
British director of th e Central Research institute (CRI) at
Kasauli, who developed the technique of preparing it at the turn
of the 20th century. The Semple vaccine replaced the Pasteur
vaccine which was made in rabbit spinal cords. Due to its
inherent defect of containing large amounts of myelin protein,
it induces an allergic encephalomyelitis (AEM) in some vaccine
recipients. For this reason, most countries outside Asia adopted
other methods to grow the vaccine strains of rabies virus in
duck embryo, new- born mouse brain (which has very little
myelin) or cell cultures. Today all countries (except India)
that used the Semple vaccine have switched to either cell
culture or purified duck embryo vaccines; countries such as
Vietnam use infant mouse brain vaccine.
The ethical issue of vaccine safety
Two recent developments must be mentioned here. The rotavirus
vaccine was recently found to be associated with the development
of intessusception in a rare vaccine recip ient infant. Although
it is an easily treatable condition, and though the vaccine
gives excellent protection against death due to diarrhoea and
dehydration, the Food and Drug Administration of the USA
directed that the vaccine is unsafe for human use. By definition
a vaccine must be safe even if not completely effective.
The second issue concerns the Sabin oral polio vaccine. The USA
and several European countries discontinued its use because it
is not completely safe, and a safe alternative vaccine is
already available in the form of enhanced potency injectable
polio vaccine (eIPV). The paralytic response to the vaccine
(vaccine associated paralytic poliomyelitis) occurs in one of
400,000 subjects.
AEM occurs in one in some 5,000 to 7,000 vaccine recipients. In
other words, the risk of a serious and often life- threatening
neuroparalytic episode from the Semple vaccine is nearly 100
times that of the Sabin vaccine. Thus, adult animal brain rabie
s vaccine is unfit for human use and only shameless and callous
societies would continue to use it. It is unethical to inject it
to any human being, since several safe rabies vaccines are
available since the 1970s. I understand that the government
under the late Rajiv Gandhi had decided to manufacture rabies
vaccine in Vero cell culture.
Reportedly, work including the construction of buildings,
procurement of equipment and training of personnel were
virtually completed when the project stopped about two years
ago. If true, the ethical issue is even more serious, since the
decision to provide an alternate vaccine was taken and then
shelved.
Ethics versus economics of Semple and other rabies
vaccines
The request to discontinue the Semple vaccine and replace it
with a safe vaccine has been debated in several conferences. The
government’s response is that it cannot afford cell culture
vaccines. The following public sector institutions manufacture
Semple vaccine: CRI Kasauli; Pasteur Institutes at Coonoor and
Shillong; Haffkine Biopharmaceutical Corporation, Mumbai; King
Institute, Chennai; Institute of Preventive Medicine, Hyderabad;
Vaccine Institutes at Belgaum and Baroda. It is estimated that 3
million persons get post- exposure rabies vaccine annually in
India (2). It is prepared in the brains of adult sheep, after
which the carcass and hide are discarded. Since its shelf life
is only six months, a huge quantity gets discarded each year on
account of time expiry.
No one seems to have costed this operation. The excuse that it
is cheap cannot be accepted without evidence. The government may
well be spending more than what it might take to manufacture an
equivalent amount of cell culture vaccine.
Cell culture vaccine has a shelf life of at least two years,
hence wastage would be minimal; the volume and number of
injections are fractions of what are used with the Semple
vaccine; perhaps two or three manufacturers can produce the
total amount; it is an exportable product. Moreover, the
government needs to provide free vaccinations mainly in public
hospitals. In private hospitals, most people would pay its cost.
However, the government could subsidise the cost of vaccine to
the amount saved by the current expense for manufacturing Semple
vaccine in the eight centres listed above.
Many major hospitals see several patients each year with AEM
following vaccination with the Semple vaccine. In some
instances, the vaccine was given without necessary indication,
amounting to medical negligence; however, the victim was not
compensated or even treated free of cost. In other instances the
victim was not taken back in the same place where the vaccine
was given. In most cases, the subjects had not been counselled
or at least warned about the risk of AEM, nor a choice offered,
once again amounting to negligence. In some in stances,
vaccination was continued despite the subject complaining of
early symptoms of reaction. In many instances, the Semple
vaccine had been given in full doses to those who had taken a
full course in the past. This also is medically prohibited, and
amounts to medical negligence.
All these unethical practices go on under the excuse that the
vaccine is given free by the government. Most victims are not
highly educated or conscious of their human and legal rights and
do not have the confidence or finances to go to court. But if
the authorities do not see these issues correctly, one court
case from a victim of AEM would change the situation.
Some practical recommendations
The Indian Academy of Paediatrics had already strongly
recommended to the government to discontinue the use of the
Semple vaccine beyond this year (3).
It must be understood that injecting myelin- containing vaccine
is a violation of human rights and an unethical practice and
should be stopped forthwith after making alternative
arrangements for sufficient safe vaccine.
The extraordinary concern for animal welfare recently shown by
the government must be extended to the hundreds of thousands of
sheep sacrificed for vaccine production. There is both need and
opportunity to substitute cell culture for whole animal. What is
being preached must be practiced by the government and must be
seen to be implemented.
The government must revive the project to manufacture Vero cell
based rabies vaccine either in the public or in the private
sector. The existing company in India producing rabies vaccine
in chick embryo cell culture could be funded for expansion. A
second manufacturing company has just been approved to produce
Vero cell based vaccine. In other words, we are not incapable of
producing safe vaccines in India. The details of subsidy and
equity in distribution of vaccine in public hospitals mu st be
quantified and established by competent agencies without any
delay.
Medical personnel must be given clear guidelines for the correct
use of rabies vaccines. The Semple vaccine is overused because
it is free; cell culture vaccine must be used only according to
strict protocol. This will reduce the number of persons
vaccinated. In hospitals with a large attendance of dog bite
victims, cell culture vaccine may be used in fractional doses
given intradermally, to reduce costs (4).
The appropriate wing of the government must assume
responsibility for the safety of children and adults in public
places such as streets, from animal bites. It is probably
cheaper to prevent stray- dog bites than to provide cell culture
rabies vaccine to bite victims. The responsibility for such
safety must be entrusted with the local administration without
interference from above.
Can we imagine the consequence if every dog bite victim and the
family of every victim of rabies or AME due to the Semple
vaccine approached the courts for the legitimate redressal of
their grievances? Do we not have sufficient national pride not
to count a few rupees against safe biologicals? And remember, we
are a nuclear power nation, no longer a poor nation vulnerable
to enemy attack. Is not rabies our enemy too?
References:
1. John TJ, Samuel R, Balraj V. Disease surveillance at
district level: a model for developing countries. Lancet 1998;
352: 58- 61
2. Park K. Park’s Textbook of preventive and social medicine.
Banarsidas Bhanot Publishers, Jabalpore. 1997; pp 207- 214
3. Committee on Immunisation, Indian Academy of Paediatrics.
Academy matters: Update on recommendations of the Academy to
other agencies on immunisation. Indian Paediatrics 1999; 36:
785- 787.
4. World Health Organization. WHO recommendations on rabies
post- exposure treatment and the correct technique of
intradermal immunisation ag ainst rabies. World Health
Organization, Geneva. 1997; pp 1- 26
Dec 12, 2005
