Diarrhea Vaccine Can Deliver Wonders: Provided We Have One

http://effectiverotavirusvaccine.blogspot.in/2014/08/diarrheavaccine-can-deliver-wonders.html

The word Diarrhea needs no introduction. The most common cause of diarrhea is the
infection of the intestines due to a virus, bacteria or parasite. Diarrhea leads to the depletion
of fluids which results in dehydration of the body. Diarrhea is often described as a Common
Illness : Global Killer. In around 40% cases of severe diarrhea in children under the age of
5, Rotavirus has been detected in the stool culture examination often along with other
pathogens. In most cases it is not possible to pin point a single organism responsible for the
diarrhea. These infections are often acquired from food or water contaminated by fecal
matter. For treating most such diarrheal illnesses, correction of dehydration of the body is the
most important intervention and in most cases the symptoms resolve within a few days. Oral
rehydration solution (ORS) either made from pre-formulated packets or with modest amounts
of salts and sugar in clean water is the treatment of choice in most cases. If the dehydration is
severe, the child has to be admitted in a hospital and fluids infused through a needle put into
the vein.

Prevention of infectious diarrhea can be achieved by improved sanitation, clean drinking

water and regular hand washing, together with better nutrition and better health. However
this requires enduring efforts in all these areas. The tardy pace of development makes it even
more difficult for these interventions to make any visible impact. Nobody knows how much
time it will take and surely we cant wait endlessly.

It is in this context that the recent decision to include four new vaccines in our Universal
Immunization Program assumes more significance. It is believed that by including vaccines
against rotavirus, rubella and polio (injectable), we will substantially and quickly reduce the
child mortality. Out of these vaccines, there has been a unique enterprise in developing a
vaccine against rotavirus in our country. The recently published trial of an Indian rotavirus
vaccine has demonstrated our capabilities in developing and evaluating a vaccine. It has to be
applauded.

There have been similar efforts for developing rotavirus vaccine made elsewhere. While
appreciating these efforts, it is also essential that we cautiously examine the benefits and side
effects observed in the evaluations of these vaccines. In 1998, a highly efficacious rotavirus
vaccine RotaShield was licensed in the United States. In the pre-clinical trials of this vaccine,
five cases of intussusception# occurred among 10,054 (0.05%) vaccine recipients; all were
among infants who received a second or a third dose of vaccine and one case of
intussusception occurred among 4,633 (0.02%) infants who received a placebo vaccine.
#
Intussusception is a medical condition in which a part of the intestine slides itself into
another section of intestine similar to the way collapsible telescope slide into one another.
This condition is not easy to diagnose without ultrasound imaging and can be life threatening
if not treated.

The RotaShield vaccine was approved and intussusception was listed as one of the side
effects on its package insert. Later it was found that RotaShield vaccine increased the risk of
intussusception by one or two cases out of the every 10,000 infants vaccinated. This was
considered unacceptable and subsequently, RotaShield was withdrawn from the market
within 9 months of its introduction.

It was realized that to critically detect a severe adverse effect occurring with a frequency of 1
to 2 per 10000, it is essential to have a large sample size which is many times more than
10,000. Thus, in subsequent new rotavirus vaccines, the trials were conducted on over 60000
children in order to demonstrate their benefits over side effects. Presently there are two
rotavirus vaccines, Rotarix and RotaTeq, approved in USA and a few other countries. These
approvals have been granted on the basis of extensive studies.

The sample size in the Indian trial was less than even the RotaShields trial. Six cases of
intussusception occurred in the vaccinated group, against two in the placebo group, but the
numbers were too small to be statistically significant. It is suggested that the excess
intussusception episodes among the vaccinated children were by chance and not due to
immunization as the intussusception occurred after third dose of the vaccine and that we will
get at the truth by doing post marketing surveillance. The picture is similar to what was seen
in the original RotaSheild trial in USA.

The other point highlighted in the study was that, with this vaccine 55 infants need to be
immunized to prevent one moderate to severe rotavirus gastroenteritis episode. The mortality
due to such episodes is close to 1%, therefore around 5000 infants will have to be immunized
to save 1 death due to rotavirus gastroenteritis. And even the limited trial mentioned above
shows that these 5000 immunizations may result in more than one cases of intussusception.
The mortality due to intussusception is 1% in the USA; if treated in time, in India the
mortality is around 10%. If undiagnosed and untreated, which can invariably happen without
a radiologist and pediatric surgeons, the mortality will be nearly 100%.

These data suggest that although we have made a remarkable beginning by developing an
Indian rotavirus vaccine, we have a long way to go. The composition of our vaccine may
have to be improved and it has to be evaluated on a large sample size to find out the correct
frequency of severe side effects. Similarly the efficacy of the 2 internationally licensed
rotavirus vaccines also need to be demonstrated in Indian conditions. Because there is
considerable variability in the serotypes of rotavirus in different geographic regions and new
serotypes are known to emerge. Also around 50% of our infants are undernourished and may
not mount an adequate response to these vaccines.

Conducting a trial on required 60000 infants is not an easy task. The cost of such evaluation
(phase III trial) for Rotarix or RotaTeq was around 150 million US dollars in 2005. In the
phase II trial of these vaccines, when these vaccines were administered to around 5000
children, the cost was nearly 1 million US dollars. Therefore it will require many times the
resources used in the recently published Indian trial. One with a more realistic approach may
say that it is not feasible to conduct such trials in India. And it is at this stage, whether we
need for such a vaccine should be reexamined. It is an extremely arduous task to develop and
establish a safe and effective vaccine.

Since we do not have infinite resources, we should prioritize our methods. The danger is that
the unseemly haste in getting the vaccines in place will eat away most of our resources and
we will continue to overlook already neglected non-vaccine approaches. We aspire to
immunize every child with a rotavirus vaccine, which is yet to prove its safety and efficacy in
our country. And yet till date, there is no enforceable provision to ensure hand washing in
any Anganwadis or in the mid-day meal program for our children. Should such efforts and
other preventive strategies and vaccine based strategy go hand in hand or the vaccine should
be the first strategy? We expect vaccine to deliver wonders; perhaps it can, but presently we
do not have such a vaccine. Until we have one, it is imperative to pay attention to non-
vaccine approaches.

http://effectiverotavirusvaccine.blogspot.in/2014/08/diarrheavaccine-can-deliver-wonders.html