A rotavirus vaccine protects children from rotaviruses, which are the leading cause of
severe diarrhea among infants and young children.
Each year an estimated 453,000 children die from diarrhoeal disease caused by rotavirus,
most of whom live in developing countries, and another two million are hospitalised.
Rotavirus is highly contagious and resistant and, regardless of water quality and available
sanitation, nearly every child in the world is at risk of infection.
There are two effective rotavirus vaccines: Rotarix by GlaxoSmithKline and RotaTeq by
Merck.
A vaccine has recently been developed in India.
Phase III trials have been conducted for the vaccine.
On June 5, 2009, the World Health Organization recommended that rotavirus vaccine be included
in all national immunization programs.
The Rotavirus Vaccine Program and the Accelerated Vaccine Introduction initiative have worked
to study rotavirus vaccines among developing-country populations to assist developing countries
in introducing rotavirus vaccines into routine immunization programs.
These partnerships are spearheaded by international non-governmental organization PATH, WHO, the
U.S. Centers for Disease Control and Prevention, and the Global Alliance for Vaccines and Immunization.
It is on the World Health Organization's List of Essential Medicines, a list of the most
important medication needed in a basic health system.
Rotarix Rotarix is a monovalent, human, live attenuated
rotavirus vaccine containing one rotavirus strain of G1P[8] specificity.
ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and
non-G1 types when administered as a 2-dose series in infants and children.
On March 22, 2010, FDA provided an early communication regarding Rotarix, manufactured by GlaxoSmithKline
Biologicals At that time, FDA recommended that clinicians and public health professionals
in the United States temporarily suspend the use of Rotarix while the agency and manufacturer
investigated the finding of DNA from porcine circovirus-1 in the vaccine.
Since that time, both FDA and GSK have confirmed the presence of PCV1 in the vaccine.
Although this contamination was thought to be benign, vaccines are supposed to be sterile.
In May 2010 the suspension of the vaccine was lifted.
RotaTeq
RotaTeq is a live, oral pentavalent vaccine that contains five rotavirus strains produced
by reassortment.
The rotavirus A parent strains of the reassortants were isolated from human and bovine hosts.
Four reassortant rotaviruses express one of the outer capsid, VP7, proteins from the human
rotavirus parent strain and the attachment protein VP4 from the bovine rotavirus parent
strain.
The fifth reassortant virus expresses the attachment protein VP4,, from the human rotavirus
parent strain and the outer capsid protein VP7 from the bovine rotavirus parent strain.
In February 2006, the U.S. Food and Drug Administration approved RotaTeq for use in the United States.
In August 2006, Health Canada approved RotaTeq for use in Canada.
Merck is working with a range of partners including governmental and non-governmental
organisations to develop and implement mechanisms for providing access to this vaccine in the
developing world.
Temporary suspension On March 22, 2010, the detection of DNA from
porcine circovirus types 1 and 2 within RotaTeq and Rotarix prompted the FDA to suspend the
use of rotavirus vaccines while conducting an investigation in collaboration with the
12 members of the Vaccines and Related Biological Products Advisory Committee.
On May 6, 2010, the FDA announced its decision to revoke the suspension, asserting that porcine
circovirus types 1 and 2 pose no safety risks in humans and concluded that health risks
involved did not offset the benefits of the vaccination.
Rotavac An Indian-made rotavirus vaccine, Rotavac,
was developed and announced in 2013.
If approved by the Drugs Controller General of India, it would be available at Rs. 54
per dose, more affordable than the two vaccines now available costing more than Rs. 1,000
per dose.
Vaccines in development Other vaccines are undergoing clinical trials.
These include: a human neonatal P[6]G3 strain, RV3, developed by Ruth Bishop and colleagues
in Australia, a human bovine reassortant vaccine developed by Albert Kapikian and presently
undergoing development and trials in different countries and a neonatal strain vaccine being
developed by Bharat Biotech in India.
This G9P(11) virus strain has the VP4 of bovine rotavirus origin, and all other segments of
human rotavirus origin.
Other approaches to the development of rotavirus vaccines are also being pursued.
Rotavirus antigens for parenteral delivery have received some attention as virus-like
particles prepared in baculovirus, expressed antigens, DNA vaccines, and killed virus.
These novel approaches are being pursued using animal models.
Effectiveness and cost A 2009 review estimated that vaccination against
rotavirus would prevent about 45% of deaths due to rotavirus gastroenteritis, or about
228,000 deaths annually worldwide.
At $5 per dose the estimated cost per life saved was $3,015, $9,951 and $11,296 in low-,
lower-middle-, and upper-middle-income countries, respectively.
The cost of rotavirus vaccination has fallen by 67 percent between 2006 and 2011 to USD
2.50 per dose, as part of an offer made by a pharmaceutical company to the GAVI Alliance.
However, the vaccine is still more expensive than most other childhood vaccines included
in the WHO's Expanded Programme on Immunization.
Safety and efficacy trials of Rotarix and RotaTeq in Africa and Asia found that the
vaccines dramatically reduced severe disease among infants in developing countries, where
a majority of rotavirus-related deaths occur.
A 2012 Cochrane review of 41 clinical trials that included 186,263 participants concluded
Rotarix and RotaTeq are effective vaccines.
Additional rotavirus vaccines are under development.
Rotavirus vaccines are licensed in more than 100 countries, but only 31 countries have
introduced routine rotavirus vaccination as of 2011.
The incidence and severity of rotavirus infections has declined significantly in countries that
have acted on the recommendation to introduce the rotavirus vaccine.
In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus
vaccine, the diarrheal disease death rates from rotavirus dropped by more than 65% among
children age two and under during the 2009 rotavirus season . In Nicaragua, which in
2006 became the first developing country to introduce the rotavirus vaccine, investigators
recorded a substantial impact, with rotavirus vaccine preventing 60% of cases against severe
rotavirus and cutting emergency room visits in half.
In the United States, vaccination has reduced rotavirus-related hospitalizations by as much
as 86% since 2006.
The vaccines may also prevent illness in non-vaccinated children by limiting exposure through the
number of circulating infections.
In September 2013, the vaccine will be offered to all children in the UK, aged between two
and three months, and it is expected to halve the cases of severe infection and reduce the
number of children admitted to hospital because of the infection by 70 percent.
History In 1998, a rotavirus vaccine was licensed
for use in the United States.
Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100%
effective at preventing severe diarrhea caused by rotavirus A, and researchers had detected
no statistically significant serious adverse effects.
The manufacturer of the vaccine, however, withdrew it from the market in 1999, after
it was discovered that the vaccine may have contributed to an increased risk for intussusception,
or bowel obstruction, in one of every 12,000 vaccinated infants.
There then followed 8 years delay until rival manufacturers were able to introduce new vaccines
which due to different adjuvant were shown to be more safe and effective in children:
Rotarix by GlaxoSmithKline and RotaTeq by Merck.
Both are taken orally and contain disabled live virus.
The experience, however, provoked debate about the relative risks and benefits of a rotavirus
vaccine.
This is because rotavirus is responsible for 29% of deaths from diarrhea in children below
5 years worldwide, and thus 4.2 million deaths could be avoided during that 8 years in different
parts of the world.
Meanwhile, other countries such as Brazil and Mexico undertook their own independent
epidemiological studies which demonstrated that 4 deaths were attributable to vaccine,
while it had prevented approximately 80,000 hospitalization and 1300 deaths from diarrhea
each year in their countries.
This example shed light on the importance of careful country-specific epidemiology which
enables rational balancing between benefit and risk.
References
External links DefeatDD.org
National Clearinghouse Guideline: Prevention of rotavirus gastroenteritis among infants
and children.
Recommendations of the Advisory Committee on Immunization Practices.
PATH Rotavirus Vaccine Program Vaccine Information Statement from the US
Centers for Disease Control and Prevention Vaccine Resource Library: Rotavirus