E-DRUG: BBC: Diarrhoea vaccine tests 'hopeful'
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The BBC reports on two promising new vaccines against diarrhoea. I've
included the BBC story, as well as the abstracts from both articles in the
New England Journal of Medicine. Happy New Year to all E-Druggers and your
families!
Libby Levison
public health consultant
Boston, MA
http://news.bbc.co.uk/2/hi/health/4580482.stm
Diarrhoea vaccine tests 'hopeful'
Promising findings from two studies are offering the hope of a safe and
effective vaccine against the most common cause of childhood diarrhoea.
Rotavirus kills about 500,000 children a year in developing countries, and
accounts for a third of hospital admissions from diarrhoea worldwide.
The New England Journal of Medicine reports on tests of vaccines Rotateq
and Rotarix involving 130,000 children.
The studies found them to be 98% and 85% effective respectively, it says.
Rotavirus is endemic and infections occur in almost all children by the
time they are two or three.
The severity of infection ranges from no symptoms, through vomiting, fever,
abdominal pain and watery diarrhoea to dehydrating gastroenteritis, which
can be fatal.
In the UK, it is estimated that 1 in 38 children will be hospitalised for
rotavirus gastroenteritis by the age of five, and that each year 14
children under five will die.
Most infections occur in children under two.
It is so devastating to children in the developing world because of the
lack of prompt access to treatment and hospital care.
The quest for a safe and effective vaccine against the virus was thought to
be over in the late 90s when a previous vaccine was developed.
But that had to be withdrawn from the market after it was associated with
an uncommon, but potentially life-threatening condition called
intussusception, where the bowel folds in on itself, causing an intestinal
blockage.
Side effect checks
The first study - involving more than 68,000 infants aged six to 12 weeks -
found a vaccine called Rotateq being developed by the pharmaceutical
company Merck could safely prevent 98% of severe cases of viral diarrhoea
and vomiting.
Rotateq targets five major strains of rotavirus, which account for 90% of
rotavirus disease.
The trial involved infants in the US, Belgium, Costa Rica, Finland,
Germany, Guatemala, Italy, Jamaica, Mexico, Sweden and Taiwan.
Half were given the vaccine and half a dummy version.
All were monitored to ensure there were no side effects, including
intussusception.
There were no more side effects seen in the vaccine group than their peers.
The results of a trial of another oral vaccine called Rotarix, developed by
GlaxoSmithKline, showed it was effective against the most common strain of
rotavirus and able to prevent 85% of severe cases.
Over 63,000 infants were studied in 11 Latin American countries and Finland
for between three months and a year.
Again, no difference was seen in complication rate between children given
the vaccine and those given a dummy version.
Both studies found vaccination significantly reduced the number of children
who had to be treated in hospital due to rotavirus.
Writing in the NEJM, Dr Roger Glass and Dr Umesh Parashar, of the US
Centers for Disease Control, welcomed both studies as showing promising
results.
"As vaccines become licensed and used in the US and Europe, we should
expect to see a substantial reduction in winter hospitalisations, visits to
doctors and clinics and parents' workdays lost to childhood diarrhoea,"
they said.
But they warned: "Both vaccines will need to demonstrate their efficacy in
the difficult settings of developing countries if we are to achieve our
goal of maximally decreasing global deaths from diarrhoea."
Dr David Brown, from the Health Protection Agency said: "The results of
these large studies are significant because they demonstrate that these two
vaccines have good efficacy against severe rotavirus disease and are not
associated with intussusception."
-- Abstract 1 --
Safety and Efficacy of an Attenuated Vaccine against Severe
Rotavirus Gastroenteritis
G.M. Ruiz-Palacios and Others
<http://content.nejm.org/cgi/content/full/354/1/11?query=TOC>
Background The safety and efficacy of an attenuated G1P[8] human rotavirus
(HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.
Methods We studied 63,225 healthy infants from 11 Latin American countries
and Finland who received two oral doses of either the HRV vaccine (31,673
infants) or placebo (31,552 infants) at approximately two months and four
months of age. Severe gastroenteritis episodes were identified by active
surveillance. The severity of disease was graded with the use of the
20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of
20,169 infants (10,159 vaccinees and 10,010 placebo recipients).
Results The efficacy of the vaccine against severe rotavirus
gastroenteritis and against rotavirus-associated hospitalization was 85
percent (P<0.001 for the comparison with placebo) and reached 100 percent
against more severe rotavirus gastroenteritis. Hospitalization for diarrhea
of any cause was reduced by 42 percent (95 percent confidence interval, 29
to 53 percent; P<0.001). During the 31-day window after each dose, six
vaccine recipients and seven placebo recipients had definite
intussusception (difference in risk, 0.32 per 10,000 infants; 95 percent
confidence interval, 2.91 to 2.18; P=0.78).
Conclusions Two oral doses of the live attenuated G1P[8] HRV vaccine were
highly efficacious in protecting infants against severe rotavirus
gastroenteritis, significantly reduced the rate of severe gastroenteritis
from any cause, and were not associated with an increased risk of
intussusception.
-- Abstract 2 --
Safety and Efficacy of a Pentavalent Human-Bovine (WC3)
Reassortant Rotavirus Vaccine
T. Vesikari and Others
<http://content.nejm.org/cgi/content/full/354/1/23?query=TOC>
Background Rotavirus is a leading cause of childhood gastroenteritis and
death worldwide.
Methods We studied healthy infants approximately 6 to 12 weeks old who were
randomly assigned to receive three oral doses of live pentavalent
humanbovine (WC3 strain) reassortant rotavirus vaccine containing human
serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in
a blinded fashion. Active surveillance was used to identify subjects with
serious adverse and other events.
Results The 34,035 infants in the vaccine group and 34,003 in the placebo
group were monitored for serious adverse events. Intussusception occurred
in 12 vaccine recipients and 15 placebo recipients within one year after
the first dose including six vaccine recipients and five placebo recipients
within 42 days after any dose (relative risk, 1.6; 95 percent confidence
interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency
department visits related to G1G4 rotavirus gastroenteritis occurring 14
or more days after the third dose by 94.5 percent (95 percent confidence
interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any
G1G4 rotavirus gastroenteritis through the first full rotavirus season
after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to
79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95
percent confidence interval, 88.3 to 100 percent). The vaccine reduced
clinic visits for G1G4 rotavirus gastroenteritis by 86.0 percent (95
percent confidence interval, 73.9 to 92.5 percent).
Conclusions This vaccine was efficacious in preventing rotavirus
gastroenteritis, decreasing severe disease and health care contacts. The
risk of intussusception was similar in vaccine and placebo recipients.