Meningococcal
epidemic - fighting a killer
18.02.2002
Plans to vaccinate everyone
aged under 20 against meningococcal disease depend on the success of a trial
starting in Auckland shortly. ANDREW LAXON reports.
In
a few months volunteers should start walking through the doors of the
University of Auckland medical school, rolling up their sleeves and giving
blood samples.
The
90 human guinea pigs will then be given an injection against meningococcal
meningitis, the disease that has killed 184 New Zealanders, many of them
children, in the past decade.
Thirty
will get a new vaccine, developed specifically for New Zealand. Thirty will get
a variation on this vaccine, and the rest will get the Norwegian vaccine, which
served as model for our version.
The
18-to-50-year-olds taking part in this clinical trial - possibly Auckland
Hospital doctors and nurses if other Aucklanders are reluctant to come forward
by May - will take away a diary to record any reactions, such as a sore arm or
a temperature.
Six
weeks later, they will be back for another dose and another blood test to see
if the vaccine is working. In six more weeks, they will return for their final
dose and blood test (all sent to Government laboratories for evaluation, with
checks by international experts).
Then
scientists will start to know whether the $100 million experiment to stop New
Zealand's worst infectious disease is working.
For
Professor Diana Lennon, the childhood infectious diseases specialist running
the trial, an even more important test will come in the next phase.
If
the vaccine works on adults, she hopes to start trials among 100 to 150 older
schoolchildren this year, before moving on to the same numbers of toddlers and
babies. She describes this as the absolute "stop-go" point of the
trial - children under 5 with poorly developed immune systems are the disease's
biggest victims.
If
the second phase works, the vaccine will gradually be introduced into high-risk
areas such as South Auckland. If it brings the disease rate down with no severe
side-effects, the vaccine will be used to immunise a million New Zealanders
under the age of 20.
After
that, meningococcal B vaccine could become part of the child immunisation
schedule given at six weeks, three months and five months (with shots against
hepatitis B, diphtheria and measles, mumps and rubella) within the next five
years.
All
this involves a lot of "ifs", but the scale of meningococcal disease
has given the search for a vaccine a sense of urgency. Since 1991 New Zealand
has suffered 184 deaths and the epidemic is expected to last another decade,
with 4000 more cases and 200 more deaths.
One
in every 100 Maori and Pacific Island children under 5 can expect to catch
meningococcal disease, which is strongly linked to poverty.
Although
no one knows exactly what causes it to spread, Auckland researchers have shown
that the risk here increases with household overcrowding. Overseas research has
suggested a link with passive smoking, but not enough to account for all the
cases.
As
a result, public health specialists regard an effective vaccine as the best
hope of fighting meningococcal meningitis. The problem is that finding one for
the New Zealand strain has been challenging scientists for decades.
All
vaccines work by giving the body a tame version of the real disease which
gradually builds up the body's natural defences. The trick in developing a new
vaccine is to find the substance in the bug carrying the disease which will
provoke human antibodies into a hostile reaction.
Although
the presence of antibodies does not guarantee a successful vaccine, it is
considered a reliable guide. Scientists scrutinising the blood tests in the
Auckland clinical trial will therefore be looking for a certain level of
antibodies - Professor Lennon says the exact "pass rate" is still to
be determined - to see if the vaccine is working.
In
the case of meningococcal meningitis, the disease comes in three main types -
A, B and C. Since the late 1960s, vaccines based on purified sugar molecules
known as polysaccharides from capsules on the outer coat of the bacteria have
been used against groups A and C.
But
these vaccines do not work against meningococcal B. There is an added danger
that the polysaccharide-based vaccine has a chemical which resembles substances
in brain tissue. In theory, this could trick the immune system into attacking
the brain as well as the disease.
So
researchers in the 1970s decided to change tack. They reasoned that since most
people who came down with meningococcal B disease seemed to be immune to second
episodes, the meningococcal B bacterium itself must contain the tools for
immunity.
Studies
showed that the blood of patients recovering from meningococcal B contained antibodies
which had formed against the outer membrane protein (OMP) and a
lipopolysaccharide (LPS), a lipid-sugar molecule.
There
have since been encouraging but mixed results with this method in three
countries closely studied by New Zealand researchers - Cuba, the Netherlands
and Norway.
In
the 1980s, Cuban researchers reported an 80 per cent success rate among 106,000
students with an OMP-based vaccine. But when the same vaccine was given to 2.4
million Brazilian children aged 3 months to 6 years old, it proved only 47 per
cent effective for 2-to-4-year-olds and did not seem to work at all for
children under 2.
New
Zealand eventually rejected the Cuban vaccine. However, Professor Lennon says,
the poor result in Brazil may have been caused by a badly conducted trial,
rather than the vaccine itself, which later showed promise in Chile.
In
1996, New Zealand came close to an agreement with Dutch public health
officials, who had been working on a similar vaccine.
But
neither country pursued the idea hard enough - Professor Lennon says the
epidemic here had waned and some officials thought it might be over - so
momentum was lost.
Meanwhile,
Norwegian researchers had put together a vaccine which initially did not seem
as promising. It was only 58 per cent effective when tested on 171,800 children
aged 12 to 16 and protection levels later fell away. Not surprisingly,
Norwegian public health specialists did not recommend that all children should
be given the vaccine.
Professor
Lennon says the results turned out to be better than they looked. As in the
Brazilian trial, the children had been given only two doses instead of three.
The vaccine had protected 87 per cent after 10 months, suggesting that a third
dose could lock in the immunity.
The
other potential problem was that experience showed every strain of
meningococcal B was different, so the proteins collected from one strain had
limited effectiveness against another.
The
answer was to take a protein from the New Zealand strain and use the Norwegian
technique to make a new "designer" vaccine.
That
was the approach taken by American vaccine maker Chiron - whose meningococcal C
vaccine has been widely used in Britain and Canada - in collaboration with
Norway's National Institute of Public Health.
Their
proposal secured the contract with the Ministry of Health, announced by the
Government last month.
Ministry
public health specialist Dr Jane O'Hallahan says the Norwegian-Chiron bid was
not just the best product. One of the main difficulties in getting a vaccine
had been finding a company able to supply more than three million doses for the
New Zealand market.
Chiron
met several important criteria, including manufacturing capacity and company
expertise to back up its product.
Dr
O'Hallahan says she is 90 per cent confident that the vaccine will work, based
on positive comments by a panel of international experts which the Health
Research Council has commissioned to check on the ministry's work.
For
Professor Lennon, the immediate hurdle is gaining ethical approval to begin
trials in May. It looks likely, but as the trials continue, obstacles are bound
to become tougher.
For
instance, she says, half the children in the second-phase trials will be given
the new meningococcal B vaccine. The other half - the control group - will
receive a jab for meningococcal C, which gives limited protection, rather than
a placebo such as water.
This
is for ethical and practical rather than scientific reasons, she explains.
It
is hard enough to persuade parents to volunteer their children for tests of an
unproven vaccine, without the prospect that the children will not benefit at
all.
ALL
INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR
GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE
KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED
AS PROVIDING MEDICAL OR LEGAL ADVICE. THE DECISION WHETHER OR NOT TO
VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU
ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.