E-drug: Malaria vaccine (cont)
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An interesting idea, but some difficult issues to resolve. Being in Africa
at the moment I don't have access to some papers I have that may be
relevant (ie estimating the required vaccine efficacy and duration of
protection for a useful malaria vaccine). So some general comments...
The vast majority of malaria death and disease is due to
P.falciparum, so to start with the vaccine must target this species.
Its generally said that 90% of deaths occur in sub-shaharan Africa,
and 90% of deaths are young children. By late childhood, immunity to
malaria is pretty substantial in areas with endemic malaria so its
rare in most African countries for adults to get severe malaria (or
to die of malaria). Therefore any vaccine must reduce mortality in
children and be effective in Africa. It is important to clarify that
a vaccine must reduce disease, not necessarily reduce infection. Many
infections are asymptomatic, and certainly only a minority of
infections lead to severe disease.
It is unusual for children to get severe malaria in the first year of
life so a vaccine could conceivably be incorporated into the EPI - a
suitable and practical dosing schedule would be needed (eg a maximum
of 3 doses?).
Some have suggested that any vaccine might need only to be about 30%
effective to substantially reduce the prevalence and transmission of
malaria in an endemic area. With up to 3 million deaths each year, a
30% efficacy could potentially translate into 1m lives saved. Also,
probably pretty hard to confidently detect in a clinical trial a
difference between vaccine and placebo of less than 30%.
Determining the appropriate duration of action is a hard one. In malaria
endemic areas the vaccine response might be frequently 'boosted' by
repeated natural infections. So a short duration of protection in
non-malaria exposed volunteers in the west may not be the same when
given in a malarious area. Determining the minimum boosting interval
probably needs to be determined on economic and practical terms.
Pregnant women constitute the second group at high risk of malaria.
They are much more susceptible to malaria than non-pregnant adults
and infection leads to low birthweight babies, the biggest risk
factor for early infant death in the tropics. The current thinking is
that adolescent girls might receive boosters to protect pregnancies.
An alternative would be to give the vaccine very early in pregnancy,
but often women don't present to health clinics until quite late in
pregnancy.
In terms of the 'contract' suggested, I would think it would have to
include outcome measures or data from trials in malaria endemic areas
as there is really no other accurate way of measuring its usefulness.
Also, carefully defining practical issues relevant to target
populations (particularly rural populations who are at most risk)
will be critical.
Regards,
James
Dr James Beeson
Research Scientist
Walter and Eliza Hall Medical Research Institute
Melbourne
Australia
[currently in Malawi}
James Beeson
c/-<srogerson@malawi.net>
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