Antimalarial drug resistance is a major cause
of
the increasing
burden
due to
P. falciparum
malaria. Artemisinin-based combination therapies
(ACTs)
are now
recognised to
be the ideal
choice for the first-line treatment of uncomplicated
malaria,
in
order to
achieve two
beneficial
outcomes: improvement of treatment efficacy
and
delay in the
development
of
drug
resistance.
However uncertainties remain about the current and
future
benefits,
risks
and costs of
ACTs
and
in particular how these outcomes are
affected
by differences in
malaria epidemiology,
health
care settings, human behaviour and implementation strategies.
This thesis seeks to address these uncertainties
by
creating a comprehensive,
dynamic, bio-
economic model of malaria transmission and
the
spread
of
drug
resistance, which
incorporates
vector factors, human immunity, human behaviour, drug
characteristics
and costs.
Central to
the model is a biological model, developed in
collaboration with
a
mathematician,
which
outputs the proportion of drug resistant
infections
and the
incidence
of
new
and recrudescent
infections. Parasite biomass is also tracked in
order
for
human
"infectiousness" to
be
measured
and fed-back into the model. Sub-models are used
to
calculate
severe malaria,
deaths,
costs
and
cost-effectiveness.
Data were obtained to develop and populate the
model.
This included
a community
drug
usage
survey in Cambodia, which was undertaken
in
order
to
document the
adherence
and
coverage
rates to ACT following the implementation of
locally blister-packaged
ACT.
Coverage
was
found to be extremely low, and the use of artemisinin
derivatives
on their
own
was
widespread.
However, both of these outcomes were
improved
by interventions to increase
coverage,
particularly village malaria volunteers.
Application of the model in a low transmission setting suggests
that
with
a
10-year time-frame,
switching from monotherapy to an ACT is
very
cost-effective
and
results
in
overall
cost savings
in a range of scenarios. High coverage rates
with
an
ACT
are required
to
delay the
spread
of
drug resistance if resistance has already arisen
to
one of the
partner
drugs. Running the
model
with data from Cambodia suggests that even
in
settings
with
low
coverage, the
change
will
be
cost-effective and significant benefits are
gained
from the
implementation
of
the
specific
delivery interventions. Strategies for optimising
the
implementation of
ACTs
are
discussed in light of the findings.
