Drug-Resistant Malaria - libdoc.who.int - World Health Organization

CONTROL / 61
DRUG USE AIMING AT PREVENTING, DELAYING OR REVERSING
THE SELECTION OF RESISTANT P.FALCIPARUM1
Introduction
Among the factors to be considered before attemtpting to
formulate policies regarding the management of drug resistance 1n
falciparum malaria are the type of drug deployment most likely to
be associated with the emergence of resistance, the currently
available antimalarials, the events responsible for the
development of resistance and its spread, and possible measures
that can be adopted to deal with the problem. Insofar as drug
resistance is due to the selection under drug pressure of
potentially resistant mutant organisms, it follows that the rate
of selection will be directly proportional to (a) the dose of drug
used, including the total amount in a given geographical area, Cb)
the number of parasites exposed to the drug, (c) the frequency
with which resistant mutants are present in a given parasite
population, and (d) the influence, if any, of the drugs on
parasite transmission through anopheline vectors.
Dose and Pattern of Drug Use
This will depend upon several factors such as:
the drugs given for prophylaxis or treatment. In the
former case a smaller quantity may be given per dose,
but over a longer period of time; in the latter, a
larger dose will be given on a single occasion only;
the number of people receiving prophylaxis or treatment;
the duration of prophylaxis.
Since the antifols, proguanil and pyrimethamine, may affect
developing pre-erythrocytic stages of P. falciparum, at least in
sensitive strains, the number of parasites exposed to such
compounds is comparatively small when these compounds are used for
prophylaxis. However, this advantage has been widely lost since
most of the P.falciparum isolates are now resistant to DHFR
inhibitors. Chloroquine 1S active only against asexual
erythrocytic stages. Thus when it is used for prophylaxis it is
available to attack the relatively few intra-erythrocytic
parasites or1g1nating from merozoites that first enter the
circulation from the liver, as well as subsequent generations that
lAntimalar-{al drugs and their use are reviewed in Appendix 5.