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Guidelines for the treatment of malaria – 2 edition

ANNEX 6
resistance to antimalarial medicines

a6.1 introduction

Currently, there are no bedside tests for determining the susceptibility of the malaria
parasite to antimalarials. Monitoring is, therefore, needed to determine geographical
trends in susceptibility and the emergence and spread of drug resistance. The information
obtained will help guide treatment choices and predictions about future resistance
patterns.

The greatest problem with drug resistance occurs with Plasmodium falciparum. Resistance
of P. falciparum is of particular concern because of the enormous burden of disease caused
by this species, its lethal potential, the propensity for epidemics, and the cost of candidate
replacement drugs for areas with established drug resistance. Chloroquine resistance
does occur in P. vivax, especially in western Oceania, but there are very few reports of
resistance in P. malariae or P. ovale (although there have also been very few studies).

This annex defines resistance, examines how it arises and spreads, and describes ways
in which it can be monitored.

a6.2 definition

Antimalarial drug resistance is defined as the ability of a parasite strain to survive and/
or multiply despite the proper administration and absorption of an antimalarial drug in
the dose normally recommended. Drug resistance to an antimalarial compound results
in a right shift in the concentration-effect (dose-response) relationship (Fig. A6.1). As
the pharmacokinetic properties of antimalarials vary widely in different individuals, the
definition of resistance should probably also include a “normal” plasma concentration
profile for the active drug concerned or, in the case of a prodrug (a drug that is not active in
the ingested form and requires chemical conversion through metabolic processes to become
pharmacologically active), a “normal” profile of the biologically active metabolite.
Antimalarial drug resistance is not necessarily the same as malaria “treatment failure”,
which is a failure to clear malarial parasitaemia and/or resolve clinical symptoms despite
the administration of an antimalarial. So while drug resistance may lead to treatment

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