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ANNEX 6. Resistance to antimalarials medicines

failure, not all treatment failures are caused by drug resistance. Treatment failure can
also be the result of incorrect dosing, problems of treatment adherence (compliance),
poor drug quality, interactions with other drugs, compromised drug absorption, or
misdiagnosis of the patient. Apart from leading to inappropriate case management, all
these factors may also accelerate the spread of true drug resistance by exposure of the
parasites to inadequate drug levels.

Figure A6.1 Drug resistance to an antimalarial compound showing a right
shift in the concentration-effect (dose-response) relationship
E max

A E max
B
C

Eect EC 50

EC 50

A6
Log concentration
Note: Resistance is a rightward shift in the concentration–effect relationship for a particular parasite
population. This may be a parallel shift (B) from the “normal” profile (A) or, in some circumstances,
the slope changes, and/or the maximum achievable effect is reduced (C).

a6.3 emergence and spread of antimalarial resistance

The development of resistance can be considered in two parts: the initial genetic event,
which produces the resistant mutant; and the subsequent selection process in which
the survival advantage in the presence of the drug leads to preferential transmission of
resistant mutants and, thus, the spread of resistance. In the absence of the antimalarial,
resistant mutants may have a survival disadvantage. This “fitness cost” of the resistance
mechanism may result in a decline in the prevalence of resistance once drug pressure
is removed.

Resistance to one drug may select for resistance to another where the mechanisms
of resistance are similar (cross-resistance). There are many parallels with antibiotic

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