Gametocytocidal activity in antimalarial drugs speeds the spread of drug resistance.
OBJECTIVE
Antimalarial drugs kill the asexual parasites responsible for causing disease and some, notably chloroquine and the artemisinins, also kill the sexual transmission stages known as gametocytes. It is invariably argued by malariologists that gametocytocidal activity is beneficial because it reduces the rate at which resistance evolves by 'reducing the transmission of resistant parasites'. This seems dubious from a population genetics perspective, where intuition would lead to the opposite conclusion. The objective was to reconcile these differing views.


METHODS
The effect of gametocytocidal drug activity was quantified mathematically and calibrated using field data.


RESULTS
It appears to be a robust result that gametocytocidal activity actually promotes the spread of resistance through a population; the underlying reason is that gametocytocidal activity reduces transmission of drug-sensitive forms to a greater extent than the drug resistant, thereby increasing the spread of the latter. The increased rate of spread of resistance is quantified and appears to be small providing drug coverage is moderate or low.


CONCLUSIONS
Citing reduced spread of resistance as a justification for deploying gametocytocidal antimalarials is unjustified; the deliberate use of a gametocytocidal antimalarial at high coverage to reduce transmission may ultimately be counterproductive through its rapid promotion of drug resistance.
Hastings
Ian M
IM
Liverpool School of Tropical Medicine, Liverpool, UK. hastings@liverpool.ac.uk
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D005075:Biological Evolution; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005828:Genetics, Population / Q000379:methods; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology / Q000635:transmission; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology
D000962:Antimalarials