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ANNEX 4. Antimalarials and malaria transmission

a4.3 strategies to reduce the transmission of drug-resistant parasites

The continued use of a medicine to which parasites are partially resistant will confer a
selective advantage to resistant parasites and favour their transmission. In the presence
of the drug, partially resistant infections produce higher gametocyte densities than
those that are sensitive (6,7,10,11,16,17). Drug resistance leads to recrudescences, which
are associated with higher rates of gametocyte carriage than primary infections. Thus,
cumulatively drug resistant infections generate more gametocytes than sensitive ones.
Secondly, gametocytes carrying resistant genes have been shown to be more infectious
to mosquitoes. They produce higher densities of parasites (oocysts) in the mosquitoes,
and they infect a higher proportion of mosquitoes than those carrying sensitive genes
(7,8,12). Molecular studies on the transmission of two P. falciparum genes linked to
chloroquine resistance PfCRT and PfMDR have shown that gametocytes carrying these A4
genes produce more oocysts and are also more infectious to mosquitoes than gametocytes
of the sensitive genotype (17).
Two things important to note are that:
• the continued use of a failing medicine will selectively increase the transmission of
drug resistant parasites and hasten their spread;
• early treatment of malaria patients with an effective antimalarial has the greatest chance
of limiting the spread of drug-resistant parasites.
A decrease in transmission rates as achieved, for example, by vector control, will curtail
the spread of parasites of both sensitive and resistant strains, but evidence suggests that,
in the absence of drug pressure, resistant parasites would be at a survival disadvantage
compared to sensitive strains (18, 19). Stringent transmission conditions resulting from
mosquito-control measures will, therefore, tend to selectively eliminate drug-resistant
parasites (20). This is supported by field experiences in:
• Zimbabwe, where house spraying with insecticides to reduce malaria transmission was
associated with a decrease in drug resistance (21);
• focal regions in India and Sri Lanka, where a combination of intense vector-control
measures and switching to an effective medicine led to a significant reduction and, in
some instances, even elimination of chloroquine-resistant P. falciparum from the foci;
and
• western Thailand, where high levels of mefloquine resistance prevailed in the 1990s
and the deployment of insecticide-treated nets and an ACT for malaria treatment was
followed by an increase in vitro susceptibility of P. falciparum to mefloquine (22).
When parasites become resistant to a medicine used for curative purposes, having anti-
infective properties in the same medicine is not likely to help reduce the spread of resistant
parasites – it will, to the contrary, favour the spread of resistant parasites over sensitive
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