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4. Resistance to antimalarial medicines

4.1 impact of resistance
Initially, at low levels of resistance and with a low prevalence of malaria, the impact
of resistance to antimalarials is insidious. At the early onset of resistance, the initial
symptoms of the infection resolve and the patient appears to be better for a short period
of time; however, symptoms recur (usually between three to six weeks after treatment),
anaemia may worsen and there is a greater probability of carrying gametocytes (which in
turn carry the resistance genes). The patient and the treatment provider mostly interpret
these early features of resistance as a newly acquired infection. Unless clinical drug trials
are conducted at this stage, resistance may go unrecognized. As resistance worsens, the
interval between primary infection and recrudescence shortens; eventually symptoms fail
to resolve following treatment, with malaria incidence likely to rise in low-transmission
settings, and mortality is likely to rise in all settings.

4.2 Global distribution of resistance

Resistance to antimalarials has been documented for P. falciparum, P. malariae and
P. vivax. In P. falciparum, resistance has been observed in all currently used antimalarials
(amodiaquine, chloroquine, mefloquine, quinine, and sulfadoxine-pyrimethamine) and,
more recently, in artemisinin derivatives. The geographical distributions and rates of
spread have varied considerably.
P. vivax has developed resistance rapidly to sulfadoxine-pyrimethamine in many areas,
while resistance to chloroquine is confined largely to Indonesia, Papua New Guinea,
Timor-Leste and other parts of Oceania. There are also reports on resistance from Brazil
and Peru. P. vivax remains sensitive to chloroquine in most of South-East Asia, the Indian
subcontinent, the Korean peninsula, the Middle East, north-east Africa, and most of
South and Central America.

4.3 assessing efficacy and resistance

The following methods are available for assessing efficacy and resistance to
antimalarials:
1
■ in vivo assessment of therapeutic efficacy;
■ molecular genotyping to distinguish between re-infections and recrudescence ; 2
■ in vitro studies of parasite susceptibility to drugs in culture. 3
■ molecular markers.

3 Basco LK. Field application of in vitro assays for the sensitivity of human malaria parasites to antimalarial drugs.
Geneva, World Health Organization, 2007
http://apps.who.int/malaria/docs/drugresistance/OMS_FieldApplicationInVitroAssays.pdf, accessed 29 Oct. 2009).
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