Abstract
There are more than half a billion cases of malaria every year. Combinations of an artemisinin with other antimalarial drugs are now recommended treatments for Plasmodium falciparum malaria in most endemic areas. These treatment regimens act rapidly to relieve symptoms and effect cure. There is considerable controversy on how artemisinins work and over emerging indications of resistance to this class of antimalarial drugs. Several individual molecules have been proposed as targets for artemisinins, in addition to the idea that artemisinins might have many targets at the same time. Our suggestion that artemisinins inhibit the parasite-encoded sarco–endoplasmic reticulum Ca2+-ATPase (SERCA) PfATP6 has gained support from recent observations that a polymorphism in the gene encoding PfATP6 is associated with in vitro resistance to artemether in field isolates of P. falciparum.
Highlights
The importance of artemisinins as antimalarials Artemisinin derivatives (Figure 1) are uniquely important antimalarial agents
A study has shown that artesunate reduces mortality compared with quinine in the treatment of severe Plasmodium falciparum malaria [3], this study has raised some interesting issues [4,5]
The World Health Organization (WHO) publicly requested pharmaceutical companies to end the marketing and sale of ‘single-drug’ artemisinin malaria medicines to prevent malaria parasites from developing resistance to this drug. This call comes at a time when several observations challenge the notion that artemisinin resistance does not develop. These include: (i) the development of stable resistance to artemisinin after selection pressure in an animal model [14]; (ii) the observation of in vitro resistance to artemether in isolates from French Guiana [15]; and (iii) the first longitudinal clinical study that demonstrated a link between reduced in vitro artemisinin susceptibility and loss of clinical efficacy of artesunate monotherapy [16]
Summary
The importance of artemisinins as antimalarials Artemisinin derivatives (Figure 1) are uniquely important antimalarial agents. These include: (i) the development of stable resistance to artemisinin after selection pressure in an animal model [14]; (ii) the observation of in vitro resistance to artemether in isolates from French Guiana [15]; and (iii) the first longitudinal clinical study that demonstrated a link between reduced in vitro artemisinin susceptibility and loss of clinical efficacy of artesunate monotherapy [16].
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