2. Malaria treatment (References: PubMed, Google, Ginsburg H and Golenser J publications)

4. CHING-HAO (Artemisinin) is isolated from Artemisia annua and used in chinese medicine

5. Trophozoite- EM

6. Labile iron in P.falciparum infected erythrocytes induce fragmentation of DNA Fe 2+ + H 2 O 2 ----> Fe 3+ +.OH + OH -

7. Ridley RG, Nature. 2003, 424 (6951): 887-9

8. Artemisinin inhibits plasmodia by two mechanisms: 1.Production of free radicals which affects different macromolecules. 2. Specific interference with PfATP6 (Ca- 2+ ATPase (SERCA)). This interference is also mediated by iron induced damage. Thapsigargin is an inhibitor of SERCA, has structural similarity to artemisinin, lacks peroxide bridge and interferes with the anti-plasmodial activity of artemisinin. Iron chelator (Desferal) abrogates artemisinin effect on SERCA. The first mechanism explains the non-specific effect on various eukaryotic cells (ED 50  M). The second one explains the specificity towards Plasmodium falciparum (ED 50 nM).

10. Spread of chloroquine resistance

12. The Mechanism of Accumulation of Chloroquine in the Parasite Food Vacuole Chloroquine travels down a pH gradient and inside the parasite becomes diprotonated. This form of the drug (shown in blue) is impermeable to biological membranes.On the right of the figure is a generic structure of a parasite targeted artemisinin derivative

14. Hb FP HZ FP : CQ CQ Hb Glu Cys Gly {} NADP NADPH GSH GSS G HM S GRGR FP Fe 3+ Fe 2+ O 2 +H + O 2 H 2 O 2 O 2 +H 2 O GSH GSSG CQ GPx Reductone de novo synthesis K+K+ Na + Host cell Food vacuole Parasite 1 2 9 10 11 36 8 7 45 - Enzyme

15. H V RS VH P

16. Table 1. Reported polymorphisms on the Plasmodium falciparum chloroquine resistance transporter gene, pfcrt, on chromosome 7. Wernsdorfer, Curr Opin Infect Dis, 2003, 16, 553-558.