Fig. 1

Relationship between early parasite clearance and drug resistance. This hypothetical example shows how the parasite clearance curve might change as drug resistance progressively compromises an artemisinin-based combination therapy (ACT). Parasite clearance curves are shown for fully sensitive (blue), early resistance (green), established resistance (orange), and advanced resistance (red) scenarios. The earliest event in the progression of resistance is delayed early parasite clearance – but drug activity may still be sufficient to clear the total body parasite burden and achieve cure. As resistance becomes established, initial parasite killing may be sufficient for parasitemia to fall below the threshold of microscopic detectability (dashed line) but not to eliminate the entire body parasite burden – leading to recrudescence and late treatment failure. Complete failure to clear parasites (early treatment failure) will only occur once resistance to both drugs in an ACT combination has become very advanced