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Fig. 1 | Malaria Journal

Fig. 1

From: Measuring windows of selection for anti-malarial drug treatments

Fig. 1

Potential problems with using patent parasitaemia to estimate ‘windows of selection’ (WoS). Field studies typically measure the WoS by comparing the times different genotypes become detectable (‘patent’) in patients. As an example, the clinical data of Sisowath et al. [3], showed that resistant parasites bearing the pfmdr1 D1246Y mutation (top row; blue squares) first become patent in patients approximately 20 days after treatment and about 15 days earlier than sensitive parasites (bottom row; green squares). Each new infection was assumed to comprise 105 parasites emerging from the liver and to become patent if/when their numbers reached 108 parasites (horizontal dashed lines). The black line shows the decrease in drug concentration over time (using a single drug dose for illustration). Lines A and B show two clones that emerge on the same day but grow at different rates because of their differing IC50s and become patent several days apart. Here, field estimates based on patent parasitaemia would quantify a WoS of around 5 days when in fact there is none. Lines C 1 –C 3 illustrate how the earliest emerging parasites may not necessarily correspond to the first patent infection. C 1 is the earliest emerging clone but residual drug levels cause an initial drop in parasite numbers and so C 2 , which emergences slightly later, is able to become patent sooner. Similarly, by the time C 3 emergences from the liver, drug levels have fallen sufficiently that it no longer effects the newly emerged clone and so C 3 becomes patent before both C 1 and C 2 . The ‘clinical’ WoS is actually wrong: the true order of survival is C 1 , C 2 , C 3 but the clinical order is C 3 , C 2 , C 1.

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