The parasite clearance curve

Abstract

Parasite clearance rates are important measures of anti-malarial drug efficacy. They are particularly important in the assessment of artemisinin resistance. The slope of the log-linear segment in the middle of the parasite clearance curve has the least inter-individual variance and is the focus of therapeutic assessment. The factors affecting parasite clearance are reviewed. Methods of presentation and the approaches to analysis are discussed.

Figure 1

Two P. falciparum parasite clearance curves with identical therapeutic responses illustrating the dependence of the parasite clearance time on pre-treatment parasite density.

Figure 2

Sources of variance in the P. falciparum parasite clearance curve.

Figure 3

The proportion of patients with falciparum malaria remaining parasitaemic after receiving rectal artemisinins or parenteral quinine in a series of randomized trials reviewed by Gomes et al, with permission [47].

Figure 4

Normalized P. falciparum parasite clearance curves showing the fraction of initial parasitaemia versus time in patients treated with artesunate in Western Cambodia and Western Thailand. Parasite clearance was significantly slower in Western Cambodia. From Dondorp et al, with permission [37].

Figure 5

Normalized raw data from the Cambodian study shown in Figure 4.

Figure 6

The P. falciparum normalized parasite clearance curve. Underneath the duration of variance derived from asynchronous schizont rupture and sequestration is shown.

Figure 7

The proportion of patients with fully artemisinin sensitive P. falciparum infections who are slide positive on day 3 are shown with 95 and 99% confidence intervals. From Stepniewska et al with permission [45].