Estimating Total Parasite Burden in Severe Malaria

Estimation of the total body parasite burden from plasma PfHRP2 has been described in detail in Asian adults with severe malaria and requires incorporation of an elimination half-life estimate [15] (link). This was assessed separately in African children because clearance might be dependent on immunity (antibodies against PfHRP2), which has a higher level in high transmission settings, and PfHRP2 production is parasite strain dependent [20] (link). Plasma PfHRP2 half-life was assessed in 30 patients from Tanzania from samples taken on admission and after 3 and 7 days following treatment. Separate ethical approval for this sub-study was obtained from the Ethics Committee of the National Institute for Medical Research, Tanzania. These data were analysed using WinNonlin statistical package (Pharsight, Mountain View, California, US). Individual PfHRP2 concentration-time curves were fitted according to a first-order elimination model. From this, a mean (95%CI) plasma elimination half-life (t_½) was estimated as 1.10 (0.91 to 1.29) days, or 0.55 erythrocytic cycles. Half-life was not significantly different between treatment arms, and was not correlated with renal function (estimated by blood urea nitrogen [BUN]). A parasite multiplication factor of 3 immediately before peak parasitaemia was assumed, based on in-vitro and Saimiri monkey studies of African parasite strains causing severe malaria [21] (link),[22] (link). Higher multiplication rates were explored in a sensitivity analysis [23] (link),[24] (link). The formula for total parasite burden is: P_tot = 7.3×PfHRP2×(1−Hct)×body weight [kg] ×10¹³, with PfHRP2 in g/L [15] (link). The differences in the current formula with the one used earlier in adult Asian patients result from the different estimates for plasma PfHRP2 half-life and parasite multiplication rates. The circulating parasite burden was calculated from the peripheral blood: parasites/µl×10⁶×blood volume ( = 0.08×weight [kg]) [15] (link). The sequestration index was calculated as total parasite burden/circulating burden [25] (link).