Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence

Abstract

Two potential malaria virulence factors, parasite multiplication rate (PMR) and red blood cell selectivity (measured as selectivity index [SI]), were assessed in Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not differ significantly between uncomplicated and severe malaria cases. Malian isolates from hyperparasitemic patients had significantly lower PMRs (median = 1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n = 23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test). Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98; Mali geometric mean SI = 1.6, n = 104), and there was no significant association between the SI and malaria severity. Therefore, in contrast to previous results from Thailand, we found no association of PMR and SI with malaria severity in African children. This raises the possibility of differences in the mechanisms of malaria virulence between sub-Saharan Africa and Asia.

Figure 1

Parasite multiplication rates (PMRs) of A, Kenyan and B, Malian Plasmodium falciparum isolates from children diagnosed with uncomplicated or severe malaria. Isolates from Malian children diagnosed with hyperparasitemia (Hyperpt.) are shown as a separate group. Equivalent children with hyperparasitemia and no other symptoms or signs of severe malaria occur in Kenya, but they were not recruited because of the study design. The median PMR for each group is indicated by the closed circle and line.

Figure 2

Scatter plots indicating the negative correlation between the parasite multiplication rate and host parasitemia of Plasmodium falciparum isolates from A, Kenya (n = 33) and B, Mali (n = 61).

Figure 3

Scatter plots indicating the negative correlation between the selectivity index and host parasitemia of Plasmodium falciparum isolates from A, Kenya (n = 98) and B, Mali (n = 104).

Figure 4

Geometric mean selectivity index (SI) of Plasmodium falciparum isolates from A, Kenya and B, Mali separated by patient malaria severity (black bars = uncomplicated; white bars = severe, gray bars = hyperparasitemia) and host parasitaemia group. Errors bars show 95% confidence intervals. Four samples with an SI of 0 (i.e., no multiple-infected cells) were excluded (two Kenyan and two Malian). max = maximum.

Figure 5

Scatter plots indicating the relationship between the parasite multiplication rate (PMR) and selectivity index (SI) of Plasmodium falciparum isolates from A, Kenya (n = 29) and B, Mali (n = 60). These samples are the subset from the SI data shown in Figure 3 for which there is corresponding PMR data.