Even though Ang-1 and Ang-2 concentrations correlate with disease severity, the results of the correlation between Ang-1 or Ang-2 concentrations in
P. falciparum infection and parasitaemia, sequestration or rosetting vary between the studies [
25,
28,
33,
34,
43,
46,
49]. The lack of a consistent correlation of the Ang-1 concentration, Ang-2 concentration and Ang-2/Ang-1 ratio with parasitaemia may be due to the fact that this parameter is determined in peripheral blood and does not reflect the true parasite load as sequestered parasites are not adequately taken into account. A correlation between
PfHRP2, which reflects total parasite load during
P. falciparum infection and Ang-2 was found in three studies [
34,
43,
46], but sequestration [
46] and rosetting corrected for disease severity [
49] did not correlate with Ang-1 and/or Ang-2 concentrations. The correlation between Ang-2 with parasite load but not with sequestration and rosetting might be due to: (1) the fact that
PfHRP2 levels [
34,
43,
46], measuring sequestration with a OPD device [
46] and IgG antibody levels [
49] are all markers that may not estimate their biological phenomena similarly; (2) a temporal dissociation of the determinations [
46]; (3) loss of correlation due to the fact that locally observed phenomena (sequestration and rosetting) were compared to a systemic phenomenon (Ang-2 release) [
46]; or, (4) the infected erythrocytes may activate endothelial cells not by direct, physical contact, but indirectly by inducing other endothelial cell activators, such as cytokines [
69,
70]. Next to the quantity of parasite biomass, the
Plasmodium strain and the host response might contribute to the variations in Ang-2 increase, although it should be noted that an included study [
49] did not show a relation between Ang-2 and group A-like
PfEMP expression if corrected for disease severity. However, the possible differences in other genes were not examined in that study. Taken together, the host-response-related marker Ang-2 might be a good or better biomarker for disease severity and treatment follow-up than pathogen-related markers, such as parasite load or parasitaemia.