Of particular concern is the fact that at least 10% of
patients with knowlesi malaria develop severe disease,
with 1–2% of infections resulting in death [10]. Prospective
clinical studies show that P. knowlesi parasitaemia correlates
with clinical and laboratory markers of disease severity
[11], such that those patients with the highest
parasitaemias are the ones most likely to have severe
symptoms. The factors that determine whether a particular
patient will develop high parasitaemia are expected to
be numerous, and host genotype and immune status are
likely to have significant roles. However, P. knowlesi parasites
are genetically diverse [12–14], and this variability
may contribute to the differential severity of infection
observed between patients with knowlesi malaria. In other
species of malaria parasites, variable invasion gene expression
has been implicated in differences in red blood cell
invasion pathway utilization (reviewed in [3,15]).