Plasmodium knowlesi malaria is a newly described zoonosis
in Southeast Asia. Similarly to Plasmodium falciparum,
P. knowlesi can reach high parasitaemia in the
human host and both species cause severe and fatal
illness. Interpretation of host–parasite interactions in
studies of P. knowlesi malaria adds a counterpoint to
studies on P. falciparum. However, there is no model
system for testing the resulting hypotheses on malaria
pathophysiology or for developing new interventions.
Plasmodium knowlesi is amenable to genetic manipulation
in vitro and several nonhuman primate species are
susceptible to experimental infection. Here, we make a
case for drawing on P. knowlesi as both a human pathogen
and an experimental model to lift the roadblock
between malaria research and its translation into human
health benefits.