Can malaria parasites be spontaneously cleared?

A large body of evidence demonstrates that Plasmodium falciparum infections are chronic in malaria endemic areas; however, the notion of spontaneous clearance in the absence of antimalarial drug treatment is rarely discussed. In this opinion article, we review and reinterpret data to postulate that spontaneous clearance of P. falciparum infections occurs frequently, has been demonstrated in a range of transmission settings, and confirmed by the most sensitive malaria diagnostic techniques. We also discuss factors which may influence the likelihood, measurement, and conclusions of spontaneous clearance. A greater understanding of the phenomenon of spontaneous clearance will advance our knowledge of malaria epidemiology, transmission potential of malaria parasites, as well as inform interventions for malaria control and elimination.