Plasmodium knowlesi: The Fifth Human Malaria Parasite

Abstract

In 1932, when Knowles and Das Gupta [1] succeeded in transmitting to humans the monkey malaria they had discovered, it appeared that a new agent for malaria therapy had been discovered. Since the Nobel Prize-winning research of Julius Wagner-Jauregg, malaria therapy had become widely used for the treatment of general paralysis of the insane (neurosyphilis), one of the main reasons for admission to psychiatric institutions. But it soon became apparent that this infection could rapidly become uncontrollable, and after several fatalities, its use was largely discontinued in favor of the less virulent human parasite Plasmodium vivax. Malaria parasites are generally rather choosy, both about their mammalian, avian, or reptilian hosts and their respective mosquito vectors. Transmission of Plasmodium knowlesi, for malaria therapy, from human to human was by blood passage. So initially, it was uncertain whether natural infection could take place and, thus, whether this could be a zoonosis. In 1960, Eyles et al. [2] demonstrated the first experimental mosquito transmission of a simian malaria organism to humans (Plasmodium cynomolgi), and in 1967, Chin et al. [3] showed that P. knowlesi could also be transmitted from monkeys to humans. The mosquitoes used were Anopheles balabacencis (part of the Anopheles leucosphyrus group, which has undergone extensive taxonomic revision in recent years). This is an important vector of human malaria in forested areas of Southeast Asia, where the natural hosts of P. knowlesi—the long-tailed and pig-tailed macaques (Macaca fasicularis and Macaca nemestrina, respectively)—normally live. But the zoonotic potential of P. knowlesi has, until recently, seemed limited, with only sporadic case reports of human infection.