The role ofPlasmodium knowlesiin the history of malaria research

Abstract

In recent years, a malaria infection of humans in South East Asia, originally diagnosed as a known human-infecting species, Plasmodium malariae, has been identified as a simian parasite, Plasmodium knowlesi. This species had been subject to considerable investigation in monkeys since the 1930s. With the development of continuous culture of the erythrocytic stages of the human malarial parasite, Plasmodium falciparum in 1976, the emphasis in research shifted away from knowlesi. However, its importance as a human pathogen has provoked a renewed interest in P. knowlesi, not least because it too can be maintained in continuous culture and thus provides an experimental model. In fact, this parasite species has a long history in malaria research, and the purpose of this chapter is to outline approximately the first 50 years of this history.

Clinical features and management ofPlasmodium knowlesiinfections in humans

“…Although interest in naturally occurring human infections then waned, the ability of P. knowlesi to induce fatal infections in Rhesus macaques stimulated further research in non-human primate models examining immunological and pathophysiological aspects of malaria [see recent review (Butcher and Mitchell, 2016)] and for pharmacological studies including testing of novel agents [see for examples (Singh et al 1951 a , b ; Singh and Dutta, 1981; Ding et al . 1991)].…”

Functional genomics of simian malaria parasites and host–parasite interactions

“…Plasmodium knowlesi has proven for decades to be an excellent experimental model parasite (reviewed in [29, 30, 72]) and, as noted above, the Malayan strain genome sequence has been available [40, 41]. Advanced sequencing technologies are now permitting the development of whole-genome sequence data from P .…”

“…Going forward, directional RNA-seq has the potential to provide a more detailed view of gene expression across the P. knowlesi intraerythrocytic development cycle, and to confirm the presence of specific sense and antisense nc RNAs, and importantly whether they are associated with the ON or OFF states of SICAvar genes (reviewed in [72]), and if they have functional roles similar to those being unraveled in functional studies of P. falciparum var gene expression [92, 114, 115]. Furthermore, the time is ripe for functional genomics analysis of P. knowlesi in the context of the rhesus monkey where extreme virulence is the norm, and its natural human and NHP hosts where resilience is the norm (though severe situations are possible, as indicated above with regards to zoonotic infections) (reviewed in [29, 30]). Longitudinal systems biology infection experiments can begin to discern the physiological and immunological host factors and cascades that result in one outcome or another.…”

Plasmodium knowlesi: experimental model, zoonotic pathogen and golden opportunity?

“…While the hyper-susceptible phenotype in Rhesus macaques re-enforced the perception that P. knowlesi is not a suitable model for malaria pathophysiology this phenotype is not universal among Rhesus macaques, as Butcher and Mitchell point out in this issue (Butcher and Mitchell, 2016). Originally there were several P. knowlesi -Rhesus macaque models and early research described variable disease phenotypes depending on the experimental P. knowlesi line used and the origin of the Rhesus monkey (Butcher and Mitchell, 2016).…”

“…Originally there were several P. knowlesi -Rhesus macaque models and early research described variable disease phenotypes depending on the experimental P. knowlesi line used and the origin of the Rhesus monkey (Butcher and Mitchell, 2016). With time, the highly susceptible Rhesus of Indian origin became the experimental host of choice, and information on diverse disease phenotypes was effectively lost.…”