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Table 1 Multi-scale ecological and evolutionary drivers of Plasmodium knowlesi.
| Scale and description | Drivers | Gaps in knowledge |
|---|---|---|
| Continental: global spread and dispersal of pathogen | Earth history | Phylogenetic links between P. knowlesi and other related taxa, shared life-history traits |
| Regional/biogeographic: broad climatic variation or geographical boundaries restrict P. knowlesi to SE Asia | Barriers to dispersal; natural distribution of hosts and vectors and biodiversity patterns | Distribution of the hosts and vectors of the parasite and the enabling and limiting factors for this distribution |
| Local landscape: fine-scale distribution of species within the habitat | Interaction between parasite, host, and vector within a rapidly changing habitat | Changing forest cover and land use and the effects on the distribution of vectors and hosts of P. knowlesi and parasite transmission rate |
| Individual: limiting and facilitating factors of transmission to humans | Individual health, behaviour, interaction with the vector and host, level of detection and treatment | Severity of infection in Malaysian Borneo versus the rest of SE Asia; asymptomatic carriage of the parasite within communities; degree of human to human transmission |
| Cellular: disease pathways | Infection route, immunological status, previous exposure | P. knowlesi multiplication in human blood; methods for accurate diagnosis |
| Molecular: human resistance to the disease; different genotypes of the parasite | Human host resistance or susceptibility; different P. knowlesi genotypes have varying disease severity and host preferences | Genetic factors influencing disease severity, genetic factors influencing choice of hosts and vectors, erythrocyte invasion pathways |
