Table 5.

Main conclusions from identified literature with accompanying qualitative assessment of evidence

Conclusion	Evidence
Experimental human-mosquito-human transmission has been demonstrated in laboratory settings	High consistency, limited evidence
Spatio-temporal clusters of human cases have been found which may be consistent with human-mosquito-human transmission but no quantitative analyses have been performed to confirm this	Medium consistency, limited evidence
Distribution of known natural hosts and vectors for P. knowlesi correlates with areas where human cases have been reported	High consistency, robust evidence
No secondary P. knowlesi cases have been reported outside endemic areas without a history of travel	Medium consistency, limited evidence
The lack of P. knowlesi cases in malaria endemic areas is most likely due to detection bias and misdiagnosis	High consistency, limited evidence
Models suggest human-mosquito-human transmission is unlikely but still plausible within observed parameters	High consistency, medium evidence
Models suggest reproductive rates are highly sensitive to contact patterns between simian hosts, vectors and people as well as vector biting preferences and likely to be highly affected by land use change	High consistency, robust evidence
Mixed infections with P. knowlesi and human malaria species have been reported in both humans and known natural vectors across various countries in South-East Asia	High consistency, robust evidence
P. knowlesi parasites can adapt to exclusive human red blood cell culture, invading and multiplying successfully for multiple generations	High consistency, medium evidence
P. knowlesi parasites have a preference for invading young human erythrocytes, although this does not pose a significant barrier to invasion	Medium consistency, medium evidence
Multiple invasion pathways have been identified, with a range of specific proteins aiding cell invasion. This shows there are no molecular barriers to invasion of human erythrocytes other than the requirement of Duffy antigens	High consistency, robust evidence
There are genetically distinct subpopulations of P. knowlesi parasites associated with different macaque populations and human cases from different geographical areas but no clear evidence of host specific circulation as would be expected with widespread non-zoonotic transmission	Low consistency, medium evidence
There is no evidence of drug resistance in P. knowlesi	High consistency, robust evidence