Plasmodium knowlesi infecting humans in Southeast Asia: What’s next?

Abstract

Plasmodium knowlesi, a simian malaria parasite, has been in the limelight since a large focus of human P. knowlesi infection was reported from Sarawak (Malaysian Borneo) in 2004. Although this infection is transmitted across Southeast Asia, the largest number of cases has been reported from Malaysia. The increasing number of knowlesi malaria cases has been attributed to the use of molecular tools for detection, but environmental changes including deforestation likely play a major role by increasing human exposure to vector mosquitoes, which coexist with the macaque host. In addition, with the reduction in human malaria transmission in Southeast Asia, it is possible that human populations are at a greater risk of P. knowlesi infection due to diminishing cross-species immunity. Furthermore, the possibility of increasing exposure of humans to other simian Plasmodium parasites such as Plasmodium cynomolgi and Plasmodium inui should not be ignored. We here review the current status of these parasites in humans, macaques, and mosquitoes to support necessary reorientation of malaria control and elimination in the affected areas.

Natural Plasmodium inui Infections in Humans and Anopheles cracens Mosquito, Malaysia

“…P. inui sporozoites have been found naturally occurring in An. cracens mosquitoes ( 2 ). Other mosquito species from the Leucosphyrus group can transmit P. inui naturally ( 2 ).…”

“…cracens mosquitoes ( 2 ). Other mosquito species from the Leucosphyrus group can transmit P. inui naturally ( 2 ). In addition, laboratory experiments showed P. inui adapted to co-indigenous Anopheles mosquito species ( 13 ).…”

“…A surveillance study reported that the prevalence of P. inui among wild macaques in Pahang was 66.7% (26/39 macaques sampled); 76.9% of these infections were co-infections with other Plasmodium species ( 14 ). Given the high prevalence of P. inui among macaques and natural Anopheles mosquito vectors ( 2 ), humans could be exposed to P. inui via vectorborne transmission from infected macaques, particularly at a location where humans, macaque hosts, and mosquito vectors co-exist. Furthermore, studies report that P. inui often occurs in co-infections with P. knowlesi and P. cynomolgi in monkeys and mosquitoes ( 2 ), and that humans frequently can be exposed to a mix of nonhuman primate malaria sporozoites ( 15 ).…”

“…Given the high prevalence of P. inui among macaques and natural Anopheles mosquito vectors ( 2 ), humans could be exposed to P. inui via vectorborne transmission from infected macaques, particularly at a location where humans, macaque hosts, and mosquito vectors co-exist. Furthermore, studies report that P. inui often occurs in co-infections with P. knowlesi and P. cynomolgi in monkeys and mosquitoes ( 2 ), and that humans frequently can be exposed to a mix of nonhuman primate malaria sporozoites ( 15 ). Because human P. inui infections can be asymptomatic, P. inui could evolve to efficiently infect humans ( 2 ), especially considering patent human infection can be established by just a few parasites ( 8 ).…”

“…Zoonotic transmission of simian malaria parasites to humans have been occurring in Southeast Asia and South America. Among the 3 simian malaria parasites in Southeast Asia experimentally shown to infect humans ( 1 ), Plasmodium knowlesi , P. cynomolgi , and P. inui , only P. knowlesi and P. cynomolgi have been reported in cases of natural infection ( 2 ). We report 2 natural, asymptomatic P. inui human infections detected by using nested PCR (nPCR) on concentrated high-volume blood.…”