Asymptomatic Natural Human Infections With the Simian Malaria Parasites Plasmodium cynomolgi and Plasmodium knowlesi

Abstract

BackgroundIn Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed macaques (Macaca fascicularis), is an important cause of human malaria. Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.MethodsMalariometric studies involving 5422 subjects (aged 6 months to 65 years) were conducted in 23 villages in Pailin and Battambang, western Cambodia. Parasite detection and genotyping was conducted on blood samples, using high-volume quantitative PCR (uPCR).ResultsAsymptomatic malaria parasite infections were detected in 1361 of 14732 samples (9.2%). Asymptomatic infections with nonhuman primate malaria parasites were found in 21 individuals living close to forested areas; P. cynomolgi was found in 11, P. knowlesi was found in 8, and P. vivax and P. cynomolgi were both found in 2. Only 2 subjects were female, and 14 were men aged 20–40 years. Geometric mean parasite densities were 3604 parasites/mL in P. cynomolgi infections and 52488 parasites/mL in P. knowlesi infections. All P. cynomolgi isolates had wild-type dihydrofolate reductase genes, in contrast to the very high prevalence of mutations in the human malaria parasites. Asymptomatic reappearance of P. cynomolgi occurred in 2 subjects 3 months after the first infection.ConclusionsAsymptomatic naturally acquired P. cynomolgi and P. knowlesi infections can both occur in humans.Clinical Trials RegistrationNCT01872702.

The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host-switching

“…Severe and lethal outcomes have been reported in people infected with P. knowlesi in Malaysia 8 , whilst infection with P. cynomolgi in the same region appears to cause moderate/mild clinical symptoms 9 . Interestingly, both P. knowlesi and P. cynomolgi infections in the Mekong region appear less virulent than in Malaysia, and are often asymptomatic 3,10 , and this may be due to the relative virulence of the parasite strains circulating there and/or differences in the susceptibility of the local human populations. As the parasites of non-human primates have co-evolved with and adapted to their monkey hosts, it is impossible to predict their potential pathogenesis in zoonotic human infections.…”

“…There are currently eight species of malaria parasites known to cause disease in humans; Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale curtisi, Plasmodium ovale wallikeri, Plasmodium knowlesi, Plasmodium cynomolgi and Plasmodium simium . The latter three species are more commonly parasitic on non-human primates and have only relatively recently been shown to infect humans 1-3 .…”

Spatial-temporal Distribution and Demography of Knowlesi Malaria in Peninsular Malaysia, 2011 to 2018

“…Imported cases involving Malaysians were most potentially due to international travel to knowlesi malaria endemic countries. Besides Malaysia, P. knowlesi infections have been reported throughout Southeast Asia including Indonesia [23], Vietnam [24], Thailand [25], and Cambodia [26].…”

New vectors in northern Sarawak, Malaysian Borneo, for the zoonotic malaria parasite, Plasmodium knowlesi

“…It is highly likely that unidentified Plasmodium species co-infected the vectors when they fed on macaques, which have been found in Sarawak to harbour at least 7 species of Plasmodium [51]. With an increasing number of zoonotic malaria infections in the world [52][53][54], epidemiological studies of these novel species within human populations that come into close contact with macaques during activities in the forest and forest-fringe will be required to monitor potential host-switch events.…”