Plasmodium knowlesi

Plasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. It causes malaria in long-tailed macaques (Macaca fascicularis), but it may also infect humans, either naturally or artificially. Plasmodium knowlesi is the sixth major human malaria parasite (following the division of Plasmodium ovale into 2 subspecies). It may cause severe malaria as indicated by its asexual erythrocytic cycle of about 24 hours, with an associated fever that typically occurs at the same frequency (i.e. the fever is quotidian). This is an emerging infection that was reported for the first time in humans in 1965. It accounts for up to 70% of malaria cases in certain areas in South East Asia where it is mostly found. This parasite is transmitted by the bite of an Anopheles mosquito. Plasmodium knowlesi has health, social and economic consequences for the regions affected by it. The first person to see P. knowlesi was probably the Italian Giuseppe Franchini in 1927 when he was examining the blood of Macaca fascicularis and he noted that it differed from Plasmodium cynomolgi and Plasmodium inui. It was later seen by Campbell in 1931 in a long-tailed macaque imported from Singapore to the Calcutta School of Tropical Medicine and Hygiene in India. Campbell was interested in another disease, kala azar, and was working under Napier. Napier inoculated the strain into three monkeys, one of which was a rhesus macaque (Macaca mulatta), which developed a fulminating infection. Knowing that the Protozoological Department were looking for a monkey malaria strain, they handed the original infected monkey to Biraj Mohan Das Gupta, who was the assistant of Robert Knowles. Dr Das Gupta maintained the species by serial passage in monkeys until Dr Knowles returned from leave. In 1932, Knowles and Das Gupta described the species in detail for the first time and showed that it could be transmitted to man by blood passage, but failed to name it. It was named by Sinton and Mulligan in 1932 after Dr Knowles. From early in the 1930s to 1955, P. knowlesi was used as a pyretic agent for the treatment of patients with neurosyphillis. In 1957, it was suggested by Garnham et al. that P. knowlesi could be the fifth species capable of causing endemic malaria in humans. In 1960, American parasitologist Don E. Eyles and his supervisor, G. Robert Coatney (1902–1990) worked under the National Institutes of Health to carry out experiments on rhesus macaques in a Memphis laboratory with the assumption that humans were not susceptible to “monkey malaria.” Early research had concluded that macaques could not host Plasmodium vivax, the human malaria parasite. This led Eyles and Coatney to begin working with Plasmodium cynomolgi, a parasite similar enough to P. vivax to model the human malaria infection. The two exposed themselves to the infection, noting the causal itchy bite as a mere annoyance; however, Eyles fell ill with fever soon after the experiment. It was not until several days later that the two accepted the possibility that Eyles may have contracted malaria. Examination of blood films would confirm that it was in fact possible to contract “monkey malaria.” In 1965, the first case of a naturally occurring infection of knowlesi malaria in humans was reported in a 37-year-old male who worked as a surveyor for the U.S. Army Map Service. After carrying out a short trip to peninsular Malaysia, he traveled to Thailand, where he began to feel ill. Although the infecting parasite was initially identified as P. falciparum, one day later it was then identified as P. malariae and it was only confirmed to be P. knowlesi after infected blood was used to inoculate rhesus monkeys. In observing the local population where the infection took place, Dr. G. Robert Coatney and other researchers found that they were regularly exposed to the parasite, and, further, were joint hosts of the parasite along with the local monkey populations. This observation led Coatney to declare that monkey malaria is a “true zoonosis.” Prior to arranging the surveyor’s treatment, Coatney had samples of his blood sent back to his lab in Atlanta, where they would be used to infect human prison volunteer inmates and monkeys. A second report emerged in 1971 about the natural infection of a man in Malaysia with Plasmodium knowlesi followed by the description of a large focus of human infections in the Kapit Division of Sarawak, Malaysian Borneo. This was made possible due to the development of molecular detection assays which could differentiate between Plasmodium knowlesi and the morphologically similar Plasmodium malariae. Since 2004, there has been an increasing number of reports of the incidence of P. knowlesi among humans in various countries in South East Asia, including Malaysia, Thailand, Singapore, the Philippines, Vietnam, Myanmar and Indonesia. Work with archival samples has shown that infection with this parasite has occurred in Malaysia at least since the 1990s and it is now known to cause 70% of the malaria cases in certain areas of Sarawak. Based on a Bayesian coalescent approach the most probable time of evolution of P. knowlesi is 257,000 years ago (95% range 98,000–478,000). Yakob and coauthors calculated the likelihood of natural host switching from the long-tailed macaque monkey to humans using an evolutionary invasion analysis and demonstrated how this switch was contingent on relative host densities and individual-level mosquito feeding preferences.