preservation of strains of interest. history robert knowles, after whom p. knowlesi was named the italian physician giuseppe franchini first described what may have been p. knowlesi in 1927 when he noted a parasite distinct from p. cynomolgi and p. inui in the blood of a long-tailed macaque. in 1931, the parasite was again seen in a long-tailed macaque by h. g. m. campbell during his work on kala azar (visceral leishmaniasis) in calcutta; campbell's colleague lionel everard napier drew blood from the affected monkey and inoculated three laboratory monkeys, one of which was a rhesus macaque that developed a severe infection. campbell and napier gave the infected monkey to biraj mohan das gupta who was able to maintain the parasite by serial passage through monkeys. in 1932, das gupta and his supervisor robert knowles described the morphology of the parasite in macaque blood, and demonstrated that it could infect three human patients (in each case it was used to induce fever with the hope of treating another infection). also in 1932, john sinton and h. w. mulligan further described the morphology of the parasite in blood cells, determined it to be a distinct species from others described, and named it plasmodium knowlesi in honor of robert knowles. soon thereafter, in 1935 c. e. van rooyen and george r. pile reported using p. knowlesi infection to treat general paralysis in psychiatric patients. p. knowlesi would go on to be used as a general pyretic agent for various diseases, particularly neurosyphilis for which it was used until at least 1955. while cyril garnham had suggested in 1957 that p. knowlesi might naturally infect humans, the first documented case of a human naturally infected with p. knowlesi was in 1965 in a u.s. army surveyor who developed chills and fever after a five-day deployment in malaysia. based on this finding, a team at the institute for medical research in peninsular malaysia undertook a survey of people living in proximity to macaques, but failed to find evidence that simian malaria was being transmitted to humans. through the 1960s and 1970s, scientific research groups used p. knowlesi as a research model to make seminal discoveries in malaria. in 1965 and 1972, several groups characterized how p. knowlesi antigenic variation contributed to immune evasion and chronic infection. in 1975, louis h. miller and others showed that p. knowlesi required duffy factor on the surface of red blood cells in order to invade them (they would go on to show the same requirement for p. vivax a year later). work on p. knowlesi as a human malaria parasite was revitalized in 2004, when balbir singh and others used pcr to show that over half of a group of humans diagnosed with p. malariae malaria in malaysian borneo were actually infected with p. knowlesi. over the following decade, several investigators used molecular detection methods capable of distinguishing p. knowlesi from morphologically similar parasites to attribute an increasing proportion of malaria cases to p. knowlesi throughout southeast asia. work with archival samples has shown that infection with this parasite has occurred in malaysia at least since the 1990s.