Plasmodium knowlesi: finally being recognized.

In the 1960s, after the accidental laboratory acquisition by humans of infections with the simian malaria parasite Plasmodium cynomolgi via mosquito bite, there was a concerted effort to determine whether such infections are acquired under natural conditions of transmission [1, 2]. Soon thereafter, the natural transmission of a Plasmodium knowlesi infection was reported in a US traveler [3]. Subsequent volunteer studies conducted at the National Institutes of Health determined that humans were indeed susceptible to infection with the simian parasites P. cynomolgi, Plasmodium inui, and P. knowlesi via mosquito bite, but the infections were not considered life-threatening [4, 5]. At that time, definitive diagnosis of an infection with a simian parasite depended on the subpassage of blood from the infected human into a susceptible host, such as the rhesus monkey, Macaca mulatta, combined with detailed examination of Giemsa-stained blood films. Previously it had been shown that the human malaria parasites, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae, would not infect Old World M. mulatta monkeys. It was deemed possible that humans could be infected when they encroached on the areas where specific vectors and primates normally maintained the transmission cycle, with infected mosquitoes that normally preferred simians transmitting the monkey parasites to the human intruders. However, after the first report in 1965, no other confirmed reports of monkey malaria in humans appeared until the recent reports of hundreds of cases of P. knowlesi infection in humans [6, 7]. These reports, from Borneo, have been aided by the availability of molecular diagnostic tools to distinguish P. knowlesi from human malarial parasites—primarily P. malariae [6, 7]—and they have clearly demonstrated that infections of humans with monkey malaria parasites are far from rare in this area and may cause death in some cases. With the clearing of land for agricultural purposes, humans have increasingly entered the environment in which infected vectors can feed on them, transmitting parasites. P. knowlesi is transmitted by members of the Anopheles leucosphyrus group of mosquitoes. Anopheles latens, a major vector of human malaria on Borneo, is a member of this group. It feeds on humans and nonhuman primates and has the ability to transmit P. knowlesi [8]. Ecologically, the area is well suited for an interface among humans, the vector species, the malaria parasite, and the simian host: an ideal situation for the transmission of P. knowlesi to humans. There have also been recent reports of human infection with P. knowlesi in other areas scattered across southeastern Asia, coinciding with the range of the A. leucosphyrus group of mosquitoes [9–12]. Although not all members of this large group have been proved to be vectors, none of the other mosquito groups of the region have been shown experimentally to be capable of transmitting P. knowlesi [9–12]. This issue of the Journal includes a report by Putaporntip et al. [13] on an extensive survey conducted in Thailand to compare microscopic and polymerase chain reaction diagnosis of malaria infection. Of the 10 patients found to be infected with P. knowlesi, 9 were also infected with P. falciparum or P. vivax. Seven of the 10 either kept monkeys as pets or had monkeys in the vicinity. Sequence analysis demonstrated variation in the small subunit ribosomal RNA gene of the P. knowlesi parasites, indicating that the transmission to humans in Thailand was not from a single parasite population. It appears that humans are susceptible to infection with P. knowlesi strains throughout the range of distribution of this parasite. The conclusion from this and other studies is that humans can be infected anywhere within the range of distribution of the A. leucosphyrus complex of mosquitoes if infected monkeys are present. The distribution of P. knowlesi is probably defined by that of the A. leucosphyrus complex. Interestingly, P. knowlesi is lethal to M. mulatta monkeys, and it is strongly beReceived 9 January 2009; accepted 12 January 2009; electronically published 24 March 2009. Potential conflicts of interest: none reported. Financial support: none reported. The opinions expressed here are those of the authors and do not represent the views of the Centers for Disease Control and Prevention. Reprints or correspondence: Dr. William Collins, Malaria Branch, Div. of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724 (wecl@cdc.gov). The Journal of Infectious Diseases 2009; 199:1107– 8 This article is in the public domain, and no copyright is claimed. 0022-1899/2009/19908-0003 DOI: 10.1086/597415 E D I T O R I A L C O M M E N T A R Y