of P. knowlesi malaria have been reported in most countries of Southeast Asia as well as travelers from the region. Infection with P. knowlesi is associated with socioeconomic and lifestyle factors that bring people into the dense forests where the mosquito hosts are commonly found. In particular, those who work in the forest or at its margin such as farmers, hunters, and loggers are at increased risk for infection. Likely for this reason, males are infected more frequently than females, and adults are infected more frequently than children. Research P. knowlesi has long been used as a research model for studying the interaction between parasite and host, and developing antimalarial vaccines and drugs. Its utility as a research model is partly due to its ability to infect rhesus macaques, a common laboratory model primate. Rhesus macaques are highly susceptible to P. knowlesi and can be infected by mosquito bite, injection of sporozoites, or injection of blood-stage parasites. Infected monkeys develop some hallmarks of human malaria including anemia and enlargement of the spleen and liver. Infection is typically fatal if untreated, with the cause of death seemingly circulatory failure characterized by adhesion of infected red blood cells to the blood vessel walls. Monkeys can be cured of infection by treatment with antimalarials; repeated infection followed by cure results in the monkeys developing some immunity to infection, a topic that has also been the subject of substantial research. P. knowlesi is also used for in vitro research into Plasmodium cell biology. Isolated sporozoites can infect primary rhesus hepatocytes, allowing the in vitro study of the parasite liver stage. Additionally, P. knowlesi and P. falciparum are the only Plasmodium species that can be maintained continuously in cultured red blood cells, both rhesus and human. Facilitating molecular biology research, the P. knowlesi genome has been sequenced and is available on PlasmoDB and other online repositories. P. knowlesi can be genetically modified in the lab by transfection either in the rhesus macaque model system, or in blood cell culture. Blood-infecting stages and sporozoites can be stored long-term by freezing with glycerolyte, allowing the preservation of strains of interest. History 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