Authors
A J Reid4; T Brugat1; D Cunningham1; J Lin1; S McLauglin1; G Kushinga1; I Tumwine1; P Spence2; U Boehme4; M Sanders4; C Newbold3; M Berriman4; J Langhorne1; 1 The Francis Crick Institute; 2 University of Edinburgh; 3 Weatherall Institute of Molecular Medicine; 4 Wellcome Trust Sanger Institute Discussion
Understanding how Plasmodium transmission is sustained in the face of increased control efforts is essential to eradicate malaria. In low malaria transmission settings, long-lasting infection increases the likelihood of the parasite completing its life cycle. It is widely accepted that establishment of chronic infection involves evasion of adaptive immunity by antigenic variation of var genes. However, these genes have been identified in only two human malarias: P. falciparum and P. knowlesi. So how long-term infection is established in P. vivax, P. malariae and P. ovale is unclear. Here we use the rodent malaria, P. chabaudi AS, to understand how chronic infections are established in the absence of var genes. Using global transcriptomic and phenotypic approaches, we demonstrate that, among a clonally variant population, only a minority of parasites expressing one of several clusters of virulence-associated pir genes establish a chronic infection. This clonal selection is independent of adaptive immunity, showing that non-var-containing Plasmodium species use mechanisms distinct from classical antigenic variation. Furthermore, pir genes being common to most species of Plasmodium this process may be a more universal way of establishing chronic Plasmodium infections.
