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Virulence of the most deadly malaria parasite  Plasmodium falciparum  is linked to the variant surface antigen  Pf EMP1, which is encoded by about 60  var  genes per parasite genome. Although the expression of particular variants has been associated with different clinical outcomes, little is known about  var  gene expression at the onset of infection. By analyzing controlled human malaria infections via quantitative real-time PCR, we show that parasite populations from 18 volunteers expressed virtually identical transcript patterns that were dominated by the subtelomeric  var  gene group B and, to a lesser extent, group A. Furthermore, major changes in composition and frequency of  var  gene transcripts were detected between the parental parasite culture that was used to infect mosquitoes and  Plasmodia  recovered from infected volunteers, suggesting that  P .  falciparum  resets its  var  gene expression during mosquito passage and starts with the broad expression of a specific subset of  var  genes when entering the human blood phase.

Mosquito Passage Dramatically Changes var Gene Expression in Controlled Human Plasmodium falciparum Infections