The skin stage of malaria infection: biology and relevance to the malaria vaccine effort

Plasmodium sporozoites, the infective stage of the malaria parasite, are injected into the mammalian host by mosquitoes and travel to the liver where they invade hepatocytes. Recent studies demonstrating that sporozoites are inoculated into the skin, remain there for hours before exiting and that 20% of the inoculum goes to the lymph node draining the inoculation site, suggest that there is a 'skin stage' to malaria infection that may set the stage for subsequent host responses to the parasite. Here, we present an overview of what is currently known about sporozoite-host interactions at the inoculation site and the draining lymph node, and discuss the impact of the skin stage of malaria on immunity to pre-erythrocytic stages and malaria vaccine design.