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Infectivity of Plasmodium falciparum sporozoites determines emerging parasitemia in infected volunteers

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Science Translational Medicine  21 Jun 2017:
Vol. 9, Issue 395, eaag2490
DOI: 10.1126/scitranslmed.aag2490

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New insights into malaria parasite infectivity

A malaria infection starts by inoculation of Plasmodium falciparum parasites into the skin by blood-feeding mosquitoes. These sporozoites rapidly invade liver cells and mature and multiply over 6 to 7 days. Infected liver cells then release new parasites into the bloodstream, which then multiply repeatedly inside red blood cells, causing clinical symptoms. McCall and colleagues now show that sporozoites of diverse geographic and genetic origin differ in their capacity to infect and develop within human liver cells in culture. This matched their ability to form blood-stage parasites in human volunteers undergoing a controlled malaria infection. Thus, the fitness of sporozoites apparently determines their virulence.

Abstract

Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical Plasmodium falciparum isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among P. falciparum isolates from distinct geographical locales. The observed heterogeneity in infectivity among strains underscores the value of assessing the protective efficacy of candidate malaria vaccines against heterologous strains in the CHMI model.

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