Infectivity of Plasmodium falciparum sporozoites determines emerging parasitemia in infected volunteers

• Published in: Science translational medicine Vol. 9; no. 395
• Main Authors: McCall, Matthew B B, Wammes, Linda J, Langenberg, Marijke C C, van Gemert, Geert-Jan, Walk, Jona, Hermsen, Cornelus C, Graumans, Wouter, Koelewijn, Rob, Franetich, Jean-François, Chishimba, Sandra, Gerdsen, Max, Lorthiois, Audrey, van de Vegte, Marga, Mazier, Dominique, Bijker, Else M, van Hellemond, Jaap J, van Genderen, Perry J J, Sauerwein, Robert W
• Format: Journal Article
• Language: English
• Published: United States 21.06.2017
• Subjects: Female; Hepatocytes - parasitology; Humans; Malaria, Falciparum - blood; Malaria, Falciparum - parasitology; Parasitemia - blood; Parasitemia - parasitology; Plasmodium falciparum - pathogenicity; Retrospective Studies; Sporozoites - pathogenicity; Volunteers
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aag2490

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 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 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.