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Sci Transl Med. 2017 Jun 21;9(395). pii: eaag2490. doi: 10.1126/scitranslmed.aag2490.

Infectivity of Plasmodium falciparum sporozoites determines emerging parasitemia in infected volunteers.

Author information

1
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, Netherlands.
2
Institute for Tropical Diseases, Harbour Hospital, Rotterdam, Netherlands.
3
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, Netherlands.
4
Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l'hôpital, F-75013 Paris, France.
5
AP-HP, Groupe hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, F-75013 Paris, France.
6
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, Netherlands. robert.sauerwein@radboudumc.nl.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01627951 NCT02149550.

PMID:
28637923
DOI:
10.1126/scitranslmed.aag2490
[Indexed for MEDLINE]

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