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Measurement of Plasmodium falciparum Growth Rates in Vivo: A Test of Malaria Vaccines

Qin ChengMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Gregor LawrenceMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Carol ReedMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Anthony StowersMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Lisa Ranford-CartwrightMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Alison CreaseyMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Richard CarterMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Allan SaulMalaria and Arbovirus Unit and The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Brisbane, Australia

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Several prototype vaccines against the asexual blood stage of malaria are undergoing preclinical and phase I testing. Although these vaccines have been chosen for their ability to elicit an anti-parasite response, no practical and sensitive clinical trial procedure has been available for measuring their impact on parasite growth. We describe a system that allows parasite growth rates to be measured in volunteers through the incubation period. Two necessary elements of this system are developed: suitable blood-stage Plasmodium falciparum inocula, and a highly sensitive and quantitative assay to measure parasite growth during the incubation period. We infected five nonimmune volunteers with an inoculum as small as 300 parasites and demonstrated that the resultant in vivo asexual parasite growth rates were reproducible at 12–15-fold per cycle. The system allowed the infection to be followed for eight days before treatment without symptoms developing. These findings suggest that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.

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