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A New Tool to Accelerate the Development of Drugs and Vaccines against Malaria

A clinical assay establishes the optimal dose of parasite inoculation to achieve a controlled human infection that is safe and reproducible

15.05.2015
Photo: NIAID

ISGlobal has co-directed a study that evaluates the direct inocolation of Plasmodium falciparum sporozoites (the infectious form) in humans and identifies a protocol that is safe, reproducible and will facilitate the development of new anti-malarial therapies. Researchers from the Tropical Medicine Institute of Tubingen, Germany, Sanaria Inc., USA, and the Institute of Biomedical Research of Sant Pau, Barcelona also participated in the study that was published in Malaria Journal

The goal of the study was to establish an experimental model of controlled human malaria infection in order to accelerate the clinical testing of new anti-malarial drugs and vaccines. To date, this is done exposing volunteers to the bites of five sporozoite-infected mosquitoes but the variability in the infection rates is high and the logistics of maintaining infected mosquitoes is challenging.  Thus, the researchers seeked to establish another controlled infection protocol that consists in the direct inoculation of a commercial preparation of purified and cryopreserved infectious P. falciparum sporozoites (PfSPZ Challenge). The study identifies the optimal dose of sporozoites that results in a reproducible infection, comparable to that obtained by exposure to five infected mosquitoes. Importantly, the same results were obtained in Tubingen and Barcelona, using different lots of sporozoites and different intravenous administration techniques. 

The authors conclude that intravenous inoculation of PfSPZ Challenge "is safe and highly reproducible", which will facilitate the standardization of controlled infection in humans and boost the development of anti-malarial interventions. The identified dosis will also provide valuable information for ongoing vaccination assays using radiation-attenuated PfSPZ.  

Despite considerable achievements during the last decade, malaria still affects almost half of the world population and caused 584,000 deaths in 2013. The magnitude of the problem and the capacity of the parasite to adapt rapidly to human interventions require the rapid development of new anti-malarial tools, such as the strategy described in this study.