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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in drug development, deployment and resistance

Measuring parasite clearance after ACT treatment using a newly developed qPCR method.

LSHTM investigators:
Khalid Beshir & Colin Sutherland.
External collaborators:
WANECAM group (West African Network for Clinical trials of AntiMalarial drugs): Malaria Research and Training Center; Université de Bamako, Mali; Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso; Institut de Recherche en Science de la Santé, Burkina Fas; Centre National de formation et de Recherche en Santé Rurale, Guinée; Medical Research Council, The Gambia; de Recherche sur la Malaria, Université Claude Bernard, France; The malaria research unit at the Karolinska University Hospital, Sweden; Molecular-epidemiology of malaria group, University of Heidelberg School of Medicine, Germany.
Funding body:
The European and Developing Countries Partnership (EDCTP) through the WANECAM Consortium.

Parasite clearance, a measure of artemisinin response phenotype, is usually estimated using microscopic examination of thin and think blood-smears.

However, a frequent closely-spaced venous sampling will be required in order to see a significant difference in clearance time using microscopy. This approach may not be suitable in Africa where the majority of trial participants are children. In addition, some treatment failures have been reported after ACT treatments, yet no difference in parasite clearance were reported between patients who had recrudescent infection and those who were treated successfully. We have developed a rapid and sensitive qPCR assay to measure parasite clearance in the first three days after treatment. The validation of the new qPCR method on HTD samples derived from venous blood has recently been published (Beshir et al 2010). In this study, the assay was tested on DNA derived from filter-paper bloodspots taken from a 2009 clinical trial of AL and DHA-PIP in western Kenya.  The method identified a greater range of parasite clearance kinetics among children than did microscopy, allowing the analysis of phenotype-phenotype, phenotype-genotype and drug effect relationships with more statistical power. The new qPCR method will be used in WANECAM clinical trials of four ACTs.