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Open Access Review

World Antimalarial Resistance Network (WARN) II: In vitro antimalarial drug susceptibility

David J Bacon1*, Ronan Jambou2, Thierry Fandeur3, Jacques Le Bras4, Chansuda Wongsrichanalai5, Mark M Fukuda6, Pascal Ringwald7, Carol Hopkins Sibley8 and Dennis E Kyle9

Author Affiliations

1 Parasitology Program, Naval Medical Research Center Detachment, Lima, Peru

2 Laboratoire d'immunologie Clinique et Parasitaire, Institut Pasteur, Dakar

3 Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, Paris, France

4 Hospital Bichat Claude Bernard, Paris, France

5 U.S. Naval Medical Research Unit No. 2 (NAMRU-2), Jakarta, Republic of Indonesia

6 Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

7 Global Malaria Programme, World Health Organization, 20 Av. Appia, 1211 Geneva 27, Switzerland

8 Department of Genome Sciences, University of Washington, Seattle, WA, USA

9 Department of Global Health, College of Public Health, University of South Florida, Tampa, FL, USA

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Malaria Journal 2007, 6:120  doi:10.1186/1475-2875-6-120

Published: 6 September 2007

Abstract

Intrinsic resistance of Plasmodium falciparum is clearly a major determinant of the clinical failure of antimalarial drugs. However, complex interactions between the host, the parasite and the drug obscure the ability to define parasite drug resistance in vivo. The in vitro antimalarial drug susceptibility assay determines ex-vivo growth of parasite in the presence of serial drug concentrations and, thus, eliminates host effects, such as drug metabolism and immunity. Although the sensitivity of the parasite to various antimalarials provided by such a test provides an important indicator of intrinsic parasite susceptibility, there are fundamental methodological issues that undermine comparison of in vitro susceptibility both between laboratories and within a single laboratory over time. A network of laboratories is proposed that will agree on the basic parameters of the in vitro test and associated measures of quality control. The aim of the network would be to establish baseline values of sensitivity to commonly used antimalarial agents from key regions of the world, and create a global database, linked to clinical, molecular and pharmacology databases, to support active surveillance to monitor temporal trends in parasite susceptibility. Such a network would facilitate the rapid detection of strains with novel antimalarial resistance profiles and investigate suitable alternative treatments with retained efficacy.