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World Antimalarial Resistance Network (WARN) III: Molecular markers for drug resistant malaria

Christopher V Plowe1, Cally Roper2, John W Barnwell3, Christian T Happi4, Hema H Joshi5, Wilfred Mbacham6, Steven R Meshnick7, Kefas Mugittu8, Inbarani Naidoo9, Ric N Price10, Robert W Shafer11, Carol H Sibley12*, Colin J Sutherland13, Peter A Zimmerman14 and Philip J Rosenthal15

Author Affiliations

1 Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, Maryland 21201 USA

2 London School of Hygiene and Tropical Medicine, Keppel Street, London, UK WC1E 7HT

3 Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, NE MS F-13, Atlanta, Georgia 30341 USA

4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115 USA

5 National Institute of Malaria Research, 22 Sham Nath Marg, Delhi 110054, India

6 Biotechnology Centre, University of Yaounde I, Cameroon, Box 8094 Yaounde, Cameroon

7 University of North Carolina Schools of Public Health and Medicine, Chapel Hill, North Carolina 27599 USA

8 Ifakara Health Research and Development Centre, P. O. Box 53, Ifakara, Tanzania

9 Malaria Research Programme, Medical Research Council, PO Box 70380, Overport, 4067, South Africa

10 International Health Programme, Menzies School of Health Research, P. O. Box 41096, Casuarina, Darwin, NT 0811 Australia

11 Division of Infectious Diseases, Room S-169, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305 USA

12 Department of Genome Sciences, Box 355065, University of Washington, Seattle, Washington 98195 USA

13 London School of Hygiene & Tropical Medicine, Department of Infectious and Tropical Diseases, Immunology Unit, Keppel Street, London WC1E 7HT, UK

14 Case Western Reserve University, The Center for Global Health & Diseases, Wolstein Research Building, Room 4-125, 2103 Cornell Road, Cleveland, Ohio 44106 USA

15 University of California San Francisco, Box 0811, San Francisco, California 94143 USA

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Malaria Journal 2007, 6:121  doi:10.1186/1475-2875-6-121

Published: 6 September 2007

Abstract

Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason for the failure of molecular resistance markers to live up to their potential is that data on the their prevalence is scattered in disparate databases with no linkage to the clinical, in vitro and pharmacokinetic data that are needed to relate the genetic data to relevant phenotypes. The ongoing replacement of older monotherapies for malaria by new, more effective combination therapies presents an opportunity to create an open access database that brings together standardized data on molecular markers of drug resistant malaria from around the world. This paper presents a rationale for creating a global database of molecular markers for drug resistant malaria and for linking it to similar databases containing results from clinical trials of drug efficacy, in vitro studies of drug susceptibility, and pharmacokinetic studies of antimalarial drugs, in a World Antimalarial Resistance Network (WARN). This database will be a global resource, guiding the selection of first line drugs for treating uncomplicated malaria, for preventing malaria in travelers and for intermittent preventive treatment of malaria in pregnant women, infants and other vulnerable groups. Perhaps most important, a global database for molecular markers of drug resistant malaria will accelerate the identification and validation of markers for resistance to artemisinin-based combination therapies and, thereby, potentially prolong the useful therapeutic lives of these important new drugs.