LOW-LEVEL MALARIA INFECTIONS DETECTED BY A SENSITIVE POLYMERASE CHAIN REACTION ASSAY AND USE OF THIS TECHNIQUE IN THE EVALUATION OF MALARIA VACCINES IN AN ENDEMIC AREA

EGERUAN B. IMOUKHUEDE Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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LAURA ANDREWS Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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PAUL MILLIGAN Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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TAMARA BERTHOUD Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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KALIFA BOJANG Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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DAVIS NWAKANMA Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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JAMILA ISMAILI Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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CAROLINE BUCKEE Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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FANTA NJIE Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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SAIKOU KEITA Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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MAIMUNA SOWE Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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TRUDIE LANG Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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SARAH C. GILBERT Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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BRIAN M. GREENWOOD Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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ADRIAN V. S. HILL Medical Research Council Laboratories, Fajara, The Gambia; London School of Hygiene & Tropical Medicine, London, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, Oxford, UK

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The feasibility of using a sensitive polymerase chain reaction (PCR) to evaluate malaria vaccines in small group sizes was tested in 102 adult Gambian volunteers who received either the malaria vaccine regimen FP9 ME-TRAP/MVA ME-TRAP or rabies vaccine. All volunteers received the antimalarial drugs primaquine and Lapdap plus artesunate to eliminate malaria parasites. Volunteers in a further group received an additional single treatment with sulfadoxine-pyrimethamine (SP) to prevent new infections. There was substantially lower T-cell immunogenicity than in previous trials with this vaccine regimen and no protection against infection in the malaria vaccine group. Using the primary endpoint of 20 parasites per mL, no difference was found in the prevalence of low-level infections in volunteers who received SP compared with those who did not, indicating that SP did not reduce the incidence of very low-density infection. However, SP markedly reduced the incidence of higher density infections. These findings support the feasibility and potential of this approach to screen pre-erythrocytic vaccines for efficacy against infection in small numbers of vaccinees in endemic areas.

Author Notes

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    Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC, 2005. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg 73 :191–198.

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