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IN VITRO ACTIVITY OF FERROQUINE (SAR97193) IS INDEPENDENT OF CHLOROQUINE RESISTANCE IN PLASMODIUM FALCIPARUM

Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern. We tested in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.

Received October 12, 2005. Accepted for publication June 30, 2006.

Acknowledgments: The authors thank all patients for participation in the study and the staff of the General Hospital, the dispensary of Isaac, and the Albert Schweitzer Hospital for assistance. Francis Babila Ntumngia and Rolf Fendel gave valuable comments during preparation of the manuscript.

Financial support: This study was supported by the fortüne program of the University of Tübingen (project 1195-0-0).

^* Address correspondence to Benjamin Mordmüller, Medical Research Unit, Hôpital Albert Schweitzer, BP118 Lambaréné, Gabon and University of Tübingen, Department of Parasitology, Wilhelmstr. 27, 72074 Tübingen, Germany. E-mail: benjamin.mordmueller{at}uni-tuebingen.de

Authors’ addresses: Andrea Kreidenweiss, Peter G. Kremsner, and Benjamin Mordmüller, Medical Reserach Unit, Hôpital Albert Schweitzer, BP118 Lambaréné, Gabon and University of Tübingen, Department of Parasitology, Wilhelmstr. 27, 72074 Tübingen, Germany, Telephone: 49-7071-2980240, Fax: 49-7071-295189, E-mail: benjamin.mordmueller{at}uni-tuebingen.de. Klaus Dietz, University of Tübingen, Department of Medical Biometry, Westbahnhofstr. 55, 72070 Tübingen, Germany.

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