Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event

Catherine Bourguinat Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Joseph Kamgno Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Michel Boussinesq Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Charles D. Mackenzie Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Roger K. Prichard Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Timothy G. Geary Institute of Parasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada; Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier, France; Filarial Diseases Unit, Michigan State University, East Lansing, Michigan

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Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs.

Author Notes

*Address correspondence to Roger K. Prichard, Institute of Parasitology, McGill University, 21 111 Lakeshore Road, Sainte Anne-de-Bellevue, Quebec, H9X 3V9, Canada. E-mail: roger.prichard@mcgill.ca

Financial support: This study was supported by a Canadian Institutes of Health grant to RKP and by Mectizan Donation Program as part of their support to the Filariasis Research Center in Yaoundé (JK).

Authors' addresses: Catherine Bourguinat, Roger K. Prichard, and Timothy G. Geary, Institute of Parasitology, McGill University, Quebec, Canada, E-mail: roger.prichard@mcgill.ca. Joseph Kamgno, Filariasis Research Centre and Faculty of Medicine and Biomedical Sciences University of Yaoundé I, Yaoundé, Cameroon. Michel Boussinesq, Unité Mixte de Recherche 145, Institut de Recherche pour le Développement and Université Montpellier 1, Montpellier Cedex 5, France. Charles D. Mackenzie, Filarial Diseases Unit, Michigan State University, East Lansing, MI.

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