Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model

Obaldía III, N. et al. (2016) Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model. Scientific Reports, 6, p. 21216. (doi:10.1038/srep21216) (PMID:26880111) (PMCID:PMC4754742)

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Abstract

Infections with Plasmodium falciparum, the most pathogenic of the Plasmodium species affecting man, have been reduced in part due to artemisinin-based combination therapies. However, artemisinin resistant parasites have recently emerged in South-East Asia. Novel intervention strategies are therefore urgently needed to maintain the current momentum for control and elimination of this disease. In the present study we characterize the phenotypic and genetic properties of the multi drug resistant (MDR) P. falciparum Thai C2A parasite strain in the non-human Aotus primate model, and across multiple passages. Aotus infections with C2A failed to clear upon oral artesunate and mefloquine treatment alone or in combination, and ex vivo drug assays demonstrated reduction in drug susceptibility profiles in later Aotus passages. Further analysis revealed mutations in the pfcrt and pfdhfr loci and increased parasite multiplication rate (PMR) across passages, despite elevated pfmdr1 copy number. Altogether our experiments suggest alterations in parasite population structure and increased fitness during Aotus adaptation. We also present data of early treatment failures with an oral artemisinin combination therapy in a pre-artemisinin resistant P. falciparum Thai isolate in this animal model.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias
Authors: Obaldía III, N., Dow, G. S., Gerena, L., Kyle, D., Otero, W., Mantel, P.-Y., Baro, N., Daniels, R., Mukherjee, A., Childs, L. M., Buckee, C., Duraisingh, M. T., Volkman, S. K., Wirth, D. F., and Marti, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:16 February 2016

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