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Plasmodium berghei ANKA: Selection of resistance to piperaquine and lumefantrine in a mouse model |
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| Authors: | DM Kiboi B Langat S Wittlin J Chollet JK Nganga GM Rukunga A Nzila |
| Institution: | a Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, 00200 Nairobi, Kenya b Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840, Nairobi 00200, City Square, Kenya c Institute of Tropical Medicine and Infectious Diseases (INTROMID), Kenya d Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland e Malaria Research Laboratories, University of Ibadan, Ibadan, Nigeria f Dept. of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland g Kenya Medical Research Institute (KEMRI)/Wellcome Trust, Collaborative Research Program, P.O. Box 230-80108, Kilifi, Kenya h University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK |
| Abstract: | We have selected piperaquine (PQ) and lumefantrine (LM) resistant Plasmodium berghei ANKA parasite lines in mice by drug pressure. Effective doses that reduce parasitaemia by 90% (ED90) of PQ and LM against the parent line were 3.52 and 3.93 mg/kg, respectively. After drug pressure (more than 27 passages), the selected parasite lines had PQ and LM resistance indexes (I90) ED90 of resistant line/ED90 of parent line] of 68.86 and 63.55, respectively. After growing them in the absence of drug for 10 passages and cryo-preserving them at −80 °C for at least 2 months, the resistance phenotypes remained stable. Cross-resistance studies showed that the PQ-resistant line was highly resistant to LM, while the LM-resistant line remained sensitive to PQ. Thus, if the mechanism of resistance is similar in P. berghei and Plasmodium falciparum, the use of LM (as part of Coartem®) should not select for PQ resistance. |
| Keywords: | Malaria Plasmodium berghei Drug resistance Cross-resistance Lumefantrine Piperaquine |
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