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Plasmodium bergheiANKA: Selection of resistance to piperaquine and lumefantrine in a mouse model

Authors
Journal
Experimental Parasitology
0014-4894
Publisher
Elsevier
Publication Date
Volume
122
Issue
3
Identifiers
DOI: 10.1016/j.exppara.2009.03.010
Keywords
  • Malaria
  • Plasmodium Berghei
  • Drug Resistance
  • Cross-Resistance
  • Lumefantrine
  • Piperaquine

Abstract

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% (ED 90) 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 (I 90) [ED 90 of resistant line/ED 90 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.

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