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

D. M. Kiboi; B. N. Irungu; B. Langat; S. Wittlin; R. Brun; J. Chollet; O. Abiodun; J. K. Nganga; V. C.S. Nyambati; G. M. Rukunga; A. Bell; A. Nzila

doi:10.1016/j.exppara.2009.03.010

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

D. M. Kiboi, B. N. Irungu, B. Langat, S. Wittlin, R. Brun, J. Chollet, O. Abiodun, J. K. Nganga, V. C.S. Nyambati, G. M. Rukunga, A. Bell, A. Nzila^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	196-202
Number of pages	7
Journal	Experimental Parasitology
Volume	122
Issue number	3
DOIs	https://doi.org/10.1016/j.exppara.2009.03.010
State	Published - Jul 2009
Externally published	Yes

Bibliographical note

Funding Information:
We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by a Global Health Research Award to A.B. and A.N. from the Irish Health Research Board (GHRA-06-03) and by the European and Developing Countries Clinical Trials Partnership (EDCTP). A.N. is an EDCTP Senior Fellow.

Keywords

Cross-resistance
Drug resistance
Lumefantrine
Malaria
Piperaquine
Plasmodium berghei

ASJC Scopus subject areas

Parasitology
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.exppara.2009.03.010

Cite this

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title = "Plasmodium berghei ANKA: Selection of resistance to piperaquine and lumefantrine in a mouse model",

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{\textregistered}) should not select for PQ resistance.",

keywords = "Cross-resistance, Drug resistance, Lumefantrine, Malaria, Piperaquine, Plasmodium berghei",

author = "Kiboi, \{D. M.\} and Irungu, \{B. N.\} and B. Langat and S. Wittlin and R. Brun and J. Chollet and O. Abiodun and Nganga, \{J. K.\} and Nyambati, \{V. C.S.\} and Rukunga, \{G. M.\} and A. Bell and A. Nzila",

note = "Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by a Global Health Research Award to A.B. and A.N. from the Irish Health Research Board (GHRA-06-03) and by the European and Developing Countries Clinical Trials Partnership (EDCTP). A.N. is an EDCTP Senior Fellow.",

year = "2009",

month = jul,

doi = "10.1016/j.exppara.2009.03.010",

language = "English",

volume = "122",

pages = "196--202",

journal = "Experimental Parasitology",

issn = "0014-4894",

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T1 - Plasmodium berghei ANKA

T2 - Selection of resistance to piperaquine and lumefantrine in a mouse model

AU - Kiboi, D. M.

AU - Irungu, B. N.

AU - Langat, B.

AU - Wittlin, S.

AU - Brun, R.

AU - Chollet, J.

AU - Abiodun, O.

AU - Nganga, J. K.

AU - Nyambati, V. C.S.

AU - Rukunga, G. M.

AU - Bell, A.

AU - Nzila, A.

N1 - Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by a Global Health Research Award to A.B. and A.N. from the Irish Health Research Board (GHRA-06-03) and by the European and Developing Countries Clinical Trials Partnership (EDCTP). A.N. is an EDCTP Senior Fellow.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Cross-resistance

KW - Drug resistance

KW - Lumefantrine

KW - Malaria

KW - Piperaquine

KW - Plasmodium berghei

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SN - 0014-4894

VL - 122

SP - 196

EP - 202

JO - Experimental Parasitology

JF - Experimental Parasitology

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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