Chloroquine resistance of Plasmodium falciparum: a biological advantage?

Wernsdorfer, Walther H.; Landgraf, Barbara; Wiedermann, G; Kollaritsch, Herwig

doi:10.1016/0035-9203(95)90672-x

Cited by 22 publications

(13 citation statements)

References 4 publications

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“…First, the stability of CQ resistance is likely due to the marked biological advantage of CQ‐resistant over CQ‐sensitive P. falciparum . This biological advantage was suggested by Nguyen‐Dinh and Trager (1978), and confirmed in field studies (Wernsdorfer et al. 1995; Robert et al.…”

Section: Discussionsupporting

confidence: 58%

Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China

Zhang

Guan

Zheng

et al. 2009

Tropical Med Int Health

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Section: Discussionsupporting

confidence: 58%

Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China

Zhang

Guan

Zheng

et al. 2009

Tropical Med Int Health

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“…Although there was no significant difference in the average number of merozoites produced per mature schizont amongst all three strains (A), there were significantly more rings produced per D10-mdr D10 (14.1 ± 0.9) and 7G8-mdr D10 (13.2 ± 0.7) trophozoite than was produced by 7G8-mdr 7G8 trophozoites (11.4 ± 0.3). dez et al, 2002), alter sporogony in the mosquite vector (Shinondo et al, 1994), or increase parasite viability/efficiency in the human host (Wernsdorfer et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum

Hayward

Saliba

Kirk

2005

Molecular Microbiology

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SummaryEfforts to control malaria worldwide have been hindered by the development and expansion of parasite populations resistant to many first-line antimalarial compounds. Two of the best-characterized determinants of drug resistance in the human malaria parasite Plasmodium falciparum are pfmdr1 and pfcrt , although the mechanisms by which resistance is mediated by these genes is still not clear. In order to determine whether mutations in pfmdr1 associated with chloroquine resistance affect the capacity of the parasite to persist when drug pressure is removed, we conducted competition experiments between P. falciparum strains in which the endogenous pfmdr1 locus was modified by allelic exchange. In the absence of selective pressure, the component of chloroquine resistance attributable to mutations at codons 1034, 1042 and 1246 in the pfmdr1 gene also gave rise to a substantial fitness cost in the intraerythrocytic asexual stage of the parasite. The loss of fitness incurred by these mutations was calculated to be 25% with respect to an otherwise genetically identical strain in which wild-type polymorphisms had been substituted at these three codons. At least part of the fitness loss may be attributed to a diminished merozoite viability. These in vitro results support recent in vivo observations that in several countries where chloroquine use has been suspended because of widespread resistance, sensitive strains are re-emerging.

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“…Although its use started in the 17 th century, resistance to quinine was first reported in 1910 [88]. In comparison, resistance to chloroquine and proguanil emerged within only 12 [89] and 1 year [88,90] of their introduction, respectively. Resistance to quinine is usually low grade, with the drug retaining some activity but having its action delayed or diminished.…”

Section: Potential Explanations For Quinine Treatment Failurementioning

confidence: 99%

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Achan

Talisuna

Erhart

et al. 2011

Malar J

762

466

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Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

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Chloroquine resistance of Plasmodium falciparum: a biological advantage?

Cited by 22 publications

References 4 publications

Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China

Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China

pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

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