In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene - Archive ouverte HAL Access content directly
Journal Articles Malaria Journal Year : 2013

In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene

(1, 2, 3) , (4, 3) , (3) , (1, 2, 3, 4) , (1, 2, 3, 4) , (1, 2, 3) , (3) , (3) , (5) , (3) , (1, 2, 3)
1
2
3
4
5
Christophe Rogier
  • Function : Author
  • PersonId : 935289

Abstract

Background
Dihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine. Very few data are available on cross-resistance between piperaquine and chloroquine, and the data that do exist are often contradictory.
Methods
In total, 280 P. falciparum isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed ex vivo for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in pfcrt was also investigated for the 280 isolates.
Results
The IC50 for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC50 for chloroquine ranged from 5.0 nM to 1,918 nM (mean = 83.6 nM. A significant but low correlation was observed between the Log IC50 values for piperaquine and chloroquine (r = 0.145, p < 0.001). However, the coefficient of determination of 0.021 indicates that only 2.1% of the variation in the response to piperaquine is explained by the variation in the response to chloroquine. The mean value for piperaquine was 74.0 nM in the Pfcrt K76 wild-type group (no = 125) and 87.7 nM in the 76 T mutant group (no = 155). This difference was not significant (p = 0.875, Mann Whitney U test).
Conclusions
The present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 P. falciparum isolates and that piperaquine susceptibility is not associated with pfcrt, the gene involved in chloroquine resistance. These results confirm the efficacy of piperaquine in association with dihydroartemisinin and support its use in areas in which parasites are resistant to chloroquine.
Fichier principal
Vignette du fichier
1475-2875-12-431.pdf (208.73 Ko) Télécharger le fichier
Vignette du fichier
1475-2875-12-431.xml (51.45 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00911243 , version 1 (29-11-2013)

Identifiers

Cite

Aurélie Pascual, Marilyn Madamet, Lionel Bertaux, Rémy Amalvict, Nicolas Benoit, et al.. In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene. Malaria Journal, 2013, 12 (1), pp.431. ⟨10.1186/1475-2875-12-431⟩. ⟨inserm-00911243⟩
195 View
199 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More