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Volume 21, Number 10—October 2015
Research

Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure

Sandie Ménard, Tanila Ben Haddou, Arba Pramundita Ramadani1, Frédéric Ariey, Xavier Iriart, Johann Beghain, Christiane Bouchier, Benoit Witkowski2, Antoine Berry, Odile Mercereau-Puijalon, and Françoise Benoit-VicalComments to Author 
Author affiliations: Université de Toulouse, Toulouse, France (S. Ménard, T. Ben Haddou, A.P. Ramadani, X. Iriart, B. Witkowski, A. Berry, F. Benoit-Vical); Centre de Physiopathologie de Toulouse-Purpan, Toulouse (S. Ménard. X. Iriart, A. Berry); Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique, Toulouse (T. Ben Haddou, A.P. Ramadani, B. Witkowski, F. Benoit-Vical); Institut Pasteur, Paris, France (F. Ariey, J. Beghain, C. Bouchier, O. Mercereau-Puijalon); Centre Hospitalier Universitaire de Toulouse, Toulouse (X. Iriart, A. Berry)

Main Article

Table 1

Susceptibility of Plasmodium falciparum F32-ART5 and F32-TEM lineages to 10 antimalarial drugs*

Drug F32-TEM
F32-ART5
p value†
IC50 IC90 IC99 IC50 IC90 IC99
Artemisinin 14.2
(13–19.5) 20.9
(16.3–26.4) 29.2
(20.7–39.2) 17.7
(14.2–21.9) 31.2
(23–37.2) 50.7
(37.2–63.3) 0.686
Artesunate 3.9
(2.7–5.1) 6.4
(4.7–7.9) 11.1
(9.4–13.4) 3.8
(3.2–5.6) 6.1
(4.7–7.4) 11.1
(7.7–13.4) 0.886
Artemisone 0.6
(0.3–0.9) 0.7
(0.5–0.9) 0.9
(0.6–1.1) 0.5
(0.3–0.6) 1.2
(1.1–1.3) 3.5
(3.3–3.8) 1.000
Artemether 7.2
(7–7.5) 9
(8.9–9.2) 11.5
(11.2–11.7) 7.2
(6.8–7.5) 8.9
(8.7–9.2) 11.4
(11.1–11.7) 1.000
Chloroquine 32.9
(23.64–45.6) 55.9
(42.9–58.7) 66.2
(52.1–72.1) 28.2
(24.9–33.5) 46.2
(44.7–52.4) 83.4
(76.8–100.5) 0.886
Quinine 105.8
(77.8–136.1) 302.7
(219.9–420.7) 938
(718.5–1,482.5) 118.8
(84.2–156.5) 341.6
(259.7–421.5) 1,026
(742.2–1,439) 0.486
Amodiaquine 25.1
(17.1–33.1) 53.1
(51.7–54.4) 113.4
(88.7–138) 29.6
(28.4–30.9) 51.8
(47.5–56.2) 78.05
(66.5–89.7) 1.000
Mefloquine 68.2
(54.7–88.2) 142.3
(130.9–159.6) 312.9
(224–437) 63.1
(59.4–73.1) 114.1
(101–153.7) 220.9
(161.6–448.5) 0.886
Pyrimethamine 105.0
(90–120.1) 184.6
(167.1–202.1) 385.9
(288–483.8) 74.7
(73.3–76.1) 270.5
(268.7–272.3) 1,102.6
(1,076–1,129) 0.333
Atovaquone 2.8
(2–2.9) 12.7
(10.8–15.8) 95.8
(87.2–104) 1.5
(0.4–3) 7.5
(2.6–12.9) 52.1
(31–64.6) 0.486

*IC50, 50% inhibitory concentration; IC90, 90% inhibitory concentration; IC99, 99% inhibitory concentration. Values were obtained by using the standard isotopic susceptibility assay. Drug concentrations are in nanomoles/liter. Values are medians (25%–75% interquartile ranges). All assays were performed in triplicate.
†Data distribution was non-Gaussian. The p values were calculated by using nonparametric Mann-Whitney rank-sum test results for IC50s. Similar tests were performed to obtain IC90s and IC99s, and no differences were observed between F32-ART5 and F32-TEM for any drug tested.

Main Article

1Current affiliation: Universitas Gadjah Mada, Yogyakarta, Indonesia.

2Current affiliation: Institut Pasteur, Phnom Penh, Cambodia.

Page created: September 22, 2015
Page updated: September 22, 2015
Page reviewed: September 22, 2015
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