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-Vical
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)
Figure 2. Recrudescence curves of synchronous ring-stage parasites of Plasmodium falciparum F32-ART5 (dashed lines) and F32-TEM (solid lines) after a 48-h exposure to A) 11 µmol/L artemisinin; B) 62 nmol/L amodiaquine; C) 241 nmol/L mefloquine; D) 4 µmol/L pyrimethamine; and E) 7 µmol/L atovaquone. Curves show the percentage of parasite recrudescence (i.e., cultures having reached day 0 parasite density) vs. time. A log-rank (Mantel-Cox) test was used for statistical analysis, and corresponding p values are reported in Table 3. Small black vertical tick marks indicate individual F32-TEM lines whose recrudescence times have been right-censored because the parasite line did not recrudesce during the monitoring study.
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