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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In total, 280 <jats:italic>P. falciparum<\/jats:italic> isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed <jats:italic>ex vivo<\/jats:italic> for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in <jats:italic>pfcrt<\/jats:italic> was also investigated for the 280 isolates.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The IC<jats:sub>50<\/jats:sub> for piperaquine ranged from 9.8 nM to 217.3 nM (mean\u2009=\u200981.3 nM. The IC<jats:sub>50<\/jats:sub> for chloroquine ranged from 5.0 nM to 1,918 nM (mean\u2009=\u200983.6 nM. A significant but low correlation was observed between the Log IC<jats:sub>50<\/jats:sub> values for piperaquine and chloroquine (r\u2009=\u20090.145, p\u2009&lt;\u20090.001). 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 <jats:italic>Pfcrt<\/jats:italic> K76 wild-type group (no\u2009=\u2009125) and 87.7 nM in the 76\u00a0T mutant group (no\u2009=\u2009155). This difference was not significant (p\u2009=\u20090.875, Mann Whitney U test).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 <jats:italic>P. falciparum<\/jats:italic> isolates and that piperaquine susceptibility is not associated with <jats:italic>pfcrt<\/jats:italic>, 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2875-12-431","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T08:05:42Z","timestamp":1385366742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene"],"prefix":"10.1186","volume":"12","author":[{"given":"Aur\u00e9lie","family":"Pascual","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Madamet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Bertaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Amalvict","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Travers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Cren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Taudon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Rogier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Parzy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Pradines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The French National Reference Centre for Imported Malaria Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,11,25]]},"reference":[{"key":"3033_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.medmal.2006.05.005","volume":"36","author":"J Le Bras","year":"2006","unstructured":"Le Bras J, Musset L, Clain J: Antimalarial drug resistance. 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