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1. Plasmodium ovale spp dhfr mutations associated with reduced susceptibility to pyrimethamine in sub-Saharan Africa: a retrospective genetic epidemiology and functional study

Author

Abou-Bacar, Ahmed, Agnamey, Patrice, Ait-Ammar, Nawel, Angoulvant, Adela, Argy, Nicolas, Azjenberg, Daniel, Basmaciyan, Louise, Bastien, Patrick, Belaz, Sorya, Belkadi, Ghania, Bellanger, Anne-Pauline, Bemba, Dieudonné, Berry, Antoine, Botterel, François, Bouden, Vincent, Bougnoux, Marie-Elisabeth, Bouzayene, Azza, Bret, Laurent, Bretagne, Stéphane, Brumpt, Caren, Buret, Bernadette, Caraux-Paz, Pauline, Cheruiyot, Agnes, Chlilek, Alexandre, Clauser, Sylvain, Cojean, Sandrine, Cuisenier, Bernadette, Dahane, Naima, Dannaoui, Eric, Dard, Céline, Dardé, Marie-Laure, de Gentile, Ludovic, Debourgogne, Anne, Dechavanne, Célia, Delaunay, Pascal, Delaval, Anne, Deleplancque, Anne-Sophie, Desoubeaux, Guillaume, Desuremain, Nathalie, Develoux, Michel, Djènontin, Armel, Dossou, Yannelle, Durand, Rémy, Durieux, Marie-Fleur, Dutoit, Emmanuel, Eloy, Odile, Fenneteau, Odile, Fievet, Nadine, Gargala, Gilles, Garnaud, Cécile, Gay-Andrieu, Françoise, Godineau, Nadine, Gravet, Alain, Guennouni, Nadia, Guinard, Jérôme, Hamane, Samia, Huguenin, Antoine, Jumah, Jacqueline, L'Ollivier, Coralie, Landraud, Luce, Larréché, Sébastien, Lavergne, Rose-Anne, Le Govic, Yohann, Lohmann, Caroline, Machouart, Marie-Claire, Marteau, Anthony, Massougbodji, Achille, Mazars, Edith, Mechain, Matthieu, Mendes Moreira, Ana, Merat, Célia, Millon, Laurence, Mombo-Ngoma, Ghyslain, Morelle, Christelle, Morio, Florent, Mwakio, Edwin, Nabias, René, Nourrisson, Céline, Opot, Benjamin, Okhot, Raphael, Patoz, Pierre, Penn, Pascal, Perraud-Cateau, Estelle, Pihet, Marc, Pilo, Jean-Etienne, Pistone, Thierry, Poilane, Isabelle, Pomares, Christelle, Pons, Denis, Pougnet, Laurence, Pull, Lauren, Quinio, Dorothée, Raffenot, Didier, Rapp, Christophe, Receveur, Marie-Catherine, Roosen, Gabrielle, Sarrasin, Véronique, Sasso, Milene, Savini, Hélène, Senghor, Yaye, Silva, Muriel, Simon, Fabrice, Siriez, Jean-Yves, Sossou, Darius, Thellier, Marc, Thouvenin, Maxime, Toubas, Dominique, Tournus, Cécile, Touroult-Jupin, Pauline, Veletzky, Luzia, Vianou, Bertin, Zaffaroullah, Rizwana, Zoleko-Manego, Rella, Joste, Valentin, Coppée, Romain, Bailly, Justine, Rakotoarivony, Yann, Toko Tchokoteu, Francine Ghislaine, Achache, Shany, Pradines, Bruno, Cottrell, Gilles, Ariey, Frédéric, Khim, Nimol, Popovici, Jean, Mita, Toshihiro, Groger, Mirjam, Ramharter, Michael, Egbo, Timothy, Juma, Dennis W, Akala, Hoseah, Houzé, Sandrine, and Clain, Jérôme

Published
2024
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2. Plasmodium ovale spp dhfr mutations associated with reduced susceptibility to pyrimethamine in sub-Saharan Africa: a retrospective genetic epidemiology and functional study

Author

Joste, Valentin, primary, Coppée, Romain, additional, Bailly, Justine, additional, Rakotoarivony, Yann, additional, Toko Tchokoteu, Francine Ghislaine, additional, Achache, Shany, additional, Pradines, Bruno, additional, Cottrell, Gilles, additional, Ariey, Frédéric, additional, Khim, Nimol, additional, Popovici, Jean, additional, Mita, Toshihiro, additional, Groger, Mirjam, additional, Ramharter, Michael, additional, Egbo, Timothy, additional, Juma, Dennis W, additional, Akala, Hoseah, additional, Houzé, Sandrine, additional, Clain, Jérôme, additional, Abou-Bacar, Ahmed, additional, Agnamey, Patrice, additional, Ait-Ammar, Nawel, additional, Angoulvant, Adela, additional, Argy, Nicolas, additional, Azjenberg, Daniel, additional, Basmaciyan, Louise, additional, Bastien, Patrick, additional, Belaz, Sorya, additional, Belkadi, Ghania, additional, Bellanger, Anne-Pauline, additional, Bemba, Dieudonné, additional, Berry, Antoine, additional, Botterel, François, additional, Bouden, Vincent, additional, Bougnoux, Marie-Elisabeth, additional, Bouzayene, Azza, additional, Bret, Laurent, additional, Bretagne, Stéphane, additional, Brumpt, Caren, additional, Buret, Bernadette, additional, Caraux-Paz, Pauline, additional, Cheruiyot, Agnes, additional, Chlilek, Alexandre, additional, Clauser, Sylvain, additional, Cojean, Sandrine, additional, Cuisenier, Bernadette, additional, Dahane, Naima, additional, Dannaoui, Eric, additional, Dard, Céline, additional, Dardé, Marie-Laure, additional, de Gentile, Ludovic, additional, Debourgogne, Anne, additional, Dechavanne, Célia, additional, Delaunay, Pascal, additional, Delaval, Anne, additional, Deleplancque, Anne-Sophie, additional, Desoubeaux, Guillaume, additional, Desuremain, Nathalie, additional, Develoux, Michel, additional, Djènontin, Armel, additional, Dossou, Yannelle, additional, Durand, Rémy, additional, Durieux, Marie-Fleur, additional, Dutoit, Emmanuel, additional, Eloy, Odile, additional, Fenneteau, Odile, additional, Fievet, Nadine, additional, Gargala, Gilles, additional, Garnaud, Cécile, additional, Gay-Andrieu, Françoise, additional, Godineau, Nadine, additional, Gravet, Alain, additional, Guennouni, Nadia, additional, Guinard, Jérôme, additional, Hamane, Samia, additional, Huguenin, Antoine, additional, Jumah, Jacqueline, additional, L'Ollivier, Coralie, additional, Landraud, Luce, additional, Larréché, Sébastien, additional, Lavergne, Rose-Anne, additional, Le Govic, Yohann, additional, Lohmann, Caroline, additional, Machouart, Marie-Claire, additional, Marteau, Anthony, additional, Massougbodji, Achille, additional, Mazars, Edith, additional, Mechain, Matthieu, additional, Mendes Moreira, Ana, additional, Merat, Célia, additional, Millon, Laurence, additional, Mombo-Ngoma, Ghyslain, additional, Morelle, Christelle, additional, Morio, Florent, additional, Mwakio, Edwin, additional, Nabias, René, additional, Nourrisson, Céline, additional, Opot, Benjamin, additional, Okhot, Raphael, additional, Patoz, Pierre, additional, Penn, Pascal, additional, Perraud-Cateau, Estelle, additional, Pihet, Marc, additional, Pilo, Jean-Etienne, additional, Pistone, Thierry, additional, Poilane, Isabelle, additional, Pomares, Christelle, additional, Pons, Denis, additional, Pougnet, Laurence, additional, Pull, Lauren, additional, Quinio, Dorothée, additional, Raffenot, Didier, additional, Rapp, Christophe, additional, Receveur, Marie-Catherine, additional, Roosen, Gabrielle, additional, Sarrasin, Véronique, additional, Sasso, Milene, additional, Savini, Hélène, additional, Senghor, Yaye, additional, Silva, Muriel, additional, Simon, Fabrice, additional, Siriez, Jean-Yves, additional, Sossou, Darius, additional, Thellier, Marc, additional, Thouvenin, Maxime, additional, Toubas, Dominique, additional, Tournus, Cécile, additional, Touroult-Jupin, Pauline, additional, Veletzky, Luzia, additional, Vianou, Bertin, additional, Zaffaroullah, Rizwana, additional, and Zoleko-Manego, Rella, additional

Published
2024
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5. Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation

Author

Jullien, Vincent, Azoulay, Elie, Schwebel, Carole, Le Saux, Thomas, Charles, Pierre Emmanuel, Cornet, Muriel, Souweine, Bertrand, Klouche, Kadda, Jaber, Samir, Trouillet, Jean-Louis, Bruneel, Fabrice, Cour, Martin, Cousson, Joel, Meziani, Ferhat, Gruson, Didier, Paris, Adeline, Darmon, Michael, Garrouste-Orgeas, Maité, Navellou, Jean-Christophe, Foucrier, Arnaud, Allaouchiche, Bernard, Das, Vincent, Gangneux, Jean-Pierre, Ruckly, Stéphane, Wolff, Michel, Timsit, Jean-François, Timsit, Jean François, Hamidfar-Roy, Rebecca, Ciroldi, Magalie, Paugam-Burtz, Catherine, Foucrier, Arnaud, Navellou, Jean Christophe, Wolff, Michel, Timsit, Jean-Francois, Bouadma, Lila, Mourvillier, Bruno, Sonneville, Romain, Chemam, Sarah, Gruson, Didier, Souweine, Bertrand, Lautrette, Alexandre, Charles, Pierre Emmanuel, Bruyere, Rémi, Hamet, Maël, Allaouchiche, Bernard, Christian, Guillaume, Ber, Charles-Eric, Prothet, Johanne, Rimmele, Thomas, Argaud, Laurent, Simon, Marie, Cour, Martin, Hernu, Romain, Jaber, Samir, Jung, Boris, Conseil, Mathieu, Coisel, Yannael, Belafia, Fouad, Klouche, Kada, Amigues, Laurent, Machado, Sonia, Serveaux, Marianne, Chastre, Jean, Trouillet, Jean-Louis, Cousson, Joël, Raclot, Pascal, Floch, Thierry, Zeni, Fabrice, Darmon, Michael, Pichon, Matthias, Coudrot, Maud, Ninet, Sebastien, Diconne, Eric, Schlemmer, Benoit, Azoulay, Elie, Lemiale, Virginie, Maziers, Nicolas, Meziani, Ferhat, Schnell, David, Boisrame-Helms, Julie, Neagu-Anca, Raluca, Delabranche, Xavier, Martinet, Olivier, Garrouste-orgeas, Maité, Misset, Benoit, Bruneel, Fabrice, Laurent, Virginie, Lacave, Guillaume, Bedos, Jean-Pierre, Hammi, Khadija, Styfalova, Lenka, Fritzsch, Joelle, Letrou, Sophie, Estevez, Lucie, Adda, Mireille, Devaux, Therese, Dubien, Celine, Bayarassou, Soumia, Faure, Catherine Jouvene, de La Salle, Sylvie, Prades, Albert, Rodriguez, Annie, Meur, Pierre, Warchol, Magda, El Haouari, Hanane, Theodose, Igor, Fournier, Julien, Cavelot, Sebastien, Kodja, Lilia Bakir, Faure, Marie Joyeux, Maurisot, Sophie, Labat, Carole, Tacco, Frédéric, Roos, Sonia, Dupre, Karima, Abazid, Malek, Essert, Michele, Arnaud, Philippe, Papy, Emmanuelle, Ghezzoul, Bellabes, Gerbouin, Olivier, Peccoux, Sandrine Corny, Fagnoni, Philippe, Millaret, Anne, Pivot, Christine, Gerard, Cecile, Breuker, Cyril, Castet, Audrey, Charbonnier, Fanny, Legrand, Maryline, Mordini, Julia, Chambrin, Isabelle Madelaine, Clauss, Anne Hutt, Cherifi, Mohamed, Pattyn, Anne, Pichard, Camille, Cornet, Murielle, Zumbo, Christian, Smets, Aurélie, Benveniste, Eliane, Grenouillet, Fréderic, Chochillon, Christian, Accoberry, Isabelle, Pons, Denis, Mrozek, Natacha, Dalle, Frédéric, Bienvenu, Anne-lise, Picot, Stephane, Beyerle, Francoise, Bourgeois, Nathalie, Fekkar, Arnaud, Toubas, Dominique, Raberin, Hélène, Candolfi, Ermanno, Bru, Valérie, Kitzis, Marie Dominique, Senghor, Yaye, Palette, Catherine, Eloy, Odile, Ruckly, Stéphane, Vesin, Aurélien, Mira, Jean-Paul, Zahar, Jean-Ralph, Shir, Edith, Larrey, Dominique, and Zarskii, Jean-Pierre

Published
2017
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7. Diagnosis of mucormycosis using an intercalating dye-based quantitative PCR

Author

Bigot, Jeanne, primary, Godmer, Alexandre, additional, Prudenté, Lysa, additional, Angebault, Cécile, additional, Brissot, Eolia, additional, Bige, Naike, additional, Voiriot, Guillaume, additional, Leger, Pierre-Louis, additional, Petit-Hoang, Camille, additional, Atallah, Sarah, additional, Gouache, Elodie, additional, Senghor, Yaye, additional, Valot, Stéphane, additional, Hennequin, Christophe, additional, and Guitard, Juliette, additional

Published
2022
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8. A typical babesiosis in an immunocompetent patient

Author

Voisin, Olivier, additional, Monpierre, Lorra, additional, Le Lorc’h, Erwan, additional, Pilmis, Benoit, additional, Le Monnier, Alban, additional, Mourad, Jean-Jacques, additional, Senghor, Yaye, additional, and Mizrahi, Assaf, additional

Published
2021
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9. Performance of Repeated Measures of (1–3)-β-D-Glucan, Mannan Antigen, and Antimannan Antibodies for the Diagnosis of Invasive Candidiasis in ICU Patients: A Preplanned Ancillary Analysis of the EMPIRICUS Randomized Clinical Trial

Author

Dupuis, Claire, Le Bihan, Clément, Calvet, Laure, Schwebel, Carole, Cornet, Muriel, Hamidfar-Roy, Rebecca, Ciroldi, Magalie, Paugam-Burtz, Clichy Catherine, Foucrier, Arnaud, Navellou, Jean Christophe, Wolff, Michel, Timsit, Jean-Francois, Bouadma, Lila, Mourvillier, Bruno, Sonneville, Romain, Chemam, Sarah, Gruson, Didier, Souweine, Bertrand, Lautrette, Alexandre, Charles, Pierre Emmanuel, BRUYERE, Rémi, Hamet, Maël, Allaouchiche, Bernard, Guillaume, Christian, Ber, Charles-Eric, Prothet, Johanne, Rimmele, Thomas, Argaud, Laurent, Simon, Marie, Cour, Martin, Hernu, Romain, Jaber, Samir, Jung, Boris, Conseil, Mathieu, Coisel, Yannael, Belafia, Fouad, Klouche, Kada, Amigues, Laurent, Machado, Sonia, Serveaux, Marianne, Chastre, Jean, Trouillet, Jean-Louis, Cousson, Joël, Raclot, Pascal, Floch, Thierry, Zeni, Fabrice, Darmon, Michael, Pichon, Matthias, Coudrot, Maud, Ninet, Sebastien, Diconne, Eric, Schlemmer, Benoit, Azoulay, Elie, Lemiale, Virginie, Maziers, Nicolas, Meziani, Ferhat, Schnell, David, Boisrame-Helms, Julie, Neagu-Anca, Raluca, Delabranche, Xavier, Martinet, Olivier, Garrouste-Orgeas, Maité, Misset, Benoit, Brunee, Fabrice, Laurent, Virginie, Lacave, Guillaume, Bedos, Jean-Pierre, Hammi, Khadija, Styfalova, Lenka, Fritzsch, Joelle, Letrou, Sophie, Estevez, Lucie, Devaux, Therese, Dubien, Celine, Bayarassou, Soumia, Faure, Catherine Jouvene, de la Salle, Sylvie, Prades, Albert, Rodriguez, Annie, Meur, Pierre, Warchol, Magda, El Haouari, Hanane, Theodose, Igor, Fournier, Julien, Cavelot, Sebastien, Kodja, Lilia Bakir, Faure, Marie Joyeux, Tacco, Frédéric, Roos, Sonia, Dupre, Karima, Abazid, Malek, Essert, Michele, Arnaud, Philippe, Papy, Emmanuelle, Ghezzoul, Bellabes, Gerbouin, Olivier, Peccoux, Sandrine Corny, Fagnoni, Philippe, Millaret, Anne, Pivot, Christine, Gerard, Cecile, Breuker, Cyril, Castet, Audrey, Charbonnier, Fanny, Legrand, Maryline, Mordini, Julia, Chambrin, Isabelle Madeleine, Clauss, Anne Hutt, Cherifi, Mohamed, Pattyn, Anne, Cornet, Murielle, Maubon, Daniele, Benveniste, Eliane, Grenouillet, Frédéric, Chochillon, Christian, Accoberry, Isabelle, Pons, Denis, Mrozek, Natacha, Dalle, Frédéric, Picot, Stephane, Beyerle, Francoise, Bienvenu, Anne-Lise, Bourgeois, Nathalie, Fekkar, Arnaud, Toubas, Dominique, Raberin, Hélène, Candolfi, Ermanno, Bru, Valérie, Kitzis, Marie Dominique, Senghor, Yaye, Palette, Catherine, Ruckly, Stéphane, Vesin, Aurélien, Zahar, Jean-Ralph, Mira, Jean-Paul, Larrey, Dominique, Zarski, Jean-Pierre, Schir, Edith, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, Antibiotics, Gastroenterology, Major Articles, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Internal medicine, (1, Medicine, 030212 general & internal medicine, education, (1,3)-β-D-glucan, education.field_of_study, business.industry, competing risk models, Repeated measures design, invasive candidiasis, medicine.disease, Intensive care unit, 3)-β-D-glucan, 3. Good health, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Cohort, business
Abstract

Background We aimed to assess the prognostic value of repeated measurements of serum (1–3)-β-D-glucan (BDG), mannan-antigen (mannan-Ag), and antimannan antibodies (antimannan-Ab) for the occurrence of invasive candidiasis (IC) in a high-risk nonimmunocompromised population. Methods This was a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including nonimmunocompromised critically ill patients with intensive care unit–acquired sepsis, multiple Candida colonization, and multiple organ failure who were exposed to broad-spectrum antibacterial agents. BDG (>80 and >250 pg/mL), mannan-Ag (>125 pg/mL), and antimannan-Ab (>10 AU) were collected repeatedly. We used cause-specific hazard models. Biomarkers were assessed at baseline in the whole cohort (cohort 1). Baseline covariates and/or repeated measurements and/or increased biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC (cohort 2). Results Two hundred thirty-four patients were included, and 215 were still alive and free of IC at day 3. IC developed in 27 patients (11.5%), and day 28 mortality was 29.1%. Finally, BDG >80 pg/mL at inclusion was associated with an increased risk of IC (CSHR[IC], 4.67; 95% CI, 1.61–13.5) but not death (CSHR[death], 1.20; 95% CI, 0.71–2.02). Conclusions Among high-risk patients, a first measurement of BDG >80 pg/mL was strongly associated with the occurrence of IC. Neither a cutoff of 250 pg/mL nor repeated measurements of fungal biomarkers seemed to be useful to predict the occurrence of IC. The cumulative risk of IC in the placebo group if BDG >80 pg/mL was 25.39%, which calls into question the efficacy of empirical therapy in this subgroup.

Published
2021
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11. Evaluation of a New Histoplasmaspp. Quantitative RT-PCR Assay

Author

Alanio, Alexandre, Gits-Muselli, Maud, Lanternier, Fanny, Sturny-Leclère, Aude, Benazra, Marion, Hamane, Samia, Rodrigues, Anderson Messias, Garcia-Hermoso, Dea, Lortholary, Olivier, Dromer, Françoise, Bretagne, Stéphane, Woimant, Marine Gosset, blanchard, Geneviève, Silhadi, Souad, Vignier, Nicolas, Pitsch, Aurelia, Jidar, Kaoutar, Traversier, Nicolas, Poisson, Didier, Lecointre, Claire, Foulet, Françoise, Botterel, Françoise, Ammar, Nawel Ait, Amsellem, Gabriel, Frederic, Poirier, Philipe, Cornu, Marjorie, Loridant, Severine, Morio, Florent, Boutoille, David, Jeddi, Fakhri, Hasseine, Lilia, Ouissa, Rachida, Toubas, Dominique, Bailly, Eric, Désoubeaux, Guillaume, Ronez, Emily, Foulon, Guillaume, Lefrançois, Sebastien, Bonnal, Christine, Paugam, André, Dougados, Maxime, Desroches, Marine, Barazzutti, Hélène, Paleiron, Nicolas, rabodonirina, Meja, Catherinot, Emilie, Cardot-Martin, Emilie, Hiesse, Chrisian, Salvator, Hélène, Aguilar, Claire, Gigandon, Anne, de Montpreville, Thomas, Bougnoux, Marie-Elisabeth, Sitterlé, Emilie, Fekkar, Arnaud, Imbert, Sébastien, Bleibtreu, Alexandre, Senghor, Yaye, Denis, Blandine, Molina, Jean-Michel, Liegeon, Geoffroy, Munnier, Anne-Lise, Malphettes, Marion, Denis, Julie, Berlioz-Arthaud, Alain, Lange, Franciska, Chiaruzzi, Myriam, and Epelboin, Loic

Abstract

Laboratory diagnosis of histoplasmosis is based on various methods, including microscopy, culture, antigen, and DNA detection of Histoplasma capsulatumvar. capsulatumor Histoplasma capsulatumvar. duboisii. To improve sensitivity of existing real-time quantitative PCR (qPCR) assays, we developed a new RT-qPCR assay that allows amplification of whole nucleic acids of Histoplasmaspp. validated on suspected cases. The limit of detection was 20 copies, and the specificity against 114 fungal isolates/species was restricted to Histoplasmaspp. Whole nucleic acids of 1319 prospectively collected consecutive samples from 907 patients suspected of having histoplasmosis were tested routinely between May 2015 and May 2019 in parallel with standard diagnostic procedures performed in parallel. Forty-four had proven histoplasmosis attributable to H. capsulatumvar. capsulatum(n= 40) or H. capsulatumvar. duboisii(n= 4) infections. The results of RT-qPCR were positive in 43 of 44 patients (97.7% sensitivity) in at least one specimen. Nine of 863 cases (99% specificity) were RT-qPCR positive and therefore classified as possible cases. RT-qPCR was positive in 13 of 30 (43.3%) blood samples tested in proven cases. A positive RT-qPCR result in blood was significantly associated with H. capsulatumvar. capsulatumprogressively disseminated histoplasmosis with a positive RT-qPCR result in 92.3% of the immunocompromised patients with disseminated disease. This new HistoplasmaRT-qPCR assay enabling amplification of H. capsulatumvar. capsulatumand H. capsulatumvar. duboisiiis highly sensitive and allows the diagnosis of histoplasmosis advantageously from blood and bronchoalveolar lavage fluid.

Published
2021
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15. Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.

Author

Gharbi M, Flegg JA, Hubert V, Kendjo E, Metcalf JE, Bertaux L, Guérin PJ, Le Bras J, Aboubaca A, Agnamey P, Angoulvant A, Barbut P, Basset D, Belkadi G, Bellanger AP, Bemba D, Benoit-Vica F, Berry A, Bigel ML, Bonhomme J, Botterel F, Bouchaud O, Bougnoux ME, Bourée P, Bourgeois N, Branger C, Bret L, Buret B, Casalino E, Chevrier S, Conquere de Monbrison F, Cuisenier B, Danis M, Darde ML, De Gentile L, Delarbre JM, Delaunay P, Delaval A, Desoubeaux G, Develoux M, Dunand J, Durand R, Eloy O, Fauchet N, Faugere B, Faye A, Fenneteau O, Flori P, Fontrouge M, Garabedian C, Gayandrieu F, Godineau N, Houzé P, Houzé S, Hurst JP, Ichou H, Lachaud L, Lebuisson A, Lefevre M, LeGuern AS, Le Moal G, Lusina D, Machouart MC, Malvy D, Matheron S, Maubon D, Mechali D, Megarbane B, Menard G, Millon L, Aiach MM, Minodier P, Morelle C, Nevez G, Parola P, Parzy D, Patey O, Patoz P, Penn P, Perignon A, Picot S, Pilo JE, Poilane I, Pons D, Poupart M, Pradines B, Raffenot D, Rapp C, Receveur MC, Sarfati C, Senghor Y, Simon F, Siriez JY, Taudon N, Thellier M, Thouvenin M, and Toubas D

Subjects
Adolescent, Adult, Africa, Central, Africa, Western, Aged, Aged, 80 and over, Child, Child, Preschool, Drug Resistance, Female, Genotype, Humans, Infant, Longitudinal Studies, Male, Middle Aged, Parasitic Sensitivity Tests, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Travel, Young Adult, Antimalarials therapeutic use, Chloroquine therapeutic use, Malaria, Falciparum drug therapy, Plasmodium falciparum drug effects
Abstract

Background: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system., Methods: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates., Results: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3)., Conclusions: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.

Published
2013
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